上海地区儿童新型甲型H1N1流感的临床和分子流行病学特征

Clinical characteristics and molecular epidemiology of the novel influenza A （H1N1） infection in children in Shanghai

目的 了解新型甲型H1N1流感病毒自暴发流行后在上海地区儿童中的流行病学特征,监测血凝素抗原区抗原位点变异及奥司他韦耐药株.方法 在2009年6月至2012年5月连续3年间,前瞻性监测因流感样疾病就诊于复旦大学附属儿科医院的门诊患儿,收集呼吸道标本和临床资料.检测新型甲型H1N1流感病毒、季节性甲型和乙型流感病毒,分析部分新型甲型H1N1流行株血凝素（hemagglutinin,HA）基因抗原位点变异及神经氨酸酶（neuraminidase,NA）基因耐药位点突变情况.结果 共入选3475例患儿,新型甲型H1N1阳性222例（6.4％）.2009年8月至2010年2月第1次流行波和2010年12月至2011年2月第2次流行波确诊病例年龄中位数分别为53.5个月和32.0个月（Z=-4.601,P=0.000）.119例（53.6％）患儿有明确暴露史,其中68例（57.1％）暴露对象为家庭成员,47例（39.5％）暴露对象为幼儿园或学校同学.新型甲型H1N1病毒HA序列分析显示上海地区流行株与疫苗株高度同源.未检测到NA基因片段具有H275Y和N295S特征突变的奥司他韦耐药株.结论 上海地区儿童在2009至201 1年经历了2次新型甲型H1N1流感的暴发流行.家庭内和学校传播是大流行株在社区儿童传播的主要模式.疫苗可提供有效的保护作用.未检测到奥司他韦耐药株.

Objective To investigate the epidemiological features,genetic drift in the epitopes of hemagglutinin （HA） of the novel influenza A （H1N1） virus and oseltamivir-resistant variants characterized by H275Y and N295S mutations in children in Shanghai since the outbreak.Method Between June 2009and May 2012,a prospective surveillance study was carried out in Shanghainese children who attended the outpatient clinic of Children＇s Hospital of Fudan University for influenza-like illness.One-step real-time fluorescence quantitative RT-PCR was performed to detect seasonal influenza A and influenza B virus and the novel influenza A （H1N1） virus in the respiratory samples.Genetic drift from the vaccine strain in HA epitopes of the novel influenza H1 N1 virus and the molecular markers associated with oseltamivir resistance in neuraminidase （NA） were analyzed.Result Out of 3475 enrolled cases,the novel influenza A （H1N1）virus was confirmed virologically in 222 （6.4%） otherwise healthy children with 133 （59.9%） being boys and 89（40.1%） girls.The median ages of children with the novel influenza A （H1N1） virus infection during the first wave from August 2009 to February 2010 and the second wave from December 2010 to February 2011 were 53.5 months and 32.0 months,respectively （Z =-4.601,P =0.000） ; 119（46.9%） had the close contact with persons suffering from fever or respiratory infection,of whom,68 （57.1%） contacts were family members and 47 （39.5%） contacts were classmates.During the outbreak in 2009-2010 season,66 （40.9%） were exposed to primary index cases,school students were the major exposure subjects,accounting for 50.0%.The nucleotide sequences of HAI gene were highly homologous between the vaccine strain A/California/07/2009 and Shanghai circulating novel influenza A （H1N1）strains and only S83P mutation in epitope E of HA was detected inclusively in the circulating strains.The H275Y and N295S amino acid mutations associated with oseltamivir resistance were not found in the circulating novel influenza （H1N1） strains.Conclusion Two major waves of the novel influenza A （H1N1） outbreaks occurred in Shanghainese children during 2009-2011.Institutional children were the major affected individuals during the 2009 pandemic wave.Households and schools were the main sites of transmission among children during influenza pandemic.Influenza vaccination should be enhanced in children and their close family contacts.The novel influenza A （H1N1） virus in Shanghai has not undergone significant genetic changes.Oseltamivir is effective for the treatment of the novel influenza A （H1N1） virus.