- 學位論文
利用全基因體檢驗技術探討抗藥性結核病在高雄之動態傳播
Investigating Transmission of Drug-resistant Tuberculosis in Kaohsiung, Taiwan Using Whole-Genome Sequencing
摘要
背景：抗藥性結核病管理和治療持續為全球衛生的重大挑戰，了解抗藥性結核病區域性的傳播動態，可以幫助制定因地制宜的防治策略。本篇研究旨在結合基因體與流行病學調查資料，了解高雄抗藥性結核病的傳播動態與危險因子。 方法：本研究以高雄通報結核病個案作為研究對象，自2019年1月至2021年7月之間，前瞻性的蒐集通報且培養陽性之個案。將檢體送至全基因定序後，兩兩比較基因差距，將單核甘酸多型性（SNP）之位點小於5的個案視為基因群聚，並加入流行病學調查資料，找出基因群聚中的流病相關與可能的地理關連。 結果：在2,051位結核病個案中，有246位（12%）為抗藥性個案。抗藥性個案中，有32位（13%）判斷為基因群聚相關。在羅吉斯迴歸當中，相比較年齡大於65歲以上之族群，年齡小於65歲的族群有較高的風險被判斷為基因群聚（aOR=2.77）。並且在比較基因相似程度後，共有4位非抗藥與32位抗藥性個案，形成15個基因群聚，大多數基因群聚皆為2個人數。僅有2個群聚發現流病或地理相關性。從藥敏結果判斷在傳播過程可能累積抗藥性，不過在基因上沒有看到抗藥性位點變異累積。 結論：本篇研究發現在高雄，年齡和抗藥性傳播的基因群聚有顯著相關，抗藥性菌株傳播佔抗藥性結核病比例負擔不大。目前傳播群聚並未發現基因位點累積的變異，但仍無法排除抗藥性在傳播過程中累積的可能。透過全基因定序發現傳播群聚後，未來可採用回溯性的疫調方式，了解共同的傳染源或傳染地。
並列摘要
Introduction: Drug resistant tuberculosis (DRTB) is a remaining threat to global health. Knowing the local transmission dynamic can help develop DRTB control strategies. With the combination of genomic and epidemiological information, we aimed to investigate the transmission dynamic and identify potential risk factors for transmission of drug resistance. Methods: We conducted a population-based, prospective genomic study to include notified and culture-confirmed patients with tuberculosis between 2019 January and 2021 July in Kaohsiung, Taiwan. We performed whole genome sequencing (WGS) of patients’ isolates and measured the similarity of strains to classify genomic cluster, defined by a single nucleotide polymorphisms (SNPs) cutoff as 5. Epidemiological link, probable link, and genomic data were combined to illustrate transmission trees. Results: We identified 246 (12%) of DRTB from 2,051 TB cases, and 13% of DRTB cases were attributed to recent transmission. Younger age was found to increase the risk of DR transmission (aOR=2.77) compared to people age over 65. 32 DRTB and 4 non-DRTB patients were grouped into 15 genomic clusters, in which we did not observe cumulation of DR resistance. Most of the clusters contained only two cases. Limited pairs of epidemiological and probable links were found in the genomic clusters. In most of the genomic clusters, no accumulation of drug resistance was found between hosts. Conclusion: Our results demonstrate that age is associated with DRTB transmission, and the ongoing transmission of DRTB might be limited in Kaohsiung. Although no genetic mutations were accumulated between hosts, we cannot fully role out the possibility of resistance accumulating during the transmission. Seldom epidemiological and possible geographical links were found in genomic clusters, it is worth a backward investigation to find the common source or place of transmission in the future. Future study should continue to surveil the transmission of DRTB occurred in Kaohsiung.
參考文獻
延伸閱讀
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