ADAPTIVE-CHANGES IN PLASMODIUM TRANSMISSION STRATEGIES FOLLOWING CHLOROQUINE CHEMOTHERAPY

Both theory and data suggest that malaria parasites divert resources f rom within-host replication to the production of transmission stages ( gametocytes) when conditions deteriorate. Increased investment into tr ansmission stages should therefore follow subcurative treatment with a ntimalarial drugs, but relevant clinical studies necessarily lack adeq uate control groups. We therefore carried out controlled experiments t o test this hypothesis, using a rodent malaria (Plasmodium chabaudi) m odel. Infections treated with a subcurative dose of the antimalarial c hloroquine showed an earlier peak and a greater rate of gametocyte pro duction relative to untreated controls. These alterations led to corre lated changes in infectivity to mosquitoes, with the consequence that chloroquine treatment had no effect oil the proportion of mosquitoes i nfected. Treatment of human malaria commonly does not result in comple te parasite clearance. If surviving parasites produce compensatory inc reases in their rate of similar to those reported here, such treatment may have minimal effect on decreasing, and may actually increase, tra nsmission. Importantly, if increased investment in transmission is a g eneralized stress response, the effect might be observed following a v ariety of antimalarial treatments, including other drugs and potential vaccines. Similar parasite life history counter-adaptations to interv ention strategies are likely to occur in many disease-causing organism s.