Abstract
BackgroundAs a nation reduces the burden of falciparum malaria, identifying areas of transmission becomes increasingly difficult. Over the past decade, the field of utilizing malaria serological assays to measure exposure has grown rapidly, and a variety of serological methods for data acquisition and analysis of human IgG against falciparum antigens are available. Here, different immunoassays and statistical methods are utilized to analyse samples from a low transmission setting and directly compare the estimates generated.MethodsA subset of samples (n = 580) from a 2012 Haitian nationwide malaria survey was employed as sample population of low falciparum endemicity. In addition to the Haitian samples, samples from 247 US residents were used as a reference population of ‘true seronegatives’. Data acquisition was performed through standard ELISA and bead-based multiplex assays assaying for IgG antibodies to the Plasmodium falciparum antigens MSP-1p19, MSP-1p42(D), MSP-1p42(F), and AMA-1. Appropriate parametric distributions and seropositivity cutoff values were determined by statistical measures.ResultsData from both assays showed a strong positive skew, and the lognormal distribution was found to be an appropriate statistical fit to the Haitian and American populations. The American samples served as a good serological true negative population for the multiplex assay, but not for ELISA-based data. Mixture model approaches to determine seronegative and seropositive populations from the Haitian data showed a high degree of distribution overlap—likely due to the historical low falciparum transmission in this nation. Different fittings to the reversible catalytic model resulted depending upon the immunoassay utilized and seropositivity cutoff method employed. Data were also analysed through fitting to penalized B-splines, presenting another possible analytical tool for the analysis of malaria serological data.ConclusionsStandardization of serological techniques and analyses may prove difficult as some tools can prove to be more useful depending on the area and parasite in question, making clear interpretation a vital pursuit. The presented analysis in the low-endemic nation of Haiti found malaria-naive US residents to be an appropriate seronegative reference population for the multiplex assay, and this assay providing consistent estimates between MSP-1 and AMA-1 antigens of percent seropositives for this low-endemic population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0955-1) contains supplementary material, which is available to authorized users.
Highlights
As a nation reduces the burden of falciparum malaria, identifying areas of transmission becomes increasingly difficult
Since readings for immunoassays can vary widely depending on reagents and protocols, it was investigated how enzyme-linked immunosorbant assay (ELISA) and multiplex assays performed when the same dilution series was ran using the specified reagents and protocols that would be employed for the entire study
As merozoite surface protein 1 (MSP-1) and Apical Membrane Antigen-1 (AMA-1) antigens are thought to induce robust and long-lived humoral immune responses after multiple exposures to malaria infection [8, 22, 23], blood was pooled from individuals residing in a Kenya region holoendemic for P. falciparum malaria, spotted onto filter paper, eluted, and titrated using each immunoassay
Summary
As a nation reduces the burden of falciparum malaria, identifying areas of transmission becomes increasingly difficult. The field of utilizing malaria serological assays to measure exposure has grown rapidly, and a variety of serological methods for data acquisition and analysis of human IgG against falciparum antigens are available. In regions of moderate or high transmission for P. falciparum, children progressing through their first decade of life show rapid increases in the acquisition of antibodies against the parasite [3,4,5]. A peculiar finding by many groups has shown that even in historically high transmission zones, older age groups do not necessarily carry appreciable levels of long-lived IgG against P. falciparum [5, 9], even though multiple lifetime infections would have been nearly certain. The true explanation for this observation is likely multifaceted, one possibility involves the loss of antibodies over time through seroreversion [8]
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