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標題: | 以實證為基礎之愛滋病與新型冠狀病毒疾病2019全球大流行防治策略 HIV and COVID-19 Pandemic Response: an Evidence-Based Approach |
作者: | 陳怡諠 Yi-Hsuan Chen |
指導教授: | 方啟泰 Chi-Tai Fang |
關鍵字: | 人類免疫不全病毒,篩檢,世代追蹤研究,數理模式,成本效性,新型冠狀病毒疾病2019,基礎再生數,消除疫情, HIV,screening,cohort study,mathematical modelling,cost-effectiveness,COVID-19,R0,elimination, |
出版年 : | 2021 |
學位: | 博士 |
摘要: | 第一部分. 愛滋病
第一章. 例行愛滋篩檢與預後:臺灣全國世代追蹤研究 世界衛生組織與美國疾病控制和預防中心均建議擴大例行愛滋篩檢 (routine HIV testing) 以促進早期診斷與治療,但此建議迄今仍缺乏令人信服的實證基礎。本研究分析疾病管制署全國愛滋病資料庫,以確診年份進行配對,同時控制年齡、性別、感染途徑與社經狀況等干擾因子。結果顯示:相較於個人危險行為愛滋篩檢 (individual risk-based HIV testing),例行篩檢可降低 80% 晚診斷率 (adjusted odds ratio [aOR], 0.20; 95% CI: 0.18–0.23, P<0.001) 及 37% 愛滋相關死亡率 (adjusted hazard ratio [aHR], 0.63; 95% CI: 0.53–0.75, P<0.001),且不會增加非愛滋相關死亡率 (aHR, 0.94; 95% CI: 0.91–0.98, P<0.001)。針對男男間性行為者與注射藥癮者各別分析,均呈現一致結果:例行愛滋篩檢可大幅促進早期診斷及改善預後。 第二章. 全面提供例行愛滋在家篩檢的成本效性:數理模式研究 為提供我國愛滋政策參考,本研究進一步以所有參數均有實證基礎的數理模式分析:若在臺灣對年輕性活躍未婚族群不分性取向全面提供例行愛滋在家篩檢 (home testing) 的成本效性。實證資料來源包括:疾病管制署全國愛滋病資料庫及各項愛滋業務指標、中央健康保險署全民健康保險資料庫愛滋相關醫療費用數據、內政部戶政司歷年人口統計、衛福部統計處國民生命表、師大晏涵文教授 2019 臺灣大專院校學生性行為實際調查資料、及科學文獻。傳播數理模式分析顯示:臺灣異性間性行為者愛滋疫情係由男男間性行為者愛滋疫情驅動。若對所有15歲以上性活躍但未婚的年輕族群每年提供一次例行愛滋在家篩檢,在未來20年,不但可提升早期診斷而預防4,286例新愛滋病例,扣除篩檢試劑成本後還可同時為臺灣帶來新臺幣255億元的淨貨幣效益 (以3% 折現率計算)。敏感度分析顯示醫療費用、存活壽命、篩檢試劑成本、及年輕人接受度等關鍵因素估計值的不確定性範圍內,每年例行全面提供一次愛滋在家篩檢均具高度成本效益。 第二部分. 新型冠狀病毒疾病 第三章. 不同新冠肺炎防治策略對死亡率影響:跨國比較 2020年新冠疫情全球爆發。本研究分析各國實際統計數據,發現在相同疫情爆發階段且人口、文化、經濟水準相似的歐洲國家,倚靠重症醫療「緩解疾病傷害 (mitigation)」策略因應的國家(義大利、英國、西班牙、法國)之致死率、每十萬人口死亡率、及醫護人員死亡人數均大幅高於以積極篩檢隔離病患「遏制病毒傳播 (containment)」策略因應的國家(德國)。在亞洲,條件相似但採不同策略國家間比較 (日本 vs. 臺灣)也呈現相同趨勢:在疫情爆發階段,「遏制病毒傳播」是較佳的防疫策略。 第四章. 臺灣以組合式阻斷傳播策略與嚴格邊境管制遏制新冠肺炎疫情 臺灣於 2019 年底警覺武漢出現人傳人非典肺炎疫情,並迅速診斷第一例境外移入確診後,我國決策者面臨如何有效遏制此新興傳染病傳播以及是否需關閉邊境的迫切問題。本研究即時分析武漢疫情數據,計算新冠肺炎病毒的基礎再生數 (basic reproductive number, R0) 高達 3.5 以上,並發展反制策略。SEIR數理模式分析顯示:若僅以醫療端的篩檢與隔離及公衛端的接觸者追蹤,並無法將 R0 降到 1 以下,必須再加上 50% 以上民眾配戴外科口罩或保持社交距離,才能阻斷病毒持續在社區中傳播 (R0 <1),而有效控制疫情。此外,若不關閉邊境,允許病毒持續由境外移入,醫療及公衛體系將在三個月內因超過負荷而崩壞,導致疫情失控。因此,除了採檢隔離接觸者追蹤及全民外科口罩之外,還需嚴格邊境管制。實施上述策略,臺灣在 2020 年不但成功根除境內新冠病毒,確診與死亡人數極低,並讓經濟得以全面復甦。 第五章. 正確判讀新冠病毒血清流行病學數據 緊急授權使用的第一代新冠病毒血清抗體檢測試劑敏感度僅有 90%,特異度僅有 95%。若將偽陽性檢測結果錯誤判讀為無症狀感染後已具抗體,將嚴重誤判疫情。本研究發展出在真實盛行率不明的情況下,正確解讀新冠病毒抗體檢測結果的簡明判準:若血清盛行率高於9.5%,真陽性機率高於偽陽性機率;但若低於9.5%,則偽陽性機率高於真陽性機率;當血清盛行率低於 2% 時,偽陽性機率可接近 100%,不宜採信,必需以西方墨點法驗證。 第六章. 以「不限制移動」社交距離及篩檢/接觸者追蹤成功控制新冠肺炎疫情爆發:2020年二月到四月,韓國大邱 韓國大邱於2020年二月底爆發大規模新冠病毒疫情。韓國決策者面臨是否需採用封城措施,禁止民眾離家外出,才能有效控制這一波大型新冠病毒疫情的嚴峻問題。由於這一波疫情病毒株由武漢傳入,本研究以從武漢疫情數據計算得到的 R0 數值為基礎,建立韓國大邱新冠疫情爆發電腦模擬,以分析防治策略。結果顯示:根本不需要限制民眾移動,只須同時實施 (1) 降低非必要接觸「社交距離」措施(停班停課、暫停大型集會)及 (2) 採檢隔離、接觸者追蹤檢疫,即可將 R0 壓制到 1 以下,並讓新冠疫情迅速下降。採納上述策略,韓國在 2020 年二月到四月。以「不限制移動」社交距離加上篩檢/接觸者追蹤,在四週內成功地控制大邱疫情,達成公共衛生重大勝利,成為全球民主抗疫的典範。 第七章. 以「臺灣社交距離」手機應用程式壓制全球新冠病毒疫情:數理模式研究 自2020年三月至今,歐洲各國陷入封城與解封之循環,雖然今年初已開始施打疫苗,但第一代疫苗對於病毒變異株之保護力不如預期,各國依舊面臨疫情難控的困境。台灣人工智慧實驗室 (Taiwan AI Lab) 研發以藍芽技術為基礎的「臺灣社交距離手機應用程式 (Taiwan Social Distancing Application, TSD app)」,具備雙重功能,包含以近距離警示提醒民眾保持 1.8公尺社交距離,及確診者的接觸者追蹤,並以去中心化處理,保護使用者的隱私。本研究以 SEIR 數理模式模擬在英美等新冠病毒疫情嚴重國家推廣使用此軟體的流行病學效果。結果顯示:只要該國能提供採檢及隔離確診者,在鬆綁傳統社交距離規範時,50% 以上民眾安裝使用此軟體,即可有效壓制新冠病毒R0 到1 以下,並讓疫情持續下降直到歸零,不再需週期性封城,可作為全球長期抗疫的一大利器。敏感度分析顯示:即使出現疫苗無法剋制且具有比現有病毒株 R0 值更高的具高度後果 (Variant of High Consequence, VOHC) 變異株,英美現行週期性封城策略已不再能有效壓制疫情,但只要該國能持續採檢隔離確診者,提高到75% 安裝使用率的「臺灣社交距離」手機應用程式仍可有效壓制 VOHC 的 R0 到 1 以下,並讓疫情持續下降直到歸零。 Part I. HIV Chapter 1. Routine HIV Testing and Outcomes: a Nationwide Cohort Study in Taiwan To date, limited data are available on the presumed benefit of routine HIV testing to early detect HIV infection with improved outcomes. This study was based on the Taiwan national HIV/AIDS registry data to assess the outcomes of people diagnosed with HIV through routine vs. non-routine (individual risk–based) testing. We found that routine testing was associated with an 80% lower likelihood of late diagnosis (adjusted odds ratio, 0.20; 95% CI: 0.18–0.23, P<0.001), a 37% lower HIV-related mortality(adjusted hazard ratio [aHR], 0.63; 95% CI: 0.53–0.75, P<0.001), and not associated with increase in non-HIV mortality (aHR, 0.94; 95% CI: 0.91–0.98, P<0.001). Results are similar in subgroup analyses of men who have sex with men and people who inject drugs: routine HIV testing is associated with highly favorable outcomes. Chapter 2. Cost-effectiveness of Routine HIV Testing in Taiwan: a Modeling Study To inform policy, we analyzed cost-effectiveness of providing routine HIV home testing to all young sexually active unmarried persons, using dynamic models in which all of the parameters are evidence-based, including Taiwan Centers for Disease Control HIV/AIDS registry, Taiwan National Health Insurance Agency database for HIV-related medical expenditure, Taiwan vital statistics and life table by Department of Statistics, Taiwan university/college students sexual behavior surveys (2019), and scientific literature. Modeling results show that the HIV epidemic among MSM is an important driving force of the HIV epidemic among heterosexuals in Taiwan. Providing annual routine HIV home testing to all 15-44 years sexually active unmarried persons regardless of sexual orientation will avert 4,286 new HIV diagnoses, had a net monetary benefit of NTD 25.5 billion over the next 20 years, and is highly cost-effective (ICER: NTD 289,990 per QALY gained) across the uncertainty ranges of all parameters. Part II. COVID-19 Chapter 3. Mortality from COVID-19: A Cross-country Comparison We compared COVID-19 statistics of countries with similar epidemic stage and social background. In both Western Europe and East Asia, “Containment” strategy aiming to prevent transmission is consistently superior to “Mitigation” strategy that aims to provide critical care for severely ill patients, in term of case fatality rate, mortality per 100,000 population, and numbers of healthcare workers died from COVID-19, during the initial stage of the pandemic. Chapter 4. Combined interventions to suppress R0 and border quarantine to contain COVID-19 in Taiwan To inform Taiwan national policy, we modelled effects of intervention to block transmission of SARS-CoV-2, the etiological agent of COVID-19. The results showed that suppression of basic reproductive number (R0) requires simultaneous combination interventions of test-and-isolation, contact tracing, and at least 50% general public surgical mask-wearing/social distancing. Moreover, strict border quarantine is essential to prevent the collapsing of medical/public health systems from being overwhelmed by continuous influx of imported infectious cases. Applying these policies, Taiwan successfully contained COVID-19 in 2020, with few deaths and robust economy recovery. Chapter 5. A Simple Rule to Correctly Interpret COVID-19 Seroepidemiological Data We showed that the cut off values for interpreting EUA COVID-19 serological test result (with 95% specificity and 90% sensitivity) are 9.5% and 2.0%. When seroprevalence is >9.5%, a positive result will be more likely to be true than false. However, when seroprevalence is 2.0% or less, the false positive rate may reach up to 100%, and a confirmation with western blot will be necessary. Chapter 6. Effect of Non-lockdown Social Distancing and Testing-Contact Tracing During a COVID-19 Outbreak in Daegu, South Korea, February to April 2020 To help South Korea during the first large COVID-19 outbreak outside China in Spring 2020, we modelled effect of non-lockdown social distancing (avoid non-essential social contacts, without restricting the movement of people who are not patients or contacts) and testing-contact tracing. The results showed that the two interventions are synergistic, and both must be implemented to suppress the R0 to less than 1 and contain the outbreak. Applied combined interventions, South Korea rapidly controlled COVID-19 outbreak in Daegu, with a democratic and humane approach. Chapter 7. Taiwan Social Distancing (TSD) Mobile Application to Suppress the COVID-19 Pandemic Worldwide: A Modeling Study Emergence of variants of high consequence (VOHC) not covered by the first-generation vaccines is currently of grave concern. We modelled the effect of Taiwan Social Distancing (TSD) mobile application (Taiwan AI Lab), which maintains safe inter-personal distance through proximity alert and provides privacy-preserving contact tracing. The results show that, in the presence of testing and isolation, a 50% adoption rate of TSD app will suppress the R0 of SARS-CoV-2 to less than 1, with a sustained suppression of the COVID-19 epidemic in severely affected countries such as UK and USA without the negative impact of cyclic lockdown on the society. Sensitivity analyses show that, for new waves of epidemic caused by VOHC with a high R0 which cannot be controlled with the current cyclic lockdown strategy, a 75% adoption rate of TSD app can still sustainably suppress the R0 to less the 1 and contain the pandemic till reaching zero. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/83061 |
DOI: | 10.6342/NTU202104041 |
全文授權: | 未授權 |
電子全文公開日期: | 2026-10-27 |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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