Geospatial analysis of Plasmodium falciparum serological indicators: school versus community sampling in a low-transmission malaria setting

Abstract Background Due to low numbers of active infections and persons presenting to health facilities for malaria treatment, case-based surveillance is inefficient for understanding the remaining disease burden in low malaria transmission settings. Serological data through the detection of IgG antibodies from previous malaria parasite exposure can fill this gap by providing a nuanced picture of where sustained transmission remains. Study enrollment at sites of gathering provides a potential approach to spatially estimate malaria exposure and could preclude the need for more intensive community-based sampling. Methods This study compared spatial estimates of malaria exposure from cross-sectional school- and community-based sampling in Haiti. A total of 52,405 blood samples were collected from 2012 to 2017. Multiplex bead assays (MBAs) tested IgG against P. falciparum liver stage antigen-1 (LSA-1), apical membrane antigen 1 (AMA1), and merozoite surface protein 1 (MSP1). Predictive geospatial models of seropositivity adjusted for environmental covariates, and results were compared using correlations by coordinate points and communes across Haiti. Results Consistent directional associations were observed between seroprevalence and environmental covariates for elevation (negative), air temperature (negative), and travel time to urban centers (positive). Spearman’s rank correlation for predicted seroprevalence at coordinate points was lowest for LSA-1 (ρ = 0.10, 95% CI: 0.09–0.11), but improved for AMA1 (ρ = 0.36, 95% CI: 0.35–0.37) and MSP1 (ρ = 0.48, 95% CI: 0.47–0.49). Conclusions In settings approaching P. falciparum elimination, case-based prevalence data does not provide a resolution of ongoing malaria transmission in the population. Immunogenic antigen targets (e.g., AMA1, MSP1) that give higher population rates of seropositivity provide moderate correlation to gold standard community sampling designs and are a feasible approach to discern foci of residual P. falciparum transmission in an area

DataSheet_1_Spatial, environmental, and individual associations with Anopheles albimanus salivary antigen IgG in Haitian children.docx

IgG serology can be utilized to estimate exposure to Anopheline malaria vectors and the Plasmodium species they transmit. A multiplex bead-based assay simultaneously detected IgG to Anopheles albimanus salivary gland extract (SGE) and four Plasmodium falciparum antigens (CSP, LSA-1, PfAMA1, and PfMSP1) in 11,541 children enrolled at 350 schools across Haiti in 2016. Logistic regression estimated odds of an above-median anti-SGE IgG response adjusting for individual- and environmental-level covariates. Spatial analysis detected statistically significant clusters of schools with students having high anti-SGE IgG levels, and spatial interpolation estimated anti-SGE IgG levels in unsampled locations. Boys had 11% (95% CI: 0.81, 0.98) lower odds of high anti-SGE IgG compared to girls, and children seropositive for PfMSP1 had 53% (95% CI: 1.17, 2.00) higher odds compared to PfMSP1 seronegatives. Compared to the lowest elevation, quartiles 2-4 of higher elevation were associated with successively lower odds (0.81, 0.43, and 0.34, respectively) of high anti-SGE IgG. Seven significant clusters of schools were detected in Haiti, while spatially interpolated results provided a comprehensive picture of anti-SGE IgG levels in the study area. Exposure to malaria vectors by IgG serology with SGE is a proxy to approximate vector biting in children and identify risk factors for vector exposure.</p

Additional file 1 of Geospatial analysis of Plasmodium falciparum serological indicators: school versus community sampling in a low-transmission malaria setting

Additional file 1: Table S1. Remote sensing data: resolutions, units, and sources. Table S2. Prevalence of positive rapid diagnostic test results with 95% confidence intervals by survey year for Tracking Results Continuously versus Transmission Assessment Surveys. Table S3. Observed seropositivity to P. falciparum antigens by survey year with 95% confidence intervals for community members surveyed for Tracking Results Continuously, 2012-2017. Table S4. Descriptive statistics of survey-site temporal covariates. Table S5. Descriptive statistics of survey-site static covariates. Table S6. Mean estimated coefficients of covariates with 95% credible intervals