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Infection and Immunity, April 2004, p. 2248-2253, Vol. 72, No. 4
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.4.2248-2253.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Measuring the Effects of an Ever-Changing Environment on Malaria Control
Thomas F. McCutchan,1* K. Christiana Grim,1 Jun Li,2 Walter Weiss,3 Darmendar Rathore,1 Margery Sullivan,1 Thaddeus K. Graczyk,4,5 Sanjai Kumar,6 and Mike R. Cranfield4,5Laboratory of Parasitic Diseases, Section of Growth and Development, National Institute of Allergy and Infectious Diseases, National Institutes of Health,1 Division of Emerging Transfusion Transmitted Diseases, Center for Biologics Review and Research, Food and Drug Administration, Bethesda,6 Malaria Program, Naval Medical Research Center, Silver Spring,3 Johns Hopkins School of Medicine, Johns Hopkins University,4 Medical Department, The Baltimore Zoo, Baltimore, Maryland,5 Pathology Department, Saint Clare's Hospital, Denville, New Jersey2
Received 2 September 2003/ Returned for modification 26 October 2003/ Accepted 31 December 2003
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., naïve to malaria infection, vaccinated naïve, and immune) directly into an area where avian malaria, Plasmodium relictum, is endemic. In our study setting, canaries that are naïve 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 naïve 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.
* Corresponding author. Mailing address: Laboratory of Parasitic Diseases, Section of Growth and Development, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892-0425. Phone: (301) 496-6149. Fax: (301) 402-0079. E-mail: tmccutchan{at}niaid.nih.gov.
Infection and Immunity, April 2004, p. 2248-2253, Vol. 72, No. 4
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.4.2248-2253.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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