Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Antiviral Res. 2011 Oct;92(1):81-9. doi: 10.1016/j.antiviral.2011.07.004. Epub 2011 Jul 13.
Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 2009 and 2010 [A(H1N1) 2009] distributed across this period were analyzed. Of these, 19 cases of oseltamivir-resistant virus harboring the H275Y mutation in the neuraminidase (NA) were detected. The mean 50% inhibitory concentration (IC50) levels for oseltamivir- and zanamivir-susceptible A(H1N1) 2009 viruses were 1.4-fold and 2-fold, respectively, lower than for the seasonal A(H1N1) influenza viruses from 2007/2008; for oseltamivir-resistant A(H1N1) 2009 virus the IC50 was 2.9-fold lower. Eighteen of the 19 patients with oseltamivir-resistant virus showed prolonged shedding of the virus and developed resistance while on oseltamivir therapy. Sixteen of these 18 patients had an immunodeficiency, of whom 11 had a hematologic disorder. The two other patients had another underlying disease. Six of the patients who had an underlying disease died; of these, five had received cytostatic or immunosuppressive therapy. No indications for onward transmission of resistant viruses were found. This study showed that the main association for the emergence of cases of oseltamivir-resistant A(H1N1) 2009 virus was receiving antiviral therapy and having drug-induced immunosuppression or an hematologic disorder. Except for a single case of a resistant virus not linked to oseltamivir therapy, the absence of detection of resistant variants in community specimens and in specimens from contacts of cases with resistant virus suggested that the spread of resistant A(H1N1) 2009 virus was limited. Containment may have been the cumulative result of impaired NA function, successful isolation of the patients, and prophylactic measures to limit exposure.
从 2009 年 4 月底至 2010 年 5 月底，荷兰开展了针对大流行甲型 H1N1 流感病毒的感染强化监测，包括监测抗病毒药物耐药性。分析了这期间 2009 年和 2010 年（A(H1N1) 2009）分布的 1100 多例大流行甲型 H1N1 流感病毒感染病例。其中，检测到 19 例携带神经氨酸酶（NA）H275Y 突变的奥司他韦耐药病毒。对奥司他韦和扎那米韦敏感的 A(H1N1) 2009 病毒的 50%半数抑制浓度（IC50）水平分别比 2007/2008 年季节性 A(H1N1) 流感病毒低 1.4 倍和 2 倍；奥司他韦耐药 A(H1N1) 2009 病毒的 IC50 低 2.9 倍。19 例奥司他韦耐药病毒患者中有 18 例在奥司他韦治疗期间病毒持续排出并产生耐药性。这 18 例患者中有 16 例免疫功能低下，其中 11 例患有血液系统疾病。另外两例患者有其他潜在疾病。18 例患者中有 6 例死亡；其中 5 例接受了细胞毒性或免疫抑制治疗。未发现耐药病毒传播的迹象。本研究表明，奥司他韦耐药 A(H1N1) 2009 病毒出现的主要关联因素是接受抗病毒治疗以及药物诱导的免疫抑制或血液系统疾病。除了一例与奥司他韦治疗无关的耐药病毒外，在社区样本和耐药病毒病例接触者的样本中均未检测到耐药变异株，这表明耐药 A(H1N1) 2009 病毒的传播是有限的。这种控制可能是由于神经氨酸酶功能受损、成功隔离患者以及采取预防措施限制接触等综合作用的结果。
