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標題: | 以臺灣國小學童的2009年新型流感H1N1抗體評估停課與疫苗政策 Antibody Responses of the 2009 Pandemic Influenza A (H1N1) among Elementary Schoolchildren in Taiwan: Evaluation of Class Suspension and Vaccination |
作者: | Pui-I Ho 何佩怡 |
指導教授: | 金傳春(Chwan-Chuen King) |
關鍵字: | 2009新型流行性感冒,傳播模式,流感疫苗預防接種政策,停課,血清流行病學,危險因子,臺灣,公共衛生防疫策略, 2009 Pandemic Influenza A (H1N1),Transmission,Vaccination,School Closure,Seroepidemiology,Risk Factors,Taiwan,Public Health Policies, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | 新型流感H1N1(pdmH1N1)於2009年在全球肆虐,臺灣政府為了延緩其蔓延,在9月1日開始推行新的停課政策 ─「325停課標準」;並於11月16日對全國中、小學童推廣免費疫苗接種。本研究目的有四:(1)探討在停課高峰後和施打疫苗前,學童新型流感病毒之感染盛行率;(2)找出感染新型流感H1N1病毒的危險因子;(3)比較學童在接種疫苗前後其血清抗體效價之變化;及(4)評估預防接種成效之相關因子。
自2009年11月至2010年3月間,在臺北和高雄各擇選兩所國小二年級至六年級972和1,028位學童,進行血清流行病學世代研究。在獲得家長簽署同意書後,始採集臺北學童三時間點[接種疫苗前 (T1)、接種疫苗後一個月(T2)和接種疫苗後四個月(T3)]與高雄學童兩時間點[T1和T3] 的血清;續以血球凝集抑制試驗(Hemagglutination Inhibition Assay, HI) 測量參與學童對新型流感H1N1疫苗株 [A/California/07/2009(H1N1)] 的抗體反應。單變項分析是以t檢定 (Student t test) 和卡方檢定 (Chi-square test) 比較兩組 (如有、無接種疫苗,有、無停課等) 之間的差異;再以複邏輯斯迴歸 (multiple logistic regression) 、整合廣義估計方程式 [廣估式] (General Estimating Equation) 調整同班學童間的相關性以分析感染新型流感之危險因子及使用複線性迴歸(multiple linear regression)分析接種疫苗後抗體衰退之因子。 結果顯示接種疫苗前臺北學童的2009年新型流感病毒H1N1的感染率 (HI血清效價≥1:10) 遠較高雄學童(49.02% vs 29.74%, p<0.0001)。而有停課學童的感染率也高於沒有停課的學童 (59.60% v.s. 47.45%, p=0.0241)。以廣估式控制性別、年齡、身體質量指數(body mass index)、前驅病史(co-morbidity)後,發現參加課後活動和每週運動多於三小時是臺北學童感染新型流感的危險因子,其調整後勝算比(adjusted odds ratio)分別為2.47 [95% 信賴區間(Confidence Interval, CI):1.02-6.00, p=0.0458) 和2.86 (95% CI:1.19-6.86, p=0.0189);而高雄學童的危險因子為托管於安親班,其調整後勝算比為2.02 (95% CI:1.33-3.07, p=0.001)。粗估臺北與高雄學童的新型流感H1N1病毒的顯性:不顯性感染比分別是1:1-2 和 1:7-12。 在評估疫苗方面,安全性上發現有15.13%的臺北與高雄學童在接種新型流感H1N1疫苗後7天內有不良反應[其中2.35%接種者有發燒] ,但無嚴重副作用。兩地學童於T3的2009年新型流感病毒H1N1血清保護率(seroprotection rate, HI血清效價≥1:40)各為89.00% 和83.33% (p=0.0368),群體免疫力已達80%以上。有趣的是臺北國小四至六(高)年級學童有接種新型流感H1N1疫苗者的pdmH1N1血清保護率較無接種疫苗者為高 (89.60% v.s. 48.65%, p<0.0001);但在國小二、三(低)年級差異較小(88.67% v.s. 86.67%, p= 0.0545)。而高雄高低年級學童有接種疫苗者的血清保護率均顯著較無接種疫苗者為高 (低年級:78.18% v.s. 41.67%, p=0.0110;高年級:84.30% v.s. 63.64%, p=0.0010)。新型流感H1N1疫苗效益在臺北學童基於兩種自然感染定義 (在T2至T3間有至少1倍以上的上升或至少4倍上升)介於41.3% 與 79%之間。而針對接種一劑和兩劑疫苗的臺北低年級學童,兩者pdmH1N1血清保護力差別不大 [從T2至T3,一劑:由83.12%至83.72%,兩劑: 75.73%至91.80%]。在沒有接種疫苗的臺北學童中,低年級的學童在T1至T2[11.36% v.s.2.83% (p=0.0342)]與T1至T3[15.91% v.s.4.72% (p=0.0214)]的自然感染率均高於高年級。其中67.07% 接種疫苗學童的血清效價在T2至T3間下降。進一步分析學童於接種疫苗後(只包括接種一劑疫苗) 抗體衰退 (antibody waning) 的相關因子,發現在T2至T3期間,控制性別後,每週運動多於三小時 (p=0.0184) 為主要因子。重要的是家長在讓子女接種疫苗時,主要考量疫苗安全性、疫苗效果和是否有副作用。 本研究提供科學實證基礎與方向,以因應未來新型流感再侵入臺灣的公共衛生重要決策,包括:(1)以班級為單位停課確實可延緩流行,但停課效果受限於學童的行為和習慣,家長和老師應提醒學童避免於停課期間外出活動;(2)針對學童接種流感疫苗確實可阻斷流行,學童本次全面接種臺灣自製的新型流感H1N1疫苗後,血清保護率達90%,顯示其能有效地增加抗體保護和群體免疫力;及(3)若疫苗劑量不足時,及早施打一劑仍有阻斷傳播之效。未來將比較城鄉與不同年齡之流行差異,並每年追蹤流感流行的變化,貫徹瞭解不同型別流感病毒之流行特性和社區傳播模式,以建立監測系統即早偵測下一波新型流感的入侵;並經國際合作,以標準作業流程與方法評估不同策略對流行的影響,共同敦促建立跨國流感聯合防治網絡。 The pandemic influenza A/H1N1 (pdmH1N1) was occurred in 2009. To mitigate the contagion, the Taiwanese government implemented a new “325 class suspensions” strategy on September 1 and initiated a nationwide schoolchildren influenza pdmH1N1 vaccination campaign on November 16. The specific aims of this study were: (1) to investigate the seroprevalence of the 2009 pdmH1N1 virus infection in elementary schoolchildren after the peaks of class suspension and before the vaccination of the first dose, (2) to investigate the risk factors associated with the 2009 pdmH1N1 infection, (3) to compare the serotiters of anti-pdmH1N1 antibodies among schoolchildren before and after the vaccination, and (4) to evaluate vaccine effectiveness and its related factors. A pdmH1N1 seroepidemiological cohort study was conducted among schoolchildren from November 2009 to March 2010. Written informed consents were obtained from parents before blood drawing from 972 and 1028 2-6 graders each of the two elementary schools in Taipei and Kaohsiung, respectively. Serum levels of anti-pdmH1N1 antibody were measured for samples collected at three time points [pre-vaccination (T1), 1-month post-vaccination (T2) and 4-month post vaccination (T3)] for Taipei and two time points [T1 and T3] for Kaohsiung using the A/California/07/2009 (H1N1) vaccine strain as test virus for the hemagglutination inhibition (HI) assay. Univariate analysis was conducted to compare the differences between subgroups (vaccinated v.s. unvaccinated, with v.s. without class suspension) using Student t test and chi-square test. Multiple logistic regression analysis was integrated with General Estimating Equation (GEE) in adjusting correlation of students within the same class was applied to query the risk factors for acquiring the 2009 pdmH1N1 infection; multiple linear regression was conducted to analyze factors associated with the waning of antibody. The overall seroprevalence rate (HI serotiters≥1:10) of schoolchildren before vaccination was significantly higher in Taipei than that in Kaohsiung (49.02% v.s. 29.74%, p<0.0001), especially among classmates who had experienced class suspension (59.60% v.s. 47.45%, p=0.0241). After controlling for gender, grade body mass index and comorbidity were risk factors for acquiring pdmH1N1 infection among schoolchildren in Taipei were attending after-school activities [adjusted odds ratios of 2.47 [95% Confidence Interval (CI): 1.02-6.00, p=0.0458] and having exercise ≥ 3 hours/week [adjusted odds ratio of 2.86 (95% CI: 1.19-6.86, p=0.0189)]. Similarly, the factor associated with infection for Kaohsiung schoolchildren was attending day care center, with adjusted odds ratio of 2.02 (95% CI: 1.33-3.07, p=0.001). The acquisition of pdmH1N1 was ascribed to those unvaccinated yet seropositive children, for whom the symptomatic: asymptomatic infection ratios were estimated to be 1:1-2 and 1:7-12 for children in Taipei and Kaohsiung, respectively. In evaluating the pdmH1N1 vaccine, a total of 15.13% vaccinees reported having at least one post-vaccination adverse events within 7 days (fever≥38℃: 2.35%) but no one was considered serious. The overall seroprotection rates (HI serotiters≥1:40) at T3 were 89.00% and 83.33% for vaccines in Taipei and Kaohsiung (p=0.0368), respectively. For the upper (4-6) graders in Taipei, the post epidemic seroprotection rate of vaccinees was significantly higher than unvaccinated schoolchildren (89.6% v.s. 48.65%, p<0.0001) suggesting a low infection rate among the upper graders. For the lower (2-3) graders, seroprotection rate among the unvaccinated children was as high as that of the vaccinees (88.67% v.s. 86.67%, p=0.0545). The seroprotection rates of Kaohsiung vaccinated schoolchildren were significantly higher than unvaccinated ones in both grades (lower: 78.18% v.s. 41.67%, p=0.110; upper: 84.3% v.s. 63.64%, p=0.0010). The vaccine effectiveness ranged 41.3%-79%, according to the two criteria of natural infection (T3/T2 serotiter rise: ≥1-fold or ≥4-folds). In comparing the lower grade students vaccinated with one or two doses, the seroprotection rates between these two groups were alike (T2 to T3, 1 dose: 83.12% to 83.72%; two doses: 75.73% to 91.50%. The natural infection rates among unvaccinated lower graders were higher than upper graders (T1 to T2: 11.36% v.s. 2.83%, p=0.0342; T1 to T3: 15.91% v.s. 4.72%, p=0.0214). The antibody of two-thirds (67.7%) of vaccinated children showed waning titers from T2 to T3. Those who exerise≥3 hrs/wk were more likely to show antibody waning (p=0.0184, after controlling gender) in 1-dose vaccinees from T2 to T3. Questionnaire showed the main concerns of parents about vaccination against the 2009 pdmH1N1 were vaccine safety and effectiveness. This study provided evidence-based information for the public health policies in preparedness of future pandemics, including: (1)Class suspension can mitigate the epidemic, yet its effect was limited by the behaviors and habits of schoolchildren, implying that parents and teachers should remind them to avoid gathering; (2) mass-vaccination on schoolchildren did block the epidemic while seroprotection rates reached to 90%, demonstrating that Taiwan’s domestically made 2009 pdmH1N1 vaccine was effective in increasing herd immunity; and (3) prompt vaccination with one dose can block the contagion if vaccine is in shortage. Future studies will investigate the epidemiological differences in metropolitans and remote areas, in different age groups for monitoring changes in each influenza seasons; understanding the characteristics of different influenza subtypes and transmission in community, and establishing an efficient surveillance system for early detection of next pandemic. With international collaboration the impact of different public health strategies using standard operation procedures and methods can be carefully evaluated for co-establishing united prevention and control network for influenza. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/27907 |
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