台灣季節性流感使用儲備抗病毒藥物之策略與效果評估

Evaluating the strategies and effectiveness of using stockpiled antivirals for seasonal influenza, Taiwan

蘇家彬(Chia-ping Su)

指導教授 ： 方啟泰

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2020年)

https://doi.org/10.6342/NTU202002835

摘要

1.台灣季節性流感預防與控制之策略
流感對台灣仍然造成嚴重的公共衛生威脅。2017至18年間，台灣經歷了兩次季節性流感流行，分別由A/H3N2與B型流感病毒引起。台灣疾病管制署與傳染病防治諮詢會除了國家流感疫苗接種計畫以外，也針對季節性流感的預防與控制，利用多元化的策略以降低於易感族群的傳播，以及減少流感相關個案發生與死亡率。我們利用回顧此一預防與控制流感策略中的數個關鍵因素，包括加強流感監測，抗病毒藥物的儲備與管理，重症照護與醫療資源的分配，與公眾的風險溝通，以及感染管制的措施等。由於控制季節性流感流行有其複雜與挑戰性，醫療專業人士間的彼此合作對於保障台灣人民的健康具有關鍵的重要性。
2.陰性流感快篩與住院流感病患嚴重疾病之相關性
偽陰性的流感快篩結果可能誤導醫師排除流感的診斷。本研究目的為評估陰性的流感快篩結果與加護病房住院的關係。分析2009年7月至2011年2月於臺灣某教學醫院之實驗室確診流感成人住院個案，實驗室檢驗方式為反轉錄聚合酶連鎖反應或病毒培養。結果發現，在134名流感病毒感染之成年個案中，有38名(28%)曾住加護病房。相較於流感快篩陽性的個案，流感快篩陰性的個案其入住加護病房的比例顯著較高 (46% vs. 13%, p value< 0.001)。流感快篩陰性的個案有較高的比例具有下呼吸道症狀以及胸部X光片浸潤。流感快篩陰性的個案，其快篩至治療的時間相較於流感快篩陽性的個案顯著較長(1.94 days vs 0.03 days, p value< 0.001)。在入院時疾病較輕的個案當中，僅有流感快篩陰性以及延遲治療時間與入住加護病房相關。本研究結論，流感快篩陰性的流感個案更容易有嚴重疾病以及遲延抗病毒藥物治療。本結論可幫助改善流感住院病患之治療效果。
3.比較克流感與瑞樂沙之臨床效果差異: 一個全國性的觀察性研究
吸入性之瑞樂沙被認為相較於口服之克流感，其全身性抗病毒的能力較低。截至目前為止，尚未有直接比較克流感與瑞樂沙之臨床效果的全國性大型研究被報告。本研究目的為比較流感診斷後兩天內使用克流感或瑞樂沙之病患之臨床預後差別。本研究利用2013至2016年間三個流感季之全民健保申報資料庫，追蹤病患診斷後兩周內是否有因流感相關原因住院或死亡。在利用傾向分數分組與加權來校正可能之干擾因素後，計算使用兩組藥物之個案其出現研究結果之風險比。本研究期間內共找出865,032 位於研究期間使用流感抗病毒藥物之個案，其中269,135 (31.1%)使用克流感，595,897 (68.9%) 使用瑞樂沙. 本研究並未發現兩種藥物之使用者於臨床出現研究結果風險比之差異 (RR 1.01, 95% CI: 0.96–1.06). 分族群研究發現18–64 years之年輕族群使用克流感組出現臨床結果之風險較低 (RR 0.92, 95% CI: 0.85–0.99). 在此觀察性世代研究中，我們並未發現使用兩種藥物的個案在出現研究結果的風險上有重大差異。

關鍵字

流感 ； 預防與控制 ； 監測系統 ； 流感快篩 ； 抗病毒藥物治療 ； 住院 ； 流感抗病毒藥物 ； 全國觀察性研究 ； 傾向分數分組

並列摘要

1.Seasonal influenza prevention and control in Taiwan—Strategies revisited
Influenza remains a serious public health threat in Taiwan. During 2017–18, Taiwan experienced two seasonal influenza epidemics caused by A/H3N2 and B, respectively. In addition to national influenza vaccination campaign, Taiwan Centers for Diseases Control and Infectious Disease Control Advisory Committee has multi-faceted strategies for seasonal influenza prevention and control to mitigate the risk of disease transmission among vulnerable groups and decrease influenza-related morbidity and mortality. In this article, we reviewed the key elements of the prevention and control strategies—enhanced influenza surveillance, antiviral drugs stockpile and management, critical care and medical resources reallocation, public risk communication and infection control measures. Given the complexity and challenging nature of controlling seasonal influenza epidemics, collaboration between health professionals is crucial to optimize the health of Taiwanese people.
2.Correlation between Negative Rapid Influenza Diagnostic Test and Severe Disease in Hospitalized Adults with Laboratory-Confirmed Influenza Virus Infection
False-negative rapid influenza diagnostic test (RIDT) results could mislead physicians to exclude an influenza diagnosis. We sought to evaluate the association between negative RIDT and ICU admission. We reviewed data from hospitalized adults with laboratory-confirmed influenza virus infections in a tertiary referral hospital in Taiwan from July 2009–February 2011. The diagnosis was documented by real-time polymerase chain reaction (RT-PCR) or virus culture. Of 134 hospitalized adults infected with influenza virus, 38 (28%) were admitted to the ICU. Compared to RIDT-positive patients, the percentage of ICU admission was significantly higher among RIDT-negative patients (46% vs. 13%, p value< 0.001). The RIDT-negative patients had higher percentages of lower respiratory symptoms and more chest radiograph infiltrates. The time interval between the RIDT test and antiviral treatment was longer in RIDT-negative than RIDT-positive patients (1.94 days vs 0.03 days, p value<0.001). Among patients presenting with mild illness, only a negative RIDT and delayed antiviral treatment were associated with ICU admission after adjusting for potential confounding factors. To conclude, patients with a negative RIDT were more likely to have severe disease and a delay in initiating antiviral treatment. Our findings should help improve treatment outcomes of hospitalized patients with influenza infection.
3.Comparison of clinical outcome of oseltamivir and zanamivir for influenza: a nationwide observational study
Inhaled zanamivir is considered as having less systematic antiviral activity than oral oseltamivir. To date, no direct comparisons of effectiveness of oseltamivir and zanamivir in national observational database have been reported. Our objective was to compare clinical outcomes among patients with influenza and treated with either oseltamivir or zanamivir in a real-world setting. This retrospective observational study included patients with first outpatient visit of influenza diagnosis and treated with oseltamivir or zanamivir within 2 days from the National Health Insurance Database from three influenza seasons between 2013 and 2016. Patients were followed for an outcome of influenza-related hospitalization or death within 2 weeks after the diagnosis. After propensity score fine-stratification and weighting to account for confounders, we calculated the hazard ratios for the outcome comparing two groups of users. A total of 865,032 influenza patients who initiated antiviral during the study period was identified; 269,135 (31.1%) initiated oseltamivir, and 595,897 (68.9%) initiated zanamivir. We did not observe significant difference in outcomes between oseltamivir and zanamivir users (RR 1.01, 95% CI: 0.96–1.06). Results from subgroup analysis revealed that patients aged 18–49 years initiating oseltamivir had a lower hazard ratio of clinical outcome (RR 0.92, 95% CI: 0.85–0.99). In this observational cohort study, we did not observe substantial differences in clinical outcomes between those who initiated oseltamivir vs. zanamivir.

並列關鍵字

Influenza ； Prevention and control ； Surveillance ； rapid influenza diagnostic test ； antiviral treatment ； hospitalization ； influenza antiviral treatment ； nationwide observational study ； propensity score stratification

參考文獻

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