Scientific Publications by FDA Staff

Infect Immun 2004 Apr;72(4):2248-53

Measuring the effects of an ever-changing environment on malaria control.

McCutchan TF, Grim KC, Li J, Weiss W, Rathore D, Sullivan M, Graczyk TK, Kumar S, Cranfield MR

McCutchan TF, NIAID, Parasit Dis Lab, Sect Growth & Dev, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Parasit Dis Lab, Sect Growth & Dev, NIH, Bethesda, MD 20892 USA US FDA, Ctr Biol Review & Res, Div Emerging Transfus Transmitted Dis, Bethesda, MD 20014 USA USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20903 USA Johns Hopkins Univ, John Hopkins Sch Med, Baltimore, MD USA Baltimore Zoo, Dept Med, Baltimore, MD USA St Clares Hosp, Dept Pathol, Denville, NJ USA

The effectiveness of malaria control measures depends not only on the potency of the control measures themselves but also upon the influence of variables associated with the environment. Environmental variables have the capacity either to enhance or to impair the desired outcome. An optimal outcome in the field, which is ultimately the real goal of vaccine research, will result from prior knowledge of both the potency of the control measures and the role of environmental variables. Here we describe both the potential effectiveness of control measures and the problems associated with testing in an area of endemicity. We placed canaries with different immunologic backgrounds (e.g., naive to malaria infection, vaccinated naive, and immune) directly into an area where avian malaria, Plasmodium relictum, is endemic. In our study setting, canaries that are naive to malaria infection routinely suffer approximately 50% mortality during their first period of exposure to the disease. In comparison, birds vaccinated and boosted with a DNA vaccine plasmid encoding the circumsporozoite protein of P. relictum exhibited a moderate degree of protection against natural infection (P < 0.01). In the second year we followed the fate of all surviving birds with no further manipulation. The vaccinated birds from the first year were no longer statistically distinguishable for protection against malaria from cages of naive birds. During this period, 36% of vaccinated birds died of malaria. We postulate that the vaccine-induced protective immune responses prevented the acquisition of natural immunity similar to that concurrently acquired by birds in a neighboring cage. These results indicate that dominant environmental parameters associated with malaria deaths can be addressed before their application to a less malleable human system.