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In a randomized controlled trial, chloroquine monotherapy was compared with the combination of artesunate and chloroquine for treating uncomplicated Plasmodium falciparum malaria in 536 Gambian children. Chloroquine-treated children exhibited a 28-day clinical failure rate of 15% (95% confidence interval [CI] = 9.2-22%) compared with 11% (7.8-15%) among children receiving the combination (P = 0.08, by Wilcoxon test). Seventy-three percent of chloroquine-treated children exhibited parasitemia during follow-up compared with 49% of children receiving the combination (relative risk = 1.5, 95% CI = 1.3-1.7; chi2 = 21.18, P < 0.001). A significant reduction in clinical and parasitologic treatment failure in the combination group occurred in the first two weeks following treatment, but this was eroded over weeks three and four of follow-up. The impact of combination therapy on the transmission of chloroquine-resistant parasites is discussed. Chloroquine plus artesunate is not sufficiently efficacious to justify its introduction as a replacement for chloroquine monotherapy in The Gambia.

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Individuals in communities in which different strains of pathogen are circulating can acquire resistance by accumulating immunity to each strain. After considering susceptibility, models of infection and immunity are defined for vector-borne diseases such as malaria and trypanosomiasis. For these models the prevalence of infection, the number of infections per individual, and the mean duration of infection, increase rapidly in young individuals, but decrease in older individuals as immunity is acquired to the various strains of pathogen; the mean interval between successive infections lengthens with age. The bivariate Poisson distribution is shown to be a close approximation to some stochastic processes. The models explain observed cross-sectional patterns of age prevalence, and longitudinal patterns in which individuals typically continue to become infected as they age, albeit with decreasing frequency. In these models the time spent infected depends on parasite diversity, as well as the inoculation and recovery rates. It is shown that control measures can cause an increase in the number of infections and the prevalence of infection in older individuals, and in the average prevalence in the community, even when strain-specific immunity is life-long.