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

Background and Objectives Cotrimoxazole prophylaxis, currently recommended in HIVexposed, uninfected (HEU) children as protection against opportunistic infections, also has some antimalarial efficacy. We determined whether daily cotrimoxazole prophylaxis affects the natural development of antibodymediated immunity to bloodstage Plasmodium falciparum malaria infection. Methods Using an enzymelinked immunosorbent assay, we measured antibodies to 8Plasmodium falciparum antigens (AMA1, MSP1(19), MSP3, PfSE, EBA175RII, GLURP R0, GLURP R2 and CSP) in serum samples from 33 HEU children and 31 HIVunexposed, uninfected (HUU) children, collected at 6, 12 and 18 months of age. Results Compared to HIVuninfected children, HEU children had significantly lower levels of specific IgG against AMA1 at 6 months (p = 0.001), MSP1(19) 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.