Abstract
BackgroundPeople living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection.MethodsCross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA.ResultsWithin a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1.ConclusionAvidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as well as their clinical consequences will require additional investigation, ideally utilizing longitudinal data and investigation of a broader array of responses.
Highlights
People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections
Antibody levels in three sites in Uganda Antibody levels and avidity index (AI) were measured in samples from cross sectional surveys conducted at three sites in Uganda
Consistent with published data on antibody prevalence [31], the proportion of all cross-sectional survey samples included in this study increased with transmission intensity for AMA-1 (29.1, 43.6, and 67.7% for Walukuba, Kihihi and Nagongera, respectively) but not merozoite surface protein 1-19 (MSP1-19) (14.6, 34.5, and 27.3% for Walukuba, Kihihi and Nagongera, respectively)
Summary
People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. People living in endemic areas acquire protection from the most severe manifestations of malaria relatively quickly, but protection from uncomplicated clinical disease and control of parasitaemia takes longer and is often acquired only after many years of repeated infections [2]. Passive transfer of immunoglobulin from clinically immune donors to Ssewanyana et al Malar J (2017) 16:67 non-immune individuals with P. falciparum infection alleviated clinical symptoms and reduced the levels of blood stage parasites, indicating that antibodies play a central role in clinical immunity to malaria [3, 4]. The qualities of protective antibodies and precise mechanisms by which they mediate protection are not fully understood
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