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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林先和(Hsien-Ho Lin) | |
| dc.contributor.author | Chih-Chan Lan | en |
| dc.contributor.author | 藍之辰 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:08:59Z | - |
| dc.date.copyright | 2022-10-17 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-27 | |
| dc.identifier.citation | Alene, Kefyalew Addis, Hengzhong Yi, Kerri Viney, Emma S. McBryde, Kunyun Yang, Liqiong Bai, Darren J. Gray, Archie C. A. Clements, and Zuhui Xu. 2017. “Treatment Outcomes of Patients with Multidrug-Resistant and Extensively Drug Resistant Tuberculosis in Hunan Province, China.” BMC Infectious Diseases 17 (1): 573. https://doi.org/10.1186/s12879-017-2662-8. Al-Ghafli, Hawra, Thomas A Kohl, Matthias Merker, Bright Varghese, Anason Halees, Stefan Niemann, and Sahal Al-Hajoj. 2018. “Drug-Resistance Profiling and Transmission Dynamics of Multidrug-Resistant Mycobacterium Tuberculosis in Saudi Arabia Revealed by Whole Genome Sequencing.” Infection and Drug Resistance 11 (November): 2219–29. https://doi.org/10.2147/IDR.S181124. Amita, Jain, Tiwari V, and R. S. Guleria. 2002. “Qualitative Evaluation of Mycobacterial DNA Extraction Protocols for Polymerase Chain Reaction.” Mol Bio Today. Baddeley, Adrian, Ege Rubak, and Rolf Turner. 2016. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84342 | - |
| dc.description.abstract | 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。 | zh_TW |
| dc.description.abstract | 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. | en |
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| dc.description.tableofcontents | 中文摘要 i Abstract ii Chapter 1 Introduction 1 1.1 Epidemiology of Drug-resistant Tuberculosis 1 1.2 Development and Transmission of Drug-resistant Tuberculosis 2 1.3 Risk Factors Associated with Drug-resistance among Tuberculosis Patients 4 1.4 Molecular Epidemiology of Tuberculosis Transmission 5 1.5 Investigation of Drug-resistant Tuberculosis Transmission using Whole Genome Sequencing 7 1.6 Research Gap and Study Aim 9 Chapter 2 Material and Methods 10 2.1 Study Setting and Study Design 10 2.2 Sample Collection 10 2.3 Whole Genome Sequencing 11 2.4 Genomic Cluster Identification 13 2.5 Epidemiological and Clinical Information 13 2.6 Statistical Analysis 15 2.6.1. Spatial Analysis 15 2.6.2. Descriptive Analysis and Regression Analysis 16 Chapter 3 Results 17 3.1 Description of Drug-Resistant Tuberculosis in Kaohsiung 17 3.2 Identifying the Potential Risk Factors for Genomic Clustering 18 3.3 Spatial Analysis of Genomic-Clustered Cases 19 3.4 Description of Genomic Clusters 20 Chapter 4 Discussion 23 4.1 Main Findings 23 4.2 Interpretation of Results 23 4.3 Strengths and Limitations 27 4.4 Study Implications and Further Research 27 Reference 36 Appendix 51 Appendix A. Summary of risks factors associated with drug resistance tuberculosis 51 Appendix B. Supplementary for drug resistance profiles 52 Appendix C. Supplementary for spatial analysis 53 Appendix D. Supplementary for phylogeny and transmission trees 54 Table 1 Characteristics of drug resistant and drug susceptible tuberculosis 30 Table 2 Drug resistance profiles obtained from drug susceptibility results 30 Table 3 Characteristics of genomic clustered and unique DRTB cases defined by whole-genome sequencing 31 Table 4 Univariate logistic regression on the risk factors associated with DRTB clustering 32 Table S1 Risk factors associated with drug resistance among tuberculosis patients from previous studies 51 Table S2 Prevalence of any drug resistance in tuberculosis patients defined by drug susceptibility test 52 Figure 1 Illustration of drug resistance emergence mechanisms 3 Figure 2 Flowchart of the inclusion and exclusion of isolates from January 2019 to July 2021 for whole genome sequencing analysis 29 Figure 3 Risk ratio estimation (A) of being a case relative to control and its corresponding p value (B) 33 Figure 4 Distribution of genomic cluster size 34 Figure 5 Distribution of paired SNP distance in genomic cluster 34 Figure 6 Phylogenetic tree for 246 drug-resistant tuberculosis and 4 drug-susceptible tuberculosis isolates 35 Figure S1 Kernel density maps of unique (A) and genomic-clustered (B) drug-resistant tuberculosis 53 Figure S2 Geographic paired distance in genomic clustered cases 53 Figure S3 Phylogenetic tree for drug-resistant tuberculosis isolates of Lineage1 54 Figure S4 Phylogenetic tree for drug-resistant tuberculosis isolates of Lineage2 54 Figure S5 Phylogenetic tree for drug-resistant tuberculosis isolates of Lineage4 56 Figure S6 The phenotypic and genotypic resistant profiles of genomic clusters 57 Figure S7 The transmission trees of genomic clusters 61 | |
| dc.language.iso | en | |
| dc.title | 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 | zh_TW |
| dc.title | Investigating Transmission of Drug-resistant Tuberculosis in Kaohsiung, Taiwan Using Whole-Genome Sequencing | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 盧柏樑(Po-Liang Lu),江振源(Chen-Yuan Chiang),范怡琴(Yi-Chin Fan),安亞克(Andrei Akhmetzhanov) | |
| dc.subject.keyword | 抗藥性結核病,結核病,全基因定序,動態傳播,抗藥性傳播, | zh_TW |
| dc.subject.keyword | drug resistant tuberculosis,Mycobacterium tuberculosis,whole genome sequencing,Taiwan,transmission, | en |
| dc.relation.page | 61 | |
| dc.identifier.doi | 10.6342/NTU202203899 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-09-27 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2024-09-24 | - |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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