Experimentally induced blood-stage Plasmodium vivax infection in healthy volunteers

Abstract

Background: Major impediments to development of vaccines and drugs for Plasmodium vivax malaria are the inability to culture this species and the extreme difficulty in undertaking clinical research by experimental infection.

Methods: A parasite bank was collected from a 49-year-old woman with P. vivax infection, characterized, and used in an experimental infection study.

Results: The donor made a full recovery from malaria after collection of a parasite bank, which tested negative for agents screened for in blood donations. DNA sequence analysis of the isolate indicated that it was clonal. Two subjects inoculated with the isolate became polymerase chain reaction positive on days 8 and 9, with onset of symptoms and positive blood smears on day 14, when they were treated with artemether-lumefantrine, with rapid clinical and parasitologic response. Transcripts of the parasite gene pvs25 that is expressed in gametocytes, the life cycle stage infectious to mosquitoes, were first detected on days 11 and 12.

Conclusions: This experimental system results in in vivo parasite growth, probably infectious to mosquitoes. It offers the opportunity to undertake studies previously impossible in P. vivax that will facilitate a better understanding of the pathology of vivax malaria and development of antimalarial drugs and vaccines. Trial Registration. ANZCTR: 12612001096842.

Keywords: Plasmodium vivax; experimental infection; malaria.

Figures

Figure 1.

The course of Plasmodium vivax parasitemia (A; circles) and pvs25 transcript levels (B; diamonds) in subjects 1 (gray) and 2 (black). Solid and dashed lines represent pre- and posttreatment findings, respectively. Data points marked with X represent time points when blood smears were positive for malaria parasites.