Course of Clinical Nursing, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan.
Virol J. 2010 Mar 5;7:53. doi: 10.1186/1743-422X-7-53.
Oseltamivir is the preferred antiviral drug for influenza, but oseltamivir-resistant A(H1N1) viruses have circulated worldwide since the 2007-2008 influenza season. We aimed to determine the rate of oseltamivir resistance among A(H1N1) isolates from Yamagata, Japan, to compare the virological characteristics between isolates from the 2007-2008 and 2008-2009 seasons, and to evaluate the clinical effectiveness of oseltamivir.
Oseltamivir resistance, determined by detecting the H275Y mutation in the neuraminidase (NA) gene, was observed in 2.5% (2 of 79) and 100% (77 of 77) of isolates from the 2007-2008 and 2008-2009 seasons, respectively. Antigenic analysis suggested that antigenically different variants of A(H1N1) viruses circulated in the 2008-2009 season. Growth testing demonstrated that the ability of the 2008-2009 isolates to replicate in MDCK cells was similar to those of the oseltamivir-susceptible isolates from the 2007-2008 season. A phylogenetic analysis revealed that two oseltamivir-resistant viruses isolated in the 2007-2008 season were closely related to other oseltamivir-susceptible viruses in Yamagata but were different from oseltamivir-resistant viruses isolated in Europe and North America in the 2007-2008 season. The oseltamivir-resistant viruses isolated in Japan in the 2008-2009 season were phylogenetically similar to oseltamivir-resistant isolates from Europe and North America during the 2007-2008 season. Furthermore, the median duration of fever after the start of oseltamivir treatment was significantly longer in oseltamivir-resistant cases (2 days; range 1-6 days) than in oseltamivir-susceptible cases (1.5 days: range 1-2 days) (P = 0.0356).
Oseltamivir-resistant A(H1N1) isolates from Yamagata in the 2007-2008 season might have acquired resistance through the use of oseltamivir, and the 2008-2009 oseltamivir-resistant isolates might have been introduced into Japan and circulated throughout the country. Influenza surveillance to monitor oseltamivir-resistance would aid clinicians in determining an effective antiviral treatment strategy.
奥司他韦是治疗流感的首选抗病毒药物，但自 2007-2008 年流感季节以来，抗奥司他韦的 A(H1N1) 病毒已在全球传播。我们旨在确定日本山形县 A(H1N1)分离株的奥司他韦耐药率，比较 2007-2008 年和 2008-2009 年季节分离株的病毒学特征，并评估奥司他韦的临床疗效。
通过检测神经氨酸酶 (NA) 基因中的 H275Y 突变，分别在 2007-2008 年和 2008-2009 年季节的 2.5%（79 个分离株中的 2 个）和 100%（77 个分离株中的 77 个）的分离株中观察到奥司他韦耐药。抗原分析表明，2008-2009 年流行的 A(H1N1)病毒存在抗原不同的变体。生长试验表明，2008-2009 年分离株在 MDCK 细胞中的复制能力与 2007-2008 年奥司他韦敏感分离株相似。系统发育分析显示，2007-2008 年分离的两株奥司他韦耐药病毒与山形县其他奥司他韦敏感病毒密切相关，但与 2007-2008 年欧洲和北美的奥司他韦耐药病毒不同。2008-2009 年日本分离的奥司他韦耐药病毒与 2007-2008 年欧洲和北美的奥司他韦耐药分离株在系统发育上相似。此外，奥司他韦耐药病例（2 天；范围 1-6 天）发热开始后奥司他韦治疗的中位持续时间明显长于奥司他韦敏感病例（1.5 天；范围 1-2 天）（P=0.0356）。
山形县 2007-2008 年的奥司他韦耐药 A(H1N1)分离株可能通过奥司他韦的使用获得了耐药性，而 2008-2009 年的奥司他韦耐药分离株可能已传入日本并在全国传播。流感监测以监测奥司他韦耐药性将有助于临床医生确定有效的抗病毒治疗策略。
