Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
Burnet Institute, Melbourne, Australia.
Malar J. 2022 Mar 5;21(1):75. doi: 10.1186/s12936-022-04111-y.
Malaria remains a major public health threat and tools sensitive to detect infections in low malaria transmission areas are needed to progress elimination efforts. Pregnant women are particularly vulnerable to malaria infections. Throughout pregnancy they access routine antenatal care, presenting a unique sentinel population to apply novel sero-surveillance tools to measure malaria transmission. The aim of this study was to quantify the dynamic antibody responses to multiple antigens during pregnancy so as to identify a single or multiple antibody response of exposure to malaria in pregnancy.
This study involved a secondary analysis of antibody responses to six parasite antigens [five commonly studied merozoite antigens and the variant surface antigen 2-chondroitin sulphate A (VAR2CSA), a pregnancy-specific erythrocytic antigen] measured by enzyme-linked immunosorbent assay (ELISA) over the gestation period until delivery (median of 7 measurements/woman) in 250 pregnant women who attended antenatal clinics located at the Thai-Myanmar border. A multivariate mixture linear mixed model was used to cluster the pregnant women into groups that have similar longitudinal antibody responses to all six antigens over the gestational period using a Bayesian approach. The variable-specific entropy was calculated to identify the antibody responses that have the highest influence on the classification of the women into clusters, and subsequent agreement with grouping of women based on exposure to malaria during pregnancy.
Of the 250 pregnant women, 135 had a Plasmodium infection detected by light microscopy during pregnancy (39% Plasmodium falciparum only, 33% Plasmodium vivax only and 28% mixed/other species), defined as cases. The antibody responses to all six antigens accurately identified the women who did not have a malaria infection detected during pregnancy (93%, 107/115 controls). Antibody responses to P. falciparum merozoite surface protein 3 (PfMSP3) and P. vivax apical membrane antigen 1 (PvAMA1) were the least dynamic. Antibody responses to the antigens P. falciparum apical membrane antigen 1 (PfAMA1) and PfVAR2CSA were able to identify the majority of the cases more accurately (63%, 85/135).
These findings suggest that the combination of antibodies, PfAMA1 and PfVAR2CSA, may be useful for sero-surveillance of malaria infections in pregnant women, particularly in low malaria transmission settings. Further investigation of other antibody markers is warranted considering these antibodies combined only detected 63% of the malaria infections during pregnancy.
疟疾仍然是一个主要的公共卫生威胁，需要能够检测低疟疾传播地区感染的敏感工具来推进消除疟疾的努力。孕妇特别容易受到疟疾感染。在整个孕期，她们会接受常规的产前保健，这使她们成为应用新型血清监测工具来测量疟疾传播的独特哨点人群。本研究的目的是定量检测孕期多种抗原的动态抗体反应，以确定单一或多种与孕期疟疾感染相关的抗体反应。
本研究对 250 名在泰缅边境的产前诊所就诊的孕妇进行了二次分析，这些孕妇在孕期直至分娩时（每名孕妇平均有 7 次测量）通过酶联免疫吸附试验（ELISA）检测了六种寄生虫抗原[五种常见的裂殖体抗原和变体表面抗原 2-硫酸软骨素 A（VAR2CSA），一种妊娠特异性红细胞抗原]的抗体反应。采用贝叶斯方法的多变量混合线性混合模型，根据整个孕期对所有六种抗原的纵向抗体反应将孕妇聚类为具有相似反应的组。计算变量特异性熵，以确定对将孕妇分类为聚类的影响最大的抗体反应，并根据孕妇在孕期接触疟疾的情况对其分组进行后续评估。
在 250 名孕妇中，有 135 名孕妇在孕期通过显微镜检查发现疟原虫感染（单纯恶性疟原虫感染 39%，单纯间日疟原虫感染 33%，混合/其他物种感染 28%），定义为病例。对所有六种抗原的抗体反应均能准确识别未在孕期发现疟疾感染的孕妇（93%，115 名对照）。对恶性疟原虫裂殖体表面蛋白 3（PfMSP3）和间日疟原虫顶膜蛋白 1（PvAMA1）的抗体反应最不具有动态性。对恶性疟原虫顶膜蛋白 1（PfAMA1）和 PfVAR2CSA 的抗体反应能够更准确地识别大多数病例（63%，85/135）。
这些发现表明，PfAMA1 和 PfVAR2CSA 抗体的组合可能有助于孕妇疟疾感染的血清学监测，特别是在低疟疾传播地区。考虑到这些抗体联合检测仅发现了孕期 63%的疟疾感染，需要进一步研究其他抗体标志物。
