流行性感冒和禽流感的抗病毒治疗

早期抗病毒治疗是改善流行性感冒和禽流感患者预后的关键。目前临床用于抗流感病毒的药物按作用机制可大致分为两类,一类作用于病毒表面的糖蛋白神经氨酸酶,另一类作用于离子通道M2蛋白。我国目前常用的抗流感病毒药物主要有奥司他韦、扎那米韦、金刚烷胺和金刚乙胺。抗流感病毒治疗应在发病后48h内尽早进行;在缺乏耐药检测结果的情况下,甲型流感病毒可选用奥司他韦、扎那米韦、金刚烷胺或金刚乙胺进行治疗,乙型流感病毒选用奥司他韦或扎那米韦治疗。耐药分析表明,对于甲型H1N1型流感、H5N1型禽流感和H7N9型禽流感应首选神经氨酸酶抑制剂治疗,疗程通常为5d,对重症患者可增加药物剂量并延长治疗时间。流感病毒耐药性的出现给抗流感病毒治疗带来了挑战,可考虑采用具有不同作用机制的抗流感病毒药物联合治疗耐药流感病毒感染。     

禽流感及抗禽流感病毒药物

禽流感是由正粘病毒科中A型流感病毒引起的禽烈性传染病。本文介绍了禽流感的病原学以及禽流感和人禽流感的相互关系，回顾了禽流感在人群中的流行概况；对目前正在使用和开发中的抗禽流感病毒药物进行了综述，重点介绍了神经氨酸酶抑制剂扎那米韦和奥司他韦。     

Socioeconomics of influenza and influenza vaccination in Europe

Although the effectiveness of influenza vaccination is established vaccination policies and their implementation differ considerably across Europe. Historically the selective policies for influenza vaccination were based on the proven efficacy of influenza vaccine in healthy volunteers, and recognition that influenza complications and death occur mostly in elderly people with chronic medical conditions. Healthcare providers are faced with increasingly aging populations and costly new technologies and are more likely to extend immunisation policies if new initiatives are cost effective compared with accepted measures. Few studies of vaccine effectiveness focus on elderly cohorts with and without high risk conditions. Accordingly, healthcare providers in Denmark, Sweden, The Netherlands and the UK may require further data on vaccine effectiveness in elderly people without high risk conditions before reconsidering their policies. Scandinavian countries may also require data demonstrating benefits in people with diabetes. Review of recent US studies indicates that the available data on vaccine effectiveness in preventing influenza-related hospitalisation and death are applicable in Europe, but vaccine costs and cost effectiveness, and the overall economic burden of inpatient and outpatient care, need to be assessed country by country.     

季节性流感疫苗接种对大流行流感的影响研究

加拿大研究发现,季节性流感疫苗接种增加2009年大流行甲型流感(H1N1)感染的危险性,而澳大利亚研究未能证实这个发现.雪貂实验结果表明,以前的季节性流感感染能防御大流行甲型流感(H1N1),但以前的季节性流感疫苗接种则不能.模型研究显示,流感感染可导致对不同亚型的暂时性免疫.这些观察可以解释加拿大和澳大利亚的不一致发...     

French economic evaluations of influenza and influenza vaccination

The cost-of-illness studies of influenza performed in France or the years 1985 and 1989 have shown that the major economic consideration in the respective sizes of indirect and direct costs. Depending on the point of view (from the perspective of National Health Insurance or the societal perspective) and the method used for measuring indirect costs, it was estimated that they could be between 1.5 and 9 times higher than direct costs. A cost-benefit study of influenza vaccination for the employed adult population showed that vaccination is a cost-saving strategy, although this was also contingent upon the problems associated with measuring indirect benefits as well as the effectiveness rate of vaccination in real conditions.     

Oseltamivir for influenza

Oseltamivir (pronounced os-el-ta-mi-veer; Tamiflu--Roche), an oral anti-influenza drug that inhibits influenza virus neuraminidase, is now available in the UK. It has recently been licensed throughout the EU for use, when influenza is circulating in the community, in the treatment of patients with early influenza-like symptoms, and for prophylaxis in people who have had close contact with someone with influenza. Oseltamivir is the second neuraminidase inhibitor to be licensed in the UK, the other being zanamivir (Relenza--GlaxoSmithKline), which is taken by inhalation and licensed only for treatment. Previously, we concluded that there was insufficient evidence that treatment with zanamivir prevented serious complications in people most at risk from influenza to recommend its use. Here we review the efficacy and safety of oseltamivir and discuss its role in the management of influenza.     

Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1

Effective diagnostic and therapeutic strategies are needed to control and combat the highly pathogenic avian influenza virus (AIV) subtype H5N1. To this end, we developed human monoclonal antibodies (mAbs) in single chain fragment variable (scFv) format towards the H5N1 avian influenza virus to gain new insights for the development of immunotherapy against human cases of H5N1. Using a biopanning based approach a large array of scFvs against H5N1 virus were isolated from the human semi-synthetic ETH-2 phage antibody library. H5N1 ELISA-positive scFvs with unique variable heavy (VH) and light (VL) chain gene sequences showed different biochemical properties and neutralization activity across H5N1 viral strains. In particular, the scFv clones AV.D1 and AV.C4 exerted a significant inhibition of the H5N1 A/Vietnam/1194/2004 virus infection in a pseudotype-based neutralization assay. Interestingly, these two scFvs displayed a cross-clade neutralizing activity versus A/whooping swan/Mongolia/244/2005 and A/Indonesia/5/2005 strains. These studies provide proof of the concept that human mAbs in scFv format with well-defined H5N1 recognition patterns and in vitro neutralizing activity can be easily and rapidly isolated by biopanning selection of an entirely artificial antibody repertoire using inactivated H5N1 virus as a bait.     

Polymeric inhibitor of influenza virus attachment protects mice from experimental influenza infection

Synthetic sialic acid-containing macromolecules inhibit influenza virus attachment to target cells and suppress the virus-mediated hemagglutination and neutralize virus infectivity in cell culture. To test the protective effects of attachment inhibitors in vivo, mice were infected with mouse-adapted influenza virus A/Aichi/2/68 (H3N2) and treated with synthetic polyacrylamide-based sialylglycopolymer PAA-YDS bearing moieties of (Neu5Acalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1)2-3,6Manbeta1-4GlcNAcbeta1-4GlcNAc. Single intranasal inoculations with PAA-YDS 30 min before or 10 min after infection increased the survival of mice (P<0.01). Multiple treatments with aerosolized PAA-YDS on days 2-5 post infection also increased survival (P<0.01), alleviated disease symptoms, and decreased lesions in the mouse lungs. These data suggest that synthetic polyvalent inhibitors of virus attachment can be used for prevention and treatment of influenza.