title: Delayed acquisition of Plasmodium falciparum antigen-specific CD4(+) T cell responses in HIV-exposed uninfected Malawian children receiving daily cotrimoxazole prophylaxis.
abstract: Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4(+) T cells-mediated immunity in HEU children is still not fully understood.
  
  
  
  Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4(+) T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay.
  
  
  
  There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis.
  
  
  
  The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells leads to higher risk to malaria disease remains unknown and warrants further investigation.
authors.affiliation: Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi. herbert.longwe@gmail.com.|Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi. herbert.longwe@gmail.com.
authors.forename: Herbert
authors.initials: H
authors.lastname: Longwe
authors.affiliation: Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi.|Department of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Kamija S
authors.initials: KS
authors.lastname: Phiri
authors.affiliation: Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi.|Department of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Nyanyiwe M
authors.initials: NM
authors.lastname: Mbeye
authors.affiliation: Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi.|Department of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Thandile
authors.initials: T
authors.lastname: Gondwe
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
authors.forename: Wilson L
authors.initials: WL
authors.lastname: Mandala
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. Kondwani.Jambo@lstmed.ac.uk.|Liverpool School of Tropical Medicine, Liverpool, UK. Kondwani.Jambo@lstmed.ac.uk.
authors.forename: Kondwani C
authors.initials: KC
authors.lastname: Jambo
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018890:Chemoprevention / Q000379:methods*; D016207:Cytokines / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology*; D008295:Malawi; D008297:Male; D018811:Maternal Exposure; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*
chemical_list: D000962:Antimalarials; D016207:Cytokines; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
keywords: CD4+ T cells; Cotrimoxazole; HIV-exposed children; Plasmodium falciparum