Background. We investigated the effect of influenza vaccination on disease severity in adults hospitalized with laboratory-confirmed influenza during 2013–14, a season in which vaccine viruses were ...antigenically similar to those circulating. Methods. We analyzed data from the 2013–14 influenza season and used propensity score matching to account for the probability of vaccination within age strata (18–49, 50–64, and ≥65 years). Death, intensive care unit (ICU) admission, and hospital and ICU lengths of stay (LOS) were outcome measures for severity. Multivariable logistic regression and competing risk models were used to compare disease severity between vaccinated and unvaccinated patients, adjusting for timing of antiviral treatment and time from illness onset to hospitalization. Results. Influenza vaccination was associated with a reduction in the odds of in-hospital death among patients aged 18–49 years (adjusted odds ratios aOR = 0.21; 95% confidence interval CI, 0.05 to 0.97), 50–64 years (aOR = 0.48; 95% CI, 0.24 to 0.97), and ≥65 years (aOR = 0.39; 95% CI, 0.17 to 0.66). Vaccination also reduced ICU admission among patients aged 18–49 years (aOR = 0.63; 95% CI, 0.42 to 0.93) and ≥65 years (aOR = 0.63; 95% CI, 0.48 to 0.81), and shortened ICU LOS among those 50–64 years (adjusted relative hazards aRH = 1.36; 95% CI, 1.06 to 1.74) and ≥65 years (aRH = 1.34; 95% CI, 1.06 to 1.73), and hospital LOS among 50–64 years (aRH = 1.13; 95% CI, 1.02 to 1.26) and ≥65 years (aRH = 1.24; 95% CI, 1.13 to 1.37). Conclusions. Influenza vaccination during 2013–14 influenza season attenuated adverse outcome among adults that were hospitalized with laboratory-confirmed influenza.
2009 pandemic influenza A/H1N1 (A(H1N1)pdm09) was first detected in the United States in April 2009 and resulted in a global pandemic. We conducted a serologic survey to estimate the cumulative ...incidence of A(H1N1)pdm09 through the end of 2009 when pandemic activity had waned in the United States.
We conducted a pair of cross sectional serologic surveys before and after the spring/fall waves of the pandemic for evidence of seropositivity (titer ≥40) using the hemagglutination inhibition (HI) assay. We tested a baseline sample of 1,142 serum specimens from the 2007-2008 National Health and Nutrition Examination Survey (NHANES), and 2,759 serum specimens submitted for routine screening to clinical diagnostic laboratories from ten representative sites.
The age-adjusted prevalence of seropositivity to A(H1N1)pdm09 by year-end 2009 was 36.9% (95%CI: 31.7-42.2%). After adjusting for baseline cross-reactive antibody, pandemic vaccination coverage and the sensitivity/specificity of the HI assay, we estimate that 20.2% (95%CI: 10.1-28.3%) of the population was infected with A(H1N1)pdm09 by December 2009, including 53.3% (95%CI: 39.0-67.1%) of children aged 5-17 years.
By December 2009, approximately one-fifth of the US population, or 61.9 million persons, may have been infected with A(H1N1)pdm09, including around half of school-aged children.
Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are ...conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury.
We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010-2013 seasons.
We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2-8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation <93% (47.6%) and respiratory rate >24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or <36.0°C (7.1% vs 27.1%), respiratory rate >24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation <90% (14.3% vs 31.4%), white blood cell count >15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%).
We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.
Summary Background Influenza causes substantial morbidity and mortality worldwide. Few data exist for the efficacy of neuraminidase inhibitors, which are the only readily available influenza ...treatment options, especially in low-income settings. We assessed the efficacy of treatment with the neuraminidase inhibitor oseltamivir to reduce patient illness and viral shedding in people with influenza, in whom treatment was started within 5 days of symptom onset, in an urban setting in Bangladesh. Methods We undertook a double-blind, randomised, controlled trial between May, 2008, and December, 2010. Patients with a positive rapid influenza test identified by surveillance of households in Kamalapur, Bangladesh were randomly allocated on a 1:1 basis to receive oseltamivir or placebo twice daily for 5 days. Randomisation lists for individuals enrolled less than 48 h and 48 h or longer since illness onset were generated with permuted blocks of variable length between two and eight. Participants and study staff were masked to treatment group. Participants provided nasal wash specimens at enrolment and 2, 4, and 7 days later, and were visited daily to record symptoms. All specimens were tested for influenza with reverse-transcriptase PCR, and if the result was positive, we isolated the virus. The primary endpoints were duration of clinical illness and viral shedding in patients treated less than and more than 48 h since illness onset and the frequency of oseltamivir resistance during treatment. Analyses were intention to treat unless otherwise specified. This trial is registered with ClinicalTrials.gov , number NCT00707941. Findings Overall, 1190 people with a median age of 5 years (IQR 2–9) were enrolled: 794 (67%) less than 48 h since symptom onset and 396 (33%) 48 h or longer since symptom onset. 592 participants were assigned to placebo and 598 to oseltamivir. The median duration of symptoms was shorter in the oseltamivir group (3 days, IQR 1–5) than in the placebo group (4 days, 1–6; p=0·01). When stratified by timing of treatment initiation, in participants enrolled 48 h or longer since illness onset, the median duration of symptoms was similar in both groups (oseltamivir 3 days IQR 2–5, placebo 3 days 1–5; p=0·04). The median duration of symptoms was reduced by 1 day in the group given oseltamivir who were enrolled less than 48 h since symptom onset compared with those given placebo, but this difference was not significant. In those with all swab specimens (n=1134), oseltamivir significantly reduced virus isolation on days 2 (placebo 374 66% vs oseltamivir 321 56%; difference 15·2%, 95% CI 9·5–20·8, p=0·0004), 4 (241 43% vs 174 30%; difference 30·2%, 95% CI 24·6–35·8, p<0·0001), and 7 (68 12% vs 36 6%; difference 47·5%, 95% CI 44·2–50·8, p=0·0009). In participants enrolled 48 h or longer since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2 and 4, but not day 7. In participants enrolled less than 48 h since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2, 4, and 7. The emergency of resistance to oseltamivir during treatment was rare overall (<1%) and in influenza A H1N1pdm09 viruses (3·9%). Interpretation Oseltamivir treatment resulted in a modest reduction in the duration of symptoms and virus shedding in people with uncomplicated influenza infections, even when treatment was started 48 h or longer after illness onset. Funding Centers for Disease Control and Prevention (in agreement with the International Centre for Diarrhoeal Disease Research, Bangladesh).
The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some ...viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.
Background. Few data exist describing healthcare-seeking behaviors among persons with influenza-like illness (ILI) or adherence to influenza antiviral treatment recommendations. Methods. We analyzed ...adult responses to the Behavioral Risk Factor Surveillance System in 31 states and the District of Columbia (DC) and pediatric responses in 25 states and DC for January-April 2011 by demographics and underlying health conditions. Results. Among 75 088 adult and 15 649 child respondents, 8.9% and 33.9%, respectively, reported ILI. ILI was more frequent among adults with asthma (16%), chronic obstruction pulmonary disease (COPD; 26%), diabetes (12%), heart disease (19%), kidney disease (16%), or obesity (11%). Forty-five percent of adults and 57% of children sought healthcare for ILL Thirty-five percent of adults sought care ≤2 days after ILI onset. Seeking care ≤2 days was more frequent among adults with COPD (48%) or heart disease (55%). Among adults with a self-reported physician diagnosis of influenza, 34% received treatment with antiviral medications. The only underlying health condition with a higher rate of treatment was diabetes (46%). Conclusions. Adults with underlying health conditions were more likely to report ILI, but the majority did not seek care promptly, missing opportunities for early influenza antiviral treatment.
The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2–4 June, 2015. With emerging resistance to ...the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focused on the discovery and development of inhibitors of several virus targets and key host cell factors involved in virus replication or mediating the inflammatory response. Virus targets included the influenza haemagglutinin, neuraminidase and M2 proteins, and both the respiratory syncytial virus and influenza polymerases and nucleoproteins. Therapies for rhinoviruses and MERS and SARS coronaviruses were also discussed. With the emerging development of monoclonal antibodies as therapeutics, the potential implications of antibody-dependent enhancement of disease were also addressed. Topics covered all aspects from structural and molecular biology to preclinical and clinical studies. The importance of suitable clinical trial endpoints and regulatory issues were also discussed from the perspectives of both industry and government. This meeting summary provides an overview, not only for the conference participants, but also for those interested in the current status of antivirals for respiratory viruses.
•The International Society for Influenza and other Respiratory Viruses held an Antiviral Group conference in June, 2015.•This report covers oral presentations, including therapies against influenza and respiratory syncytial virus infections.•Therapies for rhinovirus, MERS and SARS coronavirus infections were also topics at the conference.•Some speakers focused on monoclonal antibodies as therapeutics and antibody-dependent enhancement of disease.•The importance of suitable clinical trial endpoints and regulatory issues were also discussed.
In this randomized trial, oseltamivir, when initiated an average of 5 days post symptom onset, did not reduce clinical failure in hospitalized patients with influenza-associated lower respiratory ...tract infection (I-LRTI). Oseltamivir may not reduce failure in hospitalized patients with I-LRTI.
Abstract
Background
Influenza-associated hospitalizations result in high morbidity and mortality. We sought to determine if early empiric anti-influenza therapy improves outcomes of hospitalized patients with influenza-associated lower respiratory tract infections (I-LRTIs).
Methods
This was a randomized, unblinded, trial of adult patients hospitalized with I-LRTIs in Kentucky during 2009-2012. Patients were randomized to group A (standard of care) or group B (standard of care plus oseltamivir as early as possible but within 24 hours of enrollment). The primary outcome was development of clinical failure (composite variable including failure to reach clinical improvement within 7 days, transfer to intensive care 24 hours after admission, or rehospitalization or death within 30 days). Intent-to-treat (ITT) (all LRTI) and per-protocol (PP) (I-LRTI) analyses were done.
Results
A total of 1107 patients were enrolled and included in the ITT analysis, 556 in group A and 551 in group B. The median time from symptom onset to hospital admission was 5 days (interquartile range, 5) for both groups; oseltamivir was initiated median day 6 in group B. There was no difference in the development of clinical failure (group A, 25%, and group B, 24%; P = .561). In the PP analysis, 11 of 45 (24%) patients in group A and 4 of 29 (14%) patients in group B had clinical failure (P = .414).
Conclusions
Initiation of oseltamivir more than 5 days after illness onset did not reduce clinical failures among hospitalized patients with I- LRTIs. However, we did not enroll our projected sample size of I-LRTI.
Clinical Trials Registration
NCT01248715.
The detection of influenza virus in respiratory specimens from ill individuals is the most commonly used method to identify influenza virus infection. A number of respiratory specimen types may be ...used, including swabs, brush, aspirate, and wash, and specimens may be collected from numerous sites, including the anterior and posterior nasopharynx, oropharynx, and nares. Traditionally, respiratory specimens from the nasopharynx have been considered to have the highest sensitivity for viral detection. However, as molecular assays such as reverse transcription-PCR (RT-PCR) have increased the sensitivity of viral detection from respiratory specimens, the use of less-invasive and easier-to-obtain specimens has increased for the detection of influenza virus. This review presents and evaluates the sensitivities of respiratory specimen methods used in epidemiologic studies that used RT-PCR to detect influenza virus in respiratory specimens from ill patients. This literature review suggested that a combination of two less-invasive swabbing methods, such as nasal and oropharyngeal swabs, had about the same sensitivity as did nasopharyngeal specimens for influenza virus detection by RT-PCR. By combining two less-invasive collection methods, it may be possible to reduce barriers to enrollment without compromising influenza virus detection sensitivity.
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