2021-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/670348"結核病為國內重要法定傳染病之一，且在防治上的重大挑戰，是因為可傳播期與潛伏期均長，所以常規疫情調查不容易確立個案之間的關聯性，且常有未被發現之疫情。這代表公共衛生端可能錯過及早發現疫情且加以介入控制(包含活動個案發現以及潛伏個案之預防性投藥)之最佳時機。為達到更佳之疫情防治，近年來國際上紛紛將傳統結核病分子流行病學工具，逐漸進化至全基因定序(whole genome sequencing)，並發現其在公衛端廣泛應用之可能性，然相關研究在國內卻是闕如。 本研究將在高雄建立長期且具有地理覆蓋性之流行病學研究，預計將所有結核菌培養陽性之病患檢體進行全基因定序與生物資訊分析。以精準結核病防治(precision tuberculosis control)為核心概念，我們將把全基因定序結果與常規結核病防疫資料結合，並且同時使用地理空間分析工具。研究將探討與深入剖析高雄地區可能的結核病群聚，找出結核病傳播之危險因子與空間群聚，探討使用定序資料決定群聚時之適當SNP切點，以及推測傳播可能發生途徑之可能傳播樹(transmission tree)。 本研究設計結合基因體學、流行病學與空間資訊之多元大數據資料，將對於全基因定序在國內甚至國際公共衛生傳染病防治之應用，產生重大之指標性意義。研究結果亦將對國內結核病疫情控制之政策制定有重大幫助。" "Tuberculosis (TB) remains a leading infectious cause of mortality and morbidity in Taiwan and globally. Uncovering and intervening on ongoing transmission is essential for TB control. However, identifying community transmission of TB (i.e., the transmission outside household) through routine public health investigation has shown to be difficult because of the airborne nature of the disease and the non-specific symptoms. Recently, Taiwan CDC has started to provide diagnosis of latent TB infection followed by preventive therapy. In order to expand the impact of LTBI treatment, preventive therapy has to be scaled up to other latently infected populations who are at the greatest risk of progression. This too requires a good understanding of TB transmission dynamics in the community in order to identify those who are at the highest risk of transmission and progression. Previous molecular epidemiological studies of TB transmission in Taiwan were mostly hospital-based studies or collected convenient samples using a nonpopulation- based approach, and relied on conventional molecular epidemiologic tools (MIRU-VNTR and spoligotyping) which only examined specific locations of M.tb genome. The emergence of whole genome sequencing (WGS) provides an unparalleled opportunity to obtain molecular fingerprinting at the finest genomic level. We propose to conduct a four-year, multi-center, population-based epidemiologic study of TB transmission in Kaohsiung City. The central theme and novelty of this study is the universal whole genome sequencing of all culture-confirmed cases in the catchment area and combining the genomic information with public health information. For this purpose we already assembled a strong study team including the head of major medical centers in Kaohsiung, the head of national TB reference laboratory, and Kaohsiung Department of Health. An anticipated 900-970 cases of TB will be sequenced annually. The public health information will be obtained through routine TB program data from Kaohsiung Department of Health. The two sources of information will be combined for inference under strict patient protection. Specifically we aim to conduct the following analyses: 1. Identifying transmission clusters of TB using information from the WGS analysis, supported by epidemiologic evidence; 2. Determine the SNP (single nucleotide polymorphism) cutoff for defining transmission cluster using extern information; 3. Investigating the determinants of and high risk groups or locations of TB transmission; 4. Inferring on the directed infection networks (“who infected whom”) in the study population. To summarize, combining the detailed genomic information with public health information, our proposed study will for the first time uncover the comprehensive picture of TB transmission dynamics in a metropolitan city in Taiwan. We predict that WGS-based precision public health investigation will soon be a major tool for infectious disease control (not limited to TB) in Taiwan and globally and will take advantage of this project to train the academicians and practitioners on the use of this new tool. The valuable information and lessons learned in this study, and the knowledge and skills gained during the study process, will be valuable in the near future when Taiwan as well as the global public health society enters the era of precision public health."