早期抗病毒藥物治療降低兒童流感相關住院風險: 多中心病例對照研究

Abstract

研究背景與研究目的 季節性流感持續對全球兒童健康造成重大公共衛生威脅，特別是在五歲以下幼童中，更是導致住院與死亡的重要原因之一。在美國，2010年至2023年間，此年齡層每年約有6,000至25,000名流感相關住院個案。雖然世界衛生組織（WHO）與美國感染症醫學會（IDSA）均建議早期使用神經胺酸酶抑制劑或其他抗病毒藥物，因其已證實可縮短症狀持續時間，但在預防流感相關住院的效果，尤其針對幼兒族群，仍缺乏有力的證據。本研究旨在評估兒科門診及急診病童接受早期抗病毒治療對於降低流感相關住院風險的有效性。

研究方法 本研究採用配對病例對照研究設計，納入2020年1月1日至2023年10月31日間，於台灣北部馬偕紀念醫院體系就醫並經實驗室確診為流感之18歲以下兒童與青少年。病例組定義為流感相關住院或死亡，並依就診年份、月份及年齡分層進行配對。早期抗病毒治療定義為自上呼吸道或發燒等症狀開始後兩日內使用抗病毒藥物。主要研究結果為接受早期抗病毒治療與未接受早期抗病毒治療者之流感相關住院風險，並以校正勝算比（adjusted odds ratio, aOR）表示。校正變項包括年齡、性別、潛在疾病、早期抗生素使用、早期類固醇使用及其他合併感染。我們也進一步進行分層分析，以探討5歲以下及5歲以上兒童的治療效果，也針對不同種類的抗病毒藥物進行分層分析，比較之間的治療效果。

研究結果 本研究共納入1,492名兒童（病例組354人，對照組1,138人），平均年齡為7.1歲（範圍2.5–11.7歲）。流感相關住院的顯著危險因子包括：年齡較小（aOR 每增加一歲為0.93；95% CI, 0.87–0.99）、潛在疾病（aOR, 2.76；95% CI, 1.91–3.99）、早期使用抗生素使用（aOR, 7.32；95% CI, 5.14–10.42）以及合併感染（aOR, 3.88；95% CI, 1.99–7.59）。早期抗病毒治療與顯著降低流感相關住院風險相關，在所有兒童中顯著降低81% 流感相關住院風險（aOR, 0.19；95% CI, 0.14–0.27），在五歲以下兒童中降低80% 住院風險（aOR, 0.20；95% CI, 0.12–0.32）而在五歲以上的兒童與青少年中中降低83% 住院風險（aOR, 0.17；95% CI, 0.10–0.28）。

結論 本研究結果顯示，對於經實驗室確診的流感兒童，早期使用抗病毒藥物治療可以顯著降低80% 流感相關住院的風險。此保護效果在五歲以下幼童中同樣存在。本研究為首篇針對幼兒族群評估早期抗病毒藥物治療對兒童流感相關住院風險影響的研究。研究結果支持現行WHO與IDSA的治療指引與建議，並強調提升抗病毒藥物之及時可近性與快速診斷能力，對於減輕兒童流感疾病負擔具有重要意義。

Background and Study Aim Seasonal influenza remains a significant public health concern for children globally, particularly those under five years of age, among whom it is a leading cause of hospitalization and mortality. In the United States, influenza resulted in an estimated 6,000 to 25,000 hospitalizations per year in this age group between 2010 and 2023. While both the World Health Organization (WHO) and the Infectious Diseases Society of America (IDSA) recommend early initiation of neuraminidase inhibitors or other antiviral agents based on their efficacy in reducing symptom duration, the evidence remains inconclusive regarding their effectiveness in preventing influenza-related hospitalization—especially in young children. To evaluate the effectiveness of early antiviral therapy in preventing influenza-associated hospitalization in pediatric outpatients.

Method This matched case-control study included all children (<18 years) with laboratory-confirmed influenza who sought care at MacKay Memorial Hospital System in northern Taiwan from January 1, 2020, to October 31, 2023. Cases were defined as influenza-related hospitalization or death and matched to controls by year, month of visit, and age strata. Early antiviral therapy was defined as initiation within 2 days of symptom onset during the influenza episode. The primary outcome was the adjusted odds ratios (aOR) for influenza-associated hospitalization in subjects who received early antiviral therapy, compared with those who did not receive early antiviral therapy. Adjusted variables included age, sex, underlying conditions, early antibiotic use, early steroid use, and co-infection. The subgroup analyses assessed effects in children younger than 5 years and those 5 years or older.

Results Among 1,492 participants (354 cases and 1,138 controls), the mean age was 7.1 years (range, 2.5–11.7 years). Risk factors for influenza-related hospitalization included younger age (aOR per one-year increment, 0.93; 95% CI, 0.87–0.99), underlying conditions (aOR, 2.76; 95% CI, 1.91–3.99), early antibiotic use (aOR, 7.32; 95% CI, 5.14–10.42), and co-infection (aOR, 3.88; 95% CI, 1.99–7.59). Early antiviral therapy was associated with a reduction in influenza-related hospitalization by 81% in all children (aOR, 0.19; 95% CI, 0.14–0.27), by 80% in children younger than 5 years (aOR, 0.20; 95% CI, 0.12–0.32), and by 83% in children aged 5 years or older (aOR, 0.17; 95% CI, 0.10–0.28).

Discussion and Conclusion Our findings show that early antiviral therapy was significantly associated with reduced risk of influenza-associated hospitalization in children with confirmed influenza infection. This protective effect persisted in children under five years of age, even after adjusting for potential confounders including age, sex, underlying medical conditions, early antibiotic or corticosteroid use, and co-infections. To our knowledge, this is the first study to specifically evaluate the impact of early antiviral treatment on hospitalization risk in this highly vulnerable age group. These findings reinforce the current WHO and IDSA guidelines and underscore the importance of timely antiviral access and rapid diagnostic capacity in mitigating the pediatric burden of influenza.