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

Abstract

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. falciparum infection was increased only 2-fold, with no age effect. The density of recurrent P. falciparum was 14-fold greater in the HI group, and there was a striking association between age and parasitemia > or = 5000/microL. Fever was the only clinical manifestation attributable to parasitemia and only when the parasite density was > or = 5000/microL. Sixty-four percent of children with > or = 20,000 parasites/microL versus 10% with 1-4999/microL were febrile when parasitemic. Recurrent P. falciparum infection as a vaccine trial end point can be studied year-round among children < or = 6 years [corrected] in western Kenya. However, high-grade parasitemia (> or = 5000 or 20,000/microL) with or without elevated temperature will be optimally studied in the high transmission season among children < 2 years.