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- 李侗曾副主任医师
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医院:
首都医科大学附属北京佑安医院
科室:
综合感染科
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- 李兰娟:《柳叶刀》人感染禽源性甲型流感H7N9病毒临床分析和病毒学特征
- 作者:李侗曾|发布时间:2013-05-01|浏览量:532次
Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome
Background
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.
《人类感染活禽市场来源的新发H7N9亚型禽流感病毒:临床分析和病毒基因组特征》
背景:2013年2月在中国东部发现人类感染禽流感H7N9病毒,可能与这些人家禽接触史相关。我们报告在浙江感染甲型H7N9流感病毒的患者的临床特点和微生物特征,并且比较了人类病毒和中国市场家禽的病毒的基因组特征的患者。
结果:
我们分析了4名感染者,平均年龄58岁,在发病前3到8天曾经有禽类接触史,临床表现首先是发热,并迅速进展为肺炎,抗生素治疗无效。患者白细胞及淋巴细胞减少,伴有肝肾功能损害,血清细胞因子或趋化因子浓度明显升高,并随着疾病进展出现弥散性血管内凝血。两名患者死亡。痰标本更容易比咽拭子样本H7N9病毒测试呈阳性。从患者标本中分离的病毒和其接触的活禽市场的鸡体内分离的病毒相似,所有的病毒基因片段是禽流感的起源。与病毒H7部分最接近的H7N3病毒是来自浙江的鸭子,而N9是最接近韩国的野鸟的H7N9病毒。我们注意到人类病毒H7的Gln226Leu 和 Gly186Val突变导致病毒与α-2,6-链接的唾液酸受体的亲和力增加,PB2的 Asp701Asn突变与哺乳动物适应型增加有关,Gly186Val替换。病毒M2片段的Ser31Asn突变与金刚烷胺耐药相关。
Methods
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.
Findings
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.
Interpretation
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.
Funding
Larry Chi-Kin Yung, National Key Program for Infectious Diseases of China.
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