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.

Herbert Longwe,Wilson L Mandala,Chris Drakeley,Kondwani C Jambo,Kevin K A Tetteh,Tom Hall,Thandile Gondwe,Kamija S Phiri,Nyanyiwe Mbeye,Adrian J.F Luty

doi:10.1371/journal.pone.0121643

Abstract

Background and ObjectivesCo-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.MethodsUsing an enzyme-linked immunosorbent assay, we measured antibodies to 8Plasmodium 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.ResultsCompared 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.ConclusionsCo-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.

Highlights

Plasmodium falciparum malaria infection is still one of the main causes of under-five child morbidity and mortality in Sub-Saharan Africa [1]
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
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

Summary

Introduction

Plasmodium falciparum malaria infection is still one of the main causes of under-five child morbidity and mortality in Sub-Saharan Africa [1]. Passive transfer studies from adults who are immune to malaria have shown that naturally acquired antibodies to P. falciparum are protective against malaria infection [6,7]. Exposure to P. falciparum antigens in children is essential for the acquisition of an effective antibody immune response and substantial disruption of this exposure may delay the development of this humoral immunity against malaria. Antibodies are surrogates of exposure to P. falciparum and acquisition of effective immune responses [10]. We determined whether daily co-trimoxazole prophylaxis affects the natural development of antibody-mediated immunity to blood-stage Plasmodium falciparum malaria infection

Methods

Results

Conclusion