Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
mBio. 2022 Dec 20;13(6):e0190022. doi: 10.1128/mbio.01900-22. Epub 2022 Oct 26.
Estimates of incidence based on medically attended cholera can be severely biased. Vibrio cholerae O1 leaves a lasting antibody signal and recent advances showed that these can be used to estimate infection incidence rates from cross-sectional serologic data. Current laboratory methods are resource intensive and challenging to standardize across laboratories. A multiplex bead assay (MBA) could efficiently expand the breadth of measured antibody responses and improve seroincidence accuracy. We tested 305 serum samples from confirmed cholera cases (4 to 1083 d postinfection) and uninfected contacts in Bangladesh using an MBA (IgG/IgA/IgM for 7 Vibrio cholerae O1-specific antigens) as well as traditional vibriocidal and enzyme-linked immunosorbent assays (2 antigens, IgG, and IgA). While postinfection vibriocidal responses were larger than other markers, several MBA-measured antibodies demonstrated robust responses with similar half-lives. Random forest models combining all MBA antibody measures allowed for accurate identification of recent cholera infections (e.g., past 200 days) including a cross-validated area under the curve (cvAUC) of 92%, with simpler 3 IgG antibody models having similar accuracy. Across infection windows between 45 and 300 days, the accuracy of models trained on MBA measurements was non-inferior to models based on traditional assays. Our results illustrated a scalable cholera serosurveillance tool that can be incorporated into multipathogen serosurveillance platforms. Reliable estimates of cholera incidence are challenged by poor clinical surveillance and health-seeking behavior biases. We showed that cross-sectional serologic profiles measured with a high-throughput multiplex bead assay can lead to accurate identification of those infected with pandemic Vibrio cholerae O1, thus allowing for estimates of seroincidence. This provides a new avenue for understanding the epidemiology of cholera, identifying priority areas for cholera prevention/control investments, and tracking progress in the global fight against this ancient disease.
基于医疗就诊的霍乱发病率估计可能存在严重偏差。霍乱弧菌 O1 会留下持久的抗体信号，最近的进展表明，这些信号可用于从横断面血清学数据中估计感染发病率。目前的实验室方法资源密集且难以在实验室之间标准化。多重珠状分析（MBA）可以有效地扩大测量抗体反应的广度，并提高血清学发病率的准确性。我们使用 MBA（针对 7 种霍乱弧菌 O1 特异性抗原的 IgG/IgA/IgM）以及传统的杀菌力和酶联免疫吸附测定法（2 种抗原，IgG 和 IgA），对孟加拉国 305 例确诊霍乱病例（感染后 4 至 1083 天）和未感染接触者的血清样本进行了检测。虽然感染后杀菌力反应大于其他标志物，但 MBA 测量的几种抗体均表现出相似半衰期的强大反应。结合所有 MBA 抗体测量值的随机森林模型可准确识别近期霍乱感染（例如过去 200 天），包括交叉验证曲线下面积（cvAUC）为 92%，而更简单的 3 种 IgG 抗体模型具有相似的准确性。在感染窗口 45 至 300 天之间，基于 MBA 测量值训练的模型的准确性不亚于基于传统检测的模型。我们的结果说明了一种可扩展的霍乱血清监测工具，可纳入多病原体血清监测平台。可靠的霍乱发病率估计受到较差的临床监测和健康寻求行为偏差的挑战。我们表明，使用高通量多重珠状分析测量的横断面血清学特征可准确识别感染大流行霍乱弧菌 O1 的人群，从而可以估计血清学发病率。这为了解霍乱的流行病学、确定霍乱预防/控制投资的优先领域以及跟踪全球抗击这种古老疾病的进展提供了新途径。
