RLD THE MAGAZINE OF THE WORLD HEALTH ORGANIZATION · JUNE-JULY-AUGUST 1990

tropical diseases research CE> Target Diseases TDR represents a coordinated attack by the world's scientific community on six major diseases of the tropics: malaria. schistosomiasis. filariasis (including onchocerciasis). trypanosomiasis (sleeping sickness in Africa. Chagas disease in Latin America). leishmaniasis and leprosy. TDR is jointly sponsored by the UN Development Programme. the World Bank and WHO.

2 W ORLD HEALTH, June-July-August 1990 TROPICAL DISEASES RESEARCH Cover: Taking a skin WORLD I-£AUH snip for research in leprosy co ntrol in Eth iopia. Applying WHO/J. Maurice

IX ISSN 0043-8502 World Health is the official illustrated what we learn magazine oft he World Hea lth Organ ization. by Dr Hiroshi Nakajima Editor: Director-Genera/ of the Wo rld Health Organization John Bland esearch is one of the achievements. In this last decade of Deputy Editor: corner-stones for the the century, we see ever more clearly Christiane Vi edma development o f that the development of technology is, Art Editor: ]Reffective health care by itself, rarely sufficient. What we Peter Davies policy. Equally impor- learn in the shape of new technology tant is the training and manpower has to be applied in the field to News Page Editor: development needed to carry out that control difficult and dangerous Philippe Stroot research. WHO has always emphasised diseases that strike in an almost World Health appears six times a year in English .• French. Portuguese. Russian and Spanish. and research and training, and these prin­ infinitely varying environment of eco­ four times a year in Arabic and Farsi . The German ciples are clearly developed in the two logical conditions, economic edition is obtainable from: German Green Cross. Schuhmarkt 4. 3550 Marburg, FRG . interdependent objectives of the potentials and political realities. It is Articles and photographs not copyrighted may UN DP/ World for this reason be reproduced provided credit is given to the World Health Organization. Signed articles do Bank/ WHO that WHO is not necessarily reflect WHO's views. The designations employed and the presentation of Special Pro­ intensifying its material published in World Health do not imply gramme for efforts to con­ the expression of any opinion whatsoever on the part of the Orga nizati on concerning the legal Research and trol these tro­ status of any country. territory or other area or of Training in pical diseases, its authorities. or co ncerning the delimitation of its frontiers or boundaries. Tropical by strengthen­ Diseases ing countries' (TOR): capability to - research apply the ef­ and develop- o fective tools Contents ment to obtain ~ which have re­ Tropical Diseases Research: new and im­ sulte d from Applying what we learn proved tools Collecting larvae of the malaria-carrying the research by Hiroshi Nakaj ima ...... 3 anopheles mosquito for subsequent for the control carried out Getting wet of major tropi­ laboratory examination. under the by Tore Godal ...... •...... 4 cal diseases; auspices of the UNDP: improving the human - strengthening of the research Special Programme. condition capabilities of endemic countries. To have realistic hopes of achieving by Ti mothy Rothermel ...... 6 Through a global network of partici­ sustainable results, we must realis­ World Bank: a powerful pating institutions and scientists, TOR tically assess the total environment of partnership is promoting the development of an the communities we seek to protect. by Bernhard Li ese ...... 7 impressive catalogue of new and This implies new challenges in terms An aim and a hope improved tools for diagnosis, preven­ of diagnosis, epidemiology, planning Interview with Ralph H. Henderson .. . 8 tion, patient care, treatment and con­ and evaluation. And, of course, Where the action is trol in relation to its target diseases - nothing can be achieved without the by John Maurice ...... 10 malaria, schistosomiasis, filariasis, full and active cooperation of our trypanosomiasis, leishmaniasis and international partners and the com­ Vaccines for the Third World leprosy. The Programme's globally munity we serve. All this gives added by Barry R. Bloom ...... 13 coordinated research and research importance to technical develop­ TOR: Training Grants ...... 16 training activities - and their positive ments, to social and economic A good mix results - make us confident that we research, to field support and coop­ Interview with Sune Bergstrom ...... 18 can improve our capability for con­ eration with national governments, Breaking new ground trolling these diseases and provide and to communications. by Carol Vlassoff ...... 20 real relief from suffering to those TOR has an important place in A global response to climate afflicted. It is heartening, too, to WHO's work. It provides a mature change record that these are achievements of example of international cooperation by Enrique H. Bucher ...... 23 a "special programme" that does not from which much can be learnt. This Planetary responsibility operate independently of the rest of issue of World Health describes some Interview w ith Pierre Joly ...... 25 WHO but is thoroughly integrated with aspects of its activities, and explains Developing new drugs its other relevant programmes. why we can have every confidence in by David E. Davidson J r...... 28 However, the TOR Programme its continued success in the future. • cannot rest on the laurels of its past Hiroshi Nakajima, M.D., Ph.D. News Page ...... 30-31

WOR LD HEALTH . June-July-August 1990 3 Getting wet by Dr Tore Godal Director of the Special Programme for Research and Training in Tropical Diseases

ou hear a shout from parasitology research programmes within the brain. And we have identi­ the river. A man is were set up by private foundations and fied some of the molecules that the struggling in midstream. government agencies. And WHO parasite uses to make these red cells So you jump in and started its TOR programme, not only stick to the capillary walls. pull him out. A fev.~ days to mobilise scientists throughout the - We now know that the sleeping later,Y another man is in the river. So in world to seek ways of improving the sickness parasite changes its coat of you go again and pull him out. After a health of the tropical populations but surface molecules so as to avoid fev.~ days of this, you wonder: "Isn't it also to involve those populations in the recognition and attack by the human about time I found out who's pushing research process. immune system, and that it does so by all these people into the river?" shuffling its genes. We have also This was how Or Adetokunbo learned that the disease itself is partly Lucas, my predecessor as director of due to over-production by the infected the UNDP/World Bank/ WHO Special person of a molecule known as Programme for Research and Training cachectin, or "tumour necrosis factor," in Tropical Diseases (TOR), saw the used by the body to "summon" need for research on tropical diseases. immune cells to tissues under attack by For centuries, millions of people in the parasite. the Third World have been struggling with diseases that are unknown or just * * * historical curiosities in the developed ~ So we are beginning to find out world. Some people, like those in the ~ what is pushing the people into the river, have been saved through the ~ river. Can we now use this knowledge successful build-up of their own 1 to prevent it from happening? And to immunity. Or through the discovery of ~ find ways of pulling them out? "natural" remedies like quinine or its :g. Since TOR appeared on the scene, modem derivatives. Or simply through ~ research, with direct or indirect support the tender loving care of their families - ~ from TOR, has come up with about 60 and communities. Millions - particu- ~ different tools that could be life-saving: larly children - have died and many l...------" drugs, diagnostic kits, vaccines and millions more are still dying or suffer­ vector control substances, devices or ing because of these diseases. Clearly, The tsetse fly - biting vector of sleeping strategies. Most of them are still being it's time to take a closer look at how sickness. tested. But about 20 are actually in the disease-causing micro-organisms use. Some examples: do their damage. These initiatives began to produce - A combination of the antileprosy Around the turn of the century, in results during the last decade. First, drugs dapsone, rifampicin and clofazi­ the infancy of modem biomedical some unquantifiable effects: mine, known as "multidrug therapy," is research, scientists and physicians - We know much more about how being used in all but a half-dozen of identified the causative agents of most the parasites cause disease. We know, the 150 countries in the world with of these diseases and worked out how for example, much more about how leprosy cases. It has released more they were transmitted. Interest in tropi­ the malaria parasite attaches to and than 800,000 patients from long cal diseases, however, subsequently penetrates human red cells. We have months, even years, of treatment and waned. even begun reproducing in the labora­ in the last five years has brought the By the middle of the century, scienti­ tory some of the parasite's genes and number of registered leprosy cases in fic research into disease had become a the molecules that it uses to invade the world from over five to under four major discipline in northern countries. these cells. This research is a basis for million. But with some notable exceptions (the work on malaria vaccines. - Mefloquine and halofantrine, two Institut Pasteur in France is one), most - We have identified molecules and nev.1 anti-malarial substances related to scientists were concentrating on the mechanisms that enable malaria para­ quinine, are potential alternatives to so-called diseases of the "West" - sites to resist the effects of drugs, and chloroquine, whose effectiveness is cancer, heart disease, diabetes and we are finding clues as to how we diminishing with the spread of malaria the like. might prevent them from becoming parasites resistant to this traditional But by the late 1960s and early resistant. anti-malarial drug. 1970s, scientists were ready and eager - We know that, in brain damage - Ivermectin, a nev.1 drug against fila­ to apply their nev.1 techniques- immu­ experienced by some people with ria! infections, is now being introduced nology, then molecular biology, gene­ malaria, infected red cells are clogging widely in Africa and Latin America to tics and biotechnology - to tropical . up blood vessels (capillaries) in the treat people with onchocerciasis (river diseases. During the 1970s, several brain and thereby disturbing blood flow blindness).

4 W ORLD HEA LT H. 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 Taking blood-samples from school­ strengthening all serve - and are Onchocerciasis Control Programme in children in Nigeria to check for malaria served by - this system of concentric, West Africa (OCP) to hold in check infection. intersecting networks. The ultimate populations of blackflies that transmit aim is not to train developing country river blindness. The toxin also kills the afloat how best we can help them. scientists or to strengthen this or that larvae of mosquitos that carry malaria In TOR terms that means more field institution in the country. It is to and lymphatic filariasis (elephantiasis). research and more participation of produce a disease control tool or a local scientists and local communities research finding. It is to produce a in the design of disease control stra­ scientific outcome - whether a drug or tegies and in the field testing of new a vaccine or a diagnostic kit or an * * * disease control tools. insecticide - that is usable in the local It means building up among these situation and may prove of benefit to local scientists and communities the the greatest number of people who Without wishing to overstretch Or practical experience and the confi­ need it. Lucas' metaphor, I would say that, dence to adopt a more pragmatic, thanks to research over the past problem-solving approach to the con­ Priority needs decade or so, we now have a pretty trol of diseases they have been living Perhaps, with such networks, we good choice of ropes and lifebelts to with for so long. may be getting closer to those people pull the people out of the river - at To foster this kind of operational in midstream. Meanwhile, we still don't least for diseases such as leprosy, "research-cum-training" approach we have enough equipment. But we have sleeping sickness, schistosomiasis and have decided to create a network reached a stage, now, where we can Chagas disease. But we are discover­ system based on local field research choose and can concentrate our ener­ ing more and more people who are projects. Known as FIELDLINCS gies on priority needs. For instance: harder to reach because they're in (Field Links for Intervention and Con­ - We need new drugs, particularly for midstream or in inaccessible creeks. trol Studies), this system will allow malaria, in anticipation of resistance to Some of them have got used to the young local scientists to participate in mefloquine and halofantrine. Some water or have learned to swim so that and learn from field research projects. new drugs, like artemisinin, are in the they don't want to be pulled out or Through local and regional workshops, offing but problems of cost could hold don't trust the new ropes and hooks or through scientific literature and expert up the development process. don't want to be saved by strangers. So advice in the pertinent disciplines, TOR - New ways of developing drugs are we have to find better ways of using links each local network with others in needed. Declining pharmaceutical our equipment, ways more suited to the region and, indirectly, with the interest in drugs for Third World the needs, habits and budgets of the 2,000-or-so scientists taking part in the diseases has prompted TOR to set up people we're trying to help. We now global TOR network. a simple, low-cost system of carrying have to plunge into that river ourselves Scientific and economic research, out the early (preclinical) stages of to ask those who are struggling to keep epidemiology and research capability drug development. In this "drug corn-

W ORLD HEALTH. J une-J ul y-August 1990 5 Getting wet

pany without walls," the development process is taken in hand by a product developer, employed by TOR to work UNDP: improving the with pharmaceutical companies and university research groups in identi­ fying promising new compounds and screening them for anti-disease activity. human condition The leading candidate compounds are then submitted to the next stages in the drug development process. by Timothy Rothermel - Vaccines are needed. As disease Director, Division for Global and lnterregional Programmes, UNDP, New York control tools, they can be decisive (witness the eradication of smallpox and the virtual disappearance of polio­ myelitis in the Americas). Basic bio­ he United Nations demonstration activities. It is through medical research - including the Development Pro­ the Global Programme that the UNDP cloning of about 100 parasite genes - gramme, UNDP, bases its Governing Council has endorsed has produced an array of "candidate" longstanding commit­ support for TOR since its inception. vaccine molecules. Several possible ment to improving Why should an organization like molecules are being studied for healthT in the developing countries on UNDP, whose work is mostly directed at malaria and schistosomiasis vaccines. solid economic grounds, as well as country-specific activities, attach impor­ Meanwhile, traditional (killed whole a concern for improving the quality tance to research and training in parasite) vaccines are being tested in of human life. As the world's lar­ tropical diseases? Or for that matter, to human subjects for protection against gest provider of grant technical research and training in other fields of leprosy and leishmaniasis. But overall, co-operation, UNDP receives nearly health, such as water supply and vaccine work is in its early stages. US $1,300 million per year in volun­ sanitation or agriculture? The short These age-old parasites have had time tary contributions. Through a network answer is that, while it is essential for to learn how to evade the human of offices in 112 developing countries, development activities to be under­ immune system, and the task is prov­ and in cooperation with over 30 taken on a country-by-country basis, ing harder than was first thought. For international and regional agencies, it UNDP recognises that such efforts must some of the tropical diseases, like works with 152 governments to pro­ also be accompanied by a search for African trypanosomiasis, Chagas mote higher standards of living and new knowledge and for approaches disease and filariasis, a vaccine is still a economic growth. which strike at both the symptoms and fond dream. But the battle is on and Over the past two decades, UNDP's causes of under-development. science has taken up the challenge. Global Programme has supported Many problems that are commonly Back to the river. Thanks to scienti­ worldwide collaborative research and found in developing countries can fic research, we know much more disseminated the results through most effectively be approached within about what's doing the damage and training, institutional strengthening and a global framework of cooperation that how. We've also found a few ways of permits an exchange of knowledge putting a stop to it. A crucial task now and experience. The process of search­ is to find ways of putting these results Clean water on tap in a Himalayan ing for new knowledge and disseminat­ to good use. But to do that, we may all village. UNDP helps countries to ing it has enabled developing countries have to get a bit wetter. • achieve a healthier environment. - 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 i being achieved. Farmers will be Q) returning to the fertile Volta River c 0 basin, no longer fearing the scourge of :;:1 l river blindness. New approaches to E malaria and leprosy control, the bio­ 8 .s logical control of vectors, and efforts to 0 strengthen research capacity in .1: Q. developing countries are but a few of 0 the achievements of TOR. Additional ~ areas where UNDP is privileged to be a .ill ] partner in improving the human condi­ tion include the tripling of cassava yields, the introduction of highly nutri­ ~ tious quality protein maize, and z~ improved technologies and ~ approaches to serving the unserved :i with clean water, sanitation and a c.: healthier environment. •

6 WORLD HEALTH. June-July-August 1990 WORLD BANK: apowerful partnership by Dr Bernhard Liese Senior Public Health Specialist with the World Bank, Washington D. C.

t may seem unlikely for the such as malaria, schistosomiasis and Pulling together: a simple but effective World Bank - whose principal others had emerged. means of irrigating parched land. The function is to provide loans for By the mid-1970s, the Bank had World Bank has long experience in J[ development projects in order decided that it should systematically water development projects. to strengthen the economies consider the possible health impacts of of borrowing countries - to take a Bank-supported projects, minimise any keen interest in tropical disease such adverse effects, and make key research and control. But health has interventions to improve the health the fruits of TOR-supported research been an important dimension of the status of low-income groups. Between have become incorporated in aspects Bank's overall efforts to promote 1970 and 1980, more than 100 health of Bank-financed disease control pro­ economic development. components were included in Bank­ jects. I believe that "if TOR did not In 1989, World Bank investment in financed projects, and about 30 per exist today, it would certainly have to development projects accounted for cent of them dealt with tropical be invented." How important TOR is over US $20 billion. Within .this total, diseases. to the World Bank can be measured an important component is formed by Last year, Bank loans of about directly; of all the World Bank's Special investment in national health infra­ US $136 million supported tropical Grant Programmes in Health, TOR structure and services, disease surveil­ disease control projects in five coun­ now receives the largest contribution. lance and control programmes, and tries. Of particular importance have The Bank has also ventured into institutional development of health been projects against malaria, schisto­ another important area of tropical systems. somiasis, leishmaniasis, Chagas disease disease control - the Onchocerciasis It was with the "discovery of the and tuberculosis. Schistosomiasis con­ Control Programme (OCP) which rural poor," as expressed by Mr Robert trol has become an important aspect covers 11 nations in West Africa. McNamara - then President of the of our irrigation and dam construction This international effort to combat World Bank - in a speech in Nairobi in projects. river-blindness was launched after Mr 1974, that health activities became McNamara saw for himself the devas­ firmly anchored in the Bank's portfolio. Control problems tating effects of this debilitating disease. Prior to that, although several rural, When the Special Programme for The Bank has acted as the eo-sponsor agricultural and irrigation projects had Research and Training in Tropical and fund-raiser for this programme contained health components, the Diseases was conceived in 1974, atten­ throughout its 15 years of activity. overall emphasis on health had been tion to tropical disease was in decline. I believe the Bank's involvement relatively small. Concern for health There were serious problems in with TOR, OCP and other aspects of issues stemmed, first, from the new disease control technology, and work tropical disease research and control, perspective on poverty which went to develop new tools was not moving has demonstrated the power of such beyond simple measures of income quickly. The World Bank became a partnerships in combating tropical levels, and second, from the Bank's "founding member" of the TOR, now diseases. Bank involvement has been experience in water development pro­ the central international focus for tro­ perceived by donors as helpful, contri­ jects. Whenever health risks were not pical disease research. Moreover, as buting to efficient programme organi­ considered in project design, diseases the Programme has matured, many of zation and management. •

WORLD HEALTH. J une-July-August 1990 7 An aim and a hope

At the beginning of this year, WHO created a Tropical Diseases Control Division, which will work closely with the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TOR) , set up in 1976 to promote research on tools to control the tropical diseases. Dr Ralph H. Henderson, for the past 13 years head of the Expanded Programme on Immunization, was appointed an Assistant Director-General of WHO with the responsibility, among other things, of overseeing TOR and the new control division. In an interview with World Health, he described how research and control of tropical diseases could be part of a greater effort to translate the ideal of primary health care into a worldwide reality.

WH: How do you see the two tropical how the drug can be matched with RH: Yes. The new structure will mean disease programmes - one for control, other products so as to produce an that the researchers (those who the other for research - working overall health package. Such a pack­ develop the drugs, the vaccines and so together? age might include vitamins to prevent on) will work more closely with the RH: Rather like team-mates in a relay malnutrition and blindness, vaccines control people (those who have to use race. For many diseases TOR, through against several diseases, oral rehyd­ these drugs and vaccines). It will also its research promoting efforts, has a ration salts for children with diarrhoea, mean more intensive work on control number of "batons" such as drugs, health education counselling, advice of specific diseases. A more integrated candidate vaccines and diagnostic kits, on birth spacing, promotion of breast approach will ensure that the leprosy which they are ready to pass to the feeding, and so on. Delivering a dozen people are not just interested in control people. And the new control or so of the most essential health items leprosy, the schistosomiasis people in division will provide a home for these to whole communities might not cost schistosomiasis and so on, but they are products. But as in a relay race, very much more than delivering a all looking for ways to apply technolo­ passing the baton between research single drug like ivermectin. gies and strategies in several areas, as and control sometimes goes quickly, part of an integrated programme to sometimes not so quickly. We are improve community health. And a seeing the need for more applied third level is bringing the community research in cases where control pro­ into the picture, so that when a child grammes experience difficulties in with diarrhoea is brought to a health using the tools which research has care facility, for example, the health provided. worker doesn't just "turn on" the WH: For example? diarrhoea intervention. He looks at the RH: Ivermectin, the new drug against overall health problems of the child, river blindness, is a good example. the child's family, and the community. TOR has been involved in getting the WH: All these elements of the health drug to the point where it can be safely package have been part of WHO's and effectively used in the field to stop overall efforts for years now. Do you people going blind. Merck and Com­ feel that the next decade has a better pany, the manufacturer, is even provid­ chance than previous decades of ing the drug at no cost to countries bringing these efforts to fruition? with river blindness. So far · so good. 1 RH: In the 1980s, we've been spinning But to deliver the drug to the people ~ individual threads, corresponding to who need it costs about US $5 per g. the different WHO programmes, such person. Few developing countries can ~ as those dealing with diarrhoea! afford this, so as a result too few diseases, acute respiratory infections, countries have been taking advantage immunization, essential drugs, tropical of Merck's offer. It follows that there is Gotcha! Using himself as living bait, a disease research, and so on. The still a lot of work to be done to catcher in the Onchocerciasis Control 1990s will have to be the decade in determine how the drug can best be Programme in Burkina Faso captures which we weave these threads into a got to people and administered in a the blackfly pest that spreads river comprehensive primary health care safe, effective and cheap way. Plann­ blindness. fabric. And we do stand a better ing, training and management are all chance of succeeding now: while we've involved. This is an area where both WH: You're really talking about three been spinning the threads, we've been programmes - research and control - levels of coordination or synergy: learning how to deal with the relatively will have to work together to find a between research and control, between simple elements of each programme - solution. the different control products, and training, management, monitoring and WH: What kind of solution? between these products and all the evaluation systems, and so forth. RH: One solution might be to study other elements of primary health care? As we have built up each individual

8 W ORLD HEALTH, June-July-August 1990 WHO/J. Mohr control efforts and .may not wait while we weave, what can we do to contain the problem? RH: Yes, malaria is a real problem, and one that is growing as the parasites learn to resist anti-malarial drugs and the mosquito vectors learn to resist insecticides. Until a universal tool such as a vaccine becomes available, we may have to put aside thoughts of controlling, let alone eradicating, malaria infection. We may have to step backwards for a while and see if we can't at least drastically reduce the number of deaths, mostly child deaths, from the disease. We should aim at providing children with anti-malarial drugs as soon as they become sick, so as to get them over their first infection and allow them to build up some degree of immunity to subsequent attacks by the parasite. We can also ask communities what they can do to reduce the problem, even if it means turning to less sophis­ ticated solutions, like insecticide­ impregnated bednets or curtains, like repellents or other means of avoiding mosquitos at peak biting times. On a global level, in response to concerns raised at the meeting of WHO's Executive Board in January, WHO is planning a ministerial confer­ ence on malaria to be held within the next tvJo years, to try and sensitise political leaders to the problem. WH: You mentioned smallpox eradi­ cation and the expanded immuni­ zation programme, widely regarded as tvJo of WHO's success stories. You have been associated with both. What is the secret of running an effective health programme within a large international bureaucracy like WHO? RH: Ensuring the right match bet:vJeen simple tools and good managers. The secret of the immunization programme has been in having vaccines that are so simple, effective and inexpensive that they cut right through the constraints of a heavy bureaucracy, not only at WHO headquarters in Geneva but out in the regions and the individual countries. Management was a question of boiling down immunization Researchers like these in central Africa name but tvJo examples. And with the schedules to a simplified scheme, easy are engaged in a life-and-death struggle maturing of each programme, it to teach and easy to put into effect in against malaria. becomes easier to add on other pro­ local situations. Once in a while you grammes and gradually to weave all see that match bet:vJeen a "do-able" the threads together into the overall technology and managers who can programme, we have been building a fabric. That's how I see our job for the make sure its done, and then the sky's critical mass of managerial skills at the next decade. We have to be good the limit. With the new tools that are national level, able to deliver technolo­ weavers! emerging from tropical disease gies where they're needed. We're now WH: Learning to be a good weaver research and the new management seeing a real impact at the peripheral sounds fine, but when countries are in structures that are being set up to use level. We have a mature immunization a life-or-death struggle against a the tools, we may well be setting the capability and a relatively mature diar­ disease like malaria, a disease that scene for some more success stories. rhoea! disease control initiative, to seems to be thumbing its nose at our That's the aim and that's the hope. •

WORLD HEALTH, June-July-August 1990 9 Where the action is by John Maurice Geneva-based writer on health and biomedical science

A "grassroots" view of two disease control tools - ivermectin, a new drug for river blindness, and multigrup therapy, a new combination treatment for leprosy- developed with TOR support.

Kouman, Vina Valley, northern Anybody who doesn't take the medi­ drinks the water without taking the pill; Cameroon cine could give the disease to other absent-mindedness or stock for his people: so everybody must come. We amateur pharmacy? Another puts the he village straddles the also tell them that we will come back ivermectin into his mouth but refuses road that follows the every day for a week after the or is unable to swallow. The plastic fast-flowing Vina, a river treatment day to see if anyone has any cups are a big success, though, bran­ infested with the problems, and we warn them that they dished as trophies by the young boys blackflies that carry river might feel a bit unwell after taking as they leave the ivermectin table. blindness1L. It is four in the afternoon. ivermectin." Two boys compare the itching Two white jeeps roll into the central symptoms they have felt of river clearing that serves as a village square. blindness. One of them declares: Most of the 200 inhabitants are in the "Contaminated food. That's where the fields sowing cotton. A few women, disease comes from." "No," says the some with calabashes on their heads, other. "It's from drinking contaminated watch as the team pulls its mobile clinic river water. That's why they call it the from the jeeps: tables, chairs, scales, river disease." gas lamps, several battered green From the nearby female line an old metal trunks and a stapler. woman leaning on a crutch interrupts: French parasitologist Or Jacques "I know why I'm going blind. It's worms Prod'hon beckons to Noel Sorobal, in my eyes, and I know where they the village chief, and asks him to form come from. Many years ago, before I the villagers into two lines in front of ~ met my husband, he got a job at the the tables, one for females, one for ~ cotton plant in T ouboro. Then he males. The square is beginning to fill ~ married me and we had three children, up as men return from the fields and ~ two boys and a girl. Things were going shuffle into line. The male line appears ] too well for us - a good job, a good almost drab and sullen compared with ~ marriage, fine children. Someone in the female line, which spills over with _s our village here got jealous and put a colour, chatter and laughter. Both lines ~ curse on us. That's how it all started. grow lively, noisy, writhing tails as the ·~ First, my husband fell asleep in the children fall into place behind the o '------l gin-roller at the mill and died when adults. they started it up. They said he died of Several men, staring blindly in front The blackfly's bite transmits a heart attack but I know better. Then I onchocerciasis - river blindness. of them, now and then raising their fell and broke my hip. As a result I've eyes to the sky, tall and quietly had to walk with a crutch ever since. dignified against the babble and chatter Ivermectin distribution begins in the Then these worms came and I can of the thronging lines, are led at the fast-fading daylight. The two lines draw hardly see any more. I don't know end of long white sticks by small boys together at the far end as the children who's doing the witchcraft but I know towards the distribution tables. The move to the centre to see the action at it's jealousy. Maybe this white man's other members of the team - three the ivermectin tables. medicine will cure my hip so I can walk Cameroonians and two young French "Mbondo Jean, twenty-eight!" The again." doctors - are busy pulling pills out of first man in the line hands over his Seven o'clock. Night is falling, but if tinfoil wrappings. yellow registration card to Or Prod'hon anything the lines are longer. Gas "We've told the village chiefs," Or and steps on the scales. Forty-six kilos! lamps create an altar-like halo around Prod'hon explains, "that we have a He is handed his ivermectin and a the ivermectin tables. The villagers step new drug that stops the itching and plastic cup of water. up to the tables with their cards, as if prevents blindness, although it can't "Next!" making an offering to a beneficent restore sight to someone who is Shrieks of mirth from the female deity, before bending forwards to already blind. We tell them that we've line as a young woman trips over her receive the sacramental drug. By ten come to examine everybody and that long orange-white dress as she steps o'clock, the lines have dwindled to the later we'll give everybody the medicine. on to the scales. A 14-year-old boy last few "supplicants." The centre of

10 WORLD HEALTH, June-Jul y-August 1990 Leprosy patients in an upland township of Ethiopia swallow their multi-drug pills which will eventually cure them.

Kembatinya by a leprosy "scout". Each phrase elicits a chorus of "ishi" (right!) from the group of patients. A man in an intricately patterned blue skull cap raises his hand: "This treatment turns my skin black. I don't like it at all. And it makes me itch." He points to his legs. Flies are crawling between the blackish scales, trying to reach into the bleeding cracks in the skin. This is the clofazimine in the treatment, he is told. "When you stop treatment, your legs will return to their normal colour and the dryness and flakiness will eventually disappear." Another man, who has been using a "' horsetail swat to keep flies away, ·§ complains: "When I first came here ~ many months ago I was told my -:i patches would disappear with the new ~treatment. Today is supposed to be my ~ last day of treatment. But I still have many patches. I am not cured. How interest suddenly shifts from ivermectin goats, mules, sheep and horses, to set can I stop treatment?" The lesions will to the thousands of flying ants now out their wares - scraggy hens, eventually disappear, he is assured. swirling around the gas lights. Women watermelons, chickpeas and piles of When finally the jeep leaves the tree and children rush to eat or catch as red peppers. An occasional red clinic, three patients run after it, many of these airborne peanut-tasting umbrella is carried for shade or social holding out their stubs of hands in a delicacies as they can. Some of the distinction. begging gesture. Multidrug therapy insects are eaten on the spot. Most are Behind one of the hills, sheltered coordinator Zerihun Desta smiles and slapped into basins or calabashes from bustle, but within earshot of the sighs: "We tell them they don't need where they flounder and die in a few music, five men are gathered under a treatment any more. From a control inches of water. A free meal, courtesy tree. A sixth "parks" his mule near a programme standpoint they're cured. of the TOR ivermectin project. hut nearby and walks up to the group, But they show us their deformed who greet him with loud cries. More hands, the ulcers on their feet, their people are arriving, including three eyelids that they can't close - all the * * * women. They all seem to know each the things that multidrug therapy can't Multidrug therapy for leprosy is a other, and they all have green cards in do anything about. How can we tell combination of three drugs - dapsone, their hands and tiny plastic vials, some them they're cured? a drug used for the past 40 years, and with a few white pills in them. Nearly two newer drugs, rifampicin and clofa­ all the men wear white robes thrown -)(- zimine. This scheme was devised by carelessly but elegantly over their * * WHO in 1981 to replace the traditional shoulders. They are leprosy patients. Srikakulam District, State of treatment with dapsone alone, which They have come for their monthly Andhra Pradesh, India had become increasingly ineffective as supply of multidrug therapy pills. Gampadi T ata Rao pedals as fast as a result of the spread of resistant Senior leprosy supervisor Alamo he can along the narrow road that strains of the leprosy bacillus. The new Gabre-Jesus clears his throat and snakes through the rice fields towards drug combination has already released addresses the group under the tree: the village of Vanjangi. His bicycle, a over 800,00 patients from therapy and "For some of you, today is the last day bale of hay heaped over the back has brought down the number of of multidrug therapy. Patients gen­ mudguard, wobbles as he tries to registered cases worldwide from over 5 erally do not want this new treatment maintain both balance and speed. He million to 3.8 million in the last five to stop. They are afraid they will be is in a hurry for two reasons. A years. unwell when they stop. They are afraid burrakatha is being held tonight in the the white patches will come back. But village square, with music and actors. Bonosha Township, southern Shoa, although the treatment stops, we will The theme is a new treatment for Ethiopia still be here. Health worker T amru leprosy. All the villagers will be there, Saturday is market day in this Tadese will come every two weeks. Do including the chief and the elders. And parched hill town 170 km south-west you understand? If you have any some important people from Hyder­ of Addis Ababa. From dawn, people problems at all come and see him abad, the state capital. have been crowding into a vast natural here." T awards the far end of the village, a arena between three scrubby hills near He speaks in Amharic, the language floodlit stage is surrounded by a sea of the town centre. Some have staked of the area around Addis Ababa. His faces. Loudspeakers amplify the out a few square feet among the cattle, words are translated into the local sounds of a sitar and drums, and

WOR LD HEALTH. J une-July-August 1990 11 Where the action is voices declaiming theatrically. Every­ thing is light and colour: the actors and musicians' clothes, silken gold and pink and white and red and green, and their ~ ornate instruments, and their faces painted bluish-white with rouged lips. "You have a white patch?" "Yes, I have a white patch?" "Where?" "On my arm." "What did you do about it?" "I went to the herbalist." "What did he say?" "He said I should go to a leprosy doctor." "Why did he say that?" A crescendo of drums and twanging cords. Then silence. The villagers - there must be at least 2000 squatting around the stage - wait, many of them open-mouthed: "Because he says I have the big disease and he says the leprosy doctor has a new treatment for it." "A new treatment for leprosy?" "Yes. He says it's called pulse treatment." Or G. Srikrishna, Additional Director of Medical and Health Services (Leprosy) for the State of Andhra Pradesh, leans towards his neighbours in the audience and whispers: 'That's what we call multidrug therapy in India. Pulse therapy. A pulse a month. Regular as a heartbeat." The actors and musicians resume their show, chanting a health edu­ signs of advanced leprosy. Manuel was After 15 months of treatment, hardly a put on multidrug therapy. cation litany: "Leprosy is not inherited. single white patch - tell-tale sign of "I can't believe it. My pains have Leprosy is not a curse of God. Leprosy leprosy - can be found on this is not a venereal disease. Early Venezuelan boy. disappeared. My fever too. And Senor detection and early treatment prevent Reyes cleans out my ulcer regularly. I deformity. Multidrug therapy is a boon can walk almost normally again." Or to leprosy patients. Leprosy is curable. Zulueta puts a hand on his knee. "Do Leprosy is curable. Leprosy is cur­ About five years ago I started having you realise you'll be cured now? That able ..." difficulty breathing through my nose - you won't give the disease to your always blocked. Then an ulcer children or your grandchildren? Do appeared on the sole of my foot, with you realise that you won't lose your * * pus coming from it. And my elbows fingers or your toes? And that you Guanarito, Portuguesa State, and knees began to hurt. I found it won't go blind?" Venezuela hard to walk. Couldn't work, of course. Manuel covers his tears with a towel. Manuel Cardenas, a tall, wiry 45- I went to a doctor, who said it was Amalia, his wife turns away. "It's been year-old cattle herd with a sad expres­ sinusitis. Then a specialist, who said it so long," she says, shaking her head. sion topped by a hyphen of a mousta­ was arthritis. A hundred and fifty Shyly, she allows herself to be led into che, sits on the porch of his wooden bolivares (US $5) each time. Finally I the sooty, chimneyless kitchen, where slatted hut. His bandaged left foot sold our cow for a thousand bolivares Or Zulueta and Alexis Reyes help her dangles over one knee. Beside him is to pay for more visits to the doctor and to take off her dress, and then examine his wife. Facing him is National Multi­ the medicines, aspirin I think. But it her chest and back. Yes, she has the drug Therapy Coordinator Ana Maria only got worse." telltale white patches. Or Zulueta puts Zulueta. All around, a tangle of sugar Eight months ago, 25 years after his an arm around her shoulders: "You cane, papaya, orange and lemon trees ordeal began, Manuel was spotted by don't have to worry, either. Just take screens the homestead from the forest leprosy health worker Alexis Reyes at these pills. In a year or two, you'll be savana and the vast plains beyond. the Guanarito cattle market. Reyes fine. You'll be cured. "It started with numbness in my left recognized his swollen earlobes, the Turning to Alexis Reyes, she adds: foot. I was 20 years old. Then pains in nodules on his face, the scaly skin of "Before multidrug therapy, I couldn't my head and fever a lot of the time. his legs and his inflamed hands as the have told her that." •

12 W ORLD HEALTH. June-July-August 1990 vaccines for the Third world by Dr Barry R. Bloom Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, USA.

Where there is no vision, the people perish ... Proverbs 29:18

he Third World is the Clearly, the easy vaccines have already for Research and Training in Tropical place where three­ been made; new vaccines pose greater Diseases, a component was mandated quarters of the people challenges for research. in addition to the scientific research of this planet live, where "It's only a matter of implemen­ programmes for "institutional research 86 per cent of all births tation." There are few more porten­ strengthening" in the countries worst andT 96 per cent of child and infant tous words than these to be found in afflicted. This support, representing 25 deaths occur. At both a national and a any health document. For most per cent of the budget, has been used human level the diverse problems of scientists engaged in the development to set up and modernise laboratories, the developing countries are of of new health interventions, the fulfil­ and to train bright students abroad staggering proportions. Most have ment of their research is a product that (and, occasionally even to make it heavy foreign debt and, as a conse­ goes through clinical testing and is sufficiently attractive for them to return quence, these countries now transfer eventually licensed for use. In interna­ home.) As a consequence, in many to the developed countries more hard tional health, the historical record developing countries there are labora­ currency than they receive. Most are belies such optimism. For example, all tories that are able to tackle tropical burdened by disease; the reality is that of the vaccines in the EPI programme diseases. millions of people are sick because were available before 1974, but only 5 What has been largely overlooked, they are poor, and poorer because per cent of the world's children however, is the role of field and they are sick. The trends have not received them - it was clearly only a epidemiological research in developing been encouraging. Per capita income matter of implementation. countries. Almost all incentives - finan­ has declined over the past five years cial, working conditions and personal and the percentage of national recognition - motivate people to go budgets spent on health has been into medical practice, laboratory-based unchanged or has diminished for eight research or, most commonly, admin­ years.· istration. There are few rewards for Yet one aspect of life there has health workers in the field. Yet the field improved profoundly. The number of worker is the mainstay for acquiring children receiving immunizations has information about local health prob­ risen from 5 per cent in 1974 to over lems, for evaluating new interventions 60 per cent in 1989. WHO's Expanded and for integrating, maintaining and Programme on Immunization (EPI) monitoring them in control program­ prevented the deaths of 2.2 million -~ mes. Recognition of their importance children last year. Through the efforts ~ through the development of appro­ of 25,000 professional national and ~ priate career structures and edu­ international staff and hundreds of ] cational and material incentives is a thousands of field workers, 60 million cc major challenge to the developing children are now vaccinated annually ~ countries. against diphtheria, pertussis, tetanus 01 At the same time, the development (OPT), polio, measles and tuberculosis. ·§ of new drugs and vaccines (38 new The number of cases of paralytic~ products that have resulted from the poliomyelitis has declined in the Amer- .______...:;._____, TOR programme are currently in field icas from 4,500 ten years ago to fewer trials) provides a unique opportunity than 200 this year, and WHO has just The sandRy is the carrier of the for building scientific and field infras­ made the eradication of polio one of debilitating and disfiguring disease, tructures in the Third World. Field­ its goals. leishmaniasis. research and control infrastructures Immunization is the most cost­ need no longer be tied directly to one effective weapon for disease preven­ Certainly, the main limiting factor is drug or vaccine, but can be continuing tion in developing countries, and new cost, but it is not the only one. The mechanisms to assess different health molecular and genetic technologies scientific infrastructure for evaluating strategies and disease-control activities. are making new types of vaccines new drugs and vaccines relevant to Much of the same technology can be feasible. The eradication of smallpox Third World diseases is also limiting. It used in the same place to assess the demonstrated that they can be is difficult and expensive to carry out distribution of parasites in mosquitos effective everywhere. What is lacking is clinical trials in industrialised countries and the incidence of multiple infec­ the will to make the advances of in which the diseases do not occur. tions by multiple pathogens in the modem biomedical science available to From the beginning of the UNDP/ population. The epidemiological tools the poorest people of the world. World Bank/ WHO Special Programme for testing different drugs against one

W ORLD HEALTH. J une-July-August 1990 13 Vaccines for the Third World disease are often applicable to trials against another and can be adapted to evaluating vector control and vaccines as well. The result of this research is not papers; it is the control of disease. Much ink has been spilled on "appropriate technology" for the Third World, but there has been almost no consideration of "appropriate science." Research on vaccines involves a know­ ledge of molecular biology, genetics, immunology and epidemiology, and could serve as a stimulus to the educational and scientific advance­ ment important to development. Even the poorest countries have need for expertise and access to biomedical science; they cannot afford to squan­ der their resources on iron lungs.

Programme costs It is ultimately a matter of priorities. The annual budget for the entire World Health Organization is US $327 million. The IDR Programme for six tropical diseases has a budget of $35 million, and the budget for the pro­ gramme for vaccine development amounts to $2.8 million. The annual cost of childhood immunization is some $500 million, averaging about $10 per immunized child. The vac­ cines themselves represent less than 10 per cent of the cost of immuni­ zation; of the remaining costs for personnel, transport and logistics, 70 per cent is borne by the countries themselves. The major advance in vaccine cover­ age has been accomplished largely through the combined efforts of the EPI of WHO, UNICEF, the World Bank, and the UN Development Programme, with support from non-governmental organizations, particularly the Rockefeller Foundation, Rotary Inter­ national and the Save the Children Fund, which together coordinate their efforts through the Task Force for Child Survival. Behind the scenes, scientists trying to develop new or improved vaccines scramble for support, most of it coming from the US National Institute for Allergy and Infectious Diseases or the Department of Defense, or from WHO's Special (extrabudgetary) Programmes for Research and Training in Tropical Diseases, for Human Reproduction, or for vaccine development. A decade ago, some foundations were generous

A woman in Orissa, eastern India, waits patiently for her child to receive the vaccine that will protect its life ... Amita Prasher, New Delhi, India. WHO photo competition entry © 14 W ORLD HEALT H. June-J uly-August 1990 Vaccines for the Third World

... while in the Philippines, a child both to contribute and to gain. Failing billion ($287 per adult) is spent protests vigorously at the needle. that, developing countries that can annually on alcohol, $38 billion on afford it will have to rely on their own tobacco and $22 billion on toys. We abilities, intellectual and material, for can afford to do more for health in the contributors to research on diseases of developing their own biotechnology. Third World. Conscience should moti­ the Third World, but their interest This is already happening in Brazil, vate us to do so, and self-interest seems more to have reflected fashion Cuba, India and Mexico. supports the claims of conscience. In than a serious commitment to the Several new vaccines now in field the first place, good public health problem. And one must add that, trials have, in fact, been developed by translates into good economics. We regrettably, few Third World leaders scientists in the Third World - vaccines save over $0.5 billion per year in no have made health a high priority. against leprosy (developed in Vene­ longer having to control smallpox (the There has been only limited interest zuela and India), leishmaniasis (Vene­ global figure is $2.5 billion). Second, in by the private sector in development of zuela and Brazil) and dengue our world there is nothing which is vaccines for the industrialised world, haemorrhagic fever (Thailand). Finally, truly remote and no one from whom and virtually none in vaccines for the many Third World countries have we are disconnected. AIDS has again Third World. The reasons are simple. enormous foreign debt, much of which demonstrated that; another example, Vaccines account for only one per cent will clearly have to be written off. If dengue haemorrhagic fever, which has of the profits of the pharmaceutical even a small portion of that debt were been ravaging the Caribbean, and for industry, and a greater percentage of restructured to be spent in local cur­ which an effective vaccine has not yet their liability. Because of the numbers rency for health and education, several been marketed, is predicted to spread of people involved there must be of the problems affecting the quality of in epidemic proportions to parts of the incentives to develop and deliver vac­ life in the Third World could be United States. cines and essential drugs to the Third addressed. Finally, it is becoming more and World. It should at least be possible to more clear that poverty and disease establish cost-plus agreements with One world have not only a moral impact but a international agencies to develop The First World is the place where political price. Ultimately, what is the potentially useful interventions, or joint 13 per cent of the world's people cost of political turmoil? We have the ventures or affiliations in developing consume the major part of the planet's resources to make vaccines and countries. crude resources, most of which come essential drugs available to the people The imagination and resources of from the Third World. In the United of the Third World; what we need are the private sector that were so instru­ States we spend annually over $300 the imagination and the will. • mental in developing biotechnology billion on "defence:" a single B-2 should be engaged, and the private "stealth" bomber costs $532 million. In • Dr Bloom published a longer version of this sector may find that it has something terms of personal consumption, $55 article in Nature, Vol. 342, November 1989.

W ORLD HEALTH , June-J ul y-August 1990 15 Training Grants

One of the ways in which TOR helps tropical countries is by making training grants widely available to well-motivated research-workers

he UNDP/World Bank/WHO Special Pro­ gramme for Research and Training in Tropical Diseases (TDR) has recruited into its worldwide network some 5,000 scientists from 135 countries. They 1Linclude men and women working in a wide range of disciplines, from molecular biology and pharmacology to epidemiology and sociology. TDR has a two-fold objective: to support research directly, and to strengthen the capability of countries to carry out research. In this second field, it is clear that research directly related to the control of tropical diseases should begin and end with the reality of field conditions; and it should ideally be carried out by scientists most closely in touch with that reality. On these pages we show some of the eager young scientists who have benefited from TDR training grants, with the intention of then returning to their home countries to "plough back" what they have learnt in very practical applications in the field.

Above: Mr Pradya Somboon from Thailand, Eliza­ beth L. Makubalo from Zambia and Mrs Manisri Puntalarp from Thailand - research trainees at the London School of Tropical Medicine and Hygiene. Above right: A research grant-aided worker exam­ ines a blood sample in Cote d'lvoire for signs of sleeping sickness infection. Right: Dr Thomas C. Nchinda, from Cameroon, vetting grant applicati~ns with two other members of the TOR staff in Geneva. Institutions usually find that it takes as much as a year for their applications for research grants to be processed.

16 A social worker discusses the control of lymphatic filariasis with villagers in Kerala, India. Priority is given to field-related research training in the context of strategies to control one or more of TOR's target diseases. Applicants for grants must have an aptitude for research, and must be willing to return home after training and work there for at least three years.

WORLD HEALTH. June-July-August 1990 17 to push forward the development process of these and other com­ pounds. WH: Where do you think TOR should Agood mix place its main efforts over the next decade? SB: I'd say we have a real need for Swedish researcher Professor Sune Bergstrom, who in new diagnostic tools, especially as we 1982 shared the Nobel Prize for his work on prostaglan­ now have the biotechnology to pro­ dins, participated in the creation of TOR in the mid-1970s duce them. If we can get cheap, effective diagnostic tools into the field , and has since kept a close watch on its progress. He we could really map the extent of these was asked for an "interested researcher's" view of TOR . diseases and pinpoint where control efforts should be focused.

WHO/Zafar WH: How do you see the role of a programme like TOR in the interna­ tional scientific community? SB: TOR is really a collection of international research councils. Each steering committee - on malaria vac­ cines, leprosy drugs, biological vector control tools and so on - is made up of independent scientists, experts in the different fields. They decide how much money should be spent on a research project, who will do it, and ultimately whether the results are good, bad or indifferent. They make the decisions that matter scientifically. But they are not bothered with the bureaucracy. It's the secretariat in Gen­ eva that ensures the day-to-day run­ ning of the programme. That's the reason for the success of TOR, I'd say. Like a scientific research council, the scientists can enlist the enthusiasms and energies of other scientists much more easily than the bureaucrats. And a steering committee is not like an advisory committee, whose advice can be taken or not. Its decisions must be 1DR made it possible to coordinate acted upon. Its scientists are fully trials of multidrog therapy for leprosy in involved in the action wherever it is ten countries. Right: The annadillo taking place. selVes researchers as a host in which to WH: On what basis do you judge TOR cultivate the leprosy bacillus for vaccine to be successful? production. SB: Look at the standing WHO has gained in the scientific community over maceutical industry? WH: Do you think TOR is achieving the last 15 years. That is largely due to SB: TOR's strength in relation to the the right balance between field and TOR and to the other programmes in drug industry is in the setting up and laboratory or basic research? WHO that have been modelled on running of clinical trials of drugs and SB: Yes. Again, leprosy is a good TOR. Consider how the scientific com­ vaccines in the developing world. Take example. TOR has supported research munity has been mobilised: about leprosy. I can't imagine how it would on several fronts at the same time: 5,000 scientists are now part of TOR's have been possible, without TOR, to drug development and combination network - no mean achievement, organize a coordinated trial of the new therapy, both in the lab and in the when you think that for the decade combination drug therapy for leprosy, field; the setting up of armadillo farms after the end of the colonial period, the so-called multidrug therapy, simul­ in several parts of the world and the between 1950 and 1960, few taneously in ten countries. collection of infected armadillo organs, developed country scientists in the Also, when TOR started in the their despatch to London for purifi­ universities and industry had much mid-1970s, there were many cation of the bacillus, and the supply of interest in the tropics. Research on promising drug leads lying around, like pure bacilli to all interested immunolo­ tropical diseases was stagnating or the new anti-malarials mefloquine and gists; then trials of killed Mycobacter­ even declining. That situation has halofantrine. Nothing was being done ium leprae vaccines, while at the same been completely turned around, about them because industry could see time fundamental research on a new thanks to TOR. no chance of a return for its invest­ generation of vaccines is under way in WH: Also in the case of the phar- ment. TOR can take credit for helping the United States and elsewhere. Yes, I

18 W ORLD HEALTH. June-Jul y-August 1990 think it's a good mix. bureaucrats decide what research has course of TOR? WH: You are painting an idyllic picture to be done and where the money SB: I think the programme should of TOR and its work. No problem goes. And then you have TOR's two expand. Funding should double (from areas? main management bodies: the Joint the current US $35 million a year). SB: Of course there are. One problem Coordinating Board, through which And I hope cooperation with the drug is now how to make sure the products the donors to the programme can industry will increase. The big question, of the research will be rapidly follow operations and withdraw their of course, is: How long should such a developed, manufactured and made support if TOR risked losing its opera­ programme exist? Let me answer that available to the least developed coun­ tional independence; and the Scientific with another question: How long tries. Another problem area, a pitfall and Technical Advisory Body (STAC), should a national scientific research really, is the danger of bureaucrati­ TOR's scientific watchdog committee, council exist? No-one would think of sation, or "institutional petrification." which would safeguard against institu­ dismantling a national medical True, TOR has some built-in mechan­ tional stagnation. research council. Why dismantle an isms that should protect it from this WH: How do you see the future international one? I think most of the danger, such as a fairly fast statutory world's health problems should have turnover of personnel, with about "TORs" to do research on them. As for three-quarters of steering committee TOR itself, if some of the diseases secretaries changing every three years A vaccine arrives at the delivery point. become so well controlled that further or so. Then, the research council "/ think most of the world's health research won't be needed, TOR approach that I already mentioned problems should have TDRs' to do research on them.,, could take on other diseases, like ensures that scientists rather than tuberculosis. •

W ORLD HEALTH. J une-July-August 1990 19 Breaking new ground by Or Carol Vlassoff Secretary, TOR Steering Committee on Social and Economic Research

esearch on tropical targeted to the communities most in out in the neighbouring district of diseases is coming need of them. Kilosa, with its 168 schools and closer to where the The Swiss researchers noted that 15,000 schoolchildren and proved action is. By its nature using a country's health system to equally successful. The teachers them­ and objectives, social investigate the prevalence of a disease selves were found to be capable of and economic research is primarily had, in addition to speed and low cost, being taught to counter-check the concerned with on-the-spot field the merit of involving several sectors of children's questionnaire results quite issues. Here are some examples of the community - village elders and accurately by dip-stick testing of urine dogma-toppling findings of such local party chiefs, the district admin­ samples. In an extension of these pilot research, some of it supported by istration and education systems, and studies, the school questionnaire IDR. the children of the villages. They also method is being tested in a further To find out how severe a problem foresaw the possibility of using teachers urinary schistosomiasis is in a district of to administer schistosomiasis drug the United Republic of Tanzania, a treatment to children identified as Bulinus truncatus, the water-snail team of scientists from the Swiss being infected. which transmits schistosomiasis to Tropical Institute in Basle found that The method was subsequently tried human beings. asking teachers and children in schools gave information almost as reliable as that provided by a complicated, expen­ sive scientific field study. It is certainly faster and cheaper, reports Marcel Tanner, who headed the Institute's project. For the school project, simple ques­ tionnaires were sent to the head teachers and to all children aged between seven and 14 in the 77 schools of Kilombero District, in eastern Tanzania. Village chairmen in the 4 7 villages of the district received the same questionnaire as the head teachers: both groups were asked to rank by severity a list of diseases common in the area. The children's questionnaire asked them to tick off the diseases for which they had had symptoms during the previous month. Questionnaire results were compared with those from a mobile laboratory that tested the urine of children in 54 of the schools for schistosome eggs and blood (the main signs of urinary schistosomiasis). Within four weeks, results were available from the school question­ naires as compared with three months for the village chairmen and for the mobile laboratory. Information from the school questionnaires showed a 95 per cent concordance with that from the mobile laboratory tests - at about one hundredth of the cost. Although the method does not provide a quanti­ tative evaluation of disease severity, it was, Or Tanner reports, certainly accurate enough to enable anti­ schistosomiasis interventions to be 20 eight African countries: Cameroon, Congo, Ethiopia, Malawi, Nigeria, Zaire, Zambia and Zimbabwe. The researchers believe such methods could also be used for other diseases, such as river blindness (onchocerciasis) and sleeping sickness. * * * Venezuelan peasants and the triato­ mine bugs that transmit Chagas disease unfortunately like the same kind of housing, with mud walls and palm thatch roofing. The bugs live in cracks in the mud walls and glue their eggs to the palm roofing. Spraying these houses with insecticide is expen­ sive, as well as unpleasant for the house owners. Government schemes for providing the campesinos with "bug-proof" modern prefabricated houses have foundered; the poorest peasants, those at highest risk of the disease, find them too expensive and uncongenial. More than one-third of 200,000 such houses under construc­ tion in Venezuela over the past ten years have remained unfinished because the owners default on house loan repayments. A new pilot scheme, using such local building materials as earth, wood and stone to improve houses or provide new ones more in line with the traditional dwellings, is meeting with considerable success, according to Roberto Bricefio-Le6n, sociologist at the Venezuela Central University. He heads a research team running the scheme in collaboration with the Housing Department of the State of Cojedes. The villagers were shown how to build the houses and were paid to participate in the construction work. They received loans for the materials used. Twenty houses were built, all com­ pleted within three months compared with more than ten years for the government's prefabricated houses. All the owners repaid their loans before the due date. The least expensive "bahareque" houses cost between US $150 and $300, and the better­ equipped houses using stabilised soil blocks $1,300. The government houses cost $2,000 and $4,000 respectively. Tests conducted after the houses were built showed that they were all free of triatomine bugs. On the strength of these results, the

Schoolchildren and their teachers in Tanzania proved to give as reliable information on schisto as an expensive Held study.

WHO/ ILO W ORLD HEALTH. J une-July-August 1990 21 Breaking new ground Venezuelan Ministry of Health is planning a similar project to provide 3,000 homes in regions where Chagas disease is endemic. One spin-off from the scheme reported by Or Briceno­ Le6n was a boost to the self-esteem of the campesinos, who are often regarded as social outcasts. Many of them are now building houses of their own, without government help, using techniques they learned during the scheme. Another spin-off was the preparation of a manual which pro­ vides simple instructions on how to improve or build low-cost rural hous- . ing. The Pan American Health Organi­ zation (PAHO) is distributing this throughout Latin America. * * * Setting up a primary health care service in a developing country, how­ ever well-organized and well­ intentioned, by no means guarantees that it will be used by the local population, according to growing evi­ dence from sociological research. Health workers overlooked One study conducted in a fertile, fairly well-developed district of Burkina Faso found that villagers turn to community health workers in only three per cent of cases of serious illness and nine per cent of cases of mild illness. In the vast majority of instances, other members of the family or professional nurses are the first to <» be consulted. Only two per cent of ~ toddlers are taken by their mothers to ~ the community health workers. Even 0 with diarrhoea, a condition considered ~ by WHO to be eminently treatable with oral rehydration therapy through a A health inspector engaged in the hunt Gerais, Belo Horizonte. Malaria epi­ primary health care service, community for mosquito larvae reflects sunlight into demics, sometimes reaching alarming health care workers are consulted in a water barrel, a common source of proportions, have been breaking out only three per cent of cases. local malaria epidemics among among workers attracted to the new These findings are in line with low Brazilian gold miners. areas being opened up for settlement utilisation rates reported for com­ and economic development. munity health worker programmes in Gold miners, who work and sleep other developing countries: 0.6 to 35 studies pointing to under-utilisation of outdoors, run a more than lOO-fold per cent in different studies in Indone­ modem health care services provided risk of the disease compared with sia, two per cent in a Thailand study, in the name of primary health care other categories of workers in the area, 19 per cent in Tanzania and Peru, and seems to be that these services ought the study found. But the miners were 54 per cent in India. to take into account the health care not unhappy about the danger A social and economic research needs of community members as they because it kept down the numbers of project funded by TOR in the Philip­ themselves perceive them. newcomers to the area and hence pines, found that people with swelling potential competitors for the limited of the scrotum due to filariasis pre­ labour market. They were therefore ferred to consult folk healers. Their * * * unwilling to cooperate in malaria con­ methods of applying heated stones, Gold miners in Brazil's Amazon trol activities. On the strength of these herbs and abdominal massage were region view malaria as a blessing in findings, the malaria control efforts of considered by the patients to be as disguise, according to a recent study the Brazilian public health control effective as those of modem medicine, made by the Centre for Regional agency SUCAM will focus on control much less costly and more accessible. Development and Planning (CEDE­ of local epidemics among the gold The message from these and other PLAR) at the University of Minas miners. •

22 WORLD HEALTH, June-July-August 1990 Aglobal response to climate change by Dr Enrique H. Bucher Centre for Applied Zoology, University of Cordoba, Argentina

)though scientists are the forest species would probably the triatomine bugs. As winter tem­ still not certain, it is decline, a process hastened by a peratures rose, there might also be a reasonable to suppose greater frequency of forest fires and lengthening of the insects' summer that an increase in the loss of the soil moisture needed for reproduction and disease transmission proportion of "green­ forest regrowth. Urban forms of leish­ period in temperate areas like Argen­ house gases" in the atmosphere - maniasis, on the other hand, may tina and Chile. As vegetation changed, carbon dioxide, methane and chloro­ spread into newly warmed-up areas bugs with greater potential for trans­ fluorocarbons - could lead to global towards the poles. mitting the disease could in certain warming. What is certain is that there regions predominate over bugs with has been a steady increase in carbon less or no disease-transmitting dioxide in the atmosphere over the potential. past 40 years or so. The other gases In Africa, diminished rainfall and may have increased to an even greater subsequent progressive desertification extent. If present trends continue, by may restrict the areas of vegetation in the year 2100 there could be a rise in which the tsetse fly vectors of sleeping sea levels of between one and three sickness (African trypanosomiasis) live. metres and, by the middle of the next Increased rainful would have the century, an increase of between 2.5 opposite effect. and 5.5 degrees Centigrade in the planet's overall temperature, accom­ Large scale migration panied by a greater frequency of .g The effects of global climatic change severe storms. 0:- on schistosomiasis, a typically water­ Such climatic changes could affect j related disease, would vary depending the epidemiological patterns of the ] on local changes in water patterns. tropical diseases in several ways. 1:0 Where these become more irregular, Increases in rainfall and temperature, ~ the breeding habits of the water snail - for example, could expand the areas of ~ the intermediate host of the schisto­ the world inhabited by malaria-canying ·~ some worms - could be disturbed. On Anopheles mosquitos towards the ~ the other hand, a growing water poles. The disease would thus spread '----""'------~-----' shortage could lead to large-scale into areas where it has never existed or The bloodsucking bug which transmits human migrations and an increase in where it has been eradicated. On the Chagas disease. dam building for irrigation, two factors other hand, such an effect might be that could accelerate the spread of the counterbalanced by a "drying-out" and disease into new areas. further desertification of tropicai Chagas disease, or American trypa­ Another water-related disease, fila­ regions, depriving large areas of the nosomiasis, is to a large extent isolated riasis, might also be affected by global water conditions necessary for mos­ from the effects of climatic change, warming. The blackfly vectors of quito survival. But on the whole, since the triatomine bugs that transmit onchocerciasis (river blindness) and increasing temperatures could be it tend to live in poorly constructed the mosquito vectors of lymphatic expected to increase the reproduction rural houses, a habitat unlikely to be filariasis (elephantiasis) would repro­ rates both of the parasites and their affected by global warming. But if the duce more quickly if there is a rise in vectors and hence augment transmis­ global warming and decreased rainfall the temperature and oxygen-content sion of malaria. lead to an expansion of semi-arid of water. savannas, like the Gran Chaco of Generally speaking, increased tem­ Forest habitat Argentina and Paraguay, these areas peratures would raise the reproductive In the case of leishmaniasis, conti­ might be invaded by peasant farmers rates of disease vectors, adding to nued exploitation of tropical forests culturally adapted to semi-arid condi­ vector control difficulties. As a conse­ could lead first to an increase in the tions. The result could be a replay of quence, the shorter generation times proportion of forest forms of the the sad cycle of overgrazing, forest for these vectors could favour the disease, as the parasites take advan­ destruction and poverty typical of such emergence of strains resistant to pes­ tage of greater access to potential areas elsewhere in the world. ticides. human victims. As they are gradually Poor housing, a concomitant of this So what can be done? Unless deprived of their forest habitat, though, scenario, would ensure the spread of galloping population growth, fuel burn-

W ORLD HEALTH. June- July-August 1990 23 Schistosomiasis (or bilharziasis), multi-faceted, interconnected web of disease so as to detect trends at their onchocerciasis (river blindness) and changes and their possible effects on earliest stages. Adaptive strategies will lymphatic filariasis (elephantiasis) - tropical health. Planning in anticipa­ have to be decided through coordi­ these are among the diseases that could tion of these changes will have to nated national and international be encouraged by global warming. extend much further into the future, planning, in which tropical health con­ since short-term, stop-gap solutions will cerns should be an integral part. be quickly overtaken by the rapid pace ing and deforestation can be halted in of events. A global solution time, the available evidence strongly One topic of research should investi­ In short, to deal with such a global suggests that we will experience unpre­ gate how vectors and parasites are problem, we need a global response. cedented changes in our environment. likely to respond to changing condi­ As far as health and disease are There is no time to waste. Research tions. Systems should be set up as concerned, who is more suited to will have to be organized on a far more soon as possible to monitor changes in organizing such a response than a multi-disciplinary basis to explore the vector distribution and the incidence of global body like WHO? •

24 W ORLD HEALTH, June-July-August 1990 Planetary responsibility

Or Pierre Joly, President of the International Federation of Phar­ maceutical Manufacturers Associations (IFPMA) and Chairman of the French pharmaceutical firm Roussei-UCLAF, discusses the difficulties of motivating the drug industry to deve lop drugs for tropical diseases.

WH: Is the drug industry really losing ment budget, development used to PJ: That about sums it up_ Up to the interest in tropical diseases? account for 30 to 45 per cent, and end of the 1960s, most drug firms had PJ: There is a problem. It is related to research for the rest. Now it's the a regular budget line for tropical constraints that are being put on the opposite; research rarely gets more disease research. Important discoveries drug industry by developed country than 45 per cent of the cake. This is were made by the industry, like the governments, who are having to cope also a deterrent factor in the search for sleeping sickness drug pentamidine with increasingly expensive health new drugs for tropical diseases. and the anti-onchocerciasis drug iver­ budgets and therefore tend to exert WH: You are really saying that, mectin. Nowadays, many firms still do pressure on the prices and conse­ because of financial constraints put on tropical disease research, but in defi­ quently on the profit margins of the the industry by the industrialised coun­ ance of all commercial logic - more drug industry. This tendency creates tries, drug firms cannot indulge in the out of the goodness of their hearts. three kinds of barriers to research by luxury of research on the unprofitable And if nothing is done to alleviate the industry into tropical disease drugs. Third World market? current pressures on domestic First, drug firms are obliged to narrow their choice of research fields to the least risky; from an economic point of view, tropical diseases consti­ tute the most risky area of research, where it is almost impossible to foresee or plan for future returns. Second, drug firms must choose the most profitable research area, the one which will produce the greatest returns on research and development invest­ ment; again, that tends to rule out Third World diseases. Third, the choice of molecules to be developed must be narrowed down. Given the rising costs of development, this means that if a firm finds five or six promising molecules, it will have to limit further testing and development to only one or two. WH: You say development costs are rising. To what extent? PJ: Generally speaking, developing a new drug has become a highly complex and extremely costly business. Research and development costs represented 10 to 12 per cent of sales a few years ago. They are currently about 15 per cent. The cost and difficulty of getting a drug registered are becoming enormous; it now takes 10 to 12 years and between US $100 and 150 million to develop a single drug. Within the research and develop-

A leprosy patient with his healing pills in the Philippines. "It's clearly our moral duty to produce drugs for the Third World."

WORLD HEALTH, June-July-August 1990 25 Planetary responsibility -

Left: Taking a skin sample from a patient in a leprosy ward in Pakistan_ "From an economic point of view, tropical diseases constitute the most risky area of research, where it is almost impossible to foresee or plan for future returns.,

Right: Distributing ivermectin to river blindness suHerers in Cameroon. "/ believe WHO would like the drug industry to undertake a more structured, coordinated, lasting policy towards the developing world., Below: Malaria is transmitted from human to human by the bloodleeding Anopheles gambiae mosquito.

WHO/ Zafar markets, this goodwill towards tropical help set up a kind of "orphan drug" in the saving of lives, that could diseases could dry up completely. system on the model of the US system, alleviate the suffering of millions, does WH: But even if the developed coun­ whereby drug firms which develop such a firm have the moral right to let tries remove the pressure, it still won't drugs for rare diseases receive fiscal the compound gather dust on a lab make the tropical disease market a and other incentives that compensate shelf because potential patients profitable or enticing one for the drug for the meagreness of the market for couldn't pay for it? It's clearly our industry? these drugs. If tropical disease drugs moral duty to produce drugs for the PJ: No, but you must understand that are treated as "orphans," it might be Third World. But we're not saints. We most drug firms balance their budgets possible to grant fiscal incentives to ask the developed country and recoup their losses on less profit­ drug firms doing research on tropical governments to cooperate with us, to able markets, thanks to their strong diseases. become our partners in our efforts domestic markets. This is particularly In other words, the cost of the towards developing countries. true of United States firms, but to a research could be considered as a tax WH: The problems of developing lesser extent also of European firms. If write-off in the home countries of the drugs is one aspect of the problem. profit margins are reduced on dom­ drug firms willing to do such research. What about the problems of getting estic markets, there is no leeway for The cost to governments would be drugs to the people who need them in the drug industry to develop drugs for minimal. But it would represent a the tropics? riskier markets. gesture of moral and economic risk­ PJ: During the colonial period, drug WH: As long as present trends conti­ sharing between government and drug distribution was satisfactorily organized, nue, do you see no way out? industry that could help maintain the usually through a well-disciplined PJ: There are ways out. If European drug industry's enthusiasm for doing system run by army doctors and firms became big enough, with bigger research on tropical diseases. pharmacists. This system has dis­ overall budgets, they could perhaps WH: The "barons" of the drug industry appeared in most ex-colonial countries become more adventurous and devote might be motivated, but what would and hasn't been replaced. Often the part of their budgets to tropical disease the share-holders say if a company people prescribing drugs out in the research, but again on the expectation indulges in unprofitable activities? bush are not qualified to do so. And of a major· return on their capital from PJ: Tropical disease research will never one of the big scandals of this century domestic sales. be economically profitable. But what is drug counterfeiting. A personal Another way out would be for about the moral issues? Does a drug example? I recently bought an aerosol international organizations like WHO to firm with a compound that could result presentation of a cortico-steroid in a

26 W OR LD HEALTH. J une-July- August 1990 ORSTOM © tropical country, only to find that the making these gestures. They illustrate can contained nothing but shaving the strong moral commitment towards cream. The same thing is not uncom­ Third World problems that I have been mon with antibiotics. And we have also talking about and that I warmly wel­ found instances of chloroquine tablets come. Nevertheless, from my discus­ which contain little or no active sions with Dr Hiroshi Nakajima, WHO's chloroquine. Director-General, I have the impres­ WH: Could this explain why some sion that WHO is facing a number of malaria patients don't respond to difficulties related to the deployment of chloroquine treatment and are these donated drugs. thought to have chloroquine-resistant Without minimising the humanitar­ malaria parasites? ian motives underlying these gestures, I PJ: It could indeed, although it's believe WHO would like the drug difficult to get reliable figures on this industry to undertake a more struc­ issue. What is needed is a drug tured, coordinated, lasting policy monitoring system in these countries. towards the developing world. The rich The drug industry is organizing training countries, generally, should act from a schemes to improve quality control sense of planetary responsibility and drug distribution in a number of towards the poor countries. And that tropical countries. But again we run up means participating, through WHO and against a paucity of qualified pharma­ the other international agencies, in cists. Many African countries don't activities that could make a real contri­ have a single inspector. The best bution to the development of the poor pharmacists prefer to set up their own countries. At the same time, the drug pharmacies rather than work as civil new river blindness drug, ivermectin, industry should not be expected to servants for their country's ministry of produced by Merck and Company, of bear the whole burden of the poverty health. New Jersey, USA, or the hepatitis B affecting the developing world - a WH: How do you view the gestures of vaccine of Smith Kline & French burden that stems largely from political firms that provide drugs free of charge Laboratories, of Pennsylvania, USA? problems outside the drug industry's to developing countries, such as the PJ: I take my hat off to the firms sphere of action. •

WOR LD HEALTH, June-J uly-August 1990 27 Developing new drugs by Dr David E. Davidson, Jr. Secretary of the TOR Steering Committee on Chemotherapy of Malaria (CHEMAL), and a former Director of Experimental Therapeutics at the Waiter Reed Army Institute of Research, Washington D. C.

rug discovery has example, the largest of the drug com­ available in the near future, thanks to formed the basis of a panies in terms of total drug sales, the close collaboration between TOR number of medical currently spends more than $700 and the pharmaceutical industry in adventure stories million a year on Rand D. advanced development, field testing, known to schoolchil- Often the fruits of drug research, registration and distribution. Future dren.JD The stories of Or Paul Ehrlich although originally directed against a success will depend to a great extent and his "magic l?ullet," and of the different disease, may also find an on TOR's ability to provide mechan­ green mould that fascinated Or important use against one of the isms that encourage industry participa­ Alexander Fleming and led to the tropical diseases - Merck's ivermectin tion and investment in the discovery of penicillin, are classic (Mectizan) is a good example. Origin­ chemotherapy of these diseases. examples. Careful research, laborious ally developed as a veterinary anti­ Historically, plants and animals have chemistry, the screening of thousands parasitic, ivermectin has been jointly been a rich source of medicinal of compounds - and a touch of developed by Merck and WHO substances. Quinine, extracted from serendipity (the happy accident) -are (essentially OCP and TOR) to become the bark of the cinchona tree, is still the main ways of drug discovery. the drug of choice against onchocer­ perhaps the best known "natural" But the development process doesn't ciasis. It may prove equally useful in antiparasitic drug. It is also an excellent end there. treating lymphatic filariasis. example of a compound that gave Drug development is a lengthy, scientists the vital clue to the design of costly and risky undertaking. The synthetic antimalarials based on the industry may spend up to US $150 List of new drugs quinoline nucleus - including chloro­ million over perhaps a 15-year period To a large degree, TOR acts as the quine, amodiaquine and primaquine, to develop a new drug, yet many drugs catalyst between academic researchers as well as the recently introduced will fail late in the development process - in universities and in industry - and mefloquine and halofantrine. or may have to be withdrawn soon the development power of the phar­ Other drug developments have after their introduction because of maceutical industry. The list of new stemmed from basic research into the unanticipated side-effects. Although a drugs developed with TOR support is biology and biochemistry of the target company may claim a patent on the already impressive - ivermectin for parasites, or from fundamental studies basis of a drug's chemistry or produc­ onchocerciasis, multidrug therapy regi­ of biochemical pathways. Or Gertrude tion route, such patents normally last mens for leprosy using dapsone, rifam­ Elion, currently Chairman of the TOR for 20 years - leaving only a few years' picin and clofazimine, and mefloquine Steering Committee for malaria che­ patent protection after a drug goes on and halofantrine to treat multidrug­ motherapy (CHEMAL), along with Or sale during which the company can resistant falciparum malaria. Many George Hitchings, received the 1988 seek to recoup its investment. other drugs are likely to become Nobel prize for medicine for their When we consider drugs against tropical diseases - especially those that mainly affect the poorest communities in some of the poorest nations - the chances of a company recovering its investment on such new drugs will appear most unlikely to such a com­ pany's market analysts. On the multi­ billion dollar world pharmaceutical market, sales of drugs against tropical diseases contribute far less than one per cent. Yet new drugs are being developed. Indeed, the pharmaceutical industry invests a much higher proportion of turnover in research and development (R and D) than most industries of comparable complexity. Merck, for

Computer-drawn molecular models of the anti-malarial drugs mefloquine and halofantrine.

28 W ORLD HEALTH , June-J uly-August 1990 important research on folic acid basis for techniques of "molecular Research workers in Ethiopia testing metabolism. This work led directly to modelling" which aim to design drug urine samples for schistosomiasis eggs. the development of antifolate com­ molecules on an entirely rational basis. pounds which have become important By identifying, isolating and purifying a as anticancer drugs, antibacterials and parasite's drug receptor molecule, a bination therapy may further improve antifungals, as well as antimalarials. pure crystal of this receptor can be treatment efficacy. Trials of ketocona­ In recent years, a revolution of analysed by x-ray crystallography to zole suggest that this antifungal may scientific technology promises a range determine its three-dimensional atomic provide effective oral therapy for some of new tools for drug discovery and arrangement. Using this information forms of cutaneous leishmaniasis, and design. TOR has supported a diversi­ (and very large computers with three­ trials of a topical ointment based on fied programme of fundamental dimensional graphics), chemical mole­ paramomycin are showing promise. research into the target parasites at the cules can be designed with a shape Operational use of ivermectin to molecular level. Knowledge gained that binds to that receptor and exerts treat onchocerciasis is being expanded, from this research has already identi­ the required action. Already this and clinical trials of this drug against fied many biochemical differences approach has helped our understand­ different forms of lymphatic filariasis between parasite and host cells which ing of the mode of action of some are currently in progress. Clinical trials can be exploited for the design of traditional anti-parasitics, such as of eflornithine continue to show selective drugs. To date, over 100 suramin used against African trypano­ success against Gambian sleeping parasite genes have been cloned and somes, and the "designer" technology sickness - particularly in late-stage carefully analysed. For example, two is rapidly evolving. cases with neurological involvement genes cloned from Plasmodium falci­ The continuous efforts of TOR and that usually resist treatment. And for parum have been shown to be its collaborative partnerships with leprosy, there are now several new amplified in chloroquine-resistant industry and research institutions . compounds entering clinical trials. parasites, and appear to be directly throughout the world are bringing to But all these developments would involved in the process by which light many new candidate drugs. Some remain mere curiosities if the develop- resistant parasites excrete chloroquine of these may fail as increasingly . ment process were interrupted. That and thereby escape its antimalarial stringent clinical assessments of safety development process only begins with action. and efficacy are made, but a number the research, design and identification Following the recent discovery that have advanced sufficiently to justify of new compounds. It must then calcium channel-blockers such as vera­ optimism. proceed through the long sequence of pamil and desipramine can reverse this Therapy of severe malaria should be testing, testing and more testing, process of chloroquine resistance, improved by better strategies for the before registration can be granted. The TOR now supports further research use of quinine and by introducing testing still continues as the product is into this mechanism of resistance and artemisinin derivatives; drugs to modu­ evaluated on a progressively larger the design of improved resistance­ late chloroquine-resistant malaria scale, and even after the drug is put on reversing drugs. This has opened up should soon be available for clinical the market or placed into operational entirely new opportunities for drug evaluation, and an improved analogue use. This is why the symbiotic part­ discovery and design using the new of primaquine will also soon enter nerships between industry, the tools of molecular biology. clinical trials. For leishmaniasis, academic world and - in the specific Recent developments in chemistry improved treatment regimes of anti­ case of tropical diseases - TOR are so and molecular biology provide the monials will be introduced, and corn- important and must continue. •

WORLD HEALTH, J une -J uly-August 1990 29 ..:: .: ..:. ..:: ....:::: ...::: ...::: ...:::...... :::: ..:::...... :::::. ... .:::.:::::::...... :: ..:: .=:· ....:::: ...::: ...::: ...:::: ....:::. :::... ::::...... ::: .••••...... ::::::: ...... Editor: Philippe Stroot

people infected with tropical The toll of disease. most live in coun­ tries with less than US $400 tropical per capita income per year, where governments are so diseases poor that they spend an average of only US $4 per Almost half a billion people - one person in ten - person per year on health care. today suffer from tropical Most people with tropical diseases. according to a new disease are in Africa. The analysis made by WHO. Call­ entire population of the con­ ing for major new research tinent - 500 million people ­ and control initiatives to curb is at risk from at least one a worsening situation, WHO estimates the following tropical disease. Eighty per cent - 400 million - of the numbers of people are infected. some of them with African population live in areas where little has been more than one disease ··Fight AIDS Worldwide·· - Malaria - 270 million done to control malaria transmission and where the (more than 90 per cent of the problem remains virtually UN carriers live in sub-Saharan The Postal Administra ­ eva. Vienna and New York. Africa); schistosomiasis - unchanged or is worsening tion has issued a set of They are also available to The most rampant diseases in 200 million ; lymphatic fila­ postage stamps on the theme stamp collectors at UN offices riasis, the cause of elephant­ Africa are malaria, schisto­ of AIDS which may inspire around the world. Produced iasis - 90 million; Chagas somiasis. river blindness. and individual countries to follow in cooperation with WHO, African sleeping sickness disease - 16 to 18 million; suit with their own AIDS­ these UN stamps were Asia is estimated to have onchocerciasis (river related stamps. At a cere­ des ig ned by artists from more than 100 million cases UN blindness) - 17 million; mony held to launch the Colombia. the Federal leishmaniasis - 12 million of tropical disease per year issue. Or Hiroshi Nakajima. Republic of Germany, the leprosy - 10 to 12 million: The most serious diseases are Director- General of WHO Republic of Korea and malaria. schistosomiasis and African sleeping sickness - said: "I congratulate the UN Poland. 25.000 new cases a year. filariasis. In Central and Postal Administration on its The stamps have as their These scourges cause tre­ South America. more than 35 decision to issue these six slogan "Fight AIDS million people are infected. mendous pain and suffering stamps. From this day on, let Worldwide." and Or Naka­ - ranging from ulcers, inter­ There, the most serious us use these stamps to help Jima has urged the 166 nal organ damage and disa­ diseases are Chagas. schisto­ to fight AI OS." member countries of WHO to somiasis and malaria. bling anaemia. to gross Six million of the stamps ­ issue their own stamps on Even Europe is not free of deformities of face and limb. four of which are illustrated this theme. either as part of tropical diseases. Leish­ blindness. brain damage - above - constituted the first World AI OS Day held each and death. maniasis is still endemic in all printing. and are valid for year on 1 December. or on count ries around the Some 2.100 million people postage only at United an appropriate national - half the world's population Mediterranean. and Turkey Nations post offices in Gen- date. • - are at risk of malaria, living still reports cases of malaria in areas where the disease is and leishmaniasis • common; 1.6 billion are at risk of leprosy; more than 900 million of lymphatic fila ­ riasis; 600 million of schisto­ somiasis; 350 million of leishmaniasis; 90 million ri sk Chagas disease; another 90 million risk river blindness; 50 million risk African sleeping sickness. "Beyond their toll of indi ­ vidual illness and death these tropical diseases hav~ insidious effects on society". says Or Hiroshi Nakajima, Director-General of WHO. "They impede national and individual development. make fertile land inhospit­ able. impair intellectual and physical growth, and exact a huge cost in treatment and control programmes." Of the almost half-billion

30 North-South Media Meeting Ne\Nsbriefs By a happy coincidence. Medical schools. Since the publication of the sixth edition the eve of World Health Day. of the World directory of medical schools. the government of on Friday 6 Apri l. coincided the United Arab Emirates has informed WHO of the setting up. with the prize awards cere ­ four years ago. of the Dubai Medical Coll ege for Girls. mony at the end of the 6th In add ition. the government of Trinidad and Tobago has North-South Media Meeting. announced that a Bachelor of Medicine/ Bachelor of Surgery Held under the auspices of course opened last October at the Faculty of Medical the University of Geneva. the Sciences. on the St Augustine campus of the U n1vers1ty of four-day meeting afforded an the West lndies. in Trinidad. opportunity for television fi lm- makers from man y Dentists' gathering. Several hundred specialists in oral countries to sc reen their health are expected to converge on Singapore from 8 to 14 documentary films on a September for the World Dental Congress Held under the variety of social and health auspices of the International Dental Federation - a bodv in subjects official collaboration with WHO - the Congress will encourage Some 48 producers - indi­ exchanges of views on technological advances in dentistrv as viduals. internationa l bodies well as offering a number of svmposia on technical aspects of If you would like to and n o n-governmental the science. A dental trade exhibition is expected to feature obtain the catalogue organizations - entered their some 300 booths. and the social amenities of Singapore will of WHO publications, films. which ranged from not be forgotten. "Clean up the ci ty" made by or receive sample the National Television of Education for health. Singapore is also to be the host copies of other WHO Burundi to "A su blime work of the regional conference of International Union of Health periodicals which you of love" - Cuban Television's Education {IUHE) in Julv Th e Union emphasises that health want to evaluate be­ account of efforts being education is an essential element in the world's health made to integrate hard-of­ programmes and touches all aspects of our lives - through fore pla,cing a sub­ hearing youngsters into childhood. motherhood. working life and old age. The scription~, please con­ society. conference. from 17 to 20 Julv. with its theme "Education tact: World Health Th ree prizes were awarded towards Hea lth for all." offers an opportunitv for internation­ Organization, Distri­ at the end of the Media allv known experts and health professionals from all over the Meeting. The International world to exchange information and gain access to the latest bution and Sales, Television Prize of Geneva in health education technologv This regional meeting will 1211 Geneva 27, was offered for the best f ilm also review the results of the XIV World Conference on Switzerland on the Th ird World and on Health Education, held in June in Helsinki aspects of North-South deve lopment. The Pierre­ * Vaccination handbooks. The Pans-based Agencv for Aiain Donnier Prize - offered Cultural and Technical Cooperation has published two by Te l evisio n Suisse handbooks under the title Daily routine of vaccination Romande - was for the best (Vacciner au quotidien), aimed at health workers in specific entry portraying the human countries. Liberallv illustrated with easv- to- understand dimension of development WORLD HEALTH drawings and graphics. the handbooks are intended for for readers everywhere And the South-North Prize. workers in the Expanded Programme During 1990 there will be no given by Rad io Quebec and on Immunization of Djibouti and change in the cost of a one-year the Ottawa-based Research subscription. (Two-year and Rwanda respectivelv. but readilv lend three-year subscriptions have Centre for Inte rnational themselves to adaptation elsewhere. Development went to the been discontinued). The rates are: The Agencv. set up in 19 70 to serve US$ Sw.fr. best "South" fi lm dealing D 0 French-speaking countries. can One year 20.- 25.- either with South- South supplv copies without charge. on cooperation or w ith North­ WHO also offers its " Health Hori­ request to. Agence de Cooperation zons·· combined subscri ptions to South relations. culture/le et technique. Direction both World Health (six issues per Severa l of the participating year) and the quarterly World Education. 13 qual Andre- Citroen. Health Forum. groups also manned stalls 15015 Paris. France which exhibited aspects of The annual price will be: the efforts being made in the Drug-use during pregnancy. A three-dav conference ~i! D ~5.!r D field of North-South devel­ held in Dublin. Ireland. 14- 16 September. will discuss DES. a ORDER FORM opment while many of the svnthetic estrogen prescribed as an anti-miscarriage drug films and excerpts from the Please enter my one-year from 194 7 to the late 19 70s. DiEthviStilbestrol caused health subscription to debates were transmitted problems to women who took the drug, and to their children. World Health D to a w id e public by local Participants will examine the problems of prescribing drugs Health Horizons D cable TV. during pregnancv. and /iabilitv for drug-induced injurv A special "WHO Even ing" Further information from: DES Action, Maliesingel 46, 3581 I enclose cheque/internationa l was arranged for 5 Apri l. BM Utrecht. Netherlands. • postal order in the amount of: when environmental health specia lists from WHO took part in a public debate. Th e In the next issue Name: guest of honour was the French vu lcanolog ist Haroun The South-East Asia Region of WHO comprises a w id e Street: Tazieff. formerly Minister of range of countrie s. from populous India to the scattered City: Environment of France. • archipelago of the Maldives. The next issue of World Health magazine w ill put the spotli ght on the spec ial Country: ..... heal th concerns of this reg ion and the measures that World Health. The human dimension of develop­ countries are taking to counter these problems. WHO, Avenue Appia. ment in the Third World 1211 Geneva 27. Switzerland

WORLD HEALTH , June-July-August 1990 31 TropJcal dDeases may lurk in the most innocent-looking environment