TropIKA Blog Portal

Partnership deal will support development of potential new antimalarial

A new treatment for malaria could be on the way with the announcement that the Medicines for Malaria Venture (MMV) and Anacor Pharmaceuticals have entered into a development agreement relating to an Anacor compound - AN3661. MMV is a not-for-profit public-private partnership that aims to reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of new, effective and affordable antimalarial drugs. Anacor is a US biopharmaceutical company focused on discovering, developing and commercializing novel small-molecule therapeutics derived from its boron chemistry platform. Under the agreement, Anacor and MMV will work together on the development of AN3661 through human proof-of-concept studies. AN3661 was developed as part of a research agreement signed last year; AN3661 is the first candidate arising out of this agreement to move into preclinical development. Anacor is also active in the search for treatments for other infectious diseases of poverty and has established partnership arrangements with: the Global Alliance for TB Drug Development; with the Drugs for Neglected Diseases initiative (human African trypanosomiasis, visceral leishmaniasis and Chagas disease); the University of California San Francisco and the New York Blood Center (onchocerciasis); and with the Institute for OneWorld Health (diarrhoeal disease.) More details are available in an Anacor press release.

Vietnam's plan to eradicate malaria

Vietnam's health ministry has drafted a national strategy to eradicate malaria over the next 20 years through early diagnoses, effective treatment and preventative measures. The proposed strategy covers the period 2011-2020. The aim would be to eliminate the disease in 40 provinces and cities by 2020, and reduce the infection rate in the remaining areas to fewer than 15 per thousand persons and the fatality rate to under 2 per 10 million. The health ministry then envisages that full eradication of the disease would take place by 2030. Further details available from Bamoi.com.

mHealth: diagnosing infections with mobile phones

TropIKA.net has carried many reports on the rise of mHealth - the use of mobile (cell) phones in health care. mHealth initiatives have included improving communications between remotely located health workers and HQ, recording and transmitting data, and reminding TB patients to take their medication. A report from CNN describes the work of Aydogan Ozcan of the University of California, Los Angeles, who has invented a cheap, portable microscope that uses a mobile phone camera sensor. Ozcan's LUCAS device (lensless, ultra-wide-field cell monitoring array platform based on shadow imaging) clips on to to the back of a standard cell phone (minus its lens) and comprises an LED light, a spatial filter, and a slot for a medical slide. The aim is to use the microscope, which could cost as little as $5-$10, in the diagnosis of malaria, tuberculosis and other infectious diseases of poverty. Like a lot of other mHealth initiatives this is still at an early stage. Pilot projects in the field and a full evaluation of what is achieved will, as always, be necessary.

Health concerns as malaria programmes increase use of DDT

The insecticide DDT is used to control malarial mosquitoes in 14 malaria-endemic countries and its reintroduction is planned in several more. The World Health Organization recommends indoor residual spraying of homes with DDT as an effective tool for inclusion in malaria control programmes. But there have always been concerns about the effects of DDT on the environment and human health. A newly published review article [1] concludes that the evidence from several recent studies suggests associations between DDT exposure and adverse health effects, including spontaneous abortions, infertility, leukaemia, pancreatic cancer and breast cancer and diabetes. The article - written by Henk van den Berg, an entomologist at the University of Wageningen, the Netherlands - appears in Portuguese in a little known journal Ciência & Saúde Coletiva. It is discussed in an article on SciDev.Net. van den Berg argues that, "To reduce reliance on DDT, support is needed for integrated and multipartner strategies of vector control". But others would like to see more use of DDT. Restrictions on its use have become regarded as a symbol of unnecessary government intervention by right-wing groups in the USA, and the controversial US-based group Africans Fighting Malaria also advocates for expanded use; it has described concerns about the insecticide's adverse effects as "largely illegitimate". Reference 1. Van den Berg (2011). Estado global do DDT e suas alternativas para utilização no controle de vetores para prevenção de doenças. Ciênc. saúde coletiva; 16(2)575-590. Available online in Portuguese but with abstract in English: http://www.scielo.br/cgi-bin/wxis.exe/iah/

Stopping TB patients from getting malaria

Patients who have been hospitalized for tuberculosis treatment are still vulnerable to other infections. Malaria is one threat to those who live in countries where this disease is endemic. The TB National Reference Centre in Guinea-Bissau, West Africa embarked on a project to reduce the high mortality rate amongst its patients during each rainy season. In 2005, patients were issued with insecticide-treated bednets. To this intervention was added, a year later, environmental disinfection with insecticides. And in 2007 prophylactic treatment was begun, using the antibiotic cotrimoxazole which is known to provide a level of protection against malaria. The rainy season mortality rate decreased after the introduction of each of the three interventions. Death/discharge ratios were 0.79, 0.55 and 0.26 in 2005, 2006 and 2007 respectively. Mortality during the dry season remained unchanged. This was not a controlled trial and full information on the cause of mortality amongst patients who died is not supplied in the report of the study [1]. But these are encouraging findings, which lead the authors to claim that, "Malaria prevention in African tertiary care hospitals seems feasible with limited costs". The total cost of the interventions per patient was around $2.50. Reference 1. Colombatti R, Penazzato M, Bassani F, Vieira CS, Lourenço AA, Vieira F, Teso S, Giaquinto C, Riccardi F (2011). Malaria prevention reduces in-hospital mortality among severely ill tuberculosis patients: a three-step intervention in Bissau, Guinea-Bissau. BMC Infect Dis;11:57. Available online: http://www.biomedcentral.com/1471-2334/11/57

Gates invests in vaccine company

In Bill Gates' most recent Annual Letter he emphasized the importance that the Gates Foundation attaches to the development of new vaccines, in order to improve control of the infectious diseases of poverty (see TropIKA.net article). The Foundation's latest commitment to vaccine research comes in the form of a $10 million investment in Liquidia Technologies, a US company launched in 2004 that specialises in particle-based vaccines and therapies. Liquidia is already collaborating with the PATH Malaria Vaccine Initiative. Further information is available in a Bloomberg report.

Use of biolarvicides against malaria to be promoted in West Africa

Should the technique known as "biolarviciding" be added to the toolkit of interventions used in the control of malaria? The Commission of the Economic Community of West African States (ECOWAS) thinks it should. Biolarvicides, based on toxins from certain strains of the bacteria Bacillus sphaericus and Bacillus thuringiensis, have been shown to be highly effective against mosquito larvae at very low doses and unharmful to non-target organisms. Some encouraging results have been achieved in trials in the field using two products - Bactivec and Griselesf. James Gbeho, says that the ECOWAS Commission, of which he is President, will champion the use of biolarvicides and that, within the next four years, factories to manufacture them will be established in Ghana, Cote d’Ivoire and Nigeria. He said biolarvicding could also be used in the control of the vectors of yellow fever, onchocerciasis, filariasis, encephalitis and dengue. Gbeho made his remarks at the launch of a biolarvidicine programme in Nigeria's Rivers State, according to a report from Xinhua News.

How many Indians die from malaria? Government launches inquiry

The World Health Organization estimates that 10,000–21,000 people die from malaria in India every year. This is higher than the Indian government's own figure of 1,000 per year. But last year researchers using the controversial technique of verbal autopsy concluded that the true annual figure could be over 200,000 - see TropIKA.net article. The uncertainty as to how big a problem India has with malaria holds back treatment and control efforts. The Indian government has therefore - according to The Times of India - set up a 16-member expert group, chaired by Dr Padam Singh, to look into the discrepancies between the various estimates and come up with a more accurate figure.

Drugs for neglected infections could be "India's gift to the world"

Peter Hotez, that indefatigable campaigner for raising the level of action against the infectious diseases of poverty, has written an article for India's The Hindu newspaper. He seeks to emphasize both the magnitude of India's own disease burden and the strong position that the country is in to produce new drugs for these infections that will benefit Indians themselves and many others in disease-endemic areas. Hotez informs his readers that, "India and its South Asian neighbours account for one-quarter of the world's intestinal worm infections such as hookworm and roundworm, and more than one-half of the world's cases of elephantiasis, leprosy, and visceral leishmaniasis". India also continues to face a major malaria problem. As is the case elsewhere, there is a lack of incentive for industry in India to produce new treatments for these neglected diseases, as they mainly affect the poor who have little purchasing power. Hotez says the solution is for India to create "new strategies to link its government institutions and its powerful private biopharmaceutical companies together in a public-private partnership to stimulate innovation for the poor". He concludes his article:

"An Indian public-private partnership for NTDs could produce a new generation of drugs, diagnostics, and vaccines that will benefit all of South Asia, and indeed the entire world's 'bottom billion' – the 1.4 billion people in the world who live in extreme poverty. Innovation for the poor could truly become India's greatest gift to the world".

A long list

The list of the infectious diseases of poverty (IDPs) is a long one. How should the individual diseases on this list be prioritized when funding is allocated for their research and control? The third G-FINDER survey reports on the sources of research funding and on how it is currently being spent. In 2009 there was an increase in the proportion of funding coming from public institutions and a corresponding decline in what was received from philanthropic organizations. Is a trend perhaps emerging? In a TropIKA.net editorial [1], we ask what happens now. According to G-FINDER there are encouraging signs that funding is being distributed more widely amongst the individual IDPs. And at TropIKA.net we continue with our efforts to report on important new developments across the full range of these diseases. Our recent articles on tuberculosis, for example, include a news story highlighting the paucity of diagnostic tools for TB in children [2]; there are also reports on research to develop new diagnostic tests [3] and treatments [4] and a guest blog from the TuBerculosis Vaccine Initiative [5]. Malaria once again has once again featured strongly on TropIKA.net, with reports of several new research initiatives, one of which focuses on vivax malaria [6] which generally receives less attention than the falciparum form of the disease. Combining the use of bednets with preventive treatment [7] and the search for a single-dose cure [8] have been the subjects of other recent studies. Controversy has surrounded new research on the potential use of species of fungi that could reduce the ability of mosquitoes to transmit malaria [9]. One research group believes that the use of genetically modified (GM) forms of the fungi offers the most promising way forward. We are increasingly hearing of the use of genetic modification in the search for new tools for the control of the IDPs – whether this involves vaccines, drugs or vector control. But hostility towards the use of any form of GM technology is now widespread in many parts of the world. The release of GM mosquitoes in Malaysia, for the control of dengue fever, went ahead in the face of protests by environmentalists [10]. Scientists should lose no time in making major efforts to address public concerns about GM. New products developed with this technology must be acceptable to communities before they can be brought into use. Dengue has also been the subject of several other new reports on TropIKA.net [11,12,13,14,]. Indeed such is the increasing level of interest in this infection, of which there are 50–100 million cases every year, that the time must surely be coming when it can no longer be described as a “neglected tropical disease”. Cholera, in contrast, does not figure prominently on the research agenda, even though the current pandemic of the disease, which began in 1961, is showing no sign of weakening and may indeed be picking up speed – as we have discussed in a TropIKA.net editorial [15]. Other diseases also featured on TropIKA.net, and which still deserve the “neglected” label, include trachoma [16] leprosy [17] cysticercosis [18] and Buruli ulcer [19]. There is also a geographical aspect to neglect. It is easy to forget, for example, that malaria is a problem – not just in Africa and Asia – but also in many Pacific countries [20] and that many IDPs are still a burden in the Americas [11,21]. Whatever the disease, access to reliable information and to the findings of research is crucial for policy makers and practitioners. TropIKA.net aims to facilitate the process of communicating such information but access to scientific journals remains a problem in many of the world’s poorest countries [22].

Is artesunate trial the study of the year?

A randomized controlled trial [1] which found that severe falciparum malaria in children can be treated more effectively with artesunate than quinine has been shortlisted for the prestigious Research Paper of the Year award run by the BMJ. The trial, in which both drugs were administered parenterally, was conducted by an international team in nine African countries, with the participation of over 5000 children. Significantly lower mortality was observed amongst children receiving artesunate. The two other studies shortlisted for the 2011 award, as described in a BMJ article, were also randomized controlled trials and, like the artesunate study, were published in the Lancet. They investigated the use of tranexamic acid to reduce bleeding after injury (a study involving over 20,000 patients in 40 countries), and sigmoidoscopy as a screening tool for colorectal cancer (a study in the UK with over 170,000 patients). All three trials were published in the Lancet. Last year's award went to a previous study [2] of the use of artesunate for malaria in African children. Reference 1. Dondorp AM, Fanello CI, Hendriksen ICE, Gomes E, Seni A, Chhaganlal KD, et al, for the AQUAMAT group (2010). Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet; 376:1647-1657. 2. Gomes MF, Faiz MA, Gyapong JO, Warsame M, Agbenyega T, Babiker A, Baiden F, Yunus EB, Binka F, Clerk C, Folb P, Hassan R, Hossain MA, Kimbute O, Kitua A, Krishna S, Makasi C, Mensah N, Mrango Z, Olliaro P, Peto R, Peto TJ, Rahman MR, Ribeiro I, Samad R, White NJ; Study 13 Research Group (2010). Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet; 373(9663):557-566.

Animal-friendly malaria studies

In many countries in the West, finding ways of reducing the use of laboratory animals in research is regarded as a priority concern. ScienceAlert reports that a new approach to studying cerebral malaria that avoids animal testing has been developed at the University of Sydney, Australia. It has won the university's inaugural Award for the Reduction of Use of Animals in Research. Professor Georges Grau has developed an in vitro model that could replace the customary method of inoculating mice with a rodent-specific malaria parasite. His method, using human cells obtained with informed consent, allows the study of the lesions malaria causes in small brain blood vessels.

Malaria a major issue for some Pacific nations

It is sometimes forgotten that malaria is a major health issue in parts of the Pacific region. (The problems malaria causes in Africa and Asia receive more attention.) The situation in the Pacific is discussed in a Radio Australia interview with Professor Graham Brown, Foundation Director of the Nossal Institute for Global Health at the University of Melbourne, who is also a board member of the Roll Back Malaria programme. In the interview, also available as a podcast, Professor Brown describes the progress that has been made against malaria worldwide but emphasizes that more needs to be done in Pacific countries such as Vanuatu and Solomons. The particular problems caused by the region's main form of the disease (vivax malaria, which is a relapsing condition) also receive a mention, as does the work of the Asia-Pacific Malaria Elimination Network.

Africa's substandard drug problem: disturbing new findings

A Nigerian who is being treated for malaria is more likely to be receiving a fake or substandard drug than a genuine product. This disturbing reminder of the widespread prevalence of fake drugs, particularly in Africa, emerged from the publication of a new WHO report which looked at the quality of antimalarial drugs in six African countries: Cameroon, Ethiopia, Ghana, Kenya, Nigeria and Tanzania. Nearly one in three of the products examined did not meet standards. The problems with some of the drugs were serious; for one in ten of them, their use could be life-threatening. Nigeria faces the most serious situation, according to the report, with two-thirds of antimalarials found to be fake or substandard. Ghana and Cameroon follow with 39% and 37%. Kenya and Tanzania are doing better, with less than 11%. (Things seem to have improved in Kenya; a survey in 2003 found that over half of the country's drugs were fake or substandard.) All the samples examined by WHO in Ethiopia were found to be genuine, where the government maintains a tight regulatory regime. More information available in a report from allAfrica.com.

Researcher repeats vivax malaria warning

Speaking at a meeting of the American Association for the Advancement of Science, researcher Peter Zimmerman from Case Western Reserve University School of Medicine has repeated his warning that the immunity to vivax malaria possessed by people who do not express the Duffy blood-group protein may not in fact protect against newer strains of the Plasmodium vivax parasite. He fears that vivax malaria could soon become a serious problem amongst Africans, most of whom are Duff-negative. See Scientific American story. Zimmerman bases his warning on his study [1] in Madagascar in which he found that 10% of Duffy-negative subjects were in fact infected with Plasmodium vivax (see also TropIKA.net article). But other experts have claimed that vivax infection in Duffy-negative Africans is nothing new and that an explosion of this form of malaria in Africa is therefore unlikely. Reference 1. Ménard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR, Ratsimbasoa A, Thonier V, Carod JF, Domarle O, Colin Y, Bertrand O, Picot J, King CL, Grimberg BT, Mercereau-Puijalon O, Zimmerman PA (2010). Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA; 107(13): 5967-5971. http://www.scientificamerican.com/podcast/episode.cfm?id=malaria-parasite-infects-people-tho-11-02-22 But as we noted in our earlier article http://www.tropika.net/svc/research/Chinnock-20100409-Research-Duffy-vivax

Malaria's competitive streak may be a weakness

New research [1] suggests that different strains of the malaria parasite behave competitively when they encounter each other in their host. The study, led by researchers at the University of Edinburgh (UK) shows how the malaria parasite focuses on producing cells that replicate quickly to cause infection, rather than cells that can be taken up by a feeding mosquito and spreading the disease. Since malaria infections usually consist of multiple, competing strains of the parasite, this attack strategy is the best way to beat the competition. 'If the mechanisms underlying these behavioural changes in malaria parasites can be identified,' say the researchers, 'it may be possible to manipulate their behaviour in clinically beneficial ways.' The international team of researchers studied the malaria parasite Plasmodium chabaudi, which affects rodents. They watched how different genetic strains – genotypes – of the parasite behaved when they were the only one present and what happened when another genotype was introduced. They found that the parasites changed their survival strategy in the face of competition, so when more than one genotype was present they would invest more energy in replicating within the host, and less in spreading. 'We found that when parasites compete with each other, they respond with a sophisticated strategy to safeguard their long-term survival,' said Laura Pollitt of the University of Edinburgh's School of Biological Sciences, who led the study. 'They opt to fight it out in the bloodstream rather than risk everything on the chance of infecting mosquitoes in the short term.' Further information available from University of Edinburgh press release. Reference 1. Pollit LC, Drew DR, Schneider P, Colegrave N, Reece SE (2011). Competition and the Evolution of Reproductive Restraint in Malaria Parasites. American Naturalist; Published online 28 January 2011. Available online (abstract only): http://www.jstor.org/pss/10.1086/658175

Computer model predicts spread of malaria in Europe

Increasing use is being made of computer models in attempts to predict the changes that are likely to occur in the number of cases of infectious diseases, and in their geographical range. The website Click Green reports a study that has concluded, "By 2080, parts of Western Europe could be susceptible to the spread of malaria for up to six months a year". Many parts of Germany are calculated to be potentially at risk by that date, with around 90% of the country facing the spread of the disease in an annual transmission window of three months or more. Unfortunately, Click Green does not give details as to where the study itself was published. As we have often said on TropIKA.net, this is an important area for research. New findings should be shared widely but their origins and methods should be clearly apparent.

Plan to spread genes that would make mosquitoes resistant to infection with malaria or dengue

A new study [1] proposes the use of genetic engineering in the fight against mosquito-borne diseases including malaria and dengue fever. The so-called 'Semele' system describes a new way of spreading genes amongst the mosquito population that confer resistance to the pathogens that the insects transmit to humans. The Semele system is explained in an article on Deutsche Welle, which notes that one barrier to the implementation of such a disease control system is the widespread hostility to any use of genetic engineering technologies. Reference 1. Marshall JM, Pittman GW, Buchman AB, Hay BA (2011). Semele: a killer-male, rescue-female system for suppression and replacement of insect disease vector populations.

"Drop all taxes on antimalarial tools"

The Malaria Taxes and Tariffs Advocacy Project (M-TAP) says it "uses research to identify areas where governments, donors, NGOs, and the private sector can work together to roll back barriers to progress on malaria through evidence-based policy advocacy". It is supported by the Bill & Melinda Gates Foundation and the Roll Back Malaria Partnership. Reuters reports that M-TAP has urged governments to drop all taxes and tariffs on medicines, mosquito nets and other anti-malaria tools, in order to help reduce their costs and speed up their delivery.The majority of drugs and other products used to fight malaria are imported from overseas, so dropping taxes and tariffs would have a major impact. M-TAP's research has shown that taxes and tariffs on anti-malaria products provide only minimal revenues, the loss of which would be offset by reducing health costs and in curtting the productivity losses for which malaria is responsible. M-TAP points out that only six countries worldwide have completely removed tariffs on products used to fight the disease, despite a promise 10 years ago from African leaders to do so.

Indians in "tribal" district received outdated malaria treatment

There can be few clearer examples of the gap between policy and practice, in the treatment of malaria, than the findings of a study [1] from India. Researchers from the Indian Council for Medical Research (ICMR), who were investigating epidemic levels of malaria in a district of Madhya Pradesh state, found that the majority of patients treated for the disease had been given the drug chloroquine, against which the malaria parasite has for some years been resistant. The drug was given by local health centres despite national guidelines directing that chloroquine should be replaced with artemisinin-based combination therapies (ACT). The district is a remote forest region in one of India's "tribal" areas. The Telegraph newspaper says that nearly all patients examined by the researchers had received chloroquine, as ACTs were not available either through government or private health centres: "The district headquarters did initially have a stock of about 3,300 courses of ACTs which, public health officials say, was grossly inadequate to meet the actual requirement. ACT costs about Rs 150 [about three US cents] for a course, in contrast to Rs 8 for chloroquine therapy". The researchers conclude in their published study: "Evidence suggests that the non-availability of artemisinin-based combination therapy and rapid diagnostic tests along with an immunogenically vulnerable population each played an important role [in the epidemic] Detection and control of epidemics requires greater attention, and mechanisms to ensure the quality of interventions are essential". Reference 1. Singh N, Shukla MM, Chand G, Bharti PK, Singh MP, Shukla MK, Mehra RK, Sharma RK, Dash AP (2011). Epidemic of Plasmodium falciparum malaria in Central India, an area where chloroquine has been replaced by artemisinin-based combination therapy. Trans R Soc Trop Med Hyg; [Epub ahead of print]. Article not available with open access but abstract is accessible here: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B75GP-5235B8S-1&_user=10&_coverDate=02%2F02%2F2011&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d44f831637eabe02670e3029efc400e7&searchtype=a

Mosquito named after South African researcher

There are many honours that can be bestowed upon researchers for their work. One of these is to have a species of animal or plant named after them. A South African scientist, recognized for her research on malaria, has just had her name given to a mosquito. The name of Professor Maureen Coetzee, Director of the Malaria Entomology Research Unit at the University of the Witwatersrand, now appears as the sub-genus of an unusual black and white mosquito found in the Indian Ocearn area - Aedes (Coetzeemyia) fryeri. A team at the prestigious Smithsonian Institution in the US recently renamed the mosquito in an article [1] in a journal of taxonomy, Zootaxa. Ironically perhaps, considering Professor Coetzee's malaria background, Aedes (Coetzeemyia) fryeri is not a malarial mosquito. Indeed, while other Aedes mosquitoes are responsible for the transmission of viral diseases such as dengue and yellow fever, this mosquito is not known to transmit any infection affecting humans. "I don't want a deadly mosquito named after me!", says Maureen Coetzee. An interview with Professor Coetzee may be read here: http://www.timeslive.co.za/sundaytimes/article895162.ece/Mozzie-honour-a-buzz-for-Wits-prof Reference 1. Huang Y, Wayne NM, Wilkerson RC (2010). Coetzeemyia, a new subgenus of Aedes, and a redescription of the holotype female of Aedes (Coetzeemyia) fryeri (Theobald) (Diptera: Culicidae). Zootaxa; 2638:1-24. Available: http://www.mapress.com/zootaxa/2010/f/z02638p024f.pdf

GM mosquitoes could help control malaria

A news story in a US newspaper (the Sacramento Bee) describes the work of scientists at the Universities of Arizona and California Davis, who have created a genetically modified (GM) mosquito that is resistant to infection with malaria. A gene within the mosquito produces a protein that disrupts the development of malaria parasites. Potentially, mass releases of these mosquitoes could be used in malaria control programmes. Professor Shirley Luckhart at University of California Davis says the intention would be to "drive the gene through the [mosquito] population". Time magazine recently named the development of the mosquito as one of the 50 best inventions of 2010 and gave it the No. 1 spot in the health and medicine category. However, hostility to the use of any form of GM technology for any purpose is widespread internationally. Protests recently met the release of GM mosquitoes with the aim of controlling dengue fever in Malaysia - see TropIKA.net News.

Will border conflict aid the spead of drug-resistant malaria?

When countries fall out because of a dispute over their national borders, the potential consequences are always of concern. In the case of recent hostilities along the border separating Thailand and Cambodia, there is a danger that it could potentially impede efforts to hold back the spread of strains of the malaria parasite resistant to the first-line treatment, artemisinin. Artemisinin combination therapies (ACTs) are crucial to malaria control and it is along the Thai-Cambodia border that resistance first appeared. Holding it in check is a global health priority; should resistance spread to areas with very high levels of malaria, particularly in Africa, millions of lives could be lost. Consequently, the World Health Organization and the Roll Back Malaria partnership launched the Global plan for artemisinin resistance containment in January this year. But cross-border cooperation will be essential and this could be difficult to maintain since the clashes (described in a Voice of America report) that began when Thai activists seeking to reclaim a disputed area of territory were arrested by the Cambodian authorities, who have now sent troops to the area. Observers say the situation has arisen because of the continuing political difficulties within Thailand itself. Whatever the reasons, it is to be hoped that both countries will recognise the need to work together against malaria.

Unusual cases of malaria transmission

When the quality of research evidence is ranked, case studies appear at the bottom of the hierarchy (with systematic reviews and clinical trials at the top). Nevertheless, a good case study can often alert us to new developments or remind us of an important, but perhaps neglected issue. A case study from France [1] provides such an example. The vast majority of cases of malaria are transmitted by mosquitoes, but other means of transmission do exist. A woman who worked as a technician in a clinical laboratory was admitted to Bordeaux Hospital after seven days with a fever, which turned out to be malaria. The patient later recalled that two weeks before admission she had been injured by a broken, blood-contaminated, malaria diagnostic (QBC) test tube at work. (Believing it to be a trivial incident, she did not report it at the time.) Hers was therefore a case of malaria due to occupational exposure. The source of the blood was a patient who had recently returned to France from Congo. The same hospital, a few weeks earlier, had admitted a 15-day-old girl who was referred from Dakar, Senegal. She was the third child of a Lebanese family who had no known genetic illness and who lived in an air-conditioned house. She too was diagnosed with malaria, the source was a blood donation she had received in Dakar for neonatal anaemia. Lessons can be learned from both cases. The first underlines the importance of reporting accidental injury in healthcare settings. Diagnosis of this patient would have been accomplished much sooner had this been done; with malaria, delayed diagnosis can have fatal consequences. It is generally assumed that babies as young as the second patient are able to counteract infection with malaria. (This is because fetal haemoglobin, which does not sustain the full development of the malaria treatment, is the dominant form of haemoglobin in the child at this early stage.) But the transfusion of adult blood, as well as infecting the child, may have compromised her ability to resist the infection. In most malaria-endemic countries (including Senegal) adults who receive transfused blood are routinely given antimalarial treatment but young children are not. (There is no validated and convenient therapeutic antimalarial regimen for this age group.) Even where malaria is not endemic, it should be considered as a cause of unexplained acute fever. Patients who have had accidents involving blood or have received blood transfusion can be infected via these routes. Reference 1. Vareil MO, Tandonnet O, Chemoul A, Bogreau H, Saint-Leger M, Micheau M, Millet P, Koeck JL, Boyer A, Rogier C, Malvy D (2010). Unusual Transmission of Plasmodium falciparum, Bordeaux, France, 2009. Emerg Infect Dis; 17(2):248-50. Available online: http://www.cdc.gov/eid/content/17/2/248.htm?source=govdelivery

Single-dose cure for malaria edges closer to the clinic

With the emergence - and likely spread - of strains of the malaria parasite resistant to the standard treatment, artemisinin, new drugs are urgently needed. An article [1] in this week's Proceedings of the National Academy of Sciences describes the discovery and properties of a potential antimalarial drug, OZ439. The drug has already successfully completed Phase 1 clinical trials, where it was shown to be safe, and has progressed to trials in malaria patients [2]. OZ439, described as a "novel synthetic peroxide", is designed to provide a single-dose oral cure for malaria. It belongs to the ozonide class of compounds and its molecular structure is different from that of artemisinin, and from drugs that are derivatives of artemisinin. The development of artemisinin resistance should not therefore affect the susceptibility of malaria parasites to OZ439. Studies have shown that new drug may be of value in the prevention of malaria in addition to its treatment. OZ439 is being developed by Medicines for Malaria Venture (MMV) in partnership with three academic institutes: University of Nebraska Medical Center, USA, Monash University, Victoria, Australia, and the Swiss Tropical and Public Health Institute. According to Tim Wells, MMV’s Chief Scientific Officer: “OZ 439 holds a great deal of promise to power the eradication of malaria as it fits the bill on the two most crucial features of the ideal medicine: the potential for a one-dose cure and a treatment for artemisinin-resistant strains. If the clinical development proceeds as planned we can expect to see a new combination medicine launched by 2016. This will be a great day for malaria treatment and a real credit to the power of partnerships.” References 1. Charman SA, Arbe-Barnes S, Bathurst IC, Brun R, Campbell M, Charman WN, Chiu FC, Chollet J, Craft JC, Creek DJ, Dong Y, Matile H, Maurer M, Morizzi J, Nguyen T, Papastogiannidis P, Scheurer C, Shackleford DM, Sriraghavan K, Stingelin L, Tang Y, Urwyler H, Wang X, White KL, Wittlin S, Zhou L, Vennerstrom JL (2011). Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. Proc Natl Acad Sci U S A; [Epub ahead of print]. Available in full online: http://www.pnas.org/content/early/2011/02/02/1015762108.long 2. Olliaro P, Wells TNC (2009). The global portfolio of new antimalarial medicines under development. Clin Pharmacol Ther; 85:584-595.

Bednet passes the test in evaluation of long-term use

Long-lasting insecticidal nets (LLIN) are now standard for the prevention of malaria but only products recommended by the World Health Organization should be used, and evaluation of the effectiveness of an LLIN should include an assessment of its performance after three years of field use. The Malaria Consortium has just published a report of its evaluation of a polyester-based LLIN - BASF's Inceptor brand - which has already received an interim recommendation from the WHO Pesticide Evaluation Scheme (WHOPES). Malaria Consortium's report is based on four years of field testing in an area of Western Uganda where other LLIN brands are also in use, allowing for direct comparisons. In five villages, 190 Inceptor™ LLINs and 90 conventionally treated nets were distributed randomly and used by families. A baseline survey was carried out and following that a household survey was conducted every six months to look at use, washing habits and physical condition of the nets. Randomly selected nets were collected after six, 12, 24, 36 and 48 months and tested for remaining insecticide content and ability to knock-down and kill malaria transmitting mosquitoes. The study showed that after four years 29% of the nets were still in good condition while 13% were seriously torn, with no difference between the LLIN and control nets. The conventionally treated nets quickly lost insecticide and after 24 months only 7% of the original dose remained. Optimal effectiveness in bio-assays was found in 83% of the sampled LLINs after three years and 71% after four years. The study concluded that Inceptor fulfilled the criteria for level III of WHOPES over three years, based on the conditions in Western Uganda of moderate climate and the frequency of washing. Data from a four-year follow-up suggests that performance does not drop radically but gradually, indicating a ‘useful life’ of the product for approximately four years in these settings. The full report is available from Malaria Consortium on http://www.malariaconsortium.org/userfiles/file/Uganda/Interceptor%20report%20to%20BASF%20Uganda%20final.pdf.

Concerns over identification of 'new' malarial mosquito

Anopheles gambiae mosquitoes are the most important vectors of malaria in sub-Saharan Africa. Researchers report that they have identified a sub-type of A. gambiae, which seems to have evolved relatively recently, that is significantly more susceptible to malaria infection than other sub-types. It is also more difficult to control. The worrying findings appear in research published [1] in Science. Working in Burkina Faso, the French and US researchers found that the previously unreported sub-type does not live inside homes and is very much an outdoor mosquito. This is unfortunate as far as vector control is concerned as the current focus is on indoor residual spraying with insecticide and the use of insecticide-treated bednets, rather than seeking to spray the entire environment. While the researchers have not yet established whether the new sub-type takes blood meals from humans, nor how large its home range is, the appearance of the 'new' mosquito is of some concern. The published report notes that a control project in Nigeria during the 1970s failed because genetically distinct outdoor-resting mosquitoes allowed malaria transmission to persist despite the use of indoor insecticides. Reference 1. Riehle MM, Guelbeogo WM, Gneme A, Eiglmeier K, Holm I, Bischoff E, Garnier T, Snyder GM, Li X, Markianos K, Sagnon N, Vernick KD (2011). A cryptic subgroup of Anopheles gambiae is highly susceptible to human malaria parasites. Science. 2011 Feb 4;331(6017):596-8. The abstract of this study only is freely available online: http://www.sciencemag.org/content/331/6017/596.abstract

A brief report on the study that appears in USA Today includes a short video summarizing the findings.

Nigeria's plants: a source of new antimalarials?

A review [1] has been conducted of studies carried out across Nigeria into the use of plant remedies to treat malaria. The practice is very common in this country and the review confirms that a wide variety of plants are regarded, in Nigerian folklore, as being useful in the treatment of malaria and/or other fevers. A table within the review lists 102 such plant species. The authors go on to note that, "Pharmacological studies have demonstrated in vitro antiplasmodial and/or in vivo antimalarial activities of extracts from 45 plant species used in Nigerian folk medicine out of the 51 species tested". Often traditional remedies turn out to be ineffective (and in some cases harmful) but many scientifically proven treatments for disease had their origins in herbal medicines. Malaria is indeed a case in point: quinine is an extract of the bark of the cinchona tree and artemisinin is derived from Artemisia annua (sweet wormwood). So far, however, there is no established treatment for malaria based on a plant occurring naturally in Africa. (The article does note that extracts of Alstonia boonei and other herbs have been sold in tablet form as malaria treatments in Nigeria.) As the authors of the review point out: "Tropical rainforest plants are known to have higher concentrations of natural chemical defenses and a greater diversity than plants from any other biome, thus they are potential sources of new medicines. It seems logical then to encourage studies on plants from these regions, especially since the major proportion of malaria-attributable deaths occur in sub-Saharan African regions". Africa's rainforests may well have much to offer in the search for new antimalarials and the plants regarded by local populations as being useful against the disease deserve further investigation. Reference 1. Adebayo JO, Krettli AU (2011). Potential antimalarials from Nigerian plants: a review. J Ethnopharmacol; 133(2):289-302. Available online: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T8D-51H1DK5-2&_user=10&_coverDate=01%2F27%2F2011&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1635554376&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93afdceb1ab566cf91c83e283d533754&searchtype=a#sec0040

Washington Post on Global Fund fraud

Recent reports of cases of fraud within programmes supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria have led to much publicized criticisms of the the Fund, and the withdrawal by some countries of their support for its activities. The Global Fund's own investigations uncovered the cases of fraud (in four African countries. Right-wing commentators have argued that, as a result of such instances of corruption, most development aid is wasted. An article in The Washington Post puts the issue in perspective, pointing out that "the $34 million in fraud that has been exposed represents about three-tenths of 1 percent of the money the fund has distributed [by the Global Fund]". Going on to note that the Fund pursues its anti-corruption activities with great vigour, and that some programmes have been suspended following the recent revelations, the article concludes: "In global health, corruption kills. The most important response, however, is to make sure the right people get punished - not an African child who needs a bed net, or the victim of a cruel and wasting disease. They had no part in the controversies surrounding the Global Fund, but depend, unknowingly, on their outcome. An overreaction to corruption can also cost lives". This last point is well made and well worth bearing in mind.

A time to be bold

Sometimes everyone must choose whether to make relatively minor changes to the world around them or to set a much bolder goal. The international community has in recent years devoted increased attention to malaria with the aim of improving the control of the disease, and indeed the progress made has been encouraging. But the global eradication of the disease has not been on the agenda for many years. Should researchers now set their sights much higher and seek to develop new tools that would make eradication possible? The Malaria Eradication Research agenda (malERA) was established in 2007 with that very purpose in mind. malERA is a TropIKA.net partnership organization and we report [1] that after two years work, with the participation of over 250 scientists, the agenda for research has been published in the form of a series of 12 rigorously peer-reviewed articles, available as a collection within the open-access journal PLoS Medicine. The UK’s Department for International Development has been drawing up its own malaria agenda [2], focusing on the part it will play in international efforts to achieve the Millennium Development Goals relating to the disease. DFID has opted for an evidence-based approach and the publication of its malaria “framework for results” is accompanied by the release of a comprehensive “evidence overview” document that could be of considerable value to other malaria policy makers. One new tool that now seems set to play a useful part in improving malaria control is the RTS,S vaccine, which has been shown in a trial [3] to provide protection that extends at least 15 months post-vaccination. It is quite clear, however, that the level of protection is only around 50%. This could potentially save many lives but, if eradication is the goal, then better vaccines will be needed. But in addition to effective tools to control or eradicate malaria we need to know where this disease is going. Will it be more widespread and will case numbers increase as a result of global warming? Helping to inform the debate on this important question is a new study [4] in which meteorological data demonstrated that temperatures have risen in a part of the Kenyan highlands where malaria cases are known to have increased. While malaria has accounted for much of the new content appearing in TropIKA.net since the start of the year, our coverage of other infectious diseases of poverty has been far ranging. Early-stage research conducted in Denmark [5] has achieved encouraging results with a tuberculosis vaccine intended to protect against both new infection and the emergence of the latent form of the disease. New data has confirmed that TB threatens the poor wherever they live [6] and shown that the high prevalence of the disease found in many prisons spills over to impact the wider population [7]. An issue we have previously highlighted on TropIKA.net is the danger posed by inaccurate serological tests for TB; WHO has now issued a negative policy recommendation (the ﬁrst of its kind for the organization) that the tests should not be used [8]. Meanwhile, an outspoken article from Bangladesh [9] claims that TB control efforts are wrongly focused, and that the level of progress towards the targets that have been set has been exaggerated. New research on other infectious diseases of poverty has produced both encouraging and disappointing findings. In Brazil three-quarters of the patients given the drug miltefosine were cured of cutaneous leishmaniasis [10], compared with only half of those on the standard treatment. But bednets failed to protect against leishmaniasis in trial in India and Nepal [11]. Meanwhile, Sierra Leone has increased the coverage rate of in its lymphatic filariasis drug administration programme [12]. Other diseases recently featuring on TropIKA.net have included sleeping sickness [13], schistosomiasis [14] and rabies [15]. With the right level of commitment, the control of all these diseases could be improved but global eradication seems an unrealistic proposition. Or do we lack the vision and the courage to make the paradigm shift required in our thinking?

Modelling the impact of climate change on malaria and dengue

Rising global temperatures could in theory extend the geographical range of the mosquitoes responsible for the transmission of malaria and of dengue fever. But is this actually happening and what is likely to occur in the future? It is a subject on which there has been considerable speculation. News of funding for research that will help answer these questions is therefore to be welcomed. The US National Science Foundation (NSF) has announced it is awarding $250,000 to Dr Kathleen Schreiber, Professor of Geography at Millersville University of Pennsylvania to conduct a modelling study that will seek to determine how environmental temperature change influences the risks of the two diseases. Two climate models will be used in the project: a downscaling model which produces the localized temperature projections and an epidemiological model. Schreiber says that when the two are combined, researchers can predict the future risk of infection. “Temperature affects the biting rate of mosquitoes and the incubation of parasites,” said Schreiber. “With a higher temperature, for example, malaria incubation in the mosquito does not take as long. Therefore, the mosquito is more likely to become infected before dying and transmit the disease to others.” Further information is available in a University press release.

Vaccines dominate in Bill Gates' "annual letter"

Such is the scale of the Bill & Melinda Gates Foundation's support for global health programmes, the publication of the "Annual Letter from Bill Gates" has become an important event. While described as a "personal account" of Bill Gates' priorities, it provides an indication of which areas the Foundation intends to emphasize in the assistance it provides to health care programmes and to research. From the 2011 Annual Letter, which runs to 24 pages, it would appear that vaccination dominates Bill Gates' current thinking. Focusing on polio eradication as a key example of the value of vaccines, the letter reminds us that this disease is on the threshold of becoming only the second disease ever eradicated. “We are so close," says Gates, "but we have to finish the last leg of the journey”. He goes on to argue that "Eradication would energize the global health field by showing the real impact of health investments – particularly investments in vaccines". To quote further from the letter, "This year 1.4 million children will die from diseases for which there are already vaccines - diseases like measles, pneumonia, and tetanus. Those lives can be saved if we can reduce the costs of vaccines and raise enough money to buy and distribute them". Gates also notes that progress is being made in the search for vaccines against malaria, tuberculosis and HIV. The letter also has sections on the tragically high neonatal death rates of many developing countries and on the fight against malaria which is said to be "making very good progress". The word "research" appears only three times in the document, which is surprising given the level of support the Foundation has provided to researchers. The only research findings referred to specifically are those from a study finding an association between IQ and infectious disease burden. (See TropIKA.net article on the study.) It is a piece of research that has attracted some criticism. The dominance of vaccines in the letter will raise some concerns amongst those whose focus is on other ways of reducing the burden of disease. New diagnostic tools and improved vector control, for example, are urgently needed but they do not receive a mention. Poverty reduction programmes, health systems strengthening and water, and sanitation programmes also fail to appear in this year's letter. As Bill Gates stresses throughout the letter, new vaccines and wider use of those we already have could potentially achieve major reductions in the disease burden, but they are only part of what is needed. The Foundation has provided invaluable support to research in a range of fields relevant to the infectious diseases of poverty. Any move towards a much narrower focus would be disappointing.

Drug-resistant malaria could reach Africa "within months"

Following the publication of an action plan to prevent the further spread of strains of the malaria parasite resistant to the key treatment drug artemisinin (see TropIKA.net article), a leading specialist has spoken of a continuing lack of urgency in efforts to address the problem. He believes that, within months, artemisinin resistance could arrive in the part of the world where serious cases of malaria are most common - Africa. Professor Nick White of Mahidol University in Bangkok played a leading role in identifying artemisinin resistance when it first appeared along the Cambodia-Thailand border in 2007. Speaking to Reuters, he described the new action plan as "anodyne". In White's view, "What seems to be lacking is a sense of urgency. People talk in terms of years. I think we should be thinking in terms of months. Time is crucial." He continued, "It is a time bomb, it is ticking. It has the potential of killing millions of African children. A migrant worker who doesn't even show symptoms could spread the resistant parasite beyond Asia". Professor White also called for more resources to fund research efforts to develop new malaria treatments.

New chairs for infectious disease group in US congress

The Congress of the United States of America established in 2008 a special interest group ('caucus') to focus on the impact of malaria on global health. The group was subsequently enlarged to cover additionally other infectious diseases of poverty and is now known as the Malaria and Neglected Tropical Diseases Caucus. The names of the new co-chairs of the group - Congressmen Donald Payne (Democrat) and Jeff Fortenberry (Republican) - have just been announced. Fortenberry commented: "Every 45 seconds, a child in Africa dies from malaria. Every day, countless children are left disfigured, blinded, developmentally debilitated, and killed by NTDs. These diseases form a heartbreaking global health emergency. As the United States' own public health experience has demonstrated, diseases like malaria are treatable, preventable, and curable. I share the Caucus' goal of ending malaria deaths by 2015, and working to curb the spread of NTDs among our world's most vulnerable". Further details are available from allAfrica.com.

India launches monitoring system for resistance to key antimalarial

The potential for the spread of strains of the malaria parasite that are resistant to the first-line treatment, artemisinin, continues to be a major concern for the global health community. Resistance was first detected in the Thailand-Cambodia border region. India has now put arrangements in place to monitor the situation there. The head of the National Vector Borne Disease Control Programm, Dr A Dhariwal, told the Times of India that the National Institute of Malaria Research was now monitoring artemisinin resistance in 15 sites, mainly in the northeastern states, and in Jharkhand, Chhattisgarh, Madhya Pradesh and Orissa. India's action is most welcome, especially in the light of to a recent report, which found that only a third of the countries where malaria is endemic are attempting to monitor the efficacy of antimalarial drugs - see TropIKA.net article. The World Health Organization is backing efforts worldwide to stop the spread of artemisinin resistance. The greatest concern is that parasites that are no longer sensitive to the drug could emerge in regions where the death rate due to malaria is highest, particularly in Africa. To reduce the chance of resistance appearing, it is essential that the drug is only used in the form of artemisinin combination therapy (ACT) - i.e. it is given with one of the older antimalarial drugs. However, a few manufacturers continue to defy international pressure and still produce the drug in monotherapy form.

"Jet lag" reduces ability of parasite to cause malaria

The more we know about the parasites that cause malaria, the better we will be able to find new ways to fight the disease. Sometimes new findings appear to have no immediate potential in malaria control efforts but are nevertheless intriguing. An example is a study [1] that found that one species of the Plasmodium parasite was less able to cause disease in mice when it was "jet-lagged" - i.e. when its circadian clock was no longer in alignment with that of its host. The cyclical nature of malaria infections is well known and the researchers were able to demonstrate that a "perturbation of parasite rhythms" halved the organism's ability to cause infection and spread disease. The researchers housed the host mice in different rooms with different schedules of lighting (on-off). The behaviour of the mice was in accordance to the rhythm of the lighting schedule. After giving the mice two weeks to adjust, they were infected, thus creating parasites that were also "matched" to the schedule. Later, these parasites were used to infect further mice - either on the same schedule or on the alternative schedule, to which they were "mismatched". Reduced effectiveness was found in the mismatched group. Speaking to BBC News, Dr Sarah Reece, of Edinburgh University's School of Biological Sciences, who led the research, said: "For this study, we effectively gave the parasites jet lag. "Our findings suggest that parasites have developed some clever tricks to get their timing right and cause an infection. This is rare evidence that organisms whose body clock is in sync with their environment have a better chance of survival". This is a long way from developing a new way of preventing or treating malaria but the research has revealed a new factor influencing what determines how effective Plasmodium is in causing disease. Reference 1. O'Donnell AJ, Schneider P, McWatters HG, Reece SE (2011). Fitness costs of disrupting circadian rhythms in malaria parasites. Proc Biol Sci; Epub ahead of print. http://rspb.royalsocietypublishing.org/content/early/2011/01/05/rspb.2010.2457.long

Making 2011 a landmark year

Once again it is time to wish all readers of TropIKA.net a Happy New Year. Let us hope that 2011 will bring renewed progress in the worldwide efforts to reduce the impact of the infectious diseases of poverty (IDPs). As each year goes by we learn more about the organisms responsible for the IDPs. For example, in the closing weeks of 2010, research was published expanding our understanding of how tuberculosis persists in the human body [1] and why it is that the efficacy of BCG, still the only vaccine in use against TB, varies so widely [2]. Establishing the priorities for future research is not easy, however. A recent article [3] discussed ways in which the priority setting process for TB research could be improved. And the social context in which the IDPs occur is one area of research that should undoubtedly be higher on the priority list, as discussed in another of the papers we have highlighted on TropIKA.net [4]. It is always encouraging when research leads to the development of new tools to combat the IDPs and programmes are launched to bring such interventions to those who need them; the first vaccine designed specifically for Africa has been launched in the continent’s “meningitis belt” and could prevent the many thousands of deaths that occur during epidemics of meningococcal A meningitis [5]. However, it is important to monitor the performance of interventions in the field. A newly published study [6] has, for example, cast doubts on the value of the recommendation that pregnant women should be included in mass drug administration programmes that seek to control soil-transmitted helminthiases. Even when interventions have been shown to work, it is still important to see whether they can be improved; another recent study [7] compared the use of the antibiotic azithromycin in the control of trachoma, given in the form of eye drops instead of the standard oral administration, with encouraging results. One consequence of the weaknesses of health systems in the world’s poorest countries is that the tools for IDP control generally perform less well than expected. Concerns have, for example, been expressed that the RTS,S vaccine (expected to become the first malaria vaccine to come into widespread use) may end up sitting “on the shelf” in medical stores because of inadequate planning [8]. Most IDP research still takes place in the wealthier nations, with the result that in disease endemic countries (DECs) there is an absence of a feeling of “ownership” of new tools once they are developed. Does this perhaps explain why intervention programmes using these tools are often not pursued with the level of commitment they deserve? Clearly we need to find ways of stimulating innovation within DECs themselves. A new collection of papers illustrates the triumphs and the troubles experienced by African initiatives focused on local healthcare needs [9]. The use of research to help strengthen health systems has featured often on TropIKA.net during 2010. We have recently highlighted another paper on this topic [10] and Bill Brieger, in a guest contribution to our blog [11], argues that health systems reform is an important aspect of achieving universal coverage of malaria interventions. The most ambitious programme to reform a national health system is, however, taking place in China which is seeking to bring universal health coverage to over 1.3 billion people. Professor Siân Griffiths, Dean of the School of Public Health and Primary Care at the Chinese University in Hong Kong is one researcher who will be studying how successful China is in these efforts. Professor Griffiths is the subject of the latest in our series of Profile articles [12]. But during the holiday period much of the activity on TropIKA.net has been within our blog. Here we have reported on new developments relating to many conditions recognised as being IDPs, amongst them leishmaniasis [13, 14], schistosomiasis [15] and onchocerciasis [16]. But also we highlight a systematic review [17] that has shown the rate of hospital-acquired infections to be much higher in poorer nations. Journalists and scientists are professional groups who do not always work well together, but one thing they have in common is an ability to promote change. Another TropIKA.net blog [18] reports the latest statement from the African Media and Malaria Research Network, a group of African journalists and scientists that seeks “to promote timely communication of malaria research findings and outcomes in Africa through strengthened collaboration between malaria researchers and journalists”. The group has called on African governments and policy makers to step up their commitment to fight malaria. It is an appropriate time of the year to make such a call. If 2011 brings an increased level of political commitment towards the control of all the infectious diseases of poverty, it will be remembered as a landmark year. Paul Chinnock Editor, TropIKA.net

Rwanda's malaria prevalence "lower than published figures"

In the World Health Organization's recently published World Malaria Report 2010, Rwanda in Central Africa emerged as one country where cases of the disease have increased, in contrast to reductions reported in several other nations. However, the malaria situation may better than the WHO figures indicate. Malaria researcher Dr Corine Karema has pointed out that WHO's report uses data from 2009, a year in which Rwanda experienced problems that led to delays in the distribution of insecticide-treated bednets. Since then much had been achieved, particularly with regard to net distribution and indoor residual insecticide spraying. Dr Karema said that malaria cases in August 2010 were 40% down on the figure for August 2009. She said that the situation demonstrated the need for monthly monitoring of surveillance data, to demonstrate disease trends. In most African countries, monitoring systems would have to be strengthened to make this possible. Dr Karema is Director of TRAC Plus, founded in 2007 to serve as a national centre for infectious diseases control and prevention in Rwanda. More details available from allAfrica.com.

Malaria elimination: El Salvador shows the way

Only 15 cases of malaria were reported in El Salvador in 2010 and, of these, five were imported from other countries. This means that the small, but densely populated, country in Central America is drawing closer to the goal of eliminating the disease. A consultant from the Pan American Health Organization, Marcelo Aguilar, says the situation is encouraging and that an elimination plan will be initiated in 2011. (More information in news report from InsideCostaRica.)

Health systems in World Malaria Report 2010

Bill Brieger writes... Since the World Malaria Report 2010 was published, the main news reports have focused on the numbers - including increases in malaria programme financing, numbers of people protected by malaria interventions, number of cases confirmed through parasitological diagnosis, and number of artemisinin combination therapies (ACTs) procured. Key reductions were reported in the number of confirmed malaria cases and malaria mortality and burden. There is a recognition that not all locations experienced the positive trends. Quoting the report: “There was evidence of an increase in malaria cases in three countries in 2009 (Rwanda, Sao Tome and Principe, and Zambia). The reasons for such resurgences are not known with certainty. The increases in malaria cases highlight the fragility of malaria control and the need to maintain control programmes, even if numbers of cases have been reduced substantially.” The report stressed the importance of surveillance systems in detecting these challenges. These contrasting findings show that we need to identify the factors responsible for fragility or strength in health systems in order make malaria control progress possible. The 2010 World Malaria Report differs little from its predecessors in that it does not provide much of substance to document which health systems interventions have made gains possible and retreats unfortunate. For example, the report lets us know generically that, “Much of the support for malaria control activities derives from existing health systems in countries. This is true especially for the treatment of acute disease – where health workers, hospitals, clinics and other infrastructure are typically provided by the national governments or supported by non-governmental organizations.” We also find statements such as, “The monetary value of such benefits (from increased diagnostic testing) is uncertain, but there is consensus that these are worthwhile objectives for health systems”. Concerning country case studies, we are told that, “...they reflect the burden that malaria places on the health system. Changes in the numbers of cases and deaths reported by countries do not, however, necessarily reflect changes in the incidence of disease in the general population, because …” of inadequacies in health information systems. It would be most helpful to share examples and evidence of health information systems that actually work to help countries target interventions more effectively. Again the obvious is stated … “Policies may vary according to the epidemiological setting, socioeconomic factors and the capacity of the national malaria programme or country health system. Adoption of policies does not necessarily imply immediate implementation, nor does it indicate full, continuous implementation nationwide.” We would love to see evidence of successfully implemented policies that have made a difference. We have a belief that health systems reform and health systems strengthening are important aspects of achieving universal coverage of malaria interventions. We would really like to have our belief backed by evidence presented in future World Malaria Reports. Bill Brieger is a Professor in the Health Systems Program of the Department of International Health at Johns Hopkins University as well as the Senior Malaria Adviser for the university's family and reproductive health affiliate, JHPIEGO.

Malaria control strategy: another view

Ecologist Dr William Jobin of Blue Nile Associates, Colorado, USA writes... Based on about 50 years experience in control of tropical diseases in Africa and the rest of the tropics, I have put together some suggestions for a more realistic approach to malaria control, which I hope will be of use to policy makers and practitioners. In my 2010 monograph "A realistic strategy for fighting malaria in Africa" published by Boston Harbor Publishers, I examine the global history of malaria control, including four recent projects in Africa which failed, and current efforts by WHO, the Global Fund, and also the US President's Malaria Initiative (PMI), which I helped start in Angola. I also recount my experience with the Blue Nile Health Project in Sudan. First of all it is apparent that current approaches to malaria control in Africa are unsustainable and will not endure. They will eventually fail because of costs and resistance problems. Current strategies overemphasize drugs, biocides and bednets, all of which will have to be continually renewed. An immediate solution is to add permanent methods such as improved water management in irrigation systems, better community drainage, and window screens and closure of other points of mosquito entry to houses. By adding these permanent measures to the current unsustainable ones, we can gradually increase the number of people living in areas where malaria prevalence is easily held down to acceptably low levels. One of the most obvious faults in the current strategies used in the PMI and by WHO, is the absence of control measures against anopheline larvae, despite several possible approaches, including chemical or biological larviciding, habitat drainage, and improved irrigation techniques. We should use all these available measures in a rational combination, integrating them in what we called the "kitchen sink strategy" in Sudan. For 10 years we were thus able to hold the prevalence down to about 0.1%, only to be foiled when we were unable to implement our exit strategy - a comprehensive drainage system. WHO is severely underfunded for malaria control, with less than one fourth the money it needs, and funds are shrinking. Thus instead of trying to cover all of Africa, WHO should first build expertise in the stable countries which have already made progress, such as South Africa, Zambia, Ghana, Senegal, Tanzania and Mozambique. As these progress, WHO could then establish training centres in the French, English and Portuguese languages to train people for the national malaria control programmes of neighbouring countries. WHO should also help the ministries of health in these countries to set up career tracks for malaria control personnel, ensuring them of the chance to use their training as entomologists, lab technicians and epidemiologists. We must become more realistic and be conscious of our cost limitations, and of the need for adding permanent control measures to the ephemeral ones presently used. This will make possible gradual but sure progress in the fight against malaria in Africa. Malaria will not disappear from Africa in our lifetimes; so I propose that we take the long approach. The book is available through: http://www.bostonharborpublishers.com/ Special arrangements have been made to supply the book to customers in Africa. Dr Jobin may be contacted on: blue.nile@earthlink.net

Influence of climate change on malaria will be studied in Nigeria

Will rising global temperatures have an impact on the prevalence of malaria and other infectious diseases of poverty? The issue has been much discussed but there is a lack of data to inform the debate. A research project involving Nurses Across the Borders, a Nigerian health NGO, and SeaTrust Institute, a US-based scientific and educational non-profit organization could help provide more information. IRIN News reports that Nurses Across the Borders will be collecting data on cases of malaria. “The nurses will note if malaria is recorded in any area where it usually isn’t, and all this information will be fed into a climate model which will help prepare health-related climate change projections for the country,” said Dr Lynn Wilson, executive director of the SeaTrust Institute. About 500 nurses will be involved in the project which is set to begin next year.

Award for Kenyan malaria researcher

Kenyan researcher Collins Ouma has received a prize to the value of $95,000 for his research into severe malarial anaemia (SMA). The award is from the UK's Royal Society and is sponsored by Pfizer, with the intention to "recognise a research scientist, at an early stage of their research career, who is making an innovative contribution to the biological sciences, including basic medical science, which contributes significantly to capacity building in Africa". Dr Ouma’s research focuses on the genetic and immunological basis of SMA. Part of the funding that he receives through the prize will be used to establish a teaching and research laboratory at Maseno University in Kenya. For further information see Royal Society press release. and report from Business Daily.

"Before we used to get sick all the time": positive reaction to bednets used in malaria programme

Insecticide-treated bednets are known to be efficacious in preventing malaria but there have been concerns that, when the nets are made available through distribution programmes, recipients may not always view them favourably and may not use them properly - if they use them at all. A qualitative study from western Kenya has produced some reassuring findings. Researchers from Kenya, Uganda and the USA conducted qualitative interviews with 34 people who had received long-lasting insecticide-treated nets (LLINs) as part of a comprehensive malaria prevention package of goods and services. One month after distribution, the recipients were asked about their attitudes and beliefs regarding malaria, and about their use of LLINs. Virtually all of them noted that mosquitoes were involved in causing malaria, though nearly half (47%) also mentioned an incorrect cause in addition to mosquitoes; e.g. cold weather or eating bad food. Most of them used the LLINs they were given and most mentioned positive benefits from their use, namely reductions in malarial illness and in the costs associated with diagnosis and treatment. Noting the positive response, the researchers conclude that: "With improved understanding and clarification of the direct (mosquitoes) and indirect (e.g ., standing water) causes of malaria, it is likely that LLIN use can be sustained, offering effective household-level protection against malaria". Reference 1. Tye TDV, Apodi R, Luganda ES, Kahn JG, Smith J, Othoro (2010). "Before we used to get sick all the time": perceptions of malaria and use of long-lasting insecticide-treated bed nets (LLINs) in a rural Kenyan community. Malaria Journal; 9:345. Available online: http://www.malariajournal.com/content/9/1/345

Resistance to antimalarials: should eradication be the response?

For the last three years, the Guardian newspaper (UK) has invited both amateur and professional journalists to enter its International Development Journalism Competition by submitting a feature article on one aspect of development. Amongst several fine winning articles this year, is a feature that looks at malaria in Thailand. Professional journalist Ann Morgan's visited Thailand, supported by the Malaria Consortium, to focus on the problems caused by the emergence of strains of the malaria parasite resistant to the main first-line treatment - artemisinin combination therapy (ACT), and also by the large-scale movement of migrant workers across the Thai-Cambodia border that adds to the difficulties of containing drug resistance. Containment, however, may not be possible and, as Morgan reports, there is a growing view that - while today's malaria drugs are still effective - a major effort should be made to eradicate malaria. The full article is accessible online.

Vector control: Gates funds continuation of insecticide development programme

The Innovative Vector Control Consortium (IVCC), a product development partnership hosted by the Liverpool School of Tropical Medicine, has received $50 million from the Bill & Melinda Gates Foundation to enable it to continue its work to develop new insecticides for the improved control of mosquitoes and other insects that transmit the infectious diseases of poverty. A wide range of these diseases - including malaria, dengue, filariasis, leishmaniasis and trypansomiasis - have insect vectors. Current insecticides used against these vectors have limitations that affect the way they can be used, and they are threatened by the emergence and spread of insecticide resistance. IVCC was established in 2005 with an initial grant of $50.7 million over five years from the Gates Foundation. Since then, it has established a pipeline of new, reformulated and repurposed insecticides with leading global chemical companies. A suite of information systems and diagnostic tools for the more effective and efficient use of insecticides has also been developed. These products now nearing the end of their development phase and it is expected that they will be launched within the next year. Professor Janet Hemingway - Director of the Liverpool School and IVCC's CEO - said: "The need for new insecticides has never been greater. Increased funding for control programmes is saving thousands of lives but malaria is still killing one child in Africa every 45 seconds. Resistance to insecticides is increasing at an alarming rate and we must find new alternatives even if we are to stay still in our battle against this and other vector borne diseases. "This award allows us continue the pioneering work we're doing in partnership with the chemical industry to find and develop totally new classes of insecticide to help put an end to this needless loss of life. Our strategic aim is to provide three new active ingredients for use in public health insecticides by 2020."

Research needed at all levels

Research has led to the development of new tools to address the infectious diseases of poverty but so often the new breakthroughs fail to reach the people who need them most. It is time, therefore, to apply rigorous research methods to the task of improving health systems themselves. The First Global Symposium on Health Systems Research addressed this key issue, 16-19th November in Montreux, Switzerland. Some 1200 delegates were present in person but, to enable others who recognize the importance of health systems research (HSR) to participate “virtually”, TropIKA.net created a knowledge hub [1] which – in addition to feature articles and commentaries on background papers – provided reports of the proceedings at the main plenary sessions. Interestingly, these reports were themselves written by a virtual participant – me – working through the medium of the webcam in the main conference hall. The exercise has shown that it is possible to be part of the proceedings at international conferences, even from a distance. In my closing comments [2] on the Symposium, I pointed out that much of the debate focussed on developing new methodologies suitable for use in HSR; it’s easy to say that policy should be evidence-based but there are different ideas as to the most appropriate methods to use to compile the evidence base. We must hope that the new ideas and principles debated in Montreux will soon be put to use. We have also reported on another recent meeting, the International Colloquium on Neglected Protozoan Diseases [3] and on two important new documents published by the World Health Organization. This year’s World Health Report focused on how health systems are financed. Dr David Evans, WHO’s head of health systems financing told TropIKA.net that, “Most countries could be doing better than they are doing now” [4]. Working to overcome the global impact of neglected tropical diseases is a WHO report published in October. We sought the reaction of a number of leading figures in the neglected tropical disease (NTD) field, who expressed concern that the role of research was insufficiently emphasized in the report [5]. A forthcoming publication of great significance is the Global Report for research on infectious diseases of poverty, initiated by the Special Programme for Research and Training in Tropical Diseases (TDR). Much will depend on the efforts of the distinguished experts chosen to write this report. TropIKA.net continues its series of in-depth Profiles on these authors. Most recently featured in the series are Yongyuth Yuthavong [6], a biochemist who became Thailand’s minister for science and technology and is now a malaria researcher; and Ulisses Confalonieri [7], an enthusiast for multi-sectoral research who works at Fiocruz, the research institute that advises the Brazilian minister of health on policy. Much of the rest of our recent coverage on TropIKA.net has concerned the two leading infectious diseases of poverty – tuberculosis and malaria. Encouraging news from South Africa is that a clinical trial using a combination of three drugs will seek to treat both drug-sensitive and multidrug-resistant TB; it could reduce MDR-TB treatment from two years to less than six months [8]. But controlling the infectious diseases of poverty requires more than good treatments. Diagnosis continues to be a neglected area. The commercial development of rapid tests to diagnose TB might therefore seem to be a useful step forward. But Mycobacterium tuberculosis is a pathogen with some unusual characteristics – it affects over half the world’s population of whom only about 10% will ever develop the clinical disease. The tests therefore give many false positive results. Their misuse in India is very worrying [9]. The “holy grail” in malaria control still seems to be regarded as the development of a vaccine. A four-country trial has been launched of the African Malaria Network Trust’s vaccine candidate [10]. But an area of concern was emphasized in a new report. Since the emergence of resistance to the mainstay of malaria treatment (artemisinin combination therapy) in the Cambodia–Thailand border region, WHO has strongly urged all malaria-endemic countries to routinely monitor the efficacy of their first- and second-line antimalarials, but it has emerged [11] that only about a third of these countries are attempting to do so. Should artemisinin resistance emerge elsewhere, in Africa for example, then it is important that it should be detected rapidly. Also on malaria, we look at the reaction to the findings of a study that concludes that, from a cost-saving point of view, eliminating malaria has no advantage over improving its control [12]. The TropIKA.net Blog [13] also continues to report news items of interest. We note, for example, that the Gates Foundation has announced a continuation of funding for six of the 45 projects supported by its Grand Challenges Explorations programme [14]. The programme aims “to support innovative, early-stage research to expand the pipeline of ideas to improve global health”. However, observers say [15] that early-stage research now seems to play a smaller part in the overall Gates Foundation vision. The intention now is to “focus on technologies with the biggest health payoffs and near-term applications”. There are concerns that funding bodies that take this view are underestimating the importance of scientific research at the “basic” level. The welcome new enthusiasm for health systems research should not be accompanied by reduced commitment to research at other levels. Paul Chinnock Editor, TropIKA.net

Nigerian drug development institute faces funding crisis

Research at Nigeria's National Institute for Pharmaceutical Research and Development (NIPRD) is said to have "ground to a halt" due to a lack of funds. A grant from the US National Institute of Allergy and Infectious Diseases (NIAID) has expired and the support provided by the Nigerian government is less than one fifth of what the Institute needs to cover its running costs, according to a news story in Nature. NIPRD specializes in research on traditional herbal medicines, with the aim of developing potential new drug candidates for conditions that are common in Africa. There is evidence that a drug (Nicosan) which it developed for the treatment of sickle cell disease is effective in relieving symptoms. Promising results are also said to have been achieved with potential malaria and tuberculosis treatments. Plans to continue research on all of these drugs are on hold. (Meanwhile, a US company that was manufacturing Nicosan in Nigeria has closed its factory there and the drug is no longer available.) Karniyus Gamaniel, NIPRD's director, says hopes to get funding from the World Bank.

Audience impressed by artesunate trial

One of the presentations at the meeting caught the attention of sciencemag.org, which reported the excitement of the audience when it was announced that a trial in Africa confirmed that artesunate is a more effective treatment for severe malaria than quinine. See: http://news.sciencemag.org/sciencenow/2010/11/new-malaria-drug-could-save-tens.html?ref=hp The trial results have also now been formally reported in the Lancet [1]. See also a press release from the Wellcome Trust which funded the research. Reference 1. Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, Kivaya E, Agbenyega T, Nguah SB, Evans J, Gesase S, Kahabuka C, Mtove G, Nadjm B, Deen J, Mwanga-Amumpaire J, Nansumba M, Karema C, Umulisa N, Uwimana A, Mokuolu OA, Adedoyin OT, Johnson WB, Tshefu AK, Onyamboko MA, Sakulthaew T, Ngum WP, Silamut K, Stepniewska K, Woodrow CJ, Bethell D, Wills B, Oneko M, Peto TE, von Seidlein L, Day NP, White NJ; for the AQUAMAT group (2010). Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010 Nov 7. [Epub ahead of print]

African clinical trial for new malaria vaccine

The African Malaria Network Trust (AMANET) has launched a multi-site phase IIb clinical trial of the candidate malaria vaccine GMZ2 to assess its efficacy and safety among young children at high risk of malaria. The trial, supported by a grant from the European and Developing Countries Clinical Trials Partnership (EDCTP) is taking place in Burkina Faso, Gabon, Ghana and Uganda. For further details see AMANET press release. The project profile is also available on the EDCTP website.

Intermittent preventative therapy in pregnancy with sulphadoxine-pyrimethamine (SP); 42 day in-vivo follow-up study among asymptomatic parasitemic pregnant women in an area with high SP resistance in Southern Malawi

TropIKA Reporting Sunday, November 7th Symposia and Scientific Sessions Reporters: Ambroise Ahouidi, Aida Badiane, Amy Bei, Regina Joice HSPH, Boston, USA and Cheikh Anta Diop University, Dakar, Senegal Session Title: Malaria- Chemotherapy: Implementation, Evaluation and Impact Scientific Session # 177 Speaker Name: Linda Kalilani (could not attend. Talk was given by a colleague). Study Aim: to determine the effectiveness of IPTP-SP in pregnant women in Blantyre, Malawi. Approach: Several measurements were made, including (A) the % of women with drug resistance to IPTP as assessed by molecular markers, (B) the % of women who had no parasites at day 42 following treatment, (C) the % of women who got placental malaria. The study was conducted in over 100 women in the 2009/2010 transmission season at the Queen Elizabeth Central Hospital in Blantyre, Malawi. Results/Conclusions: Approximately one third of the women in the study had parasitemia at Day 42 (though the presenter could not yet confirm the rate of reinfection because MSP typing results had not yet been completed). The study revealed that for women on their first or second pregnancy, each additional dose of SP did not reduce their risk of getting placental malaria. However, for multigravid women, there was a slight trend suggesting that SP may slighly reduce risk in this population. Molecular marker analysis suggest that drug resistant mutations against SP are approaching fixation in the population. Commentary/Questions: Interesting discussion followed regarding whether in Southern Malawi, policy should be changed and a new treatment regimen should be given to pregnant women. It was suggested that - given the return of chloroquine sensitivity in Malawi - that the previously recommended drug for IPTP (chloroquine) or may be a better option for IPTP in this area. Significance: It was reported a few years ago that IPTP-SP was 50% effective from 1996-2000, and had dropped to 10% effective by 2000-2003. This study showed that the IPTP-SP regimen is no longer an effective treatment against placental malaria in Southern Malawi.

Milestones

A milestone event concerning the infectious diseases that are the biggest killers of the world’s poorest people will take place next year when TDR (the Special Programme for Research and Training in Tropical Diseases) will publish a Global Report on research and development into the infectious diseases of poverty. In preparation, TropIKA.net is interviewing some of the distinguished authors contributing to the report. Already published are Profile articles featuring Dr Enriqueta Bond, a medical research champion and former head of the Burroughs Wellcome Fund [1], Dr Mushtaque Chowdhury of the Rockefeller Foundation [2] and Dr Georgio Roscigno of the Foundation for Innovative New Diagnostics (FIND) [3]. More of these articles will appear soon. Another important occasion will take place 16–19th November, when the First Global Symposium on Health Systems Research will be held in Montreux, Switzerland. TropIKA.net is covering the meeting with a knowledge hub [4], which will also provide an opportunity for participants (both those in Montreux and those who are ‘virtually’ present) to comment on reports and activities. The hub is already up and running; a selection of background papers [5] that will help participants prepare for the meeting is amongst the resources available. Our latest knowledge hub comes hard on the heels of the heels of a similar facility [6] we created for the annual meeting of the American Society for Tropical Medicine & Hygiene. Amongst the eight sessions at this meeting that were summarised in TropIKA.net reports, was a workshop in which the TropIKA.net project itself and our plans for the future came under discussion. Meanwhile, back on the main section of TropIKA.net [7] and on the TropIKA.net blog [8], we have continued to report on a variety of developments of direct relevance to the infectious diseases of poverty. The inadequacy of currently available tests for the diagnosis of tuberculosis is one of the biggest barriers holding back progress against the disease, but there has been encouraging news to report. Most importantly, a new molecular test developed by Dr Roscigno’s organization, FIND, has performed well in an evaluation [9]. A new robust, affordable, lightweight microscope [10] may also help by making sputum microscopy possible on the frontline of care. A TropIKA.net editorial [11] commented on a controversial new study from India that found a considerable disparity between existing estimates of the number of malaria cases and the much higher figure reached through the use of the verbal autopsy technique. A controversy of much longer standing, but one which doesn’t seem to go away, is whether malaria programmes should aim at improving control of the disease or set the much bolder goal of eliminating it as a public health problem, or even eradicating it. A review of available data has concluded that, from a cost-saving point of view, eliminating malaria has no advantage over improving its control. We look at the reaction to this finding from other malaria specialists [12]. Malaria eradication featured recently too in the TropIKA.net, where we reported the opinion of a distinguished malariologist that it should be considered an ‘aspiration not a priority’. Another news story, reported in our increasingly busy blog site, also concerned diseased eradication. For the second time ever an infectious disease has – subject to confirmation – been eradicated globally. The first such success was against smallpox; this time it is an infection of animals – rinderpest [13]. Nevertheless, rinderpest has in its long history had a major impact on many poor communities by destroying their cattle herds. Its eradication is a major step forward and provides us with hope that success will soon also be achieved against such human diseases as dracunculiasis (guinea worm disease) and polio. In the longer term, malaria too could be added to the list of diseases consigned to history.

Malaria chemotherapy: Clinical trials and pharmacokinetics

TropIKA Reporting 4th November 2010. Reporters: Ambroise Ahouidi, Aida Badiane, Amy Bei, Regina Joice HSPH, Boston, USA and Cheikh Anta Diop University, Dakar, Senegal Longitudinal trial of chloroquine monotherapy and combination therapy for uncomplicated P. falciparum malaria in children in Blantyre, Malawi. Miriam Laufer Study aim: to determine the efficacy of chloroquine monotherapy and combination therapy in Malawi, a country of recent chloroquine sensitivity. The study also looked at the impact of these treatments on malarial anemia, measured by hemoglobin concentration. Approach: 4 treatment arms were initiated with 160 children in each arm to evaluate the impact of chloroquine monotherapy (CQ), chloroquine +artesunate (CQ +AS), chloroquine + azithromycin (CQ + Azithro) and chloroquine + atovaquone proguanil (CQ+AP). Results/Conclusions: After the first treatment arm, there was no difference in parasite clearance rates for the chloroquine monotherapy compared to combination therapies, and all were effective. Hemoglobin levels (measured at months 4, 8, and 12 after treatment) increased in children under 3 in all treatment arms, with the most significant increase occurring by month 12 in children treated with chloroquine+azithromycin. This study interestingly showed no significant advantages to chloroquine combination therapy over monotherapy. Commentary/Questions:

While the authors found no difference in asexual parasitemia, they did not look at differences in gametocyte carriage (which presumably would be much lower with a chloroquine + artesunate combination). It was suggested that looking at gametocytes carriage would be an important aspect as it would impact transmission of the parasite and might help elucidate an “ideal” treatment regime

While the mutant allele of PfCRT responsible for CQ resistance in Malawi was been characterized and studies genetically and shown to confer a strong fitness disadvantage to the parasites, the wild-type allele appears to confer resistance to lumefantrine. The suggestion was made that a chloroquine + lumefantrine combination may limit the parasite’s options for drug resistance by optimally decreasing fitness.Significance: Malawi was one of the first countries in which chloroquine sensitivity had been described after widespread resistance, which posed interesting questions regarding parasite adaptability to drug pressure. It appears that chloroquine once again is a viable anti-malarial option. While the authors noticed no difference in effectiveness between monotherapy and combination therapy, they noted that clearly monotherapy would not be recommended as national drug policy.

Identification of 11 potential malaria vaccine candidates using bioinformatics

Dr Raul Isea has asked us to highlight his recently published research. Identification of 11 potential malaria vaccine candidates using bioinformatics. Abstract In this paper, we suggested 11 protein targets to be used as possible vaccines against Plasmodium falciparum , the causative agent of almost two to three million deaths per year. A comprehensive analysis of protein targets have been selected from the small experimental fragment of antigen in the P. falciparum genome, all of them common to the four stages of the parasite life cycle (i.e., sporozoites, merozoites, trophozoites and gametocytes). The potential vaccine candidates should be analyzed in silico using various bioinformatics tools. The possible protein target according to PlasmoDB gene ID are PFC0975c, PFE0660c, PF08_0071, PF10_0084, PFI0180w, MAL13P1.56, PF14_0192, PF13_0141, PF14_0425, PF13_0322, y PF14_0598. Isea R (2010). Identification of 11 potential malaria vaccine candidates using bioinformatics. VacciMonitor; 19(3)15-19. Full paper available online (Spanish only): http://sites.google.com/site/isearaul/home/vaccimonitor-isea.pdf Dr Raul Isea works at the Instituto de Estudios Avanzados (IDEA) in Baruta, Venezuela.

Malaria eradication an aspiration not a priority, says KEMRI professor

From Dr Onome Akpogheneta… Malaria eradication “should be our aspiration, but not our priority” advised Professor Kevin Marsh, Director of the Kenya Medical Research Institute (KEMRI)–Wellcome Programme and Oxford University Professor of Tropical Medicine, during his discussion with Professor A C Grayling for the BBC World Service’s Exchanges at the Frontier series. The movement towards malaria eradication and elimination has grown in confidence and capacity over the last few years. Heartened by reports of reduced incidences of malaria in East and West Africa in particular, many leaders in malaria research are creating momentum in the drive towards malaria elimination. Marsh commented on the “enormous interest and excitement” in the possibility of eradicating or eliminating malaria. While this growing confidence is to be applauded, the enthusiasm could have adverse consequences for those at risk of the disease if goals are set but not met. The global malaria eradication campaign of the 1950s to 1970s led to disappointment and frustrated hopes; the knock-on effect was inadequate funding for research and targeted malaria reductions. If they do not achieve success on a significant scale, malaria elimination drives could take malaria research and intervention strategies in a similar direction. Noting that “no country has ever eliminated malaria that hadn’t reached a substantial level of social and economic development”, Marsh emphasizes the importance of economic development in determining malaria elimination. He also advises that “corruption in some countries is not the issue it’s made out to be,” suggesting that this potential hurdle may not be such a difficulty to overcome. The number of malaria cases has continued to show marked reductions over the last 15 years or so, but Marsh says that the “big drop preceded the widespread implementation of bed nets”. The widespread use of bed nets has a proven effect in reducing malaria cases, but “coverage still isn’t high enough”. However, he does admit that sustained investment in “doing what works” will likely not result in eliminating this politically and socially complex disease. Marsh emphasizes that “we know what works to the extent that it works but it won’t be enough”. With any occurrence of fever being treated as "malaria" in many malaria endemic countries (analogous to the treatment of common colds as influenza according to Marsh), counterfeit malaria drugs are becoming increasingly common. This international counterfeit market creates “a definite anxiety” for Marsh. Marsh admits that he “used to be much more pessimistic” about the possibility of a viable malaria vaccine. But a likely malaria vaccine is currently undergoing trials, and a vaccine with increased efficacy is becoming more and more feasible. However, Marsh warns that without sustained investment in long-term basic malaria research as well as in capacity for organization and delivery of interventions, we will be led to “regret” this lack of investment “20 years down the line”. The Exchanges at the Frontier discussion with Kevin Marsh will be broadcast on the BBC World Service from 2nd November. Dr Onome Akpogheneta is a freelance consultant writer and researcher based in the UK.

Artemisinin project aims to improve extraction and increase absorption

Since artemisinin combination therapy (ACT) became the first-line treatment for malaria, there have been problems in securing sufficient supplies of the herb, Artemisia annua, from which artemisinin is extracted. Because artemisinin is sensitive to oxidisation and heat, a significant proportion of it is lost during extraction. A further issue is the high dose rate that must be given because, due to its poor solubility, the amount of the drug absorbed into the bloodstream can be as low as 20%. British and Chinese researchers are now addressing both of these problems; they aim to create a version of the drug that retains more of the active ingredient during manufacture and can be taken up more easily by the body. If they are successful it will become possible to treat more people with less artemisinin, and for a lower cost. The project is a collaboration between experts in drug design and delivery at the University of Bradford and scientists from Jilin University and the Shanghai Institute of Materia Medica – where artemisinin was first extracted in the 1960s. The team will use a drug manufacturing process developed at Bradford, called the Super Critical Fluid (SCF) process, which is carried out at relatively low temperatures and is more benign than conventional extraction methods. The research will also look at ways to improve the rate of solution and absorption of artemisinin through the SCF process, by modifying the size and form of the drug particles and possibly incorporating hydrophilic polymer into the drug particles. Absorption studies and chemical analysis will be carried out by the Chinese project partners. Further details are available in a University of Bradford press release.

Profile of WHO-AFRO disease control chief

It's always good to get to know a little about the key figures in policy making on the infectious diseases of poverty. New Vision has interviewed Ugandan Dr David Okello, the director of the Cluster on AIDS, Tuberculosis and Malaria at the World Health Organization's regional office for Africa (WHO-AFRO). Dr Okello's career started at Ngora Hospital in eastern Uganda where he worked as a medical officer. Later he moved to Mulago Referral Hospital, going on to lecture Makerere Medical School for almost 13 years. He has held various roles with WHO over the last ten years. He tells New Vision of his achievements and plans for the future.

Thai-Cambodian efforts to contain resistance to key antimalarial

One of the biggest worries in global efforts to control malaria has been the appearance, along the Cambodia-Thailand border, of drug resistance to artemisinin - the drug that is now the mainstay of malaria treatment. A report from Deutsche Presse-Agentur news agency says that efforts to combat the resistant strain of the malaria parasite are making progress, though more still needs to be done. The report also quotes Dr Charles Delacollette, co-ordinator of the WHO's Mekong Malaria Programme, as saying that the members of the Association of South-East Asian Nations (ASEAN) need to 'be more aggressive' in their anti-malaria efforts. Thailand and Cambodia are receiving support from international agencies (including WHO and the Gates Foundation) to help their efforts to contain and eliminate artemisinin resistance. The main elements of the strategy employed are to: eliminate the drug-tolerant parasites by detecting all malaria cases in target areas and ensuring effective treatment, reduce exposure of the parasites to artemisinin to limit emergence of resistance, and prevent transmission of artemisinin-tolerant malaria parasites through mosquito control and personal protection. It is regarded as a priority to prevent what has been seen previously with resistance to antimalarials - resistant strains have appeared first in Southeast Asia and then spread to other regions, including Africa where the burden from the disease is highest.

Researcher profiled

There is an encouraging trend in parts of the popular media to publish articles that feature the lives, not of rock musicians and movie stars, but of medical researchers. An article from Canada looks at the contributions of Raymond Hui, a principal investigator with the University of Toronto’s Structural Genomics Consortium. Hui started out as a robotics engineer but moved on to genomics, where his research includes diseases such as malaria, tuberculosis and sleeping sickness (human African trypanosomiasis). He explains in the article that he hopes his work on the three-dimensional structure of proteins in disease-causing organisms will lead on to the development of new treatments.

Malaria vaccine trial disappoints

One of the several vaccines for malaria currently under development has performed disappointingly in a trial. Reuter's news agency reports that Dr Stephen Hoffman of Sanaria told a conference, 'Malaria Vaccines for the World' held in Washington DC, that out of 80 volunteers vaccinated with the company's experimental malaria vaccine, only five were protected from infection. A subsequent comment posted on the Reuter's website claims that the number protected was even lower - two. Formal publication of the results of the trial is still awaited. Sanaria is a biotechnology company dedicated to the production of a vaccine protective against P. falciparum malaria. Dr Hoffman also told the meeting that Sanaria has now exhausted the funds provided for its work by the PATH Malaria Vaccine Initiative but that it would be seeking support elsewhere in order to continue its efforts. The front runner in the race to bring an effective malaria vaccine into widespread use remains GlaxoSmithKline's RTS,S. Progress with this vaccine was also discussed at the conference, which according to an AFP report heard that some 12,000 children have already been enrolled in the Phase III trials in Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and Tanzania. The enrollment target is 16,000 children.

Malaria funding only 40% of what is needed

Researchers have looked at the malaria burden faced by 93 countries where the disease is endemic and have gone on to calculate the 'biological need' and 'economic need' to achieve comprehensive control. They concluded that, overall, the present funding available from external sources for malaria control is 60% lower than what is needed [1]. The study dies not, however, allow for funding originating within the disease-endemic countries themselves. The researchers - based in the UK, Switzerland and Kenya - note that funding for malaria control has increased substantially in recent years, particularly in Africa. Nevertheless, it still falls considerably short of the estimated $4.9 billion required each year. The situation varies considerably between countries; 21 countries (12 of them in Africa) now receive adequate donor money but a further 50 do not get enough from the international community. As the researchers point out, there is considerable anxiety that the present global economic problems could lead to a decline in the funding provided for malaria control. Not only would this lead to a resurgence of the disease, they say, but it would also mean that the money so far invested in control efforts ($9.9 million since 2002) will have been wasted. A useful summary of the research is provided in a BBC news story. Reference 1. Snow RW, Okiro EA, Gething PW, Atun R, Hay SI (2010). Equity and adequacy of international donor assistance for global malaria control: an analysis of populations at risk and external funding commitments. Lancet. [Epub ahead of print]. Available online (registration required): http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(10)61340-2

Monitoring insecticide resistance in malarial mosquitoes

A new technique pioneered at Liverpool School of Tropical Medicine (LSTM) is improving the detection and monitoring of insecticide resistance in field populations of an important malaria-carrying mosquito. Researchers at LSTM, led by Dr Charles Wondji have developed a new technique that encourages female Anopheles funestus mosquitoes to lay eggs, which are then reared into adult mosquitoes to provide sufficient numbers to determine levels of insecticide resistance and to characterise the underlying mechanisms. Explaining the significance, John Morgan, who designed the technique, said: “The An. funestus mosquito is difficult to collect and rear from the field and hence published studies of insecticide resistance in this species are limited. This new forced egg laying technique encourages the females to lay eggs which we were then able to rear into viable populations. “This allowed us to study levels of resistance to particular insecticides and in doing so, we have been able to find the first documented resistance to pyrethroid/DDT insecticides in East Africa. This will enable researchers to map the distribution of this resistance and allow [Uganda's] Ministry of Health to modify its vector control programme, thereby increasing its effectiveness and helping to reduce the transmission of malaria.” The research is published in PLoS ONE, where Morgan, Wodji and colleagues have reported high levels of resistance to pyrethroid insecticides in both Mozambique [1] and Uganda [2]. References 1. Cuamba N, Morgan JC, Irving H, Steven A, Wondji CS (2010). High Level of Pyrethroid Resistance in an Anopheles funestus Population of the Chokwe District in Mozambique. PLoS ONE 5(6): e11010. Available online: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0011010. 2. Morgan JC, Irving H, Okedi LM, Steven A, Wondji CS (2010) Pyrethroid Resistance in an Anopheles funestus Population from Uganda. PLoS ONE 5(7): e11872. Available online: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0011872.

Malaria: it started with a gorilla

Many human diseases originated when the pathogen responsible "jumped" from another species. It has been suggested that malaria may be one such disease and that the most likely species from which it originated was the chimpanzee. New research, however, provides evidence that the source was in fact a gorilla. In a study [1] - conducted by researchers from several institutions in the US, Democratic Republic of Congo, and UK - malaria parasites were isolated from hundreds of primate faecal specimens, originally collected for studies on the origins of HIV. From their analysis, the researchers estimated that 32-48% of wild chimpanzees and western gorillas are infected with malaria parasites. Genetic analysis found that none of the chimpanzee malaria parasites were closely related to the most important human malaria parasite, Plasmodium falciparum, but one subtype of gorilla parasite was nearly identical. The genetic lineage of the parasite suggests that it evolved after making a single jump from gorilla to human. Dr Crickette Sanz, assistant professor of anthropology in Arts & Sciences at Washington University, St. Louis, and a co-principal investigator in the study said in a press release that: “Chimpanzees and gorillas in Central Africa are subject to many threats, including logging and poaching. Not only do we risk losing our closest living ape relatives, but this also greatly compromises our ability to study the origins of such pathogens as P. falciparum.” She also noted that, "This research emphasizes the crucial need to continue long-term research on the health and behaviour of wild apes in the remote forests of the Congo Basin". Another member of the research team, Beatrice Hahn of the University of Alabama, Birmingham, said: "When you take all the sequences that have been published for all human Plasmodium falciparum worldwide, and when you put it in this family tree analysis, you see that they all have one single common ancestor. That tells you that this was the result of a single cross-species transmission event". It must also be hoped that this new knowledge will be of use in the development of improved programmes to control and ultimately eliminate malaria. Reference Liu W, Li Y, Learn GH, Rudicell RS, Robertson JD, Keele BF, Ndjango JB, Sanz CM, Morgan DB, Locatelli S, Gonder MK, Kranzusch PJ, Walsh PD, Delaporte E, Mpoudi-Ngole E, Georgiev AV, Muller MN, Shaw GM, Peeters M, Sharp PM, Rayner JC, Hahn BH (2010). Origin of the human malaria parasite Plasmodium falciparum in gorillas. Nature; 467(7314):420-425.

Kenya investigates whether resistance has developed to new antimalarials

A report in Kenya's Daily Nation says that the government is conducting research to establish whether resistance to the current first-line treatment for malaria (artemisinin combination therapies [ACTs]) has appeared in the country. Strains of the malaria parasite resistant to artemisinin have already been found in Asia (in the Cambodia-Thailand border region) and experience with previous generations of antimalarials has shown that, once there is resistance in Asia, it spreads to Africa. Researchers from the Division of Malaria Control and the Kenya Medical Research Institute (KEMRI) are already at work in Nyando and Siaya districts, where they will assess the effectiveness of two ACTs - dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL). Both drugs are already used across Kenya. ACTs are a vital part of treatment and control programmes. The results of this research will be of interest, not just in Kenya, but across Africa.

Integrated management of malaria and pneumonia: a Zambian success story

Integrating the treatment of childhood infections has long been seen as desirable but has proved hard to implement in practice. New research carried out in Zambia [1] gives cause for optimism. Community health workers were able to provide integrated management of pneumonia and malaria, safely and effectively, to communities by dispensing amoxicillin to children with non-severe pneumonia and artemether-lumefantrine to children with malaria. A key part of the process was the use of rapid diagnostic tests. In the study, 3125 children with fever and/or fast breathing were managed by community health workers over a 12-month period. Community health workers were matched and randomly allocated to the intervention arm (in which community health workers performed rapid diagnostic tests, treated rapid diagnostic test-positive children with the anti-malarial drug, artemether-lumefantrine, and treated children with non-severe pneumonia with amoxicillin) and the control arm (in which community health workers did not perform rapid diagnostic tests, treated all febrile children with artemether-lumefantrine and referred those with signs of pneumonia to the health facility, as per the Zambian Ministry of Health policy). A significant proportion of children managed in the intervention arm [68.2% (247/362)] received appropriately-timed antibiotic treatment for non-severe pneumonia compared with 13.3% (22/203) in the control arm. There was also a significant decrease in inappropriate use of antimalarials when treatment was based on the results of rapid diagnostic tests. In the intervention group 27.5% (265/963) of children with fever received malaria treatment compared with 99.1% (2066/2084) of children in the control group. The intervention, therefore, achieved a significant increase in the proportion of appropriately-timed antibiotic treatment for non-severe pneumonia and a significant decrease in inappropriate use of antimalarials. The authors conclude: "The capacity of [community health workers] to use [rapid diagnostic tests], artemether-lumefantrine and amoxicillin to manage both malaria and pneumonia at the community level is promising and has the potential to reduce over usage of artemether-lumefantrine as well as to provide early and appropriate treatment to children with non-severe pneumonia". Reference 1. Yeboah-Antwi K, Pilingana P, Macleod WB, Semrau K, Siazeele K, et al. (2010) Community Case Management of Fever Due to Malaria and Pneumonia in Children Under Five in Zambia: A Cluster Randomized Controlled Trial. PLoS Med 7(9): e1000340. doi:10.1371/journal.pmed.1000340. Available online: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000340

Malaria vaccine conference reviews progress

The PATH Malaria Vaccine Initiative (MVI) has this week been holding a conference in Washington DC, which it says is intended to "to showcase the scientific push for 'next generation' products". Topics discussed included:

Plasmodium vivax

More details can be found in an MVI press release. The optimistic mood of researchers at the conference is also highlighted in a press agency report from AFP.

Malaria preventive therapy withdrawn in Kenya's highlands

One of the most encouraging new tools in efforts to control (and eventually eliminate) malaria is intermittent preventive therapy (IPT) for children and pregnant women. However, malaria control efforts should be tailored to local situations, and the health authorities in Kenya have concluded that IPT is not been of any value in areas of low malaria incidence, such as Nairobi and the highlands. New treatment guidelines just released say that IPT should no longer be given in these parts of the country, but should be continued in Nyanza, Western and Coast provinces, where transmission rates are higher. Other features of the new guidelines include, for the first time, that anyone being treated for malaria must first have been tested to confirm infection. Further information is available in a Daily Nation report.

Becoming a malaria researcher

A California online media publication (pressdemocrat.com) has a section called "DigitaleStories", featuring people with an interesting story to tell. This kind of website would not be expected to feature the infectious diseases of poverty, so it is a great pleasure to find an interview with Amy Bei, a doctoral student in the Department of Immunology and Infectious Diseases at the Harvard School of Public Health. She describes how she became involved first with schistosomiasis and then with malaria, and her experiences in the field in Tanzania. It all makes for interesting reading and hopefully will encourage other young researchers to consider a career focusing on global health priorities.

Warning on dangerous "miracle" cure for malaria

It is not unusual in many developing countries for a local healer to offer, as a treatment for a common condition, a medicine that turns out to have toxic effects. It is a more serious state of affairs when a dangerous substance is promoted for its alleged curative powers on an international basis. A product classified by the US Food and Drug Administration as a powerful industrial bleach has apparently been given to many Africans as a malaria cure. American Jim Humble says that his "Miracle Mineral Solution" (MMS) can successfully treat cancer, AIDS, malaria and most other health problems. He has been actively promoting its use in Africa, where up to 100,000 people (most of them in Kenya and Uganda) may have taken the toxic sodium-chlorite-based treatment. In Kenya, according to the Daily Nation, MMS was first introduced at St James Ematsayi Clinic in Kakamega where Mr Humble claims to have treated 1,000 cases. As Humble's treatment is now banned in the US and Canada, he may well be planning to expand his activities in developing nations. It is important that the health community in these countries should be alerted to this threat. Further information on MMS is available in a report from the Guardian (UK).

UN launches new strategy for health of women and children

A UN Summit intended to boost progress towards meeting the eight Millennium Development Goals has focused on the health of mothers and their children. The meeting saw the launch of the Global Strategy for Women's and Children's Health. With pledges of more than $40 billion over the next five years, the Global Strategy will seek to save the lives of more than 16 million women and children. Amongst its objectives are preventing 33 million unwanted pregnancies, protecting 120 millions of children from pneumonia and 88 million children from stunting, advancing the control of infections diseases such as malaria, and ensuring access for women and children to quality facilities and skilled health workers. Further news on the launch of the new strategy is available on the website of the Global Strategy for Women's and Children's Health. The G8, the world's richest countries, agreed upon the MDGs in 2000. The deadline set for their achievement was 2015. Progress on the fifth goal – a pledge to cut the numbers of women dying in pregnancy and childbirth by three-quarters – is the furthest behind.

Nigerians "losing confidence in antimalarials"

Many Nigerians claim that the malaria drugs they have been prescribed have failed to cure them of the disease. This is said to be the case even when recommended treatments (artemisinin combination therapies [ACTs]) have been given. Dr Babajide Coker, Coordinator of the National Malaria Control Programme (NMCP), has said that public concerns over this issue will be taken seriously and that 14 sentinel sites have been established across Nigeria to monitor the efficacy of the drugs currently being used. The problem may well be attributable to counterfeit drugs; it is well known that many of the antimalarials available on the Nigerian market (including ACTs) are fake or substandard. However, the NMCP must be applauded for addressing what seems to be a growing belief in the country that even the recommended treatments for malaria are no longer effective. Dr Coker is reported to have stated that he can vouch for the effectiveness of recommended antimalarials but that public concerns "will not be treated with kid gloves". Dr Coker made his comments at a workshop at which concerns were also raised as to the lack of information provided to the public on the correct use of insecticide-treated mosquito nets. Further details area available in an allAfrica.com report.

The European dimension

European support for research focused on the infectious diseases of poverty has come under the spotlight in some recent TropIKA.net articles. The position adopted by the European Union on research funding has often been criticized, as we discuss in the light of the latest funding call published in July this year [1]. But the EU’s entire approach to global health research has been undergoing review in recent months and changes are on the way; these will include the appointment of the EU’s first global health coordinator [2]. Meanwhile, the European Commission has been conducting a consultation on the future of the European and Developing Countries Clinical Trials Partnership and a preliminary analysis of the comments received has now been published [3]. Whilst its member states vary considerably in their level of commitment towards global health, the EU itself has the potential to transform the research landscape and the reforms may now make this possible. One of our aims at TropIKA.net is to provide a forum for debate. We have lately featured the views of some guest contributors: the organization Riders for Health [4] argues that transport is crucial for strengthening health systems and Lenias Hwenda [5], a Zimbabwean currently working in Switzerland, claims that a new study concluding that infectious diseases probably cause low intelligence is based on flawed deductive reasoning. We continue to interview key individuals actively involved in research. The organization Policy Cures has recently been launched and we have an interview with its Director of Research, Dr Javier Guzman [6]. TropIKA.net commentaries deal with a wide range of new findings from "basic" studies to operational research. Recent examples include the discovery of genetic differences between people who develop active TB and those in whom the infection remains latent [7], and a study of the obstacles encountered in the implementation of a lymphatic filariasis programme in a remote part of Indonesia [8]. Most of our commentaries on the latest research are written by the TropIKA.net team but we welcome guest contributions. We also have news of a forthcoming initiative – the TropIKA.net Journals Clubs [9]. Our blog [10] features short items highlighting a range of new developments that we believe will be of interest to anyone involved in research or control activities relating to the infectious diseases of poverty. Malaria [11,12], Chagas disease [13], leishmaniasis [14] and onchocerciasis [15] are amongst the conditions that have been dealt with in the blog over the last few weeks. We have also reported progress in the rapidly growing area known as "mHealth": mobile phones are now being used to assist in surveillance programmes on zoonotic diseases [16] and to provide a means of determining whether a drug is genuine or a fake [17]. Paul Chinnock Editor, TropIKA.net

Preventing malaria pays off

Days before a major MDG Review Summit in New York, a new report from Tulane University, Johns Hopkins University, the World Health Organization and PATH confirms that investment in malaria control is saving lives and that increased funding will contribute significantly to achieving the Millennium Development Goals for health. Saving Lives with Malaria Control: Counting Down to the Millennium Development Goals, published by the Roll Back Malaria Partnership(RBM) reports that close to three quarters of a million children in 34 African countries are estimated to have been saved in the past 10 years through the use of insecticide-treated bed nets, indoor residual spraying and preventive treatment of malaria during pregnancy. According to the report, an estimated three million additional lives could be saved by 2015 with continued increases in investment in tackling the disease. The Lives Saved Tool (LiST), developed to be used across major childhood diseases, is being applied to malaria prevention throughout Africa. The report provides the first assessment of lives saved based on the level of coverage achieved with currently available malaria prevention tools. However, it is likely to be an underestimate, given that data on lives saved from diagnosis and treatment is not included. "This is a vital tool which can help strengthen the country planning and guide us all as we focus on 2015," said Awa Coll Seck, RBM Partnership Executive Director. "Robert Newman, director of the Global Malaria Programme at the WHO echoed that, arguing that the report "demonstrates the critical importance of malaria control efforts to reaching the health-related MDGs by 2015." Without continued investment in malaria, he added, "child survival is unlikely to be reached in Africa."

Ivermectin as insecticide?

Since its introduction more than 25 years ago, ivermectin has proved to be one of the most successful therapeutic drugs in veterinary medicine and the basis for one of the most successful public health programs of the past century--Merck & Co., Inc's Mectizan Donation Program. Currently in use in two global disease elimination campaigns--the Onchocerciasis Elimination Programme of the Americas (OEPA) and the Global Programme to Eliminate Lymphatic Filariasis (GPELF)--the microfilaricide is administered through sustainable community-directed distribution programs first developed by TDR.(1) In addition to ivermectin's potent anti-parasitic properties, however, the drug has also demonstrated significant activity against blood-sucking insects, including increased mortality and reduced fertility of Tsetse flies, triatomine bugs, ticks, sandflies and adult mosquitoes. (2) These findings have led some researchers to suggest that ivermectin could serve as an important tool for the control of arthropod vector-borne diseases, and were the impetus for a recent study (3) of the drug's effect on Anopheles gambiae, the major vector of malaria in Africa. The study, a partially-blinded, randomized controlled trial by researchers at the London School of Hygiene and Tropical Medicine (LSHTM), attempted to assess the impact of ivermectin on mosquitos fed on human blood. Volunteers were randomly assigned to receive a single oral dose of 200 ug/kg of ivermectin or no dose at all, and mosquitos were fed by both groups twice over a 12 day period. The results were promising: "At day 9 after feeding, the earliest time at which a mosquito becomes infectious, the mortality in the ivermectin group was significantly higher than in the control group (96% vs 73%)," write the authors. Moreover, the mean duration of survival of the mosquitos in the ivermectin group was 2.38 days (95% confidence interval [CI], 1.52--3.24 days) compared with 5.52 days for the control group (95% CI, 4.65--6.40 days). Still, the drug's short duration of activity limits its usefulness in a number of situations. (When the blood meal was taken 14 days after treatment, the difference in mortality between treatment and control groups was not apparent). The authors argue that one situation in which a systemic insecticide like ivermectin might be appropriate is in combination with antimalarials in areas such as the Thai-Cambodian border, where signs of resistance to a major drug class have been observed. References 1. Omura S, Crump A. (2004). The life and times of ivermectin--a success story. Nat Rev Microbiol. 2:984-989. 2.Tesh RB, Guzman H. (1990). Mortality and infertility in adult mosquitoes after the ingestion of blood containing ivermectin. Am J Trop Med Hyg. 43:229-233. 3. Chaccour C, Lines J, Whitty C. (2010). Effect of ivermectin on Anopheles gambiae mosquitos fed on humans: the potential of oral insecticides in malaria control. Journal of Infectious Diseases. 202(1):113-116.

Uganda is buying the wrong drugs

The performance of national medical supply agencies should be monitored. Uganda's Auditor General has produced a report on the country's National Medical Stores (NMS) that has some disturbing findings. NMS has, for example, often run short of malaria drugs but, within the last year, has purchased supplies of the anti-ulcer drug Ranitidine sufficient to last 27 years. (This drug has a shelf-life of 2-4 years.) The report, discussed in detail in a New Vision article, concluded that wastage of expired drugs at NMS is at an unacceptable level, while poor procurement policies result in "perennial stock-outs" of the most needed treatments, especially antimalarias. How can drug supplies in the world's poorest countries be better managed? Clearly, it is an area where research is needed.

Is your drug genuine? Phone to find out

A large proportion of the drugs available in developing countries are fake or substandard. A report from Associated Press describes the launch in Nigeria of a system that will allow patients with mobile phones to find out whether a drug is genuine. "mPedigree" assigns a unique code to genuine malaria medicines, printed on the back of medicine blister packs under a sheet that is scratched off like a lottery ticket. Customers send a text message to a central hot line with the code and get an "OK" response telling them if the drug is registered. The Nigerian government has adopted the system for antimalarials but intends extending its use to other drugs. mPedigree is another example of the use of mHealth (mobile phones for health), a topic that has often been discussed in articles in: TropIKA.net and the TropIKA.net blog

Accessing malaria articles in Elsevier journals

Many key research findings on malaria appear in the journals of leading publisher Elsevier. These journals include the Lancet, Lancet Infectious Diseases, Transactions of the Royal Society of Tropical Medicine and Hygiene, and the International Journal for Parasitology. Elsevier has now launched a new knowledge hub, www.malarianexus.com, where the latest malaria research papers in its journals will be highlighted. The new website will also publish feature articles and interviews with malaria researchers. The feature articles and interviews will be freely accessible for three months after publication. Unfortunately, however, free access to other research articles on malaria in Elsevier journals is not available through www.malarianexus.com. Those wishing to read these articles will have to take out subscriptions to the Elsevier journals in which they appear. (The abstracts are of course already available on the journal websites and on PubMed.) Nevertheless, visitors to www.malarianexus.com may find it convenient to have new papers in Elsevier journals highlighted in one place, and the features and interviews are likely to be of value. (Currently available is an intereview with John Beier of the Abess Center, Professor in the Department of Epidemiology and Public Health (DEPH) at the Miller School of Medicine, and Co-Director of the Center for Global Health Sciences in DEPH.) Registration (free) is required to use www.malaria.nexus.com.

Malaria Elimination Initiative seeks new personnel

Allison Phillips - Program Manager of the Malaria Elimination Initiative - writes to TropIKA.net... The Global Health Group at the University of California, San Francisco is seeking candidates for two new positions:

Lead

here.

Economist

here

Both appointees will be a member of the academic staff or adjunct faculty of the University of California, San Francisco. The Global Health Group (GHG) is an “Action Tank” led by Sir Richard Feachem, formerly the founding executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria, that works across the spectrum from analysis, through policy formulation and consensus building, to catalyze implementation in collaborating low- and middle-income countries. The Malaria Elimination Initiative (MEI) is one of three initiatives at the GHG. The MEI works with a wide range of partners to gather, analyze and disseminate evidence on malaria elimination, to inform strategic decision-making. The MEI also formed and convenes the Malaria Elimination Group (MEG).

Individuals count

Efforts to combat the infectious diseases of poverty continue to expand and TropIKA.net reports frequently on the launch of new initiatives, the activities of institutions, the importance of empowering communities, and the need to create networks. It is all too easy to forget that progress, nevertheless, requires contributions from individuals. Few have contributed as much as Mariano Levin, best known for his work on Chagas disease, who died earlier this year. A TropIKA.net Profile [1] reviews his life and his legacy. We have also over the last few weeks reported on a number of new initiatives. These include the wonderfully named “This Wormy World” – an open-access information resource on the distribution of soil-transmitted helminths and schistosomiasis [2]. Also launched is a new organization that seeks to accelerate the development of new pharmaceutical products for the diseases of the developing world – formerly part of the George Institute and known for its influential G-FINDER survey, Policy Cures [3] has progressed to become an independent entity. The UK Department for International Development (DFID) has long been a major player in malaria research and control programmes. It now intends to develop a new “malaria business plan” [4] and has begun a public consultation as part of this process. In the USA, the announcement of the start of a dengue vaccine trial [5] comes at the same time as news of plans to start trials with a vaccine for leprosy [6]. Vaccines, drugs and other new tools are of course much needed, but so often things go wrong when it comes to delivering them to where they are most required. Praziquantel is a cheap and effective treatment for schistosomiasis, but less than 10% of school-aged children at risk are reached by disease control programmes [7]. But disease control programmes can be made to work. The global eradication of dracunculiasis (guinea worm) is drawing closer with further progress reported from West Africa [8]. Only in the southern Sudan is the relative lack of progress a cause for concern. Research TropIKA.net continues to highlight new research findings that are of particular interest. Recent examples include epidemiological research that has made possible the completion of a global map showing populations at risk of vivax malaria [9], molecular biological findings that bring new understanding of the metabolism of the malaria parasite [10], and studies in Australia that suggest that wild mammals may play a part in the transmission of Buruli ulcer [11]. But such research often seems a long way from the delivery of effective care. How interventions are brought to the individuals who need them also requires study. Much neglected, for example, is the role played by the retail outlets (often unlicensed) through which the majority of Africans obtain their medicines. A new systematic review [12] finds that little study has been made of efforts to improve the service such shops can offer. Nevertheless, there is some encouraging evidence that training programmes do help. Paul Chinnock Editor, TropIKA.net

Malaria parasite eschews the Krebs cycle

Anyone who studies the life sciences beyond a certain level is required to learn the details of the metabolic pathway known as the Krebs cycle. Named after its discoverer Hans Krebs and also called the tricarboxylic acid (TCA) cycle, the process is central to metabolism and provides most of the energy used by the vast majority of living things ...but not the malaria parasite. Recently published research by US molecular biologists [1] has confirmed earlier suspicions that Plasmodium falciparum meets its energy needs by a very different process. An article in US News features an interview with one of the research team, Kellen Olszewski, who explains that the breakdown of sugar by the malaria parasite is completely disconnected from the Krebs cycle; it is instead fed by the amino acids glutamine and glutamate and is a branched rather than a cyclical pathway: "The parasite has basically taken the standard textbook circular cycle and broken it in half, running one half in the normal direction and the other backwards. This turns the textbook model on its head". Nothing similar has so far been found in any other parasite. The research represents a major step forward in understanding of energy and biosynthetic processes in Plasmodium parasites. This new knowledge may in time make possible the identification of potential drug targets, leading to the development of new malaria treatments. Reference 1. Olszewski KL, Mather MW, Morrisey JM, Garcia BA, Vaidya AB, Rabinowitz JD, Llinás M (2010). Branched tricarboxylic acid metabolism in Plasmodium falciparum. Nature; 466(7307):774-778.

Malaria more common in men than women, in Mumbai study

Protecting women against malaria is regarded as a priority. Pregnant women are more vulnerable to the disease, which can also harm their unborn children. However, research in Mumbai, India apparently suggests that men there are more likely than women to have malaria. The records were analysed of 30,000 patients presenting to hospitals with malaria-like symptoms. [Men were in the majority, for which there could be several possible explanations.] It was found that 12% of men but only 6% of women were infected. Dr Shobhona Sharma, one of the researchers, told the Hindustan Times that: "In children, both sexes are affected by the parasite in the same manner, but the moment one goes to the pubertal age group, men tend to show and experience the symptoms more than women. We think the hormones testosterone and oestrogen may be influencing the way immune cells react when exposed to the parasite". The research team's work has yet to be formally published but the same group, using mice, have reported a gender difference in response to malaria infection [1]. Reference 1. Basant A, Rege M, Sharma S, Sonawat HM (2010). Alterations in urine, serum and brain metabolomic profiles exhibit sexual dimorphism during malaria disease progression. Malar J;9:110.

New boost for patent pool for infectious diseases of poverty

From the Medicines for Malaria Venture (MMV)...

MMV has become the first product development partnership (PDP) to contribute intellectual property to the Pool for Open Innovation Against Neglected Tropical Diseases. The Pool was established in February 2009 by GlaxoSmithKline (GSK) and Alnylam Pharmaceuticals and has since been joined by Massachusetts Institute of Technology (MIT). It seeks to stimulate innovative and efficient drug discovery and development by providing public access to intellectual property (IP) and scientific know-how for neglected tropical disease research. The Pool is administered by BIO Ventures for Global Health (BVGH). As contributor to the Pool, MMV will make available its IP, technology and expertise in the research and development (R&D) of antimalarial drugs to researchers developing medicines for neglected diseases. “MMV is proud to be a contributor to the Pool for Open Innovation Against Neglected Tropical Diseases and to join a group of like-minded organizations dedicated to researching new health tools for neglected diseases. Our contribution to the Pool is in line with MMV’s commitment to allow any patents and technologies resulting from our R&D work, developing new, effective and affordable medicines for malaria, to be used for public good. Researchers will now have access to MMV’s know-how, free of charge, to discover and develop medicines for neglected diseases that are an enormous burden on the poorer patients in the developing world,” said Professor Patrick Nef, EVP Business Development of MMV.

TropIKA.net has reported extensively on the development of the Pool. See our articles and blogs: Open source: the way forward in the search for new treatments for the infectious diseases of poverty? Patent pool for infectious disease research: new developments Drug giant puts details of compounds that could treat malaria into the public domain Pharma giant hands over potential new antimalarial to not-for-profit group Drug giant will slash prices and share patent rights on potential drugs for neglected diseases South Africa will make use of patent pool for infectious diseases of poverty More from Witty: interview with GSK chief "Patent pools" for drugs for neglected infections: is industry doing enough?

Combining antibiotics with a "natural syringe" to fight malaria

German scientists at the Max Planck Institute for Infection Biology in Berlin are reported to be developing a new technique to give immunity against malaria. Kai Matuschewski and his research team used mosquitoes to infect test mice with the sporozoite stage of the malaria parasite. At the same time, they gave the mice antibiotics. The antibiotics prevented the next stage of the parasite (the merozoites) from infecting red blood cells, and the mice showed no malaria symptoms. Nevertheless, exposure to the parasite led the mice to develop long-term immunity. The researchers say malarial mosquitoes act as a "natural syringe" that delivers a vaccine (the sporozoites). The antibiotics used were clindamycin and azithromycin - both are generic, cheap and readily available. However, the danger of the development of drug resistance would be a major concern. Dr Matuschewski says this could be minimized by administering the drug to people at risk of malaria once per year, at the start of the rainy season. He hopes hope that clinical trials could start in sub-Saharan Africa, as early as mid-2011. Further details available from Deutsche Welle.

DFID consults to develop a "malaria business plan" for Africa

The UK's Department for International Development (DFID) says that it intends to put the fight against malaria at the forefront of its aid efforts in Africa. International Development Secretary Andrew Mitchell has announced that a comprehensive "malaria business plan" will be developed. The plan will include a specific focus on some of the high-burden countries that account for 98% of all malarial deaths. The announcement notes that there is evidence from across Africa that, whilst many of those with malaria do not get effective drugs, a large proportion of anti-malarial treatments are given to people who do not actually have malaria. In addition to increasing the availability and use of bed-nets and effective antimalarial drugs, DFID says it will help improve the diagnosis of malaria and ensure that the most effective interventions reach the most vulnerable people. It will also also support measures to reduce the spread of resistance to drugs and to the insecticides used to make bed-nets effective. To help develop the malaria business plan, DFID has commenced a public consultation. Details of the consultation may be accessed and comments submitted online: http://consultation.dfid.gov.uk/malaria2010/.

Swiss collaboration on vaccine development

The Swiss Tropical and Public Health Institute is to collaborate with a biopharmaceutical company in its efforts to develop vaccines for malaria and Buruli ulcer. The company, Telormedix, was launched in 2007 with its main focus the use targeted immunity to treat cancer and other diseases. A Telormedix adjuvant, TMX-201, intended to act as an activator of the innate immune system and enhance the process of immunisation, will be compared with a standard adjuvant in a vaccination trial with two prototype antigens, one from Plasmodium falciparum (malaria) and one from Mycobacterium ulcerans (Buruli ulcer). This pilot study will be performed under the direction of Professor Gerd Pluschke, head of the Department of Parasitology and Infection Biology at the institute. Further details on BusinessWire.

Is progress being made against artemisinin resistance?

A joint press release from WHO and the Cambodian health ministry, has claimed that "significant gains" have been achieved by efforts to contain the spread of strains of the malaria parasite that are resistant to the drug artemisinin. The press release does not, however, provide any information to explain how this conclusion has been reached. Should the claim be supported by evidence - which presumably will be published later - the news will be welcome indeed. Artemisinin is now the mainstay of malaria treatment, older drugs now being ineffective. The appearance of resistance to the drug in the Thailand-Cambodia region, which was confirmed early last year, has been the cause of much concern, with fears that resistant strains could spread to other malaria-endemic countries. A project, largely funded by the Gates Foundation, has been attempting to screen the entire population in a pilot area and to provide prompt and effective treatment to all individuals testing positive for the malaria parasite.

US health institute funds ten global malaria research centres

The US National Institute of Allergy and Infectious Diseases (NIAID) will be providing $14 million as first-year funding to ten new research centres, in order to support their work on malaria. The awards, renewable for six years, are intended to establish international centres of excellence for malaria research in regions where malaria is endemic, including parts of Africa, Asia, the Pacific islands and Latin America. Further details here.

Mouse study finds clindamycin-plus-azithromycin protects against malaria

Kenyan and German scientists have shown, in laboratory mice, that a combination of two cheap and readily available antibiotics (clindamycin and azithromycin) gives protection against malaria. They believe that it may be possible to use the combination as a preventive treatment in endemic communities, given periodically during peak transmission seasons. More details may be found in a Voice of America article.

NTD news from Colombia

Nora Cardona-Castro of the Instituto Colombiano de Medicina Tropical - Universidad CES has written to us about the work of the Institute.

The Colombian Institute of Tropical Medicine "Antonio Roldan Betancourt" ICMT-CES is a center of excellence in research, nonprofit, described by COLCIENCIAS full exaltation granted by that organization: Group A1 "Institution of Excellence in research." It was founded in 1989 as a Joint Participation Corporation for purposes of public and social interest. Currently the Institute has an operating headquarters in the CES University facilities in the town of Sabaneta and another office located in Apartado - Antioquia. The ICMT is managed by the University of Medellín CES, an institution renowned for the quality of its academic programs and unconditional support to the development of research and science, as well as the provision of services, consulting and advisory services in the Colombian health sector and Latin America. ICMT-CES Mission Working continuously for the development of science, through research and academic training of health professionals, with the aim to contribute actively in improving the health of the citizens. Our Institute has international recognition, thanks to the work associated with other research institutions and the many publications of scientific contribution. ICMT-CES focuses its research activities in all areas of Tropical Medicine, based on epidemiology and immunology of infectious diseases, supported by the most advanced techniques of molecular biology for diagnosis. They stand out for their development research in progress: leishmaniasis, Chagas disease, intestinal parasites, salmonellosis, leprosy, tuberculosis, malaria, cysticercosis, dengue, leptospirosis, diagnostic methods, medical entomology and brucellosis.

Duke Global Health Institute to conduct implementation research for malaria control

The Duke Global Health Institute, USA, has received a $2.2-million, 4-year grant from the National Institutes of Health (NIH) to support research by a Duke University-led team to promote sustainable strategies to curb the spread of malaria and protect human and environmental health in endemic areas. According to principal investigator Randall A. Kramer, professor of environmental economics at Duke's Nicholas School of the Environment at the DGHI, the team will conduct experiments in 24 villages in the Mvomero district of Tanzania to assess the effectiveness of different intervention strategies individually and in combination. Using the findings from these studies, the Duke team will refine a new tool used to improve the effectiveness and safety of malaria control strategies in different settings worldwide. Designed by Duke researchers in 2007, the Malaria Decision Analysis Support Tool (MDAST) was developed to address the controversial re-introduction of DDT in several East African countries by assessing the economic, environmental and human health risks with alternative strategies for managing malaria (1). In the Tanzania studies, villages will be randomly assigned to receive one of four disease-control strategies: no intervention; treatment with mosquito-larvicides; rapid diagnostic testing for malaria by health workers; or both larviciding and rapid diagnostic testing. "The central objective is to improve malaria control through an implementation science approach that integrates health delivery and decision support modelling to promote joint optimization of vector control and disease management strategies," says Kramer. Marie Lynn Miranda, associate professor of environmental sciences and policy and director of the Children's Environmental Health initiative at the Nicholas School, is Kramer's co-principal investigator on the new grant. Their team includes collaborators from Duke University, the University of Pretoria in South Africa, and the National Institute for Medical Research in Tanzania. References 1. Beerbohm, E. A pilot expert elicitation to assess the risks of malaria vector control strategies in East Africa. Unpublished.

Rethinking priorities

Developments reported on TropIKA.net within the last few days have challenged some common assumptions made about the infectious diseases of poverty…

most of the really poor people in the world live in Africa; most fevers in Africa are caused by malaria; persistent brain damage is an inevitable consequence of cerebral malaria; we know (roughly) the prevalence of TB in countries like South Africa; childhood TB is not a priority area; pneumonia and diarrhoea are not neglected diseases; and innovations in medical research always happen in the North, not in disease-endemic countries themselves… Whether these recent developments represent good news or bad, they call into question the ordering of many of the current priorities for research, policy and public health practice. Researchers at Oxford University have applied a new “multidimensional poverty index”, to conclude that there are more poor people in eight of India’s states than in the 26 countries of sub-Saharan Africa combined [1]. Not everyone will agree with this analysis, but the infectious disease burden of India’s poor surely deserves to be accorded a higher priority. It has for some years been believed that an African child with fever is most likely to have malaria. As confirmatory diagnostic tests are usually unavailable on the frontline of care, the practice of “presumptive” diagnosis and treatment is therefore recommended. However, a mathematical modelling study [2] has concluded that most fevers are not malaria. In some parts of Africa, 80% of children attending public clinics with fever are probably suffering from some other infection. The findings provide strong support for the new rapid diagnostic tests to be made available at all health facilities in Africa. One of the most serious consequences of malaria is the lasting cognitive damage suffered by children who develop cerebral malaria. A very “early” study [3] with laboratory mice suggests that adding antioxidants to standard malaria treatment may help prevent this. (By coincidence, this research has been published within a few days of an analysis [4] appearing to show that a high prevalence of parasitic infections holds back rises in the average IQ in disease-endemic countries.) A post-mortem study [5] in a South African hospital produced findings that are truly shocking; half of the young adults who died in this hospital were culture-positive for TB and one case in six involved a drug-resistant strain of M. tuberculosis. The country is known to have a high prevalence of tuberculosis and of drug resistance but the situation may be worse than previously believed. TB programmes usually focus on adults. However, in a recent article [6] Indian and Indonesian specialists argue convincingly that this has led to a neglect of paediatric TB. Once again the priority list has been challenged. The establishment of the Millennium Development Goals has had a major influence on policies and priorities. The latest annual report [7] on progress made towards the MDGs makes interesting reading; there have been both encouraging achievements and some disappointments. However, the report is unequivocal on one matter: “The need to refocus attention on pneumonia and diarrhoea – two of the three leading killers of children – is urgent”. Acute respiratory infections and diarrhoeal disease were at one time high on the priority list and it is unclear why they have steadily slid downwards. Now is the time to reverse that trend. The latest of our popular ‘Profiles’ series of articles on TropIKA.net [8] highlights the achievements of BIOTEC, a research centre created by the Thai government to generate biotechnology innovations. The innovatory research programme conducted at BIOTEC, which has included the development of a new malaria drug that will soon be entering clinical trials, challenges the notion that, while innovations may be evaluated in the South, the original breakthroughs will always take place in the better-resourced research environments of the North. Also on TropIKA.net... Other examples of progress towards new treatments have been reported on TropIKA.net lately. Merck & Co is investigating the potential use of one its existing drugs as a treatment for Chagas disease [9] and an agreement [10] between two non-profit groups will see potential new TB drugs tested also for their possible use against neglected conditions including Chagas, African trypanosomiasis and leishmaniasis. There has been good news on lymphatic filariasis (LF). It has been calculated that, in its first eight years, the Global Programme to Eliminate Lymphatic Filariasis has brought benefits worth $21.8 billion to individuals, and savings of $2.2 billion to the health systems of endemic countries [11]. Many national LF efforts have experienced difficulties, including the reluctance of many people at risk of infection to comply with mass drug administration programmes. A study from India [12] has shown that community education can improve compliance rates, particularly if this education includes advice on self-care of afflicted limbs for those already suffering from the distressing symptoms of this condition. The study has neatly illustrated the importance of considering not only long-term public health considerations but also the needs of individuals. Paul Chinnock Editor, TropIKA.net

GM mosquito is 'malaria-proof'

The control of malaria through the release of genetically modified (GM) mosquitoes is receiving increasing from researchers. US scientists report that they have created a mosquito that is 'malaria-proof'. Release of these insects, and the displacement of normal mosquitoes, could be used to block the transmission of malaria. The researchers introduced a gene that affected the insect's gut in such a way that the malaria parasite could not develop there. They reduced the number of infected mosquitoes by 60–99%. They report their work, in which they used the mosquito Anopheles stephensi, in PLoS Pathogens [1]. The study is discussed in BBC News, where researcher Professor Michael Riehle of the University of Arizona explains that, while the ultimate goal is to introduce malaria-resistant mosquitoes into the environment: "Before we do this, we have to somehow give the mosquitoes a competitive advantage over the disease-carrying insects". The introduction of the gene into the main mosquito species responsible for malaria transmission (such as Anopheles gambiae) will also be necessary. There is therefore some way to go before GM mosquitoes are used in control programmes. Nevertheless, it is currently an exciting area of research. Reference 1. Corby-Harris V, Drexler A, Watkins de Jong L, Antonova Y, Pakpour N, et al. (2010) Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes. PLoS Pathog 6(7). Accessible online: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001003.

The poor: where are they?

It is the world's poorest people who face the biggest infectious disease burden and who should, therefore, attract most attention in disease control efforts. But who are the world's poorest people and where do they live? The focus is generally upon Africa. For example, in the best-selling book The Bottom Billion, it was argued that the countries in which the poorest one billion people live are almost all in Africa. New research suggests, however, that a large proportion of the world's ultra-poor are in India. The Guardian (UK) reports that specialists at Oxford University have devised a new "multidimensional poverty index", according to which there are more poor people in eight of India's states than in the 26 countries of sub-Saharan Africa combined. The index uses 10 major variables including education, nutrition and sanitation. According to the index, more than 410 million people live in poverty in the eight Indian states, and the intensity of the poverty is equal or worse than what is found in Africa. For example, the Democratic Republic of the Congo (population 62 million) is perhaps the poorest nation in Africa, but India's vast central Indian Madhya Pradesh state (70 million) has a near-identical level of poverty. Many laudable efforts have been made in recent years to address poverty and disease in Africa. India's poor, in comparison, have been neglected. This is all the more tragic, given the impressive growth of India's national economy. From the research perspective, India's needs must help shape the agenda. Vivax malaria, dengue, visceral leishmaniasis and leprosy are amongst the infections which threaten the poor in many parts of India.

Nigerian herbal medicines and malaria

The prospects of finding an effective treatment for malaria amongst the many herbal preparations used by traditional healers have been discussed in an article in Nigerian Tribune. The article focuses on research at the University of Ibadan, first announced three years ago, in which 164 plants were found to be used by healers in malaria treatment in Nigeria's Middle Belt alone. Twelve of these were particularly commonly used, and one of them, Enatia chlorantha, was studied further by the researchers. They found it to be active against malaria in mice, but mice that received it regularly died. Determining an appropriate dose rate would therefore be essential before human trials could be conducted. As healers in other parts of Africa use a different range of herbal preparations for malaria, there certainly remains much work to be done to screen all these preparations both for effectiveness and for safety.

Climate change and malaria

A helpful discussion on how climate change might impact on the prevalence of malaria has been published in the US online newspaper The Faster Times. Written by a scientist - Anome Akpogheneta PhD, whose own doctoral research focused upon malaria immuno-epidemiology - the article makes it clear that there are different views as to whether global warming will have a significant impact on the number of malaria cases. Different modelling studies have produced conflicting results. Dr Akpogheneta quotes Professor Steve Lindsay of the London School of Hygiene & Tropical Medicine who says that while models can help provide a "broad brush understanding" they should not be taken too seriously. Professor Paul Reiter at the Institut Pasteur has also said that many models "sidestep factors that are key to the transmission and epidemiology of the disease: the ecology and behaviour of both humans and vectors, and the immunity of the human population". The author concludes that, "Over-emphasis on global warming in relation to malaria misses the mark on the immediate need to address persistent socio-economic and political factors which drive malaria transmission". It is unusual to see such balanced and well-informed discussion in the "popular" media. More scientists should write like this.

US FDA looks for new ways to stimulate private-sector development of drugs for neglected infections

A Reuter's report says that, later this year, a US Food and Drug Administration (FDA) panel will discuss how to make it easier and cheaper for drug companies to develop treatments for "neglected diseases such as malaria and tuberculosis". It's deliberations will be along similar lines to those of a panel that is looking at the development of treatments for rare conditions such as cystic fibrosis and Huntington's disease. In both cases, the underlying issue is that the market for new treatments is relatively small and offers the companies very few opportunities for profit. As reported on TropIKA.net, FDA has already tried to stimulate private-sector research on neglected infections through its priority review voucher scheme but, as we have also reported, this has proved to be controversial. The panel's ideas for further initiatives in this area will be awaited with interest.

Most paediatric fevers not caused by malaria

More than half the paediatric fevers treated in public health clinics in Africa are caused by diseases other than malaria, according to a study by Oxford University and other research groups, whose authors caution against the "continued indiscriminate use of anti-malarials for all fevers across Africa." Of the 183 million children with malaria symptoms treated by public health clinics in 2007, only 43 percent were diagnosed with malaria, but many more most likely received anti-malarial medication. "Malaria is still routinely made as the diagnosis of convenience in response to paediatric fever," the study's lead researcher, Peter Gething, told IRIN. "This in part stems fromofficial guidelines that have only recently been updated, and in part because often the only treatments available in front-line clinics are anti-malarials." In 2006 the World Health Organization (WHO) recommended that health workers in countries with a high number of suspected cases of malaria treat children with fevers - the main clinical symptom of malaria - for the disease, even without a diagnosis. There was little else to do at the time, said WHO expert Peter Olumese. "The probability was high that the fevers were from malaria, the disease could turn fatal quickly and there was no time to lose, and there were no proven diagnostic tools," he told IRIN. Since then, rapid diagnostic testing for malaria has become available, making it possible to confirm diagnoses without health workers, a microscope or a laboratory. In 2008, 11.5 million of these tests were distributed in Africa; in 2009, the Global Fund to Fight AIDS, Tuberculosis and Malaria financed 74 million tests, and another 105 million in 2010, according to the Roll Back Malaria Partnership. People in communities have been trained to test one another for malaria. In Senegal, people of all ages are treated for malaria in government-funded health centres only once there is a positive result from a laboratory or rapid test. In sub-Saharan Africa 31 countries have a policy of "universal diagnostic testing", while another 15 countries in the region have set a goal of testing before treatment in children aged five and older, judging it too risky to delay treatment in younger patients.

More on malaria from IRIN

BURKINA FASO: When is malaria not malaria?

GLOBAL: Spoonfuls of sugar could save malaria patients

MALI: Combating malaria misdiagnosis

TIMOR-LESTE: Rebuilding infrastructure poses challenge to tackling malaria

Yet it can be equally risky to treat someone for malaria based only on the assumption that they have the disease, the director of WHO's global malaria programme, Robert Newman, told IRIN. "You might be wasting ACT [anti-malarial artemisinin-based Combination Therapy], while increasing the risk for drug resistance; also, you are not treating the underlying febrile disease and the drug delay can be fatal. If you treat bacterial pneumonia with anti-malarials, you still have a problem." On Kinaserom, one of the islands in Lake Chad, health workers recently started using rapid tests to check patients suspected of having malaria. Mahamat Boukar Moussa, the head nurse at a clinic on the island, told IRIN he gave patients malaria medication even when test results were negative. "The tests are not accurate and we cannot risk inaction." Raoul Ngarhounoum, the regional health director overseeing the rollout of malaria rapid testing, told IRIN he agreed with the health workers' scepticism. "These are malaria-endemic areas, and just because a test says it is not malaria does not mean it is not." Gething said that besides quality control, "Simply supplying RDT [rapid diagnostic testing] universally is likely to be less effective if it is not accompanied by sufficient training for front-line health workers." The Foundation for Innovative New Diagnostics, which works with WHO to create quality control standards for rapid tests, recommends spot checking in each batch of tests ordered to ensure the tests were not poorly manufactured, or had been damaged in transit or storage. Malaria treatment would not change overnight, said Gething. "In an ideal world, all fevers reaching clinics in Africa would be tested for malaria, using a reliable diagnostic test ... As always, the reality on the ground is more complex. For years the advice has been to treat all fevers as malaria, and changing that dogma is likely to take time."

Source: IRIN

Dengue, not malaria, is Sri Lanka's most serious mosquito-borne disease

As discussed in a recent TropIKA.net article, which focused on Zanzibar, some malaria-endemic areas have now reached a position where it would be technical feasible to eliminate the disease as a public health within the next few years. Now, Sri Lanka's health minister Maithripala Sirisena is reported by the country's Daily News as saying that malaria will be eradicated* there by 2015. The minister pointed out that annual malaria case numbers have declined in recent years, whereas ten years ago 200,000 cases per year were reported. He went on, however, to comment on the Sri Lanka's growing problems with dengue - like malaria a disease transmitted by mosquitoes: "We are facing another problem. That is the dengue fever. Over 35,000 dengue patients were reported in 2009 and 360 people died due to this. The present dengue situation is similar to that of 2009. Over 16,000 dengue cases were reported and over 90 people have died in 2010. This is very serious problem." He said that dengue control could not be achieved by the government alone; it was a "social responsibility". *The term disease "eradication" is usually taken to mean a complete absence of cases, whereas reducing locally-acquired cases to zero is described as "elimination". It is likely that Sri Lanka has set elimination as a target.

Disease elimination: when is it a realistic prospect?

Some of our recent articles on TropIKA.net have involved use of the E word – elimination. There comes a time when it becomes realistic for a control programme that seeks merely to reduce case numbers to progress to the more ambitious goal of eliminating an infectious disease as a public health problem. The elimination of malaria from some of the territories where it is endemic is now technically feasible, though many barriers will still have to be overcome. As we report [1], the health authorities in Zanzibar, where there have been substantial reductions in malaria in recent years, have been asked to decide whether there is sufficient political will to tackle the financial and operational challenges that would have to be overcome to achieve elimination there. Zanzibar is much better placed to realize such a goal than most parts of mainland Africa but it would, nevertheless, be a bold move to make elimination the official policy. If Zanzibar takes this step, could it inspire similar policy switches elsewhere? (Meanwhile, although less is usually heard from South America’s national malaria programmes, the TropIKA.net blog reports that in both Brazil [2] and Venezuela [3] rises in case numbers have been noted, and have been associated with increased exploitation of the rain forest.) Elimination of the disfiguring and disabling disease lymphatic filariasis (LF) has been set as a worldwide goal for 2020. A meeting [4] of the Global Alliance to Eliminate Lymphatic Filariasis concluded that efforts to meet this deadline are on track. Recent successes in the Philippines [5] provide an example of the progress that has been made. However, researchers in Tanzania [6] found that encouraging reductions in LF, following the launch of a mass drug administration programme, soon levelled off. The study demonstrates that it is essential to monitor elimination programmes to determine how they are performing in specific locations. But elimination will always need more than a technical fix. As Bill Gates recently noted, there is a “human piece” in global health. Following his intervention as a major donor, the Global Polio Eradication Initiative will introduce new elements into its strategic plan. These include: training for health care workers on hygiene and sanitation; interventions aimed at increasing access to clean water and zinc supplementation; and the sensitization of communities to the importance of personal hygiene, routine immunization and breastfeeding. Gates has been noted for his focus on the use of technology in disease control. As we discuss in a TropIKA.net Editorial [7], his new enthusiasm for the human piece could have far-reaching implications. Tuberculosis is sadly an example of a disease where there are no prospects for elimination in the foreseeable future, but a recent conference on TB vaccine research did hear that potential new tools against the disease are in the pipeline [http://www.tropika.net/svc/news/20100607/Chinnock-20100607-News-TBVI#page-comments]. A protein that protects against TB has also been [9] identified. Less encouraging news is the finding that, in African countries that have expanded their mining industries, the whole population (not just the miners themselves) faces a higher risk of TB [10]. Also of concern is that, despite the growing rates of multidrug-resistant TB in South Africa, nurses there seem to have very little knowledge of the condition [11]. The remit of TropIKA.net extends beyond the more widely known infectious disease of poverty, such as malaria, TB and polio. We recently highlighted a review [12] that argues for more action against neurocysticercosis – a consequence of tapeworm infection – which is responsible for many cases of epilepsy. A conference [13] on this much neglected condition will take place in Uganda in July. The TropIKA.net blog continues to publish many items of interest. We report for example [14] that three research institutions in Kenya have combined their expertise to develop a scientific model that can predict surges in malaria. They claim to be able to achieve accuracy levels of 80–100%. Such achievements demonstrate what African scientists can achieve – in Africa – if given sufficient opportunities to do so. It is welcome news therefore [15] that the new $38 million Human Heredity and Health in Africa Project (H3 Africa) will employ African scientists in the search for new insights into genes, environment and health among African populations. Paul Chinnock Editor, TropIKA.net

Fish for mosquito control

Dr Jonathan Matias of Poseidon Sciences writes... "I just wanted to update you on our recent publication on biological control using fish that can be disseminated in the form of hibernating eggs to control mosquitoes in temporary pools. Here is the link to this new article: http://www.malariaworld.org/article/open-access-use-annual-killifish-biocontrol-aquatic-stages-mosquitoes-temporary-bodies-fresh Hoping that this stimulates interest and collaboration to move this project towards more practical use."

Sock scent could lure mosquitoes in malaria control

It has often been noted that mosquito species that transmit malaria are attracted by human sweat. A Dutch scientist has noted that the smell of sweaty socks seems to be particularly attractive and she is hoping to use the odour to lure the mosquitoes into traps. The aim is to reduce mosquito numbers as a part of malaria control programmes. Dr Renate Smallegange of the University of Wageningen says she is working to create a synthetic odour suitable for use in such traps. However, there are several components to human sweat and she has not yet been able to identify them all. More details on AfricaNews.com.

Global Fund freezes its funding for Zambia

The Global Fund to fight AIDS, Tuberculosis and Malaria has frozen its grants to the Zambian health ministry. A Global Fund press release states: "The freeze in disbursement came after Zambian authorities last year uncovered fraud within its own Ministry of Health. Further investigations by the Global Fund showed that the Ministry of Health was not able to safely manage grants. The organization has demanded the return of US$8 million in unspent funds from the Ministry of Health. The Global Fund has also demanded that Zambia takes action against individuals found to be involved in the unaccounted expenditures that led to the freezing of grant disbursements". The Fund hopes to recommence its Zambian funding programme within a few months, but through the UN Development Programme instead of the health ministry. Other African countries, including Kenya and Uganda, have previously seen their grants from the Fund suspended for similar reasons. The Fund recently announced its mid-year results, which show that it has so far provided seven million people with effective TB drugs treatment. This is a 30% increase from mid-2009. Progress is also reported in the fight against malaria, with a cumulative total of 122 million insecticide-treated bed nets delivered with Fund support - a rise of 39% from 88 million nets distributed one year ago. However, the Fund has made it clear that it can only maintain activities at this level if donor nations can be persuaded to continue their support, despite the continuing global economic problems. The Fund estimates that it will need $17-20 billion to respond to demand from developing countries for resources to fight the three diseases during the next three years. In October, UN Secretary-General Ban Ki-moon will chair a meeting of the Fund’s donors where they will pledge resources for this period.

Resistance to key antimalarial is said to be spreading

The progress that is being made against malaria in several parts of the world could be derailed if the parasite becomes resistant to the drug that is now the mainstay of treatment - artemisinin. Such resistance is already known to be present along the borders of Cambodia and Thailand. (First detected in 2007, this was confirmed in research published last year - see TropIKA.net article.) Now, a US expert says it has spread to other parts of Southeast Asia. According to a report from AFP, Timothy Ziemer, the US government's global coordinator against malaria, signs of resistance to artemisinin have been found in southern Myanmar and possibly on the Chinese-Myanmar border, and in southern Vietnam near Cambodia. Ziemer, who was speaking at a regional conference in Hanoi, said that, nevertheless, malaria case numbers are down in several parts of the region. In Vietnam, for example, they had fallen from about 190,000 in 1991 to 15,000 by 2008. WHO is overseeing a programme that seeks to hold the spread of artemisinin resistance in check (see TropIKA.net article). One of the key elements of this programme will be to act against the spread of fake and substandard antimalarials.

Researchers show deforestation is associated with malaria risk

US and Brazilian researchers[1] have found a significant association between the destruction of the rain forest and the incidence of malaria. They used satellite data showing changes in tree cover in one county in Brazil's Amazon region, together with health records showing diagnosed cases of malaria. Over a four-year period, 4.2% of the county's tree cover was cleared and there was a 48% increase in cases of malaria. The deforestation was a result of both logging and subsistence farming. To explain the association, the researchers point out that: "Human-altered landscapes provide a milieu of suitable larval habitats for Anopheles darlingi mosquitoes, including road ditches, dams, mining pits, culverts, vehicle ruts, and areas of poor clearing". An increase in the number of fish farms may also have led to a rise in the number of breeding sites for mosquitoes. The research team propose that that land use measures may be one method to employ in malaria control. It has been estimated that that 19,000 square km of forest are cleared in Brazil each year. Reference 1. Olson SH, Gangnon R, Silveira G, Patz JA. Deforestation and malaria in Mâncio Lima County, Brazil. Emerg Infect Dis. 2010 Jul; [Epub ahead of print]. Accessible here.

Aid dollars and malaria

A feature story in the current issue of Time Magazine looks at the massive increase in aid for malaria over the past five years and the pivotal role UN special envoy Ray Chambers has played in prodding Western governments to open their wallets. The writer suggests that Chambers' group, Malaria No More, which he founded in 2006 and which has the official endorsement of the WHO, represents "a new way of giving. "With its ethos that "aid should be seen not as a noble act of charity but as something that's in everyone's interest," Malaria No More "stands as a case study that aid can change," argues the writer, Alex Perry, Time's Africa bureau chief. But can that progress be sustained? That may be the true test of aid's effectiveness - especially given that, short of eradication, nothing is permanent when it comes to controlling malaria. Perry points to Zanzibar as a prime example of the need to maintain momentum; the Tanzanian island, which is now on the cusp of launching a malaria elimination campaign, has twice before eliminated malaria - not "eradicated" it, as Perry stresses - only to reimport it from the heavily-infected mainland. "Kenya has slipped," he adds. Dambisa Moyo, author of the 2009 best-seller "Dead Aid: Why Aid is Not Working and How", popularized the notion that charity hasn't worked. Moyo's message echoes the late race-bating, gay-bashing senator of North Carolina, Jesse Helms, infamous for his tirades against greater funding for AIDS research, who once dismissed foreign aid as "money down a rat hole." Moyo has been criticized for being light on the facts and for glossing over positive trends directly attributable to health and humanitarian aid, among them the halving of malaria deaths in nine African countries since 2000. But if Moyo questions Africa's progress against malaria and what it actually means, she isn't alone. "Roll Back Malaria claims its interventions have had an impact in places like Eritrea, Sao Tome and The Gambia, where there's either a history of bed net use or, in the case of Eritrea, there's been a drought for four years," says David Molyneux, director of the Lymphatic Filariasis Support Centre at the Liverpool School of Tropical Medicine. "So surprise, surprise, you have an impact on malaria." Molyneux adds that when it comes to malaria's success, one has to ask, "How long have we got?" Bed net efficacy, he says, is already being eroded by resistance to pyrethroids. "We know there's quite a lot of resistance already in West Africa. And there's nothing in the pipeline to replace them." Indeed, rather than joining the chorus of applause, Molyneux asks why the world isn't holding the malaria community accountable: "They have failed to reach targets they set themselves," he says. "It wasn't that other people set the targets. They set the target of universal bed nets by 2010. Of course you fail when you set that kind of target." A veteran researcher and vocal advocate for the control of lymphatic filariasis (LF), Molyneux has often criticized what he calls a "siloed" malaria community. "They don't have the structures or ability or interest in engaging with other people who have different ideas," he says. "That's the point I've been making and will continue to make: why are you ignoring LF? It's not a question of whether I'm technically correct: free drugs and mass drug administration have been shown to increase bed net uptake. So why don't they look at that and say, 'What can we learn from this? It's not going to cost us anything.' I don't understand it."

Advocacy group under fire

The organization Africa Fighting Malaria, which is run from an office in Washington DC, continues to come in for criticism. Since its launch in 2000, this advocacy group has focused most of its attention on one issue - the desirability of using DDT in mosquito control programmes. Blogger Ed Darrell adds another critical voice, asking "Can anyone tell me, what has Africa Fighting Malaria ever done to seriously fight malaria?" He points out that while the organization portrays itself as a lonely voice struggling to promote the use of indoor residual insecticide spraying, the practice is already supported by WHO, the Gates Foundation, African governments and others.

Sector-wide approach fails to improve health

A Comment article in the Guardian (UK) criticises the performance of "sector-wide" aid programmes (SWAps) in addressing health issues. The article defines the approach, now much favoured by the World Bank and other donors, as follows: "Instead of funding a development project with a very specific focus, like tuberculosis (TB) or malaria, SWAps channel donor funds to broad health initiatives in a developing country. For instance, instead of financing the delivery of HIV medicines or bed nets in Ghana, SWAps money is provided to the government to spend toward broader goals like 'improving the public health sector' and a number of health services". However, the Guardian writers, using tuberculosis as one example, say that only limited improvements in health have been achieved through SWAps. Many governments in the North, such as the UK, have recently stated that agencies like the World Bank must improve their performance in order to justify continued funding. A close look at the sector-wide approach is therefore now needed. The article quotes the Bank as stating that the current economic downturn will increase the number of child deaths in the South by around 400,000 this year.

As promised, GSK makes chemical structures of antimalarials freely available

GlaxoSmithKline has deposited the chemical structures for more than 13,500 anti-malaria compounds in the European Bioinformatics Institute's freely available ChEMBL chemical database. In January, GSK announced its plans to make the structures freely available but did not disclose at the time how it planned to make the compounds available. More information is available on the Free Library and on the ChEMBL-NTD web page.

Kenya researchers predict malaria incidence rates

Three research institutions in Kenya have combined their expertise to develop a scientific model that can predict surges in malaria. They claim to be able to achieve accuracy levels of 80-100%. In research conducted across East Africa over the last nine years, scientists of the Kenya Medical Research Institute, the Kenya Meteorological Department, and the International Centre for Insect Physiology & Ecology have made use of weather predictions, information about the reproductive mechanisms of mosquitoes, and data on the geographical formations of particular areas. Being able to predict when epidemic levels of malaria will strike would be of great assistance to health authorities. For example, indoor residual spraying of insecticide programmes can be focused on areas where outbreaks are imminent. The full story is reported on AlertNet.

Charting the bottom ten

By Margaret Harris This is a first attempt to chart the distribution of these neglected diseases and is based on published epidemiological data. Let the maps cycle, or click on each disease name at the top to see where in the world that disease can be found. We welcome feedback, updates and suggestions on ways to improve the information provided. The interactive map on the TropIKA.net home page shows 10 diseases - some with names few can pronounce- that have been identified by the Unicef/UNDP/World Bank/WHO Special Programme for Research & Training (TDR) as the most neglected of infectious diseases, hampering the health and development of the world's poorest people. The diseases: Chagas, dengue fever, human African trypanosomiasis (HAT) onchocerciasis, leishmaniasis, leprosy, lymphatic filariasis, malaria, tuberculosis and schistosomiasis are still endemic in much of the world, particularly tropical regions. Their distribution and effects differ from disease to disease but their burden remains heavy. Africa, South America and Asia all contain countries affected by at least one of these neglected diseases of poverty. Not only do these diseases disproportionately affect impoverished populations, they reduce economic activity. The annual economic loss in Africa due to malaria has been estimated as $12 billion, representing a crippling 1.3 percent annual loss in GDP growth in endemic countries. Schistosomiasis and malaria lower child survival, while onchocerciasis and schistosomiasis hamper children's school performance. Lymphatic filariasis interferes with agricultural productivity as does onchocerciasis and schistosomiasis [1]. Leishmaniasis, human African trypanosomiasis and lymphatic filariasis are associated with an economic burden of a different kind as infected people pay excessive amounts for treatment and seek inappropriate of ineffective care [1]. Leprosy leads to social isolation and stigmatization, particularly among women who may not present for diagnosis due to fear of loss of marriage opportunities. TDR is working to identify the needs, gaps and potential for action in research for infectious diseases of poverty, including the ten that appear on this map. A think tank made of 125 experts from around the world is examining the research, debating the issues and developing options for action. Their findings will feed into the Global Report for research on infectious diseases of poverty, due to be published in 2011. Reference 1. Hotez PJ, Fenwick A, Savioli L, Molyneux DH (2009). Rescuing the bottom billion through control of neglected tropical diseases. Lancet; 373:1570-1575

Malaria cases diagnosed in Venezuela double this year

So far this year, twice as many cases of malaria have been diagnosed in Venezuela compared with the same period in 2009. A report on Times Newsline says there have been nearly 22,000 cases this year. The rise is believed to be due to government's eviction of "hundreds of thousands" of miners working illegally in forest areas. The evicted miners have moved to urban areas, where they would be more likely to be tested for malaria and more likely to spread the disease. While Venezuelans face much lower risks from malaria than the populations of most African countries, the forest zones in the south, which is rich in mineral resources, do seem to pose a significant hazards to those who are drawn there in search of work.

Burkina Faso tests indoor residual spraying

Indoor residual spraying with insecticide is seen as an important part of malaria control efforts in endemic areas. A report on IRIN News describes the launch of Burkina Faso's first trial of the technique. Funded by the US Agency for International Development (USAID), the project is expected to cover 25,000 households in the district of Diébougou – using the insecticide bendiocarb – for one season at a cost of US$1.4 million. In 2009 Diébougou experienced more than 20,000 cases of malaria, with 110 deaths.

TropIKA.net launches review series

Efforts to control the infectious diseases of poverty (IDPs) must be based on an objective consideration of all the evidence available. Policy makers, funding agencies, researchers and practitioners all need access to rigorous reviews of this evidence. We are therefore launching a series of such reviews, the first of which is now available: Dengue outbreak response: documented effective interventions and evidence gaps.
A 1000-word, plain-language summary [1] of the review is published on the main TropIKA.net website, from where there is a link to the full 7000-word document with figures and annexes. Over the next few days, a further four review summaries (with links to the full reports) will also be published on TropIKA.net: Insecticide resistance in dengue vectors Treating patients with visceral leishmaniasis in the Indian subcontinent: the evidence from clinical trials What is the best way to distribute insecticide-treated nets to help prevent malaria? Do the poor benefit from infectious disease programmes?
New tools A theme of much of the other new content on TropIKA.net has been new tools for use in IDP control. With an increasing level of research on IDPs now taking place, there has been a welcome rise in the development of such tools. For example, we note the discovery of a diagnostic test able to identify Chagas disease in asymptomatic patients – see the TropIKA.net blog [2]. But how effective are the new tools and how well are they received by those who use them in the field? We highlight a new Cochrane review [3] that was able to find insufficient evidence to quantify the benefits of indoor residual spraying (IRS) of insecticide, regarded as an component of malaria control programmes. We also feature a study from Ghana [4] in which health workers were asked about their experience using the new rapid diagnostic tests from malaria. Despite the growth in IDP research, the number of new tools that have reached approval stage is not as high as perhaps would be expected. According to a new study [5], only 26 new drugs and vaccines for “neglected diseases” reached the approval stage in the first ten years of this century. (Eleven were for malaria and ten for HIV/AIDS. One new drug and two vaccines were for diarrhoeal diseases, one vaccine was developed against bacterial meningitis, and one new drug was approved for leishmaniasis.) But the task of developing new tools often seems to be less formidable than bringing them to the front line of disease control, so that they benefit the communities and individuals at risk of IDPs. One programme that aims to do this is the sometimes controversial Affordable Medicines Facility-malaria (AMFm). The programme has now ‘gone live’ – see our interview [6] with AMFm’s Director Dr Olusoji Adeyi. Madagascar [7] is the first country to benefit. Also on TropIKA.net Our popular Profile series normally profiles key individuals involved in the war against the IDPs but the latest in the series focuses on an organization – the Public Health Foundation of India [8], which aims to boost the country’s number of trained public health staff. And also of particular interest are the following articles and blogs:

Paul Chinnock Editor, TropIKA.net

A "manifesto" for combatting NTDs

Despite evidence that the global burden of neglected diseases is as great as that of any other serious disease, financial support for elimination efforts and R&D has been inadequate, say the authors of a new "Manifesto for Advancing the Control and Elimination of Neglected Tropical Diseases", published this week. Writing in PLoS Neglected Tropical Diseases, Peter Hotez, President of the Sabin Vaccine Institute and Distinguished Research Professor of The George Washington University Medical Center, and Bernard Pecoul, Executive Director of Drugs for Neglected Diseases initiative (DNDi), outline in eight points why the global community should increase financial support for NTD control and elimination efforts and research and development. The manifesto states that:

· All NTDs are "tool ready" with cost-efficient and effective interventions that could be implemented now, even if for some diseases such tools are far from being perfect or complete.

· At the same time that NTDs are tool ready they are also tool deficient, signifying that the tools are incomplete, or inadequate, to sustain elimination efforts.

· NTDs have received little attention from the international community during the past ten years despite their large disease burden.

· Increasing evidence indicates an association between NTD prevalence and conflict and violation of human rights.

· NTDs can be particularly destabilizing and disrupt agricultural productivity and food security. Many poor societies with high NTD burdens have been recently engaged in a civil or international conflict or are currently at war.

· Sustained involvement by the WHO and other international health agencies is crucial for current and future NTD control and elimination efforts.

· Nothing is more important to the success of global NTD control than the involvement of communities themselves and disease-endemic countries' health ministries.

· Achievement of Millennium Development Goal 8 ("develop a global partnership for development") will rest with stakeholders — health ministries, affected communities, public–private partnerships, large and small non-governmental organizations, etc. — establishing a well-functioning international strategy for NTD control.

While acknowledging that policymakers are “slowly beginning to appreciate the importance of NTDs” — evidenced by the creation of a new department of Neglected Tropical Diseases at the World Health Organization; TDR’s 10-year strategic plan; and the identification, by NIH’s Francis Collins, of neglected diseases as a research priority, among other developments — Hotez and Pecoul argue that the challenge of NTDs calls for a manifesto — “a public declaration of motives by a government or by a person or group regarded as having some public importance.”

Moreover, they add, by doing more to tackle NTDs, the global health community can make progress toward Millennium Development Goals.

"[NTD control] activities have facilitated the delivery of additional interventions such as insecticide-treated bed nets, antimalarial drugs, micronutrients, and childhood immunizations," they write.

The authors urge scientists working on NTDs to increase collaboration and identify funding opportunities and cost-efficient interventions.

"By highlighting important challenges in the fight against NTDs, this 'manifesto' calls on the global community for urgent, renewed, and innovative efforts."

Can hungry plants control malarial mosquitoes?

Uganda's New Vision newspaper reports on a research project that is testing whether insectivorous plants planted around homes can decrease mosquito numbers and cut malaria transmission. The project, which is backed by funding from the Gates Foundation, is being run by Professor Jasper Okeng of the Pharmacology Department of Makerere University. Professor Okeng says this is the first time such an approach to malaria control has been attempted anywhere in the world. The New Vision article describes the project and also looks at Jasper Okeng's career as a pharmacologist.

Texting to fight fakes

The number of fake drugs on the market continues to rise. It has been estimated, for example, that over half of the antimalarials on sale in Africa are fake or substandard. Individuals who take these drugs do not receive the effective treatment they need. Also those fakes that contain a small amount of the active compound (as is often the case) promote the development of drug resistance. A new plan to help consumers identify fake products makes use of the fact that mobile telephones are now found widely across the developed world, even in rural areas. Under the plan, legitimate drugs will come with a scratch- off panel hiding 10 digits. Anyone who has purchased a drug with one of these labels can text the code to a widely advertised number, and receive a reply confirming or disputing the product’s authenticity. There is no charge. The scheme is operated by a non-profit group, mPedigree Network, in partnership with computer giant Hewlett Packard. GlaxoSmithKiline is interested in participating in the initiative and discussions are said to be taking place. Initially the focus will be on Africa. It is intended to introduce the system with malaria pills in Ghana and Nigeria by December, with expansion later to Kenya, Tanzania, Liberia, Benin and Uganda. (Full story on the Bloomberg website.)

Advance in Giardia research: could it help progress against malaria?

It is often hoped that a research advance against one parasitic infection may prove helpful in efforts to combat another. Scientists seeking to develop a vaccine for the intestinal parasite Giardia lamblia believe that their latest findings [1] may help in research targeted on other parasitic diseases, including malaria. The research team, in Argentina, noted that G. lamblia is able to make changes in the proteins on its surface and that this "antigenic variation" allows it to evade the host's immune response. They went on to show that parasites engineered to express all their surface proteins worked as vaccines that could help prevent or mitigate future infections. They conclude that, "These results constitute, to our knowledge, the first experimental evidence that antigenic variation is essential for parasite survival within hosts and that artificial disruption of this mechanism might be useful in generating vaccines against major pathogens that show similar behavior". In an interview on ScienceLive.com, the leader of the research team, Professor Hugo Luján, said that the surface proteins of parasites were needed to help them survive the acid conditions of the host gut and that the new understanding could lead to vaccines that would disrupt this protective mechanism. Vaccines against other parasites, including malaria, could be possible following the same principle. Giardia is a common cause of diarrhoea in many countries and a vaccine against it would therefore be helpful, but it is already possible to prevent infection by through the provision of safe water supplies and good hygienic practices. Reference 1. Rivero FD, Saura A, Prucca CG, Carranza PG, Torri A, Lujan HD (2010). Disruption of antigenic variation is crucial for effective parasite vaccine. Nat Med; 16(5):551-557.

Shrinking the malaria map

The Emerging Health Threats Forum has an interesting piece on efforts to “shrink the malaria map.” The article highlights a new study (1) by researchers at the London School of Hygiene and Tropical Medicine (LSHTM) who have developed a reliable way to accurately identify so-called “hot spots” of malaria transmission. According to the authors, the heterogeneity of risk of malaria within populations “creates opportunities for targeted interventions, but only if hot spots of malaria transmission can be identified.” By looking at serological markers of antibody levels, which had been obtained through a pin-prick blood test of people attending health facilities in a district in Tanzania’s Korogwe region, the researchers were able to detect spatial variation in malaria transmission at the micro-epidemiological level. “Serological markers of exposure to malaria showed a tight correlation with malaria incidence and predicted transmission hot spots with high precision,” they write. As debate continues over how best to allocate funds for disease control — to programmes aimed at eliminating malaria in areas already on the verge of doing so or into those designed to reduce the burden of disease where it is greatest — the new findings represent a potent new tool and one the researchers believe could pave the way for eliminating malaria in areas where the disease has been brought under control. References 1. Bousema T et al. (2010). Identification of hot spots of malaria transmission for targeted malaria control. J Infect Dis.

Mosquito nets go unused

Insecticide-treated bednets (ITNs) are widely recognised as an effective means of reducing malaria transmission. Massive distribution programmes are under way in many parts of Africa, and in the developed world a growing number of charities (some backed by celebrities) have been established to raise support for these programmes. However, several media outlets, for example the Los Angeles Times, have lately pointed out that many ITNs go unused; some fail to reach those who need them and it is claimed that up to half of Africans refuse to use nets. ITNs are a relatively low-cost intervention. If - after all the distribution efforts - only half of the population in malaria-endemic areas is protected by a net then it is disappointing, but many lives will still be saved. The distribution programmes will still be worthwhile. And if more attention is devoted to education and promotion of net use then, in time, more people will be willing to sleep under them. We can only hope that articles like that in the LA Times do not reduce the commitment of those who have provided support to ITN programmes.

Malaria and primary education in Mali

One reason why the infectious diseases of poverty do so much damage to individuals, communities and nations is that they can prevent people from achieving their full physical and mental potential. The impact of malaria on cognitive ability is an area in which there has been increasing interest. It is recognised that cerebral malaria or severe anaemia as the result of infection can effect a child's developing brain, and that the fetus is similarly vulnerable to malaria during pregnancy. But evidence has been lacking as to whether (and through what mechanisms) uncomplicated malaria or asymptomatic infection can damage cognition, particularly in children who suffer repeated attacks. Researchers working with children in a village primary school in Mali [1] have attempted to improve knowledge in this area. The authors, whose published paper begins with helpful tables summarising previous work on this issue, looked for an association between malaria and variation in cognitive abilities, teachers’ evaluation scores, school progression and absences. Malaria was the main cause of absence from school. In addition, asymptomatic malaria and the presence of malaria parasites were found to have a direct correlation with educational achievement and cognitive performance. The higher the level of parasites present in the blood, the lower the cognitive score. Children with clinical malaria and asymptomatic malaria both had significantly lower achievement test scores, but asymptomatic malaria had less effect on cognitive abilities than clinical malaria. (The cognitive function score used in the study was highly correlated with routine school marks given by teachers.) The authors acknowledge that it is impossible in such studies to prove beyond doubt that an observed association is causal, and the data of course come only from one village school, but these findings offer strong evidence in favour of the view that malaria parasites affect educational achievement. Everything possible should be done to reduce the risk of infection faced by children of this age in endemic areas. Reference 1. Thuilliez J, Sissoko MS, Toure OB, Kamate P, Berthélemy JC, Doumbo OK (2010) Malaria and primary education in Mali: A longitudinal study in the village of Donéguébougou. Soc Sci Med; Mar 17 [Epub ahead of print]. Available from http://bit.ly/9tydZ9.

Sourcing medicines for children

The very young are especially vulnerable to the infectious diseases of poverty but health programme managers face a challenge in sourcing appropriate and affordable medicines for children. A guide produced by UNICEF and WHO seeks to provide guidance. The second edition of Sources and prices of selected medicines for children lists sources and prices for 75% of the 612 formulations needed for the 240 medicines in the Essential Medicines List for Children. WHO and UNICEF note that more than half of the nine million preventable deaths in children annually are caused by diseases which could be treated with safe essential child-specific medicines: acute respiratory infections - pneumonia (17%), diarrhoeal diseases (17%), neonatal severe infections (9%), malaria (7%), and HIV/AIDS (2%). The number of sources for the paediatric treatment of diarrhoea and HIV/AIDS is, however, limited and there is a serious challenge to obtain child-specific medicines to treat tropical infections endemic in Africa and Asia. There are few manufacturers who produce child-specific medicines to treat infections such as filariasis, schistosomiasis and soil-transmitted helminthiases. A commentator on the website Essentialdrugs.org notes that, "UNICEF and WHO could not find a manufacturer for 144 of the 612 needed formulations. Is it lack of commercial markets? Or is it that there is not yet enough demand? Here is a good opportunity for the pharmaceutical industry to show some corporate social responsibility!"

Preventing malaria during pregnancy: trials planned of a new treatment option

Every year an estimated 30 million pregnant women in Africa are at risk of malaria. Intermittent preventive treatment in pregnancy (IPTp) is one of the new tools available to help control the disease but there is a need to increase the range of drug treatments suitable for use in IPTp programmes. A collaboration has been announced that will result, later this year, in African trials of a new combination treatment. The agreement extends to the further development and delivery of the treatment, which is a fixed-dose combination of azithromycin dihydrate (AZ) and chloroquine phosphate (CQ). Partners in the collaboration are Pfizer Inc, the Medicines for Malaria Venture (MMV) and the London School of Hygiene & Tropical Medicine. The three organizations have already been working on the project, on an informal basis, for the last two years. Further details are available in a London School press release. In another new development, MMV and California based Anacor Pharmaceuticals have agreed to explore Anacor’s novel boron chemistry platform for developing new therapeutics for the treatment of malaria - see MMV press release.

Ovale malaria caused by two distinct species

Scientists investigating ovale malaria, a form of the disease thought to be caused by a single species of parasite, have confirmed that the parasite is actually two similar but distinct species which do not reproduce with each other, according to research published in the Journal of Infectious Diseases [1]. Researchers from the London School of Hygiene & Tropical Medicine, the Hospital for Tropical Diseases (London) and Mahidol University, Bangkok collaborated last year in order to share their research after noticing that the single parasite Plasmodium ovale, though visible through a microscope, was not detected by forensic DNA tests designed to identify the species. Dr Colin Sutherland, lead researcher at the London School of Hygiene & Tropical Medicine, said "We used DNA technology to compare the parasites from 56 patients with ovale malaria, from across the tropical world. It was a great surprise to find that, not only are these two species completely distinct from each other by every test we carried out, they actually occur in people living side by side in the same African and Asian countries, and even in the same towns and villages. We hope to continue our work so we can unravel the mysterious differences between these two newly recognised human pathogens." Reference 1. Sutherland CJ, Tanomsing N, Nolder D, Oguike M, Jennison C, Pukrittayakamee S et al (2010). Two nonrecombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally. J Infect Dis; 201(10):1544-1550.

A wider view

One of the best-read sections on TropIKA.net is “Profiles”, in which we feature in-depth interviews with influential figures in research and policy whose work concerns the infectious diseases of poverty. Our latest interviewee is one of the most charismatic individuals in this field – Peter Hotez of the Sabin Vaccine Initiative and the Global Network for Neglected Tropical Diseases (NTDs). No one has done more than Professor Hotez to raise the profile of the NTDs. Speaking to TropIKA.net’s Tatum Anderson, he describes the career path that led him to specialize in this area. Peter Hotez also explains the justification for the Global Network’s current focus on just seven neglected infections: three soil-transmitted helminths (ascariasis, trichuriasis and hookworm), lymphatic filariasis, onchocerciasis, schistosomiasis and trachoma. All of these diseases could already be brought under control, if sufficient support were to be provided for mass drug administration programmes. Different strategies, Hotez says, will be needed to address other diseases of poverty. The Global Network will broaden its focus later. TropIKA.net already takes a wider view in our coverage of the infectious diseases of poverty. Our content also features new developments in such areas as malaria, tuberculosis, dengue and the kinetoplastid diseases (Chagas disease, leishmaniasis and human African trypanosomiasis [sleeping sickness]). Recent developments we have lately highlighted include research that, according to some interpretations, suggests that vivax malaria may be getting more common in Africa. We have also examined some of the new advances being made in leishmaniasis research. It is not often that molecular targets are identified for potential new treatments against the infectious diseases of poverty, so it is gratifying to be able to report that such a target has been found by researchers seeking new drugs for sleeping sickness. Other significant advances recently announced include genomic research on Mycobacterium tuberculosis, the organism that causes TB. The M. tb genome was first sequenced in 1998 but less than 40% of its genes had been “annotated”, meaning that their functions and pathways had yet to be understood and described. Important new insights have now been gained through the work of scientists at the Open Source Drug Discovery (OSDD) initiative in India. (A TropIKA.net article published in March provides more information about OSDD and the concept of open-source drug discovery.) Another area where progress is being made is in the search for vaccines to prevent dengue. We take a look at some of the initiatives that are now under way. Scientific advances such as these give us cause for hope, but there is also a need for political commitment from governments in disease-endemic countries and the global community as a whole. It has therefore been disappointing to read the findings of new research that suggests many African governments have reduced the proportion of their budgets that they are devoting to health. Finally, don't forget to visit the TropIKA.net blog where there have been some interesting postings by guest bloggers from Farmabrasilis and the Asia Pacific Malaria Elimination Network. Paul Chinnock Editor, TropIKA.net

Fellowship programme announced for malaria elimination in Asia-Pacific region

A message from Cara Smith Gueye, Program Coordinator, Malaria Elimination Initiative, Global Health Group, University of California. The Asia Pacific Malaria Elimination Network (APMEN) commemorates the third World Malaria Day, on April 25th, 2010, with the launch of the APMEN Fellowship Program. The Asia Pacific Malaria Elimination Network brings together ten founding countries in the Asia Pacific region who are working to eliminate malaria. The APMEN Fellowship Program aims to help to equip the next generation of leaders and health workers from the Asia Pacific region with the tools and training to guide malaria elimination in the critical coming decades. The Fellowships will strengthen the exchanges and lesson sharing among APMEN Country Malaria Control Programs and research institutions in the region. Up to five Fellows from the ten APMEN partner countries will be selected each year for one to three month, short-term training opportunities with a partner country malaria program or institution. Malaria elimination in the Asia Pacific will require a multi-pronged strategy involving diverse interventions and numerous communities, organizations, companies and governments. A commentary in the Lancet, to be released April 24th, describes the role of APMEN in the region’s efforts toward malaria elimination, highlighting the special challenge of Plasmodium vivax in the region. Further information regarding APMEN, the Fellowship Program, and the Lancet commentary can be viewed at apmen.org.

Is this the best we can do?

There are four strains of the virus that causes dengue fever, a disease transmitted by a mosquito – Aedes aegypti – that is present in many parts of the tropical world, including Africa. So how common is dengue in Africa? Quite incredibly, we just don’t know. Data on case numbers in South America and Asia are reasonably informative but, for the African continent, no figures are available. New research provides evidence that one dengue strain, DENV-3, has spread to West Africa during the last few years. The scientists in several European labs who have contributed to this new study are to be congratulated for adding to what is known about dengue in Africa. But sadly, their findings are the result of tests on Europeans who have visited the region and returned home with a fever – see TropIKA.net News. It is simply unacceptable that diagnostic facilities are so poor in Africa that we know more about an infectious disease in returning foreigners than we do about its prevalence in the indigenous population. Surely we can do better than this? In both the research and control of neglected tropical diseases, diagnostic testing is a neglected issue. WHO’s updated guidelines on the treatment of malaria (see TropIKA.net News in Brief) stress that more attention should be given to testing for malaria before beginning treatment. Another WHO report (on the growing prevalence of drug-resistant strains of tuberculosis) notes that because of inadequate testing facilities in most parts of Africa there is considerable uncertainty as to how many cases of drug-resistant TB are to be found there. As for dengue, this looks likely to be a bad year. Cases of the disease have increased steadily since the 1950s but years where the El Niño phenomenon occurs are known to lead to dramatic spikes in incidence – and 2010 is such a year. See TropIKA.net News. On a more positive note, we report on progress with research that may lead to more effective ways of controlling the Aedes aegypti vector. A much debated question is whether the rise of dengue and other vector-borne diseases is related to climate change. A review article that has been highlighted on TropIKA.net concludes that we do not yet know enough about the ecology of diseases such as malaria and dengue to be able to make accurate predictions. Nevertheless, the article concludes, despite our lack of knowledge there is still appropriate action that can be taken now to reduce the impact of these diseases. World TB Day In our report on World TB Day we note the opinion of TB specialists who believe the gains that have been made are “fragile” and the list of challenges is growing. And a TropIKA.net editorial describes the event as the day when, “the world confronts its collective failure to use medical advances to stop the spread of tuberculosis among the poor”. Nevertheless there are some promising new initiatives on TB, one of which – the Critical Path to TB Drug Regimens (CPTR) – we describe in some detail in a TropIKA.net Profile. Another development which could lead to new treatments for TB is the growth of the “open source” approach to drug discovery. A TropIKA.net article on this topic has already created considerable interest. Initiatives such as those reported in this article are an example of innovative thinking in this area. But much more is needed if we are indeed to do better in the fight against the infectious diseases of poverty. Paul Chinnock Editor, TropIKA.net

Tuberculosis: facing up to the issues

Tuberculosis has featured strongly in TropIKA.net in the last couple of weeks. This is appropriate as World TB Day (24th March) will soon be with us. There are many issues that must be urgently addressed if further progress is to be made in controlling this disease, which kills over one and a half million people every year. There are particular concerns over the growing numbers of cases of drug-resistant forms of TB and new understanding [1] of the mechanism of action of two drugs active against multiple-drug resistant TB may help inform the search for the new drugs that are so desperately needed. A neglected area of TB research has been diagnosis. Sputum microscopy – sometimes referred to as the “gold standard” for diagnosing TB – is time consuming, can only be conducted in the lab and often gives incorrect results. A rapid test that can be used on the front line is required. News of new funding [2] provided by the Gates Foundation to a non-profit group that focuses on this issue is much to be welcomed. Interestingly, a manufacturer of breath tests for disease diagnostics says it has developed a simple test that can diagnose active pulmonary TB within minutes – see TropIKA.net News in brief [3]. The importance of partnership is always stressed in TB control efforts. Important partners in the delivery of care include the private health care sector and it is disappointing that in India [4] many private practitioners do not apparently provide the recommended TB treatment DOTS (directly-observed therapy short course.) Good news Several recent TropIKA.net articles report good news concerning other infectious diseases of poverty. For example, a trial in India [5] found that a single transfusion of the drug amphotericin B, for which patients stayed in hospital for just 24 hours, was as effective in the treatment of visceral leishmaniasis (VL) as a course of treatment requiring a one-month hospital stay. This finding could have major implications; it would be possible to significantly increase the number of VL patients who receive treatment. When new drugs are introduced they are not always popular with patients and this is bound to affect their compliance with the treatments they are prescribed – something that is not always taken into consideration when implementing new programmes. Much depends on the switch to artemisinin-combination therapy (ACT) as the standard treatment for uncomplicated malaria and it is reassuring to learn [6] that the introduction of the ACT Coartem in Dar es Salaam, Tanzania has met with a positive reception from the local community, including mothers whose children have been treated for malaria. A TropIKA “Research in brief” article [7] includes further welcome news: a new insecticide could be in prospect for mosquito control, research at the “basic” level could lead on to the development of treatments for cholera and for the kinetoplastid diseases, and a drug already in use in veterinary medicine could be developed as a new treatment for onchocerciasis. Looking to the future, research into sleeping sickness (human African trypanosomiasis) will be boosted by new Gates funding, and the Australian government has made new grants to researchers working on malaria [8]. In both these cases the research will be based in institutions located in developed countries, but there is a pressing need for more research to be done in disease-endemic countries themselves and for it to be conducted by nationals of those countries. This was the theme of the African Expert Meeting on Pharmaceutical Innovation in Africa, held in Pretoria, South Africa [9], where a call was made for support to enable the development and production of medicines, “in Africa, by Africans”. The registration in African countries of new drugs shown to be effective against the infectious diseases of poverty was also discussed at this meeting [10]. Robust registration procedures are of course necessary but they must not lead to unnecessary delays in bringing the fruits of scientific research to those who most need them. Paul Chinnock Editor, TropIKA.net

Innovation and interpretation

TropIKA.net has often reported on projects involving the use of mobile phones in health care delivery – or “mHealth” as this has become known. These projects, most of which are small pilots, are encouraging examples of the innovative use of technology for the improvement of health, but care must be taken in the interpretation of what has so far been published about these projects. We simply don’t know how many projects are in operation; it is quite possible that we only get to hear of those that are considered to be successful. And how is success defined? If a TB programme distributes phones, so that patients can be reminded to take their treatments, then success could be considered to have been achieved once the phones have been distributed to those who need them, or on the basis of whether health workers and patients are enjoying using them. What we need is hard evidence that more patients are indeed completing their full course of treatment and that cure rates have been improved. TropIKA.net has published a review article [1] on the current progress in mHealth that describes some exciting examples of what is being done, but also looks at efforts being made by researchers to assess what these programmes are actually achieving. Innovation in drug development has been the theme of some of our other recent articles. Efforts are under way to improve the efficiency and cut the cost of producing the drug praziquantel, used in the treatment of schistosomiasis. This project involves the use of an innovative approach to research – “open-source science” [2]. Another drug, flubendazole is widely used to treat worm infestations in animals but delivered disappointing results when used in humans against the filarial worms responsible for elephantiasis (lymphatic filariasis) and river blindness (onchocerciasis). A project [3] is investigating whether a reformulation of the drug can make it viable as an effective treatment for people with these conditions. But even when effective drugs are available, getting them through to all those who need them remains a considerable barrier. One reason for this is the number of fake and substandard products on the market – see, for example a new report on substandard antimalarials [4]. A meeting in West Africa heard of the need to develop innovative techniques to stop the flow of these drugs [5]. Elsewhere on TropIKA.net we have reported some good news. The finding that Buruli ulcer, if diagnosed at an early stage, can be successfully treated with antibiotics without resorting to surgery [6] is one such development. This appalling condition is becoming more common and surgery has been recommended for all cases, despite the fact that it is often hard to access in the areas where the disease is most common and that patients do not like it. Now the challenge is to see that they are diagnosed in good time. And President Obama has, in his budget placed before Congress, proposed significant increases in what would be spent on the infectious diseases of poverty [7]. The overall budget for global health would rise by a useful amount but the re-prioritization of particular diseases and issues is perhaps of greater interest. Infectious diseases claim the lives of millions, both in peace time and in war. A study published in the Lancet [8] found that, for some 80% of the 300,000 people who died as a consequence of the war in Sudan’s Dafur region, the cause of death was not violent injury but infectious conditions, most notably pneumonia and diarrhoea. Sadly, those who seek innovative ways to deliver health care most endeavour to develop mechanisms that will also prove effective in conflict situations. Paul Chinnock Editor, TropIKA.net

Has Australian research revealed malaria's "Achilles heel"?

The transcript is available of a short ABC radio interview with Australian scientist Professor Alan Cowman who describes his recent study [1] on the so-called effector proteins that the malaria parasite uses in order to successfully invade red blood cells. Professor Cowman believes that there is one protein that "decides" how all of these proteins are to be exported. He hopes that this protein - plasmepsin V - will turn out to be the Achilles heel of malaria and that a new type of malaria drug can be developed that works by targeting plasmepsin V. The study appears in Nature in the same issue as a paper by US malaria researchers who report [2] they have found more than two dozen smell receptors in the malaria-transmitting mosquito Anopheles gambiae that enables the insect to home in on human sweat. They believe that some of the receptors "could be excellent targets" for chemicals to snare mosquitoes or repel them, References 1. Boddey JA, Hodder AN, Günther S, Gilson PR, Patsiouras H, Kapp EA, Pearce JA, de Koning-Ward TF, Simpson RJ, Crabb BS, Cowman AF (2010). An aspartyl protease directs malaria effector proteins to the host cell. Nature; 463(7281):627-631. 2. Carey AF, Wang G, Su CY, Zwiebel LJ, Carlson JR (2010). Odorant reception in the malaria mosquito Anopheles gambiae. Nature; Feb 3. [Epub ahead of print]

Further warnings on resistance to key antimalarial

The World Health Organization's representative to Myanmar (Burma) has repeated warnings that resistance to artemisinin (now the mainstay of treatment to malaria) is spreading in the region. Speaking to IRIN News, Leonard Ortega highlighted the role of increased movement of individuals and populations, and of the widespread use of fake or substandard drugs, in spreading resistant strains of malaria. He referred to studies, presented late last year at a WHO regional workshop of health officials, indicating that artemisinin resistance is present in areas along the Myanmar-Thailand, Myanmar-China and Cambodia-Vietnam borders.

Malaria vaccines could earn $ billions for manufacturers

A leading market research company forecasts that global market for malaria vaccines will reach $1.05 billion by 2017. The predictions are based on likely sales of products that are currently in the pipeline, including GlaxoSmithKline's Mosquiri (RTS,S), which continues to be investigated in several large scale Phase III trials in Africa. Mosquirix is at a more advanced stage than any other malaria vaccine but is expected to produce protection rates of only around 50%. More information available from MarketWire.

Malaria control programme in Angola comes under fire

The Internet allows open discussion to take place on a huge range of topics, including the implementation of programmes to control the infectious diseases of poverty. The excellent Topnaman blog on malaria presents a discussion of an article [1] in the Bulletin of WHO that criticised some aspects of the President’s Malaria Initiative’s (PMI) work in Angola. The intervention in question was the use of indoor residual spraying (IRS) of insecticide. The core of the criticisms made is that intervention areas were selected on the basis of reported clinical diagnoses of malaria, unsupported by laboratory findings, and that this led to expensive control efforts taking place in areas where they were not necessary. Published on the blog are a response from PMI to the original Bulletin article, followed by a comment on this from one of the article's authors, Bill Jobin. PMI say that the work conducted in a low-transmission area provided "experience and confidence" to enable subsequent activities in higher transmission areas. But Bill Jobin argues the case for programmes that are based on data from microscopic diagnoses in appropriate sentinel populations. "Then we will know what the problem really is, and where to put our efforts", says Jobin. Reference 1. Somandjinga M, Lluberas M, Jobin WR (2009). Difficulties in organizing first indoor spray programme against malaria in Angola under the President's Malaria Initiative. Bull World Health; 87(11):871-874.

Malaria: what drug should we take?

In the good old days, most cases of malaria responded to chloroquine (CQ) treatment and there was a high level of public awareness as to the name of this drug. However, as an editorial in the Tanzanian online newspaper ThisDay points out, in this era of CQ resistance, very few people have a clear idea of what drug they or their children need when they suspect they have malaria. Referring to a 2008 study [1] the article stresses that a high proportion of the antimalarials on sale in Africa are likely to be ineffective. The situation is confusing and people need guidance. ThisDay says, "There is need for the government to make an aggressive effort to remove all inappropriate and ineffective drugs (most of which are counterfeit products) from the shelves, while at the same time we look into the way of bringing down the costs of other effective drugs". Governments also need to provide more information to assist the public in their efforts to choose effective drugs from the range of products now available to them. Reference 1. Bate R, Coticelli P, Tren R, Attaran A (2008) Antimalarial Drug Quality in the Most Severely Malarious Parts of Africa – A Six Country Study. PLoS ONE 3(5): e2132.

Drugs for infectious diseases can make a profit

Research aimed at developing new treatments for the infectious diseases of poverty (IDPs) has generally been of very little interest to the pharmaceutical industry. The people with these diseases are, by definition, poor and would be unable to afford expensive new drugs. Hence there is no profit to be made. However, the economies of some of some countries with high rates of IDP incidence are now growing rapidly. China is a case in point. Tuberculosis is the country's number one infectious cause of death, claiming some 160,000 lives annually. China has the world's second highest number of TB cases, after India. But thanks to its economic success China can now pay for TB drugs. A study by the market research group ResearchAndMarkets says that China's demand for TB drugs has grown at a fast pace in the past decade. It predicts that, in the next five years, both production and demand will continue to grow. The study examines China's economic trends, investment environment, industry development, supply and demand, industry capacity, industry structure, marketing channels and major industry participants. (Unfortunately the full report is only available for a very high fee - around $6,000.) What impact will economic growth in IDP-endemic countries have on the research priorities of the pharmaceutical industry? Certainly countries that have both IDPs and money become a more interesting prospect. Many countries with growing economies are, for example, afflicted by dengue fever and by malaria. Will industry come to regard these as more attractive areas for research than previously? Some of the highest rates of infectious diseases, however, are in Africa where economies are still struggling. The profit motive for addressing their disease burden is still lacking.

Drug company wants to research neglected infections but "doesn't have a cent"

A report in Business News says that drug giant Novartis has had no success in trying to raise funds from the public and philanthropic sectors to to finance development of drugs against neglected illnesses including dracunculiasis (guinea-worm disease), malaria and tuberculosis. Novartis wants to raise about $1 billion annually for 10 years to create a fund that companies and institutions could draw on to develop treatments for diseases that get little drug-development interest because they wouldn’t be profitable. The US and European governments, the Bill & Melinda Gates Foundation and the Wellcome Trust have all apparently been approached without success. Paul Herrling, head of Novartis corporate research says, “It’s two years I’ve been working on this thing, and I don’t have a cent”.

Can yellow fever vaccine be modified to protect against malaria and dengue?

An intriguing report from Ecuador says that scientists have been given government backing to attempt to transform a vaccine used to protect against yellow fever so that it becomes active against malaria and dengue. Researchers from the University of Guayaquil will apparently use the transformed vaccine in a study based in a military hospital - see report from SperoNews.

Fake antimalarials seized in Nigeria

One reason why research is needed to develop new antimalaria drugs is the the appearance of resistance to drugs currently in use. The mainstay of malaria treatment is now artemisinin combination therapy (ACT) but many ACTs in circulation are faked or substandard versions. These products tend to contain low doses of active drugs, and when the malaria parasite is exposed to such doses the development of resistant strains is more likely to occur. Action against fakes has generally been inadequate. News that fakes have been intercepted and seized by the authorities is always welcome therefore. AllAfrica.com reports that Nigeria's National Agency of Food and Drugs Administration and Control (NAFDAC) has impounded a consignment of nine packages of the antimalarial Lonart (artemether plus lumafantrine) valued at Naira 10 million ($67 million). NAFDAC made the discovery during routine checks at Lagos airport and employed their recently acquired drug testing equipment to establish that the drugs were faked. While the story is encouraging, one can only speculate as to how many fake antimalarials (and other drugs) are still entering countries like Nigeria undetected.

Malaria and the global health system

"Support for and inclusion of local research institutions in global health research is essential to develop well-adapted health tools". This is the conclusion of an article in PLoS Medicine [1] which uses efforts to research and control efforts malaria as a case study. The article is the third in a series of articles on the changing nature of global health institutions. The authors review a century of malaria and research control activities. They note that there has been a shift from centralized. short-term programmes efforts, often relying on single interventions, toward more decentralized, continuous efforts using multiple approaches: "Malaria is no longer seen primarily as a biomedical problem, but rather as a complex ecological system in which humans, mosquitoes, and parasites are interconnected. Malaria has also increasingly been characterized as a “global” and regional rather than a national or local problem. This has led to changed concepts of governance". Reference 1. Keusch GT, Kilama WL, Moon S, Szlezák NA, Michaud CM (2010). The Global Health System: Linking Knowledge with Action - Learning from Malaria. PLoS Med 7(1): e1000179.

Malaria and more

The first month of 2010 has seen important developments in the world of malaria research. GlaxoSmithKline is putting into the public domain details of 13,500 “confirmed-hit structures” – compounds that other researchers will be free to screen for their potential use as antimalarials [1]. Meanwhile, the genome has been mapped of the plant from which the key antimalarial artemisinin is produced [2], which should pay the way for the development of higher yielding varieties. Also announced has been an extension of efforts to develop a so-called transmission blocking vaccine [3] active against the sexual stages of the malaria parasite. Such research, at the “basic” level, is essential if new tools active against malaria are to be developed, but putting effective interventions into practice is not easy. Research is also therefore needed at the implementation stage. A study in Tanzania [4] found that only a minority of women receiving bednets in a distribution programme were actually sleeping under them; studies like this one help to identify the points at which such programmes can fail. The implementation of another new antimalarial tool – the rapid diagnostic test (RDT) – also continues to be the subject of research. A Nigerian study [5] asked people whether, if they were ill, they would pay to be tested with an RDT. The majority said they would do so and, on average, the amount they were prepared to pay was greater than the current cost of an RDT in Nigeria (about $1.25). Nevertheless, the study's findings indicate that many people would not be willing (or could not afford) to be tested. It is therefore important that testing should be available free of charge. Further research in Tanzania [6] suggests that the introduction of RDTs could cut health care costs; malaria is considerably over-diagnosed and many antimalarials are given to patients who do not need them. (Tanzania is, by the way, one country where anti-malaria programmes are being significantly stepped up [7]). But programmes to treat and control malaria must be integrated with those for other infectious diseases. It is good to hear of new funding that will enable the Malaria Consortium [8] to demonstrate how government-led integrated community case management programmes (iCCM) can be scaled up, so that more children with malaria, pneumonia and diarrhoeal diseases receive appropriate treatment. A worrying story relating to the epidemiology of malaria has also been in the news during the last few days. It has become commonplace in the debate on climate change - which is likely to increase cases of many infectious diseases - to cite the rise of malaria in the East Africa highlands in order to demonstrate that global warming has already had such an impact. But where is the evidence that malaria has become more common in this part of Africa? When the UK government’s Department for International Development (DFID) issued a statement referring to the increase, an environmental campaigner asked to see the research on which the claim was based [9]. What he was sent was certainly not convincing. The need for reliable evidence on the prevalence of malaria has thus, once more, been underlined. Also in TropIKA.net News on other infectious diseases of poverty also appearing on TropIKA.net within the last few days has included an analysis of the funding provided for tuberculosis research worldwide [10] – it is growing but is still nowhere near the level that is required. It has also been demonstrated in a new study [11] that individuals with a low birth weight are particularly susceptible to TB. Recent months have seen major outbreaks of cholera across Africa for reasons that are by no means clear. A new surveillance programme [12] is therefore a welcome development. Leptospirosis is an important zoonosis (a disease of animals that can spread to people) in many countries but rarely receives attention from researchers. A study in India [13] suggests that the disease in people is spreading northwards. And a TropIKA.net opinion article [14] looks at WHO’s response to the appearance of H1N1 (“swine”) flu. This infection seemed likely to pose greater dangers for people living in the world’s poorest countries. Did WHO exaggerate the threat or was it correct to err on the side of caution? Paul Chinnock Editor, TropIKA.net

Tanzania's ambitious malaria goals

There can be no doubt that the government of Tanzania regards malaria as one of its top health priorities. It has announced that it plans to reduce case numbers by at least 80 percent over the next two years. Afrique en Ligne quotes Health and Social Welfare minister Professor David Mwakyusa as saying that the use of rapid diagnostic tests (RDTs) will play a major part in efforts against the disease. RDT kits will be used on a pilot basis in three selected regions (Coast, Iringa and Kagera) before their distribution to all parts of the country. Speaking at a launch event for the kits, Professor Mwakyusa said, "Malaria poses a great challenge, but if we play a collective role as individuals and do not leave the fight to the government alone, we will make malaria a history". Malaria is still Tanzania's leading killer, claiming 60,000-80,000 lives per year, mainly those of children under age five. Under-five malaria-related deaths have, however, already been much reduced, from 147 per 1000 live births a few years ago to 91 per 1000 in 2008. Meanwhile, Tanzania's Citizen newspaper reports that Tanzania spends over Sh850 billion (US$ 850 million) annually in fighting malaria. David Mwakyusa told the Citizen that the country spends 3.4 % of its gross domestic product on the disease. Around 29% of this is government expenditure, the rest of the figure is what individuals spend on drugs, coils, sprays and bed nets. The US President's Malaria Initiative (PMI) is amongst the biggest donors assisting Tanzania's malaria control efforts. This year the country will receive $52 million from PMI. The Tanzania mainland will be allocated $46.77 million of the total, while the remaining $5.23 million will be spent in Zanzibar where the war against malaria has already shown positive results.

"Malaria spreading in East African highlands": Where is the evidence?

A recent press release from the UK Department for International Development (DFID) suggested that millions more people in Kenya are now at risk of malaria as a result of mosquitoes colonising higher ground as global temperatures rise. But columnist and environmental campaigner Chris Goodall says that DFID has produced no evidence to back up this assertion. Chris Goodall approached DFID for details of the research on which the press release was based and was sent three papers. In his CarbonCommentary blog Goodall concludes that: "The specific claim that the Mount Kenya area has recently become vulnerable to malaria was backed up by interview data of a few years ago from a small number of families who declared a total of eight cases of malaria in the past five years compared to only three in the period of five to ten years ago. No medical analysis appears to have been carried out to determine whether the disease recorded was or was not malaria". He says that the evidence regarding the presence of mosquitoes at higher altitudes is equally insubstantial. Goodall adds that other research shows that "...the DFID assertion that malaria is increasing in highland regions of Kenya is highly questionable and that overall malaria rates are probably decreasing, although the geographic picture is complex". Climate change denialists - of whom there are many - are eager to jump on any unfounded claims made by those who advocate for action to hold back the threat. A warmer world is indeed likely to see rising rates of many infectious diseases and we must be prepared to adapt to this challenge. But unsubstantiated assertions are unhelpful and could well prove counter-productive.

Networks that will boost Africa's capacity in clinical research

A Nature Medicine news article discusses the European Clinical Development Partnership (EDCTP) and its recent achievement in contracting four regional networks that will facilitate the conducting of multicentre phase 2 and 3 clinical trials on AIDS, tuberculosis and malaria in sub-Saharan Africa. Africa hosts an increasing number of clinical trials but, for the most part, the continent lacks the basic infrastructure and expertise to conduct trials that meet international standards. EDCTP's networks are intended to improve the situation by upgrading the quality and capacity of local hospitals and research centres. EDCTP is a partnership between 47 sub-Saharan African countries and 14 European Union member states plus Norway and Switzerland. Since its launch in 2003, it has provided over $300 million to fund 45 clinical trials in 21 African countries. The fourth of its regional networks, the southern African group, was contracted in November 2009. According to Thomas Nyirenda, EDCTP’s networking and capacity development manager in Cape Town, "There are centres that are good here and there, but there’s a lack of critical mass of researchers on the continent. The driving force is to really put a structure in place that will be sustainable". Ruxandra Draghia-Akli, the European Commission’s director of health research says it is hoped to extend the trials conducted under the initiative to cover also other more neglected infectious diseases. EDCTP has also featured in other recent articles on TropIKA.net.

Novel financing mechanisms for global health

Last week’s Economist magazine takes a look at innovation in global health financing with a feature article on UNITAID and the Massive Good movement of the Millennium Foundation, among other novel mechanisms designed to leverage the wealth of populations to fund medical care for TB, AIDS, and malaria. In the 1990s, more than two-thirds of the $5.6 billion spent on global health assistance came from governments. In 2007, the Gates Foundation and other major philanthropies accounted for the bulk of total funding for health. While those models relied on a small number of large donations, UNITAID is targeting entire populations by introducing so-called “solidarity tax” on purchases of airline tickets. Founded by France and Brazil in 2006, UNITAID is hosted by the WHO and has raised more than $1.5 billion over the past four years. The organization’s primary goal is to ensure access to drugs against the most deadly global diseases by negotiating low prices for the bulk purchase of medications and to incite the development and mass production of special drugs (such as pediatric treatment for HIV/AIDS-infected children). In January, a private foundation linked to UNITAID called MassiveGood, started raising money from the public directly with the help of the Tourism and Travel industry. In his new book, “Power in Numbers: UNITAID, Innovative Financing, and the Quest for Massive Good”, UNITAID president Phillippe Douste-Blazy argues that “building solidarity” will be essential to any effort to combat disease. The article goes on to describe other new approaches, including the GAVI alliance’s strategy of issuing bonds backed by sovereign pledges of aid money in future years; the Global Fund’s exchange-traded fund aimed at both traditional investors and “socially responsible” ones; and the WHO’s effort’s to pressure the drug industry to relax patent protection and for large drug makers to share patents with more modest institutions. By pooling patents, the cost of development can be lowered and the pace accelerated. GlaxoSmithKline and Pfizer have announced they would combine their patents for HIV into a joint research effort called ViiV. Also profiled is the Affordable Medicines Facility-Malaria (AMFm) to be rolled out by the Global Fund by mid-2010. Spending $216 million over two years to subsidise the cost of ACT to wholesale buyers, the Global Fund intends to reduce the retail price to between 20 and 50 cents, although 50 cents may still be too expensive. “The flurry of innovative schemes should help,” write the authors, “but the developing world will have to mobilise its own money and willpower to tackle humanity’s great scourges.”

“You Idiots”

Patrick Adams writes... That’s the cover quote of the current issue of Rolling Stone, which kicks the New Year off with a cover piece on “The Climate Killers,” by Tom Dickson. The story, a series of rap sheets on the 17 “deniers and polluters who are derailing efforts to curb global warming,” starts off with Warren Buffett, CEO of Berkshire Hathaway and – after Bill Gates – the second richest man in the world. In 2008, he was indeed in the top spot. Buffet, who’s promised to donate roughly 85% of his fortune to the Bill & Melinda Gates Foundation and four other philanthropies, has called the climate bill passed by the US House of Representatives a “huge tax” that would mean, “very poor people are going to pay a lot more for their electricity”. But Buffett isn’t just bad-mouthing climate legislation, writes Dickson. “He’s literally banking on its failure,” with millions invested in carbon-polluting industries. Berkshire Hathaway bought 1.28 million shares of America’s biggest climate polluter ExxonMobile, and last November purchased the Burlington Northern Santa Fe railroad for $26 billion. “As a savvy investor, Buffett would only buy a coal-shipping railroad if he felt certain that Congress will fail to crack down on climate pollution,” writes Dickson. Labelled the “The Profiteer,” by Rolling Stone, Buffett’s investments certainly reflect his opinion that “capitalism is the greatest growth engine ever invented”. But is it the greatest invention for population health in developing countries? For all of his admiration for the Gates Foundation, Buffett most likely wasn’t investing with malaria in mind – or for that matter any of the diseases for which climate change represents a major risk factor. When Buffett’s donation to the Gates Foundation was first announced, back in June 2006, it was reported that whereas most people with this amount of money would typically try to create a foundation in their own image, the then-75-year-old Buffett was humbly entrusting it to a close friend 25 years his junior, who would know how to use it properly. Given that Buffett’s investments have the power to move entire markets, and that the effects of climate change on infectious diseases of poverty are likely to be rather large, one might have hoped that the “Oracle of Omaha” (as Buffet has been nicknamed) would have sought out his friend Gates – who has been highly vocal about the life-or-death consequences of climate change for the poor – for some sound advice.

New dengue guidelines show how policy is informed by research

Recently published new guidelines for the diagnosis, treatment, prevention and control of dengue (see TropIKA.net report) have been hailed by the Wellcome Trust as an example of how research can shape policy - see Trust press release. The Wellcome Trust funded some of the research on which the new guidelines are based, particularly research conducted in Viet Nam. The press release also describes how malaria policy in Kenya has been influenced by Trust-funded work.

Where would Nigerians like to get their malaria treatment?

Prompt access to appropriate and affordable treatment is a critical component of efforts to improve the control of malaria. But in low-resource nations, the limited healthcare facilities available make it difficult to provide good quality malaria management services. In seeking to improve these services in such a way that patients will make good use of them, it is important to take account of where and how people in malaria-endemic countries themselves would like to have their treatment provided. A team of Nigerian researchers has conducted a questionnaire survey of 2,250 randomly selected householders in the southeast of the country, in both rural and urban areas (1). They also recorded information to enable them to determine the socioeconomic status of their interviewees. Their findings are of some interest. The questionnaire offered respondents a choice of different sources of treatment, including public and private hospitals, public primary healthcare (PHC) centres, pharmacy shops, patent medicine dealers, home-based care by trained mothers, herbalists or community health workers (CHWs). The most preferred sources of treatment were public hospitals (30.5%), trained mothers (19%) and PHC (18.1%). Traditional healers (4.8%) and patent medicine dealers (4.2%) were the least preferred sources. Many studies have shown that it is extremely common people with a fever (or with a child who has a fever) to seek treatment first from a traditional healer or to self-medicate with drugs bought in pharmacy or other shops. In this part of Nigeria, it seems that most people doing so only take such action because of the poor availability of current health services, rather than because it is what they would actually prefer to do. The findings showed that traditional healers were more popular in rural areas, probably because rural dwellers have more familiarity with them. Other findings included a greater level of preference for hospital treatment in respondents with higher levels of SES. The authors rightly note that other factors, such as occupation and age, might also affect preferences of different sources of treatment. It is also important to emphasize that these findings apply only to the part of Nigeria in which the survey was conducted. Similar studies in other malaria-endemic areas where it is intended upgrade treatment services would be of considerable help in policy and planning. Reference 1. Uguru NP, Onwujekwe OE, Tasie NG, Uzochukwu BS, Ezeoke UE (2010). Do consumers' preferences for improved provision of malaria treatment services differ by their socio-economic status and geographic location? A study in southeast Nigeria. BMC Public Health. 2010 Jan 5;10(1):7.

Commitment and collaboration

At the turn of the year, it is always heartening to be able to report some good news. WHO’s new certification of no less than seven countries as being free of dracunculiasis (guinea worm disease) provides a demonstration of what can be achieved against an infectious diseases of poverty when there is commitment and international collaboration. The progress made against dracunculiasis is quite remarkable; it is estimated that there are now fewer than 3,500 cases of the disease worldwide when, just 20 years ago, the total was approaching three million. WHO also adopted an upbeat tone in its recently published World Malaria Report 2009. However, detailed inspection of the report reveals that, while there has been encouraging progress in prevention programmes (particularly as regards the distribution of insecticide-treated bednets), diagnosis and treatment are lagging behind. To quote from the report: “...in 18 high-burden WHO African Region countries for which data were available, 22% of the reported suspected malaria cases were confirmed with a parasite-based test ... countries received only about 50% of the ACTs [artemisinin-combination therapies] needed to treat malaria cases at health facilities in the public sector ... less than 15% of children under 5 years of age received an ACT when they had fever in 11 of 13 African countries for which survey data were available”. There is indeed cause for optimism following some of the recent achievements against malaria but there is still much to be done before the goal of eliminating the disease can be reached. It is encouraging therefore to learn of new Gates Foundation funding to support the development of one potential vaccine. The US government has also announced the award of a grant to support further research that it is hoped will facilitate the development of vaccines against malaria, and also against dengue and tuberculosis. It is very much to be hoped that such support will continue but, as we have reported on TropIKA.net, many experts believe that donor contributions have now peaked and that further increases may not be seen until the world recovers from the continuing economic crisis. Malaria is also the focus of our latest TropIKA.net Profile interview, in which Dr Laurence Slutsker, chief of the malaria branch at the Centers for Disease Control, USA speaks about CDC’s major contributions to malaria research and describes the organization’s current work in evaluating potential new tools to fight the disease. Our role on TropIKA.net is to facilitate debate, not just on malaria research, but on efforts to combat all the infectious diseases of poverty. Other recent items on the knowledge platform have concerned tuberculosis, leishmaniasis, rotavirus, dengue and zoonoses. Paul Chinnock Editor, TropIKA.net

Gates funding will support clinical product development of malaria vaccine

The Fraunhofer USA Center for Molecular Biotechnology (CMB) says it has been awarded $9.85 million by the Bill & Melinda Gates Foundation for clinical development of a transmission blocking vaccine to combat malaria. Fraunhofer USA CMB, a division of Fraunhofer USA, Inc., is a not-for-profit research organization which seeks to develop safe and effective vaccines targeting infectious diseases and autoimmune disorders. Dr Vidadi Yusibov, CMB’s Executive Director, says, "We are looking forward to beginning clinical product development following up on the exciting pre-clinical results we have achieved to date". The award has also been welcomed by Dr.Philip Russell of the Sabin Vaccine Institute, who commented, “The technology has the potential to provide the capacity and cost effectiveness required to deal with the health and economic problems caused by malaria in developing countries”. Further details are available in a Fraunhofer USA CMB press release.

Moving forward against malaria: contrasting experiences in two African countries

During the course of 2009, falls in the number of malaria cases were reported from several parts of Africa. It is widely believed, but yet to be proved, that the introduction of new tools for malaria control such as artemisinin-combination therapies (ACTs) and insecticide-treated bednets (ITNs), have been responsible for these encouraging declines. According to a report from AllAfrica.com, Zambia has reached the goal of a 50% reduction in malaria case numbers. The National Malaria Control Centre's acting coordinator, Mulakwa Kamuliwo says malaria deaths in children under the age of five prevalence levels of the malarial parasite have both been reduced, as have cases of children with severe anaemia. Dr Kamuliwo attributes the decline particularly to ITNs and indoor residual spraying (IRS). An important role has been played by the Konkola Copper Mines (KCM) initiative on which the national anti-malaria drive has been based. The support of communities for the new interventions is also regarded as crucial. Zambia continues to expand its malaria control programmes and seems set to be used as an example of what an African country can achieve against the disease. In contrast, Sierra Leone is said to be experiencing increasing numbers of cases of malaria - see report from IRIN News. The situation in Sierra Leone is blamed by WHO and UNICEF largely on a drug procurement problem. Prevention and rapid response also need to be strengthened. Just 26% of children sleep under ITNs (although this represents a five-fold increase over the last five years), and only30% of children with malaria receive treatment within 24 hours of onset. WHO and UNICEF have issued an emergency appeal for 1.3 million bednets and antimalarials for Sierra Leone, at a cost of $16.9 million. The contrasting experiences of these two African countries demonstrate the need for intervention research. We must establish just what it is that leads to success when new tools for malaria control are introduced in one country and to failure when the same measures are tried elsewhere. There is much to be learned from what is taking place in both these countries.

Malaria vaccine uses nasal route

Japanese researchers have claimed to be the first to use a nasal vaccine to successfully block transmission of the malaria parasite from mosquitoes to mice. Their finding may lead on to the development of such a vaccine for use in the prevention of malaria in humans. Malaria vaccines based on ookinete surface proteins (OSPs) of the malaria parasite are known to block oocyst development within feeding mosquitoes, thus disrupting the parasite's life cycle. The Japanese team - based at the Tropical Biosphere Research Center, University of the Ryukyus - set out to investigate whether a nasally administered OSP vaccine could effectively block parasite transmission in vivo. Writing in the journal Infection and Immunology, they report that mosquitoes that took a blood meal from nasally vaccinated mice were subsequently unable to pass on the parasite to other mice as the fertilization cycle had been interrupted. Reference Arakawa T, Tachibana M, Miyata T, Harakuni T, Kohama H, Matsumoto Y, Tsuji N, Hisaeda H, Stowers A, Torii M, Tsuboi T (2009). Malaria ookinete surface protein-based vaccination via the intranasal route completely blocks parasite transmission in both passive and active vaccination regimens in a rodent model of malaria infection.Infect Immun; 5496-500. Abstract on PubMed. (Full paper is not open access.)

Dwindling funds for malaria could reverse recent gains

Patrick Adams writes... A number of countries have made great strides in terms of malaria control, resulting in reductions of over 50% in the number of malaria cases in more than a third of affected countries. According to the World Malaria Report 2009, the progress was made possible by major increases in donor country contributions to the Global Fund, leading WHO Director General Dr Margaret Chan to declare that “development aid for health is working”. The report notes, however, that funds for malaria “are disproportionately concentrated on smaller countries with lower diseases burdens”. The report recommends that, in order to maintain the gains made to date, “more attention be given to ensuring success in large countries that account for most malaria cases and deaths”. Yet more worrying, some experts say, is the possibility that donor contributions may have peaked. Last February, it was announced that the Global Fund faces a $5 billion shortfall through 2010. In order to address the gap, the fund would impose a series of “efficiency cuts”, “uncertainty cuts” and “delays”. Reporting on the Global Fund’s 20th board meeting in Addis Ababa last month, policy analyst David Wendt speculated that these measures could put at risk more than US$ 1 billion of the US$ 2.64 billion of approved Round 9 budgets. “The prospects for increasing donor contributions to the Global Fund are small,” says Dr Matthew Lynch, director of the Global Program on Malaria at the Johns Hopkins Bloomberg School of Public Health. “Given the delays associated with Rounds 9 and 10, even maintaining the current GFATM funding levels is going to be a stretch.” And though the funding level for Round 10 has yet to be determined, he says, “it’s not likely to be huge”. Lynch adds that while the US government “is doing a lot,” and the President’s Malaria Initiative (PMI) is “fully-funded and doing a very good job,” these bilateral contributions represent just a fraction of Global Fund amounts. The global recession may be partly to blame, he says. But even so, the basic donor-recipient paradigm has to change. “I do still believe ‘cautious optimism’ is appropriate,” says Lynch, referring to WHO Director General Dr Margaret Chan’s reaction to the global report findings. “Mortality levels are declining. There are two more years to run on Round 8 funds. And I think we will demonstrate some substantial returns-on-investment. But countries are going to have to recognize those returns-on-investment and start shouldering more of the financial load.” Richard Tren, director of Africa Fighting Malaria, has been among the more vocal advocates calling for more domestic funding for malaria. He has said that external funding alone will not be sufficient, and, along with many others, he’s questioned the distribution of limited aid dollars on wealthy countries like China and India. China is the third-richest nation overall, India the fifth. In the Global Fund’s 9th round of funding since 2002, China’s total funding request for a malaria “National Strategy Application” (NSA) was roughly $ 176.5 million. (An NSA is a funding channel that allows countries to request support for strong existing national HIV/AIDS, TB and/or malaria strategies). Meanwhile, India requested more than US$ 113 million for malaria. But are these countries indeed “rich”? In per person terms, China is poorer than 132 countries; India is poorer than 166. Both have space programmes, but both also have extreme poverty. Regardless, says Lynch, it’s clear that relying on donors will be increasingly risky for endemic country governments. It’s also likely, he says, that even households will need to make contributions as well. “Malaria elimination is a long-term goal, which means a long haul for maintaining high net coverage. The era of the free nets campaign may be rapidly drawing to a close.”

Moving forward from Copenhagen: we must campaign for more research

Most observers have described the Copenhagen climate change conference as a failure. A limited and non-binding agreement – the Copenhagen Accord – has been signed but there is little doubt that, within a few years, we shall all be living in a much warmer world and suffering many adverse consequences. These will include increases in water-borne and vector-borne infectious diseases. (For more details see TropIKA.net News.) On the credit side, the Accord makes provision for additional funds to be made available to assist developing countries in adapting to climate change. New funding will begin from next year and, by 2020, $100 billion will be available for this purpose annually. It is by no means clear what this money will be spent on, or to what extent adaptation efforts will address health issues generally and infectious diseases specifically. As we reported in TropIKA.net News, adaptation efforts so far have generally ignored health. But to some extent this is understandable; we do not yet know enough about the impact that climate change will have on infectious diseases and on the most effective ways of mitigating this impact. There is a desperate need for more research, and powerful advocacy efforts will be required to ensure that some of the adaptation funding is devoted to this purpose. During the conference, TropIKA.net has interviewed a number of medical researchers with particular interests in this area. In our most recent interview, epidemiologist Jonathan Cox says that it is important that climate effects are put in the wider context of other potentially important drivers. Our “Copenhagen Blog” has also identified a number of recent climate change developments. These include the publication of an article that identifies climate factor as a factor in the growing number of cases of zoonoses, and a call for the development of R&D capacity in the South. And there is news of new US government grants made available for research intended to improve understanding of the ecological mechanisms that govern relationships between human-induced environmental changes and the emergence and transmission of infectious diseases. Elsewhere on TropIKA.net... There has always been uncertainty as to how much money is going into research into the infectious diseases of poverty, not to mention where this funding comes from and the extent to which research on specific infections is supported. The G-FINDER project was launched to provide information on such questions and this project’s latest report is now featured on TropIKA.net. The G-FINDER team concludes that, since the beginning of the global economic crisis, new financing has “ground to a standstill” and AIDS continues to receive a disproportionately large share of the total funding available. But perhaps the most interesting conclusion of the report is that India and Brazil are emerging as key players, particularly for the more neglected diseases. Also recently featured in TropIKA.net Reports section are A new “blueprint” for TB diagnostics and Dengue: guidelines for diagnosis, treatment, prevention and control. The number of distinguished researchers who have been interviewed by the TropIKA.net team has increased lately. We spoke with Dr Stephen Hoffman founder and CEO of Sanaria, a biotechnology company dedicated to the production of a sporozoic pre-erythrocytic-stage vaccine for P. falciparum malaria. And Dr Christine Moe told TropIKA.net that sanitation remains a neglected area, adding that, “I do get concerned about money and resources and effort going into vaccine development for diseases that I think would be better reduced by water and sanitation”. Finally, there is always something going on in the TropIKA.net Blog. Amongst other developments we have recently reported here are the welcome news of increased US funding for research into neglected tropical diseases, a continuation of the debate as to whether it is helpful to talk in terms of eliminating malaria, and a remarkable story from Senegal – No bednet? Pay a fine!

Ethiopia will receive US funding for malaria

The USA will be making a three-year, $40 million grant to the United Nations Children’s Fund (UNICEF) to assist Ethiopia's Oromia Region in the delivery of appropriate malaria prevention, diagnosis, and treatment services. Ethiopia is one of the focus countries under the US President's Malaria Initiative (PMI), which aims to reduce by half the number of malaria deaths in 15 African countries using proven malaria interventions. Oromia is the Ethiopia's largest administrative region and bears the brunt of the country’s malaria burden.The programme, called "Sustaining Malaria Reduction Interventions in Oromia”, will increase access to effective diagnostic tests and medicines to manage malaria cases and promote household ownership and proper use of insecticide-treated bednets. Through UNICEF, USAID will procure and distribute 3.7 million rapid diagnostic tests for use by health staff and health extension workers; distribute 9.4 million treatments of medicines to fully treat confirmed malaria infections in Oromia; and procure and distribute 3.9 million bednets and support the distribution of nets from other sources such as the Global Fund to Fight Aids, Tuberculosis and Malaria, the World Bank, the Carter Center and other partners. See US Embassy press release for more details.

No bednet? Pay a fine

In one part of Senegal, local women now conduct "bednet patrols". They have the power to fine anyone who has a bed that is not protected by an insecticide-treated net (ITN). This surprising, and many would say unduly harsh, approach to increasing the use of ITNs as part of malaria control activities, is one of the strategies employed in community initiative in the rural community of Tiénaba in the Thiès region of Senegal. An association launched in 2000 comprises 65 public health committees headed by village women who run education and awareness campaigns, and impose penalties when people do not follow "hygiene rules". The fine for not having an ITN is equivalent to US55 cents. According to IRIN News, 15 cases of malaria were reported among the 4,000 residents of Tiénaba in 2009, compared to 1,140 in 2004.

Mobile phones track where Zanzibaris travel, as part of malaria elimination programme

Zanzibar has made huge strides in its efforts to control malaria and is now seeking to eliminate the disease as a public health problem. US researchers from the University of Florida are aiding the elimination campaign by following where Zanzibar people travel. Analysing the records of mobile phone calls made by Zanzibaris, the Florida team found that most people did not leave the island; should malaria be eliminated, such people would not play a part in any subsequent re-introduction of the disease. Of those who do travel further afield, most only went as far as Dar es Salaam on the Tanzanian mainland, where they stayed just a few days. They are considered to be at relatively low risk of acquiring malaria during their travels. However, "a few hundred" Zanzibaris travel to inland parts of Tanzania which are highly endemic for the disease. They would be the most likely people to reintroduce malaria to Zanzibar. The Florida scientists say that the Zanzibar government could choose to give residents prophylactics against malaria before they travel, or it could screen all residents as they return, both very expensive propositions. Or it could launch a targeted information and/or screening campaign aimed at the high-risk travellers. (More details in University of Florida News.) Some of us feel uncomfortable about our mobile phone records being accessed without our permission to find out who we talk to and where we go. In this case, of course the information has been put to good use.

Climate change: Africans are already learning to adapt

An article in South Africa's Globe and Mail claims that innovations already under way in Africa are helping people to keep pace with the effects of climate change. New energy sources, more efficient farming methods and malaria research are all examples cited by author Geoffrey York.

Malaria: is elimination a useful concept?

Can we hope to eliminate malaria as a public health problem? 'Elimination', in this context, would mean the interruption of disease transmission, creating zero incidence of locally contracted cases. Or is it more realistic to think in terms of improved control and reductions in case numbers? The issue is hotly debated. A short Lancet Editorial reports the recent comments of Nick White at the UK Academy of Medical Sciences' annual international health lecture. He believes that there is now an opportunity to eliminate malaria in many parts of the world. He made reference to the Malaria Elimination Group's efforts to identify countries where national or subnational elimination strategies could deliver zero transmission. But at the same meeting another leading malaria specialist, Kevin Marsh said that focusing on elimination could be harmful by causing false hopes.

Nigerian fears of insecticide resistance

A worrying report from news agency AFP says that delegates at a conference in Abuja, Nigeria have expressed that mosquitoes are becoming less sensitive to insecticides. According to Peter Clearyof Vestergaard Frandsen, manufacturers of insecticide-impregnated bednets, "There is concern that the malarial vectors are becoming resistant to the entire class of insecticides the WHO approves". Amongst others interviewed by AFP was Yayo Abdulsalam, a researcher and lecturer in medical entomology. He points out that, "In cases where there is high resistance of mosquitoes to insecticides, there is high usage of agricultural pesticides". Resistance is the "first warning sign that you have to take necessary measures to ensure that the few insecticides we have... will be effective," says Sam Awolola, a scientist with Nigerian Institute of Medical Research. The impact of climate change on malarial mosquitoes was also discussed at the conference.

Loss of biodiversity linked to rise of infections

ScienceNews reports on a study, published in BioScience that is claimed to be the first to demonstrate the link between the loss of species (due to climate change) and the increase in the incidence of certain infectious diseases including: malaria, schistosomiasis Lyme disease and hantavirus.

Learning to adapt: why we need research on the health impact of climate change

Climate change provokes heated debate. Opinion polls repeatedly show that many people doubt that the world’s climate is changing and, of those who accept reality, many do not believe that the changes are man-made. The lack of public support for efforts to address climate change seems likely to hinder the progress of these efforts. As discussed in a TropIKA.net editorial, governments have focused on the impact of climate change on economies and not on the threat it poses to the health and wellbeing of individuals. Perhaps this is one reason why the public at large has yet to grasp the seriousness of the situation. There are of course many ways in which climate change threatens human health, including injury from extreme climatic events such as flooding, and food shortages caused by droughts. Many infectious diseases are also likely to become more widespread. Poor communities face the greatest threats and are least well placed to respond. Health inequalities are in consequence likely to widen. The 15th UN Climate Change Conference (COP15) is now under way in Copenhagen, 7-18th December. So far, since the conference began, very little time appears to have been devoted to the infectious diseases of poverty, although some delegates have made reference to their concerns regarding the likely increase in certain infections including malaria, dengue, pneumonia and diarrhoeal disease. The health community itself has come late to the climate change debate, seemingly content until now to leave it to climatologists and politicians but, in the run-up to the conference, the Lancet has performed a considerable service in highlighting the health dimension in a series of articles that deserves detailed scrutiny. In the first week of COP15, other medical journals are also publishing editorials on the subject but, thus far, we have not seen the publication of new data timed to coincide with the beginning of the conference. Data, however, are needed to inform the debate and to determine the action that the world must now take to address climate change. There is indeed so much that we do not yet know. As Tony McMichael of Australia’s National Centre for Epidemiology & Population Health points out in a TropIKA.net interview, how people will respond to climate change is more difficult to predict than climate change itself. Professor McMichael’s view is that far the biggest infectious disease risk from climate change is diarrhoeal disease. Others, however, have been more inclined to highlight the threats posed by vector-borne diseases particularly malaria, dengue and Chikungunya. These are not the only diseases that could become more common in a warmer world. Schistosomiasis seems to be expanding its range in many countries. In a TropIKA.net interview Dr Justin Remais of Emory University, USA discusses his use of a mathematical model to quantify environmental impacts on transmission intensity. But will there, for example, be any effect on tuberculosis as a result of climate change? We don’t know. We should not jump to too many conclusions or try to blame everything on climate change. It has been commonplace, for example, to blame the serious outbreaks of dengue now occurring in many countries on global warming, but this ignores the role of increasing urbanisation and the growth of populations in poor urban environments where vector control activities are inadequate. We need to be better informed and research will be crucial in determining the effectiveness of efforts to adapt to a changing climate. As Andrew Githeko points out in a guest blog on TropIKA.net, the organisms responsible for the transmission of infectious disease have demonstrated their ability to adapt. We must now do the same. See the TropIKA.net Copenhagen blog for other climate change developments that relate to the infectious diseases of poverty. Paul Chinnock Editor, TropIKA.net

Short-term temperature variations could influnce malaria risk

The climate change debate has largely focussed on the steady rise in average temperatures. A mathematical modelling study suggests that diurnal temperature variation (the difference between the daytime high and the night-time low) could also be a major factor in determining malaria transmission rates. The findings of the study, published in the Proceedings of the National Academy of Science, indicate that temperature fluctuation reduces the impact of increases in mean temperature. When mean diurnal variation is over 21°C, parasite development is slower than at constant temperatures. Lower levels of variation speed parasite development. The researchers conclude that, "...models which ignore diurnal variation overestimate malaria risk in warmer environments and underestimate risk in cooler environments".

How climate change will hurt Uganda

Africa's media are taking a keen interest in the Copenhagen climate change. See, as an example, an excellent article on AllAfrica.com, which examines the likely impact of climate change on human and animal diseases in Uganda. Author Frederick Womakuyu spoke to experts on health and environment based in Uganda, including WHO representative Joaquim Saweka who said that malaria, cholera, swine flu and hepatitis E were amongst the diseases that could become more common in the country.

Call for action to end malaria drug "stock-outs"

Artemisinin combination therapy (ACT) is the recommended treatment for malaria and its use has been, officially, adopted in most Africa countries. But, as we have often reported on TropIKA.net (e.g. 1, 2) health care facilities, particularly in the rural areas, are frequently out of stock of this much needed treatment. Patients only have access to older ineffective drugs and/or counterfeit products. The increasingly influential journal PLoS Medicine has added its voice to calls for a new wave of malaria activism to raise awareness of the "ACT stock-out crisis". An editorial quotes leading malaria specialist Bob Snow of the KEMRI-Wellcome Trust Research Centre in Nairobi, who says: “We abandoned chloroquine when it failed to cure one in four patients and was available everywhere.We now have a drug that cures 100% of patients but is not available in one in four clinics.” Dr Snow blames the problem on health systems issues including inadequate ordering, distribution and supply. Addressing such issues is a complex matter. The editorial's discussion of how best to proceed represents an important contribution to the debate. An initiative devoted to stock-outs does already exist. Stop Stockouts deals with all essential medicines (not just antimalarials) and its focus is on East and southern Africa.

Navrongo Health Research Centre celebrates 20 years

Ghana's internationally known Navrongo Health Research Centre, situated in the far north of the country reached its 20th anniversary on 30th November 2009. Research at the centre has included studies on many of the infectious diseases of poverty. While originally the focus was on the health problems of the Sahelian ecological belt, the centre's remit has since broadened to include issues of national and international significance. Infectious diseases currently under study at Navrongo include malaria, schistosomiasis and meningitis. For a report on the birthday celebrations see Peace FM Online. TropIKA.net wishes the Navrongo centre many happy returns!

Reporting the debate – Testing the tests

Once again, the TropIKA.net team has been out and about. We have provided in-depth coverage of Forum 2009, the latest conference of the Global Forum for Health Research (GFHR) held in Cuba. Highlights from our in-depth reports include interviews with Anthony Mbewu, President of the Medical Research Council, South Africa and next Executive Director of GFHR. He described his plans for moving the global health research agenda forward and also the steps now being taken to establish a biotechnology platform in South Africa. Also interviewed was Carlos Morel, Director of the Center for Technological Development in Health at Fiocruz, Brazil. He discussed the difficulties in transferring innovations in health technology developed in one part of the South to other countries, where circumstances may be very different. Forum 2009 made it possible for delegates to exchange their sometimes very different views on innovative approaches to health. For example a session on digital health care in rural India led to some lively exchanges. Testing the tests Rapid diagnostic tests (RDTs) will, it is hoped, play a major part in advancing efforts towards the elimination of malaria. The successful management of other infectious diseases of poverty would also benefit from the development of simple, affordable tests that can be used on the front line of care. However, such tests must themselves be tested for their accuracy and, when tests are tested, rigour is required both in the conduct of the work involved and in its reporting. It is therefore disturbing to read the findings of a review evaluating the quality and reporting of diagnostic accuracy studies in TB, HIV and malaria. It would appear that the required rigour has been lacking in much of the testing so far conducted. This does of course raise again the question of how much we can depend on the RDTs themselves. The dependability of the drug supply has for many years been a topic of great concern – a large proportion of the drugs available in developing countries are faked or substandard. It is good news that efforts to control counterfeiting are to receive a boost with new support from USAID. For some neglected infections, the drugs that are really needed do not yet exist. This is particularly the case for the three kinetoplastid diseases: Chagas disease, human African trypanosomiasis and leishmaniasis. The Drugs for Neglected Diseases initiative (DNDi) continues its remarkable work in the search for new treatments and a few days ago announced a collaboration with drug giant Pfizer, which will allow screening of its library of compounds to identify any that may have potential for use against these three diseases. Other new developments also featured on TropIKA.net include Brazilian research demonstrating that the movement of people may be more important than previously thought in the transmission of dengue fever; the findings suggest that the disease is often transmitted outside the home, for example at school or in public spaces. And from Nigeria there is worrying news that the savannah-dwelling blackflies that transmit blinding onchocerciasis are becoming more common in the southwest of the country. Meanwhile, from southeast Asia comes the unwelcome, though predictable, news that resistance to the key antimalarial artemisinin has now spread from the Cambodia–Thailand border to China, Myanmar and Vietnam. Facilitating communication between professionals seeking to address the infectious diseases of poverty is at the centre of our efforts on TropIKA.net and we are well aware of the dominance of English as the medium in which most communication on global health takes place. We welcome the news that the Portuguese-speaking health community will benefit from a newly launched email forum. Paul Chinnock Editor, TropIKA.net

Malaria researchers "losing their way"

A Dutch malariologist, Bart Knols, has accused his fellow researchers of being more interested in subsidies and getting articles in prestigious journals than in solving the problem of malaria. Dr Knols told Radio Netherlands Worldwide that too much research is now focussed on genomics and not enough on improving mosquito control. In his view: "... you turn a gene on or off in the malarial parasite and then you observe what happens to it: that’s ‘hot science’. Then, you’ll maybe get data that you can publish in Nature or Science. This, in turn, gets you your next research grant. It’s turned malaria research into a kind of industry". He points out that mosquitoes are expanding their range and, "If we’re not prepared to do everything in our power, including the use of computer technology, GPS systems, four-wheel drive trucks, and lots of money… the mosquito [will win], without a doubt." What do TropIKA.net readers think of Dr Knols' views? Use our Leave a Reply facility below to share your opinions.

Artemisinin resistance has spread to China, Myanmar and Vietnam

The greatest threat to efforts to improve the control of malaria, with the longer term aim of disease elimination, is the appearance of resistance to the treatment drug artemisinin. The first reports of resistance, confirmed in a study published in August, came from the Thailand-Cambodia border. But the Malaria Consortium says that signs of resistance have also been noted in China, Myanmar and Vietnam. As the Consortium explains: "The proportion of patients who still carry malaria parasites on the third day of treatment is currently the best measure available of slow parasite clearance and can be used as a warning system for confirmation of artemisinin resistance. Currently, the alert point for resistance is at 10% of patients retaining the parasite after day three. Levels of day three positives in Myanmar with ACT treatment, and China and Vietnam with artesunate treatment range from 12-31% in recent studies". The Consortium also reminds us that the biggest fear is that resistance will spread to Africa, which is where most of the world's malaria cases and deaths occur.

Podcasts from Nairobi

The London School of Hygiene & Tropical Medicine has made available a series of podcasts from the MIM conference. They may be accessed on the School's Audio News site. The podcasts include the following. Professor Brian Greenwood discusses the presentation he gave to the conference, in which he explained that combined prophylactic and therapeutic use of malarial drugs can play an important part in programmes to control the disease. Epidemiologist Diadier Diallo, co-ordinator of a trial of intermittent preventive treatment (IPT) for children in Burkina Faso and Mali, discusses what has been learned from this project. In another podcast, Dr Harry Tagbor describes his IPT work in Ghana. Geoffrey Targett Professor of Parasitology says the prospects for malaria elimination are good in many regions. There is also an interview with Bianca D'Souza, Manager of the ACT Consortium. Other interviews focussing on the Consortium involve Ugandan Health Ministry Commissioner Dr Anthony Mbonye and - from the School - Professor David Schellenberg and Dr Harparkash Kaur.

Scientific American publishes malaria update

The journal Scientific American has published a short article on malaria research that includes an interesting slide show examining some of the new tools being developed for control of the disease. The article also links to a video presentation shown during a recent conference held at the Johns Hopkins Malaria Research Institute (JHMRI). The article may be accessed here.

Affordable antimalarials may help hold back spread of fake products

Arguably the greatest threat to international efforts to improve malaria control, with elimination of the disease as the ultimate goal, is the appearance of resistance to the recommended treatment drug - artemisinin. As with earlier antimalarials, resistance has first appeared in Southeast Asia. Initial reports of resistant strains of the parasite in the border regions of Cambodia and Thailand in 2008 were confirmed in a research article published in August this year. Whilst it is not yet fully understood why resistance is most likely to develop in this part of the world, the ready availability of fake and substandard drugs is undoubtedly a factor. Of particular concern is the number of drugs on sale which contain low doses of artemisinin as monotherapy; the World Health Organization and other authorities say that artemisinin must only be used if combined with one of the older antimalarials, as combination therapy delays the development of resistance. People buy substandard and fake drugs because they are cheap and easy to obtain. It is therefore excellent news that, according to media reports, distribution of an affordable artemisinin combination therapy has now begun in Cambodia - see UPI report. The drug is available for around 5 US cents per dose. "No one will want to sell counterfeits when the real doses are 5 cents," says Duong Socheat, director of Cambodia's National Malaria Centre. The distribution of the drugs at this cost has been made possible as a result of the Affordable Medicines for Facility - malaria (AMFm). The Facility also plans to provide similar support to Benin, Ghana, Kenya, Madagascar, Niger, Nigeria, Rwanda, Senegal, Tanzania and Uganda.

Virtual participation

A major component of the TropIKA.net project is the “knowledge hub”, where we feature international meetings of major importance to efforts to combat the infectious diseases of poverty. A TropIKA.net team attends each meeting and – on a specially created section of the TropIKA.net website – the team posts summaries of individual sessions and overviews of each day’s proceedings. Interviews with delegates, news stories and commentaries are also provided. Not only does this service enhance the experience of those who attend the meeting, but it also allows people who are not present to become “virtual participants”. Three meetings have been featured this year, two of them within the last two weeks! Our coverage of the 5th MIM Pan-African Malaria Conference in Nairobi is our most ambitious so far, featuring interviews, news and commentaries, as well as summaries of individual sessions and day-by-day overviews. We are now in the process of covering the 13th Annual Meeting of the Global Forum for Health Research in Havana. Keep up to date with what is happening at this event by visiting the hub for this meeting. The expert deliberations in Nairobi are of course not all that is going on. TropIKA.net has reported in the last few days on epidemics of leishmaniasis in southern Sudan and dengue fever in Cape Verde. The latter is the biggest ever dengue outbreak ever recorded in West Africa. Many diseases afflict the world’s poorest people continuously and not just in the form of major epidemics. Pneumonia is both the world’s biggest infectious killer and the most common cause of death in children under five in developing countries. It can only be hoped that a new pneumonia action plan devised by the World Health Organization may be a signal this most neglected of diseases is at last winning recognition as a global health priority. Another WHO report featured on TropIKA.net has highlighted the unequal position of women in health care. As well as reports, we also continue to highlight articles published in the journals – see our Research, Reviews and Editorial opinion sections. It is always an invidious task to suggest which of the recent articles in the literature are the most significant but I should like to recommend two. A review article on the global burden of blindness due to trachoma is important in its own right – at least 1.3 million people are living with blindness as a result of this infection. However, in their discussion of the assumptions that must be made in calculating disease burden, the authors demonstrate how hard it is to reach firm conclusions for any infectious disease of poverty. In contrast, there is good evidence that prevention and treatment strategies for trachoma are highly cost effective. Whether we know precisely how many DALYs or dollars are lost, the human cost of this readily preventable disease is clearly on such a scale that every effort should be made to step up action against it. I was also impressed by the insights emerging from a systematic review of qualitative data on the barriers to effective treatment and prevention of malaria in Africa. Qualitative studies often provide such insights, and what is most striking here is the finding that only a minority of people in Africa are aware that malaria is transmitted by mosquito bites. If people do not understand how an infection is spread (or indeed that is an infection) then this will clearly have in impact on their participation in control efforts and treatment seeking behaviour. Finally, a magazine article that I can particularly recommend was referred to in our TropIKA.net blog; it deals with the encouraging growth of public-private partnerships (PPPs) in the development of new technologies to address the infectious diseases of poverty. Let us know if you spot something in the media that is worth highlighting on the blog. Paul Chinnock Editor, TropIKA.net

Re-tooling the malaria kit for elimination in the long term

Dr Roma Chilengi, head of clinical trials at the KEMRI/Wellcome Trust Research Programme in Kilifi, Kenya discusses the way forward for malaria elimination Elimination means reducing to zero the incidence of a specified disease in a defined geographical area as a result of deliberate efforts. For malaria, this means a situation where incidence of the disease is reduced to zero in a given area, and this should be demonstrable by sensitive diagnostic tests. The accepted definition of elimination is however a sobering reality for the bulk of sub-Saharan Africa. The depth from which certain places have to be lifted is daunting, as they are still way behind in malaria "control" benchmarks. Unfortunately, the health systems infrastructure, which is critical to achievement of malaria elimination, is very poor or non-existent in most places. Since the problem of malaria also does not follow political borders, variation in the burden and transmission intensity cuts across national boundaries. For example, the malaria burden within Kenya varies, such that the problem is declining on the coast while it is still a substantial problem in the western parts. Therefore, to attain elimination, health systems need to be sufficiently capable of establishing the correct burden, identifying proper interventions, deploying them, and monitoring and evaluating the process. This is why many may be pessimistic about malaria elimination as a target, believing it to be way beyond the reach of some places. Some countries will realise elimination, while others may not be able to do so within the foreseeable future, given the currently available tools. There is therefore a great need to sharpen and develop new tools altogether to help in the fight against malaria. A malaria vaccine offers a great hope of achieving significantly improved malaria control, particularly in Africa, where the ecological habitat is such that effective mosquito control has proved difficult or impossible to maintain. The success of other vaccination campaigns within Africa demonstrate that the control of major infectious diseases is achievable on a global scale: smallpox has been eradicated as a result of vaccination, polio seems close to being eliminated, and measles is virtually under control in many African countries.

Malaria Week for southern Africa

The nations belonging to the Southern African Development Community (SADC) have set themselves the goal of eliminating malaria from the region by 2015. To focus attention on the disease and on elimination efforts, next week (beginning 16th November) will be Malaria Week in the region. Events are planned in all the SADC countries and health ministers will be meeting in Limpopo, South Africa to discuss what now needs to be done to reach the elimination goal. Are you involved in Malaria Week? Let TropIKA.net readers know about the activities in which you are participating. Contact us using the 'Leave a Reply' feature below.

Highlighting public-private partnerships

Chemical & Engineering News may not sound like a publication where one would expect to find an article describing the phenomenon of public-private partnerships (PPPs) in the development of new technologies to address the infectious diseases of poverty. But the latest issue of C&EN does have, as its cover story, a very comprehensive article on this important topic. As author Lisa Jarvis rightly says, a decade ago the private sector had almost entirely abandoned research efforts on diseases like malaria, tuberculosis and the neglected tropical diseases. The advent of PPPs - "conceived of as a way to address the gulf between drug need and availability by bringing together resources across the public, private, and philanthropic sectors" - has brought industry back into the picture. Between 2000 and 2004, PPPs spent $112 million to develop a combined 46 drug projects. The article describes projects including the Novartis Institute for Tropical Diseases, the TB Alliance and the recently launched MSD Wellcome Trust Hilleman Laboratories. It also includes interviews with some of the key people involved in these initiatives. The article is highly recommended and may be accessed in full here.

The genetic basis of mosquito resistance to malaria

The ability of Anopheles gambiae mosquitoes to transmit malaria parasites is highly variable and mosquito strains have been found that are entirely resistant to the parasite. The mosquitoes' immune response to malaria is of more than academic interest; it could offer possibilities for cutting the risk of transmission from mosquito to human. Researchers of the European Molecular Biology Laboratory (EMBL) in Germany and INSERM in France set out to identify the genes that control A. gambiae's resistance to the rodent malaria parasite Plasmodium berghei. Their results, published in Science, show that that variations in a single gene explain a substantial part of the variability in parasite killing. Confirmation is needed that resistance to P. falciparum and other parasite species that attack humans is similarly determined. Nevertheless, this could be an important advance. As the researchers say, "Understanding the genetic basis of resistance to malaria parasites, as well as how the determinant polymorphisms are maintained and selected in field populations, will be of tremendous importance for the control of malaria transmission". They also state that the methods they developed to conduct this research could also be useful in moving from a whole region of DNA to an actual causative gene. While Science is not an open access publication, the PubMed abstract and commentaries from EurekAlert and GenomeWeb provide further information about the research.

Factors in transmission-blocking malaria vaccines

Ashley Birkett, director of pre-clinical development at the PATH Malaria Vaccine Initiative discusses their strategy towards new vaccine development . We’re eager at MVI to build on the progress that we’ve achieved with RTS,S. Even as we look forward to taking this first vaccine candidate through a large Phase 3 clinical trial with GlaxoSmithKline Biologicals and African scientists, we’re also moving ahead with a strategy for developing a next-generation vaccine that includes candidates that can block transmission of the parasite. A key part of our strategy is to build on current progress. RTS,S, which is a pre-erythrocytic candidate that aims to protect against the early stage of Plasmodium falciparum malaria infection, was found to be 53 percent effective against clinical disease in Phase 2 trials. As we test this candidate in phase 3 trials at 11 sites in seven African countries, we’re already working on approaches that should help us to achieve the 2025 goal of a product that is at least 80 percent effective against clinical malaria for at least four years. How do we plan to do this? Our approach involves a number of aspects. Our focus on pre-erythrocytic vaccine candidates—those that target the parasite on its journey to the liver or while it matures in an infected person’s liver cells—will continue. However, we plan to target other stages of the parasite’s development as well.  In addition to widening our focus to include transmission-blocking vaccines and other approaches, we’re also pursuing candidates that target the less deadly but more widespread P. vivax malaria. These steps to further diversify our portfolio of vaccine candidates are helping to set the stage for the malaria community’s push to control malaria and to eliminate the disease in the long term. Transmission-blocking vaccine candidates typically seek to interrupt the life cycle of the parasite by inducing antibodies that prevent the parasite from maturing in the mosquito after being taken up during a blood meal from a vaccinated person. Further, MVI has had an increasing interest in multi-stage, multi-antigen vaccines. We believe that a highly effective pre-erythrocytic, transmission-blocking vaccine that could block the parasite’s lifecycle, to reduce transmission in endemic areas, as well as provide protection from clinical disease would be a key tool in the global effort to beat back the disease.

MRI scans could advance understanding of cerebral malaria

Cerebral malaria, where the parasite breaches the blood-brain barrier and damages the central nervous system, is a life-threatening condition. Many studies have also established that children who survive cerebral malaria are left with persistent problems with memory, attention and other cognitive skills. The nature of the damage inflicted on the brain by cerebral malaria is not clear but US scientists aim to improve understanding of the problem with the use of magnetic resonance imaging (MRI) scans. They have already begun their project in Thailand. MRI scans are of course an extremely expensive technology but there are now some machines available in malaria-endemic areas. In an interview with SciDev.Net Gary Brittenham from Columbia University says that MRI research could transform understanding of cerebral malaria and lead to new therapies. He notes, however, that adapting MRI scanners to conduct malaria research in the field would present "an array of technical and logistic challenges".

The wallpaper that prevents malaria

Insecticide-treated bednets (ITNs) and indoor residual spraying (IRS) are the currently recommended methods of reducing the risk of being bitten by malarial mosquitoes. IRS, which normally involves the use of DDT, has been controversial. A new approach, tested in a study in Benin, may prove more acceptable - insecticide-treated "wallpaper". When experimental huts were wallpapered with plastic sheeting treated with carbamate insecticide, all mosquitoes died and none took a blood meal. Even when only the top third of walls was covered by the sheeting, which would prevent contact with children, 80%t of mosquitoes were killed. The researchers say that retreatment of the sheeting would only be needed every two years. An article about the research, which was formally published in Malaria Journal, can be found on SciDev.net.

Eradication - is the ‘e’ word really too risky to contemplate?

Eradication was on everybody’s lips yesterday, though not everyone agrees on how to move forward with this enormous challenge. Some, like the Malaria Eradication Agenda’s (malERA) Pedro Alonso believe we must look beyond the short-term goal of control and shift our focus to eradication (see TropIKA’s Q&A with Pedro Alonso on this topic). Alonso also has the backing of several key players in malaria: Fred Binka of the INDEPTH –Network/MCTA, Ghana; Brian Greenwood at the London School of Hygiene and Tropical Medicine, UK; and Marcel Tanner of the Swiss Tropical Institute, Switzerland, to name a few. Alonso and others are rightly worried about repeating the mistakes of the past, when over-optimism and complacency led to a subsequent massive resurgence of the disease. Those fighting against malaria, as with other diseases of the poor, must continuously battle for funding that is not only sufficient but sustainable. Understandably then, some MIM delegates told TropIKA that they were concerned that a push towards eradication – especially with the might of the Gates foundation, which often drives the direction of research, behind it – would divert funds from urgent control measures. But it should be possible to focus both on control and access to drugs as well as the long-term prize of eradication. After all, the global health community now has more funding and support than ever before; if we don’t move towards eradication, or at least think about how and when we might achieve it, when will we? It seems the least that those suffering with the burden of malaria on a daily basis deserve.

New findings: a personal selection

As Editor of TropIKA.net, I read many new research papers on the infectious diseases of poverty, the majority of which are about malaria. Identifying which are the most important is no easy task, but some do attract my particular attention. I have just written an article about seven such papers. Issues raised in my personal selection include: - the need to protect older children (i.e. those aged 5-18 years) from mosquito bites - what is the best way to prevent malaria in children with sickle cell disease - the growing popularity of window screens and ceilings as a way to prevent mosquito entry to homes - the factors that determine what sort of treatment mothers seek when their child has malaria. You can read my article here and use the TropIKA.net "Comment" facility to add your own views on my selection. (Six of the seven papers I have chosen are available with open access, so you can also read the full papers yourself.) Paul Chinnock Editor, TropIKA.net

How to decide when to take a malaria vaccine to Africa

Kevin Marsh, director of the Wellcome-KEMRI-Oxford Collaborative Research Programme, discusses malaria vaccines on this MVI guest blog: Deciding when it’s a good time to take a malaria vaccine into African countries for testing in children is not always straightforward. It’s a real issue for vaccine developers and funders and one that is the subject of debate here at MIM and in the wider malaria vaccine community. There are no absolute criteria for these decisions. For malaria vaccines, the ability to challenge—with the bites of infected mosquitoes—healthy adult volunteers who have not previously been exposed to malaria is a critical way for developers to decide whether or not a candidate vaccine has potential and should therefore move to African trials. For pre-erythrocytic vaccine candidates—those designed to prevent the parasite from getting past the liver and into the blood stream—this model has proven to be extremely valuable. One good example is RTS,S, the vaccine candidate developed by GlaxoSmithKline Biologicals and supported by the PATH Malaria Vaccine Initiative that is now being tested in the region. On the other hand, for vaccines that target the parasite later in its life cycle, during its development in human red blood cells, the human challenge model has been seen to have limitations. However, many researchers now believe these limitations can be overcome and that challenge models should form part of the selection pathway for blood-stage vaccines. Without this crucial decision point, a major question is, how do developers decide which blood-stage vaccines should go into the field? An added complication for these blood-stage vaccine candidates is the fact that adults tend to develop immunity as a result of previous exposure to the parasite. Therefore, young children who have had limited exposure and limited immunity to malaria are really the best population for evaluating whether these vaccines work. These factors create ethical dilemmas for developers and funders, given that vaccine candidates that have limited human proof-of-concept data may need to be evaluated in large numbers of children. All the important challenge models exist in developed countries. So it’s time to ask why such models are not found in developing regions, such as Africa. In Kenya, there are active discussions among ethical and research institutions to examine whether this country could take a lead in developing challenge models. There’s a strong positive feeling that this is important. In the meantime, there needs to be broad consensus among scientists, including African scientists, about when vaccines should be tested in Africa. It’s also important that African institutions and scientists are meaningfully involved throughout the process of vaccine development.

Malaria Ethics

Research ethics occupies an uncomfortable place in investigators’ hearts. On one hand, it’s at the core of their work – no clinical trial could, or should, be conducted without a strong ethical framework. But researchers also want to get their trials up and running as soon as possible, and waiting for ethics review can be immensely frustrating. In a small basement room at the MIM conference today, it became clear just how relevant these issues are for a disease like malaria. Malaria trials often involve the vulnerable segments of a population –pregnant women and children and so there are sensitive ethics issues. But the trials are almost always done in Africa, where ethics review is patchy across the region. Clearly, there is a need to mesh these conflicting factors. The members of review panels, however, have a hard time of things. They are often volunteers who have full-time jobs, few resources, and little training. So what’s the solution? Collaborative efforts by organisations like PABIN/SIDCER help tremendously by offering much needed training and funding. For their part, African scientists involved in bioethics will have to think about the issues in a broad, perhaps moral, context, rather than just ticking ethics review boxes. This is a tough challenge, but one that African scientists are more than capable of. Watch this space for a Q&A with Aceme Nyika, AMANET’s ethics coordinator.

Global health histories

Another in a series of "webinars" on the history of tropical diseases will be broadcast over the internet this week, when two leading specialists will speak on the theme "How malaria became a vector borne disease". The series, launched in April this year, was described in an article in TropIKA.net News. In the latest session, Dr Axel Kroeger of TDR (the UN Special Programme on Tropical Disease Research & Training) will be joined by Professor Randall Packard, of the Institute of the History of Medicine at Johns Hopkins University. Dr Kroeger will discuss “institutional memory loss” in the history of vector control efforts, citing the example of indoor residual spraying with insecticides. Professor Packard's focus will be on the limitations of the Roll Back Malaria approach and the consequences for the prospects of malaria elimination. The webinar will be held Wednesday 4th November 2009 (12:30 PM - 14:00 PM CET). Participation is freely available to anyone who pre-registers and has the necessary system requirements. To register and join the next webinar, go to: https://www1.gotomeeting.com/register/877471673 More about the sessions can be found at: http://lnk.nu/who.int/124x.html

What Africans need from product development partnerships

Yvette Collymore of the Malaria Vaccine Initiative talks to MIM Professor Wen Kilama, AMANET: Managing Trustee, African Malaria Network Trust (host of MIM): The Product Development Partnership model has seen a number of achievements since they began developing drugs, vaccines, and vector control solutions in 1999. However, from an African perspective, these product development partnerships (PDPs) that receive funding to address neglected diseases create a number of challenges. As I said at a session on PDPs organized by the PATH Malaria Vaccine Initiative as well as the Medicines for Malaria Venture and the Innovative Vector Control Consortiumm at the MIM conference, the PDP model addresses one disease problem with one approach. The model does not take a holistic approach to the development of these products. But a product on its own does not solve the problem. You need to go beyond that and make a product accessible. There may be hindrances to do with weak public health systems, lack of political will, poor infrastructure, corruption, traditional norms and beliefs, and prescribing practices. All these issues impinge on access. Some argue that the PDP model cannot do all things. I agree. At the same time, these PDPs can build good working relations with national and local researchers and scientists instead of relying on so-called CROs (contract research organizations)—small companies perhaps contracted through ads on the Internet who come in, do the job, and leave without contributing whatsoever to local capacity building. They come back, do the same thing, over and over again. We need to work hand-in-hand with PDPs: plan together, implement together, build up local capacity, so that local researchers can eventually carry on, without much outside input. I do not see PDPs carrying on implementation research, long-term follow-up, for example, of chronic adverse events, or disease rebound effects, pharmacovigilance—following a study population to detect rare adverse events. Another area of concern is that PDPs are not likely to analyze data inside the country of testing. The issue of data sharing is crucially important, as is that of transferring materials or specimens for analysis abroad. And when results are obtained, they are often not fed back to the country of origin, in order to benefit the national health care system. Local manufacturing and related aspects such as technological transfer are also major concerns. The local researchers and research participants might inadvertently be creating markets for foreign products.

The toll of counterfeit medicines

Would you take a drug not knowing whether it was safe or not? Whether it could kill you? For a whole host of reasons, this is exactly what many people with malaria do. The reasons are not as simple as ignorance or a lack of education. In a session on ‘pharmacovigilance’ today, Ogobara Doumbo, the director of the Malaria Research and Training at Bamako talked about some of the reasons why people still take drugs that are unsafe, and what can be done to prevent it. Some people are so used to getting medicine from their local pharmacies or shops that they don’t question the validity of the medicines. Fake drugs can enter the market in many ways; in some countries with no local manufacturers, imported drug can have questionable provenance. Some companies sell antimalarials even when after the expiration date. The consequences are serious. Some fake drugs do contain some active ingredient, but not being prescribed properly, the drugs can lead to the development of resistance in parasites – effectively working as an immunization for the parasite. In the worst cases, the drugs kill people. Doumbo said, for example, that 2500 people died in Niger in 1995. So what is the solution? Regions need to coordinate on quality assurance, and they need to educate people about the importance of getting hold of safe drugs. More importantly, and something that will be a challenge for policymakers and governments, is to ensure that safe antimalarials are available to those who need them. Until then, people with malaria may well feel that desperate times call for desperate measures.

A place to confer: TropIKA.net

As I write this blog, some 1,500 malaria specialists are taking part in the first day of a major conference being held in Nairobi this week. Many important presentations on malaria research will be delivered during the event, but a conference is a place to confer and should not be merely a series of lectures delivered to passive audiences. To help make the 5th Multilateral Initiative on Malaria Pan-African Malaria Conference a more interactive affair, TropIKA.net has established a “knowledge hub” for the meeting, where we are providing background documents, news, summaries and blogs. Everything we publish on the site allows registered users to add their own observations and opinions on the latest developments in Nairobi. TropIKA.net spoke, before the conference began, to ten researchers making presentations of particular importance. These interviews have been published within the knowledge hub. We will be conducting further interviews, in which we ask young African scientists and senior figures in malaria control for their reactions to these presentations. Some of the presenters we spoke to have views that could prove highly controversial. Frank Baiden from Ghana says we need to take a long, hard look at the data on malaria in Africa: “Do we have the numbers right?” he asks, “How confident are we that these cases are all malaria?” He and others we spoke to query whether the declines now being seen in case numbers in several parts of Africa are the result of new interventions, or whether something else is going on. James Tibenderana (Uganda) alleges that previous efforts to promote the integrated management of childhood infections have “died a natural death”. Paul Milligan (UK) says that the way in which data from vaccine trials are analysed should be changed, in order to provide better measures of their impact on disease burden. And Hilary Ranson (UK) says “alarmingly high” levels of insecticide resistance are now being recorded. Let other TropIKA.net readers know your opinion on what these researchers have told us. Thanks to the Internet, there are now also virtual places to confer and TropIKA.net provides such a facility throughout the year – not just in the present ‘conference season’. We continue to report on major new developments relating to the infectious disease of poverty. A recent example is the publication of new estimates showing that Streptococcus pneumoniae and Haemophilus influenzae type B are responsible for as many child deaths as AIDS, malaria, and tuberculosis combined. Epidemics of other infectious diseases have also featured in our pages. This has been a very serious year for meningococcal meningitis in Africa’s meningitis belt, and cholera outbreaks have afflicted many parts of the African continent, including Nairobi – a city in which ironically malaria is not actually transmitted, according to new findings. We have also highlighted reviews that provide updates on what is known about cholera and about fascioliasis, and a major report on global progress with vaccination programmes. But we do not neglect the basic end of research. It will be interesting to see whether some very preliminary findings recently reported may one day lead to a role for chocolate in malaria treatment or for anti-obesity drugs to treat dengue fever. What do you think? Let us know. Paul Chinnock Editor, TropIKA.net

Are mosquitoes biting earlier in the evening?

Kenya's Daily Nation newspaper reports that a study has found a change in the biting habits of mosquitoes. They are said to be active earlier in the evening, before most people have protected themselves and their children by using insecticide-treated bednets. The Nation speaks of the insects "circumventing" the rapidly expanding use of ITNs through this change in behaviour. Meanwhile, another study says there is evidence that by protecting young children from mosquito bites through ITN use, they are not developing immunity to malaria. This could, it is speculated, lead to an increase in cases of malaria in older children. Both studies will be presented during the Fifth Multilateral Initiative on Malaria Pan-African Conference, which is a TropIKA.net Featured Meeting.

More Gates funding for the Medicines for Malaria Venture

Medicines for Malaria Venture (MMV) has announced (see press release) that it has received its fifth and largest grant from the Bill & Melinda Gates Foundation, to fund its Research and Development pipeline with an additional $115 million over the next five years. The grant will support MMV’s ability to discover, develop and deliver affordable, safe, effective and innovative antimalarial drugs for vulnerable populations. Dr Timothy Wells, MMV’s chief scientific officer says, “This funding arrives at a critical time for us. Over the last few months, with our partners we have launched a high-quality antimalarial designed specially for children (Coartem Dispersible), submitted another antimalarial to the EMEA for regulatory approval (Eurartesim), and are in the process of collating the regulatory dossier for a third antimalarial (Pyramax). With our partners, we have built a portfolio of more than 50 new projects of which ten are in clinical development. With the emergence of resistance to Artemisinin in Cambodia, it’s clear that the ambitious goal of malaria eradication will require a wide range of new medicines. The new grant from the Foundation will enable MMV to continue the development of the next generation of antimalarial medicines.”

New mosquito net distribution programme for Africa

The Malaria Consortium, the most prominent of the non-government organisations focusing on malaria, has announced (see press release) that it has been appointed to help implement a new USAID net distribution project worth up to $110 million across Africa. The organization has already distributed around nine million mosquito nets in Africa. Since two people can sleep under one net, this amounts to protection for 18 million people. The new five-year USAID project, to be known as NetWorks, also involves the US-based John Hopkins University Centre for Communications Programmes (CCP). Partnerships and policies in each country can vary widely, and net procurement and distribution challenges frequently hamper implementation. The intention is that NetWorks project will take the unique complexity of different environments into account by emphasising the need for flexibility. However, the Malaria Consortium has recently cautioned (see press release and article in the UK Daily Telegraph) that the distribution of nets is only part of the battle. People have to be persuaded to use the nets they have received. Access to treatment for those who get malaria, particularly children, must also be improved. Malaria Consortium managing director, Dr Graham Root, told the Daily Telegraph that, while the 2010 target for universal mosquito net coverage in Africa is extremely important, it was an oversimplification. The target had been simplified to raise funds and explain to the world that malaria can be controlled relatively easy. "That simply isn't true," said Dr Root.

Chocolate - could it be used to treat malaria?

US researcher Steven Maranz, of Weill Cornell Medical College, is setting out to study the effects of chocolate, which removes from the bloodstream the cholesterol that the malaria parasite needs to survive. He believes chocolate may be able to kill most of the parasites, while leaving enough in the blood to help children develop a lifetime resistance. He has just been awarded $100,000 to pursue this line of research by the Bill & Melinda Gates Foundation. Steven Maranz's grant is just one of 76 newly announced by the Gates Foundation, all of them going to unorthodox (“outside the box”) research in global health. Other recipients, from 16 countries across 5 continents, include: – Andrew Fung of the University of California Los Angeles, who aims to develop chewing gum that can detect malaria biomarkers in saliva – Kate Edwards at the University of San Diego, who will study how a brief bout of exercise may enhance the efficiency of a pneumococcal vaccine – Ranjan Nanda of the International Centre for Genetic Engineering & Biotechnology in India, who will attempt to create a handheld “electronic nose” that gathers and analyzes breath samples to diagnose tuberculosis. The grants have been made through the Foundation’s Grand Challenges Explorations initiative. Further details about the new awards are available in a Gates Foundation press release.

Neglected diseases in neglected regions

The infectious diseases of poverty exact a massive burden on the populations of Asia and Africa, but their impact in the Americas is often forgotten. (The extent of this neglect was made clear in a research article published a year ago in PLoS Neglected Tropical Diseases). It is therefore encouraging to learn that the Inter-American Development Bank and the Global Network for Neglected Tropical Diseases intend to mobilize $30 million from the public and private sectors to raise awareness and funding for the control and elimination of neglected tropical diseases (NTDs) in the region – see TropIKA.net Blog. We also report in TropIKA.net News of new efforts to eliminate malaria and filariasis from the Americas. Meanwhile, the Drugs for Neglected Diseases initiative has announced that it has established a cooperative agreement with a pharmaceutical company for the clinical development of a drug that has been shown in lab tests to have activity against Trypanosma cruzi, the pathogen responsible for Chagas disease. This disease is confined to the Americans and kills at least 200,000 people every year. There is no vaccine and no specific treatment. Control of the disease vectors (triatomine bugs) remains the main focus of efforts to fight the disease and findings reported in a new research article will help guide control programmes in deciding when it is best to spray insecticide. Oceania is another part of the world where infectious diseases remain an important cause of ill-health but receive little attention from the international media. Nevertheless, efforts are being pursued to control or eliminate these conditions and it is heartening to read a recent report of major successes achieved against malaria in Vanuatu and Solomon Islands. TropIKA.net continues to highlight and comment upon new research findings, wherever the studies have been conducted. Our recent selections have included an important step forward in understanding how the parasite responsible for leishmaniasis establishes itself in its human host, a prevalence study that confirms the return of yaws to the Democratic Republic of Congo, and a study from China which examines the factors explaining why so many tuberculosis patients fail to complete their course of treatment. An Ethiopian study provides an illustration of the poor performance that is often seen in TB programmes, thus demonstrating the importance of monitoring and evaluation. The TropIKA.net team cannot, of course, identify all the new reports of research into the infectious disease of poverty that are of particular significance. We need the help of our readers. If a new paper strikes you as being of exceptional importance, let us know about it. One piece of good news is that an increasing amount of research is being conducted in developing countries. There has been an encouraging rise in the number of researchers in these countries, which doubled in a five-year period according to a report from the UNESCO Institute for Statistics. There is still of course a long way to go for the South to catch up. One initiative that should further speed up progress is the African Network for Drugs and Diagnostics Innovation (ANDI). The network aims to increase new health products developed in Africa by Africans. The ANDI 2009 meeting, which took place in South Africa this month, received in-depth coverage on TropIKA.net. But sometimes the problem is not a lack of basic research. We highlight an opinion article which argues that the lack of progress against schistosomiasis in Africa represents one of this decade’s greatest failures. Cheap and effective treatments already exist for this disease, the second most common parasitic condition after malaria, but only 5% of Africans who need treatment actually receive it. Progress against the infectious diseases of poverty requires that the needs of neglected people should be met, in whichever part of the world they may live. Paul Chinnock Editor, TropIKA.net

Malaria elimination efforts make progress in the Pacific

Good news from the island nations of Vanuatu and Solomon Islands. Radio New Zealand reports that cases of malaria in Vanuatu have dropped from over 190 cases in 1989 to less than 14 cases in 2008. In Solomon Islands 82 people out of 1000 had malaria in 2008, compared with 152 in 2006. The article says the reduction in case numbers is attributed to improved vector control (both the distribution of insecticide-treated bednets and house spraying), earlier case detection, and more readily available treatment. The Secretariat of the Pacific Community's public health programme manager, Dr Thierry Jubeau, says the two countries are now able to focus on eliminating the illness, rather than just controlling it.

Climate change and insect-borne disease

The team at SciDev.Net have continued their series of articles on the controversial topic of climate change and insect-borne disease. Warning against alarmism, the writers remind us that, "a whole host of non-climate factors also influence disease transmission, from living conditions and irrigation practices to drug resistance, health infrastructure and urbanisation". Global warming may not actually be a factor in the spread of malaria at all. Mathematical modelling is increasingly seen as important in improving our understanding of infectious diseases and many studies are now being published using this methodology but, on SciDev.Net, Jonathan Cox, from the London School of Hygiene and Tropical Medicine, says we should forget predictive modelling for the moment and focus on research with a better chance of improving disease control — investigating how to strengthen national surveillance systems to detect outbreaks as early as possible. All the articles in this series can be highly recommended.

The quest for a malaria vaccine: Now read the book

One of the most often asked questions in the entire field of the infectious diseases of poverty is, "Why is it taking so long to develop a vaccine for malaria?" There are of course many complex technical reasons why this particular goal has been difficult to attain. In a new book, however, Irwin Sherman, a professor emeritus of biology at the University of California, Riverside, USA argues that: "...the fault lies in the fact that the message for a protective vaccine has not been specifically addressed to a general audience so that an understanding of the problem can result. There is no recent easily accessible chronicle of the preparation of malaria vaccines nor are there descriptions of the crusaders – past and present – who have labored to produce a protective vaccine against malaria. Further, the scientific literature does not convey a sense of the drama in the pursuit". Professor Sherman's 402-page book aims to address this problem and to "...capture the controversies, missteps, wars of words, stolen ideas, and clashes of ego as researchers around the world compete to develop the first successful malaria vaccine". Here at TropIKA.net we have yet to read the book but it certainly addresses a fascinating issue. Further information is available in a press release. We would certainly be interested to hear from anyone who has read the book and wishes to comment on it. Please use the "Leave a Reply" link below.

A time to honour commitments

How many research papers have we all read that conclude with a statement that further progress against an infectious disease, while technically possible, is hampered by a lack of “political commitment”? African presidents, in common with heads of state in other parts of the world, have varied in their level of commitment to the welfare of their people and in their position on the proportion of the national budget that should be devoted to health care. The creation of the African Leaders Malaria Alliance (see TropIKA.net News) must therefore be welcomed. ALMA is the first alliance at head-of-state level to combat the disease and has the potential both to improve the efficiency of control efforts, through international cooperation, and to mobilize national populations to work towards the elimination of malaria. But commitments made by politicians are not always honoured. African presidents have previously pledged to spend 15% of their budgets on healthcare but few have delivered. Western leaders have also in many cases failed to provide the full level of development support that they have promised. Given the continuing global economic difficulties, there may be disappointments ahead. But malaria must surely be regarded as a special case. The disease burden is so great and the prospects for progress towards elimination are so much better than ever before that, if ever there were a time for commitments to be honoured, it must surely be now. Meningitis also claims many lives in Africa. The latest of our TropIKA.net Profile articles features an interview with Marc LaForce, head of the Meningitis Vaccination Project. He describes how, once the final few hurdles have been cleared, a new vaccine designed specifically for Africa will become widely available. Buruli ulcer (BU) is one of the most severely neglected of all the infectious diseases of poverty, but there have been modest increases in the funding available for research into this dreadful condition. We report on new genomic research on BU and on a planned study that should advance knowledge on the BU disease reservoir. One way we can increase the attention paid to neglected conditions is to feature them in the media, but this has to be done in the right way – accurately and without scaremongering. Pakistan is one of many countries where the media has rightly highlighted the steady advance of dengue fever, but in such a way that a dengue diagnosis is now often interpreted by patients as being a death sentence. (The case fatality rate with dengue is of course very, very small.) Somehow a balance must be struck by the media to create sufficient public concern to prompt preventive action, without leading to widespread panic. The TropIKA.net blog seeks to highlight items in the news that you may have missed. In recent days, these have ranged from the bizarre to the tragic. Some South African TB patients are reported to be selling their sputum to healthy people, who use it to fake a diagnosis of the disease and to be awarded a disability grant. In Papua New Guinea, which is experiencing its first cholera epidemic on record, fear of the disease is such that patients are said have been left to die at the side of the road, as no one is willing to take them to hospital. For progress to be made against the infectious diseases of poverty we need, not only commitment, but also a better understanding - at all levels - of the true nature of the dangers they pose. Paul Chinnock Editor, TropIKA.net

Tigecycline: a new antimalarial?

Reporting from Bangladesh, news agency UPI says that the antibiotic tigecycline is showing promise as a potential treatment for malaria. Tigecycline is an glycylcycline compound developed and marketed by Wyeth. Now researchers say they have found that the drug has significant antimalarial activity on its own and can also be administered in combination with other anti-malarial drugs.

Not-so-silly season

In the English-speaking parts of the northern hemisphere, the time of the year around August when many of the working population are on holiday is known to the media as "the silly season". There is a lack of hard news to report and much of what gets published is of a trivial nature. Infectious diseases do not, however, take a holiday. The world's poorest countries continue to suffer from the ravages of many infections. As we have reported on TropIKA.net, in Zimbabwe one of the worst cholera epidemics of recent years appears to be over but several other African countries, including Ethiopia and Kenya, are still coping with epidemic cholera. Zimbabwe itself may face a return of the disease in the forthcoming rainy season. Dengue fever continues to wreak havoc in many parts of the tropics; a report from an expert group in the Philippines concludes that many cases are treated inappropriately. The impact that swine flu will have in developing countries is not yet clear. TropIKA.net News has reported over the last few weeks on a number of initiatives to tackle the infectious diseases of poverty. Diagnosis is generally a neglected area, receiving less attention than prevention and treatment. However, the Stop TB Partnership's New Diagnostics Working Group has launched new web resource called Evidence-based Tuberculosis Diagnosis. Also several African nations are drawing up plans to revamp their laboratories to qualify for World Health Organization laboratory accreditation under a new scheme designed specifically for developing countries. There has been formal publication of data confirming the emergence of resistance to artemisinin - the drug that is the now the recommended treatment for malaria. A major international effort is already under way to combat this new public health crisis. The use of insecticide-treated bednets is another cornerstone of malaria control programmes and massive net distribution programmes now exist in many countries, but a recent study shows that many of the nets distributed are not used by the families who receive them. More encouraging news includes advances in the understanding of how the parasite responsible for leishmaniasis manages to evade the human immune system so successfully. Leishmaniasis receives woefully inadequate attention and progress of this kind is to be welcomed. We also report that a new Chinese drug could be used to kill parasitic intestinal worms in regions where parasites are developing resistance to the widely used deworming drug albendazole. And efforts to develop a new tuberculosis vaccine will be stepped up thanks to new funding. TropIKA.net's Funding section includes details of opportunities that have come to our attention. Silly season or not, several new grants have become available in the last few weeks.

Overcoming neglect: profiling the people

An important part of TropIKA.net is our Profiles section in which Tatum Anderson interviews key figures working against the infectious diseases of poverty. We are delighted that our latest interviewee is Dr Awa-Marie Coll-Seck executive director of the Rollback Malaria Partnership (RBM). She plays a crucial role in coordinating the activities of the myriad of organizations now involved in international efforts to improve malaria control. One of the many new malaria initiatives is the Affordable Medicines Facility for malaria (AMFm). There is currently much debate, for example in a recent PLoS Medicine article, as to the merits of this scheme and how it might best be implemented. Another recent Profile interviewee, Brian Greenwood, is probably best known for his work against malaria but in his long career in tropical medicine he has also focused on other diseases, among them is meningitis. We report on the launch of the African Meningococcal Carriage Consortium (MenAfriCar), to be headed by Professor Greenwood, which will make a concerted effort to understand the spread of meningococcal meningitis in Africa. We also report good news on another disease that is predominantly an African problem – onchocerciasis (river blindness). Mass administration of the drug ivermectin kills the larvae of the parasite responsible but not the adult; repeat treatments (once or twice a year) are therefore given. It has been widely believed that communities living in areas endemic for the disease would need to be given these treatments indefinitely. However, a study in Mali and Senegal found that, after 15-17 years of mass drug administration with ivermectin, only a few people were still infected and treatment could safely be stopped. Ivermectin is not, however, an ideal drug. Many patients find it extremely unpleasant to take and parasite resistance to the drug has been reported. Research to find new ways to control river blindness that do not depend on ivermectin therefore remains important – see TropIKA.net news story on the latest meeting of the SCOOTT Consortium (Sustainable Control of Onchocerciasis today and Tomorrow). Amongst the other good news has been the announcement by the International Trachoma Initiative that three more countries (Ghana, Mexico and Saudi Arabia) have now met the criteria for elimination of trachoma as a public health problem. It is unusual to see a low-, a medium- and a high-income country mentioned together for the same achievement! Tropical diseases can indeed afflict both rich and poor but it those who live in poverty who are the most vulnerable. Many of the countries where dengue fever is a problem are emerging economies in Latin America and Southeast Asia. The economic impact of the disease is therefore considerable. Probably the most comprehensive study to date seeking to quantify this impact has just been published. Infectious diseases that affect poor people are by and large neglected, but with increasing wealth in dengue-afflicted nations, perhaps the economic imperative will lead to an expansion of efforts to develop a vaccine and a treatment for this increasingly common disease. The diagnosis of the infectious diseases of poverty is itself a neglected issue. When advances are made in the treatment of a disease, rapid and reliable diagnosis becomes even more important, as was discussed in the case of malaria in a recent BMJ article. Two initiatives to address the neglect of diagnosis have made an appearance in TropIKA.net during the last few days. The African Network for Drugs and Diagnostics Innovation (ANDi) has announced that it will present its strategy and business plan in October, and the TropIKA.net blog links to an interview with Joseph Ndung’u of the Foundation for Innovative New Diagnostics (FIND) about the search for a new diagnostic test for trypanosomiasis (sleeping sickness). - For more on new developments in diagnosis, see also a recent article in TDR News. Paul Chinnock Editor-in-Chief, TropIKA.net

Philippines makes progress on malaria and filariasis

Good news from the the Philippines where the province of Sorsogoon (population three-quarters of a million) has been declared free of two vector-borne diseases - malaria and lymphatic filariasis. Making the announcement, Doctor Nestor Santiago Jr., the regional health director, described the achievement as a milestone. Sorsogoon becomes the second of the country's 40 provinces to be declared malaria and filariasis free. See reports from the Philippines Information Service and the Inquirer.

Remote sensing will help predict disease epidemics

A report from IRIN describes the work of scientists from the National Aeronautics and Space Administration Agency (NASA) who are developing remote sensing methods to monitor the environmental conditions that cause Rift Valley Fever (RVF). This viral disease, spread by mosquitoes, is a serious problem in cattle in the Horn of Africa but is also emerging as a threat to humans. Outbreaks in recent years have claimed several thousand lives. NASA hopes to use remote sensing, "a technique that uses recorded or real-time wireless sensing devices to collect information on an object or phenomenon," to determine the environmental conditions that lead to outbreaks. Details of the project were presented at a conference held in Cape Town - the International Geoscience and Remote Sensing Symposium, Earth Observation - Origins to Application. The IRIN report says also that the potential of remote sensing in the control of other infections is being investigated by the Swiss Tropical Institute and a German company, Jenoptik. According to Kathrin Weise, a Jenoptik software engineer: "The land cover classification and statistical methods ... will be used in our projects to map risk areas and environmental conditions for an outbreak of epidemics of different vector-borne diseases like malaria, meningitis, and Buruli ulcer disease".

Plasmodium, people and penguins

It is rare that TropIKA.net features a news story not directly related to human health but many of our readers will I am sure be fascinated to learn that malaria is a health threat not just to people but to penguins. Whilst mainly associated with the world's coldest places, some penguin species spend some or all of their time in warmer climes, including the Galapagos Islands. The New Scientist reports that the Galapagos Penguin, already an endangered species, is commonly infected with Plasmodium malaria parasites. Five per cent of penguins tested were found to be infected and while they were considered still to be in good health the strain of the parasite is related to a form of Plasmodium that causes serious avian malaria amongst penguins living in zoos. It seems that ships and flights bringing people to the islands have been responsible for introducing mosquitoes capable of transmitting the parasite. Global warming and declining fish stocks are already threatening the survival of the Galapagos Penguin. Malaria is the last thing they need.

Resistance to antimalarial drug: more news from Cambodia

The appearance in Cambodia of resistance to artemisinin, now the recommended treatment for malaria, is attracting media attention. A six-minute video report from World Focus includes interviews with experts and visits to clinics and pharmacy shops. The role of fake and substandard drugs in facilitating the development of resistance is highlighted in the report. Not long ago, developments (good or bad) in malaria control would have received little media coverage. The level of interest being shown is encouraging and could help in efforts to control the spread of resistant strains of the malaria parasite. For more on the situation in Cambodia see the following articles in TropIKA.net and the TropIKA.net Blog (1 , 2 , 3 ).

Evidence into policy – policy into practice

Let’s start with the good news on research targeting the infectious diseases of poverty. There has been a lot of it, as featured on TropIKA.net in the last couple of weeks, from the molecular to the public health level. A new Wellcome Trust initiative will boost research capacity in Africa, a gene map has been constructed for the parasite that causes schistosomiasis, opening up new avenues for research, and a potential new rabies vaccine has given promising results in mice. A trial has begun of a new drug for river blindness, and a trial of an improved treatment for sleeping sickness has been completed with encouraging results. Meanwhile the US government has made it clear that, following the broadening of its policies on global health, it will provide new support for the control of neglected tropical diseases (NTDs). Unfortunately, only seven infections from the long list of NTDs have been targeted by the US at this stage. (Leishmaniasis, Chagas disease and dengue fever are examples of the NTDs not yet included.) Nevertheless, this is still an exciting initiative and other countries in the North might now be expected to follow the US lead. These examples of positive developments contrast with the news from Kenya that over 70% of malaria patients there are given the wrong malaria treatment; they receive older ineffective antimalarials and not artemisinin combination therapy (ACT), the internationally recommended treatment. This finding (from the 2007 Kenya Malaria Indicator Survey, the full report of which is not yet freely available) supports observations in many African countries that ACTs are only getting through to a minority of those who need them. Coincidentally, within the same month that the Kenyan report was published, the 250 millionth dose of the most widely available ACT, Coartem, was delivered. (TropIKA.net marked the event with an interview with the head of marketing and access for the malaria initiative at Coartem’s manufacturer, Novartis.) Progress is therefore being made but there is a long way to go. An example of what a malaria control programme can achieve comes from a study conducted in the tiny island of Bioko, Equatorial Guinea where, within four years of the introduction of a multi-intervention strategy, prevalence in children dropped from 42% to 18% and all-cause child mortality fell by two-thirds. Such research demonstrates what is possible, but the challenge remains of bringing the potential benefits of research evidence to entire populations in disease-endemic countries. “Evidence into policy” is the first part of this challenge. A recent article in Lancet Infectious Diseases noted that, while national guidelines in most Africa countries now list ACTs as the recommended first-line treatment for malaria, the majority of these guidelines have not changed as regards second-line treatment, for which they still recommend oral quinine monotherapy. This is despite the fact that the World Health Organization has stated that ACTs should also be the mainstay of second-line treatment. But “policy into practice” is the next part of the challenge. In the case of ACTs, practitioners cannot give them to patients, as either first- or second-line treatment, if the drugs are not actually available. I am reminded of the British civil servant who said, after a new directive from his political masters, “If the policy is that pigs will fly, whose fault is it when they don’t?” (Sometimes those who write policy documents and guidelines need to distinguish between aspirational and operational targets.) Two other research articles highlighted on TropIKA.net have implications for policy making in child health. A systematic review concludes that WHO is wrong in its recommendation that iron supplements should not be given to children under two years, if they live in malarious regions. In contrast, a South African study provides evidence to support the WHO position that children known to be HIV-infected shown not be given BCG, even in countries where the risk of TB infection is high. The interpretation of the evidence in such studies is, however, always likely to be controversial. Putting evidence into policy and policy into practice both present formidable obstacles. Paul Chinnock Editor-in-Chief, TropIKA.net

Concerns on Affordable Medicines Facility for malaria

The Affordable Medicines Facility for malaria (AMFm) - an international partnership to reduce the price of artemisinin-combination therapies (ACTs) for malaria - has received much attention on TropIKA.net.. It has been described as "a triumph of international cooperation" but there have been criticisms. Oxfam is particularly concerned that the distribution of drugs through ordinary shops will lead to misdiagnosis and mistreatment, including the sale of incomplete courses of medicines. All this will increase the likelihood of drug-resistant malaria developing and spreading. A Lancet editorial in May made a similar point and described the launch of AMFm as "premature". Now the Lancet has published a "Reflection and Reaction" article written by authors from a right-wing US think tank, the American Enterprise Institute and the controversial US-based campaign group "Africa Against Malaria". The authors believe that, "it is sensible and commendable to work with private sector shops to deliver ACTs in the absence of a robust public health system" but they go on to warn of the dangers of encouraging the purchase of antimalarials without confirmed diagnosis. The article says there is no evidence that the AMFm process will work and expresses concerns over the opportunity cost involved in devoting scarce resources to the project when there are other interventions for the control of malaria, which are known to be effective, that also require support.

South American malaria study focuses on surface water

EnvironmentalResearchWeb has interviewed researchers involved with a recent study that used information from a malaria database compiled by the Pan American Health Organization and the Brazilian Ministry of Health. The researchers found that disease rates increased after seasonal rainfall in the southern uplands of the Amazon Basin, where there is little surface water. But, surprisingly, disease rates fell soon after seasonal rainfall in areas with abundant wetlands along the Amazon River. Thus, the amount of surface water appears to regulate the delay between rainfall and peak malaria occurrence. Jonathan Patz led the research team, which included scientists from the University of Wisconsin, USA, Montpellier University, France and the Institut de Recherche pour le Développement, Brazil. He said that health officials could use the information to help reduce the incidence of malaria in certain places, such as relatively dry regions susceptible to increased rainfall, by appropriately timing malaria campaigns and interventions. The results could also help scientists develop more precise regional models of malaria incidence across different types of landscapes as climate changes.

Latest figures show Global Fund's achievements

It is less than eight years since the launch of the Global Fund to Fight AIDS, Tuberculosis and Malaria, but the Fund says it is now responsible for 60% of international funding to fight malaria, 57% of funding for TB, and 23% of funding for AIDS. According to a Fund press release the programmes it supports have so far supplied TB treatment to more than 5.4 million people, and delivered a cumulative total of 88 million insecticide-treated bed nets to families at risk of contracting malaria. (The latter figure represents a rise of 49% from 59 million nets distributed by mid-2008.) Michel Kazatchkine, Executive Director of the Global Fund, says: “When we first began our work in 2002, few people in developing countries were being treated for AIDS or tuberculosis. Malaria was a neglected disease. Many countries simply did not have the resources to fight these diseases effectively. Now the story is changing dramatically. There is still much to be done, but we are making real progress and I am proud that the Global Fund is a leader in this global effort.”

300,000 child deaths - Nigeria's annual malaria toll

Nigeria's National Malaria Control Project estimates that 300,000 children die from the disease every year. Further statistics, presented during a training course for journalists, included that there are 30 million clinically diagnosed malaria cases in Nigeria annually, the disease accounts for 60% out-patients visits, and 11% of the deaths that occur during pregnancy. The journalists were also informed of the action federal and state health authorities are taking to control malaria as part of efforts to meet the millennium development goals. A full report is available in the Vanguard newspaper.

Global Fund faces $3 billion shortfall

According to a Reuters report the Global Fund to Fight AIDS, Tuberculosis and Malaria is facing a budget hole of about $3 billion, resulting from the worldwide economic decline. A spokesperson said the money would have to be found in order to meet commitments to programmes for 2010. One concern, should the Global Fund not be able to meet its commitments, is that it might mean many TB patients would not be able to continue with their treatment, and this would encourage the development of drug resistance. As of the end of last year, the Global Fund had provided AIDS treatment to 2 million people and tuberculosis treatment to 4.6 million people, and distributed 70 million insecticide-treated bed nets worldwide.

Major malaria success on small island

Bioko (formerly known as Fernando Po) is a small island (estimated population 130,000) that is part of the troubled African country of Equatorial Guinea. A programme to improve the control of malaria on the island is reported (1) to have achieved remarkable success. Four years after high coverage, multiple malaria control interventions were introduced: mean prevalence of infection in children aged 2-5 years fell from 42% to 18%; prevalence of moderate-severe anaemia in the same age group declined from 15% to 2%; and all-cause under-five mortality dropped by two-thirds, from 152 per 1,000 births to 55. The interventions included: artemisinin combination therapy for children and pregnant women; intermittent preventative treatment of pregnant women; distribution of long-lasting insecticide-treated nets; and indoor residual spraying. As discussed in an editorial (2), a key part of the programme was the support from the Marathon Oil Corporation which is active in Equatorial Guinea; it provided $15.8 million for malaria control on Bioko and is now providing support to expand the programme on the mainland. Further details of Marathon's support are given in a press release from the company. The reductions in malaria took place in the atypical setting of a small island and involved massive external funding. Nevertheless, the excellent news from Bioko demonstrates what can be achieved using methods already available, even in a highly-endemic setting. References 1. Kleinschmidt I, Schwabe C, Benavente L, Torrez M, Ridl FC, Segura JL, Ehmer P, Nchama GN (2009). Marked increase in child survival after four years of intensive malaria control. Am J Trop Med Hyg;80(6):882-882. 2. Steketee RW (2009). Good news in malaria control... now what? Am J Trop Med Hyg. 2009 Jun;80(6):879-880.

Most Kenyans get the wrong malaria treatment

Published this week, the 2007 Kenya Malaria Indicator Survey, provides further evidence that most people with malaria in Africa are not being given the recommended treatment - artemisinin combination therapy (ACT). The survey, understood to be the most comprehensive such study to be conducted in Kenya, found that only 29 per cent of patients received ACT. Older drugs, including chloroquine and sulphadoxine-pyrethamine were instead given. “It is unfortunate that these medicines are in high circulation in the drug chain,” said Dr Elizabeth Juma, the head of the Division for Malaria Control in the Ministry of Public Health and Sanitation. Another concern emerging from the survey was the large number of prescription-only drugs being sold over the counter. More details in a report from the Daily Nation. The Kenya Broadcasting Corporation also reports on the survey, highlighting the reduction in the number of cases and the increased use of insecticide-treated bednets (ITNs). Sixty-three per cent of Kenyan households now have at least one net. The full survey document is not yet available online.

Too many organizations, too much talk

Every few days there seems to be an announcement of the launch of a new programme or a new organization that seeks to address in some way the infectious diseases of poverty. When one considers the previous neglect of the disease burden in the world’s poorest countries, new initiatives are to be welcomed. One result, however, is that the so-called “institutional landscape” of global health is growing ever more complicated. A study in the Lancet, highlighted on TropIKA.net analysed the flow of funding for global health programmes and one of its findings was that the role of the UN system has been diluted in recent years, since the launch of new programmes and agencies. An accompanying editorial asked, “Who runs global health?” The same study confirmed the dominance of HIV/AIDS, malaria and tuberculosis in the funding provided for global health, and another Lancet study bears out the view that big programmes focusing on these diseases can harm the ability of health systems to provide comprehensive health care. There is cause for concern that the proliferation of agencies and programmes, each with their own agenda, may have harms as well as benefits. Are there now too many institutions in the landscape? Could there also be too many conferences? There are numerous TB conferences and when the annual Pacific Health Summit also chose to focus this year on drug-resistant TB one delegate told the meeting that she was tired of attending expensive gatherings hearing the same people say the same things – see TropIKA.net News. The organizers of this event did have a specific aim in mind – to get industry more involved in efforts to beat drug resistance and – while phrases like “stakeholder engagement” seem to many of us to be the worst sort of jargon – the activity they describe is important and international meetings are a part of the process. That said, many will have sympathy with the view that the global health conference circuit is getting out of hand. Does it all lead to advances in research, and to progress in the control and treatment of diseases on the front line of health care? There has certainly been no shortage of progress for us to report on TropIKA.net in recent days. There has been media interest in the continuing phase 3 trials of the most advanced vaccine under development for malaria, RTS,S. The development of further malaria vaccines may be assisted by the resources for immunologists made available by the US National Institute of Allergy and Infectious Diseases on the new website of its malaria research programme. Meanwhile, a dengue candidate vaccine is soon to enter a phase 1 trial. The TB Alliance will provide support for the further development of a promising new TB drug. Vaccination against pneumococcal disease in developing countries has come a step closer with the announcement of a $1.5 billion “Advance Market Commitment” [8]. Reports from Ethiopia describe the successful integration of trachoma and malaria control campaigns. Community level action has been shown in a study to be effective in controlling the mosquito vector of dengue fever in Cuba, and from India there are encouraging reports of community level projects for TB. All this is a long way from complex institutional landscapes and expensive conferences. However, if constant new initiatives and meetings at a global level really are essential to progress on the front line, then we shall have to learn to live with them. Paul Chinnock Editor-in-Chief, TropIKA.net

RTS,S: malaria vaccine in the news

Phase 3 trials began in Africa earlier this year of the most advanced malaria vaccine currently under development - RTS,S developed by GlaxoSmithKine (GSK) in partnership with the Malaria Vaccine Initiative (MVI) - see TropIKA.net News. Progress with the trials, taking place in seven African nations, is attracting media attention. A story in the Globe & Mail comes from one of the trial sites, Kilifi in Kenya, and focuses on the mothers of children in this highly-endemic area and on the challenges faced by the researchers carrying out the trial. An article in iafrica.com reminds us that the aim is for the vaccine to be brought into use in 2012, with the expectation that it will provide protection against malaria at around the 50% level. (In the longer term, it is hoped to develop vaccines with 80% protection or higher.) Other media covering the RTS,S trials include China's CriEnglish.com and Nature. (Information on the vaccine is also available on the GSK website.) It is good to see this level of international interest. The pressure is on GSK, MMV and all the researchers involved to complete the trials and bring the world's first malaria vaccine on to the market, while making it accessible to all who need it.

Indian malaria month is "not just about malaria"

The integration of disease control programmes is something to strive for, to avoid duplication of efforts and to improve effectiveness. When infections are spread by similar vectors, integration should be easier to achieve. Varanasi, an Indian city with a population of over three million, has an annual Malaria Month. But District Medical Officer MA Kahn told the Times of India that: "The anti-malaria month is not all about malaria, as other vector-borne diseases are also taken into consideration during the month". According to the Times of India article, there have been encouraging declines in the number of cases of malaria, dengue and filariasis in the Varanasi region during the last few years. As well as improvements in mosquito control, disease control initiatives have included mass drug administration and night blood surveys for filariasis, and wider use of test kits for dengue fever. The region hopes to eliminate filariasis within the next six years.

Uganda's stock of antimalarials improves

The treatment of people with malaria in Uganda has been hampered in recent months by a shortage of drugs. Reports indicate that the position is now improving. Primary Health Care minister James Kakooza says national supplies of the artemisinin combination therapy (ACT) Coartem are sufficient to cover the next 4-5 months. He blamed shortages on temporary problems in delivering drugs from district stores to front line health units. The New Vision newspaper reminds its readers that supply problems were caused when the Global Fund to Fight AIDS, Tuberculosis and Malaria identified problems with the way its funding for Uganda had been used. Its support for Uganda was for a while suspended. Officials found guilty of mismanaging funds are now serving prison sentences. Another New Vision report says the government has promised to provide free mosquito nets for the entire population. One net will be supplied for every two people. Initially, priority will be given to children and pregnant mothers. Six million nets have been distributed already, during the last three years, and 17.4 million nets are now to be imported. According to the health ministry, malaria kills 320 Ugandans every day. The disease accounts for about 40% of outpatient visits to health care facilities and 20% of hospital admissions.

Ghana loses 10% of its economy to malaria

Dr George Sipa Yankey, Ghana's Minister of Health, says malaria is calculated to have cost the country $760 million last year. This amounts to 10% of Ghana's gross domestic product (GDP) for 2008. Further details are given in a report, from the Ghana News Agency, of an address given by Dr Yankey at the launch of a national Malaria Vector Control Programme. The costs included in the $760m figure are said to be those for "procurement of medicines for the treatment of the disease, storage and transportation of drugs, cost of treatment and man hours lost". It is not often that one sees such a stark indication of the extent to which an infectious disease of poverty can damage a national economy and hold back its development.

Useful advice on malaria tests

The media could potentially play a huge part in providing the public with advice on infectious diseases. Nevertheless, much of the media's health coverage is inappropriate and sometimes misleading. It is good to see a relevant and practical article in Uganda's Daily Monitor. "What could affect your results?" describes what happens when a person with suspected malaria provides a blood sample for testing. Testing for other conditions is also discussed. A central issue in providing a sample is timing, the article explains.

Ugandans advised to drink artemisia tea to prevent malaria

Artemisinin combination therapy (ACT) is now the mainstay of treatment for malaria and - with no new drugs in the development pipeline - it is vital to do everything possible to delay the development of artemisinin resistance. It is known that the use of low doses of antimalarials, resulting in parasites "experiencing" the drug but at levels which allow them to survive it, is a major factor in the the development of resistance. What should we make, therefore, of the fact that people in Uganda are being recommended to drink tea made from the leaves of artemisia (the herbal source of artemisinin)? Monitor Online reports that Mr Charity Mugisha, general secretary of the National Council for Traditional Healers and Herbalists Association says: "Taking a cup of boiled artemisia leaves mixed with lemon grass every week prevents one from contracting malaria. Our counterparts in the Ministry of Health have actually proved that the artemisia mixture also improves the health of people living with AIDS just because it cures all the diseases that normally attack an AIDS patient." Mr Mugisha also says that taking a cup of boiled artemisia leaves every week cures eye infections and conjunctivitis, and that it can heal "spirit possessed persons". The Monitor also reports Patrick Ogwang a pharmacist and pharmacologist with the Ministry of Health as recommending the use of a combination of artemisia and lemon grass tea. Speaking of his involvement in a study involving several Ugandan communities, he said: "Our laboratory with me as the lead investigator monitored these communities for six months and found that it appeared that taking boiled leaves of artemisia mixed with lemon grass was giving them 80 per cent maximum protection from contracting malaria. But the safety and resistance to artemisinin was not investigated. Once this is fully investigated, we shall recommend for the official use of the mixture to fight malaria and save peoples’ lives besides stopping the heavy costs the government spends on buying malaria drugs". It is not the first time that artemisia tea has been recommended for treating or preventing malaria but, given what we now know about the development of resistance to antimalarials, there must be some concern that, should the drinking of artemisia tea become common in malaria-endemic countries, the demise of artemisinin as an effective malaria treatment might well be hastened.

Malaria: the view from Colombia

The malaria situation in Africa and Asia often receives attention, but it is unusual to see any discussion in the media concerning the disease in the Americas. An article from Colombia is therefore of interest. There are an estimated 150,000 malaria cases in Colombia every year. In 2007 there were only 19 malaria deaths, down from several hundred a few years ago. The problem is, however, more severe than in most neighbouring countries, probably as a result of the decades of civil conflict which Colombia continues to experience. The conflict has led to large numbers of people being displaced from their homes. “I think if we didn’t have this problem of displacement, the conditions here would be quite similar to other countries,” says Pablo Chaparro, who manages the country’s information system on malaria at the National Institute of Health. A five-year malaria programme, financed by the Global Fund to Fight AIDS, Tuberculosis and Malaria, is about to be launched in Colombia.

Quack remedies for TB, malaria and AIDS promoted in Africa

An article in the UK Guardian reports that a group of British scientists has appealed to WHO to publicly condemn the marketing of homeopathy and other "alternative" treatments as cures for TB, malaria and AIDS, when there is no evidence that such treatments have any effect against these diseases. A copy of the letter, which is available on line here, gives shocking examples of unsupported claims made for these treatments in five African countries. Professor Raymond Tallis, Manchester University, told the Guardian: "The catastrophic consequences of promoting irrational and ineffective treatments for serious illnesses have been demonstrated in South Africa, where Thabo Mbeki's policies have led to an estimated 365,000 unnecessary premature deaths. The prospect of replicating this reckless behaviour elsewhere in developing countries by advocating homeopathic treatments for AIDS and other potentially lethal conditions is appalling."

Nigeria's schistosomiasis

A review article on the website 'Environmental Public Health Today' is entitled 'Health Impact of Schistosomiasis and the Reduction of the Incidence of the Disease in Nigeria'. No information is provided about the author other than her name - Elizabeth Oguledo. The layout of the article makes it a little hard to read, and over half of it is a general description of the disease and is not specific to the Nigerian situation. Nevertheless, some interesting information is presented on the prevalence of the condition in Nigeria, as well as current control efforts, and public perceptions as to the cause of the disease. (Surveys have shown that a majority of Nigerians are not familiar with the cause of schistosomiasis; one of the most common beliefs is that it is sexually transmitted.) The author concludes that: "The good news is that the disease is completely preventable and can be controlled through the annual inexpensive drug treatment, and with community-based intervention with Nigeria health department initiating health education with emphasis on avoiding washing, bathing or drinking contaminated water coupled practicing basic hygiene. Also, cultural beliefs about schistosomiasis in most parts of Nigeria should be addressed through education."

Always worth a look: Malaria Matters

The Malaria Matters blog is always a great source of information on new developments that concern malaria (and related topics). Here, for example, are two contrasting recent postings to the blog. One discusses the finding, reported in the American Journal of Tropical Medicine and Hygiene, that there has been ‘remarkable malaria control progress and benefits on the island of Bioko in Equatorial Guinea over the last 4 years.’ Another "> looks at the 'club' of nations who have experienced suspension of their grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria, for reasons that include "weak project implementation, slow procurement of health products, poor data quality, and slow spending of project funds". Zambia looks like becoming the latest nation to join the club. The most famous is Uganda, where the former health minister and his two deputies are on trial with several government officials for charges relating to the misuse of Global Fund money.

India's urban malaria worries

In India malaria has been regarded as primarily a problem of the rural areas. Reports in the Times of India suggest the situation may changing. Mumbai has this year seen a steep rise in case numbers. "Since January this year 6,300 malaria cases have been reported, an increase of nearly 47% from 2,300 cases in the corresponding period last year," said K M Hargoli Assistant Health Officer (Malaria), for the Brihanmumbai Municipal Corporation (BMC). He blamed the situation on the large number of infrastructure and construction projects being undertaken, and on higher than usual temperature and humidity levels. Cities in Karnataka State have also seen more cases in recent years. Dr S K Ghosh of the National Institute of Malaria Research told the Times that, in contrast, the incidence of malaria in rural areas has declined.

More on artemisinin resistance in Cambodia

There is increasing recognition of the seriousness of reports indicating the appearance in Cambodia of resistance to the key antimalarial artemisinin. (See TropIKA.net news stories - 1 , 2 .) We await publication of peer-reviewed studies giving full details of what researchers have found in Cambodia. In the meantime, several media outlets have now given the development their attention. Professor Nick Day, director of the Mahidol-Oxford Tropical Medicine Research Unit, told the BBC: "Twice in the past, South East Asia has made a gift, unwittingly, of drug resistant parasites to the rest of the world, in particular to Africa. If the same thing happens again… there will be devastating consequences for malaria control." BBC World Service has also published two interesting podcasts on the situation. According to the FirstPost a US study in Cambodia found delayed clearance of malaria parasites in between one third and a half of patients. In a UK study, patients living in Cambodia took almost twice as long to clear the malaria parasite as a comparison group in Thailand. Even a UK mass market tabloid the Daily Mirror, which normally avoids topics such as the infectious diseases of poverty, has a news story. While its headline - 'Killer new malaria bug discovered' - is hardly helpful, it does demonstrate an awareness of the seriousness of the situation.

Iron supplementation does not increase malaria risk

The malaria parasite loves free iron. Clinicians know they must bear this in mind when treating children who have both malaria and anaemia. Giving such children iron can increase the number of parasites and the severity of their malaria. It has been speculated that children living in malaria-endemic regions might be protected when suffering from iron-deficiency anaemia. Community programmes of iron supplementation in malaria-endemic areas might, in that case, cause harm. However, the results of a systematic review presented at the 19th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) provide strong evidence that iron supplementation should not be restricted in settings where iron deficiency and anaemia affect most children, as it does not increase the risk of malaria, other infections, or all-cause mortality. The review was presented to the meeting by Dr Mical Paul of the Rabin Medical Centre, Israel, on behalf of the Cochrane Infectious Diseases Group. The review has yet to be published on the Cochrane Library. A summary of the findings is available on docguide.com.

All controversy is good controversy ...perhaps

Bill Gates is a remarkable man, now noted not only for his success in business but for his decision to devote so much of his wealth to global health and development, through the Bill & Melinda Gates Foundation. The Foundation and the way it works is now, however, the subject of controversy following an analysis published in the Lancet and featured on TropIKA.net. The Gates Foundation gives particular emphasis to finding new technological solutions – inevitable perhaps as Bill Gates made his money through technology. (We can only speculate what his approach to global health would have been had he become wealthy as a result of a career in the media, finance, energy or some other sector.) However, critics are asking whether the Foundation’s technological emphasis detracts attention from the social determinants of health, and from efforts to improve the delivery of existing interventions of proven effectiveness. Critics have also commented on the Foundation’s tendency to prioritise support for a small number of diseases; in particular there is a poor correlation between Foundation funding and the childhood disease burden. The Foundation not only provides a significant proportion of global health funding but also plays a part in setting priorities more widely. Perhaps the most important criticism is that it provides no information as to the processes it uses in deciding upon those priorities. Priority setting has also created controversy elsewhere. A renewed appeal has been made, in another article in the Lancet, for the control of “neglected tropical diseases” (NTDs) to receive more funding. The authors particularly emphasise seven of the long list of NTDs that they consider to be both the most widespread and the most amenable to control. The seven include schistosomiasis; new research on the prevalence of this condition in Mali demonstrates that if successful programmes are not sustained then progress can easily be reversed. Meanwhile, others make the point that diarrhoeal diseases are amongst the very biggest killers of poor children but have lost the position they once held on the priority list. Can we now say that they should therefore be added to the “neglected” category? A new report marks the start of attempts to restart international action against these diseases. We also carry news of a project which may lead to new treatments for diarrhoea but see, however, the cautionary note sounded in a TropIKA.net blog . The last few days, have seen the emergence or re-emergence of other controversies. The use of DDT as part of malaria control efforts – see our news story – is an issue where passions have often run high. Also in the news and also likely to be controversial is the decision of an Indian company to continue the development of a new malaria drug, despite the fact that the Medicines for Malaria Venture with which it was in partnership decided to withdraw its collaboration following disappointing trial results. And in America, details are awaited of what support the Obama administration [9] will give to global health. Announcements made from the White House have led some critics to accuse Obama of failing to deliver on his pre-election promises on, most notably, AIDS. However, the President has said that his new approach will be ‘comprehensive’. Whatever he decides will be controversial but it may be that previously neglected areas will receive more attention and that his priority setting will be more in line with the disease burden. Perhaps then it is good that the infectious diseases of poverty have lately become the subject of so much controversy. It is an indication that the issue is now receiving attention at senior levels and that efforts are being made to identify the best ways forward. Controversy, however, should not be allowed to drag on for too long. Words must give way to action. Paul Chinnock Editor-in-Chief, TropIKA.net

Kits for detection of insecticide resistance in mosquitoes

Insecticide resistance is an issue of concern to malaria programmes, in which control of the mosquito disease vector plays a key role. The Liverpool School of Tropical Medicine (LSTM) has been awarded a £1.1m grant by the US National Institutes of Health to lead a five year project to develop a Field Applicable Screening Tool (FAST) kit to detect resistance to public health insecticides in mosquitoes. Project leader Dr Martin Donnelly, Senior Lecturer in Vector Biology at LSTM said: “Malaria control in Africa is reliant upon the use of insecticides against mosquitoes. Therefore if the mosquitoes develop high levels of resistance to these insecticides the public health impact could be devastating. We are proposing to develop DNA-based tests which are sensitive enough to detect resistance when it is at a low level and thereby enable control programme staff to take action to reduce the build up of resistance.” More information is available in the LSTM press release.

Team behind key ACT antimalarial receives major honour

Artemisinin combination therapy (ACT) is now recommended as the mainstay of treatment for malaria. The artemisinin story is well known. Derived from an old herbal remedy known as Artemisia annua, or "sweet wormwood", it was used in China beginning around 168 BC to treat malaria. The herb was re-discovered in 1967 to treat malaria-stricken soldiers during the Vietnam War. To reduce the risk of the development of resistance, it was decided that artemisinin should be administered in combination with other drugs. A Chinese team, which developed the combination of artemisinin with lumefantrine (also known as benflumetol) has received a European award. Professor Yiqing Zhou and his team at the Institute of Microbiology and Epidemiology in Beijing are the winners, in the 'non-European' category, of the European Inventor of the Year Awards for 2009. They completed their successful artemisinin-lumefantrine combination in 1996. The drug is now marketed by Novartis as Coartem. The award is made by the European Patent Office (EPO) and the European Commission. The EPO website features a short interview with Professor Yiqing.

Will President Obama fulfil his promises on global health?

President Obama wants the United States to spend $8.6 billion next year - $63nb over the next six years - to fight global diseases and provide more aid for prenatal and postnatal care, children's health and fighting tropical diseases - see White House press release. The President repeated his view that, "We cannot wall ourselves off from the world and hope for the best, nor ignore the public health challenges beyond our borders". He said he wanted to launch "a new, comprehensive global health strategy". However, critics are concerned that what he is proposing for global health will fall short of the expectations he created before his election. For example, the President's Emergency Plan for AIDS Relief (PEPFAR), begun by former President Bush, seems likely to receive next year a $460 million increase over this year's budget, whereas Obama's 2007 Global AIDS Day statement spoke of a $1bn increase in PEPFAR funding annually. The Global Fund to Fight Aids, Tuberculosis, and Malaria will receive $900 million next year, the same as it received in 2009, and way below the $2.7 billion it requested from the US to help it meet a $5 billion funding gap. Interviewed by Associated Press, Christine Lubinski, director of the Center for Global Health Policy said, "With this spending request, Obama has broken his campaign promise to provide $1 billion a year in new money for global AIDS, and he has overlooked the growing threat of tuberculosis." Joanne Carter, executive director of the advocacy group Results told the Chronicle of Philanthropy that the president’s plan “halts the dramatic scale up of funding we’ve seen” for AIDS under the Bush administration, provides “disturbingly low” support for fighting tuberculosis, and provides no increase in support for the Global Fund. IRIN News reports Dr Paul Zeitz, executive director of the Washington-based Global AIDS Alliance as saying that Obama's 2010 budget "essentially flatlines support for global health". Serra Sippel, executive director of the Centre for Health and Gender Equity, was also disappointed that funding had not increased, but welcomed the comprehensive approach as a "more effective use of our aid". Meanwhile, a Kaiser Family Foundation survey found that 71% of Americans do not believe their country can afford to spend more on global health when the US is experiencing a severe recession.

Magnetic test for malaria

Professor Dave Newman, of the Department of Engineering, University of Exeter (UK) is receiving Gates Foundation support to develop a non-invasive diagnostic test for malaria that uses the principle of magneto-optics. The aim is to produce a simple, cheap, hand-held, battery-powered device. See story in Times Online.

Malaria vaccine trial planned for next year

Voice of America has published an interview with Dr Stephen Hoffman, founder and chief executive officer of Sanaria Lab, a company which has developed a malaria vaccine and is hoping to begin trials among healthy adults in Africa next year.

Reports of relevance

Banks are interested in money and their take on health issues is different ...but important. A report from the Asian Development Bank, recently featured on the TropIKA.net blog, examines the economics of climate change, based on a major 15-month study. The ADB believes that there are several mechanisms through which changes in climate will impact on the economy, one of which is via the effects on human health. For health specialists, human health and wellbeing are ends worth pursuing in their own right and not just a requirement for economic growth. Nevertheless, this report is well worth a look. The ADB notes that increases in temperature could lead to more malnutrition and more diarrhoeal disease, but the threat it discusses in most detail is further increases in dengue fever rates. Now that dengue has been officially recognised as a danger to the economy, will it remain a neglected disease or will we see an increase in funding for research and control efforts? As we noted in a recent TropIKA.net News article new directions for dengue research are opening up, but adequate support will be required for them to be pursued. Another bank, the World Bank, has just published a frank and transparent evaluation of the effectiveness of the health programmes within its ‘portfolio of investments’. Nearly half of the Bank’s health support is for action against infectious diseases. However, almost 90% of the infectious disease programmes it supports are focused on just one disease – HIV/AIDS. Critics have said that this disproportionate emphasis has distorted health priorities in countries receiving Bank assistance. Also of great concern is the fact only a minority of Bank HIV/AIDS programmes (29%) have performed satisfactorily. In contrast most (89%) of the programmes devoted to other infections are regarded as being satisfactory. There must surely be two conclusions here. Firstly, better ways must be found of addressing HIV/AIDS. (No one would argue that the Bank or the international community at large should give up on this disease.) But secondly, since the evaluation has established that action against other infections (such as schistosomiasis, leprosy, malaria and TB) offers good value for money, investment in such programmes should be increased ...if only on economic grounds. Also recently featured in the TropIKA.net Reports section is a document from UNICEF: Malaria & Children: Progress in Intervention Coverage. Although UNICEF believes that “We are, for the first time in history, poised to make malaria a rare cause of death and disability” many outstanding challenges are noted in this report. Progress in getting effective antimalarial treatment to all who need it has been slow and the number of pregnant women who sleep under insecticide-treated nets is still much too low. The latter point has been underlined by recent news from Liberia. As well as highlighting important news and reports published elsewhere, TropIKA.net continues to publish original content. Our recent extended interview with Michael Gottlieb, head of the Grand Challenges project at the Foundation for the US National Institutes of Health is of particular interest, as it comes at a time when the entire Grand Challenges in Global Health project – a research funding initiative that is worth almost half a billion dollars – is at a crossroads. Paul Chinnock Editor-in-Chief, TropIKA.net

Coartem controversy

The drug Coartem (artemether-lumefantrine) is an important antimalarial and appears on WHO's Essential Drugs List. It was first registered for use in 1999. The patent is owned by Novartis. A public-private partnership involving the company and the Medicines for Malaria Venture has developed a flavoured, dispersible form of Coartem suitable for children which has been shown to be effective in trials - see TropIKA.net blogs 1 , 2 . However, the drug has become embroiled in controversy, having been used by Novartis in the USA to obtain a voucher from the Food & Drugs Administration (FDA) that will enable it to obtain fast-track approval for another of its drugs, which (unlike Coartem) will not be one that is a treatment for an infectious disease of poverty (IDP). The voucher scheme was set up by FDA as a way of encouraging the drug industry to devote resources to the development of drugs for IDPs. The idea is that manufacturers will be more likely to turn their attention to drugs from which they will make little profit, if it results in their 'blockbuster' products (for the diseases of richer nations) getting on the market sooner. But for some time critics have warned that the voucher system could be exploited by industry - see TropIKA.net blog 3 . An article in the Lancet goes into the issue in more depth. Bernard Pécoul of the not-for-profit product development partnership Drugs for Neglected Diseases says that awarding vouchers for 'old' drugs such as Coartem does not reward or encourage innovation. Rohit Malpani, a policy adviser at Oxfam America, told the Lancet that: “Novartis is abusing the intent of the voucher programme by applying for and accepting a voucher for Coartem — a medicine that was developed and launched nearly a decade ago. Awarding Novartis with the first ever voucher under this programme sets a terrible precedent.” Sadly this vital drug has developed a tendency to run into controversy. It is in short supply in many countries (as a result of poor health systems in those countries) and is not as yet reaching as many malaria patients as had been hoped - for example see TropIKA.net blog 4 . This means that many people with malaria are still receiving older ineffective antimalarials. In at least one country, however, local manufacturers of the older drugs have condemned the arrival of Coartem in their countries as a being a threat to local industry - see TropIKA.net blog 5 . It would be disappointing if these controversies were to hold back in any way the fulfilment of the main aim in the development of Coartem - getting a malaria treatment that works to all who need it.

World Bank malaria and TB projects do better than those on AIDS

Seven of 10 AIDS projects financed by the World Bank have been found to have "unsatisfactory outcomes" according to an internal Bank evaluation. In marked contrast, nine of 10 of other infectious disease projects performed satisfactorily or better. The Bank's report is discussed in a New York Times article. The article notes that: "While the focus on AIDS accounted for nearly 60 percent of the bank’s projects on communicable diseases from 1997 to 2006, more successful efforts aimed at malaria, tuberculosis and leprosy, among others, got far fewer resources. Malaria, for example, made up 3 percent of the projects, and tuberculosis only 2 percent." It also quotes William Easterly, an economics professor at New York University, as saying that the evaluation confirmed for him “a fear that many of us have had for some time: that hugely disproportionate attention to AIDS has had a negative effect on aid efforts for all other health problems.” The evaluation concludes that AIDS projects were often over-ambitious and that many were too complex for the weak or inexperienced bureaucracies carrying them out. The evaluation is available on the World Bank website.

Climate change and the economy: increase in infectious diseases will add to the problems

"The Economics of Climate Change in Southeast Asia: A Regional Review" is a major new report from the Asian Development Bank. It is based on the results of a 15-month study, funded by the UK, which examined climate change issues in Southeast Asia, with a particular focus on Indonesia, Philippines, Singapore, Thailand, and Vietnam. The report says that: "The study observed that climate change is already affecting Southeast Asia, with rising temperature, decreasing rainfall, rising sea levels, increasing frequency and intensity of extreme weather events leading to massive flooding, landslides and drought causing extensive damage to property, assets, and human life. Climate change is also exacerbating the problem of water stress, affecting agriculture production, causing orest fires, degrading forests, damaging coastal marine resources, and increasing outbreaks of infectious diseases." Health In the report's section on human health, the startling rise in the incidence of dengue in the region, with many previously unaffected areas now reporting cases, is regarded as being of particular concern. Further increases in temperature could lead to a worsening of the position for other vector-borne infections such as malaria. Diarrhoeal disease, including cholera, is also considered likely to increase. The report concludes that: "An increase in morbidity and mortality is predicted to occur in most Southeast Asian countries due to water-borne diseases, primarily associated with floods and droughts." Other likely impacts on human health range from malnutrition to thermal stress. Despite these concerns and the potential economic impact resulting from the damage to health, agriculture and natural resources, the Asian Development Bank considers there is a positive side. Bank Vice-President Ursula Schaefer-Preuss says: "The global economic crisis provides an opportunity for the world, and Southeast Asia, to start the transition toward a climate-resilient and low-carbon economy."

Brazil-based network proposes new therapeutic approach for TB and other infectious diseases

Farmabrasilis is a non-governmental, non-profit research network bringing together Brazilian, Chilean, American and European scientists and others whose concern is: "The research and development of new medicines and technologies for the benefit of economically disadvantaged populations and individuals affected by neglected diseases". The main focus of the work of Farmabrasilis has been the development of the immunomodulator P-MAPA. Although this compound was originally intended for cancer treatment and it has been shown to have anti-tumour activity, P-MAPA also modulates the production of interferon-gamma and interleukin-10, known to be key substances in the body's defences against TB, malaria and other infectious diseases. This had led Farmabrasilis to put forward a new approach to treating patients with these conditions - including those co-infected with HIV - which would involve attempting to re-establish patients' immunocompetence by adjuvant immunotherapy with P-MAPA. This proposed new therapeutic approach was presented to delegates at the recent STOP TB Partnership Forum held in Rio de Janeiro. Farmabrasilis welcomes contact with other individuals and organizations interested in the further development of the proposed approach.

Infectious disease in the headlines

Our remit at TropIKA.net is the infectious diseases of poverty and we cover a wide range of medical conditions and associated issues. However, during the last few days, one disease – malaria – has been the dominant theme of our new content. We marked World Malaria Day 2009 with an interview with Professor Kilama of the African Malaria Network Trust and a News story summing up what happened in the build-up to the Day and the response to it. Many glitzy, glamorous events were held to mark the Day but my editorial focussed on the front line of care, where “Every day is Malaria Day”. There were also numerous new items on malaria within the TropIKA.net blog. But, since the announcement by WHO on 24th April of a major outbreak of influenza caused by the A/H1N1 virus, the world’s most talked about infectious disease has been swine flu. The TropIKA.net update on swine flu highlights the fact that the epidemic started in a poor community and that, while rich and poor are now at risk, people in the developing world are less likely to receive appropriate diagnosis and treatment. World Malaria Day and swine flu notwithstanding, we have also reported some important new developments in the fight against trachoma , tuberculosis and dengue fever. Other recent topics have included human rights , patent pools for drugs for neglected infections and the encouraging rise in the number of publications where the first-named author is from sub-Saharan Africa. TropIKA.net is an interactive project. Our articles and blogs include the facility to leave comments. Please feel free to share your views or add information that we may have missed. Paul Chinnock Editor-in-Chief, TropIKA.net

Angola has a new medical research institute

Medical research in Angola, in southwestern Africa, will receive a major boost with the opening of a new research centre in Bengo province. A report from allAfrica.com says the centre will conduct research on a number of conditions including: malaria, TB, HIV/AIDS, filariasis, schistosomiasis, trypanosomiasis and viral haemorrhagic fevers. The centre, known as CISA, is sponsored by Angolan government, Portugal and the Calouste Gulbenkian Foundation. Portugal's Health Ministry and the Agostinho Neto University Medicine Faculty are partners in the project.

World Malaria Day: four of the best

The number of statements, press releases, media stories and blogs devoted to World Malaria Day 2009 has been overwhelming, even though on the Day itself (25th April) the disease attracting by far the most media attention was swine fever. It would be impossible to write a review of everything that has been said about malaria during these last few days but here is a small personal selection. Best news Malaria deaths reported from health facilities in Zambia have declined by 66%. This result along with other supporting data indicates that Zambia has reached the 2010 Roll Back Malaria target of a more than 50% reduction in malaria mortality compared to 2000. Most worrying news Vincent Corbel, a malaria specialist with the World Health Organization, told a symposium held in Nairobi that, "Studies have indicated that two species of malaria-transmitting mosquitoes found in Kenya have developed resistance to permethrin and DDT". Most useful document A four-page policy brief from the Global Health Council describes the present malaria situation with admirable clarity. It concludes that, "Today's tools will allow us to control or eliminate malaria in some regions, assuming no changes in disease epidemiology. However, eradication requires expanding the use of and improving current tools; developing new diagnostic, prevention, and treatment technologies; and strengthening health systems." Most senior figure to renew commitment President Barack Obama said the United States wants to help meet the United Nations' goal to end malaria deaths by 2015. He said US commitment began with ending malaria as a major public health threat in Africa.

World Malaria Day in the journals

World Malaria Day (25th April) is given good coverage in this week's Lancet. In a Comment, Sir Richard Feachem and Allison Phillips discuss the rapid progress made in malaria control and elimination in the past two years, and discuss their optimism for the future. A second Comment outlines in detail the progress towards a malaria vaccine. There is also a Lancet video. Two immunology journals have published articles referring to World Malaria Day - see The hope but challenge for developing a vaccine that might control malaria in the European Journal of Immunology and, in the Journal of Immunology, World Malaria Day 2009: what malaria knows about the immune system that immunologists still do not. The authors of both articles believe that the development of a highly effective vaccine will require a better understanding of several features of the immune response to malaria.

Marking World Malaria Day

World Malaria Day (Saturday 25th April) continues to prompt people and organizations across the world to come forward and say what they are doing to help fight malaria. As UK government aid agency DFID says, this is a good time to take stock. World Malaria Day has been chosen by a maker of bed nets to announce that it is stepping up production. Many Christian organizations (1, 2) are involved with World Malaria Day fund raising and awareness efforts. More surprising than the participation of faith-based organizations is the interest shown by oil companies (1, 2). Many oil fields are in malaria-endemic countries and it is good business sense to try to keep workers and their families free from malaria. Even the Wall Street Journal, which focuses on matters economic, has published an article about World Malaria Day. CNN is also providing good coverage. But it is not just the international media; from Ghana to Canada national and local newspapers are finding ways of drawing attention to World Malaria Day. Celebrities have decided to get involved. In many cases they are celebrities who this blogger has not actually heard of but their support is welcome. And the blogosphere is alive with World Malaria Day comments and opinions. If you see some good ones, share them with TropIKA.net - click Leave a Reply (below).

World Malaria Day: TDR highlights the need for research

Yesterday TropIKA.net produced a summary of some of the activities taking place to mark World Malaria Day - see TropIKA.net News Section. As World Malaria Day (Saturday 25th May) draws closer, further organizations are making their contributions and we will try to keep you up to date. The UN Special Programme for Research and Training in Tropical Diseases (TDR), has released an update on recent malaria research with which the organization has been involved. This includes studies of the home management of malaria, rectal artesunate, and community-directed interventions. TDR emphasises that, "Research plays a critical role in identifying what works and what new solutions can be added." TDR has also published a report of an evaluation of some of the rapid diagnostic tests for malaria that are now on the market, which could play a role in malaria control programmes. The evaluation found that the tests vary considerably in their performance. Some perform exceptionally well in tropical temperatures and can detect even low parasite densities in blood samples, while other tests were only able to detect the parasite at high parasite densities.The findings will serve as a tool for countries to make informed choices, from among the dozens of tests commercially available, on the purchase and use of rapid diagnostics that are best suited to local conditions. The full report, an executive summary and a press release are all freely available online from TDR.

Malaria: KeNAAM's 'Fresh air' conference

KeNAAM - the Kenya NGO's Alliance Against Malaria seeks to supplement the efforts of the Kenyan government to control malaria. One of KeNAAM's functions is to organize the annual "Fresh Air" conference on malaria, the most recent - the fifth to date - took place in November last year. Edward Mwangi of AMREF, one of the NGOs in the alliance, has announced that the report of the meeting is now available. He may be contacted on: edward.mwangi@amref.org. [The document has not yet been added to the '"Reports" section of the KeNAAM website. Nevertheless, there is much of interest on this site about the organization and its work, and the malaria situation in Kenya.] “Sustaining Public-Private Partnerships” was the theme of last year's two-day meeting, at which 21 reports were presented. Participants heard that although malaria in pregnancy is still unacceptably high in Kenya, malaria admissions have fallen by half nationally, paediatric deaths have been significantly reduced, funding for malaria control has increased 63-fold over the past five years to $63 million, and Kenya has assumed a leading role in malaria research worldwide. Universal access to insecticide-treated bednets (two ITNs per household countrywide) will be incorporated into Kenya's revised malaria strategy. But, to quote the Executive summary of the meeting: "Seemingly, little can be done to hasten the speedy translation of drugs, such as ACTs, from “prescription only” status to “over the counter” status, due to the need to satisfy legal and ethical norms." A range of current malaria control initiatives, including advocacy programmes, were also discussed at the meeting. Planning for the next "Fresh air" event is now under way

Free access to Nature malaria articles

During 2008, Nature published a number of articles describing advances in the deployment of existing malaria-control tools and the basic science of malaria. With sponsorship provided by the Special Programme for Research and Training in Tropical Diseases (TDR), the Medicines for Malaria Venture (MMV) and GlaxoSmithKline, the journal has brought these articles together in a supplement which may be accessed free online for three months. A free print copy may also be requested. In addition to the 2008 articles, the supplement also includes (again with free access) research papers from 2002 describing the genome sequence of Plasmodium falciparum and Plasmodium yoelii yoelii. Nature has not embraced the concept of open-access publishing but many key papers on the infectious diseases of poverty are published in this distinguished journal. The sponsors of the supplement are to be congratulated for their role in making the articles which have been included accessible to a wider audience.

Vector control should target the older mosquito

The development of insecticide resistance by disease vectors is as worrying as the development of drug resistance by disease agents themselves. Mosquito control remains a key part of action against malaria and more needs to be known as to how insecticide resistance appears. US and UK scientists have conducted a modelling exercise, reported in PLoS Biology, from which they conclude that "...if insecticides targeted old mosquitoes, and ideally old malaria-infected mosquitoes, they could provide effective malaria control while only weakly selecting for resistance. This alone would greatly enhance the useful life span of an insecticide." The authors continue: "However, such weak selection for resistance can easily be overwhelmed if resistance is associated with fitness costs. In that case, late-life–acting insecticides would never be undermined by mosquito evolution. We discuss a number of practical ways to achieve this, including different use of existing chemical insecticides, biopesticides, and novel chemistry. Done right, a one-off investment in a single insecticide would solve the problem of mosquito resistance forever." A news story about the paper, with interviews with the authors will be found in the UK's Independent newspaper. Sadly, the Independent opts for a headline which describes this modelling exercise as a "Breakthrough in fight against malaria". (Why must journalists do that sort of thing?) It may not be a breakthrough but it does suggest some interesting new directions for research.

Tanzania aims to 'kick out' malaria by 2015

The National Malaria Control Programme of Tanzania says that between 16 and 18 million cases of malaria occur in the country each year, causing more than 100,000 deaths. Malaria accounts for some 30 per cent of the country's disease burden. However, the government hopes to achieve elimination of the disease within six years. Commenting on the publication of the latest map from the Malaria Atlas Project (see TropIKA.net news story), The Deputy Minister of Health and Social Welfare deputy said that the release of the map would enhance Tanzania's fight against malaria and that, "With more knowledge about the disease and its prevalence across the country so that we can kick it out by 2015. The map will be of use to health workers, policy makers, researchers and other players in the war on malaria. It will help them in more easily identifying the places worst hit and thus enable them to focus on them faster". (Full story on IPP Media.) Tanzania has set a bold target and the country should be wished every success.

A time for maps: sleeping sickness

The creation of epidemiological maps for infectious diseases is a growing area of interest. We recently highlighted on TropIKA.net the latest progress made in the Malaria Atlas Project. Now a research article in the International Journal of Health Geographics describes the HAT Atlas initiative. HAT is human African trypanosomiasis or sleeping sickness, a potentially fatal disease of which there are somewhere in the region of 70,000 to 300,000 cases every year. (A TropIKA.net update article recently looked at new developments in HAT research.) Up-to-date as well as historical data collected by national sleeping sickness control programmes, non-governmental organizations and research institutes have been collated over many years by WHO, but it has mainly been unpublished. It is now being screened, harmonized, and analysed by means of database management systems and geographical information systems (GIS). The paper describes the input data, methodology, preliminary results and future prospects for the HAT Atlas initiative, which they authors say will allow major improvements in the understanding of the spatial distribution of the disease. They believe that: "The Atlas of HAT will lay the basis for novel, evidence-based methodologies to estimate the population at risk and the burden of disease, ultimately leading to more efficient targeting of interventions." HAT is one of the most neglected of diseases and even with the creation of a map there will still be a considerable way to go before more effecdtive control of the disease can be achieved. However, it is encouraging to see HAT receiving such attention and it is another demonstration of what can be achieved when GIS is applied to the infectious diseases of poverty.

Progress in Mozambique is marred by cholera

The current cholera epidemic in Africa is producing some worrying statistics ...and news headlines. Mozambique for example has released new figures showing that, since the start of this year, over 13,000 Mozambicans have been diagnosed with the disease, compared with about 12,000 for all of 2008. There have been 140 deaths so far this year; there were 150 in the whole of 2008. Mozambique has a long border with Zimbabwe, which currently has the most severe cholera problem and has become a major exporter of the disease. However, Mozambique has progress to report as regards other infectious diseases of poverty. Leprosy is no longer regarded as a public health problem in the country. In 2008, all provinces in Mozambique recorded less than one case of leprosy per 10,000 inhabitants. Measles vaccination campaigns have led to a dramatic reduction in notified cases, by over 95 per cent in three years. In 2005, the health authorities recorded 12,598 measles cases but in 2008 the figure fell to 278. From 2007 to 2008 the number of known cases of malaria also fell by 24%. The health ministry attributes this to recent campaigns of of insecticide spraying against mosquitoes, and improvements in malaria diagnosis and treatment. (Malaria of course often does vary greatly from one year to the next.) The figures were released by Health Minister Ivo Garrido during a meeting of his ministry's Coordinating Council. They are reported on allAfrica.com.

Will the poor suffer most?

What impact will the global economic decline have on the lives of the poor? Will it reduce the already inadequate funding for research and control programmes devoted to the infectious diseases of poverty? Kofi Annan fears that it may indeed be the poor who suffer most and he calls for a “coordinated global stimulus” which will benefit the least developed countries. But there is simply less money around just now. No one can avoid the effects of the financial crisis – sadly not even the Gates Foundation, which plays such a crucial role in global efforts to eliminate infectious disease. Infectious diseases add of course to the economic burdens faced by developing nations. Nevertheless, it is hard to quantify their impact. TropIKA.net has recently published a summary of preliminary calculations made by the Indian Institute of Management, Ahmedabad seeking to calculate the economic cost of dengue fever. This comes at a time when there are indications that, in Asia, dengue may be more common than shown in official figures. The prevalence and incidence of many other diseases may also be under-estimated. A recent survey suggests that India’s progress towards the elimination of leprosy may be less impressive than has been claimed. It is good to know therefore that a useful dialogue on issues related to leprosy still continues. Playing a part in this is the Leprosy Mailing List, one of the mailing lists featured in our Networking section. It is not disputed that rates of tuberculosis are high in China but the consequences may be even more serious than recognised. A new study provides evidence that the infection increases the risk of lung cancer. My selection of new content on TropIKA.net does seem to have focused on the bad news this time around, so let me finish with a positive research finding – chloroquine, once the mainstay of malaria treatment, has been found to be active against two emerging threats to health, the Nipah and Hendra viruses. This is a drug which should not be consigned to history. At a time like this we need some old friends around us! Paul Chinnock Editor-in-Chief, TropIKA.net

Indonesia is ready to produce key antimalarial on a large scale

The recommended first-line treatment for malaria is artemisinin combination therapy (ACT) but shortages of artemisinin, which is derived from the plant Artemisia annua, poses a problem. In several parts of the world projects are under way to grow more of the plant. A news report describes the excellent progress being made by Indonesia. The plant has been cultivated since 2006 at a field managed by the Health Ministry’s Agency for Research in Medicinal Plants and Traditional Medicines in Tawangmangu, Central Java Province. The agency says that it is now ready to start production on a large scale and that local farmers are being encouraged to switch from other crops to Artemisia. Further details are in the news story from IRIN, the news service of UN Office for the Coordination of Humanitarian Affairs

Death ray would strike down mosquitoes

The laser death ray remained for many years in the realm of science fiction. Then in the 1980s US President Ronald Regan put forward what became known as his "Star Wars" programme - a defence system involving laser beams that wold knock out Soviet missiles. Now, according to the Wall Street Journal some of the same scientists involved with that project are now aiming their lasers at another target: the mosquito. The intention is to create a new form of vector control to combat malaria. The team has already succeeded in killing small numbers of mosquitoes and they seem optimistic that they can go on to create laser shields around individual homes or whole villages. They say that it would be possible to kill mosquitoes trying to penetrate the shield, without harming humans or beneficial insects. If this works, then one would imagine that the vectors of other diseases could also be targeted. Presently the vector control strategy for malaria involves indoor residual spraying with DDT and the use of insecticide-treated mosquito nets. The worry is that one day the mosquito will become resistant to these insecticides, so it is good to know that other vector control technologies are being investigated. But it is difficult to imagine how a programme to shield every home in every malaria-endemic community in the world could ever be put in place. Like Star Wars, is this an idea that would only work in a world of fantasy in a galaxy far, far away? Now

Potential for a new antimalarial?

An an article on Scienceline discusses progress made in the synthesis of FR900098 - a compound first identified nearly 30 years ago and known to possess both antibiotic and antimalarial properties. Fujisawa Research, the Japanese pharmaceutical company isolated FR900098 from a common soil bacterium Streptomyces rubellomurinus. Synthesis of the compound has been achieved in the laboratory but this is expensive and it would be difficult to produce it on a large scale. The Scienceline report focuses on the work of a team at the University of Illinois which has isolated a gene that controls the production of FR900098. To quote the report: "By cloning this gene and inserting it into an easily manipulated bacterium E. coli, the team created a tiny biological factory." While team members say they still need to make their process more efficient, they hope that industry may then be able to use it to manufacture FR900098. With concern growing over the appearance of resistance against the current first-line antimalarial artemisinin (see TropIKA.net blog), a potential new malaria treatment would be very welcome. (A scientific paper describing the work of the Illinois team was published last year - see abstract on PubMed.)

Losing artemisinin?

For many months there have been reports from Cambodia of cases of malaria showing resistance to what is now the mainstay of malaria treatment – artemisinin combination therapy (ACT) – see for example a Science paper featured on TropIKA.net last year. There was confirmation of this disturbing finding in a conference presentation in November (see TropIKA.net blog) and in a paper in the New England Journal of Medicine in December. Now, in TropIKA.net News, we publish details of the launch of a programme seeking to contain the spread of artemisinin resistance. It must be hoped that these efforts will achieve some success. The loss of this drug would be calamitous for malaria control globally. Since it was first established that artemisinin offered an effective replacement for the older malaria treatments to which the malaria parasite had become resistant, massive investments have been made with the aim of making ACT drugs accessible to those who need them. While these efforts still face many challenges, some resulting from insufficient supplies of artemisinin, there has been encouraging progress. Steps towards the production of a synthetic version of artemisinin (see TropIKA.net blog) have added to the sense of optimism as to what can be achieved. However, should artemisinin resistance now spread rapidly from Southeast Asia to Africa and other malaria-endemic areas, then these investments may turn out to have been wasted. The sale of substandard ACTs containing inadequate levels of the active drug and the use of artemisinin as a monotherapy both promote the development of resistance. It is essential that these practices should be halted. And the good news Not all of the new developments featured on TropIKA.net recently have been so bleak. Two new moves are likely to boost research into the infectious diseases of poverty. See: - African initiative launched to strengthen health research - India plans to boost investment in research for drugs for the infectious diseases of poverty. Some national programmes aiming to eliminate infectious diseases of poverty are achieving success: - Lymphatic filariasis eliminated from province in the Philippines Elsewhere existing control efforts are being reinvigorated: - Kenya plans to eliminate trachoma - Nigeria tries again on polio And, somewhat belatedly, the Australian government is getting to grips with a major cause of blindness in its indigenous people: - Trachoma: Australia’s government at last promises to take action Paul Chinnock Editor-in-Chief, TropIKA.net

Malaria: a breakthrough in artemisinin production?

The recommended treatment for malaria is artemisinin-combination therapy but the treatment is in short supply. One problem is that supplies of plant-derived artemisinin are subject to the seasonality and volatility common to many plant-based commodities, leading to fluctuations in the price of artemisinin. If artemisinin could be produced synthetically on a large scale and at an affordable price, it would be a major step forward in the battle against malaria. A study just published in PloS ONE reports the production of amorphadiene, a precursor of the antimalarial agent artemisinin. Amorphadiene has been produced previously but only in very small quantities. Researchers at Amyris Biotechnologies have used fermentation techniques in a step forward towards a more efficient process. There is still some way to go but non-plant-derived artemisinin could be on the way.

Malaria: contrasting experiences

An article published on allafrica.com compares the recent experiences of Zanzibar and Uganda with regard to the control of malaria. Zanzibar has received international praise for its reduction in malaria case numbers and it is progressing towards elimination of the disease as a public health problem. Uganda, however, is struggling. According to outgoing State Minister for Primary Healthcare, Dr Emmanuel Otaala, there are over 400 new cases every day and at least 30% of them, mostly children, are likely to die from the disease. A range of problems, including disagreements between the Ugandan government and donor agencies, have led to a shortage of the recommended treatment drug, Coartem. The National Medical Stores ran out of the drug four months ago and it is estimated that new supplies are at least five months away. Meanwhile vector control efforts are also in disarray as - following a High Court injunction by politician, John Ken Lukyamuzi, who apparently believes that the use of DDT is more harmful to health than death from malaria - the government has been forced to halt indoor residual spraying. The article may be read here.

The woman with the leg

Sometimes one can read a great number of research articles on infectious diseases and come away with just a single case uppermost in one’s in mind. In our look at recent research articles on lymphatic filariasis, one paper we featured was a qualitative study on the impact of social stigma on women with this disease in two countries, the Dominican Republic and Ghana. My thoughts keep returning to the comment, recorded by the researchers, of a woman in Ghana: “If it had not been for my nasty leg, I could have gone to school and been a teacher. I would have been someone, not just the woman with the leg.” The tragedy of a person whom society defines by the parasitic condition from which she suffers and the waste of her capabilities clearly sets out, in just two sentences, why such diseases can no longer be neglected. It also demonstrates one of the advantages of qualitative data – a single human story is often more moving, more memorable, and more effective as an advocacy tool than any qualitative statistic. The considerable impact of stigma revealed in this study adds to the case for more social research on the infectious diseases of poverty. A recent review article considers the current status of such research. Elsewhere on TropIKA.net there have been a number of good news stories lately: • a small study has examined a new way of addressing the life-threatening complication of hypoglycaemia in children with malaria • a reduction in trachoma case numbers has been reported from Nepal • a new initiative will facilitate the conduct of high-quality clinical trials in Africa. And there have been curious stories too: • the introduction of a new malaria drug is seen as a threat to local industry TropIKA.net is of course an interactive knowledge platform. Please use our Comment function or the blog to give your own views on any of these developments. Paul Chinnock Editor-in-Chief, TropIKA.net

Outpatient diagnosis: new manual published by AMREF

The African Medical and Research Foundation (AMREF) is an unusual organization in several respects. It is, to begin with, rare to find an international NGO focusing on health that has its headquarters in Africa; AMREF's HQ is in Kenya where the agency began 50 years ago. Today, AMREF implements its projects through country programmes in Kenya, Ethiopia, Uganda, Tanzania, Southern Sudan and South Africa. Training and consulting support are provided to an additional 30 African countries. It is also unexpected that an organization which says its strategy is to, "seek to strengthen health systems and to design and enhance interventions that improve people’s access to health through their active participation" should also have a publishing arm. AMREF has an extensive range of books and other training materials. The most recent addition to the list is titled Clinicians' Guide to Quality Outpatient Diagnosis. Written by Dr Jane Carter of AMREF Clinical Laboratories, the book is written for clinicians working in outpatient curative clinics in primary level hospitals and health centers in sub-Saharan Africa, as a guide to improving their diagnostic skills. The manual is divided into four chapters covering quality outpatient diagnostic services; clinical examination and use of laboratory and other investigations; an approach to commonly presenting conditions in outpatient practice; and an approach to disease outbreaks. AMREF says the book has been tested with a wide range of users and suggested changes have been incorporated into the manual. Details of the new book and of other publications from AMREF may be found here.

Study finds rapid malaria tests compare badly with presumptive diagnosis

TropIKA.net recently reported on the debate as to whether, now that rapid diagnostic tests for malaria have been developed, it is time to change the present recommendation that African children with fever should be treated 'presumptively' as having malaria. There are strong views on the subject, both in favour of change and opposing it. (See also the TropIKA.net blog.) A new cost-effectiveness study (1), involving 300 patients with malaria in Mali, seems to provide evidence in favour of the current recommendations. The authors of the study conclude from their findings that: "For children aged 0-5 years in a high-transmission area of sub-Saharan Africa, use of the RDT was not cost-effective compared with the presumptive treatment of malaria with an ACT. In older patients, use of the RDT did not reduce costs." Wisely, they add that: "The question remains whether either of the strategies investigated can be made affordable for the affected population." Respond to this blog to give your views as to whether the era of presumptive malaria diagnosis should now be over. Reference 1. Willcox ML, Sanogo F, Graz B, Forster M, Dakouo F, Sidibe O, Falquet, J, Giani S, Diakite C, Diallo D (2009). Rapid diagnostic tests for the home-based management of malaria, in a high-transmission area. Ann Trop Med Parasitol; 103(1):3-16.

New malaria drug "a threat to local industry"

The Ugandan New Vision online newspaper says that the arrival of a new malarial drug in the country has been met with "mixed feelings", as it is considered to be a threat to local industry. The drug in question, Coartem Dispersible, provides artemisinin combination therapy (ACT) in a form suitable for children. ACT is now recommended to be the core of malaria treatment efforts, older drugs no longer being effective. Coartem Dispersible has been developed by the Medicines for Malaria Venture (MMV), a non-profit organisation and Novartis, a multinational pharmaceutical company. Under the MMV/Novartis partnership, the medicine will be sold in Uganda at the equivalent of $0.37 per treatment. “This is the first paediatric malaria cure that is dispersible, sweet and has stringent regulatory approval,” the partnership has announced. Most of the antimalarials on sale in Africa continue to be of poor quality - both the older types of drugs and those which are ACTs, or claim to be. Quality ACTs are usually priced beyond the reach of most people who need them. See the following news stories and blogs on TropIKA.net: 1 ; 2 ; 3 ; 4 . Surely then the arrival of an effective drug for children with malaria at a more affordable price should be welcomed unequivocally? New Vision, a publication which gives a high level of attention to health care issues, does not develop the notion that Uganda's drug industry is threatened, nor does it publish any quotes from people who believe this to be the case. However, hostility towards the appearance of Coartem Dispersible in Uganda may be widespread in the country. It would be interesting to hear from anyone who knows more about this. Please respond to this blog if you have any knowledge about the situation. There is of course no doubt that it would be desirable for a country like Uganda to manufacture the drugs it needs for common and serious conditions like malaria. However, in the short-term, the priority is to improve the access to effective treatment for the nation's vulnerable children. The New Vision article may be read here.

Should the Global Fund and other malaria donor agencies pay for deworming?

The question is posed in a blog by Karen Grepin which is well worth reading.

Indonesia's parliament hears that nearly half the population is at risk of malaria

The parliament of the world's fourth most populous country, Indonesia, has been considering the extent of its malaria problem. Health minister Siti Fadilah Supari said 45% of the country's 243 million people lived in areas where they were at risk of infection. The minister told parliament that malaria was endemic in 424 of Indonesia’s 495 districts and cities. She said that Jakarta, the capital, and Bali, a major tourist destination, were considered malaria free. The provinces of Moluccan Islands, Papua, North Sumatra and East Nusa Tenggara have the highest prevalence. In such areas there are over five cases per 1,000 population in an average year. See report on Bloomberg.com.

The AAAS, climate change and malaria

The potential impact of global climate change on malaria continues to receive attention at this year's meeting of the American Association for the Advancement of Science. TropIKA.net has already reported on the contribution to the debate made by entomologist Matthew Thomas - see our News section. The journal Scientific American has now published the comments of ecologist Mercedes Pascual who wisely says that it would be misguided to see the spread of the disease into previously malaria-free highland areas of Africa as being either the result of climate change or of drug resistance. Both factors are likely to involved. And that surely is the issue. It would be absurd to take the view that the spread of malaria is all down to climate change and that the health sector is consequently powerless to hold back the advance of the disease. However, to deny the impact of climate change would be equally irresponsible. The epidemiology of malaria has always been complex and it is becoming more so.

Asia Pacific Malaria Elimination Network

We reported briefly on the launch of the Asia Pacific Malaria Elimination Network in Brisbane, Australia - see TropIKA.net News. The Network is an organisation with, as yet, no website or contact details but it is clearly an initiative of some importance and we will keep our readers up to date with developments as we learn of them. The Australian Broadcasting Corporation's website features an interview, focusing on the Network, with Professor Sir Richard Feachem who is its first Chair. Please use the contact features on TropIKA.net if you have information on the development of this project.

No downturn here

Action against malaria and tuberculosis is now highly dependent on support from the Global Fund, so it is disturbing to learn that it is facing a shortfall: see TropIKA.net News. The Fund has stressed that the current problem is not related to the present economic ‘downturn’. However, many are worried that the downturn will lead to financial cutbacks in key areas. There has, however, been no downturn in the activities of TropIKA.net. We have lately added several items of particular interest. It’s good to have news stories on two diseases that seldom receive adequate attention. See: Leishmaniasis conference hears that patients lack adequate diagnosis and drugs Typhoid still a major public health problem Unusually, our latest Profile is an interview with two researchers who work in industry. Their team is achieving encouraging results in the search for a new treatment for tuberculosis: TropIKA.net interviews Larry Geiter and Charles Wells of Otsuka Pharmaceuticals We aim to highlight the current key debates, and to add to the discussion. See our article describing a debate in the journal PLoS Medicine: Time To Move from Presumptive Malaria Treatment to Laboratory-Confirmed Diagnosis and Treatment in African Children with Fever We continue to seek out research articles of particular interest and also review articles. Malaria has been the focus of many recent reviews and a new TropIKA.net article is devoted to a discussion of many of these: Malaria: a time to take stock? Paul Chinnock Editor-in-Chief, TropIKA.net

Fever in the African child: is it wise to presume that it is malaria?

A recent debate article in PLoS Medicine, summarised here on TropIKA.net, presents the arguments for and against a change in the current policy that a child with fever in Africa should be given malaria treatment. The present approach has been justified because: 1) malaria has been by far the most common cause of fever, and 2) obtaining a diagnosis takes too long. But in recent years, malaria has become responsible for a lower proportion of fevers than previously, and rapid diagnostic tests (RDTs) have become available. The PLoS Medicine authors who call for a new policy, under which a child with fever would be positively diagnosed by RDT before getting malaria treatment, note that careful planing would be needed before such a change is attempted. The authors who oppose a new policy do so largely because they feel that Africa's health services are not yet in a position to cope with all that would be required. As they note, African health systems are not performing well in the task of delivery drugs to patients; a new commodity like RDTs would present greater changes. Clearly it is desirable to treat children for infections that they have and not for infections that they might have. The difference between the two sides in this debate would seem to be mainly an issue of timing. It is a question of whether (after a short time for 'planning') we can move to what would undoubtedly be a more rational approach, or whether some years must first be allowed for health systems themselves to be improved before such a change becomes practical. I must express my own scepticism about a policy change at this stage. My scepticism is born of having seen in practice too many burdens (and too many bright new ideas!) thrust open a health service which was still struggling to cope with its existing responsibilities. The planning called for by one side of the debate would be a formidable task and would have to involve a number of pilot programmes involving the use of RDTs. However, there are always issues with Africa-wide policies. Too often the African continent is treated as if all its countries had exactly the same problems - the same disease burdens, the same resource levels, the same standards of health care provision. It must be up to the policy makers within individual countries to decide whether they wish to adopt (after a planning phase of course) the change in the approach to the treatment of the febrile child which has been advocated.

Mali's Malaria Research and Training Center

One of the features of our knowledge platform is Tell TropIKA.net, where we invite readers to share information about the projects they are working on. The aim is to facilitate networking within the 'community' of people who are actively involved in fight against the infectious diseases of poverty. Dr Zoumana Isaac Traore used Tell TropIKA.net to send us information about the Malaria Research and Training Center (MRTC), in Mali. His comments follow below. "MRCT was set up in 1989 as part of a collaborative effort between the staff of the Faculty of Medicine, Pharmacy and Odonto-Stomatology and the National Institutes of Health in the United States (NIH), the Rockefeller Foundation and the World Health Organization. Significant support was subsequently obtained from a number of United States Agency for International Development (USAID) programmes, as well as from other charitable institutions. The MRTC now forms a unitary organization, in which the work is planned, directed and executed by Malian staff. The MRTC is involved in all aspects of research on malaria. All the work at the MRTC is aimed at developing and testing appropriate strategies for the eventual control of malaria and the reduction of the burden of disease in the people of Mali, the region, and Africa as a whole. The centre is directed by Dr. Ogobara Doumbo, as is the vaccine testing programme that the MRTC carries out together with the Malaria Vaccine Development Unit of the NIH Laboratory of Parasitic Diseases. Likewise, the MRTC leads the way in technologies which can detect the presence of resistant parasites from a single drop of blood collected and dried on filter paper, thus allowing malaria's resistance to certain drugs to be combated." MRTC has a website. We are grateful to Dr Traore for telling us about the work of his organization. Please use Tell TropIKA.net to let other peole know about your own project.

Cambodia reports reduced malaria case load

The number of reported malaria cases and deaths in Cambodia respectively are said to have dropped by 8.5 percent and 25 percent in 2008 over the previous year. See report in China View. Some half million Cambodians live in forested regions where malaria transmission is intense. The number of confirmed malaria cases decreased to 59,840 in 2008 from 54,784 in 2007, and deaths to 184 from 241. The fall is attributed to the use of insecticide-treated mosquito nets and to improved treatment. Nevertheless, it has been reported elsewhere that resistance to the main treatment drug (artemisinin) is starting to be seen in Cambodia - see TropIKA.net blog. Cambodia, in contrast to other countries in the region, has also recently reported a fall in the number of cases of dengue fever - see TropIKA.net news story. they said they had less dengue too??

"The only drug that matters is the drug that is swallowed": the challenge of getting a new malaria drug to the children who need it

Coartem Dispersible is a new cherry-flavoured antimalarial tablet that should overcome one problem with malaria pills - children find them difficult to swallow. There have been encouraging results with the use of this new treatment - see TropIKA.net news story. However, an article in the Wall Street Journal describes the problem of getting the drug to the children who need it. The article notes that "Efficient channels to distribute the products are rare, giving rise to what health workers call "pile-up" of drugs trying to reach villages and health clinics." The cost of the drug poses another barrier. As Daniel Vasella, Chief Executive of manufacturers Novartis, observes: "In the end the only drug that matters is the drug that is swallowed".

Malaria test on a card

Tests for diseases should ideally be fast and easy to use. For example, health-care workers in developing countries might have just one visit to diagnose and treat a patient. Research for improved diagnostic tests is therefore of key importance. A malaria test on a disposable card small enough to fit into a wallet, with its chemical contents dehydrated so they last for months without refrigeration has been developed by a team at the University of Washington, according to a report in the Seattle Times. The 'DxBox' includes a portable, fully automatic reader to process the card-based disposable tests. The work has been made possible by funding from the Bill and Melinda Gates Foundation's Grand Challenges in Global Health Initiative.

A Collaborative Solution for Tropical Diseases: The LusoAmerican Response - July 8-10 2009 Lisbon, Portugal

The second of a series of three research conferences on infectious diseases conducted as a collaboration between the LusoAmerican Development Foundation (FLAD) in Lisbon, Portugal and the US National Institute of Allergy and Infectious Diseases (NIAID) will take place 8-10th July, 2009, in Lisbon. Unlike the first meeting, which focused on the treatment, diagnosis and prevention of tuberculosis in Africa, this meeting is dedicated to scientific collaborations and searching for collaborative solutions. The call for abstracts has just been opened and includes a variety of topics such as malaria drugs, diagnostics, vaccines, malaria epidemiology, vector/parasite biology, insecticides and resistance, as well as the role of research networks, PPPs, and development. You can submit your information via email to Kathleen Collins (ollinska@niaid.nih.gov) or Rui Vallera (rui.vallera@flad.pt). The meeting is of particular interest to Lusophone African, Portuguese and Brazilian researchers, as well as American researchers working on malaria projects. Additional information can also be found using the following links: www.fladtropicaldiseases.com www.niaid.nih.gov/news/events/meetings/LusoAmerican/default.htm

'Street drugs' used to treat malaria

A report from Brazzaville, Congo describes how the treatment people seek first when they or their families have suspected malaria is medicines from unlicensed drug sellers. These drugs are based on chloroquine, which is no longer recommended for malaria treatment. These 'street drugs' are in any case likely to be poor-quality, faked products. It is estimated that only around 40% of malaria cases in Brazzaville are treated with the recommended artemisinin-combination therapy (ACT). The government decided in 2007 to provide ACT to pregnant women and children under-five free of charge but the report says, "...the effects of this on public health have yet to be seen." The report is published by IRIN, the news service of the UN Office for the Coordination of Humanitarian Affairs, which has also recently reported on the problem of fake drugs in Tanzania.

New malaria centre for Togo

A report on the China View website says that a new centre for the prevention and treatment of malaria has been opened in the Togolese capital, Lomé, with support from the Chinese government. Togolese Health Minister Komlan Mally and the Chinese Ambassador to Togo Yang Min attended the opening ceremony of the China-Togo Center of Prevention and Treatment of Malaria. Ambassador Yang said the construction of the centre was part of measures announced by the Chinese government at the Beijing Summit of the Forum on China-Africa Cooperation in November 2006.

New plant-sourced malaria treatment in prospect?

The mainstay of malaria treatment is now artemisinin-combination therapy. Artemisinin is derived from the plant Artemisia annua, also known by other names including sweet wormwood and qīnghāo. It was discovered by Chinese scientists. Now, Indian scientists claim to have identified another plant - 'gommostama' - with antimalarial properties. Ambitiously, they say that they will have a new drug based on the plant ready for the market within two years. The work is taking place at the Gwalior and Tezpur laboratories of the Defence Research and Development Organisation (DRDO). DRDO chief controller in R&D in life sciences, W Selvamurthy speaking at the 96th Indian Science Congress said: "We have found the extracts from gommostama effective in developing a drug for malaria. Our experiments on animals are encouraging. We will soon experiment on human beings. The drug is expected to be in the market within two years." Dr Selvamurthy's announcement has received widespread media coverage - for example see the report in India's Financial Express. However, no further details have been made available. The identity of 'gommostama' is not clear. Without more information - and given that it would be unrealistic to have a drug on the market within two years - it is necessary to view the claims with some scepticism. Nevertheless, with the story of artemisinin in mind, it seems quite possible that other plant-sourced antimalarials could one day be developed. DRDO's efforts will be followed with some interest.

When the best target is in the victim itself

How to fight an enemy that despite so many efforts keeps killing millions of people every year? How to develop efficient drugs and treatments against a disease that results from the works of three different species? What is the best target? According to an international network against malaria, the best targets are ourselves, humans, the victims. Established in 2005 with funds from the Bill & Melinda Gates Foundation (through the Foundation for the National Institutes of Health) and from the Wellcome Trust, MalariaGen is an international network of scientists that believe that the best strategy against Plasmodium falciparum is in the natural resistance that some individuals have against the parasite. For instance, why do some children get malaria while others don’t and why, among those infected, do only some develop severe malaria? In an attempt to find an answer for these million-dollar questions, the group wants to investigate the genetic basis of resistance to malaria using genome wide associations analysis (GWA) by searching the genome of millions of individuals. In analysis of this kind, thousands of individuals are genotyped at strategic positions known as single nucleotide polymorphisms (SNPs) as a way to find associations between specific spots in the genome and malaria resistance. When these spots are found researchers zoom in at those locations and look for genes that can be accounted for the resistance. But the technical aspects of the research may be the easiest one of the initiative, as described in a commentary written by MalariaGen’s members and published recently in Nature. When working with humans, and in such a large scale, numerous issues need to be addressed. Some of them, to mention a few, are on how to collect enough blood from sick patients living in Africa and under poor conditions, the need of creating standard practices, creation of rules on data sharing, ownership and intellectual propriety and lastly the ethical issues. Also important is how to work together in a network that includes members from many different countries and who do research under different standards and conditions? All these issues may raise a river of complexity that needs to be addressed so another and much more complex issue can be dealt with effectively: the parasite.

Bednets: do they get too much credit for reducing malaria?

An interesting feature article in Uganda's Daily Monitor cautions that the recent declines in the incidence of malaria, reported in several locations, cannot be entirely attributed to the distribution of insecticide-treated bednets. Thomas Omondi of the NGO Malaria Control Network says in some areas where the decline in malaria cases has been recorded, the use of nets is either low or inappropriate. He says, "There must be other factors contributing to the decline of malaria cases, which even us researchers may not be aware of.” “It would be extremely dangerous to focus so much on the nets since new drugs are also proving to be more potent and long-lasting in tackling the parasite,” says Dr Salim Abdullah, the Director of Bagamoyo Research and Training Unit (BRTU) in Tanzania. He attributes the declining cases of malaria in several locations across East Africa to a multiplicity of factors. These include improvements in treatment and in mosquito control.

Going to Africa? Don't forget to take your pills!

A study recently published in the Irish Medical Journal investigates the reasons for an increase in malaria cases in Ireland in recent years. While malaria incidence between 1988 and 1998 was 14 cases per year on average, in 2006 alone there were 91 cases of malaria. If no malaria mosquitoes have been found flying around in Ireland, how can this increase in malaria incidence be explained? The reason, the study points out, is travelling. However, for malaria to become a problem in Ireland, and in other countries for that matter, the mosquitoes do not need to bother flying continental distances. They can simply wait in their local and endemic regions for the unwary or uninformed traveller who goes to Africa to see friends and family, according to the study. Between July 2005 and April 2006, five children were diagnosed with malaria caused by Plasmodium falciparum in the Our Lady of Lourdes Hospital Drogheda, in Ireland. Of these five, four were born in Ireland while the fifth was born in Nigeria. They all lived in Ireland but went to Africa in the previous months to the diagnosis to visit friends and family. What the study shows is that travellers to Africa have failed to take appropriate prophylaxis for the correct period of time as a way to be protected against malaria. In this study, none of the children received adequate prophylaxis. The five children were treated with quanine and clindamycin and were able to leave the hospital. The final message is clear: “Families who intend travelling to endemic areas need to be aware of the potential risks if adequate prophylaxis is not taken or if compliance is inadequate.” For more information, the full study, Out of Africa: Traveller Malaria in Paediatric Patients Presenting to Our Lady of Lourdes Hospital Drogheda, is freely available.

Kenyan newspaper calls for action against fake drug cartels

One of the greatest barriers to improving the effectiveness of malaria control efforts is the growing prevalence of fake antimalarial drugs. In an outspoken Editorial, Kenya's Daily Nation newpaper says: "It is becoming quite clear that the Government knows the identities of those who have been compromising the national fight against malaria." The editorial continues: "According to a report prepared by the Ministry of Health, most of the medicines to treat malaria in the local market are either substandard, or they are not recommended, or even registered. The report blames local companies for importing the drugs from India." And it asks: "Who is protecting these killers and why?" It calls for urgent government action against the criminals. Antimalarials are of course not the only drugs being faked. The problem is now well recognised internationally and, as the Nation says, it is important for national governments to come down hard on offenders operating in their countries.

More support still needed ...but also more realism

Before I begin my latest personal selection of some of the new items featured on the TropIKA.net knowledge platform, may I wish all of our regular readers a very happy New Year. I hope that your own endeavours in the battle against the infectious diseases of poverty will bear fruit this year. It is heartening to learn that new initiatives continue to be launched to provide funding both for research and for control efforts. However, it is clear that much more financial support is still needed. A US consumer group has reported on government expenditure on neglected infections and says it is not enough. Also in the US, the Institute of Medicine has called upon the incoming President to make health a pillar of foreign policy and to double US funding for global health initiatives within the next four years. Of the diseases which we feature on TropIKA.net, malaria and tuberculosis attract the most funding and in consequence there is always more for us to report regarding new research findings. However, recent weeks have seen the publication of a number of studies on schistosomiasis. One that we have featured concerns the role of hygienic bathing in the transmission of the disease. (Do visit our Research Articles section to see the other studies that we have recently highlighted.) We also report that schistosomiasis control in China will benefit from the use of satellite technology and that new funding from the Gates Foundation will be used for operational research on the control of the disease. The development of effective new interventions against the infectious diseases of poverty is only part of the process. Their effective delivery is also crucial. This is well illustrated by vaccination programmes. Many programmes are still failing to reach targets and a worrying study published in the Lancet now suggests that some programmes over-report their success rates. As we go forward into the New Year it is important to maintain a positive position on what it being achieved but also that we should be realistic; our efforts should be informed by accurate data and not by over-estimates. Paul Chinnock Editor-in-Chief, TropIKA.net

Malarial parasites in tree-dwelling rats have close evolutionary relationship with P. falciparum

Scientists at the Sackler Institute for Comparative Genomics at the American Museum of Natural History say they have shown that malarial parasites in tree-dwelling rats have close evolutionary relationship with P. falciparum. The claim is based on so far unpublished data but has been reported in an online news service Huliq News. Susan Perkins, Assistant Curator of Invertebrate Zoology at the Museum is quoted as saying: "This is the first time that a relationship has been found between human and rodent malaria. In all past studies, P. falciparum seemed to not be closely related to anything else but the chimpanzee parasite. But this study places it in a sister group of parasites from rodents ... The link between human malaria and rodent malaria is exciting because, if they really are that closely related, our laboratory models might be more powerful for helping to study how to fight the disease."

Translational research for neglected diseases

Translational research can be defined as the process that leads from evidence based medicine to sustainable solutions for public health problems, with the ultimate goal of improving the health of the population. It is a novel approach to medicine and research that also takes basic and social sciences into consideration when seeking new solutions for old public health problems. As such, neglected infectious diseases are very good candidates to be approached under the view of translational research. In Brazil the first steps in this direction were taken last November in Rio de Janeiro, when a small working group that included researchers, politicians, private funding agencies and business representatives spent two days debating the requirements and applied strategies for a translational research for neglected diseases programme to be successfully established in Brazil. The first need noted by the working group is that the cycle between poverty and neglected diseases must be broken. Poverty leads to the emergence and establishment of neglected diseases but the contrary is also true, with the occurrence of neglected diseases leading villages and populations into poverty. According to the working group, this catch 22 can only be broken when neglected infectious diseases are considered as a priority by governments. This has been the goal of a new programme created in Brazil that gives special attention to seven diseases, namely Chagas' disease, dengue, leishmaniasis, leprosy, schistosomiasis, malaria and tuberculosis. The programme has received around US$10 million in the last two years (2006-2007) from the Brazilian Ministries of Health and of Science and Technology. For this and other programmes to be transformed into translational research programmes, the working group stressed the need for more and better compounds that can work as antigens to be used for the development of new medication and vaccines against these diseases. Equally important is the creation of mechanisms that facilitate the implementation of pre-clinical studies and clinical trials, and the involvement of the Brazilian agency responsible for the approval of new drugs, toxicology tests, and the importing of equipment and consumables for research. The group suggested as the next step that a list of projects be selected for receiving funding provided by partnerships between the government and private companies interested in fostering translational research for neglected diseases. More details, in Portuguese, can be found in the website of the Brazilian Ministry of Health.

Could a fungus help control malaria?

Tanzania's Ifakara Health Institute is investigating the potential of two fungi to control malarial mosquitoes, according to the Institute’s Acting Director Dr Salim Abdulla, interviewed by the country's Daily News. Dr Abdulla says that there have already been some encouraging preliminary findings and that over the next two years trials will take place at household level, village level and then on a larger scale. He commented that, “If it will become a success, it could become one of the easiest, safe and effective interventions of controlling malaria infections in the country”. Dr Abdulla named the species of fungi it is investigating as Beauveria bassiana and Metarhizium anisopliae. This is not the first time that the use of these fungi as biological insecticides has been proposed. The article (which can be accessed here) also discusses some of the Institute's other activities, including its work against schistosomiasis and sexually transmitted infections.

Malaria vaccine: approved and in use by 2012?

According to reports from this year's meeting of the American Society of Tropical Medicine and Hygiene, it has been claimed that the RTS,S malaria vaccine could be licensed by 2011 and in use by 2012. The Los Angeles Times attributes the claim to Joe Cohen, vice president for vaccines for emerging diseases at GlaxoSmithKline, who has worked on RTS,S since its inception 22 years ago. Read the LA Times story here. The vaccine is about to begin a series of phase 3 clinical trials involving 16,000 children accross Africa - see TropIKA.net news story here. However, during the ASTMH meeting two smaller completed trials were reported. In the first, conducted in Kenya and Tanzania, 894 children aged 5-17 months were inoculated either with the three-dose experimental malaria vaccine or a rabies vaccine as a control group. In the eight-month follow-up period, researchers found that children receiving RTS,S had 53% fewer diagnosed cases of malaria. In the second study, conducted in Tanzania, the vaccine was given to 340 infants along with vaccines against polio, diphtheria, tetanus, pertussis (whooping cough) and Haemophilus influenzae B, without lessening the safety or effectiveness of the vaccines. The researchers found that infants who received the malaria vaccine had 65% fewer infections, over a six-month period than those who did not. Another story in the LA Times (here) cautions that more than one vaccine will be needed to control malaria and mentions some of the other vaccines under development. If - as seems likely - the effectiveness of malaria vaccines is going to be around the 60% level (a low figure for vaccine effectiveness), then there will still remain a need for other approaches to control of the disease, including effective drugs and vector control. - To mark the ASTMH meeting, TropIKA.net has published an exclusive interview with the organisation's President, Claire Panosian Dunavan.

Biomarker announces malaria presence

Placental malaria affects thousands of African women in their first pregnancy. Although these women acquire some partial immunity throughout their lives due to overexposure to the parasite, when they get pregnant and have their first baby the parasite sees the opportunity to strike its host by teasing its immune system. A group of researchers in Canada recently found that women with placental malaria carry high levels of a protein in the blood called C5a. When this protein is activated by malaria infection, it causes a great inflammation that leads to abnormal vessel growth in the placenta. This may cause either spontaneous abortions or the death of thousands of low-weight infants. Knowing about the abnormal levels of circulating C5a biomarker may allow early detection of placental malaria, which opens up for the opportunity of treating these women before the damages caused by the disease is already irreversible.The finding was announced by Dr. Kevin Kain, Director of the Sandra A. Rotman Laboratories, at the annual meeting of the American Society of Tropical Medicine and Hygiene which took place dur7-11th December. Further details may be seen here.

Summer school in Indonesia

The central role of TropIKA.net is to allow people involved in the fight against infectious diseases of poverty to communicate and share ideas. In particular, it is good when we can share information about initiatives which might inspire others to do something similar. I was therefore very pleased to receive a message from Dr Mochamat Helmi describing the International Tropical Medicine Summer School organized annually by Faculty of Medicine Universitas Muhammadiyah Yogyakarta, Indonesia. The programme combines academic and student activities. The aim is to broaden students’ knowledge of tropical and emerging infections and to enable them to enhance their skills in physical examinations, laboratory work, diagnosis and treatment. Use is made of a modified problem based learning (PBL) system. The next summer school will be held 6th to 26th July 2009. The venue will be the Medical Faculty Universitas Muhammadiyah Yogyakarta and affiliated hospitals. The maximum quota will be 50 participants. The main topics will be: dengue haemorrhagic fever, malaria, typhoid, tuberculosis, avian influenza, helminthes. Further details can be found on the summer school's Facebook page: go to www.facebook.com and search for ITMSS. Dr Helmi also tells me that he would be very interested to hear from potential visiting lecturers for the summer school. He can be contacted on drhelmi@fk.umy.ac.id / emailhelmi@yahoo.com. We wish all those involved with the summer school every success.

Vaccine research on the front line

As described in a TropIKA.net news story here, large-scale trials of the RTS,S malaria vaccine in which 16,000 children will participate are about to begin in Africa. An excelllent report from Reuters looks at the trials from the perspective of those on the front line. The Reuters correspondent, Andrew Quinn begins with the comments of Dr Zena Mtajuka, 'an exhausted warrior on the frontlines of the fight against one of the planet's most devastating diseases' at Bagamoyo District Hospital north of Tanzania's capital Dar es Salaam. Bagamoyo is one of almost a dozen research sites where the RTS,S trials will take place. Scientists and health workers in Kilifi, Kenya were also interviewed for the report, which can be accessed here.

Malaria genome database updated

Plasmo DB, the malaria genome database, is a repository for proteomic and genomic data of several species of the malaria parasite. The database has existed for some time (around 10 years) but its latest and updated version includes new information and tools. The data now includes genomic and functional information on eight specie of Plasmodium, including P. falciparum, P. vivax, P. yoelii, P. berghei, P. chabaudi, and P. knowlesi. The data on these species consist of microarray information, gene knock-out mutants of P. falciparum and of P. berghei, and gene expression and protein transcription on the multiple stages of P. yoelii, to mention a few. Also found in Plasmo DB is the EST information, collected from over 130 libraries. Besides the raw information that is available and the possibility of retrieving information by searching for an exact gene name, ID or product, the repository allows users to perform queries such as “Find sequence similarity using BLAST”, or “Identify gene expressed at specific life-cycle stages”, or “Identify genes with specific protein attributes”. Plasmo DB is an essential tool to anyone adopting a cellular or molecular approach to studying or understanding malaria. The database is free and open to anyone and can be found at http://plasmodb.org/plasmo/

Blogger attacks US priority voucher scheme

The USA's Food and Drug Administration (FDA) recently introduced its "Tropical Disease Priority Review Voucher" law, which gives any company that develops a new drug for neglected diseases of the developing world a "priority review" voucher that can be used for any other drug brought before the agency. The intention is to stimulate the development of drugs for neglected diseases. (For details see our TropIKA.net news story here.) However, the scheme is already under attack. One of its critics is blogger Merrill Goozner of the Center for Science in the Public Interest. He describes (here) the scheme as 'ill-conceived' and uses the example of a voucher that has been obtained by Novartis on the basis of its development of the antimalarial drug Coartem. Goozner points out that Coartem is already in widespread use in the countries which actually need it and obtaining approval for its use in the US serves no useful purpose. However, the company now holds a voucher that will allow it to obtain faster registration of a new 'blockbuster' drug for a first-world medical condition. (Alternatively it is allowed to sell the voucher to another company.) The FDA registration process is lengthy and, with a priority voucher, a company can get its products on to the lucrative US market some 6-18 months sooner. There is no doubt that this scheme is well intentioned but are its critics right when they say that it will be misused? Let us know your views.

Blame the builders?

Some years ago, I worked in The Gambia and when, one rainy season, the number of mosquitoes seemed to be greater than usual the cry went up that this could be blamed on road builders currently undertaking a major project in the area. The theory was that poor practices had left numerous unfilled trenches and small ponds in which stagnant water had accumulated, facilitating mosquito breeding. I was therefore interested to read on the excellent Ghanaian news service Joy Online that a recent workshop on malaria prevention '...identified the activities of road contractors ... as a major contributory to the increasing incidence of malaria in the country'. The workshop 'Mobilising against Malaria' was attended by community health volunteers and funded by Ghana Social Marketing Foundation (GSMF) in collaboration with Family Health International (FHI). The theory that road building activities can increase the total number of mosquitoes (and the number of mosquito bites!) sounds reasonable to me but it is worth remembering that Anopheles mosquitoes which transmit malaria favour clean water for breeding. Stagnant water is favoured by nuisance biting Culicine mosquitoes, which are not malaria vectors. Stagant water near dwelling places is not to be recommended, but the attribution to road builders of the blame for increased cases of malaria is likely to be misplaced.

Trachoma and malaria: Ethiopia opts for an integrated approach

Integrated disease control programmes are increasingly being recommended. The activities required to combat one condition often complement those required for another; health personnel travelling to a remote village can undertake tasks related to more than just one disease. It is thus pleasing to read a brief report of a short integrated control campaign which has been announced in Ethiopia - see story from the Walta Information Center here. In the light of recent research in the Sudan (1-3) suggesting that trachoma may be much more common in the Horn of Africa region than previously recognised, it is also encouraging to see that it is malaria and trachoma activities that are being integrated. Reference 1. Ngondi J, Ole-Sempele F, Onsarigo A, Matende I, Baba S, et al. (2006) Prevalence and Causes of Blindness and Low Vision in Southern Sudan . PLoS Med 3(12): e477 doi:10.1371/journal.pmed.0030477 2. Ngondi J, Ole-Sempele F, Onsarigo A, Matende I, Baba S, et al. (2006) Blinding Trachoma in Postconflict Southern Sudan. PLoS Med 3(12): e478 doi:10.1371/journal.pmed.0030478 3. King JD, Ngondi J, Gatpan G, Lopidia B, Becknell S, et al. (2008) The Burden of Trachoma in Ayod County of Southern Sudan. PLoS Negl Trop Dis 2(9): e299. doi:10.1371/journal.pntd.0000299

Under attack: the Affordable Medicines Facility for Malaria (AMFm)

Uganda's Independent newspaper has published an attack on the Affordable Medicines Facility for Malaria (AMFm). AMFm is an initiative to increase access to effective malaria treatment for people in endemic countries, by making artemisin combination therapies (ACTs) available at a much lower price. The article (which can be read online here) argues that the initiative is expensive and there is no evidence that it will cut infant mortality and general sickness or that it will be cost-effective or maintain quality control. The author is Roger Bate who is a Resident Fellow of a right-wing think-tank known as the American Enterprise Institute, which says its purposes are 'to defend the principles and improve the institutions of American freedom and democratic capitalism - limited government, private enterprise, individual liberty and responsibility, vigilant and effective defense and foreign policies, political accountability, and open debate.' Bate is particularly concerned by AMFm's emphasis on locally produced drugs, which he argues are often of very low quality. He also points out that, '...in rural Africa, the availability of prevention and treatment is poor, regardless of price. Public dispensaries are rare and most people get their medicines from private shops and travelling traders. The AMFm would provide subsidised medicines through wholesalers to this rural private market, reaching far more people than any scheme working just with the public sector. Yet rural markets in Africa are not sufficiently understood.' Roger Bate says that the $2bn which AMFm will cost over the next five years '...could probably save many more lives in existing preventative efforts such as indoor insecticide spraying or treated mosquito nets.' There are many who will disagree with him. Getting effective treatment to those who need it is an essential part of malaria control and subsidising the cost of ACTs is surely the only way this can be done. If proper safeguards are put in place, then the quality of locally produced drugs can hopefully be assured. Do you share the views expressed in this article? Let us know by responding to this blog.

Good news on malaria ...from Canada

Malaria does now appear in the popular media more frequently. However, this tends to involve brief mentions within news items. A well-written, feature-length article on the subject in a major newspaper in a developed country is still something of a rarity. A recent article in Canada's Globe and Mail, which focuses on the encouraging reduction in malaria cases in Kenya, is therefore well worth a look. Have you seen any similar articles? Share them with TropIKA.net readers by responding to this blog.

'Solving the malaria epidemic'

The American Association for the Advancement of Science (AAAS) has held a series of forums in Washington on they have called "global challenges". One forum focused on 'Solving the malaria epidemic'. A report on the Voice of America website sums up the meeting. Of note is the finding that a search of three major US newspapers over a period of three months found 120 mentions of the word 'malaria'. Something that would have been unthinkable a few years ago. This, and indeed the AAAS Forum itself, does show an increased US awareness of the disease and this is most encouraging. It would of course be interesting to know how many times those newspapers mentioned words like 'leishmaniasis' or 'Chagas disease'! The neglected diseases, with their massive combined morbidity and mortality, are surely also worthy of a Forum.

Artemisinin: is resistance appearing in Cambodia?

There have been sporadic reports from Southeast Asia suggesting that malarial parasites are developing resistance to what is now the mainstay of treatment for the disease - the drug artemisinin. These reports appear to be supported by new data from Cambodia (1), presented at a joint meeting of the Infectious Diseases Society of America and the American Society of Microbiologists. An account of the presentation may be found on the Science News website. Dr Arjen Dondorp of Mahidol University in Bangkok and colleagues tested 40 malaria patients in western Cambodia and 40 others being treated in nearby Thailand. Patients in Cambodia took more than 80 hours on average to clear the parasite from their bodies after receiving a standard combination therapy that included an artemisinin. In Thailand, clearance took only 48 to 60 hours after a similar treatment. There were more cases of treatment failure in the Cambodian group. Conditions in Cambodia would seem to favour the appearance of drug resistance. It is reported that, despite the WHO recommendation that artemisinin should only be used in combination with other drugs, in most Cambodian cases it is used as monotherapy. Many patients do not complete treatment and about half of the artemisinin pills in circulation are fakes, typically containing only 10% of the recommended dose. The movement of migratory workers in the area also makes it possible for strains of the parasite to mix, which is believed to allow gene recombination leading to mutations which might include new drug-resistant strains. The Science News article quotes Philip Rosenthal, an infectious disease physician at the University of California, San Francisco as saying: 'If we lose the artemisinins, that would be a major problem. The pipeline for new antimalarial drugs … is very limited now. We’re dependent on artemisinins to be the backbone of therapy for years to come.' More data is required but, should these findings be confirmed, then there is a catastrophe in the making. Experience has shown that Southeast Asia is generally the place where resistance to antimalarials first appears but resistant strains then make their way to the parts of the world where malaria is most prevalent - notably Africa. At a time when we are at last seeing some success stories on malaria control in Africa, in which improved treatment with artemisinin combination therapies seems to have played a key role, the news from Cambodia is extremely worrying. Reference 1. Dondorp A (2008). Resistance to artemisinin-based malaria treatment regimens: Does it exist?Joint meeting of the Infectious Diseases Society of America and the American Society of Microbiologists, Washington DC, 27 Oct. 27, 2008. Abstract # 3643

How does DEET work and what is that mosquitoes do (or don't) smell?

The insect repellent DEET is effective against a variety of disease vectors. It is particularly valued for its action against mosquitoes and it is estimated that some 200 million people across the world now use products containing DEET to protect them against the discomfort of mosquito bites and against diseases (most notably malaria and dengue fever) transmitted by various mosquito species. Nevertheless, exactly how DEET works remains unclear, despite a number of studies seeking to address this question. A study earlier this year (1), which was also the subject of a TropIKA.net blog, provided support for the notion that mosquitoes do not actually 'smell' DEET but instead it masks the odour of lactic acid in human sweat, effectively making humans 'disappear' from the insect's point of view. A new study (2) seems to contradict this. Researchers in the US performed recordings functional olfactory receptor neurons (ORNs) on the antenna and maxillary palps of Culex quinquefasciatus and found an ORN that respondedd to DEET in a dose-dependent manner. From this, and other findings in their study, they conclude that: 'Our research shows that mosquitoes smell DEET directly and avoid it.' Clearly more research is needed and it is certainly a possibility that different mosquitoes respond to DEET in different ways. It is all interesting stuff and, if better idea is obtained of how DEET works, then it could lead to the development of further insect repellents. However, the people who are most at risk of mosquito-borne infections are the very poor. They are unlikely to be able to afford regular supplies of such products for daily use. References 1. Ditzen M, Pellegrino M, Vosshall LB (2008). Insect Odorant Receptors Are Molecular Targets of the Insect Repellent DEET. Science 319 (5869), 1471. DOI: 10.1126/science.1153121. 2. Syed Z, Leal WS (2008). Mosquitoes smell and avoid the insect repellent DEET. Proc Natl Acad Sci USA; 105(36):13195-6. [Full study freely accessible here.]

Microfinance and malaria

Since it was first established that many cases of malaria, and many lives, can be saved through the use of insecticide-treated bednets (ITNs), there has been much debate as to the most effective means of achieving widespread use of the nets. One view has been that social marketing of ITNs as a commercial product is the only way forward, but evidence is accumulating that free distribution is required. On a blog by researchers at the Institute for Financial Management and Research in India, it is reported that a project is under way in which microloans for the purchase of ITNs are being given to low-income households in a malaria-infested region of Western Orissa. When the evaluation of the project is complete it will no doubt doubt add to the evidence available on this topic. Read the blog here.

Paving the steps into Chinese biomedical knowledge

Chinese medicine has been considered by many as an unveiled biomedical treasure, with abundant information and knowledge still unknown to the western world. In an interesting study done by Liu and collaborators and published in a thematic series inEmerging Themes in Epidemiology, the group of Chinese researchers use the example of schistosomiasis to show how relevant biomedical information can be accessed in two main Chinese databases, namely the China National Knowledge Infrastructure (CNKI) and VI Information (VIP). The group performed a search for articles on schistosomisais published between 1990 and 2006. For the 16-year period, the authors found 10,244 articles in CNKI and 5,975 in VIP. Most were articles published in Chinese and were not available in PubMed, although most of them have at least the abstract written in English. The study seems to be an attempt to call attention to the flood of biomedical information available in Chinese journals and databases that are still unknown to the rest of the world. In some cases, the world is made aware of Chinese medical findings when they are finally published in a top of the line journal, as was the case with artemimisin, the malaria drug. The drug was discovered by Chinese scientists in the 1970s and first published in specialized Chinese journals. It took a decade (mid-1980s) for the findings to be finally published in Science magazine. Unfortunately, it is possible that the world may never find out about some of the great discoveries in Chinese biomedical research, unless access to Chinese biomedical findings is facilitated and improved, and information is not kept in a box. The series can be found at http://www.ete-online.com/

Conferences, reports and vaccines

The 39th Union World Conference on Lung Health has been held at a time when there are many exciting developments to report on tuberculosis but the need for increased funding for research is nevertheless apparent. Another important event within the last couple of weeks has been the publication of the annual World Health Report. It appears almost exactly 30 years after the historic Alma Ata conference which led to an emphasis on primary health care (PHC). The World Health Organization says that, to address persisting health inequalities, a return to the spirit of Alma Ata is required. China has undergone many changes in recent years. The impact of these changes has been discussed in a series of articles in the Lancet. There is no doubt at all that China has much to contribute towards the global battle against the infectious disease of poverty. TropIKA.net has recently highlighted a number of studies on infectious diseases conducted within China from which there are lessons for other nations. For example, a trial has been reported which examined the safety and efficacy of combined praziquantel and artemether treatment for schistosomiasis. Another Chinese trial has shown the drug tribendimidine to be effective against hookworm, roundworm, whipworm, tapeworm and threadworm. Research that will lead to the development of new vaccines is often reported on TropIKA.net but the development of an efficacious vaccine should never be regarded as the final goal. There are many diseases which can be prevented by vaccines already available, but strategies must still be found to deliver those vaccines to those who need them. Pneumococcal disease is one of the biggest infectious killers of poor people, particularly children. There is now a vaccine and it is coming into use in richer nations. A UK parliamentary group is campaigning for the vaccine to be introduced in developing countries, and also for other action to be taken against this infection. And of course even effective vaccines can be improved. Encouraging news comes from Nigeria where a polio vaccine that only requires one dose, instead of three, has been shown to be effective. Amongst the recent research that has been the subject of commentaries on TropIKA.net, have been two important genomic studies on malaria. The completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this relatively neglected species. The genome of the simian and human malaria parasite P. knowlesi has also been published. Both studies were published by Nature which is not of course an open-access journal. However, Nature has taken the decision to make these two articles freely available. Other important studies on which we have commented include a systematic review which looked at hookworm-related anaemia during pregnancy. Based on their findings, the reviewers call for improved deworming programmes for pregnant women. And there is good news from Peru, where a study found that extensively drug-resistant tuberculosis could be successfully managed in out-patients. (The patients in the study were not HIV infected.) Paul Chinnock Editor-in-Chief, TropIKA.net

The plant that cures malaria

We have already reported on the BBC's 'Survival' series on tropical diseases. See our report here. A new addition to the series - 'The plant that cures malaria' - focuses on the use of artemisin combination therapies (ACTs) in Africa. Efforts are being made to grow the medicinal herb Artemisia annua in Africa itself. The film looks at the experience of a pioneer in this field - a Ugandan farmer Clovis Kabaseke who has been selling his artemisia crop to a company that supplies Novartis. The drug giant will use it in the manufacture of its ACT Coartem. As well as helping assure an adequate supply of artemisin for use in Africa, such initiatives can be a valuable source of income for small farmers. Clovis Kabaseke points out that artemisia is a very easy crop to grow. The work of community medicine distributors also features in this film. When the infectious diseases of poverty receive attention from the media, it usually involves a very cursory treatment. This series of programmes is up-to-date and detailed, as well as being accessible to those with no previous knowledge.

Pharmacists' knowledge of malaria treatment guidelines

A recent study, published in the East African Journal of Public Health, found poor knowledge of malaria treatment guidelines among drug dispensers in private pharmacies in Tanzania. Private pharmacies are an important part of the health care equation in Africa and it is disturbing to learn that most drug dispensers had to rely on the radio and other news media for information on malaria treatment policy. Given this, it is not surprising that 60% of the dispensers in some 600 pharmacies were unaware of a forthcoming change from sulfadoxine pyrimethamine (SP) to artemether-lumefantrine (AL). The full text of the article may be seen here. * With thanks to Abdrahamane Anne, University of Bamako, Mali, who highlighted this study in a contribution to the HIFA2015 mailing list.

A call for integration in infectious disease control

A short article on the excellent Malaria Matters website calls for increased integration of infectious disease programmes. Bill Brieger uses as an example lymphatic filariasis (LF) and malaria, both of which are carried by mosquitoes. The distribution of bednets and of the drugs used in the control of LF can be done by the same workers, who can also make available information on disease prevention. There has been some research on such integration with encouraging results but more is needed. The article concludes: "Since the Global Fund programs have yet to focus on neglected tropical diseases, these examples of integration between malaria and lymphatic filariasis, may be the best way to ensure parasite-free populations in endemic areas." Anyone who does not know of Malaria Matters should in any case take a look at this wonderful website, where it is also possible to sign up for daily or weekly articles from the prolific Bill Brieger which highlight noteworthy developments in newspapers and scientific journals that concern malaria and related topics.

Malaria and more

TropIKA.net continues to provide in-depth coverage of key meetings relating to the infectious diseases of poverty. The latest such meeting is the First Meeting of the African Network for Drugs and Diagnostics Innovation(ANDI). Malaria has been much in the news during the last couple of weeks. We have seen a three-billion dollar boost to funding for the global battle against the disease and the launch of Global Malaria Action Plan (GMAP). A five-year plan has also been announced by the Medicines for Malaria Venture. The journal Nature has expressed concerns that basic research is not receiving enough attention but, as we note, basic research is only one of many issues that must be addressed. A report from Médecins Sans Frontières sounds a salutary note; improved control programmes often fail to reach the very poorest people, unless diagnosis and treatment are free. While more funding is still needed, the attention malaria is now receiving does makes it quite clear that it can no longer be described as a neglected tropical disease (NTD). While the NTDs receive grossly inadequate attention from the international community, their profile also may be starting to rise. A series of excellent films from the BBC is focusing on these diseases and will surely raise awareness. NTDs have even emerged as an issue in the debates between the two US presidential candidates. One neglected disease in Africa, guinea worm disease, is to receive new funding and it is claimed that it could be eradicated within five years. It is too easy to think of NTDs as confined to Africa and Asia but they are important causes of sickness and death elsewhere. A recent article has highlighted the disease burden due to NTDs in Latin America and the Caribbean. An encouraging development has been the announcement of plans by the Carter Center, Haiti and the Dominican Republic to eliminate lymphatic filariaisis and malaria from the island of Hispaniola, their last reservoir in the Caribbean. There have been other developments which have caught my eye in the last few days. Diarrhoeal disease is still one of the biggest infectious killers of poor children; rotavirus is often the disease agent responsible. Many countries are considering whether they can afford to introduce rotavirus vaccine to their national programmes. A study from Mexico, which found that such a move would be cost-effective, is of great interest. The use of ivermectin in the control of onchocerciasis is now well established but a study in Ecuador has shown there can be beneficial side effects; the drug is also active against some soil-transmitted helminths. Paul Chinnock Editor-in-Chief, TropIKA.net

Innovations and lessons from history

Examples of the innovative use of new technology to help to control the infectious diseases of poverty are often featured on TropIKA.net. The mobile phone is a piece of new technology that has been adopted enthusiastically across the developing world and the ready availability of these now ubiquitous devices has been put to good use by a team of software developers. An application which can be downloaded to mobiles has been used within a successful campaign to bring under control Kenya’s first polio outbreak for 21 years. See Mobile phone technology helps contain disease outbreak. Of the diseases on the TropIKA.net priority list, it is tuberculosis that has been most in the headlines over the last few weeks. We have summed up some of the most important developments in our article, Tuberculosis profile rising. Malaria also receives more attention from the international media than was previously the case. The World Malaria Report for 2008 was reported by many newspapers worldwide and (as I write this latest Editor’s Choice column) news is coming in of agreement at the UN for major new funding for malaria control. However, the excitement over new developments and innovations should not mean that the lessons of history are forgotten – see Malaria control: ‘faulty intelligence’ led to mistakes. One such lesson is that gains made in infectious disease control so easily can be lost. Having brought rabies under control for several years, China now seems to be facing a resurgence of the disease – see Renewed rabies vigilance needed in China. The increasing number of dengue fever cases is a major problem affecting a much wider area. The situation in the Asia-Pacific region and also Latin America is of increasing concern. One recent research article that has been the subject of a commentary on TropIKA.net is a systematic review examining dengue outbreak prediction and detection tools – see What does dengue disease surveillance contribute to predicting and detecting outbreaks and describing trends? As well as commenting on recently published research article, TropIKA.net highlights review articles of particular importance. Sleeping sickness and Chagas’ disease are often featured on our knowledge platform and a recent review is relevant to both of them – see Trypanosomiasis vector control in Africa and Latin America. An infectious disease that also takes a major toll but which is often forgotten and has not previously appeared on TropIKA.net is bacterial sepsis – see Strategies to Reduce Mortality from Bacterial Sepsis in Adults in Developing Countries. >blog. Responses to what our bloggers are saying are always welcome. Paul Chinnock Editor-in-Chief, TropIKA.net

Plasmodium knowlesi, the fifth agent

A recent case of monkey malaria has been reported in a Finish traveller, after coming back from Malaysia 1). The traveller, a 53-year old man, spent four weeks travelling in peninsular Malaysia. Soon after returning to Finland, he developed a fever that persisted for days, and until he was admitted to a local hospital in Finland. After examination, malaria was the suspected culprit for the symptoms the man presented. A blood smear was positive for plasmodium organisms and the specific species was believed to be P. falciparum, the most common causative agent of malaria. The patient started to take intravenous (IV) quinine dihydrochloride and oral doxycycline but his symptoms didn’t improve. He was then transferred to the Helsinki University Central Hospital. Because the blood smears were somehow unusual, doctors suspected a co-infection of P. falciparum and P. malarial. To find the right identification of the parasite, a PCR analysis was done. Blast analysis of the PCR sequence revealed the sequence to be identical to a sequence from P. knowlesi that has been found in a single individual in Malaysia and in a monkey (Maccaca mulata) in Colombia. The IV quinine was then replaced by oral quinine hydrochloride, while doxycycline was maintained. The patient had a hypoglycaemia attack during treatment and transient mild visual and hearing loss, and transient lymphopenia. He recovered after treatment was finished and had no recurrence in the 12 months follow-up period. Although rare, infection by P. knowlesi, the fifth agent known to cause malaria, is potentially dangerous and doctors and health-care personnel should be aware of this disease. It is important that tests other than microscopic visualization are performed when blood smears show atypical characteristics, so the parasite can be properly identified. Reference 1. Kantele A., Hanspeter M., Felfer I., Muller D., Jorikanta S (2008)Monkey Malaria in a European Traveler Returning from Malaysia. Emerging Infectious Diseases;14(9):1434-1436. Available from http://www.ncbi.nlm.nih.gov/pubmed/18760013

Keystone Symposia

Pathogenesis and Control of Emerging Infections and Drug-Resistant Organisms is part of the Keystone Symposia Global Health Series, which is supported by the Bill & Melinda Gates Foundation. The symposium will take place in Bangkok, Thailand from 22nd to 27th October, 2008. The meeting will focus on the cellular and molecular biology of the many processes involved in a number of infectious diseases, including malaria and tuberculosis. The main goal of this meting is to review how new discoveries in these fields (molecular and cellular biology) can be used for the development of new tools, such as diagnostic assays, new drugs or vaccines. An emphasis will be given to neglected infectious and parasitic diseases, and issues such as drug resistance. Participants in this meeting include William R Jacobs, from the Albert Einstein College of Medicine (AECOM), USA, who is going to talk about a recombinant M. smegmatis that elicits bactericidal immunity against virulent M. tuberculosis. Dr Jacobs belongs to the AECOM TB Research Group that uses basic and applied research to better understand pathogenesis and immune defence and to pursue a more effective vaccine against TB. Also in the symposia will be Dr Alexandre Alcaïs, of the University of Paris René Descartes-INSERM in France who studies infectious diseases from the perspective of our genetic variability. Dr Alcaïs also works at the Human Genetics of Infectious Diseases, a lab that works on the basis that infectious agents are necessary, but not enough, to trigger the development of a full infectious disease, and that it is our immunological and genetic background, combined with the presence of the infectious agents, that will determine how the disease will (or not) develop. Workshops on malaria, TB, the biology of infection agents, and vaccine development are also included in the programme. The complete programme for this interesting meeting can be found at http://www.keystonesymposia.org/Meetings/viewMeetings.cfm?MeetingID=995&subTab=program

Frog's venom against malaria and leishmaniasis?

A group in Brazil at the Instituto Adolfo Lutz and Instituto Butantan, two traditional research institutes in the country, have reported the isolation of two steroids from frog’s venom (Rhinella jimi) that are effective against leishmaniasis (L), Chagasi promastigotes and Trypanosoma cruzi trypomastigotes. Different secretions previously isolated from frogs have been shown to be potential sources of compounds against bacteria, human pathogenic yeasts, and parasites. The compounds recently isolated by Tempone and collaborators are two steroids that belong to the group of bufadienolides, which include cardioactive steroids isolated from animals and plants. The two molecules recently isolated and named telocinobufagin and hellebrigenin have shown to present leishmanicidal effects by inhibiting promastigote growth. As for T. cruzi, trypomastigotes have been shown to be susceptible against hellebrigenin only, but not to telocinobufagin. Rhinella jimi, popularly known in Brazil as 'sapo-cururu', is an endemic species in a region in the country that is extremely dry. It is possible that the animal uses the molecules to protect itself against bacteria and other parasitic infections. If it has worked for this animal, which has been around for millions of years, well, it may also work for us as a weapon against leishmaniasis and malaria. The next step is to perform further studies that may contribute to drug design and development of these compounds into new medicines against these diseases. The study of Tempone and collaborators has been published in the July issue of Toxicon (Toxicon 52: 13-21 -2008).

The effects of erratic spraying of DDT: new discussions

Two important news about the negative impact of DDT, have been published recently One in the web page of African Science News on 24 July 2008 and the other one in National Geographic News 12 May 2008. DDT was discovered by Paul Müller in Basel in 1940 and was used on a major scale in agriculture but also during Malaria Eradication Programme, from 1950 until the middle 1980s. The massive use in agriculture had a high negative environmental and ecological impact; in birds, for example, DDT breaks down into DDE, which can block calcium absorption and cause the birds to lay eggs with thinner shells. It was also its detected in human breast milk. This led to a global ban on DDT. However, considering all the facts, WHO has recommended use of DDT under particular conditions of malaria control in low-income countries. There was also a clear suggestion to use DDT for malaria control at minimal concentrations (< 5 mg/l), far below the concentrations used in agriculture before. Last year, the Uganda Government launched a programme to spray DDT and a pyrethroid, Lambda-Cyhalothrin, as part of the malaria control and elimination program. The Government launched indoor spraying of DDT in several malaria-prone districts in south-western and northern Uganda (1). However, the spraying of DDT had to be stopped due to petitions filed by farmers, traders and conservationists.Researchers have now reported that some poisonous chemicals that had been locked in ice for decades are now being released as a consequence of climate change melting Antarctic glaciers (2). The chemicals, including the pesticide DDT, are seeping into the polar ecosystem and finding their way into wildlife populations. The scientists made the discovery when studying the levels of pollutants in the fat and eggs of Adélie penguins (see photo). The researchers hoped to find lower levels in the ice, given that this chemical was no longer in widespread use. It is surprising that DDT has been metabolised to this extent and they want to investigate the route of DDT to reach the penguins or Antarctic. It is interesting, that this penguin species does not go out of the Antarctic. The project also includes measuring the levels of DDT in the countries currently using this insecticide for malaria control and elimination. Several aspects must be considered when DDT and other insecticides are used to reduce Anopheles spp.: (i) Successful transmission control through the indoor residual spraying may reduce natural immunity against malaria (ii) Inadequate spraying strategies of DDT, e.g. interruption of spraying, can produce enhance the development of resistance; particularly in Africa, and (iii) DDT-use in malaria control and elimination requires well tailored sustainable policies for long-term spraying combined with other options for control. References 1. Report asks Uganda govt to shelve aside DDT use. Available on http://africasciencenews.org/asns/index.php?option=com_content&task=view&id=572&Itemid=2 . Accessed on 24 July 2008 2. Antarctic Melt Releasing DDT, Tainting Penguins. Available on http://news.nationalgeographic.com/news/2008/05/080512-penguins-ddt.html. Accessed on 24 July 2008 Photography by George F. Mobley. An Adélie penguin walking on snow

Role of Intermittent Preventive Treatment : A public policy to reduce malaria

The Institute of Medicine (IOM) convened a committee to provide guidance to the Bill and Melinda Gates Foundation on a number of scientific, clinical, and programmatic issues related to Intermittent Preventive Treatment in Infants, IPTi. These included the evaluation of the efficacy data from studies in order to support continued investment in IPTi-SP as a useful tool to reduce morbidity from malaria in infants in some regions of sub-Saharan Africa. The committee met this year for three days. The committee focused on three main tasks: 1. to review clinical trial methods and data analyses used in the studies conducted by the Intermittent Preventive Treatment in Infants (IPTi) Consortium (the Consortium); 2. to formulate consensus conclusions as to the advisability of further investment in IPTi using sulfadoxine-pyrimethamine (SP), on the basis of the results of six efficacy studies conducted over the last decade; and 3. to consider drug safety (of prophylactic antimalarial drug use in infants in general and of treatment with SP in particular) and drug resistance; dosage regimens; potential collateral effects on other childhood healthcare programmes (e.g., immunization); cost-effectiveness; and programme management. The committee found substantial evidence indicating that IPTi-SP diminished (by approximately 20-30 percent) the incidence of clinical malaria in infants living in areas of high and moderate intensity of transmission. However, less robust were the cumulative data supporting an effect on hospitalization with malaria parasites, anaemia and all-cause hospitalization. Additional studies, including case control studies, were recommended to complement current information. On the other hand, the committee found that the clinical effectiveness of SP for treating acute malaria in children is not an accurate indicator of IPTi-SP effectiveness, and that IPTi-SP has measurable efficacy in the face of the moderate to high prevalence of SP resistant parasites that is common in much of sub-Saharan Africa. In IPTi-SP, the malarial parasites are exposed to selective concentrations in an immunologically naïve infant with a potential for growth and transmission of resistant parasites. However, preliminary data showed no evidence of increasing prevalence of SP resistance markers at the population level as a result of IPTi-SP. On the basis of this evidence presented, the committee concluded that a decrease in the malariaburden in infancy would be expected to ensue after programmatic implementation of IPTi-SP in areas with a high incidence of clinical malaria. The committee further concluded that continued investment in the strategy appears warranted but cautions that drug supply and logistics, monitoring and resistance, and community acceptance and reaction to IPTi-SP could arise as problems in conjunction with large-scale implementation. Particular consideration is required in Latin American or Asian endemic areas. For instance in Latin America, and given the low endemic level of most areas, IPTi resistance surveillance must be strengthened. Additionally – and considering the studies of Prof. Gabaldon in Venezuela in the middle sixties – active case detection for these areas could be an excellent option to identify clusters of asymptomatic patients with parasitaemia. Reference Institute of Medicine (2008). Assessment of the role of intermittent preventive treatment for malaria in infants: Letter report. Washington, DC: The National Academies Press. (Available at http://www.iom.edu/CMS/3783/48783/56178.aspx. Purchase required.) Photo by MV Valero, Sierra Nevada de Santa Marta, Colombia

Malaria: a matter of organization

As well as original articles, TropIKA.net highlights interesting items that have been recently published elsewhere. Development economist Jeffrey Sachs always seems to be in the news. As an economist he is often inclined to consider health care interventions in terms of whether they offer a good bargain. In a recent article in Scientific American he says that the estimated $3 billion needed annually for effective malaria control is ‘one of the world’s great bargains’. Not for the first time, he argues that treatment and preventive strategies already available can bring about huge cuts in mortality and morbidity. According to Sachs, ‘The challenge of controlling the disease in Africa by 2010 is fundamentally organizational, not technical.’

Award for International Health Cooperation on malaria control

“International relations and co-operation cannot be developed if states simply rely on supremacy and power. The new international order must not become a cloak for the naked self-interest of states but must be based on solidarity and international law”. Nelson Mandela, Oviedo, 1992 Prince of Asturias Award The Ifakara Health Research and Development Centre, Tanzania, the Malaria Research and Training Centre in Bamako, Mali, the Kintampo Health Research Centre, Ghana, and the Manhiça Health Research Centre, Mozambique are to receive the 2008 Prince of Asturias award for International Cooperation. This is in recognition of the efforts of four research groups involved for a long time in developing novel strategies for integrated malaria control. The award marks the role they played and continue to play in: (i) encouraging research, (ii) implementing new strategies of control from vaccine and drug testing to community-based interventions, (iii) contributing to improvements of health and economic conditions in the endemic region and (iv) training of scientists and health workers from the endemic areas. The award also marks how interdisciplinary and intersectoral collaboration and partnership between North and South, not only produces relevant research data, but also directly contributes to poverty alleviation through concrete public health action. This type of partnership model, combining the public and the private sectors at national and international levels, offers new approaches for reaching the Millennium Development Goals (MDGs). Health is central to the achievement of MDGs and the two essential targets – (i) reduction of poverty and (ii) combating infectious diseases – are highly interrelated. The vicious circle is well known: the impactof poverty on ill health is recognized and extensively documented as well as thatill health can also be an important cause of poverty. The big question remains: How to achieve the MDGs for 2015? One of the most important requirements is to consider the social, cultural and economic heterogeneities around the world. Governments cannot adapt strategies from other regions without tailoring them to the locally prevailing conditions. Moreover, each institution and the state must also analyze the eight MDGs within the framework of fundamental human rights. Given this fact and the well known evidence that health indicators and democracy are close interrelated, a substantial political action portfolio is also required that includes free access to the information for the whole population. References United Nations Millennium Declaration. New York: United Nations, 2000. (United Nations General Assembly Resolution 55/2. www.un.org/milleennium/declaration/ares552e.pdf (accessed 20 Jun 2008).) Haines A. and Cassels A. Can the millennium development goals be attained? BMJ 2004;329:394-397 (14 August), doi:10.1136/bmj.329.7462.394

Vivax malaria – a neglected tropical disease?

Our Research Editors continue to scan the literature for new research that seems worthy of comment. A paper chosen for such a commentary is one of a pair of articles published in PLoS Medicine, presenting new clinical data on patients with malaria caused by Plasmodium vivax. Most malaria research and control efforts are devoted to malaria due to P. falciparum. This is because P. vivax malaria, though widespread, is usually regarded as relatively ‘benign’. The two new studies add to the weight of evidence suggesting that many severe (and some fatal) malaria cases are actually caused by P. vivax. In recent years, the welcome increase in funding for malaria has led to general agreement that it should no longer be described as a neglected tropical disease. Vivax malaria seems to be a different matter; many researchers argue that we should accord it that ‘neglected’ label.

Infectious diseases of the nervous system: Pathogenesis and worldwide impact

Infectious diseases of the nervous system: Pathogenesis and worldwide impact is an international conference that will take place in Paris,10-13^th September, 2008. The conference aims to gather a group of experts in a number of infectious diseases that attack our nervous system. The two keynote lectures on the opening day will be [The brain, Africa’s finest and most vulnerable product’ given by Professor Malcolm Molyneux of the Malawi-Liverpool-Wellcome Trust Clinical Research Programme in Blantyre, Malawi and ‘Community-based care for infectious diseases in rural areas of developing world’ given by Professor Paul Farmer, who is a Professor of Medical Anthropology at the Harvard Medical School and Director of Partners in Health Clinics in Haiti and Rwanda. The scientific programme includes the following lectures: ’Trypanosoma Brucei triggers its own multi-step entry into the brain’, by Krister Kristensson at the Karolinska Institute in Stockholm, Sweden; ’Importance of microvesiculation in the immunopathology of cerebral malaria’, by Professor Georges Grau of the Institute for Biomedical Research at University of Sydney, Australia; and ’Signaling mechanisms for survival of leprosy bacteria in the peripheral nervous system’, by Anura Rambukkana at Rockefeller University in New York, USA; among others. More information about the conference, including the complete scientific programme can be found on the conference website.

Dialogue – easy to say, difficult to do!

Algiers – How researchers can interface with policy makers for the implementation of research was an issue raised time and again in different sessions during the Conference. The Regional Director for the African Region, Dr Luis Sambo, urged researchers to create a demand for evidence, and to examine how this evidence is presented to policy-makers. He commented that a significant amount of grey literature bearing significant outcomes of research was stored at research institutions, but there was a missing link between the research projects and the ministries of health and other health sectors. If some of the most important public health problems in Africa can be solved with existing knowledge, we have to ask why we don’t make significant progress. The conference has highlighted some reasons why, ranging from poor health information systems, human and institutional capacity gaps, and funding. It may be more useful to look at what has worked. The African Programme on Onchocerciasis Control (APOC) could provide some clues. Following initial research on the drug Ivermectin which proved effective in preventing Onchocerciasis, the drug was distributed to communities on a large scale. This community approach to distribute Ivermectin was unique, proving that a community-directed approach could work: 70 million people are currently covered by this drug, with the aim of reaching 100m by 2010. APOC was asked to see whether this community directed approach could be used in multi-interventions for other diseases. APOC launched a multi-country study at seven country sites, in 35 health districts, covering 2.4 million people. The most complex of the interventions was the co-treatment with malaria. The result was that anti-malarial treatment for children doubled in 24 hours, proving that - contrary to expectations - the uptake of Ivermectin was not negatively affected, because it was linked with malaria control which communities felt passionate about as it addressed their immediate need. After APOC established that this approach could be used for other interventions, countries have developed policies to scale up interventions. (This work on how public health could gain from the Onchocerciasis approach is available on the TDR website) . The key, believes TDR’s Robert Ridley, is that if the research output is owned by the policymakers, then policy development is rapid. APOC engaged policymakers from the outset, and gave feedback about research results on an ongoing basis so the decision-makers knew what was coming down the pipeline. “Engage them from the start of the process, and set agendas,” was his advice. South Africa’s Lindiwe Makubalo suggested that since many researchers do work closely with ministries and policy-makers, we should look at models and tools on how to influence ministers. “We need to share lessons on how we have been able to influence policy and being the interface as senior officials by working closely with researchers and policy-makers. We do have a voice; we need to think about how we can leverage this.” Agreed, says Dr Edwin Muguti, a specialist consultant surgeon from Zimbabwe. Usually technocrats have the answers to health problems but they are unable to effectively communicate that knowledge to help policy-makers translate it into action. We need a new breed, a “transgenic” or hybrid between pure politician and scientist, who is both technically trained and politically orientated so the gap between implementation of policy and research is narrowed. “Our policies need to be guided by research, but I suspect that half the time some politicians don’t understand what it’s all about. A transgenic person would help solve this problem.” So it seems the answers are multifaceted: we need to convince policy-makers of the importance of evidence in a way they will understand; we should scratch them where they’re itching from the start so they have a sense of ownership of the results. And possibly the best way to achieve this is for health ministries to be populated with “transgenics”. Underpinning all these pragmatic suggestions is communication. Insular scientists need to adapt to changing environments and embrace new ways of working through which their work can be appreciated, understood and implemented. The world is shifting, and the African research agenda is moving inexorably forward with political and donor commitment. Researchers can no longer afford the luxury of isolation; we have to communicate effectively. In Africa, it is a matter of life and death.

Plasmodium finger printing

If, in the near future, you happen to spot a doctor or another health practitioner working in a malaria stricken community carrying a rugged shoe box-sized apparatus and then apparently trying to read their patients’ hands, while uttering words like ‘magnetism’, ‘crystals’ and ‘red light’, please do not look for any mystical or arcane explanation. Believe me, you would probably be witnessing a strictly scientific approach to diagnosis! Researchers from Exeter and Coventry universities in the UK have teamed up to develop an interesting device intended to bring down costs while delivering faster and more reliable malaria diagnosis in poor malaria endemic areas. The underlying theory is quite ingenious and has been published in a study at in the April issue of the Biophysical Journal. As soon as they enter our red blood cells, Plasmodium parasites start feeding on the oxygen-carrying molecules of haemoglobin, excreting molecular-sized ‘stools’ called haemozoin. These tiny examples of biochemical dung, which assume the aspect of rectangular rod-like crystals with long axes pointing in random directions, carry within them atoms of iron as one of their central molecular bricks. Therefore, they are prone to be attracted to magnetic fields. Eureka! As soon as they are submitted to a magnetic field, the crystals become oriented in the same direction as the field – something similar to combing straight a formerly reluctant hair piece. But that is not all. These crystals have also another interesting property. They absorb polarised red laser light more strongly along their length than their width – a phenomenon known as optical dichroism. Making use of these two features, the scientists have designed a device which applies a directional magnetic field, combined with a laser photodetector that takes optical measurements proportional to the haemozoin concentration. This should reveal the presence of Plasmodium in a given sample. The plan is to start tests with a prototype that does not need the use of blood samples at all. Instead, the patient will only have to stick their fingertip into the device. A harmless laser beam and a magnetic field will allow the apparatus to take readings from the blood vessels beneath the fingernail. The prototype instrument is now undergoing testing at the Royal Tropical Institute (KIT), in Amsterdam. Clinical trials are planned to take place in Kenya. Can we use fingerprinting to help us apprehend that dangerous criminal Plasmodium? ‘Elementary’ – as would have said the worldwide known fictional detective from Baker Street. Reference 1. Newman DM, Heptinstall J, Matelon RJ, Savage L, Wears ML, Beddow J, Cox M, Schallig HD, Mens P (2008). A magneto-optic route towards the in-vivo diagnosis of malaria: preliminary results and pre-clinical trial data. Biophys J. 2008; Apr 4. [Epub ahead of print]Click here to read doi:10.1529/biophysj.107.128140 © 2008 by the Biophysical Society.

Alligators’ resistance to infection could lead to new drugs

The popular expression ‘crocodile tears’, meaning insincere weeping, is of course not based on biological science. The blood of another reptile has, however, recently come under the research spotlight and with interesting results. Researchers from Louisiana State University (LSU) say their work on the blood serum of alligators could lead to promising new drug development against some major human pathologic bacteria and virus species. The announcement (1) was made during the 235th American Chemical Society National Meeting (ACS), held in New Orleans, United States, 6-8th April, 2008. According to the study, alligators are born with an innate immune system; they can react against antigens with which they have not previously come into contact. Study co-author Lancia Darville, from LSU, believes that peptides (fragments of proteins) within alligator blood help the animals avoid otherwise potentially fatal infections. ‘We are in the process of separating and identifying the specific peptides in alligator blood. Once we sequence these peptides, we can obtain their chemical structure to potentially [create new] drugs’, said Darville, as reported by National Geographic. According to the researcher, such peptides are also found in the skins of frogs and toads, as well as in komodo dragons and crocodiles. The research team exposed 23 species of bacteria to the serum extracted from alligator blood and as a result all the bugs were killed. Humans typically can defeat only eight of the bacteria. Co-author Mark Merchant, a biochemist at McNeese State University in Lake Charles, Louisiana, was among the first to notice alligators’ unusual resistance to infection. Initial tests, however, have revealed that higher concentrations of the reptile’s serum are toxic to human cells. Therefore, it is still going to be a while before we can expect to find ‘croc tablets’ replacing antibiotics. Reference 1. Darville, L.N.F., K.K. Murray, and M.E. Merchant (2008). Proteonomic analysis of the American alligator (Alligator mississippiensis) serum using 2-D-gel separation and mass spectrometry (Presentation ANYL 81). American Chemical Society meeting. April 6-10. New Orleans.

Turner has faith in malaria fight

Sometimes action against infectious diseases of poverty can result in surprising new alliances. Variations on the headline ‘Media tycoon Ted Turner establishes partnership with Lutherans and Methodists to fight malaria in Africa and launches a $200 million initiative’ have appeared in the international media recently.

The founder of CNN is noted for his generous donations to humanitarian causes; his New York-based United Nations Foundation was created in 1998 with a historic $1 billion gift to help support UN activities. However, many were surprised by his decision to join forces with two Christian organizations – the United Methodist Church (UMC) and the Lutheran World Relief (LWR) – as Turner once allegedly stated that Christianity was a ‘religion for losers.’

Nevertheless, as the philanthropist told a press conference, ‘As I get older, you know, I get more, you know, more tolerant.’ Turner’s foundation has already been working with many groups, including the Methodists, on the Nothing But Nets campaign, which provides insecticide-treated bed nets in poor communities. Lutheran World Relief has been helping malaria-infected cities and villages. According to UN Foundation, the new global effort intends to educate and mobilize the UMC and LWR’s combined constituency of more than 20 million people concerned with malaria and related diseases of poverty and advance the churches’ on-the-ground health missions. It will also provide financial support to the Global Fund to Fight AIDS, Tuberculosis, and Malaria, as well as support malaria prevention and health system strengthening efforts. During the initiative’s official announcement to the United Nations General Assembly, the media entrepreneur said: ‘You’ve got to have faith to build a better world.’ Religious beliefs aside, one thing even the most atheist or agnostic is compelled to agree: protestant and other religious groups have been working overseas to fight poverty and prevent disease for more than a century. And nowadays, in order to fight pernicious infectious diseases in such a globalized world, interdisciplinary and ecumenical approaches have become almost mandatory.

Insect repellent makes humans disappear

A curious experiment recently published in Science magazine has unveiled the mechanism by which the popular DEET insect repellent works: to begin with, by not working as a repellent at all! A team of molecular neurobiologists at Rockefeller University, in New York City, has found out that, instead of repelling, DEET chemicals interfere with an insect’s olfactory capability, therefore masking the compellingly attractive body odours produced by humans. According to the study, during their target recognition flight – before choosing their victim for a juicy bloody meal – female mosquitoes usually sniff out the lactic acid in human sweat and the carbon dioxide and 1-octen-3-ol alcohol in our breath (present even among the most abstemious). It is somehow similar to when an illusionist like David Copperfield makes that huge airplane simply vanish in front of the eyes of his audience. The difference is that DEET acts through making us disappear from the insect’s ‘noses’, so to speak. Interesting as it may look, it is too early to say if these findings are going to lead to concrete developments that will protect people living in the poor areas of the world, where several insects are vectors for infectious diseases. So far, DEET-based and other repellents have been useful to tourists, explorers, soldiers and researchers, but the expense has put them beyond the reach of indigenous populations. Reference 1. Ditzen M, Pellegrino M, Vosshall LB (2008). Insect Odorant Receptors Are Molecular Targets of the Insect Repellent DEET. Science 319 (5869), 1471. DOI: 10.1126/science.1153121.

Malaria billion dollar moment

While much remains to be done, malaria is no longer generally regarded as a neglected tropical disease. In the last decade alone, the global budget for malaria control and treatment efforts has increased ten times, from $100 million to $1 billion. This amazing growth is due to important initiatives from organizations such as the Bill and Melinda Gates Foundation; the Global Fund to Fight Aids, Tuberculosis and Malaria; the World Bank; the President’s Malaria Initiative; the International Olympic Committee and even the Spanish soccer team Royal Madrid. The excitement around current malaria global funding figures is understandable. After all, this disease claims the life of one child every 30 seconds worldwide – mostly in sub-Saharan Africa. And for the first time, people are starting to feel more confident in the efforts – coordinated by the Roll Back Malaria (RBM) Partnership – to reach the global goal of cutting the number of malaria cases by half by 2010. However, some experts have sounded notes of caution. In a high-profile article in Nature (1), Dr Mark Grabowsky of the Global Fund to Fight Aids, Tuberculosis and Malaria, argued that ‘Without high-quality surveillance, the billion-dollar malaria effort is flying blind’. He estimated that, ‘It would cost about $10 million annually to get useful, monthly, surveillance data and to support regional monitoring, laboratory and surveillance networks’. Contrasting with those who claim that eradication is achievable, Dr Grabowsky prefers, to think of sustainability rather than quick wins. Grabowski and colleagues raised this same issue last year in an article published in the Journal of the American Society of Tropical Medicine and Hygiene (2), regarding the more efficient use of insecticide-treated bed nets (ITNs) to protect against the vector of malaria. In the absence of an effective vaccine, the use of ITNs remains probably the most important preventive strategy. References 1. Grabowski M (2008). The billion-dollar malaria moment. Nature 451, 1051-1052. doi:10.1038/4511051a. 2. Lengeler C, Grabowsky M, McGuire D, deSavigny D (2007). Quick Wins Versus Sustainability: Options for the Upscaling of Insecticide-Treated Nets. Am J Trop Med Hyg., 77(6_Suppl), 222-226.

TropIKA: an expanding resource

During the last month much has been added to the content of TropIKA.net. Most of it has been in the News section, where some 20 stories relevant to tropical disease have appeared. We hope soon to be publishing around 10 news stories every week. We have also had two excellent Editorial Opinion articles, which we hope will stimulate some productive controversy. The second of our series of interviews with leading figures in tropical disease research and control is about to go live in our Stakeholders section. There is also a short announcement about our plans to commission specially written articles for the Reviews section, which will play a central role in TropIKA.But TropIKA is not just a place where new articles are published. We seek to provide a portal that will allow anyone with an interest in tropical diseases to link to what is going on in this growing field. Thus, also within the last month, we have added links to recent Reports and Policy & Strategy documents published elsewhere. We are also starting to develop our Funding Opportunities section. Sometimes, one comes across an initiative that is particularly pleasing. A new addition to the websites listed in our Resources section is a case in point. The website http://www.tsetse.org/provides highly practical ‘information to assist in the planning and implementation of tsetse control operations’. It is very encouraging that neglected tropical diseases are not neglected on the World Wide Web but it is not always easy to track down what is out there. Helping link people to resources is a key part of what we do. Paul Chinnock - TropIKA, Editor in Chief

Who wants to be a macrophage?

Web-based games could be an interesting way available for scientists and school teachers alike to spread the word against infectious diseases and to build up awareness for broader audiences in a more friendly way – especially amongst the general public, particularly children, in endemic areas. On the Nobel Foundation homepage one can learn and enjoy several science-related games, two of which are dedicated to infectious diseases – TB and malaria. Both games are fun, interactive and easy to learn. In the Tuberculosis Game, you are invited to follow the steps of German scientist Robert Koch, guided by ‘Wilma the clever virtual maid’. She will help to select lab devices and biological samples for you to perform your own experiments – always using Koch’s methods, including slide technique, staining, and plate technique. The Malaria Game is also easy to play, and very instructive regarding the way vector and parasite behave during the disease infestation period. In one phase, the player is invited to assume the anopheles mosquito point-of-view, flying around and trying to make its way to a human being, while avoiding insecticide sprays and bed nets on the way, as well as insectivorous birds and bats. In another phase, the player becomes the plasmodium parasite, swimming down a human artery in search of the liver, while shunning T-cells, macrophages, anti-bodies, etc. Although creative and highly instructive, it seems a pity that the malaria game encourages identification with the vector and the parasite but does not place the players in the position of the defenders against the disease. Many players would probably feel more stimulated by playing the role of a valiant macrophage, or maybe a smart killer T-cell. Malaria is also the theme on another interesting educational game available on the net at The Royal Society home page. Hilary Ranson, a researcher from Liverpool School of Tropical Medicine, has developed a game dealing with her main field of research: understanding the mechanisms by which insects develop resistance to insecticides. In the game, after watching a good tutorial and a video feed, the player is invited to catch three Anopheles gambiae mosquitoes and compare their three mRNA strands in order to find the only amino acid that make one of them resistant to insecticide. These few examples show that humour can be a powerful tool to foster scientific knowledge and epidemiological awareness, albeit in the midst of the sad figures related to such life-threatening infectious diseases.

Chimp virus vaccine against malaria is under trial

Not since Tarzan was aided by his animal friend Cheetah has there been so much potential human benefit from a relationship between man and chimpanzee. For the first time, researchers will try to boost the immunological response – and therefore the efficacy – of a new anti-malaria vaccine by using a virus found in chimps. The virus is an adenovirus strain known to cause colds and stomach troubles in chimps but to be completely harmless to humans. The trials will be conducted at the Jenner Institute at Oxford University, UK, where over a dozen malaria vaccines have already been developed and taken to clinical trials. The research is funded by the Wellcome Trust. The idea is to trigger a programmed T-cell immune response in order to fight the parasites inside the liver of the recipient, avoiding their further release into the bloodstream and red blood cells. According to WHO figures, malaria claims one life every 30 seconds, or more than a million a year, mainly women and young children in poor countries of Africa and Southeast Asia. Improved treatment and the use of insecticide-treated bed nets play an important role in malaria control but an effective vaccine is still badly needed.

An email group for tropical diseases

Email discussion groups are one way of keeping up to date with current debates and there are now a number of groups relevant to tropical disease research. One such group is CHILD2015, which focuses on the information and learning needs of healthcare providers in developing countries. Recently, for example, Hugh Reyburn – a clinical epidemiologist working at the Kilimanjaro Christian Medical Centre in Tanzania – has used CHILD2015 to share some of his team’s thoughts and experiences on the use of rational use of rapid diagnostic tests for malaria. TropIKA readers are recommended to take a look at what he has to say. Membership of CHILD2015 is free and is open to anyone with an interest in improving child healthcare in developing countries. For further details, please see www.dgroups.org/groups/CHILD2015/ or contact the moderator: CHILD2015-admin@dgroups.org Incidentally, this is my first blog since becoming Editor of TropIKA. I shall use my blogs to highlight interesting information on tropical diseases that has appeared elsewhere, but of course there is plenty of interest right here on the TropIKA website too. For example, we have recently published two interviews with senior figures in organisations working against tropical diseases.

“TB does not have to be the global health emergency that it is today”: TropIKA interviews Maria Freire http://www.tropika.net/svc/news/20080130/Souza20080130
New Global Forum leader seeks to turn strategy into action http://www.tropika.net/svc/interview/Anderson20080129.

Malaria Star Wars

Sun-Tzu, the author of the influential ancient Chinese book on military strategy, maintained that to fight an enemy effectively, we must do so on the enemy’s own terms. If our enemy is a flying disease-borne vector, then we should learn to fly higher and better. With the help of 14 satellites currently in orbit and the US National Aeronautics and Space Administration's (NASA) Applied Sciences Program, scientists are now able daily to collect data to monitor environmental changes. Data on vegetation and rainfall can be used to predict the intensity of disease transmitting vectors and the resulting level of risk to humans. One infectious disease targeted by NASA is malaria, which affects 300–500 million people worldwide, with 40 percent of the world at risk of infection. The Malaria Modeling and Surveillance Project, which utilizes NASA satellite technology, is currently in use by the Armed Forces Research Institute of Medical Sciences in Thailand (AFRIMS) and the U.S. Naval Medical Research Unit located in Indonesia (NAMRU-2). According to research presented by the American Society of Tropical Medicine and Hygiene (ASTMH), “All data collected at these locations is combined and used to monitor environmental characteristics that effect malaria transmission in Southeast Asia and other tropical and subtropical regions. Malaria surveillance provides public health organizations with increased warning time to respond to outbreaks and assistance in the preparation and utilization of pesticides, which leads to a reduction in drug resistant strains of malaria and damage to the environment”. John Haynes, public health program manager for NASA Earth Science Applied Sciences Program points out that “NASA satellites are also a cost-effective method for operational agencies since they are already in orbit and in use by scientists to collect data about the Earth's atmosphere”. Simple and cost-effective solutions – like anti-malaria insecticide treated bed nets – are often the best assets in the struggle against the diseases of the poor. Nevertheless, sophisticated, hi-tech approaches – sometimes with a Sci-Fi allure – may sometimes play a pivotal role. Reference 1. American Society of Tropical Medicine and Hygiene. NASA Technology Helps Predict and Prevent Future Pandemic Outbreaks; Press release 7th November 2007. http://www.astmh.org/press/nasa.cfm

Technology + Scientific knowledge = “Tech-knowledge”?

Hot off the press, a report from the International Symposium on Equitable Access to Health Care and Infectious Disease Control that was held in Rio de Janeiro last year, has fallen into my lap. Coincidentally one author of the report, which was published by UNRISD, is Claudia Travassos, a researcher at The Oswaldo Cruz Foundation (FIOCRUZ) and member of the TropIKA.net Advisory Board. The focus of the report is closely related to discussions about start this week, during Beijing’s 2007 Forum 11- namely Equitable Access. One theme that really popped out is the never-ending debate over “targeting vs. universalism” public health policies approaches and its relevance to equity in health care access. Especially the “targeting” approach quest for defining the so called “deserving poor” category?. As the Nobel Prize-winning economist Amartya Sen once has argued, “Benefits meant exclusively for the poor often end up being poor benefits”. In fact, according to Thandika Mkandawire, another author of the Rio report, “the choice between targeting and universalism approaches is ultimately a political economy problem, because it involves choosing instruments for the redistribution of resources in society and for determining levels of social expenditure”. On the other hand, as long as the spectrum of diseases covered by TropIKA.net is concerned, Mauricio Barreto, who also took part in the report, summarizes: “it will be important to develop and use international law; to clarify the moral and ethical basis for the control of infectious diseases; to enhance epidemiologic surveillance at the international level; to strengthen the means of controlling infectious diseases; to improve national and international communications to better manage outbreaks; to support the primary care basis of health systems; and to expand and strengthen North-South and South-South cooperation, and finally, to improve the development and transfer of scientific knowledge and technology”. So, what do you think now about the title of this post? Ok, it might be a pretty good pun, but it does make a lot of sense, doesn't it?