Using whole genome sequencing to characterise drug resistant Mycobacterium tuberculosis in Thailand

点击翻译按钮获取中文摘要

Tuberculosis is an infectious disease that causes a high public health burden. The World Health Organisation estimates that there are ten million new cases and nearly two million deaths each year. Thailand is classified by WHO as one of the 22 countries in the world with the highest TB burden, with 93,000 new cases each year and an overall estimated TB prevalence of nearly 130,000 cases, 16 percent of whom are also HIV positive. 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 on the Kanchanaburi province of Thailand, where there have been outbreaks of multi-drug resistant TB bacterial strains. This is a province where tuberculosis disease prevalence has been high compared other to regions in Thailand. Tuberculosis samples from patients (n=2,000) attending the largest hospital (Makarak Hospital), spanning a period from 2003 to 2019, will be genetically characterized, and important meta data (e.g. HIV status) curated. 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, and we will seek to identify those associated with drug resistance and transmissibility. Non-genetic factors affecting transmission, such as differences in the human hosts, including age, sex, diabetes, HIV infection and treatment, and contact patterns, will be investigated. We will attempt to confirm any insights into these factors using data collected and generated from other populations in Thailand and globally. Ultimately, an improved understanding of the genetic and other processes underlying transmissibility could lead to the development of improved control measures. These measures could include novel drug or vaccine targets, or identification of geographical or socially determined hotspots of transmission; thereby assisting the Thailand Ministry of Public Health with control strategies, as well as benefiting the Kanchanaburi province and wider Thailand.