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一个新千年难题:如何在社区中使用一类强效的抗流感神经氨酸酶药物(NAIs)。

A new millennium conundrum: how to use a powerful class of influenza anti-neuraminidase drugs (NAIs) in the community.

作者信息

Oxford John, Balasingam Shobana, Lambkin Rob

机构信息

Barts and The London, Retroscreen Virology Ltd, Queen Mary's School of Medicine and Dentistry, 327 Mile End Road, London E1 4NS, UK.

出版信息

J Antimicrob Chemother. 2004 Feb;53(2):133-6. doi: 10.1093/jac/dkh037. Epub 2003 Dec 19.

Abstract

Influenza A and B viruses cause serious medical problems and social disruption every year in particular countries of the world. The virus is notoriously fickle and may attack citizens in say two adjacent countries but not the third. More rarely a global pandemic virus emerges causing millions of deaths worldwide. The SARS outbreak has illuminated weaknesses in planning for sudden outbreaks of disease in a modern society and in particular how panic can grip and cause intense economic disruption. Many communities in the world are neither prepared for a global pandemic nor a very acute epidemic of influenza. The neuraminidase inhibitors (NAIs) are a new class of antiviral drug targeting a viral influenza enzyme, the neuraminidase, which acts both to facilitate virus infection of cells by clearing a passage through otherwise protective respiratory fluids and also by helping release of the virus by cutting the chemical umbilical cord which links up the virus to the infected cell. Extensive laboratory studies of the two molecules zanamivir and oseltamivir have shown that they block all influenza A and B viruses yet tested and would, in theory, even inhibit the 1918 pandemic virus. Both drugs can be used prophylactically to prevent spread of infection in families and communities where 80-90% protection has been documented. The therapeutic effects are also strong in adults and children abbreviating infection, reducing quantities of excreted virus and reducing antibiotic prescriptions. The drugs have to be taken within 48 h of the onset of symptoms. Drug resistance is not a problem at present because although such mutants occur the mutants are compromised and are less virulent than their drug-sensitive parents and they spread less easily. The two drugs could be stockpiled to prepare for an influenza pandemic but, importantly, clinical and scientific experience need to be gained by using these inhibitors in the yearly conflagrations of epidemic influenza, which unchecked do great harm to our communities.

摘要

甲型和乙型流感病毒每年都会在世界上的某些特定国家引发严重的医疗问题和社会混乱。这种病毒变化无常,可能侵袭相邻的两个国家,但不会侵袭第三个国家。更罕见的是,会出现一种全球大流行病毒,导致全球数百万人死亡。严重急性呼吸综合征(SARS)的爆发揭示了现代社会在应对突发疾病方面规划的不足之处,尤其是恐慌如何蔓延并造成严重的经济混乱。世界上许多社区既没有为全球大流行做好准备,也没有应对非常严重的流感疫情的能力。神经氨酸酶抑制剂(NAIs)是一类新型抗病毒药物,作用于一种名为神经氨酸酶的流感病毒酶。神经氨酸酶通过清除保护性呼吸道分泌物中的通道来促进病毒感染细胞,还通过切断连接病毒与受感染细胞的化学纽带帮助病毒释放。对扎那米韦和奥司他韦这两种药物进行的大量实验室研究表明,它们能阻断所有已测试的甲型和乙型流感病毒,理论上甚至能抑制1918年的大流行病毒。这两种药物都可用于预防,在家庭和社区中预防感染传播,已有记录显示其预防效果可达80% - 90%。在成人和儿童中治疗效果也很强,可缩短感染时间,减少病毒排泄量,并减少抗生素处方。这些药物必须在症状出现后48小时内服用。目前耐药性不是问题,因为虽然会出现此类突变体,但这些突变体存在缺陷,其毒性比药物敏感的亲本低,传播也不那么容易。这两种药物可以储备起来以应对流感大流行,但重要的是,需要在每年的流感疫情中使用这些抑制剂来积累临床和科学经验,因为流感疫情若不加以控制会对我们的社区造成极大危害。

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