Successful sporozoite challenge model in human volunteers with Plasmodium vivax strain derived from human donors.

Successful establishment of a Plasmodium vivax sporozoite challenge model in humans is described. Eighteen healthy adult, malaria-naïve volunteers were randomly allocated to Groups A-C and exposed to 3 +/- 1, 6 +/- 1, and 9 +/- 1 bites of Anopheles albimanus mosquitoes infected with P. vivax, respectively. Seventeen volunteers developed signs and symptoms consistent with malaria, and geometric mean prepatent periods of 11.1 days (9.3-11) for Group A; 10.8 days (9.8-11.9) for Group B; and 10.6 days (8.7-12.4) for Group C, with no statistically significant difference among groups (Kruskal-Wallis, P = 0.70). One volunteer exposed to eight mosquito bites did not develop a parasitemia. No differences in parasite density were observed and all individuals successfully recovered after anti-malarial treatment. None of the volunteers developed parasite relapses within an 18-month follow-up. In conclusion, malaria-naive volunteers can be safely and reproducibly infected with bites of 2-10 An. albimanus mosquitoes carrying P. vivax sporozoites. This challenge method is suitable for vaccine and anti-malarial drug testing.

Selection of antifolate-resistant Plasmodium falciparum by sulfadoxine-pyrimethamine treatment and infectivity to Anopheles mosquitoes.

Resistance-conferring mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Plasmodium falciparum are selected by treatment with sulfadoxine pyrimethamine (SP). We assessed the association between these mutations and transmission capacity of parasites to Anopheles mosquitoes on the Pacific coast of Colombia. Patients with uncomplicated P. falciparum malaria received SP treatment and were followed-up to compare the prevalence of DHFR and DHPS mutations before and after SP treatment. Membrane feeding assays were used to measure infectivity to mosquitoes of post-treatment gametocytes with and without these mutations. Per-protocol treatment efficacy was 95.0% (132 of 139). Gametocytes carrying resistance-conferring mutations were selected after SP treatment and were infective to mosquitoes. Seven days after treatment, infections with two DHFR mutations had a 10-fold higher probability of infecting mosquitoes than infections with no DHFR mutations (odds ratio = 10.23, P < 0.05). Low-level drug resistance mutations have the potential to enhance transmission of P. falciparum and spread resistant parasites.