Prescrire Int. 2006 Feb;15(81):21-30.
(1) Influenza is a common acute respiratory disease due to a virus that causes annual seasonal epidemics. Three major pandemics occurred in the 20th century, in 1918-1919, 1957 and 1968, mainly due to genetic variants of type A influenza virus. (2) In temperate regions the incidence of hospitalisation increases during annual influenza epidemics. More than 90% of deaths linked to influenza involve people over 65 years of age. (3) The clinical manifestations of influenza virus infection are non specific. The main complications are secondary bacterial respiratory tract infections (especially pneumonia); those most at risk are people over 65, infants less than one year old, and people with underlying chronic disorders (pulmonary, cardiac, renal or metabolic) or immune deficiencies. (4) Vaccination is the main preventive measure. During most years the vaccine strain closely matches the epidemic strain. In relative terms, vaccination of people over 65 reduces the number of deaths linked to influenza by about 80%, hospitalisation and pneumonia by about 50%, and symptomatic influenza by about 30%. Yearly vaccination is recommended for younger people with serious chronic disease. (5) Three antiviral drugs are currently approved in France for prevention or treatment of influenza: amantadine and the neuraminidase inhibitors zanamivir and oseltamivir. (6) Efficacy of antiviral drugs has not been evaluated in comparative randomised trials in which death and influenza complications were the primary outcome measures. (7) A systematic review of 20 comparative randomised trials involving about 2500 healthy people showed that amantadine reduced the frequency of flu-like syndromes by about 7% in absolute terms (26.3% versus 33.1% with placebo). Zanamivir and oseltamivir have only been shown to reduce the frequency of serologically confirmed episodes of influenza (0.4% to 2.5%, compared to 4.4% to 14.9% with placebo). (8) In a randomised placebo-controlled trial of oseltamivir, involving 548 institutionalised subjects over 65 years of age, more than 80% of whom had been vaccinated, respiratory tract infections were less frequent in the oseltamivir group, but the relevance of this result is undermined by the small number of observed cases. (9) Efficacy of antiviral drugs on avian influenza (bird flu) was studied during a 2003 Dutch outbreak due to a type A/H7N7 virus. Among the 38 exposed persons who were treated, about 3% developed symptoms, compared with about 10% of 52 exposed persons who refused treatment (p = 0.38). The low statistical power and the lack of randomisation rule out any firm conclusions on preventive effects. (10) The three antiviral drugs have different profiles of adverse effects and drug interactions. Amantadine carries a risk of neuropsychological, atropinic and dopaminergic adverse effects, and can interact with drugs that have similar effects. Zanamivir carries a risk of life-threatening bronchospasm. Oseltamivir was approved relatively recently and its full spectrum of adverse effects is not yet known; its main adverse effects appear to be mild gastrointestinal disturbances, although a few cases of serious cutaneous reactions have been reported. (11) In vitro resistance to the three drugs has been demonstrated, but the possible clinical and epidemiological consequences are unclear. (12) In situations warranting antiviral therapy for the prevention of influenza, oseltamivir, at a dose of 75 mg/day for 10 days, is the drug with the best risk-benefit balance. Its use should be limited to situations where a major potential benefit exists in order to avoid selection for resistant strains. (13) Testing of oseltamivir in children is limited. Oseltamivir should be avoided during pregnancy, because of evidence that it may harm the unborn child. (14) In practice, the use of antiviral drugs in otherwise healthy adults and children is not generally recommended. (15) Despite the lack of convincing data regarding the efficacy of oseltamivir in preventing complications of influenza, its effect on documented infections suggests it may be useful for unvaccinated individuals who are at high risk of infection and severe complications. Under these conditions, treatment should be started within 48 hours after contact with a person who has flu-like symptoms during a seasonal epidemic; residents in institutions in which influenza cases occur may also qualify for preventive treatment. Other preventive measures should also be used, including immediate vaccination, case isolation, use of face masks, and more frequent hand washing. (16) During seasonal influenza epidemics due to viral strains against which the current vaccine is of limited effectiveness, the utility, target populations and optimal duration of preventive antiviral treatment must be determined by examining the groups most at risk and the severity of complications. (17) Most flu-like syndromes are not due to the influenza virus, and the preventive effect of antiviral drugs on complications in persons at risk has not yet been demonstrated. (18) In practice, antiviral drugs are not an alternative to influenza vaccination, but may be a useful adjunct in some situations. It is best to limit their use to short-term prophylaxis of vulnerable persons in situations where the risk of contracting influenza virus infection is high.
(1) 流感是一种常见的急性呼吸道疾病,由病毒引起,每年都会引发季节性流行。20世纪发生了三次大流行,分别在1918 - 1919年、1957年和1968年,主要是由于甲型流感病毒的基因变异。(2) 在温带地区,每年流感流行期间住院率都会上升。与流感相关的死亡中,超过90%发生在65岁以上的人群。(3) 流感病毒感染的临床表现不具特异性。主要并发症是继发性细菌性呼吸道感染(尤其是肺炎);高危人群为65岁以上人群、1岁以下婴儿以及患有基础慢性疾病(肺部、心脏、肾脏或代谢性疾病)或免疫缺陷的人群。(4) 接种疫苗是主要的预防措施。在大多数年份,疫苗毒株与流行毒株密切匹配。相对而言,65岁以上人群接种疫苗可使与流感相关的死亡人数减少约80%,住院和肺炎发生率减少约50%,有症状的流感发生率减少约30%。建议患有严重慢性病的年轻人每年接种疫苗。(5) 法国目前批准了三种抗病毒药物用于预防或治疗流感:金刚烷胺以及神经氨酸酶抑制剂扎那米韦和奥司他韦。(6) 抗病毒药物的疗效尚未在以死亡和流感并发症为主要结局指标的比较随机试验中进行评估。(7) 一项对约2500名健康人进行的20项比较随机试验的系统评价表明,金刚烷胺可使流感样综合征的发生率绝对降低约7%(26.3%对安慰剂组的33.1%)。扎那米韦和奥司他韦仅显示可降低血清学确诊的流感发作频率(0.4%至2.5%,而安慰剂组为4.4%至14.9%)。(8) 在一项针对65岁以上住院患者的奥司他韦随机安慰剂对照试验中,超过80%的患者已接种疫苗,奥司他韦组呼吸道感染的发生率较低,但由于观察到的病例数较少,这一结果的相关性受到影响。(9) 在2003年荷兰因A/H7N7型病毒爆发期间,研究了抗病毒药物对禽流感(禽流感)的疗效。在38名接受治疗的暴露者中,约3%出现症状,而52名拒绝治疗的暴露者中约10%出现症状(p = 0.38)。统计效力低且缺乏随机化排除了关于预防效果的确切结论。(10) 这三种抗病毒药物具有不同的不良反应和药物相互作用特征。金刚烷胺存在神经心理、阿托品样和多巴胺能不良反应的风险,并且可与具有类似作用的药物相互作用。扎那米韦存在危及生命的支气管痉挛风险。奥司他韦相对较新获批,其全部不良反应尚不清楚;其主要不良反应似乎是轻度胃肠道不适,尽管已报告了一些严重皮肤反应的病例。(11) 已证明对这三种药物存在体外耐药性,但可能的临床和流行病学后果尚不清楚。(12) 在需要进行抗病毒治疗以预防流感的情况下,奥司他韦以75毫克/天的剂量服用10天,是风险效益平衡最佳的药物。其使用应限于存在重大潜在益处的情况,以避免选择耐药毒株。(13) 奥司他韦在儿童中的试验有限。由于有证据表明奥司他韦可能伤害未出生的婴儿,因此在怀孕期间应避免使用。(14) 在实际操作中,一般不建议在健康的成人和儿童中使用抗病毒药物。(15) 尽管关于奥司他韦预防流感并发症的疗效缺乏令人信服的数据,但其对已确诊感染的作用表明,它可能对未接种疫苗且感染和严重并发症风险高的个体有用。在这些情况下,应在季节性流行期间与出现流感样症状的人接触后48小时内开始治疗;发生流感病例的机构中的居民也可能符合预防性治疗的条件。还应采取其他预防措施,包括立即接种疫苗、病例隔离、使用口罩以及更频繁地洗手。(16) 在季节性流感流行期间,对于当前疫苗效力有限的病毒株,必须通过检查高危人群和并发症的严重程度来确定预防性抗病毒治疗的效用、目标人群和最佳持续时间。(17) 大多数流感样综合征并非由流感病毒引起,抗病毒药物对高危人群并发症的预防作用尚未得到证实。(18) 在实际操作中,抗病毒药物不是流感疫苗的替代品,但在某些情况下可能是有用的辅助手段。最好将其使用限于在感染流感病毒风险高的情况下对易感人群进行短期预防。