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 (E_max), 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.