Jefferson T O, Demicheli V, Di Pietrantonj C, Jones M, Rivetti D
Cochrane Database Syst Rev. 2006 Jul 19(3):CD001265. doi: 10.1002/14651858.CD001265.pub2.
Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in interpandemic years and in a pandemic.
To assess the effects of NIs in preventing or ameliorating influenza, its transmission and its complications in healthy adults and to estimate the frequency of adverse effects.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2004 to September, Week 4 2005), EMBASE (2003 to June 2005) and contacted manufacturers, researchers in the field, and authors of studies evaluated in the review.
Randomised or quasi-randomised placebo-controlled studies of NIs in healthy adults exposed to naturally occurring influenza.
Two authors applied inclusion criteria, assessed trial quality and extracted data. We structured the comparisons into prophylaxis, treatment and adverse events with further subdivision by outcome and dose.
We identified four prophylaxis, 13 treatment and four post-exposure prophylaxis (PEP) trials. In prophylaxis compared to placebo, NIs have no effect against influenza-like illnesses (ILI) (relative risk (RR) 1.28, 95% confidence interval (CI) 0.45 to 3.66 for oral oseltamivir 75 mg daily; RR 1.51, 95% CI 0.77 to 2.95 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (RR 0.39, 95% CI 0.18 to 0.85), or 73% (RR 0.27, 95% CI 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (RR 0.38, 95% CI 0.17 to 0.85). Neither NI has a significant effect on asymptomatic influenza. Oseltamivir induces nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for PEP has an efficacy of 58.5% (15.6% to 79.6) for households and of 68% (34.9 to 84.2%) to 89% in contacts of index cases. Zanamivir has similar performance. The hazard ratios for time to alleviation of influenza symptoms were in favour of the treated group 1.33 (1.29 to 1.37) for zanamivir and 1.30 (1.13 to 1.50) for oseltamivir. Viral nasal titres were significantly diminished by both NIs. Oseltamivir 150 mg daily prevented lower respiratory tract complications (OR 0.32, 95% CI 0.18 to 0.57). We could find no comparative data on the effects of oseltamivir on avian influenza.
AUTHORS' CONCLUSIONS: Because of their low effectiveness, NIs should not be used in routine seasonal influenza control. In a serious epidemic or pandemic, NIs should be used with other public health measures. We are unsure of the generalisability of our conclusions from seasonal to pandemic or avian influenza.
神经氨酸酶抑制剂(NI)被推荐用于在流感大流行间期和大流行期间对抗流感及其并发症。
评估NI在预防或改善健康成年人流感、其传播及其并发症方面的效果,并估计不良反应的发生率。
我们检索了Cochrane对照试验中心注册库(CENTRAL)(《Cochrane图书馆》2005年第3期)、MEDLINE(2004年至2005年9月第4周)、EMBASE(2003年至2005年6月),并联系了制造商、该领域的研究人员以及本综述中评估的研究的作者。
针对暴露于自然发生的流感的健康成年人进行的NI随机或半随机安慰剂对照研究。
两位作者应用纳入标准、评估试验质量并提取数据。我们将比较分为预防、治疗和不良事件,并按结果和剂量进一步细分。
我们确定了4项预防试验、13项治疗试验和4项暴露后预防(PEP)试验。与安慰剂相比,在预防方面,NI对流感样疾病(ILI)无效(每日口服75mg奥司他韦的相对风险(RR)为1.28,95%置信区间(CI)为0.45至3.66;每日吸入10mg扎那米韦的RR为1.51,95%CI为0.77至2.95)。每日口服75mg奥司他韦对有症状流感的疗效为61%(RR 0.39,95%CI 0.18至0.85),每日150mg时为73%(RR 0.27,95%CI 0.11至0.67)。每日吸入10mg扎那米韦的疗效为62%(RR 0.38,95%CI 0.17至0.85)。两种NI对无症状流感均无显著影响。奥司他韦会引起恶心(优势比(OR)为1.79,95%CI为1.10至2.93)。用于PEP的奥司他韦对家庭的疗效为58.5%(15.6%至79.6%),对索引病例接触者的疗效为68%(34.9%至84.2%)至89%。扎那米韦有类似表现。扎那米韦和奥司他韦缓解流感症状时间的风险比有利于治疗组,扎那米韦为1.33(1.29至1.37),奥司他韦为1.30(1.13至1.50)。两种NI均显著降低了鼻腔病毒滴度。每日150mg奥司他韦可预防下呼吸道并发症(OR 0.32,95%CI 0.18至0.57)。我们未找到关于奥司他韦对禽流感影响的比较数据。
由于其效果不佳,NI不应常规用于季节性流感防控。在严重的流行或大流行中,NI应与其他公共卫生措施一起使用。我们不确定我们从季节性流感得出的结论能否推广到流感大流行或禽流感。