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      Clinical characteristics and severity of influenza infections by virus type, subtype, and lineage: A systematic literature review

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          Abstract

          Aim

          Studies carried out in the early 2000s found that the number of influenza‐associated hospitalizations and deaths was highest in seasons dominated by A(H3N2), suggesting that the clinical presentation and severity of influenza may differ across virus types, subtypes, and lineages. We aimed to review the studies that examined this hypothesis.

          Method

          We conducted a literature review of studies published until January 2017 that compared the clinical presentation, disease severity, and case‐fatality ratio of influenza patients infected with different virus types (A, B), subtypes (pre‐pandemic A(H1N1), A(H1N1)p, A(H3N2)), and lineages (Victoria, Yamagata).

          Results

          The literature search resulted in over 1700 entries: After applying in‐ and exclusion criteria, 47 studies were included in the literature review. Studies showed a wide diversity in setting and populations. Only a minority of studies provided results adjusted by patient's age and other potential confounders. There were very few differences in the clinical presentation of patients infected with different influenza viruses. We found weak evidence that the A(H1N1)p subtype in the post‐pandemic period was more often associated with secondary bacterial pneumonia, ICU admission, and death, than the other influenza virus (sub)types.

          Conclusion

          Contrary to what is commonly assumed, the causal virus subtype does not seem to be a major determinant of clinical presentation and severity of influenza illness. However, drawing conclusions was made difficult by the low comparability and methodological shortcomings of included studies, and more well‐designed studies are warranted.

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          Most cited references50

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          Incidence and characteristics of viral community-acquired pneumonia in adults.

          In adults, viral causes of community-acquired pneumonia (CAP) are poorly characterised. The aims of this study were to characterise the viral aetiology of CAP in adults by using an extensive array of viral diagnostic tests and to compare the characteristics of viral pneumonia with those of pneumococcal pneumonia. Adults admitted to Christchurch Hospital over a 1-year period with CAP were included in the study. Microbiological testing methods included blood and sputum cultures, urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila, antibody detection in paired sera and detection of respiratory viruses in nasopharyngeal swabs by immunofluorescence, culture and PCR. Of 304 patients with CAP, a viral diagnosis was made in 88 (29%), with rhinoviruses and influenza A being the most common. Two or more pathogens were detected in 49 (16%) patients, 45 of whom had mixed viral and bacterial infections. There were no reliable clinical predictors of viral pneumonia, although several variables were independently associated with some aetiologies. The presence of myalgia was associated with pneumonia caused by any respiratory virus (OR 3.62, 95% CI 1.29 to 10.12) and influenza pneumonia (OR 190.72, 95% CI 3.68 to 9891.91). Mixed rhinovirus/pneumococcal infection was associated with severe disease. Virus-associated CAP is common in adults. Polymicrobial infections involving bacterial and viral pathogens are frequent and may be associated with severe pneumonia.
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            Estimates of US influenza‐associated deaths made using four different methods

            Abstract Background  A wide range of methods have been used for estimating influenza‐associated deaths in temperate countries. Direct comparisons of estimates produced by using different models with US mortality data have not been published. Objective  Compare estimates of US influenza‐associated deaths made by using four models and summarize strengths and weaknesses of each model. Methods  US mortality data from the 1972–1973 through 2002–2003 respiratory seasons and World Health Organization influenza surveillance data were used to estimate influenza‐associated respiratory and circulatory deaths. Four models were used: (i) rate‐difference (using peri‐season or summer‐season baselines), (ii) Serfling least squares cyclical regression, (iii) Serfling–Poisson regression, (iv) and autoregressive integrated moving average models. Results  Annual estimates of influenza‐associated deaths made using each model were similar and positively correlated, except for estimates from the summer‐season rate‐difference model, which were consistently higher. From the 1976/1977 through the 2002/2003 seasons the, the Poisson regression models estimated that an annual average of 25 470 [95% confidence interval (CI) 19 781–31 159] influenza‐associated respiratory and circulatory deaths [9·9 deaths per 100 000 (95% CI 7·9–11·9)], while peri‐season rate‐difference models using a 15% threshold estimated an annual average of 22 454 (95% CI 16 189–28 719) deaths [8·6 deaths per 100 000 (95% CI 6·4–10·9)]. Conclusions  Estimates of influenza‐associated mortality were of similar magnitude. Poisson regression models permit the estimation of deaths associated with influenza A and B, but require robust viral surveillance data. By contrast, simple peri‐season rate‐difference models may prove useful for estimating mortality in countries with sparse viral surveillance data or complex influenza seasonality.
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              Patients hospitalized with laboratory-confirmed influenza during the 2010-2011 influenza season: exploring disease severity by virus type and subtype.

               The 2010-2011 influenza season was dominated by influenza A(H3N2) virus, but influenza A(H1N1) pdm09 (pH1N1) and B viruses cocirculated. This provided an opportunity to explore within-season predictors of severity among hospitalized patients, avoiding biases associated with season-to-season differences in strain virulence, population immunity, and healthcare seeking.
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                Author and article information

                Contributors
                j.paget@nivel.nl
                Journal
                Influenza Other Respir Viruses
                Influenza Other Respir Viruses
                10.1111/(ISSN)1750-2659
                IRV
                Influenza and Other Respiratory Viruses
                John Wiley and Sons Inc. (Hoboken )
                1750-2640
                1750-2659
                20 July 2018
                November 2018
                : 12
                : 6 ( doiID: 10.1111/irv.2018.12.issue-6 )
                : 780-792
                Affiliations
                [ 1 ] Netherlands Institute for Health Services Research (NIVEL) Utrecht The Netherlands
                [ 2 ] Global Health Economics and Outcomes Research Sanofi Pasteur Lyon France
                Author notes
                [*] [* ] Correspondence

                John Paget, Netherlands Institute for Health Services Research (NIVEL), Utrecht, The Netherlands.

                Email: j.paget@ 123456nivel.nl

                Author information
                http://orcid.org/0000-0002-2262-1102
                http://orcid.org/0000-0002-1503-2481
                Article
                IRV12575
                10.1111/irv.12575
                6185883
                29858537
                61f27683-d7bd-49b2-b27c-70f688cb3f96
                © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 May 2018
                Page count
                Figures: 1, Tables: 4, Pages: 13, Words: 9617
                Funding
                Funded by: Sanofi Pasteur
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                irv12575
                November 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0.1 mode:remove_FC converted:12.10.2018

                Infectious disease & Microbiology
                clinical presentation,influenza,literature review,severity,virus type

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