École de Santé Publique de L'Université de Montréal (ESPUM), Université de Montréal, Montréal, Canada.
Centre de Recherche du Centre Hospitalier de L'Université de Montréal, Université de Montréal, Montréal, Canada.
Trials. 2024 Oct 25;25(1):717. doi: 10.1186/s13063-024-08537-4.
Retrospective and descriptive molecular epidemiology studies have shown that Mycobacterium tuberculosis whole genome sequencing can identify outbreaks and disease transmission events with higher resolution than conventional epidemiological investigations. Those studies have strengthened our understanding of genomic polymorphisms correlating with person-to-person transmission and helped resolve putative transmission clusters. To date, systematic genomic surveillance programs implemented for M. tuberculosis were only implemented in low-incidence settings. The purpose of this study is to determine whether there is an impact of routine M. tuberculosis whole genome sequencing on tuberculosis case detection in a high-incidence setting.
A cluster randomized controlled trial will be performed. Forty-eight rural village groups (or Fokontany) in the Vohibato district of Madagascar will be randomized to one of three interventions arms. Arm 1 (standard of care) involves healthcare facility-based passive case detection with smear microscopy testing. Arm 2 (best practice) consists of active case finding and Xpert MTB/RIF Ultra PCR testing followed by household contact investigations. Arm 3 (novel intervention) includes the same interventions as arm 2, with addition of sputum culture and M. tuberculosis whole genome sequencing for all newly diagnosed cases. In arm 3, molecular suggested putative outbreaks are investigated, and additional TB suspects are appropriately tested. The intervention observational period will be 2 years. The primary outcome will be the number of detected cases/100,000/year in each arm after 1 year of intervention.
This study is designed to determine whether there is an impact of prospective whole genome sequencing-based molecular typing on tuberculosis case detection in high-incidence settings. Investigating potential outbreaks and focusing active case finding in spatiotemporal settings where disease transmission is suggested by genomic typing is hypothesized to improve case detection in rural communities.
ClinicalTrials.gov NCT05406453 . Retrospectively registered on June 6, 2022.
回顾性和描述性分子流行病学研究表明，结核分枝杆菌全基因组测序可以比传统的流行病学调查更准确地识别暴发和疾病传播事件。这些研究加强了我们对与人际传播相关的基因组多态性的理解，并有助于解决疑似传播集群。迄今为止，仅在低发病率环境中实施了针对结核分枝杆菌的系统基因组监测计划。本研究旨在确定在高发病率环境中，常规结核分枝杆菌全基因组测序对结核病病例检出是否有影响。
将进行一项集群随机对照试验。马达加斯加沃希贝托区的 48 个农村村庄（或福孔塔尼）将随机分为三个干预组之一。第 1 组（标准护理）涉及医疗机构基于涂片显微镜检查的被动病例发现。第 2 组（最佳实践）包括主动病例发现和 Xpert MTB/RIF Ultra PCR 检测，然后对家庭接触者进行调查。第 3 组（新干预）包括与第 2 组相同的干预措施，此外还对所有新诊断病例进行痰液培养和结核分枝杆菌全基因组测序。在第 3 组中，对分子提示的疑似暴发进行调查，并对其他疑似结核病患者进行适当检测。干预观察期为 2 年。主要结局指标是干预 1 年后每个组中每年每 10 万人检出的病例数。
本研究旨在确定前瞻性全基因组测序分子分型对高发病率环境中结核病病例检出的影响。假设通过基因组分型提示疾病传播的时空环境中调查潜在暴发和集中主动病例发现，可以提高农村社区的病例检出率。
ClinicalTrials.gov NCT05406453。于 2022 年 6 月 6 日回顾性注册。
