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Responses after Vaccination or Natural Exposure Is Suppressed by Plasmodium falciparum1
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* Kenya Medical Research Institute, Centre for Geographical Medicine Research (Coast) Kilifi, Kenya;
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom;
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; and
Nuffield Department of Clinical Medicine, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom
Epidemiological observations suggest that T cell immunity may be suppressed in malaria-endemic areas. In vitro studies, animal models, and limited data in humans link immunosuppression with malaria, malnutrition, and other parasitic infections. However, there are no data to determine whether malaria-induced immunosuppression is significant in the long-term, or relative data comparing it with other factors in malaria-endemic areas, so as to measure the impact of malaria, other parasitic disease, nutritional status, age. and location on the acquisition and longevity of IFN-
responses in children in Kenya. We studied these factors in two cohorts of 1- to 6-year-old children in a malaria-endemic area. T cell responses were induced by vaccination in one cohort, and acquired as a result of natural exposure in a second cohort. Serial ELISPOT assays conducted over a 1-year period measured the induction and kinetics of IFN- production in response to the malaria Ag thrombospondin-related adhesion protein. Induced responses in both cohorts and the longevity of response in the vaccinated cohort were fitted to potential explanatory variables. Parasitemia was prospectively associated with reduced IFN--producing T cells in both cohorts (by 15–25%), and both parasitemia and episodes of febrile malaria were associated with 19 and 31% greater attrition of T cell responses, respectively. Malaria may reduce the efficacy vaccinations such as bacillus Calmette-Guérin and investigational T cell-inducing vaccines, and may delay the acquisition of immunity following natural exposure to malaria and other pathogens.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 P.B. holds a Wellcome Trust Training Fellowship (073597), K.M. is funded by the Wellcome Trust, and A.V.S.H. is a Wellcome Trust Principal Research Fellow. This work was supported by the Wellcome Trust and the Gates Malaria Partnership at the London School of Hygiene and Tropical Medicine.
2 Address correspondence and reprint requests to Dr. Philip Bejon, Kenya Medical Research Institute, Centre for Geographical Medicine Research (Coast). E-mail address: pbejon{at}kilifi.kemri-wellcome.org
3 Abbreviations used in this paper: BCG, bacillus Calmette-Guérin; ME, multiple epitope; TRAP, thrombospondin-related adhesion protein; MUAC, mid upper arm circumference; CI, confidence interval.
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