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. 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/µL. Fever was the only clinical manifestation attributable to parasitemia and only when the parasite density was ⩾5000/µL Sixty-four percent of children with ⩾20,000 parasites/µL versus 10% with 1-4999/µL 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/µL) with or without elevated temperature will be optimally studied in the high transmission season among children <2 years.