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      Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza

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          Abstract

          BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza

          MethodsThis was a 1-year prospective, observational study involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models

          ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log 10 copies/mL; P=.005; β, +0.86 [95% confidence interval, +0.03 to +1.68]). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β [standard error], −1.19 [0.43] and −0.68 [0.33] log 10 copies/mL for patients treated on day 1 and days 2–3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 [95% confidence interval, 0.03–0.35] and 0.30 [0.10–0.90] for patients treated on day 1–2 and day 3–4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001)

          ConclusionPatients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance

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          Most cited references35

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          Neuraminidase inhibitors for influenza.

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            Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group.

            Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. Randomized, placebo-controlled, double-blind study conducted January through March 1998. Sixty primary care and university health centers throughout the United States. A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). Duration and severity of illness in individuals infected with influenza. Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.
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              Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada.

              We conducted a prospective cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario, Canada. Patients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study. Demographic and medical data were collected by patient and physician interview and chart review. The main outcome evaluated was death within 15 days after symptom onset. Data were available for 512 of 541 eligible patients. There were 185 children (<15 years of age), none of whom died and none of whom were treated with antiviral drugs. The median age of the 327 adults was 77 years (range, 15-98 years), 166 (51%) were male, 245 (75%) had a chronic underlying illness, and 216 (71%) had been vaccinated against influenza. Of the 327 adult patients, 184 (59%) presented to the emergency department within 48 h after symptom onset, 52 (16%) required intensive care unit admission, and 27 (8.3%) died within 15 days after symptom onset. Most patients (292 patients; 89%) received antibacterial therapy; 106 (32%) were prescribed antiviral drugs. Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality (odds ratio, 0.21; 95% confidence interval, 0.06-0.80; n=100, 260). There was no apparent impact of antiviral therapy on length of stay in survivors. There is a significant burden of illness attributable to influenza in this highly vaccinated population. Treatment with antiviral drugs was associated with a significant reduction in mortality.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jinfdis
                jid
                The Journal of Infectious Diseases
                The University of Chicago Press
                0022-1899
                1537-6613
                1 August 2009
                1 August 2009
                1 August 2009
                : 200
                : 4
                : 492-500
                Affiliations
                Departments of
                [1 ]Medicine and Therapeutics and
                [2 ]Microbiology,
                [3 ]Stanley Ho Centre for Emerging Infectious Diseases,
                [4 ]Trauma and Emergency Centre,
                [5 ]Centre for Epidemiology and Biostatistics, The Chinese University of Hong Kong, Hong Kong
                Author notes
                Reprints or correspondence: Prof. Paul K. S. Chan, Dept. of Microbiology, The Chinese University of Hong Kong, 1/F Clinical Science Bldg., Prince of Wales Hospital, Shatin, New Territories, Hong Kong ( paulkschan@ 123456cuhk.edu.hk )
                Article
                10.1086/600383
                7110250
                19591575
                98a9688a-790e-4576-ac57-fe6fa38be1c2
                © 2009 by the Infectious Diseases Society of America

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 3 December 2008
                : 9 March 2009
                Categories
                Major Articles and Brief Reports
                Viruses
                Major Articles

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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