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      Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

      research-article
      , M.D., , M.D., , Ph.D., , M.D., , M.D., , M.D., , M.D., , M.P.H., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , Ph.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., M.P.H., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , M.D., , Ph.D., , M.D., , M.D., , M.D., , M.D., M.P.H., M.P.P., , M.D., M.P.H.
      The New England journal of medicine

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          Abstract

          BACKGROUND

          The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013.

          METHODS

          Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase–polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR.

          RESULTS

          Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus.

          CONCLUSIONS

          Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

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          Most cited references40

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          Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

          New England Journal of Medicine, 368(20), 1888-1897
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            Clinical findings in 111 cases of influenza A (H7N9) virus infection.

            During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).
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              Probable person-to-person transmission of avian influenza A (H5N1).

              During 2004, a highly pathogenic avian influenza A (H5N1) virus caused poultry disease in eight Asian countries and infected at least 44 persons, killing 32; most of these persons had had close contact with poultry. No evidence of efficient person-to-person transmission has yet been reported. We investigated possible person-to-person transmission in a family cluster of the disease in Thailand. For each of the three involved patients, we reviewed the circumstances and timing of exposures to poultry and to other ill persons. Field teams isolated and treated the surviving patient, instituted active surveillance for disease and prophylaxis among exposed contacts, and culled the remaining poultry surrounding the affected village. Specimens from family members were tested by viral culture, microneutralization serologic analysis, immunohistochemical assay, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis, and genetic sequencing. The index patient became ill three to four days after her last exposure to dying household chickens. Her mother came from a distant city to care for her in the hospital, had no recognized exposure to poultry, and died from pneumonia after providing 16 to 18 hours of unprotected nursing care. The aunt also provided unprotected nursing care; she had fever five days after the mother first had fever, followed by pneumonia seven days later. Autopsy tissue from the mother and nasopharyngeal and throat swabs from the aunt were positive for influenza A (H5N1) by RT-PCR. No additional chains of transmission were identified, and sequencing of the viral genes identified no change in the receptor-binding site of hemagglutinin or other key features of the virus. The sequences of all eight viral gene segments clustered closely with other H5N1 sequences from recent avian isolates in Thailand. Disease in the mother and aunt probably resulted from person-to-person transmission of this lethal avian influenzavirus during unprotected exposure to the critically ill index patient. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Journal
                0255562
                5985
                N Engl J Med
                N. Engl. J. Med.
                The New England journal of medicine
                0028-4793
                1533-4406
                18 July 2019
                24 April 2013
                06 February 2014
                24 July 2019
                : 370
                : 6
                : 520-532
                Affiliations
                The Public Health Emergency Center (Q.L., L.Z., N.X., L.M., Z.H., W.T., Y.C., L.L., F.D., B.L., M.W., Y.G., L.J., Y.Z., Z.F.) and National Institute for Viral Disease Control and Prevention (D.W., R.G., X.L., T.B., S.Z., S.W., Y.S.), Chinese Center for Disease Control and Prevention (H.L., H.Y., W.Y., Y.W.), Chinese Field Epidemiology Training Program (R.X.), and Beijing Municipal Center for Disease Control and Prevention (X.P.), Beijing, Jiangsu Provincial Center for Disease Control and Prevention (M.Z., F.T.) and Nanjing Prefecture Center for Disease Control and Prevention (Y.X.), Nanjing, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou (Z.C., E.C., C.C.), Anhui Provincial Center for Disease Control and Prevention, Hefei (F.L., Jun He), Shanghai Municipal Center for Disease Control and Prevention, Shanghai (H.W., J. Hu, F.W.), Guangdong Provincial Center for Disease Control and Prevention, Guangzhou (Jianfeng He), Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang (Q.L.), Shandong Provincial Center for Disease Control and Prevention, Jinan (X.W.), Hunan Provincial Center for Disease Control and Prevention, Changsha (L.G.), Henan Provincial Center for Disease Control and Prevention, Zhengzhou (G.L.), Fujian Provincial Center for Disease Control and Prevention, Fuzhou (Y.Y.), and Jiangxi Provincial Center for Disease Control and Prevention, Nanchang (H.Y.) — all in China; and Influenza Division, Centers for Disease Control and Prevention, Atlanta (T.M.U.).
                Author notes
                Address reprint requests to Dr. Feng at the Public Health Emergency Center, Chinese Center for Disease Control and Prevention, Beijing, 102206, China, or at fengzj@ 123456chinacdc.cn ; or to Dr. Fan Wu at Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhongshan W. Rd., Shanghai, 200336, China, or at fwu@ 123456scdc.sh.cn .
                Article
                PMC6652192 PMC6652192 6652192 hhspa1040841
                10.1056/NEJMoa1304617
                6652192
                23614499
                bec1426e-a7a7-4666-b811-713c252f1069
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