Abstract
We sought to identify a subset of Plasmodium falciparum antibody targets that would inform monitoring efforts needed to eliminate malaria in high transmission settings. IgG antibodies to 28 recombinant Pf antigens were measured in residents of two communities in western Kenya examined in 2003 and 2013, when the respective prevalence of asymptomatic parasitemia among children was 81 and 15 percent by microscopy. Annual seroconversion rates based on a sero-catalytic model that dichotomised antibody values to negative versus positive showed that rates were higher in 2003 than 2013 for 1 pre-erythrocytic and 7 blood-stage antigens. Antibody acquisition models that considered antibody levels as continuous variables showed that age-related antibody levels to Circumsporozoite Protein and 10 merozoite proteins increased at different rates with age in 2003 versus 2013. Both models found that antibodies to 5 proteins of the Merozoite Surface Protein 1 complex were differentially acquired between the cohorts, and that changes in antibody levels to Apical Membrane Antigen 1 suggested a decrease in transmission that occurred ~10 years before 2013. Further studies evaluating antibodies to this subset of Pf antigens as biomarkers of malaria exposure and naturally acquired immunity are warranted in endemic settings where transmission has been reduced but persists.
Highlights
Factors affecting this transition likely vary across endemic sites, e.g. differing levels of transmission before vector interventions were expanded; uneven distribution, use and replacement of ITN; insecticide resistance; changes in the dominant mosquito vector species and their biting behavior
We used a panel of 28 recombinant Pf proteins and compared two analytic approaches that have been used to analyze data from cross-sectional serological surveys to evaluate the impact of differing transmission dynamics on Pf antibody responses
Our multiplexed antibody assay included Pf antigens that have previously been evaluated as serologic tools, e.g. Circumsporozoite Protein (CSP), MSP1, MSP2, Apical Membrane Antigen 1 (AMA1) and EBA175 as well as those for which there is less information regarding their potential relevance to monitoring transmission intensity and age-related acquired immunity to symptomatic malaria, e.g. Liver Stage Antigen 1 (LSA1), PfCeltos, PfRH proteins, EBA181
Summary
Factors affecting this transition likely vary across endemic sites, e.g. differing levels of transmission before vector interventions were expanded; uneven distribution, use and replacement of ITN; insecticide resistance; changes in the dominant mosquito vector species and their biting behavior. Using plasma collected during a 2003 cross-sectional survey of children and adults in Kanyawegi and a 2013 cross-sectional survey in Chulaimbo, two communities in Kisumu County located 11 km from each other, we quantified IgG antibody levels to 3 pre-erythrocytic and 25 recombinant blood stage antigens and evaluated their relationship with the prevalence of asymptomatic parasitemia and age profile of uncomplicated malaria incidence in children. Antibody acquisition models are similar to sero-catalytic models except they utilize continuous measures of antibody responses rather than binary sero-positivity status We used both approaches to determine whether antibodies to a subset of these Pf antigens might be informative for evaluating differences in the two cohorts with respect to malaria exposure and age-related acquired immunity to uncomplicated malaria
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