Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome.
Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome.
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DOI：
10.1016/s0140-6736(13)60903-4
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发表时间：
2013-06-01
期刊：
影响因子：
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通讯作者：
Yuen KY
中科院分区：
文献类型：
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作者：
Chen Y;Liang W;Yang S;Wu N;Gao H;Sheng J;Yao H;Wo J;Fang Q;Cui D;Li Y;Yao X;Zhang Y;Wu H;Zheng S;Diao H;Xia S;Zhang Y;Chan KH;Tsoi HW;Teng JL;Song W;Wang P;Lau SY;Zheng M;Chan JF;To KK;Chen H;Li L;Yuen KY
人感染甲型H7N9禽流感病毒于2013年2月在中国东部出现，并与接触家禽有关。我们报道了感染甲型H7N9流感病毒的患者的临床和微生物学特征，并将人病毒的基因组特征与浙江市场禽类中的病毒进行了比较，中国。在2013年3月7日至4月8日期间，我们纳入了住院患者，如果他们有新出现的呼吸道症状、不明原因的放射学浸润物以及实验室确认的H7N9病毒感染。我们记录了血液学、生化、放射学和微生物学调查的历史和结果。我们采集咽喉和痰标本，用RT-PCR检测M、H7和N9基因，并在Madin-Darby犬肾细胞培养样本。我们测试了合并感染情况，并监测了六种细胞因子和趋化因子的血清浓度。我们从有流行病学关联的湿货市场采集了86只鸡的泄殖腔拭子，并用这些样本接种了鸡胚。通过RT-PCR测序对分离株进行鉴定和分型。对1个人和1个鸡分离株进行了RNA提取、互补DNA合成和聚合酶链式反应测序。我们对患者和鸡分离株中病毒的8个基因片段进行了表征和系统发育分析，并构建了H、N、PB2和NS基因的系统发育树。我们确认了4名患者(平均年龄56岁)，他们都在发病前3-8天接触过家禽。他们出现发烧和迅速发展的肺炎，对抗生素没有反应。患者白细胞和淋巴细胞减少，肝或肾功能受损，血清细胞因子或趋化因子浓度显著升高，随着疾病的进展弥漫性血管内凝血。两名患者死亡。与咽拭子样本相比，痰样本更有可能检测出H7N9病毒阳性。患者身上的病毒分离株与一只与流行病学有关的市场鸡的病毒分离株非常相似。所有的病毒基因片段都来自禽类。分离出的病毒H7与浙江家鸭H7N3病毒最接近，而N9病毒与韩国野禽H7N9病毒最接近。我们注意到人类病毒H7中的Gln226Leu和Gly186Val替换(与α-2，6-连接的唾液酸受体的亲和力增加有关)和PB2 Asp701Asn突变(与哺乳动物适应相关)。在M2病毒中发现Ser31Asn突变，该突变与金刚烷胺耐药有关。这种新的重组H7N9病毒的跨物种家禽传人与人类的严重肺炎和多器官功能障碍有关。对病毒演变的监测和对疾病发病机制的进一步研究将改善疾病管理、流行病控制和大流行准备。容志坚，中国传染病国家重点项目。
Human infection with avian influenza A H7N9 virus emerged in eastern China in February, 2013, and has been associated with exposure to poultry. We report the clinical and microbiological features of patients infected with influenza A H7N9 virus and compare genomic features of the human virus with those of the virus in market poultry in Zhejiang, China. Between March 7 and April 8, 2013, we included hospital inpatients if they had new-onset respiratory symptoms, unexplained radiographic infiltrate, and laboratory-confirmed H7N9 virus infection. We recorded histories and results of haematological, biochemical, radiological, and microbiological investigations. We took throat and sputum samples, used RT-PCR to detect M, H7, and N9 genes, and cultured samples in Madin-Darby canine kidney cells. We tested for co-infections and monitored serum concentrations of six cytokines and chemokines. We collected cloacal swabs from 86 birds from epidemiologically linked wet markets and inoculated embryonated chicken eggs with the samples. We identified and subtyped isolates by RT-PCR sequencing. RNA extraction, complementary DNA synthesis, and PCR sequencing were done for one human and one chicken isolate. We characterised and phylogenetically analysed the eight gene segments of the viruses in the patient's and the chicken's isolates, and constructed phylogenetic trees of H, N, PB2, and NS genes. We identified four patients (mean age 56 years), all of whom had contact with poultry 3–8 days before disease onset. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Patients were leucopenic and lymphopenic, and had impaired liver or renal function, substantially increased serum cytokine or chemokine concentrations, and disseminated intravascular coagulation with disease progression. Two patients died. Sputum specimens were more likely to test positive for the H7N9 virus than were samples from throat swabs. The viral isolate from the patient was closely similar to that from an epidemiologically linked market chicken. All viral gene segments were of avian origin. The H7 of the isolated viruses was closest to that of the H7N3 virus from domestic ducks in Zhejiang, whereas the N9 was closest to that of the wild bird H7N9 virus in South Korea. We noted Gln226Leu and Gly186Val substitutions in human virus H7 (associated with increased affinity for α-2,6-linked sialic acid receptors) and the PB2 Asp701Asn mutation (associated with mammalian adaptation). Ser31Asn mutation, which is associated with adamantane resistance, was noted in viral M2. Cross species poultry-to-person transmission of this new reassortant H7N9 virus is associated with severe pneumonia and multiorgan dysfunction in human beings. Monitoring of the viral evolution and further study of disease pathogenesis will improve disease management, epidemic control, and pandemic preparedness. Larry Chi-Kin Yung, National Key Program for Infectious Diseases of China.