Antimalarial drug resistance
Nicholas J. White
Nicholas J. White
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Antimalarial drug resistance

Abstract

Malaria, the most prevalent and most pernicious parasitic disease of humans, is estimated to kill between one and two million people, mainly children, each year. Resistance has emerged to all classes of antimalarial drugs except the artemisinins and is responsible for a recent increase in malaria-related mortality, particularly in Africa. The de novo emergence of resistance can be prevented by the use of antimalarial drug combinations. Artemisinin-derivative combinations are particularly effective, since they act rapidly and are well tolerated and highly effective. Widespread use of these drugs could roll back malaria.

Authors

Nicholas J. White

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Opportunities for the de novo selection of antimalarial drug resistance ...
Opportunities for the de novo selection of antimalarial drug resistance in an area of high transmission (entomological inoculation rate 50 per year; each inoculation is depicted as a green arrow) in a young child treated for acute falciparum malaria with a slowly eliminated drug such as mefloquine (red dotted line). The initial infection (infection 1) is eliminated. The next infection acquired (infection 2) is also eliminated. Infections 3 and 4 are suppressed temporarily but eventually reach detectable densities. Infections 5 and 6 are under no selection pressure and also reach detectable densities. The inset shows the pharmacodynamic events, the relationship between concentration (C) and effect (E). When mefloquine levels fall below the minimum parasiticidal concentration (MPC) giving maximum parasite killing (Emax), then the rate of decline in parasitemia (PRR) falls until the PRR reaches 1. This results from an MIC of mefloquine and occurs in infection 3. Thereafter, parasitemia rises again and becomes detectable nearly 6 weeks after initial treatment.