Determining the importance of different locations to Mycobacterium tuberculosis transmission in high tuberculosis burden settings

确定高结核病负担环境中不同地点对结核分枝杆菌传播的重要性

• 批准号: MR/P002404/1
• 负责人: Richard White
• 金额: $ 50.09万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP002404%2F1
• 关键词: Determining; importance; different; locations; Mycobacterium

Over nine and a half million people worldwide developed tuberculosis (TB) in 2014, and 1.5 million died from the disease. Current control strategies are insufficient, with global TB incidence falling by only 1-2% per year. Despite its importance as a global public health problem, very little is known about where Mycobacterium tuberculosis transmission (M.tb., the bacterium that causes the majority of TB disease) occurs, particularly in high burden countries such as South Africa. This is primarily because it is difficult to know whether someone has been recently infected, and it can be decades between infection and disease. Studies of social contacts have been useful in giving some indication of which locations may be important to M.tb. transmission. However, these studies are insufficient to estimate where the majority of transmission occurs, for three main reasons:1) There is a lot of variation in the infectiousness of people with TB disease, and in how susceptible people are to infection and disease (e.g. people living with HIV are at increased risk). For this reason, chance meetings between the most infectiousness and susceptible people are likely be very important to overall transmission in a population. These meetings are most likely to occur in the places where numbers of new people met are highest, but these locations may not be the places where people spend most time, or where people meet the most other people per visit.2) Transmission is likely to occur more often in crowded, badly ventilated buildings with little natural light.3) Transmission is likely to be more common in places that are both visited by people with TB, and also visited by the people most susceptible to TB (e.g. clinics). In this study, we will develop a better understanding of where M.tb. transmission occurs in high TB burden countries, and use this information to inform strategies to reduce TB death and suffering. We will use Cape Town, South Africa, as a case study. We have four main tasks:1) Develop a model of people's contacts and infection transmission to investigate how variation in susceptibility and infectiousness affects where transmission occurs, for M.tb. and other infections.2) Collect new data using questionnaires that will allow us to estimate the proportion of contacts that are between people who have not met before, by location. We will also collect data on the levels of ventilation and natural light in different types of location.3) Using the new data we have collected, as well as existing data, build a model of M.tb. transmission by location. Using this model, we will estimate the proportion of transmission that occurs in different locations in Cape Town.4) Adapt the model to represent contact patterns, susceptibility levels (e.g. HIV prevalence), and levels of M.tb. transmission in other high burden sub-Saharan African settings. We can then estimate in what types of location transmission may be common in other countries. We will also investigate what the most effective locations are to target using infection control interventions (e.g. improving ventilation or installing ultraviolet (U.V.) lights).This study will help to fill a major gap in our understanding of TB: where does transmission occur? This has very real, practical implications. Trials of U.V. lights suggest that they may reduce transmission by 70-80%, and improving ventilation can also be very effective in preventing infections. These infection control measures are often implemented in TB clinics, but we currently do not know where else they should be targeted. Our results will inform the targeting of infection control measures, and if successful, should lead to reductions in M.tb. transmission, and in TB death and suffering. Our new understanding should also contribute to meeting the 2025 WHO End TB Strategy targets in high TB burden settings, the settings most in need of novel, innovative, and cost effective prevention strategies.

2014年，全世界有超过950万人患上结核病，150万人死于结核病。目前的控制战略是不够的，全球结核病发病率每年仅下降1-2%。尽管其作为全球公共卫生问题的重要性，但关于结核分枝杆菌传播（M.tb.，这种细菌导致大多数结核病）的发生，特别是在南非等高负担国家。这主要是因为很难知道某人最近是否被感染，而且感染和疾病之间可能需要几十年的时间。对社会接触的研究有助于说明哪些地点可能对结核病很重要。传输然而，这些研究不足以估计大多数传播发生在哪里，主要原因有三个：1）结核病患者的传染性以及人们对感染和疾病的易感性（例如艾滋病毒感染者的风险增加）存在很大差异。出于这个原因，最具传染性和易感人群之间的偶然相遇可能对人群中的总体传播非常重要。这些会议最有可能发生在新结识的人数最多的地方，但这些地方可能不是人们花费最多时间的地方，或者人们每次访问时遇到最多其他人的地方。通风不良的建筑物，几乎没有自然光。3）传播可能更常见于结核病患者访问的地方，也是最易感染结核病的人群（如诊所）的就诊地点。在这项研究中，我们将开发一个更好地了解结核病。结核病传播发生在结核病高负担国家，并利用这一信息为减少结核病死亡和痛苦的战略提供信息。我们将使用南非的开普敦作为案例研究。我们有四个主要任务：1）开发一个人的接触和感染传播的模型，以研究易感性和传染性的变化如何影响结核病的传播发生。2）使用问卷收集新数据，这将使我们能够估计以前从未见过的人之间的接触比例，按地点划分。我们还将收集不同类型位置的通风和自然光水平的数据。3）使用我们收集的新数据以及现有数据，构建M. tb模型。通过位置传输。使用这个模型，我们将估计在开普敦不同地点发生的传播比例。4）调整模型，以表示接触模式，易感性水平（如艾滋病毒流行率）和结核病水平。在其他高负担的撒哈拉以南非洲环境中传播。然后，我们可以估计在其他国家可能常见的位置传输类型。我们还将调查使用感染控制干预措施（例如，改善通风或安装紫外线（U. V.）这项研究将有助于填补我们对结核病认识的一个主要空白：传播发生在哪里？这具有非常真实的、实际的影响。紫外线灯的试验表明，它们可以减少70- 80%的传播，改善通风也可以非常有效地预防感染。这些感染控制措施通常在结核病诊所实施，但我们目前不知道还应该在哪里实施。我们的研究结果将为感染控制措施的目标提供信息，如果成功的话，应该会导致结核病的减少。结核病的死亡和痛苦。我们的新认识还应有助于在结核病高负担环境中实现2025年世卫组织终止结核病战略目标，这些环境最需要新颖、创新和具有成本效益的预防战略。

项目成果

Additional file 1: of Guidelines for multi-model comparisons of the impact of infectious disease interventions

附加文件1：传染病干预措施影响多模型比较指南

• DOI: 10.6084/m9.figshare.10034417
• 发表时间: 2019
• 作者: Boon S

Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis.

• DOI: 10.1371/journal.pmed.1003566
• 发表时间: 2021-04
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Calderwood CJ;Wilson JP;Fielding KL;Harris RC;Karat AS;Mansukhani R;Falconer J;Bergstrom M;Johnson SM;McCreesh N;Monk EJM;Odayar J;Scott PJ;Stokes SA;Theodorou H;Moore DAJ
• 通讯作者: Moore DAJ

Correction to: Small contribution of gold mines to the ongoing tuberculosis epidemic in South Africa: a modeling-based study.

更正：金矿对南非持续的结核病流行的贡献很小：一项基于模型的研究。

• DOI: 10.1186/s12916-018-1238-9
• 发表时间: 2018
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Chang ST

Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy.

优化 SARS-CoV-2 接种中的疫苗剂量，一项旨在最大限度提高疫苗安全性和功效的多因素优化建模研究。

• DOI: 10.3390/vaccines9020078
• 发表时间: 2021-01-22
• 期刊: Vaccines
• 影响因子: 7.8
• 作者: Benest J;Rhodes S;Quaife M;Evans TG;White RG
• 通讯作者: White RG

Additional file 1: of Small contribution of gold mines to the ongoing tuberculosis epidemic in South Africa: a modeling-based study

附加文件 1：金矿对南非当前结核病流行的微小贡献：一项基于模型的研究

• DOI: 10.6084/m9.figshare.6132308
• 发表时间: 2018
• 作者: Chang S