Seroepidemiology of trachoma for the elimination endgame

消除残局沙眼血清流行病学

• 批准号: 10580743
• 负责人: Benjamin F Arnold
• 金额: $ 40.38万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580743
• 关键词: Advisory Committees; Africa; Age; Antibiotics; Antibodies; Antibody Response; Antigens; Area; Azithromycin; Blindness; Blood; Blood specimen; Centers for Disease Control and Prevention (U.S.); Child; Chlamydia trachomatis; Clinical; Communities; Country; Data; Data Set; Decision Making; Diagnosis; Disease; Ensure; Epidemiologic Methods; Epidemiology; Ethiopia; Evolution; Geography; Heterogeneity; Immunoglobulin G; Immunology; Individual; Infection; International; Knowledge; Language; Measures; Methods; Modeling; Molecular; Monitor; Niger; Pattern; Persons; Phase; Play; Population; Population Programs; Prevalence; Public Health; Recombinants; Research; Sampling; Series; Seroepidemiologic Studies; Serology; Seroprevalences; Statistical Methods; Structure; Surveys; Symptoms; Testing; Time; Trachoma; Translating; Work; World Health Organization; age related; assay development; computer studies; design; field study; global health; immunogenic; improved; interest; meetings; member; multiplex assay; novel strategies; population based; programs; semiparametric; seroconversion; serosurveillance; serosurvey; transmission process

Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindness worldwide and been targeted for global elimination as a public health problem by 2030. As we approach the endgame, there is broad interest in the use of serologic surveys to support control programs. IgG antibody responses to C. trachomatis in children enable accurate population-level assessments of trachoma endemicity because they integrate exposure over time and reflect recent transmission. After years of assay development, a key gap in the field is to formalize the epidemiologic methods used for trachoma serology surveys. Our overall objective is to advance the methods used for the design and analysis of trachoma serology surveys. We will assemble a large, contemporary global dataset for trachoma serology across a gradient of endemicity, paired with clinical signs and molecular measures of infection (>100,000 blood specimens tested in 19 studies from 2010-2024). Aim 1 will develop robust methods to translate antibody response into population- level measures of transmission from endemic settings to post-elimination. We hypothesize that as populations approach elimination age-seroprevalence curves will flatten and seroconversion rates, a measure of force of infection, will approach zero. We will estimate age-seroprevalence curves semi-parametrically, and derive summary measures from the curves (e.g., seroprevalence, force of infection). We will compare serologic measures between populations of different endemicity. We further hypothesize that different serologic summary measures (mean IgG levels, seroprevalence, force of infection) will provide similar information about heterogeneity in transmission. We will compare serologic measures with one-another and with separate measures of trachoma (PCR infection, clinical signs) across geographic scales from villages to districts. Aim 2 will determine if model-based geostatistics improve the efficiency of serological survey design and enable finer scale targeting of control programs as populations approach elimination. We hypothesize that as trachoma approaches elimination, it will become more focal with “hotspots” of elevated seroprevalence among children that shrink in scale from districts down to individual villages. We hypothesize that if surveys account for this spatial structure in their design they will more efficiently monitor trachoma than random samples alone, and control programs that use spatial predictions to make treatment decisions at smaller spatial scales could more narrowly target antibiotic distribution. In analyses of 11 georeferenced studies that span a range of endemicity, we will apply recent advances in geospatial design to trachoma serology and compare prevalence estimates using the new approach with the current standard, population-based random samples. We seek to identify the most efficient sampling strategies to inform decision making as populations approach elimination, and to study the impact of using spatial predictions to target azithromycin at finer spatial scales. Completion of these aims will lead to significant advances in the seroepidemiologic methods used to support the trachoma endgame.

沙眼由眼沙尚有感染引起，是失明的主要感染原因 到2030年，全球范围内的全球淘汰作为公共卫生问题。当我们接近时 最终游戏，对使用血清学调查来支持控制程序有广泛的兴趣。 IgG抗体 儿童对沙眼炎的反应能够准确的人口水平评估对沙眼内构性 因为它们会随着时间的推移整合并反映了最近的传播。经过多年的评估发展， 该领域的一个关键差距是正式化用于沙眼血清学调查的流行病学方法。 我们的总体目的是推进用于三根瘤血清学设计和分析的方法 调查。我们将组装一个大型的当代全球数据集，用于沙眼学血清学， 内构性与临床体征和感染的分子测量配对（在 19 2010-2024的研究）。 AIM 1将开发出可靠的方法来将抗体反应转化为种群 - 从内在环境到淘气后传播的水平度量。我们假设这是人口 进近消除年龄呈现曲线的曲线将变平和血清阳性率，这是一种衡量力量的量度 感染将接近零。我们将半票面估算年龄呈现曲线，并得出 曲线的摘要测量（例如血清阳性，感染力）。我们将比较血清学 不同内在性种群之间的措施。我们进一步假设不同的血清学 摘要测量（平均IgG水平，血清阳性，感染力）将提供有关的类似信息 传输中的异质性。我们将将血清学测量与另一种和单独的 从村庄到地区的地理量表的沙眼（PCR感染，临床体征）的度量。目标2 将确定基于模型的地统计学是否提高了血清学调查设计的效率，并使更精细 将控制程序作为人口接近的范围定位。我们假设这是沙眼 消除方法，随着儿童的血清阳性升高的“热点”，它将变得更加焦点 从地区到个别村庄的规模收缩。我们假设如果调查说明这一点 他们设计中的空间结构将比单独的随机样品更有效地监测沙眼瘤，并且 使用空间预测以在较小的空间尺度上做出治疗决策的控制程序可以更多 狭窄靶向抗生素分布。在分析11项跨越一系列内在性的地理参与研究的分析中， 我们将应用地理空间设计的最新进展来进行沙丘瘤血清学并比较患病率估计值 使用新方法与当前标准，基于人群的随机样本。我们试图确定 最有效的抽样策略，以告知决策，以消除人口，并研究 使用空间预测以更细的空间尺度靶向阿奇霉素的影响。这些目标的完成 将导致用于支持沙眼最终游戏的血清ePIDEMIologic方法的重大进展。