Antibody dynamics in children with first or repeat Plasmodium falciparum infections.

Immunoglobulin (Ig) production during and after infection with Plasmodium parasites is one of the greatest adaptive immune defenses the human host has against this parasite. Infection with P. falciparum has been shown to induce different B cell maturation responses dependent upon the age of the patient, number of previous exposures, and severity of the disease. Described here are dynamics of Ig responses to a panel of 32 P. falciparum antigens by patients followed for 42 days and classified individuals as showing characteristics of an apparent first P. falciparum infection (naïve) or a repeat exposure (non-naïve). Six parameters were modeled to characterize the dynamics of IgM, IgG1, IgG3, and IgA for these two exposure groups with differences assessed among Ig isotypes/subclasses and unique antigens. Naïve patients had significantly longer periods of time to reach peak Ig titer (range 4-7 days longer) and lower maximum Ig titers when compared with non-naïve patients. Modeled time to seronegativity was significantly higher in non-naïve patients for IgM and IgA, but not for the two IgG subclasses. IgG1 responses to Rh2030, HSP40, and PfAMA1 were at the highest levels for non-naïve participants and may be used to predict previous or nascent exposure by themselves. The analyses presented here demonstrate the differences in the development of the Ig response to P. falciparum if the infection represents a boosting response or a primary exposure. Consistency in Ig isotype/subclasses estimates and specific data for P. falciparum antigens can better guide interpretation of seroepidemiological data among symptomatic persons

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

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