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      Comparison of Patients Hospitalized With Influenza A Subtypes H7N9, H5N1, and 2009 Pandemic H1N1

      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 11 , 12 , 9 , 10 , 5 , 13 , 10 , 11 , 12 , 5 , 9 , 10 , 11 , 12 , 5 , 14 , 15 , 6 , 16 , 5 , 5 , 10 , 5 , 10 , 6 , 7 , 8 , 17 , 10 , 18 , 11 , 12
      Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
      Oxford University Press
      influenza A(H7N9), influenza A(H5N1), clinical epidemiology

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          Hospitalization with H7N9 virus infection is associated with older age and chronic heart disease, and patients have a longer duration of hospitalization than patients with H5N1 or pH1N1. This suggests that host factors are an important contributor to H7N9 severity.


          Background.  Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections.

          Methods.  We compared individual-level data from patients hospitalized with infection by H7N9 (n = 123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses. We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population.

          Results.  The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P < .001) and a higher proportion was male (71%; P < .02). After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 9.68; 95% confidence interval, 5.24–17.9). H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients ( P < .005). H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients ( P < .001), and the median time from onset to death was 18 days for H7N9 ( P = .002) vs 11 days for H5N1 and 15 days for pH1N1 ( P = .154).

          Conclusions.  The identification of known risk factors for severe seasonal influenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity.

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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 features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus.

            Human infection with an avian influenza A virus (subtype H5N1) was reported recently in Hong Kong. We describe the clinical presentation of the first 12 patients and options for rapid viral diagnosis. Case notes of 12 patients with virus-culture-confirmed influenza A H5N1 infection were analysed. The clinical presentation and risk factors associated with severe disease were defined and the results of methods for rapid virus diagnosis were compared. Patients ranged from 1 to 60 years of age. Clinical presentation was that of an influenza-like illness with evidence of pneumonia in seven patients. All seven patients older than 13 years had severe disease (four deaths), whereas children 5 years or younger had mild symptoms with the exception of one who died with Reye's syndrome associated with intake of aspirin. Gastrointestinal manifestations, raised liver enzymes, renal failure unrelated to rhabdomyolysis, and pancytopenia were unusually prominent. Factors associated with severe disease included older age, delay in hospitalisation, lower-respiratory-tract involvement, and a low total peripheral white blood cell count or lymphopenia at admission. An H5-specific reverse-transcription PCR assay (RT-PCR) was useful for rapid detection of virus directly in respiratory specimens. A commercially available enzyme immunoassay was more sensitive than direct immunofluorescence for rapid viral diagnosis. Direct immunofluorescence with an H5-specific monoclonal antibody pool was useful for rapid exclusion of H5-subtype infection. Avian Influenza A H5N1 virus causes human influenza-like illness with a high rate of complications in adults admitted to hospital. Rapid H5-subtype-specific laboratory diagnosis can be made by RT-PCR applied directly to clinical specimens.
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              Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection

              Abstract Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.

                Author and article information

                Clin Infect Dis
                Clin. Infect. Dis
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                15 April 2014
                31 January 2014
                31 January 2014
                : 58
                : 8
                : 1095-1103
                [1 ]Institute of Respiratory Medicine , Beijing Hospital, National Health and Family Planning Commission
                [2 ]Department of Respiratory Medicine, Capital Medical University
                [3 ]Beijing Institute of Respiratory Medicine
                [4 ]Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders
                [5 ]Division of Infectious Disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention , Beijing, China
                [6 ]Oxford University Clinical Research Unit–Wellcome Trust Major Overseas Programme , Hanoi, Vietnam
                [7 ]Centre for Tropical Medicine , Nuffield Department of Clinical Medicine, Oxford University , Oxford, United Kingdom
                [8 ]Singapore Infectious Disease Initiative
                [9 ]Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University , Beijing
                [10 ]Division of Epidemiology and Biostatistics, School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region
                [11 ]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Hangzhou
                [12 ]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, the First Affiliated Hospital , College of Medicine, Zhejiang University , Hangzhou
                [13 ]Department of Respiratory and Critical Care Medicine, Peking University People's Hospital , Beijing, China
                [14 ]National Hospital for Tropical Diseases
                [15 ]National Hospital for Pediatrics , Hanoi
                [16 ]Hospital for Tropical Diseases , Ho Chi Minh City, Vietnam
                [17 ]ISARIC, Centre for Tropical Medicine, University of Oxford, Churchill Hospital , Oxford, United Kingdom
                [18 ]Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia
                Author notes

                These authors contributed equally to this work.

                Correspondence: Luanjuan Li, MD, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China ( ljli@ 123456zju.edu.cn ).
                © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 26 September 2013
                : 27 November 2013
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                Infectious disease & Microbiology
                influenza a(h7n9),influenza a(h5n1),clinical epidemiology


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