Experimental Challenge of Volunteers with Malaria

As physicians sworn to “do no harm” and clinical investigators working to develop malaria vaccines and drugs, my colleagues and I have had to repeatedly ask ourselves whether it is ethical to conduct experimental studies of malaria challenge in volunteers. We have discussed that question with members of human trial committees, volunteers, colleagues, and friends and family, many of whom have initially been incredulous to hear that persons volunteer to be infected with the parasites that cause malaria.

Because malaria is a major threat to U.S. troops [1] and persons who travel abroad, the Department of Defense provides funding for us to develop vaccines and drugs to protect nonimmune persons from malaria. As tropical infectious disease specialists, we are also committed to developing vaccines and drugs to reduce the impact of a disease estimated to affect 300 to 500 million persons and kill 1.5 to 2.7 million persons annually [2]. In other words, every 2 to 4 years, malaria kills more persons than AIDS has killed since it was recognized. Given the magnitude of the problem, the fact that the studies have been considered safe and crucial to development of vaccines and drugs, and the fact that that the volunteers have understood the risks and provided informed consent, there has been consensus that infecting volunteers with malaria organisms is acceptable.

Understanding the safety and importance of these studies depends on understanding the life cycle of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale, the parasites that cause malaria in humans. Anopheles species mosquitoes transmit malaria by inoculating small numbers of sporozoites into the recipient's bloodstream. The sporozoites rapidly enter the liver, where they generally develop in hepatocytes during a period of …