A game of chess / by Michel Lebras

A game of chess t a time when the malaria parasite's resistance to chloro- quine is spreading throughout Africa, all the way from the southern Sahara to South Africa, while resistance to qui- nine and many other drugs-whether taken singly or together-is advancing in certain parts of Asia, tropical Amer- ica and East Africa, pharmacological research has put at our disposal new therapeutical weapons. These are mefloquine, halofantrine, and the derivatives of a Chinese plant called qinghaosu-artesunate and artemether. Operational research is meanwhile helping us to plan the strategies for using these drugs. Studies are being made of their efficacy based on an evaluation of the rates of cures achieved, of their harmlessness (by measuring the degree of tolerance in patients), of their cost (taking into account not only the price of the drug but also the cost of not treating malaria victims), and finally of their accessibility and the degree to which patients observe the prescribed regimens. "Does the large-scale use of the drugs have any overall impact on the malaria situation?" is another impor- tant question. In fact, field trials have already shown that the correct use of these drugs has cut down mortality and considerably reduced morbidity from malaria. A thinking parasite? The malaria parasites are haematozoa-that is, they live in human blood-and it is the small anopheles mosquito which transmits the parasites by biting, at random, first a malaria patient then a healthy per- son. These parasites-and this is more true for Plasmodium falciparum than for any other-have a remarkable capacity for adapting themselves to drugs and thus escaping their effect. For instance, in certain foci in South- The parasite has a remarkable capacity to develop resistance to drugs. Scientists are working hard to find new ones. The microscope slide shows the Plasmodium falciparum inside a red blood cell. WOR LD HEALTH . September-October 1991 by Michel Lebras East Asia, over 50% of the falciparum malaria found are already resistant to mefloquine even though this drug has only been in use since 1984. So it is vital to discover new medicaments. Research workers , exploring various avenues, are thinking up new ways to attack the haemato- zoa; their affinity for certain lipids (fats), for example, seems to offer a potential strategy for creating new drugs. The most serious forms of malaria could be controlled by using drugs which would prevent the infected red blood cells from adhering to the wall of the deep capillary vessels, the for- mation of clusters of red cells in the form of "rosettes", and the release of toxic substances, all of which result in such complications as bleeding and the formation of blood clots in the smallest blood vessels. Promising tests have been made with the antibodies of immunized people, and with chloro- quine, which could play a role in inhibiting the harmful effects of toxic substances. A great number of molecular substances are at present being exper- imented with, either in the laboratory on cell cultures, in animals or in man. Natural substances extracted from the traditional pharmacopoeia, such as the qinghaosu mentioned above, are not being overlooked in these tests. But at present a most promising approach is one which would enable us to overcome resistance to chloro- quine by keeping the drug in contact with the parasite. Certain substances used in the treatment of cardiovascular diseases, such as antagonists of ~ "8 ::::l <Ji ---0 ~ ~ 5: Catching mosquitos to enable research workers to learn more about the enemy. calcium or certain antidepressants and antihistamines, seem to be capable of playing this role when they are admin- istered with chloroquine. Recognizing the parasite Diagnosing malaria at present depends on detecting the haematozoa in the blood by use of the microscope. But this technique, in use for more than a century, is of limited value when there are only a few parasites in the blood. In fact, microscopy does not enable us to distinguish between human carriers of the disease who show no symptoms and active malaria, which calls for treatment. New tests are at pr~ent under development. Thanks to the use of molecular probes we can detect different fragments of the parasite in the blood. One particularly promising tech- nique, already being applied in the field, calls for the blood sample to be separated by centrifuge in capillary tubes and then coloured with acridine orange. This makes it possible to detect the parasites, even when they are few and far between. Today this method is the most sensitive and the quickest. However, its main drawback is the lack of specificity, since it may sometimes give a positive result even when there is no malaria. Also, special microscopes are needed. All the same, molecular biology is undoubtedly 30 making giant strides and gives us plenty of grounds for optimism. And a vaccine? All research aimed at controlling malaria comes up against the complex nature of the parasite. It is possible to interrupt the development of the para- site at several points. The identification and choice of antigens which could form the basis for design of "candidate vaccines" can be narrowed down by analysing the natural history of malarial immunity. Long-term research carried out in the little village of Dielmo in Senegal has given us a better under- standing of how the mediators of immunity operate. In an area where the transmission of malaria still con- tinues, some children have several attacks of fever each month, while others never have them. The research workers are trying to find out why. A new technique now being developed should make it possible to multiply some of the fragments of the parasite which stimulate immunity. These might be used to prepare an effective vaccine. No contact with mosquitos, no malaria If we could prevent all contact between man and the anopheles mos- quito which transmits malaria, this disease would not exist. The advent of synthetic pyrethroids which are cap- able of repelling the mosquitos, such as permethrin and deltamethrin, has given us high hopes of considerably reducing this insect-and-man contact. A game of chess - Deltamethrin in particular is desirable for its efficacy, its long-lasting action (as long as six months) and its harmless- ness for man and the environment. The optimal ways of using these substances depend on the biology of the mosquitos, and this ought, there- fore, to form part of initial entomologi- cal studies. Bednets, especially when they are impregnated with deltameth- rin, have proved to be effective in many evaluation studies. However, a good deal of research still needs to be done before we can say exactly what is the role of impregnated bednets under various epidemiological conditions. There must be no letting up of research. We have to find other weak points in the haematozoa. We need to know more about how to use anti- malarial drugs more effectively, to find better diagnostic techniques for the different forms of malaria, and to improve the planning, programming, management and evaluation of control measures. The haematozoa is ingenious, dauntless and apparently gifted with eternal life. We are playing a game of chess with it. At stake are the lives of the 2000 children who succumb to malaria every day in the world. • Professor Michel Lebras is Director of the Rene Labus- quiere Institute at the Uni- versity of Bordeaux 11 , 146 rue Leo- Saignat , 33076 Bordeaux Cedex, France. WORLD HEALTH. September-October 1991