Multiple comparisons analysis of serological data from an area of low Plasmodium falciparum transmission

Malaria Journal

Research

Ito Journel¹  Ryan Wiegand²  Kimberly Mace²  Delynn Moss²  Michelle Chang²  John W. Barnwell²  Eric Rogier²  Jeff Priest²  Venkatachalam Udhayakumar²  Sheetij Dutta³  Evelina Angov³  Samuel E. Jean⁴  Jean Frantz Lemoine⁵ 

[1] Laboratoire National de Santé Publique (LNSP)/Ministère de la Santé Publique et de la Population (MSPP), Port-au-Prince, Haiti;Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Center for Global Health, Atlanta, GA, USA;Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA;Population Services International/Organisation Haïtienne de Marketing Social pour la Santé, Port-au-Prince, Haiti;Programme National de Contrôle de la Malaria/MSPP, Port-au-Prince, Haiti;

关键词: Serology;    Plasmodium falciparum;    Multiplex;    ELISA;    Distribution;   

DOI  :  10.1186/s12936-015-0955-1

 received in 2015-08-26, accepted in 2015-10-21,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Rogier et al. 2015