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系統識別號 U0026-1407201717011400
論文名稱(中文) 感染登革熱病毒之人體IgM抗體持久性
論文名稱(英文) IgM persistence in dengue virus infected people
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 105
學期 2
出版年 106
研究生(中文) 劉子瑚
研究生(英文) Zi-Hu Liu
學號 S76044117
學位類別 碩士
語文別 中文
論文頁數 39頁
口試委員 指導教授-郭浩然
共同指導教授-簡玉雯
口試委員-彭貴春
口試委員-陳國東
中文關鍵字 登革熱  IgM抗體持續性  無症狀感染 
英文關鍵字 dengue virus  IgM persistence  asymptomatic 
學科別分類
中文摘要 背景:
由於登革熱症狀不具有特異性,因此在臨床診斷時必需仰賴實驗室的證據,其中在診斷急性或近期感染時,以檢驗IgM抗體的表現是最為廣泛應用的指標。雖然世界衛生組織的指導手冊與許多文獻回顧文章引用早年的研究指出IgM抗體在發病後二到三個月就會衰減至檢驗不到濃度,但近期有一研究指出其能夠持續存在至六個月。然而過去的研究族群多是針對年齡較小甚至未知受試者年齡分布,且儘管登革熱有高比例是無症狀感染,卻沒有太多關於此族群IgM抗體的研究。
目的:
探討成人感染登革熱病毒後IgM抗體的持久性與有無症狀對IgM抗體的持久性是否有影響。
方法:
追蹤2015年台南登革熱爆發末期時,在各疫情熱點所進行的血清調查中IgM抗體呈現陽性的受試者,於六個月與十二個月後收集其周邊血液檢體,以兩種商用的酵素結合免疫吸附法試劑分析IgM抗體的變化(SD ELISA與Focus ELISA),同時也使用快速篩檢試劑檢測IgM抗體。研究結果使用費雪精確檢定類別變項,利用線性迴歸模型估計IgM抗體的衰減率以及抗體的持久性。
結果:
本研究共追蹤44名受試者,其中61.4%是無症狀感染。使用兩組酵素結合免疫吸附法試劑的結果在第六個月與第十二個月檢驗受試者所呈現的IgM抗體陽性率之間有顯著差異(p<0.0001)。且感染有無症狀表現與IgM抗體持久性在統計上沒有相關性。線性迴歸估計有症狀感染者,使用SD ELISA指出感染者在發病後338.3(95% CI 279.7 – 446.9)天其IgM抗體才衰減至無法檢測到的濃度,而使用Focus ELISA檢驗則IgM抗體在持續175.7(95% CI 121.9 – 221.1)天後就無法檢測到。在血清調查初期、第六個月與第十二個月依序有86.4%、68.2%和35.9%的受試者使用快速篩檢能夠在血液樣本裡檢驗到IgM抗體。
結論:
本研究顯示感染登革熱病毒後人體內IgM抗體的持久性與先前文獻相比還要長,因此不論是臨床或是疾病監測時,尤其是在前一年有登革熱大流行的地區,利用IgM抗體作為急性或近期感染的指標是需要更多的考量與審慎的評估。另外透過研究認為IgM抗體的持久性與感染是否有症狀之間沒有相關性。
英文摘要 INTRODUCTION:
Dengue fever (DF) is one of the most important vector-borne diseases worldwide. Diagnosis of DF requires laboratory confirmation because the clinical symptoms are non-specific. Detection of dengue specific Immunoglobulin M (IgM) is a widely used diagnostic tool to identify acute or recent infections. Many reviews and guidelines cite studies decades ago and state that IgM persists only for 2-3 months. However, the duration of IgM persistence remains controversial. Furthermore, the majority dengue infections are asymptomatic but IgM persistence among them is still unclear. The aim of this study was to investigate IgM persistence in adults using currently available commercial kits and compare it between symptomatically and asymptomatically infected people.
MATERIALS AND METHODS:
Serum samples were collected during 2015 dengue outbreak in Tainan. Among volunteers with positive IgM who agreed to participate the study 6 and 12 months later, ELISA kits from Standard Diagnostics (SD) and Focus Diagnostics as well as the SD rapid diagnostic test (RDT) were used to detect IgM among participants. Fisher’s exact tests were performed to compare proportion of positive IgM between different groups. Linear regression models were used to estimate the decay rate and persistence of IgM after acute infection.
RESULTS:
Overall 44 subjects were enrolled in our study; the average age were 55 years and 61.4% of them were asymptomatically-infected. Detection of anti-DENV IgM rates of the two commercial ELISA kits were significantly different at 6 and 12 months (p<0.0001). At the 6 and 12 months, 70.5% amd 46.2% of the subjects still remain IgM-positive using the SD ELISA. For the Focus ELISA, only 13.6% and 7.7% of them had detectable IgM level. There was no significant difference in the IgM persistence between symptomatic and asymptomatic people after 6 and 12 months. Regression analysis estimated that IgM reached undetectable level after 338.3 days (95% CI 279.7 – 446.9) by the SD ELISA (Figure 1A) and 175.7 days (95% CI 121.9 – 221.1) by the Focus ELISA (Figure 1B), respectively, among people with symptomatic infection. For the SD RDTs, there were 86.4%, 68.2% and 35.9% subjects had definitely positive IgM results at initial, 6 months and 12 months respectively (Table 3).
CONCLUSION:
Our study showed that anti-DENV IgM persisted much longer than previously thought, indicating that it’s crucial to reconsider how to interpret the detection of anti-DENV IgM for the diagnosis or surveillance purpose, particularly when a large dengue outbreak have occurred in the previous year. Also, we found there was no difference in the persistence of anti-DENV IgM between people with symptomatic and asymptomatic infection.
SUMMARY:
Our study showed that anti-DENV IgM persisted much longer than previously thought, indicating that it’s crucial to reconsider how to interpret the detection of anti-DENV IgM for the diagnosis or surveillance purpose, particularly when a large dengue outbreak have occurred in the previous year. Also, we found there was no difference in the persistence of anti-DENV IgM between people with symptomatic and asymptomatic infection.
論文目次 摘要 I
Extended Abstract III
致謝 V
表目錄 IX
圖目錄 X
壹、緒論 1
1.1登革熱介紹與全球流行概況 1
1.2台灣登革熱疫情歷史與近況 4
貳、文獻探討 7
2.1人體感染病毒後體內變化及其在臨床實驗診斷方法的應用 7
2.1.1分離病毒(Virus isolation) 7
2.1.2檢驗病毒核醣核酸(Viral RNA detection) 8
2.1.3檢驗抗原(Antigen detection) 8
2.1.4檢驗抗體(Antibody detection) 9
2.2抗體檢驗實驗方法的發展 10
2.3 IgM抗體的廣泛應用與其持續時間 11
2.4無症狀感染 11
參、研究的重要性 14
肆、研究動機與目的 15
伍、材料與方法 16
5.1樣本採集 16
5.2樣本分析 17
5.2.1酵素結合免疫吸附法(Enzyme-linked immunosorbent assay, ELISA) 17
5.2.2抗原抗體快速篩檢(Duo rapid diagnostic tests, RDT) 18
5.3統計分析 18
Ethics statement 19
陸、研究架構 20
柒、研究結果 21
7.1受試者人口學描述 21
7.2兩組酵素結合免疫吸附法之實驗套件分組比較 23
7.3有無症狀感染與IgM抗體持續性相關性 23
7.4快速篩檢檢驗IgM結果 25
7.5 感染登革熱病毒之IgM抗體持久性 26
捌、討論 28
8.1 感染登革熱病毒後IgM抗體持久性 28
8.2 採用IgM抗體輔助診斷的可行性 29
8.3 無症狀感染者定義與其抗體持久性 30
8.4 兩組酵素結合免疫吸附法之敏感度與特異性 30
8.5 優勢與限制 31
玖、結論 33
拾、參考文獻 34
附錄 39
2015血清調查受試者問卷 39
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