Impact of transmission intensity and age on Plasmodium falciparum density and associated fever: implications for malaria vaccine trial design

To facilitate design of vaccine trials, malaria was studied in 6-month- to 6-year-old Kenyans during high (HI) and low intensity transmission seasons. During 84 days after cure, exposure to infected mosquitoes was 9-fold greater in the HI group, yet incidence of P. jalciparum infection was increased only 2-fold, with no age effect. The density of recurrent P. jalciparum was 14-fold greater in the HI group, and there was a striking association between age and parasitemia ~5000/f.l,L. Fever was the only clinical manifestation attributable to parasitemia and only when the parasite density was ~5000/IlL Sixty-four percent of children with ~20,000 parasites/ILL versus 10 % with 1-4999/ ILL were febrile when parasitemic. Recurrent P. jalciparum infection as a vaccine trial end point can be studied year-round among children ~6 years in western Kenya. However, high-grade parasitemia (~5000 or 20,000/ILL) with or without elevated temperature will be optimally studied in the high transmission season among children <2 years. To provide a foundation for developing optimal methods for conducting malaria vaccine trials, we evaluated the epidemiol-ogy of Plasmodium falciparum infection in children ~ 6 years of age in western Kenya over a 2 l-month period. Initial report