Hayden F G, Gubareva L V, Monto A S, Klein T C, Elliot M J, Hammond J M, Sharp S J, Ossi M J
University of Virginia, Charlottesville, USA.
N Engl J Med. 2000 Nov 2;343(18):1282-9. doi: 10.1056/NEJM200011023431801.
As prophylaxis against influenza in families, amantadine and rimantadine have had inconsistent effectiveness, partly because of the transmission of drug-resistant variants from treated index patients. We performed a double-blind, placebo-controlled study of inhaled zanamivir for the treatment and prevention of influenza in families.
We enrolled families (with two to five members and at least one child who was five years of age or older) before the 1998-1999 influenza season. If an influenza-like illness developed in one member, the family was randomly assigned to receive either inhaled zanamivir or placebo. The family member with the index illness was treated with either 10 mg of inhaled zanamivir (163 subjects) or placebo (158) twice a day for 5 days, and the other family members received either 10 mg of zanamivir (414 subjects) or placebo (423) once a day as prophylaxis for 10 days. The primary end point was the proportion of families in which at least one household contact had symptomatic, laboratory-confirmed influenza.
The proportion of families with at least one initially healthy household contact in whom influenza developed was smaller in the zanamivir group than in the placebo group (4 percent vs. 19 percent, P<0.001); the difference represented a 79 percent reduction in the proportion of families with at least one affected contact. Zanamivir provided protection against both influenza A and influenza B. A neuraminidase-inhibition assay and sequencing of the neuraminidase and hemagglutinin genes revealed no zanamivir-resistant variants. Among the subjects with index cases of laboratory-confirmed influenza, the median duration of symptoms was 2.5 days shorter in the zanamivir group than in the placebo group (5.0 vs. 7.5 days, P=0.01). Zanamivir was well tolerated.
When combined with the treatment of index cases, prophylactic treatment of family members with once-daily inhaled zanamivir is well tolerated and prevents the development of influenza. In this study there was no evidence of the emergence of resistant influenza variants.
作为家庭中流感的预防措施，金刚烷胺和金刚乙胺的效果并不一致，部分原因是耐药变异株从接受治疗的索引患者传播。我们进行了一项关于吸入扎那米韦治疗和预防家庭流感的双盲、安慰剂对照研究。
在1998 - 1999年流感季节前招募家庭（成员两至五名，至少有一名五岁或以上儿童）。如果一名家庭成员出现流感样疾病，该家庭被随机分配接受吸入扎那米韦或安慰剂。患有索引疾病的家庭成员接受10毫克吸入扎那米韦（163名受试者）或安慰剂（158名），每日两次，共5天，其他家庭成员接受10毫克扎那米韦（414名受试者）或安慰剂（423名），每日一次作为预防，共10天。主要终点是至少有一名家庭接触者出现有症状、实验室确诊流感的家庭比例。
扎那米韦组中至少有一名最初健康的家庭接触者患流感的家庭比例低于安慰剂组（4%对19%，P<0.001）；这一差异表明至少有一名受影响接触者的家庭比例降低了79%。扎那米韦对甲型和乙型流感均有预防作用。神经氨酸酶抑制试验以及神经氨酸酶和血凝素基因测序未发现扎那米韦耐药变异株。在实验室确诊流感索引病例的受试者中，扎那米韦组症状的中位持续时间比安慰剂组短2.5天（5.0天对7.5天，P = 0.01）。扎那米韦耐受性良好。
当与索引病例的治疗相结合时，家庭成员每日一次吸入扎那米韦进行预防性治疗耐受性良好，并可预防流感的发生。在本研究中，没有证据表明出现耐药流感变异株。
