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研究生:柯靜芬
研究生(外文):Ching-Fen Ko
論文名稱:台灣東部地區2000年至2010年桿菌性痢疾分子流行病學研究
論文名稱(外文):Molecular Epidemiological Study on Shigellosis in Eastern Taiwan during 2000-2010
指導教授:林念璁林念璁引用關係
指導教授(外文):Nien-Tsung Lin
口試委員:李茹萍曾義雄王豊裕李永盛林念璁
口試委員(外文):Ru-Ping LeeYi-Hsiung TsengLi-Yu WangYeong-Sheng LeeNien-Tsung Lin
口試日期:2013-08-29
學位類別:博士
校院名稱:慈濟大學
系所名稱:醫學科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:102
語文別:中文
論文頁數:149
中文關鍵詞:桿菌性痢疾分子流行病學脈衝式凝膠電泳預防性投藥抗生素抗藥性接觸傳染帶菌者
外文關鍵詞:Shigellosismolecular epidemiologypulsed-field gel electrophoresis (PFGE)prophylaxisantibiotic resistanceperson-to-person contactcarrier
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背景:桿菌性痢疾(Shigellosis)是因痢疾桿菌(Shigella spp.)感染而引起的急性腸道傳染病。全球每年大約有一億六千五百萬名桿菌性痢疾病例,並造成全球110萬人死亡。桿菌性痢疾在台灣是法定傳染病,2000至2010年期間每10萬人口發生率介於0.4~6.0人。桿菌性痢疾是台灣東部重要公共衛生議題之ㄧ,但長期的流行病學分析資料尚未被有系統的建立。

方法:彙整台灣東部歷年桿菌性痢疾個案人時地資料及其糞便分離菌株,並應用脈衝式凝膠電泳分析(pulsed-field gel electrophoresis,PFGE)、電泳圖譜BioNumerics分析、抗生素敏感性試驗(antimicrobial susceptibility testing,AST)等技術,進行分子流行病學分析。

結果與討論:台灣東部在2000至2010年間共發生920例桿菌性痢疾病例,其中527例(57.3%)感染Shigella sonnei,393例(42.7%)感染S. flexneri。每10萬人口發生率,除2008年與2009年外,其餘9年均遠高於台灣地區。適合度檢定結果顯示,在年份、性別、年齡、季節、縣市及城鄉別之病例數有顯著差異存在(P值均<0.05)。S. flexneri 1a、4a的分布呈現平地化、機構化現象,S. flexneri 2a則呈現山地化、社區化現象。台灣東部某長期精神照護機構(VNC)在2001至2006年間陸續發現83例有症狀及12例無症狀感染者的桿菌性痢疾疫情,為控制疫情,VNC曾於2004年採取大規模預防性投藥trimethoprim-sulphamethoxazole(SXT)。蒐集自VNC的108株S. flexneri 4a菌株,可分成15種基因型與8種抗藥型,其中具SXT抗藥性的F與J抗藥型在預防性投藥後出現。2名照服員與5名受其照顧住民的發病日相近且基因型相同,顯示VNC疫情可能為人傳人的接觸模式。台灣東部某山地鄉(ZX)桿菌性痢疾每10萬人口平均發生率是台灣的60.2倍,2000至2007年期間ZX山地鄉的38株S. flexneri 2a可分成11種基因型與2種抗藥型,各村或部落的基因型與抗藥型各有其獨特性,顯示痢疾桿菌交叉傳播並不頻繁,可能與山區交通不便及族群不同有關。群聚個案多有同住、玩伴與同學關係,可能為社區內人傳人的接觸傳播模式。

結論:台灣東部桿菌性痢疾個案分佈有其特殊性,S. flexneri 1a與S. flexneri 4a呈現平地化、機構化現象,而S. flexneri 2a則有山地化、社區化現象。VNC與山地鄉是桿菌性痢疾群聚事件好發地,人傳人接觸傳播可能是主要的傳播模式,無症狀帶菌者增加了防治困難。大規模預防性投藥造成選擇性壓力,誘發抗藥性菌株的產生。公共衛生介入措施仍是控制桿菌性痢疾疫情的有效方法。
Background: Shigellosis is an acute enteric infection caused by bacteria of the genus Shigella. In Taiwan, shigellosis is a notifiable disease, with an annual incidence of 0.4–6.0 cases per 100,000 persons (2000–2010). In eastern Taiwan, shigellosis has been one of the major public health issues. However, there was no systematic research of the epidemiological characteristics among the shigellosis events.

Method: The epidemiological data were collected from Taiwan Centers for Disease Control. In this study, we used pulsed-field gel electrophoresis (PFGE), BioNumerics analyses, antimicrobial susceptibility testing (AST) to explore the molecular epidemiology and transmission route of Shigella spp. in eastern Taiwan.

Results: During 2000-2010, there were 920 shigellosis confirmed cases in eastern Taiwan. Among the confirmed cases, 527 cases (57.3%) were infected with Shigella sonnei and 393 cases (42.7%) were infected with S. flexneri. S. flexneri 4a caused sustained outbreaks in a large long-stay psychiatric center (VNC), in eastern Taiwan, 2001–2006. Trimethoprim-sulphamethoxazole (SXT) prophylaxis was administered in 2004. We recovered 108 S. flexneri 4a isolates from 83 symptomatic and 12 asymptomatic subjects. These characteristics altered significantly after SXT prophylaxis (P<0.05), with concomitant emergence of SXT-resistant isolates. P4a01 genotype, caused infection in two caregivers and five patients under their care; two P01 isolates were recovered from the same patient 6 months apart. Thirty-eight S. flexneri 2a were identified from 2000–2007 in the eastern mountainous township of Zhuoxi (ZX). AST results indicated that most isolates in C2a01 were resistant to ACSSuX; all isolates in C2a02 were resistant to ACSSuTX. Genotypes were primarily unique to different villages or tribes. An outbreak (OB2) in 2004 in village V2 was caused by different clonal strains.

Conclusions: The geographical distribution of shigellosis cases in eastern Taiwan was particular. S. flexneri 1a and 4a cases were restricted in VNC and S. flexneri 2a was widely spread in mountainous communities. Transmission of shigellosis likely occurred via sustained person-to-person contact. The long-term convalescent, asymptomatic or caregiver carriers limited the control of shigellosis. The emergence of SXT-resistant strains was likely induced from selective pressure by SXT prophylaxis. The successful public health intervention was helpful to control the endemic disease.

致謝
中文摘要
英文摘要
論文目錄
表目錄
圖目錄

第一章、緒論
第一節、研究背景
一、桿菌性痢疾的流行病學
(一)全球流行狀況
(二)台灣流行狀況
二、桿菌性痢疾介紹
三、病原菌
四、分子分型技術
五、抗藥性
六、傳染力與耐酸性
七、傳染模式
八、感染窩與傳染期
九、慢性帶菌情形
十、免疫力
十一、致病機轉
十二、重症與死亡
十三、治療
(一)藥物治療
(二)併發症治療
十四、預防
第二節、研究動機
第三節、研究目的

第二章、材料與方法
第一節、台灣東部地區2000年至2010年桿菌性痢疾流行病學分析
一、個案流行病學資料
二、痢疾桿菌菌株
三、脈衝式凝膠電泳分析(pulsed-field gel electrophoresis, PFGE)
四、電泳圖譜分析
五、菌株親緣相似度分析(clonal similarity relationship)
六、統計分析
第二節、S. flexneri 4a於某長期精神照護機構內(VNC)的傳播模式與大規模預防性投藥的影響
一、研究機構與對象
二、抗生素敏感性試驗
三、電泳圖譜與菌株親緣相似度分析
四、統計分析
第三節、S. flexneri 2a於某山地鄉(ZX)的傳播模式
一、研究地區與對象
二、抗生素敏感性試驗
三、電泳圖譜與菌株親緣相似度分析
四、統計分析

第三章、結果
第一節、台灣東部地區2000年至2010年桿菌性痢疾流行病學分析
一、桿菌性痢疾個案分析
(一)性別分析
(二)年齡群分析
(三)發病月份分析
(四)居住縣市分析
(五)血清型分析
(六)居住城鄉與血清型分析
(七)機構分析
二、PFGE分子分型分析
(一)S. flexneri 1a PFGE基因型分析
(二)S. flexneri 2a PFGE基因型分析
(三)S. flexneri 4a PFGE基因型分析
(四)S. sonnei PFGE基因型分析
(五)花蓮縣花蓮市某高中與玉里鎮某國小流行事件基因型分析
三、台灣東部地區Shigella spp.基因型地理分布
第二節、S. flexneri 4a於某長期精神照護機構內(VNC)的傳播模式與大規模預防性投藥的影響
一、VNC機構內桿菌性痢疾發生與流行病學監測情形
二、藥物敏感性試驗分析
三、PFGE分子分型分析
四、11名分離出2至3株菌株的個案分析
第三節、S. flexneri 2a於某山地鄉(ZX)的傳播模式
一、ZX山地鄉桿菌性痢疾發生情形
二、抗生素敏感性試驗分析
三、PFGE分子分型分析

第四章、討論
第一節、台灣東部地區2000年至2010年桿菌性痢疾流行病學分析
一、S. flexneri 2a山地社區化、S. flexneri 1a及4a平地機構化
二、人口學討論
三、Shigella spp.基因型地理分布討論
第二節、S. flexneri 4a於某長期精神照護機構內(VNC)的傳播模式與大規模預防性投藥的影響
第三節、S. flexneri 2a於某山地鄉(ZX)的傳播模式

第五章、結論

參考文獻
圖表
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