Reducing Malaria Transmission: The Epidemiology and Treatment of Plasmodium falciparum Gametocytemia

Gametocytes are the sexual stage of the Plasmodia life cycle which render malaria cases infectious to mosquitoes. The proportion of P. falciparum malaria cases with gametocytemia and the duration of gametocytemia are varied. Interventions for detecting and treating gametocytemia also differ from those used against asexual parasitemia. In areas of low transmission, such as most of India, the size of the infectious reservoir drives transmission. The purpose of this dissertation was to 1) determine the epidemiology and risk factors for gametocytemia in order to better target interventions, and 2) estimate the effect of primaquine in addition to artesunate+sulphadoxine-pyrimethamine (AS+SP) to guide policy for reducing post-treatment malaria transmission. Using data from therapeutic efficacy studies conducted through the National Antimalarial Drug Resistance Monitoring System from 2009 to 2010, we measured the prevalence of gametocytemia in relation to various clinical and demographic factors. We found that all age groups, including adults, contribute substantially to the reservoir for potential transmission. We identified four risk factors - younger age group, previous antimalarial drug intake, sex, and region - from which we created a clinical algorithm for predicting gametocytemia. The predictive power of the model was low, suggesting the need for a universal approach for anti-gametocyte interventions. We compared trial sites which used primaquine to sites which did not to estimate the additional effect of primaquine. AS+SP with primaquine increased the rate of gametocyte clearance, prevented the development of new gametocytemia, and reduced the area under the gametocyte density over time curve over the study follow-up compared to AS+SP alone. Primaquine was well tolerated and no serious adverse events were reported. Adding primaquine to AS+SP for the treatment of P. falciparum infection in India would decrease the potential for post-treatment malaria transmission.Doctor of Philosoph