title: The induction and persistence of T cell IFN-gamma responses after vaccination or natural exposure is suppressed by Plasmodium falciparum.
abstract: 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.
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medicine Research (Coast) Kilifi, Kenya. pbejon@kilifi.kemri-wellcome.org
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Jedidah
authors.initials: J
authors.lastname: Mwacharo
authors.forename: Oscar
authors.initials: O
authors.lastname: Kai
authors.forename: Stephen
authors.initials: S
authors.lastname: Todryk
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.forename: Brett
authors.initials: B
authors.lastname: Lowe
authors.forename: Trudie
authors.initials: T
authors.lastname: Lang
authors.forename: Tabitha W
authors.initials: TW
authors.lastname: Mwangi
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Norbert
authors.initials: N
authors.lastname: Peshu
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000704:Analysis of Variance; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D016015:Logistic Models; D008213:Lymphocyte Activation / Q000276:immunology*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D015999:Multivariate Analysis; D018512:Parasitemia / Q000276:immunology / Q000517:prevention & control; D012044:Regression Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*