Current and future antiviral therapy of severe seasonal and avian influenza.
Current and future antiviral therapy of severe seasonal and avian influenza.
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DOI：
10.1016/j.antiviral.2008.01.003
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发表时间：
2008-04
影响因子：
7.6
通讯作者：
Bray, Mike
中科院分区：
文献类型：
--
作者：
Beigel, John;Bray, Mike
关键词：
目前流行的甲型流感病毒H3 N2和H1N1亚型在大多数成人和儿童中引起短暂的发热性上呼吸道疾病（“季节性流感”），但婴儿、老年人、免疫缺陷和慢性病患者可能会发生危及生命的原发性病毒性肺炎或并发症，如细菌性肺炎。相比之下，禽流感病毒，如最近在东南亚出现的H5 N1病毒，当从家禽转移到以前健康的人身上时，可引起严重疾病（“禽流感”）。大多数H5 N1患者表现为发热、咳嗽和呼吸急促，并迅速发展为成人呼吸窘迫综合征。在季节性流感中，病毒复制仍然局限于呼吸道，但有限的研究表明，H5 N1感染的特点是系统性病毒传播，高细胞因子水平和多器官衰竭。胃肠道感染和脑炎也会发生。获得许可的抗流感药物（M2离子通道阻滞剂金刚烷胺和金刚乙胺，以及神经氨酸酶抑制剂奥司他韦和扎那米韦）对无并发症的季节性流感有益，但尚未确定严重季节性或H5 N1病毒感染的适当给药方案。治疗选择可能会受到快速出现的耐药病毒的限制。利巴韦林也在有限程度上用于治疗流感。本文综述了正在开发的许可药物和治疗方法，包括高剂量奥司他韦;非肠道给药的神经氨酸酶抑制剂，帕拉米韦和扎那米韦;扎那米韦的二聚体形式; RNA聚合酶抑制剂T-705;利巴韦林前药，韦拉米啶;多价和单克隆抗体;以及联合治疗。
The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a transient, febrile upper respiratory illness in most adults and children (“seasonal influenza”), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral pneumonia or complications such as bacterial pneumonia. By contrast, avian influenza viruses such as the H5N1 virus that recently emerged in Southeast Asia can cause severe disease when transferred from domestic poultry to previously healthy people (“avian influenza”). Most H5N1 patients present with fever, cough and shortness of breath that progress rapidly to adult respiratory distress syndrome. In seasonal influenza, viral replication remains confined to the respiratory tract, but limited studies indicate that H5N1 infections are characterized by systemic viral dissemination, high cytokine levels and multiorgan failure. Gastrointestinal infection and encephalitis also occur. The licensed anti-influenza drugs (the M2 ion channel blockers, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir) are beneficial for uncomplicated seasonal influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral infections have not been defined. Treatment options may be limited by the rapid emergence of drug-resistant viruses. Ribavirin has also been used to a limited extent to treat influenza. This article reviews licensed drugs and treatments under development, including high-dose oseltamivir; parenterally administered neuraminidase inhibitors, peramivir and zanamivir; dimeric forms of zanamivir; the RNA polymerase inhibitor T-705; a ribavirin prodrug, viramidine; polyvalent and monoclonal antibodies; and combination therapies.
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