Getting wet / Tore Godal

Getting wet by Dr Tore Godal Director of the Special Programme for Research and Training in Tropical Diseases Y ou hear a shout from the river. A man is struggling in midstream. So you jump in and pull him out. A fev.~ days later, another man is in the river. So in you go again and pull him out. After a fev.~ days of this, you wonder: "Isn't it about time I found out who's pushing all these people into the river?" This was how Or Adetokunbo Lucas, my predecessor as director of the UNDP /World Bank/ WHO Special Programme for Research and Training in Tropical Diseases (TOR), saw the need for research on tropical diseases. parasitology research programmes were set up by private foundations and government agencies. And WHO started its TOR programme, not only to mobilise scientists throughout the world to seek ways of improving the health of the tropical populations but also to involve those populations in the research process. For centuries, millions of people in the Third World have been struggling with diseases that are unknown or just historical curiosities in the developed ~ world. Some people, like those in the ~ river, have been saved through the ~ successful build-up of their own 1 immunity. Or through the discovery of ~ "natural" remedies like quinine or its :g. modem derivatives. Or simply through ~ the tender loving care of their families -~ and communities. Millions - particu- ~ larly children - have died and many l...----------------" millions more are still dying or suffer- ing because of these diseases. Clearly, it's time to take a closer look at how the disease-causing micro-organisms do their damage. Around the turn of the century, in the infancy of modem biomedical research, scientists and physicians identified the causative agents of most of these diseases and worked out how they were transmitted. Interest in tropi- cal diseases, however, subsequently waned. By the middle of the century, scienti- fic research into disease had become a major discipline in northern countries. But with some notable exceptions (the Institut Pasteur in France is one), most scientists were concentrating on the so-called diseases of the "West" - cancer, heart disease, diabetes and the like. But by the late 1960s and early 1970s, scientists were ready and eager to apply their nev.1 techniques- immu- nology, then molecular biology, gene- tics and biotechnology - to tropical . diseases. During the 1970s, several 4 The tsetse fly - biting vector of sleeping sickness. These initiatives began to produce results during the last decade. First, some unquantifiable effects: - We know much more about how the parasites cause disease. We know, for example, much more about how the malaria parasite attaches to and penetrates human red cells. We have even begun reproducing in the labora- tory some of the parasite's genes and the molecules that it uses to invade these cells. This research is a basis for work on malaria vaccines. - We have identified molecules and mechanisms that enable malaria para- sites to resist the effects of drugs, and we are finding clues as to how we might prevent them from becoming resistant. - We know that, in brain damage experienced by some people with malaria, infected red cells are clogging up blood vessels (capillaries) in the brain and thereby disturbing blood flow within the brain. And we have identi- fied some of the molecules that the parasite uses to make these red cells stick to the capillary walls. - We now know that the sleeping sickness parasite changes its coat of surface molecules so as to avoid recognition and attack by the human immune system, and that it does so by shuffling its genes. We have also learned that the disease itself is partly due to over-production by the infected person of a molecule known as cachectin, or "tumour necrosis factor," used by the body to "summon" immune cells to tissues under attack by the parasite. * * * So we are beginning to find out what is pushing the people into the river. Can we now use this knowledge to prevent it from happening? And to find ways of pulling them out? Since TOR appeared on the scene, research, with direct or indirect support from TOR, has come up with about 60 different tools that could be life-saving: drugs, diagnostic kits, vaccines and vector control substances, devices or strategies. Most of them are still being tested. But about 20 are actually in use. Some examples: - A combination of the antileprosy drugs dapsone, rifampicin and clofazi- mine, known as "multidrug therapy," is being used in all but a half-dozen of the 150 countries in the world with leprosy cases. It has released more than 800,000 patients from long months, even years, of treatment and in the last five years has brought the number of registered leprosy cases in the world from over five to under four million. - Mefloquine and halofantrine, two nev.1 anti-malarial substances related to quinine, are potential alternatives to chloroquine, whose effectiveness is diminishing with the spread of malaria parasites resistant to this traditional anti-malarial drug. - Ivermectin, a nev.1 drug against fila- ria! infections, is now being introduced widely in Africa and Latin America to treat people with onchocerciasis (river blindness). W ORLD HEALTH. June-July-August 1990 - Praziquantel, an ideal drug (developed independently of TOR) for the treatment of schistosomiasis but for a long time too expensive for wide- spread use, is now available at low cost (currently under one US dollar for a full adult treatment). Through large- scale field studies, new ways are being explored of using the drug even more cost-effectively than at pt:esent. - A simple "card" test is now used in a dozen African countries to detect people infected with the parasites that cause sleeping sickness, and in certain areas new insecticide-impregnated traps have virtually wiped out popu- lations of tsetse flies that carry the disease. - Chagas disease could now be con- trolled in large areas of Latin America through well-planned campaigns against the triatomine bug vector. It is now possible, thanks to field research, to target insecticide spraying very pre- cisely, followed by the application of ~ new insecticidal paints and insecticide- ~ releasing fumigant canisters. Making ~ houses less hospitable to the vector o bug is also proving a critical element of ~ such campaigns. - A toxin produced by a bacterium (Bacillus thuringiensis, strain H-14) is being used by the 11-country Onchocerciasis Control Programme in West Africa (OCP) to hold in check populations of blackflies that transmit river blindness. The toxin also kills the larvae of mosquitos that carry malaria and lymphatic filariasis (elephantiasis). * * * Without wishing to overstretch Or Lucas' metaphor, I would say that, thanks to research over the past decade or so, we now have a pretty good choice of ropes and lifebelts to pull the people out of the river - at least for diseases such as leprosy, sleeping sickness, schistosomiasis and Chagas disease. But we are discover- ing more and more people who are harder to reach because they're in midstream or in inaccessible creeks. Some of them have got used to the water or have learned to swim so that they don't want to be pulled out or don't trust the new ropes and hooks or don't want to be saved by strangers. So we have to find better ways of using our equipment, ways more suited to the needs, habits and budgets of the people we're trying to help. We now have to plunge into that river ourselves to ask those who are struggling to keep W ORLD HEALTH. J une-J uly-Au gust 1990 Taking blood-samples from school- children in Nigeria to check for malaria infection. afloat how best we can help them. In TOR terms that means more field research and more participation of local scientists and local communities in the design of disease control stra- tegies and in the field testing of new disease control tools. It means building up among these local scientists and communities the practical experience and the confi- dence to adopt a more pragmatic, problem-solving approach to the con- trol of diseases they have been living with for so long. To foster this kind of operational "research-cum-training" approach we have decided to create a network system based on local field research projects. Known as FIELDLINCS (Field Links for Intervention and Con- trol Studies), this system will allow young local scientists to participate in and learn from field research projects. Through local and regional workshops, through scientific literature and expert advice in the pertinent disciplines, TOR links each local network with others in the region and, indirectly, with the 2,000-or-so scientists taking part in the global TOR network. Scientific and economic research, epidemiology and research capability strengthening all serve - and are served by - this system of concentric, intersecting networks. The ultimate aim is not to train developing country scientists or to strengthen this or that institution in the country. It is to produce a disease control tool or a research finding. It is to produce a scientific outcome - whether a drug or a vaccine or a diagnostic kit or an insecticide - that is usable in the local situation and may prove of benefit to the greatest number of people who need it. Priority needs Perhaps, with such networks, we may be getting closer to those people in midstream. Meanwhile, we still don't have enough equipment. But we have reached a stage, now, where we can choose and can concentrate our ener- gies on priority needs. For instance: - We need new drugs, particularly for malaria, in anticipation of resistance to mefloquine and halofantrine. Some new drugs, like artemisinin, are in the offing but problems of cost could hold up the development process. - New ways of developing drugs are needed. Declining pharmaceutical interest in drugs for Third World diseases has prompted TOR to set up a simple, low-cost system of carrying out the early (preclinical) stages of drug development. In this "drug corn- 5 @ i Q) c 0 :;:1 l E 8 .s 0 .1: Q. 0 ~ .ill ] ~ ~ z ~ :i c.: Getting wet pany without walls," the development process is taken in hand by a product developer, employed by TOR to work with pharmaceutical companies and university research groups in identi- fying promising new compounds and screening them for anti-disease activity. The leading candidate compounds are then submitted to the next stages in the drug development process. - Vaccines are needed. As disease control tools, they can be decisive (witness the eradication of smallpox and the virtual disappearance of polio- myelitis in the Americas). Basic bio- medical research - including the cloning of about 100 parasite genes - has produced an array of "candidate" vaccine molecules. Several possible molecules are being studied for malaria and schistosomiasis vaccines. Meanwhile, traditional (killed whole parasite) vaccines are being tested in human subjects for protection against leprosy and leishmaniasis. But overall, vaccine work is in its early stages. These age-old parasites have had time to learn how to evade the human immune system, and the task is prov- ing harder than was first thought. For some of the tropical diseases, like African trypanosomiasis , Chagas disease and filariasis, a vaccine is still a fond dream. But the battle is on and science has taken up the challenge. Back to the river. Thanks to scienti- fic research, we know much more about what's doing the damage and how. We've also found a few ways of putting a stop to it. A crucial task now is to find ways of putting these results to good use. But to do that, we may all have to get a bit wetter. • 6 UNDP: improving the human condition by Timothy Rothermel Director, Division for Global and lnterregional Programmes, UNDP, New York T he United Nations Development Pro-gramme, UNDP, bases its longstanding commit-ment to improving health in the developing countries on solid economic grounds, as well as a concern for improving the quality of human life. As the world's lar- gest provider of grant technical co-operation, UNDP receives nearly US $1,300 million per year in volun- tary contributions. Through a network of offices in 112 developing countries, and in cooperation with over 30 international and regional agencies, it works with 152 governments to pro- mote higher standards of living and economic growth. Over the past two decades, UNDP's Global Programme has supported worldwide collaborative research and disseminated the results through training, institutional strengthening and Clean water on tap in a Himalayan village. UNDP helps countries to achieve a healthier environment. demonstration activities. It is through the Global Programme that the UNDP Governing Council has endorsed support for TOR since its inception. Why should an organization like UNDP, whose work is mostly directed at country-specific activities, attach impor- tance to research and training in tropical diseases? Or for that matter, to research and training in other fields of health, such as water supply and sanitation or agriculture? The short answer is that, while it is essential for development activities to be under- taken on a country-by-country basis, UNDP recognises that such efforts must also be accompanied by a search for new knowledge and for approaches which strike at both the symptoms and causes of under-development. Many problems that are commonly found in developing countries can most effectively be approached within a global framework of cooperation that permits an exchange of knowledge and experience. The process of search- ing for new knowledge and disseminat- ing it has enabled developing countries - in many cases on their own - to help resolve problems which have histori- cally plagued humankind. While sometimes the process of seeking new knowledge falls short of expectations, many positive results are being achieved. Farmers will be returning to the fertile Volta River basin, no longer fearing the scourge of river blindness. New approaches to malaria and leprosy control, the bio- logical control of vectors, and efforts to strengthen research capacity in developing countries are but a few of the achievements of TOR. Additional areas where UNDP is privileged to be a partner in improving the human condi- tion include the tripling of cassava yields, the introduction of highly nutri- tious quality protein maize, and improved technologies and approaches to serving the unserved with clean water, sanitation and a healthier environment. • WORLD HEALTH. June-July -August 1990