Laboratory methods for the conduct of experimental malaria challenge of volunteers

Experimental malaria challenge trials of volunteers are conducted to determine whether candidate sporozoite vaccines generate protective immunity against the bites of infected mosquitoes. The absence of patent erythrocytic-stage infection and clinical sequelae suggests sterile immunity among vaccinated volunteers. Sterile immunity is validated through laboratory studies that (1) demonstrate the capacity of erythrocytes and serum obtained from each volunteer before challenge to support parasite growth in vitro; (2) confirm parasitaemia by blood culture, and (3) evaluate each volunteer's blood for surreptitious use of antimalarial agents. The bites of experimentally infected laboratory-reared anophelines must elicit a 100% attack rate among non-immunized volunteers. This report presents guidelines for the laboratory methods used to validate the clinical findings during experimental Plasmodium falciparum anti-sporozoite vaccine efficacy trials.