奥司他韦和扎那米韦治疗 H274Y 突变的甲型 H1N1 流感病毒的临床效果：2007-2008 年和 2008-2009 年流感季节的日本多中心研究。
Clinical effectiveness of oseltamivir and zanamivir for treatment of influenza A virus subtype H1N1 with the H274Y mutation: a Japanese, multicenter study of the 2007-2008 and 2008-2009 influenza seasons.
机构信息
Japan Physicians Association, Tokyo, Japan.
出版信息
Clin Infect Dis. 2009 Dec 15;49(12):1828-35. doi: 10.1086/648424.
BACKGROUND
Influenza A virus subtype H1N1 with the H274Y mutation emerged and spread worldwide. However, the clinical effectiveness of the neuraminidase inhibitors, oseltamivir and zanamivir, has not been adequately reevaluated.
METHODS
Data from 164 patients with H1N1 virus infection and 59 patients with H3N2 virus infection during the 2008-2009 influenza season and 68 patients with H1N1 virus infection during the 2007-2008 influenza season who received a neuraminidase inhibitor were analyzed. The duration of fever (body temperature 37.5 degrees C) after the first dose of oseltamivir or zanamivir and from onset of symptoms was calculated from patient reports. The influenza virus was isolated, and its subtype was determined by hemagglutinin inhibition assay and polymerase chain reaction. The H274Y neuraminidase mutation status was determined by sequencing the neuraminidase segment.
RESULTS
Of 68 patients with H1N1 virus infection during the 2007-2008 season, 41 were treated with oseltamivir, and 27 were treated with zanamivir. During the 2008-2009 season, 77 patients with H1N1 virus infection were treated with oseltamivir, and 87 were treated with zanamivir; 31 and 28 patients with H3N2 virus infection were treated with oseltamivir and zanamivir, respectively. All 49 analyzed H1N1 virus isolates obtained during the 2008-2009 season, but none of the isolates obtained during the 2007-2008 season, contained the H274Y mutation. The mean +/- standard deviation duration of fever after the start of oseltamivir therapy was significantly longer for patients with H1N1 virus infection (49.1+/-30.2 h) than it was for patients with H3N2 virus infection (33.7+/-20.1 h; P < .01) during the 2008-2009 season and patients with H1N1 virus infection during the 2007-2008 season (32.0+/-18.9 h; P < .001). The duration of fever was significantly longer after the first dose of oseltamivir than it was after the first dose of zanamivir for patients with H1N1 virus infection during the 2008-2009 season (P <.001). The duration of fever from onset of H1N1 virus infection was significantly longer for children 15 years of age during 2008-2009 (70.6+/-34.5 h) than it was for such children during 2007-2008 (48.4+/-21.2).
CONCLUSION
The effectiveness of oseltamivir, but not that of zanamivir, decreased significantly for H1N1 virus infection during the 2008-2009 season.
背景
具有 H274Y 突变的甲型 H1N1 流感病毒已经出现并在全球范围内传播。然而，神经氨酸酶抑制剂奥司他韦和扎那米韦的临床疗效尚未得到充分评估。
方法
分析了 2008-2009 流感季节 164 例 H1N1 病毒感染和 59 例 H3N2 病毒感染患者，以及 2007-2008 流感季节 68 例接受神经氨酸酶抑制剂的 H1N1 病毒感染患者的数据。根据患者报告计算了服用奥司他韦或扎那米韦后首次剂量和症状开始后发热（体温 37.5°C）的持续时间。通过血凝抑制试验和聚合酶链反应分离流感病毒，并确定其亚型。通过测序神经氨酸酶片段确定 H274Y 神经氨酸酶突变状态。
结果
在 2007-2008 季节的 68 例 H1N1 病毒感染患者中，41 例接受了奥司他韦治疗，27 例接受了扎那米韦治疗。在 2008-2009 季节，77 例 H1N1 病毒感染患者接受了奥司他韦治疗，87 例接受了扎那米韦治疗；31 例和 28 例 H3N2 病毒感染患者分别接受了奥司他韦和扎那米韦治疗。在 2008-2009 季节获得的所有 49 株分析的 H1N1 病毒分离株均含有 H274Y 突变，但在 2007-2008 季节获得的分离株均未含有 H274Y 突变。与 2008-2009 季节的 H3N2 病毒感染患者（33.7+/-20.1 h；P<.01）和 2007-2008 季节的 H1N1 病毒感染患者（32.0+/-18.9 h；P<.001）相比，接受奥司他韦治疗的 H1N1 病毒感染患者的发热持续时间（49.1+/-30.2 h）明显更长。与接受扎那米韦治疗的患者相比，接受奥司他韦治疗的 2008-2009 季节 H1N1 病毒感染患者首次剂量后的发热持续时间明显更长（P<.001）。2008-2009 季节，15 岁以下儿童的 H1N1 病毒感染从发病开始的发热持续时间明显长于 2007-2008 年（70.6+/-34.5 h）（48.4+/-21.2 h）。
结论
2008-2009 年，奥司他韦对 H1N1 病毒感染的疗效显著下降，而扎那米韦的疗效则没有明显下降。
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