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

2014年，全球有超过950万人患上了结核病，其中150万人死于这种疾病。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%。尽管它作为一个全球公共卫生问题很重要，但人们对结核分枝杆菌在哪里传播(结核分枝杆菌是导致大多数结核病的细菌)知之甚少，特别是在南非等高负担国家。这主要是因为很难知道某人是否最近被感染，感染和疾病之间可能需要几十年的时间。对社会联系的研究在给出哪些地点可能对结核分枝杆菌很重要的一些指示方面是有用的。变速箱。然而，这些研究不足以估计大多数传播发生在哪里，这主要有三个原因：1)结核病患者的传染性以及人们对感染和疾病的易感性存在很大差异(例如，艾滋病毒携带者的风险增加)。因此，最具传染性的人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接触人数最多的地方，但这些地点可能不是人们花费时间最多的地方，也不是人们每次访问时遇到其他人最多的地方。2)传播可能更频繁地发生在拥挤、通风不良的建筑物中，几乎没有自然光。3)传播可能更常见于既有结核病患者去过的地方，也有最容易感染结核病的人去过的地方(如诊所)。在这项研究中，我们将更好地了解结核分枝杆菌在哪里。传播发生在结核病负担高的国家，并利用这些信息为减少结核病死亡和痛苦的战略提供信息。我们将以南非开普敦为例进行研究。我们有四个主要任务：1)建立一个人的接触和感染传播的模型，以调查易感性和传染性的变化如何影响传播发生的地方，例如结核分枝杆菌。和其他感染。2)使用问卷收集新数据，使我们能够按地点估计素不相识的人之间的接触比例。我们还将收集不同类型地点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，建立M.tb的模型。按位置传输。使用这一模型，我们将估计在开普敦不同地点发生的传播比例。4)调整该模型以表示接触模式、易感性水平(例如艾滋病毒流行率)和结核分枝杆菌水平。在撒哈拉以南非洲其他高负担地区的传播。然后，我们可以估计哪些类型的位置传播在其他国家可能很常见。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(UV))最有效的目标位置。这项研究将有助于填补我们对结核病理解中的一个主要空白：传播发生在哪里？这具有非常真实、实际的影响。紫外线灯的试验表明，紫外线灯可以减少70%-80%的传播，改善通风也可以非常有效地预防感染。这些感染控制措施经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这些措施。我们的结果将为针对感染控制措施提供信息，如果成功，应该会导致结核分枝杆菌的减少。在结核病的传播和死亡和痛苦中。我们的新理解还应有助于在高结核病负担环境下实现世卫组织2025年结束结核病战略目标，这些环境最需要新的、创新的和具有成本效益的预防战略。

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.