Effect of chemotherapy on malaria transmission among Yanomani Amerindians: Simulated consequences of placebo treatment

To determine whether chemotherapy effectively reduces Plasmodium falciparum malaria transmission in isolated human populations, we followed two abrupt sequential outbreaks of malaria infection among Yanomami Amerindians and modeled the effect of chemotherapy and the consequences if no drug was available. A Macdonald-type mathematical model demonstrated that both outbreaks comprised a single epidemic event linked by an Invisible outbreak in vector mosquitoes. The basic reproductive number, R-0, from fitted values based on the treated epidemic was 2 during the initial phase of the epidemic, and waned as vector density decreased with the onset of the dry season. In the observed epidemic, 60 (45%) of 132 village residents were affected, and che treated outbreak ended after two months. Although the initial chemotherapy regimen was only marginally effective, the duration of human infectivity was reduced from an expected nine months to two weeks. In the absence of this intervention, the initial R-0 value would have been 40, more than 60% of the population would have been infected, and more than 30% would have remained parasitemic until the next rainy season (about six months later). Another outbreak would then have ensued, and malaria probably would have remained endemic in this village. Our simulated placebo treatment permits us to conclude that even partially effective chemotherapeutic interventions, such as those in our study, interrupt serial transmission of P. falciparum among isolated human populations that are exposed to infection seasonally.