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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus.
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Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus.

机译：奥司他韦治疗在雪貂中感染H5N1流感病毒不同进化枝的功效。

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Highly pathogenic H5N1 influenza viruses have infected an increasing number of humans in Asia, with high mortality rates and the emergence of multiple distinguishable clades. It is not known whether antiviral drugs that are effective against contemporary human influenza viruses will be effective against systemically replicating viruses, such as these pathogens. Therefore, we evaluated the use of the neuraminidase (NA) inhibitor oseltamivir for early postexposure prophylaxis and for treatment in ferrets exposed to representatives of two clades of H5N1 virus with markedly different pathogenicities in ferrets. Ferrets were protected from lethal infection with the A/Vietnam/1203/04 (H5N1) virus by oseltamivir (5 mg/kg of body weight/day) given 4 h after virus inoculation, but higher daily doses (25 mg/kg) were required for treatment when it was initiated 24 h after virus inoculation. For the treatment of ferrets inoculated with the less pathogenic A/Turkey/15/06 (H5N1) virus, 10 mg/kg/day of oseltamivir was sufficient to reduce the lethargy of the animals, significantly inhibit inflammation in the upper respiratory tract, and block virus spread to the internal organs. Importantly, all ferrets that survived the initial infection were rechallenged with homologous virus after 21 days and were completely protected from infection. Direct sequencing of the NA or HA1 gene segments in viruses isolated from ferret after treatment showed no amino acid substitutions known to cause drug resistance in conserved residues. Thus, early oseltamivir treatment is crucial for protection against highly pathogenic H5N1 viruses and the higher dose may be needed for the treatment of more virulent viruses.
机译：高致病性H5N1流感病毒在亚洲感染了越来越多的人，死亡率高，并且出现了许多不同的进化枝。尚不知道能有效对抗当代人类流感病毒的抗病毒药物是否能有效对抗诸如这些病原体的系统复制病毒。因此，我们评估了神经氨酸酶（NA）抑制剂oseltamivir在暴露后早期预防和治疗暴露于两个H5N1病毒代表的雪貂中的用途，雪貂的致病性明显不同。接种病毒后4小时给予奥司他韦（5 mg / kg体重/天）保护雪貂免受A / Vietnam / 1203/04（H5N1）病毒的致死性感染，但每日剂量更高（25 mg / kg）接种病毒24小时后开始治疗时所需。为了治疗感染病原性较低的A / Turkey / 15/06（H5N1）病毒的雪貂，每天10 mg / kg /天的奥司他韦足以减少动物的嗜睡，显着抑制上呼吸道炎症，以及阻止病毒传播到内部器官。重要的是，所有在初次感染后幸存的雪貂在21天后都会被同源病毒再次攻击，并受到完全保护，免受感染。处理后从雪貂分离出的病毒中NA或HA1基因片段的直接测序结果表明，没有氨基酸取代可导致保守残基产生耐药性。因此，早期的奥司他韦治疗对于预防高致病性H5N1病毒至关重要，并且可能需要更高剂量才能治疗更具毒性的病毒。

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