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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-gamma 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-gamma 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-gamma-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.

Original publication

DOI

10.4049/jimmunol.179.6.4193

Type

Journal article

Journal

Journal of immunology (baltimore, md. : 1950)

Publication Date

09/2007

Volume

179

Pages

4193 - 4201

Addresses

Kenya Medical Research Institute, Centre for Geographical Medicine Research (Coast) Kilifi, Kenya. pbejon@kilifi.kemri-wellcome.org

Keywords

T-Lymphocyte Subsets, Cells, Cultured, Humans, Parasitemia, Malaria, Falciparum, Malaria Vaccines, Analysis of Variance, Multivariate Analysis, Logistic Models, Regression Analysis, Double-Blind Method, Lymphocyte Activation, Child, Child, Preschool, Infant, Interferon-gamma