WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia.
J Infect Dis. 2012 Jul 15;206(2):148-57. doi: 10.1093/infdis/jis337. Epub 2012 May 4.
Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported.
Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses.
Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution.
This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.
甲型 H1N1pdm09 流感病毒对奥司他韦的耐药性罕见,尤其是在未经治疗的社区病例中。此前并未报告持续性社区传播。
通过哨点监测、医院和全科医生网络收集亚太地区的流感标本。收集感染奥司他韦耐药病毒患者的临床和流行病学信息。
2011 年 5 月至 9 月期间,在澳大利亚新南威尔士州亨特地区(HNE)采集的 191 株甲型 H1N1pdm09 病毒中,有 29 株(15%)含有导致奥司他韦耐药的神经氨酸酶 H275Y 取代。只有 1 例患者在标本采集前接受过奥司他韦治疗。耐药株在遗传上非常密切相关,提示单一变异株的传播。90%的病例居住在 50 公里范围内。在 HNE 之外还检测到 3 种遗传上相似的奥司他韦耐药变异株,包括来自珀斯的 1 株,距离约 4000 公里。计算分析预测,这些病毒中的神经氨酸酶取代 V241I、N369K 和 N386S 可能抵消了 H275Y 取代的不稳定性效应。
该聚集代表 H275Y 奥司他韦耐药甲型 H1N1pdm09 流感的首次广泛社区传播。这些病例和关于潜在许可突变的数据表明,目前流行的甲型 H1N1pdm09 病毒在存在 H275Y 突变的情况下仍保留病毒适应性,奥司他韦耐药株的广泛出现可能更为可能。