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.

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!

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

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

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

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.