title: The effect of daily co-trimoxazole prophylaxis on natural development of antibody-mediated immunity against P. falciparum malaria infection in HIV-exposed uninfected Malawian children.
abstract: OBJECTIVE
  Co-trimoxazole prophylaxis, currently recommended in HIV-exposed, uninfected (HEU) children as protection against opportunistic infections, also has some anti-malarial efficacy. We determined whether daily co-trimoxazole prophylaxis affects the natural development of antibody-mediated immunity to blood-stage Plasmodium falciparum malaria infection.
  
  
  METHODS
  Using an enzyme-linked immunosorbent assay, we measured antibodies to 8 Plasmodium falciparum antigens (AMA-1, MSP-119, MSP-3, PfSE, EBA-175RII, GLURP R0, GLURP R2 and CSP) in serum samples from 33 HEU children and 31 HIV-unexposed, uninfected (HUU) children, collected at 6, 12 and 18 months of age.
  
  
  RESULTS
  Compared to HIV-uninfected children, HEU children had significantly lower levels of specific IgG against AMA-1 at 6 months (p = 0.001), MSP-119 at 12 months (p = 0.041) and PfSE at 6 months (p = 0.038), 12 months (p = 0.0012) and 18 months (p = 0.0097). No differences in the IgG antibody responses against the rest of the antigens were observed between the two groups at all time points. The breadth of specificity of IgG response was reduced in HEU children compared to HUU children during the follow up period.
  
  
  CONCLUSIONS
  Co-trimoxazole prophylaxis seems to reduce IgG antibody responses to P. falciparum blood stage antigens, which could be as a result of a reduction in exposure of those children under this regime. Although antibody responses were regarded as markers of exposure in this study, further studies are required to establish whether these responses are correlated in any way to clinical immunity to malaria.
authors: Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi.
authors: Herbert
authors: H
authors: Longwe
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
authors: Kondwani C
authors: KC
authors: Jambo
authors: Tropical Haematology Research Unit, College of Medicine, University of Malawi, Blantyre, Malawi.
authors: Kamija S
authors: KS
authors: Phiri
authors: Department of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi.
authors: Nyanyiwe
authors: N
authors: Mbeye
authors: Department of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi.
authors: Thandile
authors: T
authors: Gondwe
authors: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Tom
authors: T
authors: Hall
authors: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Kevin K A
authors: KK
authors: Tetteh
authors: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Chris
authors: C
authors: Drakeley
authors: Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
authors: Wilson L
authors: WL
authors: Mandala
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D000917:Antibody Formation / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects*; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008295:Malawi; D008297:Male; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D007074:Immunoglobulin G; D015662:Trimethoprim, Sulfamethoxazole Drug Combination