Seroepidemiology of trachoma for the elimination endgame

消除残局沙眼血清流行病学

• 批准号: 10181859
• 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/10181859
• 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; 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; antibody test; 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.

沙眼由眼沙眼衣原体感染引起，是导致失明的主要传染性原因 并被定为到2030年全球消除这一公共卫生问题的目标。当我们接近 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 答案C。儿童沙眼患者能够准确评估沙眼流行的人群水平 因为它们整合了暴露时间并反映了最近的传播。经过多年的检测开发， 这一领域的一个关键差距是将沙眼血清学调查所用的流行病学方法正规化。 我们的总体目标是改进沙眼血清学的设计和分析方法 调查。我们将收集一个大型的，当代全球沙眼血清学数据集， 流行性，与感染的临床体征和分子测量配对（在2010年测试了> 100，000份血液样本）。 2010-2024年19项研究）。目标1将开发强有力的方法，将抗体反应转化为群体- 从流行环境到消灭后的传播水平措施。我们假设， 接近消除年龄-血清阳性率曲线将变平，血清转换率，一个衡量 感染率将接近于零我们将半参数地估计年龄-血清阳性率曲线，并推导出 来自曲线的概括测量（例如，血清阳性率、感染力）。我们将比较血清学 不同地方性人群之间的措施。我们进一步假设，不同的血清学 汇总指标（平均IgG水平、血清阳性率、感染力）将提供类似的信息， 传播的异质性。我们将比较血清学措施与彼此和单独的 从村庄到地区的地理范围内的沙眼测量（PCR感染，临床体征）。目的2 将确定基于模型的地质统计学是否能提高血清学调查设计的效率， 随着人口接近消灭，控制计划的规模目标。我们假设沙眼 接近消除，它将成为更集中的“热点”，儿童血清阳性率升高， 从地区到村庄的规模缩小。我们假设如果调查能解释这一点 空间结构在他们的设计中，他们将比单独随机样本更有效地监测沙眼， 使用空间预测在较小的空间尺度上做出治疗决策的控制程序可能会更好地 狭窄的抗生素分布目标。在对11项地理参考研究的分析中，这些研究涵盖了一系列地方性， 我们将把地理空间设计的最新进展应用于沙眼血清学， 使用新的方法与目前的标准，人口为基础的随机样本。我们试图找出 最有效的抽样策略，以告知决策，因为人口接近消除，并研究 在更精细的空间尺度上使用空间预测来靶向阿奇霉素的影响。实现这些目标 将导致用于支持沙眼终局的血清流行病学方法的重大进展。