Controlled human malaria infection

Abstract

Background: Since 1986, investigators at Walter Reed Army Institute of Research (WRAIR) have been using controlled human malaria challenge (CHMI) in malaria-naive adults in order to define the protective efficacy of a malaria vaccine and thus guide programmatic decisions on vaccine candidates. Adapting this model to the dengue field could provide similar evidential support for a vaccine or therapeutic product.

Methods: After completing a vaccine regimen, volunteers are bitten by 5 malaria-infected female Anopheles mosquitoes in a controlled environment. Volunteers are then monitored daily for peripheral parasitemia in a hotel setting with 24-hour access to a nurse and physician. If a single verified parasite is detected, effective antimalarials are promptly administered.

Results: The vast majority of the over 1000 volunteers having participated in CHMI clinical studies have done so at US military research centers. Numerous pre-erythrocytic and erythrocytic vaccine candidates have been evaluated safely and without any related serious adverse events using this model, including the soon-to-be licensed RTS,S malaria vaccine.

Conclusion: The lessons learned from over 25 years of experience in consistent, careful preparation and execution of the CHMI model at WRAIR can provide a foundation from which the dengue field can begin to develop a rigorous and safe "CHDI" model.

Keywords: clinical trial; efficacy; malaria; challenge; mosquito.