WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention (CDC), 1600 Clifton RD NE, MS-G16, Atlanta, GA, 30329, United States.
Global Influenza Programme, World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland.
Antiviral Res. 2017 Oct;146:12-20. doi: 10.1016/j.antiviral.2017.08.004. Epub 2017 Aug 10.
Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) assessed antiviral susceptibility of 14,330 influenza A and B viruses collected by WHO-recognized National Influenza Centres (NICs) between May 2015 and May 2016. Neuraminidase (NA) inhibition assay was used to determine 50% inhibitory concentration (IC) data for NA inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Furthermore, NA sequences from 13,484 influenza viruses were retrieved from public sequence databases and screened for amino acid substitutions (AAS) associated with reduced inhibition (RI) or highly reduced inhibition (HRI) by NAIs. Of the viruses tested by WHO CCs 93% were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 0.8% (n = 113) exhibited either RI or HRI by at least one of four NAIs. As in previous seasons, the most common NA AAS was H275Y in A(H1N1)pdm09 viruses, which confers HRI by oseltamivir and peramivir. Two A(H1N1)pdm09 viruses carried a rare NA AAS, S247R, shown in this study to confer RI/HRI by the four NAIs. The overall frequency of A(H1N1)pdm09 viruses containing NA AAS associated with RI/HRI was approximately 1.8% (125/6915), which is slightly higher than in the previous 2014-15 season (0.5%). Three B/Victoria-lineage viruses contained a new AAS, NA H134N, which conferred HRI by zanamivir and laninamivir, and borderline HRI by peramivir. A single B/Victoria-lineage virus harboured NA G104E, which was associated with HRI by all four NAIs. The overall frequency of RI/HRI phenotype among type B viruses was approximately 0.6% (43/7677), which is lower than that in the previous season. Overall, the vast majority (>99%) of the viruses tested by WHO CCs were susceptible to all four NAIs, showing normal inhibition (NI). Hence, NAIs remain the recommended antivirals for treatment of influenza virus infections. Nevertheless, our data indicate that it is prudent to continue drug susceptibility monitoring using both NAI assay and sequence analysis.
四个世界卫生组织（WHO）流感参考和研究合作中心以及一个 WHO 流感监测、流行病学和控制合作中心（WHO CC）评估了 2015 年 5 月至 2016 年 5 月间，由世界卫生组织认可的国家流感中心（NIC）收集的 14330 株甲型和乙型流感病毒对神经氨酸酶（NA）抑制剂（NAIs）奥司他韦、扎那米韦、帕拉米韦和拉尼米韦的抗病毒敏感性。采用神经氨酸酶抑制试验（NAI）测定 50%抑制浓度（IC）数据，以确定对 NAIs 的抑制（RI）或高度抑制（HRI）降低的相关氨基酸取代（AAS）。从公共序列数据库中检索了来自 13484 株流感病毒的 NA 序列，并对与奥司他韦和帕拉米韦的 HRI 相关的氨基酸取代（AAS）进行了筛选。在 WHO CC 测试的病毒中，约 93%来自三个世界卫生组织区域：西太平洋、美洲和欧洲。大约 0.8%（n=113）的病毒对四种 NAI 中的至少一种表现出 RI 或 HRI。与以往季节一样，最常见的 NA AAS 是 A（H1N1）pdm09 病毒中的 H275Y，它对奥司他韦和帕拉米韦产生 HRI。两种 A（H1N1）pdm09 病毒携带一种罕见的 NA AAS，S247R，本研究表明该病毒对四种 NAI 均具有 RI/HRI。与 RI/HRI 相关的 A（H1N1）pdm09 病毒中含有 NA AAS 的总体频率约为 1.8%（125/6915），略高于上一季（0.5%）。3 株 B/Victoria 谱系病毒含有新的 AAS，即 NA H134N，对扎那米韦和拉尼米韦产生 HRI，对帕拉米韦产生边界性 HRI。单一的 B/Victoria 谱系病毒含有 NA G104E，与四种 NAI 均与 HRI 相关。B 型病毒中 RI/HRI 表型的总体频率约为 0.6%（43/7677），低于上一季。总体而言，由 WHO CC 测试的绝大多数（>99%）病毒对四种 NAI 均敏感，表现出正常抑制（NI）。因此，NAIs 仍然是治疗流感病毒感染的推荐抗病毒药物。然而，我们的数据表明，使用 NAI 测定和序列分析继续进行药物敏感性监测是谨慎的。
