Seroepidemiology of trachoma for the elimination endgame

消除残局沙眼血清流行病学

• 批准号: 10359762
• 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/10359762
• 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; base; 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.

沙眼是由眼部沙眼衣原体感染引起的，是导致失明的主要原因 并计划到 2030 年在全球范围内消除这一公共卫生问题。 最后，人们对使用血清学调查来支持控制计划产生了广泛的兴趣。 IgG抗体 儿童对沙眼衣原体的反应能够对沙眼流行病进行准确的人群水平评估 因为它们整合了一段时间内的暴露情况并反映了最近的传播情况。经过多年的检测开发， 该领域的一个关键差距是正规化用于沙眼血清学调查的流行病学方法。 我们的总体目标是推进沙眼血清学设计和分析的方法 调查。我们将收集一个大型的当代全球沙眼血清学数据集，涵盖梯度 流行性，并结合感染的临床症状和分子测量（在 100,000 份血液样本中进行了检测） 2010-2024 年 19 项研究）。目标 1 将开发稳健的方法将抗体反应转化为群体反应 从流行地区到消除后的传播水平测量。我们假设随着人口 消除方法年龄-血清流行率曲线将趋于平坦，血清转化率（衡量感染力的指标） 感染率将趋近于零。我们将以半参数方式估计年龄-血清流行率曲线，并得出 曲线的汇总测量（例如，血清流行率、感染力）。我们将比较血清学 不同流行病人群之间的测量。我们进一步假设不同的血清学 总结措施（平均 IgG 水平、血清流行率、感染力）将提供有关以下方面的类似信息： 传输的异质性。我们将相互比较血清学测量值以及单独的血清学测量值 从村庄到地区的不同地理范围内的沙眼测量（PCR 感染、临床症状）。目标2 将确定基于模型的地质统计学是否可以提高血清学调查设计的效率并实现更精细的研究 随着人口接近消除，控制计划的规模目标。我们假设沙眼 接近消除，它将更加关注儿童血清流行率升高的“热点” 规模从地区缩小到个别村庄。我们假设如果调查考虑到这一点 他们设计的空间结构比单独随机样本更有效地监测沙眼，并且 使用空间预测在较小空间尺度上做出治疗决策的控制程序可能会更有效 狭隘地针对抗生素分布。在对涵盖一系列流行病的 11 项地理参考研究的分析中， 我们将把地理空间设计的最新进展应用于沙眼血清学并比较患病率估计值 将新方法与当前标准的基于人群的随机样本结合使用。我们寻求确定 最有效的抽样策略，可以在种群接近消除时为决策提供信息，并进行研究 使用空间预测在更精细的空间尺度上靶向阿奇霉素的影响。完成这些目标 将导致用于支持沙眼最终结果的血清流行病学方法取得重大进展。