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研究生:梁淑媛
研究生(外文):Shu-Yuan Liang
論文名稱:HLA-Cw*0801與嚴重急性呼吸道症候群(SARS)—和平醫院院內SARS感染之血清流行病學及其HLA病例對照研究
論文名稱(外文):HLA-Cw*0801 and SARS—Seroepidemiology of SARS infection in Hoping hospital and HLA case-control study
指導教授:陳宜民陳宜民引用關係
指導教授(外文):Ying-Ming Chen
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:公共衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
中文關鍵詞:嚴重急性呼吸道症候群和平醫院人類白血球抗原
外文關鍵詞:severe acute respiratory syndromeHoping hospitalhuman lymphocyte antigen
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嚴重急性呼吸道症候群(SARS)的致病原是一種新的冠狀病毒—SARS冠狀病毒(SARS-CoV)。它造成全球31個國家及地區的8,400多民眾感染,超過800多人的死亡(WHO)。台灣自2003年3月至7月,共有671個SARS 可能病例,已造成84人死亡。這些感染SARS的病例多是院內感染,尤其是以和平醫院爆發院內感染規模最大,共有137位與和平醫院有關的SARS可能病例,其中45位(33%)是醫院工作者,有26位(19%)死亡。本研究的目的有三:一、探討SARS爆發期間和平醫院院內感染SARS的可能危險因子,並且觀察是否有無症狀感染者。二、比較不同SARS血清學診斷方法。三、以和平醫院員工之性別、年齡及工作單位配對的病例對照研究來探討HLA class I及class II基因型與SARS感染的相關性。
本研究將658位和平醫院員工以ELISA做初步篩檢,之後將ELISA陽性及疑似個案,以Western blot做確認,最後有20(3%)位員工血清呈陽性反應,且其中有一位為無症狀感染。與血清陰性個案組相比,發現職務、工作地點、症狀分布以及是否曾照顧過SARS病患方面在兩組間有統計上顯著差異(p < 0.01)。
SARS血清學診斷方面,使用重組蛋白的西方墨點法與中和性抗體試驗結果一致性很高(kappa=0.9283)。整體而言,IFA、ELISA及快速篩檢的敏感度及特異度都大於80%,皆可以作為不錯的診斷方法。
在病例對照研究方面,HLA class I的HLA-Cw*0801對偶基因分布在兩組間有顯著差異(p= 0.01),血清陽性個案組有22.5%(9/40)的對偶基因為Cw*0801,對照組只有6.1%(5/82),帶有此型的人感染SARS的危險性是4.47倍(95%CI=1.39-14.40; p < 0.01)。而HLA class I中HLA-A及B與HLA class II中HLA-DR及DQ的基因型在病例及對照組間則沒有統計上顯著差異。從表現型來看,與兩對偶基因皆不是Cw*0801相比,兩個對偶基因和其中一基因為Cw*0801的人,其得SARS的危險性分別是6.0倍和4.2倍。以條件式邏輯斯迴歸分析(conditional logistic regression)結果發現,在考慮了年齡的影響下,具有HLA-Cw*0801的人感染SARS的危險性是3.52倍(p< 0.05)。這是全球第一個使用病例對照法研究HLA與SARS感染的關係。
HLA-Cw*0801基因型可能是感染SARS的易感受性因子。在台灣地區與中國大陸帶有此基因型的人都有較高的比率,較美國和德國的白種人高出許多,與SARS感染情形相呼應,所以HLA-Cw*0801可能是感染SARS的一個重要標記,可作為預防疾病的參考。
The etiology for severe acute respiratory syndrome (SARS) is a new coronavirus-SARS-CoV. In 2003, more than 8,400 persons in 31 countries or regions had SARS and resulted in more than 800 deaths. In Taiwan, there were 664 probable SARS cases including 84 deathes. Most of the SARS cases in Taiwan were due to nosocomial infection, among those hospitals with nosocomial infection, Hoping hospital were most affected. Therefore, there were three specific aims of this study: 1. To analyze risk factors associated with SARS infection in Hoping hospital; 2. To compare different diagnostic tests for SARS-CoV infection; 3. To study the association of HLA class I and class II genotypes with SARS infection.
Blood samples and questionnaires were collected from 658 employees from Hoping hospital. An enzyme immunoassay (EIA) using SARS-CoV recombinant nucleocapsid protein was developed to screen all the serum samples and the resultant positive cases were further confirmed by using Western blot assay (WB).The results showed that here were 20 (3%) seropositive cases and one of them was asymptomatic. Compared between seropositive and seronegative groups, we found that occupations, workplaces, related symptoms and have taken cared of SARS patients were risk factors associated with SARS-CoV infection (p< 0.01).
SARS serological diagnosis, high coidentity results of western blot and neutralizing antibody tests (kappa=0.9283). Overall, sensitivity and specificity of IFA, ELISA and Quick test were above 80%.

In the case-control study, the HLA-Cw*0801 allelic frequency in the seropositive and seronegarive control groups were 22.5% (9/40) and 6.1% (5/82), respectively (p< 0.01; Odds ratio= 4.47). Compared with non-HLA-Cw*0801 genotype, the relative risks of contracting SARS among people who were heterozygous or homozygous HLA-Cw*0801 were 6.0 and 4.2, respectively. Conditional logistic regression analysis controlled by age demonstrated that the risk for people carring HLA-Cw*0801 to be infected with SARS-CoV was 3.52 (p<0.05).
This is the first study using a case-control study design to analyze high risk HLA genotype with SARS-CoV infection. Since people with HLA-Cw*0801 genotype is more susceptible factor for SARS infection, it can be used for screening high-risk health care workers for SARS-CoV in the future.
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