Integrating genomic and spatial approaches for targeted control of HIV-associated tuberculosis epidemics

整合基因组和空间方法有针对性地控制艾滋病毒相关结核病流行

• 批准号: 10676990
• 负责人: THEODORE H COHEN
• 金额: $ 64.96万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10676990
• 关键词: Adult; Africa; Area; Calibration; Caring; Cause of Death; Censuses; Cities; Collection; Communities; Data; Diagnostic; Epidemic; Exclusion; Genomics; Geographic Locations; Goals; HIV; HIV Infections; HIV Seropositivity; Health; Health Benefit; Health Status; Heterogeneity; Home; Incidence; Individual; Infection; Infection Control; Institution; Interruption; Intervention; Investments; Location; Malawi; Maps; Methods; Modeling; Mycobacterium tuberculosis; Notification; Outcome; Patients; Pattern; Phylogenetic Analysis; Policies; Population; Predisposition; Prevalence; Resolution; Resources; Risk; Risk Factors; Site; Source; Southern Africa; Specimen; Surveys; Tuberculosis; Work; analytical method; analytical tool; antiretroviral therapy; burden of illness; case finding; cost; cost effectiveness; cost estimate; density; design; economic cost; genome sequencing; genomic data; improved; intervention program; mathematical model; models and simulation; novel; novel sequencing technology; novel strategies; pathogen; pathogen genomics; programs; prospective; public health priorities; spatiotemporal; tool; transmission process; urban area; whole genome

PROJECT SUMMARY Tuberculosis (TB) remains the leading infectious cause of death due to a single pathogen and is a leading cause of death among individuals living with HIV. Improved TB control in high HIV prevalence settings requires new approaches for interrupting TB transmission. Recent studies have revealed substantial heterogeneity in community risk factors for TB, as well as in TB transmission and prevalence, even within high-density urban centers in Africa. Untargeted community-based interventions for active TB case finding in high HIV prevalence settings demand substantial resources to implement yet have not reliably produced population-level benefits. We hypothesize that more precisely targeted TB interventions, informed by whole genome sequencing of M. tuberculosis isolates from all culture-positive TB patients, will result in more effective TB control, and may also have efficiency benefits when compared with less focused community-based interventions in high HIV burden settings. Based on previous studies and preliminary data from our study site in Blantyre, Malawi (where adult HIV prevalence is around 20% and nearly 80% of notified TB cases are HIV seropositive), we believe that HIV care settings and other locations will be identified as TB transmission hotspots where infectious TB cases are in contact with highly susceptible individuals under poor infection control conditions. In this project, we propose to use data and specimens that have been collected from notified TB patients from all diagnostic centers in the city of Blantyre, Malawi between 2015 and the start of our study to accomplish three specific aims: (Aim 1) To synthesize prospectively-collected demographic, spatial and genomic data to illuminate patterns and critical drivers of local TB transmission dynamics in high HIV prevalence settings; (Aim 2) To develop and apply locally-calibrated mathematical models to investigate the potential impact and cost- effectiveness of spatially-targeted TB interventions informed by high-resolution information on locations and sources of infection in high HIV prevalence settings, and (Aim 3) To formally assess the value of information afforded by whole genome sequencing and to estimate the costs and cost-effectiveness of building local capacity for sequencing and analysis of pathogen genomic data.

项目摘要 结核病（TB）仍然是由单一病原体引起的主要传染性死亡原因，并且是导致死亡的主要原因。 艾滋病毒感染者的死亡原因。在艾滋病毒高流行率环境中改善结核病控制需要 阻断结核病传播的新方法。最近的研究表明， 结核病的社区风险因素，以及结核病的传播和流行，即使在高密度的城市 中心在非洲。在艾滋病毒高流行率地区对活动性结核病例发现的非针对性社区干预 环境需要大量资源来执行，但尚未可靠地产生人口层面的惠益。 我们假设，更精确的针对性结核病干预措施，通过全基因组测序M。 从所有培养阳性的结核病患者中分离出结核病菌株，将导致更有效的结核病控制， 在艾滋病毒高负担地区，与重点不那么突出的社区干预措施相比， 设置.根据以前的研究和我们在马拉维布兰太尔的研究地点的初步数据（那里的成年人 艾滋病毒感染率约为20%，近80%的结核病病例是艾滋病毒血清阳性），我们认为，艾滋病毒 医疗机构和其他地点将被确定为结核病传播热点， 在感染控制条件差的情况下与高度易感者接触。 在这个项目中，我们建议使用从已报告的结核病患者收集的数据和样本， 所有诊断中心在城市的布兰太尔，马拉维之间的2015年和我们的研究开始，以完成 三个具体目标：（目标1）综合前瞻性收集的人口、空间和基因组数据， 阐明艾滋病毒高流行率环境中当地结核病传播动态的模式和关键驱动因素;（目的 2)开发和应用本地校准的数学模型，以调查潜在的影响和成本- 通过高分辨率的地点信息， （目标3）正式评估信息的价值 全基因组测序所提供的，并估计成本和成本效益， 病原体基因组数据测序和分析能力。

项目成果

Spatial modeling of Mycobacterium tuberculosis transmission with dyadic genetic relatedness data.

使用二元遗传相关性数据对结核分枝杆菌传播进行空间建模。

• DOI: 10.1111/biom.13836
• 发表时间: 2023
• 期刊: Biometrics
• 影响因子: 1.9
• 作者: Warren,JoshuaL;Chitwood,MelanieH;Sobkowiak,Benjamin;Colijn,Caroline;Cohen,Ted
• 通讯作者: Cohen,Ted

Re-evaluating the health impact and cost-effectiveness of tuberculosis preventive treatment for modern HIV cohorts on antiretroviral therapy: a modelling analysis using data from Tanzania.

• DOI: 10.1016/s2214-109x(22)00372-2
• 发表时间: 2022-11
• 期刊: LANCET GLOBAL HEALTH
• 影响因子: 34.3
• 作者: Zhu, Jinyi;Lyatuu, Goodluck;Sudfeld, Christopher R.;Kiravu, Anna;Sando, David;Machumi, Lameck;Minde, John;Chisonjela, Fikiri;Cohen, Ted;Menzies, Nicolas A.
• 通讯作者: Menzies, Nicolas A.

Neighbourhood prevalence-to-notification ratios for adult bacteriologically-confirmed tuberculosis reveals hotspots of underdiagnosis in Blantyre, Malawi.

• DOI: 10.1371/journal.pone.0268749
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7

Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

• DOI: 10.1016/s2352-4642(23)00004-4
• 发表时间: 2023-05
• 期刊: LANCET CHILD & ADOLESCENT HEALTH
• 影响因子: 36.4
• 作者: Gunasekera, Kenneth S.;Marcy, Olivier;Munoz, Johanna;Lopez-Varela, Elisa;Sekadde, Moorine P.;Franke, Molly F.;Bonnet, Maryline;Ahmed, Shakil;Amanullah, Farhana;Anwar, Aliya;Augusto, Orvalho;Aurilio, Rafaela Baroni;Banu, Sayera;Batool, Iraj;Brands, Annemieke;Cain, Kevin P.;Carratala-Castro, Lucia;Caws, Maxine;Click, Eleanor S.;Cranmer, Lisa M.;Garcia-Basteiro, Alberto L.;Hesseling, Anneke C.;Huynh, Julie;Kabir, Senjuti;Lecca, Leonid;Mandalakas, Anna;Mavhunga, Farai;Myint, AyeAye;Myo, Kyaw;Nampijja, Dorah;Nicol, Mark P.;Orikiriza, Patrick;Palmer, Megan;Sant'Anna, Clemax Couto;Siddiqui, Sara Ahmed;Smith, Jonathan P.;Song, Rinn;Thuong, Nguyen Thuy Thuong;Ung, Vibol;van der Zalm, Marieke M.;Verkuijl, Sabine;Viney, Kerri;Walters, Elisabetta G.;Warren, Joshua L.;Zar, Heather J.;Marais, Ben J.;Graham, Stephen M.;Debray, Thomas P. A.;Cohen, Ted;Seddon, James A.
• 通讯作者: Seddon, James A.

Spatially-targeted tuberculosis screening has limited impact beyond household contact tracing in Lima, Peru: A model-based analysis.

• DOI: 10.1371/journal.pone.0293519
• 发表时间: 2023
• 期刊: PloS one
• 影响因子: 3.7