Gooskens Jairo, Jonges Marcel, Claas Eric C J, Meijer Adam, van den Broek Peterhans J, Kroes Aloyj M
Department of Medical Microbiology, E4-65, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
JAMA. 2009 Mar 11;301(10):1042-6. doi: 10.1001/jama.2009.297. Epub 2009 Mar 2.
The sudden emergence and rapid spread of oseltamivir-resistant influenza A(H1N1) viruses with neuraminidase (NA) gene H274Y amino acid substitution is the hallmark of global seasonal influenza since January 2008. Viruses carrying this mutation are widely presumed to exhibit attenuated pathogenicity, compromised transmission, and reduced lethality.
To investigate nosocomial viral transmission in a cluster of patients with influenza A(H1N1) virus infection.
DESIGN, SETTING, AND PATIENTS: Descriptive outbreak investigation of 2 hematopoietic stem cell transplant recipients and an elderly patient who developed hospital-acquired influenza A virus infection following exposure to an index patient with community-acquired H274Y-mutated influenza A(H1N1) virus infection in a medical ward at a Dutch university hospital in February 2008. The investigation included a review of the medical records, influenza virus polymerase chain reaction and culture, phenotypic oseltamivir and zanamivir susceptibility determination, and hemagglutinin chain 1 (HA(1)) gene and NA gene sequence analysis.
Phylogenetic relationship of patient cluster influenza A(H1N1) viruses and other 2007-2008 seasonal influenza A(H1N1) viruses.
Viral HA(1) and NA gene sequence analysis from the 4 patients revealed indistinguishable nucleotide sequences and phylogenetic clustering of H274Y-mutated, oseltamivir-resistant influenza A(H1N1) virus, confirming nosocomial transmission. Influenza virus pneumonia (3 patients) and attributable mortality (2 patients) during active infection was observed in patients with lymphocytopenia at onset.
Seasonal oseltamivir-resistant influenza A(H1N1) viruses with NA gene H274Y mutation are transmitted and retain significant pathogenicity and lethality in high-risk patients.
自2008年1月以来，具有神经氨酸酶（NA）基因H274Y氨基酸取代的耐奥司他韦甲型H1N1流感病毒的突然出现和迅速传播是全球季节性流感的标志。普遍认为携带这种突变的病毒致病性减弱、传播能力受损且致死率降低。
调查一群甲型H1N1流感病毒感染患者中的医院内病毒传播情况。
设计、地点和患者：对2例造血干细胞移植受者和1例老年患者进行描述性暴发调查，这3例患者于2008年2月在荷兰一家大学医院的内科病房接触了1例社区获得性H274Y突变的甲型H1N1流感病毒感染的索引患者后发生了医院获得性甲型流感病毒感染。调查包括查阅病历、进行流感病毒聚合酶链反应和培养、奥司他韦和扎那米韦表型敏感性测定以及血凝素链1（HA(1)）基因和NA基因序列分析。
患者群甲型H1N1流感病毒与其他2007 - 2008年季节性甲型H1N1流感病毒的系统发育关系。
对4例患者的病毒HA(1)和NA基因序列分析显示，H274Y突变的耐奥司他韦甲型H1N1流感病毒的核苷酸序列无法区分且存在系统发育聚类，证实了医院内传播。发病时淋巴细胞减少的患者在活跃感染期间出现了流感病毒肺炎（3例患者）和可归因死亡（2例患者）。
具有NA基因H274Y突变的季节性耐奥司他韦甲型H1N1流感病毒在高危患者中具有传播性，并保留了显著的致病性和致死率。
