Evaluation of Immunoglobulin G Responses to Plasmodium falciparum and Plasmodium vivax in Malian School Children Using Multiplex Bead Assay

Abstract

Malaria serology through assaying for IgG against Plasmodium spp. antigens provides evidence into the infection history for an individual. The multiplex bead assay (MBA) allows for detection of IgG against multiple Plasmodium spp., and can be especially useful in many regions where Plasmodium falciparum is of primary clinical focus, but other species are co-endemic. Dried blood spots were collected from 805 Malian children attending 42 elementary schools in the regions of Mopti, Sikasso, Koulikoro, and Bamako capital district, and IgG assayed by MBA. As southern Mali is known to be holoendemic for P. falciparum, merozoite surface protein 1 19-kDa subunit (MSP-142) and apical membrane antigen 1 (AMA-1) antigens were included for serology against this parasite. Responses to these antigens both provided high estimates for lifetime exposure, with 730 (90%) children with IgG antibodies for MSP-142, 737 (91%) for AMA-1, and 773 (96%) positive for either or both. Also included was the antigen Plasmodium vivax MSP-119, against which 140 (17.4%) children were found to have antibodies. Increases in antibody titers with older age were clearly seen with the P. falciparum antigens, but not with the P. vivax antigen, likely indicating more of a sporadic, rather than sustained transmission for this species. The MBA provides effective opportunities to evaluate malaria transmission through serological analysis for multiple Plasmodium species.

Trial registration: ClinicalTrials.gov NCT01787058.

© The American Society of Tropical Medicine and Hygiene.

Figures

Figure 1.

Map of southwestern Mali showing school locations and malaria antibody prevalence by school. (A) Schools within the regions of Bamako (N = 2), Mopti (N = 4), Sikasso (N = 16), and Koulikoro (N = 20) were all included in the study. (B) Percent of children in each school sampled with IgG antibodies against the Plasmodium falciparum antigen merozoite surface protein (MSP-142). (C) Percent of children in each school sampled with IgG antibodies against the P. falciparum antigen apical membrane antigen 1 (AMA-1). (D) Percent of children in each school sampled with IgG antibodies against the Plasmodium vivax antigen MSP-119.

Figure 2.

Scatterplots of median fluorescence intensity with background subtracted (MFI-bg) signal for antigen Plasmodium falciparum merozoite surface protein (MSP-142) with the P. falciparum apical membrane antigen 1 (AMA-1) and Plasmodium vivax MSP-119 antigens from all the children in the study (N = 805). Scatterplots show MFI-bg signal between the two P. falciparum antigens, and between the P. falciparum and P. vivax MSP-1 homologs. Diagonal line represents y = x reference line.

Figure 3.

Histograms for signal intensities of the three antigens used in the study. The distribution of median fluorescence intensity with background subtracted (MFI-bg) signal for the children in the study is plotted as log-transformed on the x axis. Hashed vertical lines signify the seropositivity cutoff value for each antigen. Note that the histogram for each antigen has a unique y-axis scale.

Figure 4.

Connecting boxplots of ln(MFI-bg) for all antigens by age of participants in the study. Boxplots signify the mean (diamond) and display the interquartile range with whiskers extending 1.5 times the interquartile range (IQR) above and below. Outliers displayed as circles outside of 1.5× IQR. Bins connected at means between age divisions. For each, age(n): 5(4), 6(16), 7(23), 8(27), 9(35), 10(85), 11(74), 12(80), 13(51), 14(46), 15(16), 16(5).