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標題: | 疫苗族群免疫效益之統計分析與經濟評估:以台灣流行性感冒為例 Statistical and Economic Aspect of Herd Immunity in Vaccination: An Illustration with Influenza in Taiwan |
作者: | Sen-Te Wang 王森德 |
指導教授: | 陳秀熙(Hsiu-Hsi Chen) |
關鍵字: | 流行性感冒,流行性感冒疫苗,集團免疫,動態模型,成本效益分析, Influenza,Influenza vaccine,Herd immunity,Dynamic model,Cost-effectiveness analysis, |
出版年 : | 2009 |
學位: | 博士 |
摘要: | 摘要
前言 已有許多研究證實流行性感冒疫苗(以下簡稱流感疫苗)可以有效降低流行性感冒相關併發症及死亡率,大規模實施流感疫苗接種政策亦成為許多國家重要公共衛生政策。流行性感冒疫苗不但可以保護接種疫苗者,亦可以降低流行期間族群中感染人數,進一步保護未接種疫苗者減少接觸感染者的機會及降低感染率,此現象稱為族群免疫,藉由族群免疫效益,將族群的疫苗接種率提高至一定比率即可有效阻斷疾病傳遞並控制疫情。多數流感疫苗相關研究忽略族群免疫效益,往往會低估疫苗帶給族群的實際效果與經濟效益。此外流行性感冒(以下簡稱流感)有別於多數傳染性疾病,會因流感病毒基因的變異性產生同一個流感季節有數波流行的現象,每波流行爆發導因於不同的病毒株,過去流行性感冒相關研究往往忽略此現象。以上過去流感疫苗研究常忽略的問題,是本研究處理的重要議題。 研究目的 1. 以傳染病動態模型(Dynamic model)及實際流行病學資料模擬不同波段流行性感冒流行趨勢,估算各種疾病傳遞相關參數。 2. 以傳染病動態模型估算不同波段傳染病基礎再生率及預測根除流感傳遞之最低疫苗涵蓋率。比較疫苗政策實施與否是否改變傳染病之基礎再生率。並與傳統固定模式(Fixed model)推估之基礎再生率做比較。 3. 以傳染病動態模型建構成本效益分析架構,處理疫苗的族群免疫效益,以上述模擬推估之傳染病傳遞相關參數進行疫苗成本效益分析,並與傳統固定模式(Fixed model)推估之成本效益做比較。 研究方法 因為流行性感冒疫苗施打優先對象是老年族群,另為分析疫苗對於接種者家戶成員之族群免疫效益,本研究主要目標族群是65歲以上老年人口及其家戶成員,以此原則於台北縣抽樣出73,465人及全國6,862,885人。連結健保資料庫取得研究對象流感疫苗接種情形及因流感至門診就醫或住院情形。台北縣及全國至2001年十二月止疫苗涵蓋率約為15%。本研究探討2001~2002年流感季節,流感疫苗施打期間為2001年十月至2001年十二月,流感流行期間為2001年十二月至2002年三月。依據疾病管制局疫情通報紀錄及病毒實驗室資料,推估該流感季節於台北縣及全國皆有五波爆發。 因流感有別於一般傳染病,臨床表現不具專一性,無法從臨床表現確實診斷個人是否受流感病毒傳染,只能藉實驗室病毒培養或檢查證實,臨床上甚難取得傳統傳染病動態模式(SIR model)分析中所需每個時間點受感染人數之資料,本研究為解決此一問題將流感相關疾病資料(如門診就醫或住院)導入傳統動態模型中,將實際流行病學資料(疾病資料)應用於新模式中,以模擬的方式推估各種傳染病流行參數。此外本研究研發一套程式解決繁複的模擬過程。 本研究以社會觀點進行疫苗政策之成本效益分析,同時考慮疫苗與疾病之直接成本與間接成本,以TreeAge Pro 2004作為分析工具,以遞增成本效果比值(ICER)表示施打疫苗政策於每減少一例疾病個案或死亡個案所需增加之社會花費。嘗試以動態模型處理疫苗之族群免疫效應,比較使用動態模型(傳染病傳染力隨時間及感染人數變動)及固定模型(傳染病傳染力於各時間點為固定值)於成本效益分析之差異,估算忽略族群免疫效益造成疫苗經濟效益評估之低估值。 結果 以調整後之動態模型及實際疾病流行病學資料,模擬並推估出台北縣該流感季節五波流感爆發之流感傳染基礎再生率分別為 3.3,3.6,6.75,5.4,4.5;換算成有效控制疾病於族群傳遞之疫苗涵蓋率閾值分別為70%,72%,85%,81%,78%。以全國抽樣人口之疾病資料做基礎,將於台北縣所使用之動態模型及推估出之傳染病傳染參數(傳染機率、接觸率)及疾病相關參數(如門診就醫率與住院率)應用於全國傳染病流行趨勢之模擬作模型做驗正,發現該模型與台北縣參數模擬出之疾病流行趨勢完全可適用及符合全國第一波、第二波、第四波與第五波之情形。唯獨以該模型模擬全國第三波(2001年十二月中 ~ 2002年一月中)之結果,估算基礎再生率為9.6。本研究作者推測該段流行波期間於台北縣流行之流行病毒株可能有別於全國流行之病毒株,或因其他環境因素之差異影響病毒之傳遞情形。 以動態模型分析流感疫苗施打政策之介入相對於無施行疫苗接種政策其成本效益分析結果為:每預防一例流感門診就醫及流感相關住院事件施打流感疫苗需多花費社會1,620美金成本,每預防一例死亡事件施打流感疫苗需多花費社會1,705美金成本。以固定模型分析流感疫苗施打政策之介入相對於無施行疫苗接種政策其成本效益分析結果為:每預防一例流感門診就醫及流感相關住院事件施打流感疫苗需多花費社會17,443美金成本,每預防一例死亡事件施打流感疫苗需多花費社會29,273美金成本。兩種分析方式結果之差異導因於動態模式較能解釋疫苗之族群免疫效益。 結論 導入疾病狀態之傳染病動態模式可以模擬及推估流感之傳染病相關傳遞參數,並進一步估算疾病之基礎再生率及有效控制疫情之疫苗涵蓋率閾值。以動態模型應用於疫苗之成本分析以解釋族群免疫效益時發現忽略族群免疫效益確實會低估疫苗之經濟效益。 關鍵字:流行性感冒,流行性感冒疫苗,集團免疫,動態模型,成本效益分析 Abstract Introduction Vaccination can not only directly protect persons from infection but it can confer partial protection by raising the coverage rate up to a threshold value, which is so-called herd immunity. Most of the previous studies that evaluated the efficacy of influenza vaccination program lay emphasis on the comparison of the difference of outcome between the vaccinated and unvaccinated group, i.e. in the perspective of individual. The indirect benefit that unvaccinated persons accrue from vaccination policy was largely neglected. The consideration of the benefit as a result of herd immunity is worthy of being investigated. Objectives 1. Develop a generalized computer-aided software for predicting epidemic curve. 2. Apply the extended dynamic models to analyze the effect of herd immunity that the policy of massive vaccination against influenza brings to the population. 3. Apply the extended dynamic models to analyze how the policy of massive vaccination against influenza influences the basic reproductive rate. 4. Explore how the efficacy and cost-effectiveness of vaccination against influenza is underestimated when herd immunity is not considered in the analysis. Materials and Methods We begin with the development of new extended epidemic model with influenza-related complications in it. We then developed a computer-aided software for covering a series of model for producing different epidemic curves. We select influenza A as our illustration for the demonstration of computer-aided software for producing these epidemic curves by using different dynamic epidemic models. Empirical data sources on influenza in Taipei County and nationwide are applied to the extended epidemic model to estimate the transmission parameters that then were translated to the basic reproductive rate and threshold coverage rate of mass vaccination to probably eradicate the viral circulation in the studied epidemic season. The empirical data and the transmission parameters of flu estimated by simulation were applied in cost-effectiveness analysis of mass vaccination. The incremental cost-effectiveness ratio expressed by trading extra cost for per death averted, per flu-related complication (outpatient visiting or/and hospitalization) averted for vaccination against non-vaccination was calculated. We compared the result of cost-effectiveness analysis evaluated by dynamic model to that by fixed model to explore the impact of neglect of herd immunity on efficacy of vaccination. Results According to the surveillance data of CDC, there were 5 outbreaks of influenza in Taipei County in the studied season. The estimated transmission probability of five outbreaks obtained from the simulation by the extended dynamic model was 0.55, 0.6, 0.75, 0.6 and 0.75. Then the basic reproductive rate (R0) can be estimated as 3.3, 3.6, 6.75, 5.4 and 4.5. So the estimated threshold coverage rate of vaccination to eradicate influenza circulation at these 5 outbreaks was 70%, 72%, 85%, 81%, and 78%. To validate the SHIRO model, we applied the model and parameters available from the process of simulation for influenza epidemic in Taipei County to the national situation in Taiwan in the same manner. We found that the simulated epidemic curve of infection fit well to the national empirical situation only except in outbreak 3 (from 2001 Dec to 2002 Feb). In the economic evaluation of vaccination, vaccination with consideration of herd immunity, as opposed to no vaccination, could save 158 of OPD & hospitalization due to flu and 146 of deaths with extra cost of 249,000 US dollars, based on the. The incremental cost-effective ratio was 1,619 US dollars per each complication averted due to flu and 1,705 US dollars per death saved. Vaccination without consideration of herd immunity, as opposed to no vaccination, only could save 18 of OPD & hospitalization due to flu and 11 of deaths with extra cost of 322,000 US dollars. The incremental cost-effective ratio was 17,443 US dollars per each complication averted due to flu and 29,273 US dollars per death saved. Obviously, the benefit of influenza without considering herd immunity is largely underestimated. Conclusion The application of this model to immunization program of influenza in Taiwan found the basic reproductive number is reduced from 12 to 6.75 for model considering her immunity and 8.65 for the model without considering herd immunity. The benefit of vaccination without considering herd immunity has been substantially underestimated. Key words: Influenza, Influenza vaccine, Herd immunity, Dynamic model, Cost-effectiveness analysis |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41457 |
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