Antivirals for influenza in healthy adults: systematic review
Antivirals for influenza in healthy adults: systematic review
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DOI：
10.1016/s0140-6736(06)67970-1
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发表时间：
2006-01-28
期刊：
影响因子：
168.9
通讯作者：
Rivetti, A
中科院分区：
文献类型：
--
作者：
Jefferson, T;Demicheli, V;Rivetti, A
背景：为控制季节性流感和大流行性流感，建议使用抗病毒药物。我们的目的是回顾已注册抗病毒药物对健康成人自然发生的流感的有效性、有效性和安全性的证据。方法检索各数据库至2005年10月，联系生产厂家及通讯作者。我们纳入了比较预防（n=27）或治疗（n=27）对有症状或无症状流感疗效的随机对照试验。我们进行了荟萃分析，并以比例（1-相对风险[RR]）表示预防效果。对于治疗试验，由于报告不一致和非标准化，我们用均值或风险比表示连续结果。我们纳入了52项随机对照试验的51份报告。金刚烷胺可预防61% （95% Cl 35-76）的甲型流感病例和25%（13-36）的流感样疾病，但会引起恶心（OR 2.56, 1.37-4.79）、失眠和幻觉（OR 2.54,1.50-4.31）以及因不良事件而停药（OR 2.54,1.60-4.06）。对有症状病例无影响（RR 0.85, 0.40-1.80）。在治疗中，与安慰剂相比，金刚烷胺显著缩短了发烧持续时间（0.99天，- 1.26至- 0.71），但对甲型流感病毒的鼻腔脱落没有影响（0 - 93,0.71-1.21）。金刚乙胺较少的数据显示出类似的效果。在预防方面，与安慰剂相比，神经氨酸酶抑制剂对流感样疾病没有效果（每日口服奥司他韦75毫克为1.28,0.45-3.66，每日吸入扎那米韦10毫克为1.51,0.77-2.95）。更高的剂量似乎没有影响。每日口服奥司他韦75mg对症状性流感的疗效为61%(15-82)，每日150mg时为73%（33-89）。每日吸入10mg扎那米韦有效率为62%（15-83）。两种神经氨酸酶抑制剂对无症状流感均无效。奥司他韦引起恶心（OR 1 - 79, 1.10-2.93），特别是在较高的预防剂量下（2.29,1.34- 3.92）。奥司他韦在家庭暴露后预防作用中的保护效能为58.5%(15.6-79.6)，在指示病例接触者中的保护效能为68%(34.9-84.2)- 89%（67-97）。在流感病例中，与安慰剂相比，扎那米韦缓解症状所需时间的风险比分别为1.33和1.29-1.37；如果在症状出现后48小时内开始用药，奥司他韦的1.30,1.13-1.50。两种药物均显著降低病毒鼻滴度（加权平均差为-0.62,-0.82至-0.41）。每日150mg奥司他韦可有效预防流感病例下呼吸道并发症（OR 0.32, 0.18-0.57）。我们找不到关于奥司他韦对禽流感影响的可靠数据。应禁止金刚烷胺和金刚乙胺的使用。由于其有效性低，神经氨酸酶抑制剂不应用于季节性流感控制，而应仅在严重流行或大流行时与其他公共卫生措施一起使用。
Background Use of antivirals is recommended for the control of seasonal and pandemic influenza. Our aim was to review the evidence of efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults.Methods We searched various Databases to October, 2005, and contacted manufacturers and corresponding authors. We included randomised controlled trials comparing prophylactic (n=27) or treatment (n=27) efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For treatment trials, because of inconsistent and non-standardised reporting, we expressed continuous outcomes either as means or as hazard ratios.Findings We included 51 reports of 52 randomised controlled trials. Amantadine prevented 61% (95% Cl 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like illness, but caused nausea (OR 2.56, 1.37-4.79), insomnia and hallucinations (2.54,1.50-4.31), and withdrawals because of adverse events (2.54,1.60-4.06). There was no effect on symptomatic cases (RR 0.85, 0.40-1.80). In treatment, amantadine significantly shortened duration of fever compared with placebo (by 0.99 days, - 1.26 to - 0.71), but had no effect on nasal shedding of influenza A viruses (0 - 93, 0.71-1.21). The fewer data for rimantadine showed comparable effects. in prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1.28, 0.45-3.66 for oral oseltamivir 75 mg daily, 1.51, 0.77-2.95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1 - 79, 1.10-2.93), especially at higher prophylactic doses (2.29, 1.34-.3.92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58.5% (15.6-79.6) for households and from 68% (34.9-84.2) to 89% (67-97) in contacts of index cases. in influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1.33, 1.29-1.37 for zanamivir; 1.30, 1.13-1.50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference -0.62, -0.82 to -0.41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0.32, 0.18-0.57). We could find no credible data on the effects of oseltamivir on avian influenza.Interpretation The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public-health measures.