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.

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

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

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

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

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

Thankfully, some other IDPs are now receiving increased attention and there is good news to report. New findings from southern Africa and from Mexico [2] provide further evidence that the introduction of rotavirus vaccines into immunization programmes can lead to substantial reductions in diarrhoeal morbidity and mortality. (Diarrhoeal disease is, after pneumonia, the second biggest killer of children in poor countries.) Getting the vaccine to all those who need it is now the challenge.

The search for a vaccine that will protect against dengue fever [3] has been stepped up, with another candidate vaccine entering Phase 1 trials. There are now at least five potential dengue vaccines under development. Some of the countries in Asia and South America reporting increased numbers of dengue cases are amongst the world’s most rapidly growing economies. There will certainly be a significant market for products that prevent or treat dengue and thus there is an economic incentive for research and development efforts that is lacking for many other IDPs.

Many infectious diseases have now been studied using the techniques of mathematical modelling but it remains a controversial area of research. In one of our regular series of Profile interviews, Tatum Anderson speaks with one of the leaders in this field – Professor Sir Roy Anderson [4].

But probably the most influential figure in IDP research is now Bill Gates, who has been much in the news in recent days. The publication of his Annual Letter is likely to come to be regarded as a yearly landmark, as it sets out – in an informal fashion – the Gates Foundation’s own current plans and priorities, and it will have an influence on the actions taken by other donor organizations. The letter – and the announcement of major new Gates funding for vaccine research that followed a few days later – are discussed in TropIKA.net News [5].

The TropIKA.net Blog [6] continues to highlight new developments that have been reported elsewhere on the Internet. China has been reported to have made good progress against tuberculosis [7] and market research has shown it to offer enormous potential for the sale of TB drugs [8]. The achievements of China contrast with the situation in South Africa where TB rates in children are claimed to be the highest ever reported [9].

Another item of interest on the blog is the news that drug giant Novartis has been trying to create a fund that companies and institutions could draw upon to finance the development of drugs against neglected diseases. But after two years of approaching potential donors Novartis says it has not raised a cent for its proposal [10]. Industry has a major role to play in the development of new tools to control the infectious diseases of poverty and it is to be hoped that Novartis will find other ways in which it can make a contribution.

Paul Chinnock
Editor, TropIKA.net

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

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

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!