A two-year survey of the oseltamivir-resistant influenza A(H1N1) virus in Yamagata, Japan and the clinical effectiveness of oseltamivir and zanamivir.
A two-year survey of the oseltamivir-resistant influenza A(H1N1) virus in Yamagata, Japan and the clinical effectiveness of oseltamivir and zanamivir.
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DOI：
10.1186/1743-422x-7-53
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发表时间：
2010-03-05
期刊：
影响因子：
4.8
通讯作者：
Tashiro M
中科院分区：
文献类型：
--
作者：
Matsuzaki Y;Mizuta K;Aoki Y;Suto A;Abiko C;Sanjoh K;Sugawara K;Takashita E;Itagaki T;Katsushima Y;Ujike M;Obuchi M;Odagiri T;Tashiro M
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，耐奥司他韦的甲型H1N1流感病毒已在全球范围内流行。本研究旨在确定日本山形县甲型H1N1流感病毒分离株对奥司他韦的耐药率，比较2007-2008年和2008-2009年流感季分离株的病毒学特征，并评估奥司他韦的临床有效性。通过检测神经氨酸酶（NA）基因中的H275 Y突变确定的奥司他韦耐药，分别在2007-2008和2008-2009季节的2.5%（79例中的2例）和100%（77例中的77例）分离株中观察到。抗原性分析表明，2008-2009年流感季传播的甲型H1N1流感病毒的抗原性不同。生长试验表明，2008-2009年分离株在MDCK细胞中复制的能力与2007-2008年季节的奥司他韦敏感分离株相似。系统发育分析显示，在2007-2008年季节分离的两种奥司他韦耐药病毒与山形县的其他奥司他韦敏感病毒密切相关，但与2007-2008年季节在欧洲和北美分离的奥司他韦耐药病毒不同。2008-2009年季节在日本分离的奥司他韦耐药病毒与2007-2008年季节在欧洲和北美分离的奥司他韦耐药病毒在遗传学上相似。此外，奥司他韦治疗开始后，奥司他韦耐药病例的发热中位持续时间（2天;范围1-6天）明显长于奥司他韦敏感病例（1.5天：范围1-2天）（P = 0.0356）。2007-2008年季节从山形分离的奥司他韦耐药甲型H1N1流感病毒株可能通过使用奥司他韦获得了耐药性，2008-2009年的奥司他韦耐药株可能已被引入日本并在全国范围内传播。流感监测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。
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.