Understanding the transmission of tuberculosis using Mycobacterium tuberculosis sequence data

结核病是一种传染病，造成很高的公共卫生负担。世界卫生组织估计，每年新增病例900万例，死亡近200万例。确定谁向谁传播以及在哪里传播是疾病控制的基础。通过比较大规模人群研究中引起结核病的细菌的基因图谱，我们可以根据菌株的相似性来识别可能的传播。我们的工作最初将集中在马拉维的一个地区，那里的结核病发病率很高，20年来收集了近2500名患者的数据和结核病样本。推断的遗传图谱将使用比以前使用的更高比例的基因组，从而能够更准确地重建传播链。然后，将通过查看每个传输链中的数据模式来直接评估影响传播性的因素。这些因素可能是细菌本身的遗传变异，也可能是人类宿主的差异，包括年龄、性别、艾滋病毒感染和治疗以及接触模式。我们将尝试使用从其他人群收集和生成的数据来证实对这些因素的任何见解。最终，对遗传性和其他潜在遗传性过程的更好理解可能导致改进控制措施的制定。这些可能包括新的药物或疫苗目标，或者确定地理或社会决定的传播热点。

Tuberculosis is an infectious disease that causes a high public health burden. The World Health Organisation estimates that there are nine million new cases and nearly two million deaths each year. Establishing who transmits to whom and where is fundamental to disease control. By comparing the genetic profiles of tuberculosis-causing bacteria within large population-based studies we can identify likely transmissions based on the similarity of the strains. Our work will focus initially on a district of Malawi where tuberculosis disease prevalence has been high, and data and tuberculosis samples from nearly 2500 patients have been collected over twenty years. The inferred genetic profiles will use a higher proportion of the genome than used previously, allowing more accurate reconstructions of transmission chains. Factors influencing transmissibility will then be assessed directly by looking at the patterns of data within each transmission chain. These factors may be genetic variations within the bacteria themselves, or differences in the human hosts, including age, sex, HIV infection and treatment, and contact patterns. We will attempt to confirm any insights into these factors using data collected and generated from other populations. Ultimately, an improved understanding of the genetic and other processes underlying transmissibility could lead to the development of improved control measures. These could include novel drug or vaccine targets, or identification of geographical or socially determined hotspots of transmission.