Controlled Human Malaria Infection with Graded Numbers of Plasmodium falciparum NF135.C10- or NF166.C8-Infected Mosquitoes

Abstract

Controlled human malaria infections (CHMIs) with <i>Plasmodium falciparum</i> (<i>Pf</i>) parasites are well established. Exposure to five <i>Pf</i> (NF54)-infected <i>Anopheles</i> mosquitoes results in 100% infection rates in malaria-naïve volunteers. Recently <i>Pf</i> clones NF135.C10 and NF166.C8 were generated for application in CHMIs. Here, we tested the clinical infection rates of these clones, using graded numbers of <i>Pf</i>-infected mosquitoes. In a double-blind randomized trial, we exposed 24 malaria-naïve volunteers to bites from one, two, or five mosquitoes infected with NF135.C10 or NF166.C8. The primary endpoint was parasitemia by quantitative polymerase chain reaction. For both strains, bites by five infected mosquitoes resulted in parasitemia in 4/4 volunteers; 3/4 volunteers developed parasitemia after exposure to one or two infected mosquitoes infected with either clone. The prepatent period was 7.25 ± 4.0 days (median ± range). There were no serious adverse events and comparable clinical symptoms between all groups. These data confirm the eligibility of NF135.C10 and NF166.C8 for use in CHMI studies.