2007/2008年冬季荷兰的甲型H1N1流感病毒对奥司他韦耐药情况

Influenza A(H1N1) Oseltamivir Resistant Viruses in the Netherlands During the Winter 2007/2008.

作者信息

Dijkstra Frederika, Jonges Marcel, van Beek Ruud, Donker Gé A, Schellevis François G, Koopmans Marion, van der Sande Marianne A B, Osterhaus Albert D M E, Boucher Charles A B, Rimmelzwaan Guus F, Meijer Adam

机构信息

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

出版信息

Open Virol J. 2011;5:154-62. doi: 10.2174/1874357901105010154. Epub 2011 Dec 23.

DOI:10.2174/1874357901105010154

PMID:22253652

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3249654/

Abstract

BACKGROUND

Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008.

METHODS

Within the existing influenza surveillance an additional questionnaire study was performed to retrospectively assess possible risk factors and establish clinical outcome of all patients with influenza virus A(H1N1) positive specimens. To discriminate resistant and sensitive viruses, fifty percent inhibitory concentrations for the neuramidase inhibitors oseltamivir and zanamivir were determined in a neuraminidase inhibition assay. Mutations previously associated with resistance to neuramidase inhibitors and M2 blockers (amantadine and rimantadine) were searched for by nucleotide sequencing of neuraminidase and M2 genes respectively.

RESULTS

Among 171 patients infected with A(H1N1) viruses an overall prevalence of oseltamivir resistance of 27% (95% CI: 20-34%) was found. None of influenza A(H1N1) oseltamivir resistant viruses tested was resistant against amantadine or zanamivir. Patient characteristics, underlying conditions, influenza vaccination, symptoms, complications, and exposure to oseltamivir and other antivirals did not differ significantly between patients infected with resistant and sensitive A(H1N1) viruses.

CONCLUSION

In 2007/2008 a large proportion of influenza A(H1N1) viruses resistant to oseltamivir was detected. There were no clinical differences between patients infected with resistant and sensitive A(H1N1) viruses. Continuous monitoring of the antiviral drug sensitivity profile of influenza viruses is justified, preferably using the existing sentinel surveillance, however, complemented with data from the more severe end of the clinical spectrum. In order to act timely on emergencies of public health importance we suggest setting up a surveillance system that can guarantee rapid access to the latter.

摘要

背景

2008年1月挪威首次报告出现对奥司他韦耐药的甲型H1N1流感病毒后，荷兰加强了抗病毒药物敏感性监测。

方法

在现有的流感监测中，开展了一项补充问卷调查研究，以回顾性评估所有甲型H1N1流感病毒阳性标本患者的可能危险因素并确定临床结局。为区分耐药和敏感病毒，在神经氨酸酶抑制试验中测定了神经氨酸酶抑制剂奥司他韦和扎那米韦的50%抑制浓度。分别通过对神经氨酸酶和M2基因进行核苷酸测序，查找先前与对神经氨酸酶抑制剂和M2阻滞剂（金刚烷胺和金刚乙胺）耐药相关的突变。

结果

在171例感染甲型H1N1流感病毒的患者中，发现奥司他韦耐药的总体患病率为27%（95%可信区间：20 - 34%）。所检测的甲型H1N1流感奥司他韦耐药病毒对金刚烷胺或扎那米韦均不耐药。感染耐药和敏感甲型H1N1流感病毒的患者在患者特征、基础疾病、流感疫苗接种、症状、并发症以及奥司他韦和其他抗病毒药物暴露方面无显著差异。

结论

2007/2008年检测到很大比例的甲型H1N1流感病毒对奥司他韦耐药。感染耐药和敏感甲型H1N1流感病毒的患者之间无临床差异。持续监测流感病毒的抗病毒药物敏感性谱是合理的，最好利用现有的哨点监测，但需补充来自临床谱更严重一端的数据。为了对具有公共卫生重要性的紧急情况及时采取行动，我们建议建立一个能够保证快速获取后者数据的监测系统。