Morbidity and Mortality Associated With Nosocomial Transmission of Oseltamivir-Resistant Influenza A(H1N1) Virus
Morbidity and Mortality Associated With Nosocomial Transmission of Oseltamivir-Resistant Influenza A(H1N1) Virus
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DOI：
10.1001/jama.2009.297
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发表时间：
2009-03-11
影响因子：
120.7
通讯作者：
Kroes, Aloys C. M.
中科院分区：
文献类型：
--
作者：
Gooskens, Jairo;Jonges, Marcel;Kroes, Aloys C. M.
背景自2008年1月以来，具有神经氨酸酶（NA）基因H274 Y氨基酸取代的奥司他韦耐药甲型H1N1流感病毒的突然出现和快速传播是全球季节性流感的标志。携带这种突变的病毒被广泛认为表现出减弱的致病性，妥协的传播，并降低lethality. ObjectiveTo调查医院内的病毒传播在一群甲型H1N1流感病毒感染的患者。设计，设置，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，2008年2月，在荷兰一所大学医院的内科病房中，患者接触了一名社区获得性H274 Y变异甲型流感（H1N1）病毒感染的指示患者后，发生了获得性甲型流感病毒感染。调查包括病历回顾、流感病毒聚合酶链反应和培养、表型奥司他韦和扎那米韦敏感性测定，主要指标2007-2008年甲型H1N1流感病毒与其他季节性流感病毒的亲缘关系结果4例患者的病毒HA 1和NA基因序列分析显示H274 Y突变的奥司他韦耐药甲型H1N1流感病毒的核苷酸序列和系统发育聚类难以区分，证实了医院传播。结论NA基因H274 Y突变的季节性奥司他韦耐药甲型H1N1流感病毒在高危人群中传播，并保留了明显的致病性和致死性。
Context 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.Objective 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.Main Outcome Measure Phylogenetic relationship of patient cluster influenza A(H1N1) viruses and other 2007-2008 seasonal influenza A(H1N1) viruses.Results Viral HA1 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.Conclusion Seasonal oseltamivir-resistant influenza A(H1N1) viruses with NA gene H274Y mutation are transmitted and retain significant pathogenicity and lethality in high-risk patients.