Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities
Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities
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DOI：
10.1073/pnas.1501705112
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发表时间：
2015-08-11
影响因子：
11.1
通讯作者：
Greenhouse, Bryan
中科院分区：
文献类型：
--
作者：
Helb, Danica A.;Tetteh, Kevin K. A.;Greenhouse, Bryan
需要可靠测量个人和社区恶性疟原虫 (Pf) 暴露情况的工具来指导和评估疟疾控制干预措施。血清学检测有可能以低成本产生精确的暴露估计；然而，目前基于对一些特征抗原的反应的方法并不是为了估计个体的暴露程度。 Pf 特异性抗体反应因抗原而异，表明选择具有明确动力学曲线的抗原将改善对 Pf 暴露的估计。为了确定疟疾暴露的新型血清学生物标志物，我们通过蛋白质微阵列评估了 186 名乌干达儿童对 856 种 Pf 抗原的反应，这些儿童有详细的 Pf 暴露数据。使用数据自适应统计方法，我们确定了抗体反应的组合，可以最大化有关个人近期接触情况的信息。对三种新的 Pf 抗原的反应可以准确地分类一个人是否在过去 30、90 或 365 天内被感染（交叉验证的曲线下面积 = 0.86-0.93），而对六种抗原的反应可以准确地估计一个人在前一年的疟疾发病率。对不同社区中个体的交叉验证发病率预测提供了人群之间暴露的准确分层，并表明可以通过对该社区的一小部分进行抽样来获得社区暴露的精确估计。此外，来自横截面样本的血清学发病率预测表征了社区内的异质性，类似于 1 年的连续被动监测。从这里概述的成功选择策略中衍生出的简单的基于 ELISA 的检测方法的开发提供了生成丰富的流行病学监测数据的潜力，这些数据将广泛地供疟疾控制项目使用。
Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual's recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86-0.93), whereas responses to six antigens accurately estimated an individual's malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.