Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers

Abstract

A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) and five Duffy (-) subjects were randomly allocated into three (A-C) groups and were exposed to the bites of 2-4 Anopheles albimanus mosquitoes infected with Plasmodium vivax derived from three donors. Duffy (-) subjects were included as controls for each group. Clinical manifestations of malaria and parasitemia were monitored beginning 7 days post-challenge. All Duffy (+) volunteers developed patent malaria infection within 16 days after challenge. Prepatent period determined by thick smear, was longer for Group A (median 14.5 d) than for Groups B and C (median 10 d/each). Infected volunteers recovered rapidly after treatment with no serious adverse events. The bite of as low as two P. vivax-infected mosquitoes provides safe and reliable infections in malaria-naive volunteers, suitable for assessing antimalarial and vaccine efficacy trials.

Conflict of interest statement

Disclosure: Thomas L. Richie and Judith E. Epstein are service members in the U.S. Navy. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military member or employee of the U.S. Government as part of that person's official duties. The contribution of U.S. Navy staff was supported by Work Unit Number 6000.RAD1.F.A309.

Figures

Figure 1.

Probability of thick blood smear (TBS) positivity after Plasmodium vivax malarial challenge by group.

Figure 2.

(A) Relationship between times of patent blood stage infection as determined by thick blood smear (TBS) and salient symptoms. (B) Relationship between day of TBS positivity and severity of symptoms.