| 研究生: |
蔡進相 Tsai, Chin-Shiang |
|---|---|
| 論文名稱: |
新興社區腸道病原研究 Emerging Enteric Pathogens in the Community |
| 指導教授: |
柯文謙
Ko, Wen-Chien 蔡坤哲 Tsai, Kuen-Jer |
| 學位類別: |
博士 Doctor |
| 系所名稱: |
醫學院 - 臨床醫學研究所 Institute of Clinical Medicine |
| 論文出版年: | 2024 |
| 畢業學年度: | 112 |
| 語文別: | 英文 |
| 論文頁數: | 105 |
| 中文關鍵詞: | 桿菌性痢疾 、性傳播淋巴肉芽腫 、困難梭狀桿菌 、男同志族群 、愛滋病毒 |
| 外文關鍵詞: | shigellosis, lymphogranuloma venereum, Clostridiodes difficile, men who have sex with men, human immunodeficiency virus |
| ORCID: | https://orcid.org/0000-0002-9391-1561 |
| ResearchGate: | https://www.researchgate.net/profile/Chin-Shiang-Tsai |
| 相關次數: | 點閱:52 下載:0 |
| 分享至: |
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腹瀉是自古以來就困擾人類的疾病,病原從細菌、寄生蟲到病毒,千變萬化。近年有多種新興腸道病原進入台灣社區,男同志族群發生群聚。近年桿菌性痢疾台灣本土個案,占比高於境外移入個案,多為男同志或愛滋感染者。古老性傳染病:披衣菌,具侵襲性的淋巴肉芽腫(lymphogranuloma venereum, LGV),也在台灣男同志族群出現,表現直腸炎感染症狀。產毒性困難梭狀桿菌,特別是RT078家族在環境或屠宰場被發現;男同志性行為模式,可能傳播困梭桿菌。我們針對抗藥性志賀氏菌、披衣菌感染(含LGV)及RT078家族困梭桿菌,三種社區新興腸道病原 ,結合臨床實務,進行分子流行病學調查。與疾病管制署及國內11家愛滋指定醫院合作之多中心研究,顯示桿菌性痢疾本土個案占比,逐年上升。2015年以前,本土個案以食媒或不清潔水源為主要感染途徑,兒童患者占多數;2015年以後,以男同志族群或愛滋感染者為主,前驅症狀與住院天數也較長。2015-2018年桿菌性痢疾常見菌種為ciprofloxacin-resistant Shigella sonnei ,另亦有azithromycin-non-susceptible Shigella flexneri 3a流通 。2018年以後本土桿菌性痢疾個案以ciprofloxacin-resistant S. flexneri 2a為主。志賀氏菌菌株對經驗性抗生素,具抗藥性比例上升,意味著經驗性抗生素失敗機會增加,病程會延長。針對南台灣男同志族群監測,發現直腸披衣菌帶菌比例6.2% 。另發現5例直腸淋巴肉芽腫感染,都有明顯症狀,甚至表現為慢性腹瀉;四位是愛滋感染者。經14-28天doxycycline治療後康復。更發現亞洲首例L2b變異株,導致典型淋巴肉芽腫感染案例。這六個L2b檢體進行MLST分型發現以ST53為主 ,實驗室監測發現ST53已在台灣各地流通,另於多中心合作監測發現於國外曾流行之ST-58及首次發現的ST-63 、ST-39 。2020年1至9月進行男同志困梭桿菌糞便篩檢,發現愛滋感染者檢出率5.9% ,非愛滋感染者檢出率1.9% 。男同志有產毒性困梭桿菌糞便移生情況,愛滋病患者檢出率更高;其中有tcdA基因缺失產毒性困梭桿菌。我們在河川採集樣本發現產毒性、RT078家族的高毒性困梭桿菌,顯示在台灣社區有環境傳播的可能性 。我們監測顯示臨床困梭桿菌RT078家族比例逐年增加,應考慮預防或介入措施,減少傳播或防止感染發生。
Diarrhea has been a longstanding concern for humans, with pathogens ranging from bacteria, parasites, to viruses, presenting diverse challenges. In recent years, some emerging enteric pathogens from western countries entered Taiwan, particularly clustering among community of men who have sex with men (MSM). The proportion of indigenous cases of shigellosis (bacillary dysentery), especially among MSM or people with HIV (PWH), has significantly surpassed that of imported cases in Taiwan in recent years. Some sexually transmitted infections (STIs), such as lymphogranuloma venereum (LGV), a more invasive form of chlamydia, may also be circulating among MSM in Taiwan. Besides, hypervirulent strains of Clostridioides difficile, notably the RT078 lineage, have been discovered in the environment and slaughterhouses, prompting attention to the potential transmission of C. difficile via sexual behaviors among MSM. To address emerging community-acquired enteric pathogens, including antimicrobial-resistant Shigella, Chlamydia trachomatis, and C. difficile, a comprehensive molecular epidemiological investigation combined with clinical practice is imperative. Besides the collaboration with Taiwan Centers for Disease Control (CDC), a multicenter study was conducted in 11 designated hospitals for HIV management in Taiwan, and revealed the proportion of indigenous cases of shigellosis has been steadily rising. Before 2015, indigenous cases were primarily a foodborne disease and could be transmitted through contaminated water sources, with children being the majority of patients. However, since 2015, the majority of cases have been among MSM or PWH. From 2015 to 2018, ciprofloxacin-resistant Shigella sonnei was the most common strain, with Shigella flexneri 3a not susceptible with azithromycin circulating. Since 2018, indigenous cases of shigellosis have been predominantly caused by fluoroquinolone-resistant S. flexneri 2a. Patients with shigellosis after 2015 have experienced longer prodromal symptoms and hospital stays. The study also found a high proportion of inappropriate empirical use of antibiotics due to antimicrobial resistance. In a surveillance of sexually transmitted infections (STIs) among MSM in southern Taiwan, we found that the proportion of rectal chlamydia was approximately 6.2%. Among them, five cases had rectal LGV with obvious symptoms, including chronic diarrhea. Four of them were PWH. After 14-28 days of doxycycline treatment, all patients recovered. We also identified the first case of urethritis caused by the genovariant L2b in Asia. Multi-locus sequence typing (MLST) of these six L2b samples revealed that ST53 was predominant. Further multicenter laboratory surveillance showed that ST53 has been circulating throughout Taiwan, and we identified ST-58, which had previously spread abroad, and the newly discovered ST-63 and ST-39. Therefore, we have provided solid evidence of ongoing clonal spread of C. trachomatis genovariant L2b in Taiwan. In another study among MSM conducted from January to September 2020, the detection rate of toxigenic C. difficile was approximately 5.9% among PWH and 1.9% among HIV-negative individuals. Fecal toxigenic C. difficile colonization (tCdC) was observed among MSM, with a higher detection rate among PWH. We identified toxigenic C. difficile strains with tcdA deletion. Transmission of C. difficile in the community, especially toxigenic and hypervirulent strains of C. difficile including RT078 family, can be found in river, suggesting an environmental spread. There is also an increasing trend of RT078 family among clinical C. difficile isolates in our surveillance. Further interventions should be considered to reduce pathogen transmission or prevent from C. difficile infection.
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