In endemic areas, mosquito contact can be minimized with the use of house screens, in-secticide bombs within rooms, and/or insecticide-impregnated mosquito netting around beds. Those who must be outside from dusk to dawn, the period of mosquito feeding, should apply insect repellent and wear clothing with long sleeves and pants. In addition, it is possible to suppress clinical manifestations of infection, should they occur, with a weekly dose of chloroquine. In areas where chloroquine-resistant strains are common, an alternative schizonticidal agent should be used. Mefloquine or doxycycline are usually preferred. The antifolate pyrimethamine plus a sulfonamide can be taken as well. How-ever, use of this combination is occasionally accompanied by serious side effects, so it is recommended only when mefloquine- and doxycycline-resistant strains are present in the area, and then only for individuals residing in areas of intense transmission for prolonged periods of time. On leaving an endemic area, it is necessary to eradicate residual hepatic parasites with primaquine before discontinuing suppressive therapy.
Malaria control measures have been directed toward reducing the infected human and mosquito populations to below the critical level necessary for sustained transmission of disease. The techniques employed include those mentioned previously, treatment of febrile patients with effective antimalarial agents, chemical or physical disruption of mos-quito breeding areas, and use of residual insecticide sprays. An active international coop-erative program aimed at the eradication of malaria resulted in a dramatic decline in the incidence of the disease between 1956 and 1968. Eradication was not achieved, however, because mosquitoes became resistant to some of the chemical agents used, and today malaria still infects 200 to 300 million inhabitants of Africa, Latin America, and Asia. Tropical Africa alone accounts for 100 million of the afflicted and for most of the 1 to 3 million deaths that occur annually as a result of this disease. The long-term hope for progress in these areas now depends on the development of new technologies.
Three advances in the last decade have produced the hope that an effective malaria vac-cine might be within reach of medical science for the first time. The establishment of a continuous in vitro culture system provided the large quantities of parasite needed for antigenic analysis. Development of the hybridoma technique allowed the preparation of monoclonal antibodies with which antigens responsible for the induction of protective immunity could be identified. Finally, recombinant DNA procedures enabled scientists to clone and sequence the genes encoding such antigens, permitting the amino acid structure to be determined and peptide sequences suitable for vaccine development to be identified.
As immunity to malaria is stage specific, the relative advantages and disadvantages of vaccines prepared against each of the plasmodial stages found in the human host (sporozoite, merozoite, and gametocyte) need to be considered. An effective sporozoite vaccine, by blocking the invasion of hepatocytes by mosquito-introduced sporozoites, would prevent the establishment of the infection within the host and, if widely adminis-tered, would interrupt parasite transmission within a community. However, to be effec-tive, a sporozoite vaccine would have to prevent the invasion of all injected sporozoites. Theoretically, if even a single parasite reached and penetrated a liver cell, it would mul-tiply intracellularly and later enter the bloodstream to invade erythrocytes. The patient could develop clinical disease and serve as a reservoir for subsequent transmission to others. A vaccine directed at the erythrocytic or merozoite stage, although preventing neither hepatic nor bloodstream infection, would limit the severity of the parasitemia and thus moderate or abort clinical manifestations of disease. Gametogenesis, and thus parasite transmission, would probably proceed unimpaired. Antibodies formed in re-sponse to a gametocyte vaccine might block the union of male and female gametes within the mosquito gut, interrupting parasite transmission. It would, however, neither prevent nor moderate malaria in the immunized patient. The limitations of each vaccine type has led some investigators to advocate the combination of all three in a single poly-valent preparation. Unfortunately, the results of field tests of a number of candidate vac-cines have been disappointing.