Improvement of respiratory symptoms and health‐related quality of life with peramivir in influenza patients with chronic respiratory disease: Additional outcomes of a randomized,open‐label study

BackgroundTo compare peramivir 300 mg single‐dose, peramivir 600 mg repeat‐dose, and oseltamivir effects on health‐related quality of life, including respiratory symptoms and general conditions, time to symptom alleviation, time to fever resolution, incidence of exacerbations, and virus titer, in influenza patients with chronic respiratory disease.MethodsWe report additional outcomes from a 2‐week, multicenter, randomized, open‐label study in Japan (UMIN000030118). Influenza patients with chronic respiratory disease received intravenous peramivir (300 mg single‐dose [n = 66], 600 mg repeat‐dose [600 mg/d of 2 consecutive days; n = 70]) or oral oseltamivir (75 mg twice daily, 5 days; n = 72). The principal endpoint of this analysis was change from baseline to Day 14 at each time point in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) scores.ResultsBoth peramivir regimens reduced total CAT score at Day 3 more than oseltamivir (peramivir 600 mg vs oseltamivir, P = .0032; peramivir 300 mg vs oseltamivir, P = .0203). Cough/phlegm CAT scores were most improved with peramivir 600 mg. Median time to alleviation of three respiratory symptoms was longer with peramivir 600 mg (68.9 hours) than with peramivir 300 mg (50.6 hours, hazard ratio [HR] 1.57; P = .0191) and shorter with peramivir 300 mg than oseltamivir (78.8 hours, HR 0.62; P = .0141). Alleviation of seven influenza symptoms and fever resolution was shortest with peramivir 300 mg.ConclusionsRapid improvement in CAT score, including cough, and shorter time to alleviation of respiratory symptoms associated with peramivir is of potential benefit to patients with chronic respiratory disease.     

Epidemiological and clinical characteristics of community‐acquired and nosocomial influenza cases and risk factors associated with complications: A four season analysis of all adult patients admitted in a tertiary hospital

BackgroundInformation on the characteristics of patients with nosocomial influenza and associated complications is scarce. This study compared epidemiological and clinical characteristics of patients admitted with hospital‐acquired influenza (HAI) to those with community‐acquired influenza (CAI) and analyzed risk factors associated with complications.MethodsThis retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during the influenza season in Spain (October to May) from 2012‐2013 to 2015‐2016. Symptom onset before admission was included as CAI, and 2 days after admission or within 48 hours after previous discharge were considered as HAI.ResultsOverall, 666 patients with laboratory‐confirmed influenza were included; 590 (88.6%) and 76 (11.4%) had CAI and HAI, respectively. Baseline characteristics and vaccination rates were similar in both groups. Patients with HAI had significantly fewer symptoms, less radiological alterations, and earlier microbiological diagnosis than those with CAI. Eighty‐five (14.4%) and 20 (27.6%) CAI and HAI patients, respectively, experienced at least one complication, including septic shock, admission to the intensive care unit, mechanical ventilation or evolution to death (any one, P = .003). Univariate and multivariate binary logistic regression was performed to assess independent risk factors associated with the occurrence of complications: nosocomial infection, diabetes, oseltamivir treatment, having received no vaccination, microbiological delay, dyspnea, and the state of confusion were the most important significant factors.ConclusionsOur study shows the need to implement microbiological diagnostic measures in the first 48 hours to reduce HAI frequency and associated complications.     

Burden of influenza during the first year of life

BackgroundEvery year, influenza viruses infect millions of children and cause an enormous burden of disease. Young children are at the highest risk for influenza‐attributable hospitalizations. Nevertheless, most young children are treated as outpatients, and limited data are available on the burden of influenza in these children.MethodsWe carried out a prospective cohort study and followed 431 infants born in June‐August 2017 for 10 months from September 1, 2017, to June 30, 2018. The parents filled out daily symptom diaries and were instructed to bring their child for clinical examination at our study clinic each time the child had fever or any signs or symptoms of respiratory tract infection. During each visit, we obtained nasopharyngeal swab specimens for determination of the viral etiology of the illness.ResultsA total of 55 episodes of laboratory‐confirmed influenza were diagnosed among the 408 actively participating children, which corresponds to an annual incidence rate of 135/1000 children (95% Cl, 102‐175). Excluding five children with double viral infection, acute otitis media developed as a complication of influenza in 23 (46%) children. One (2%) child with influenza was hospitalized because of febrile convulsion. The effectiveness of influenza vaccination was 48% (95% CI, −29%‐80%).ConclusionsThe burden of influenza during the first year of life is heavy in the outpatient setting where most infants with influenza are managed. Effective strategies for the prevention of influenza particularly in infants under 6 months of age are needed to diminish the burden of disease in this age group.     

The burden of influenza among Kenyan pregnant and postpartum women and their infants, 2015–2020

BackgroundIn tropical Africa, data about influenza‐associated illness burden are needed to assess potential benefits of influenza vaccination among pregnant women. We estimated the incidence of influenza among pregnant women and their infants in Siaya County, Kenya.MethodsWe enrolled women at <31 weeks of gestation and conducted weekly follow‐up until 6‐month postpartum to identify acute respiratory illnesses (ARIs). We defined ARI among mothers as reported cough, rhinorrhoea or sore throat and among infants as maternal‐reported cough, difficulty breathing, rhinorrhoea or clinician diagnosis of respiratory illness. We collected nasal/nasopharyngeal and oropharyngeal swabs from mothers/infants with ARI and tested for influenza A and B using molecular assays. We calculated antenatal incidence of laboratory‐confirmed influenza among mothers and postnatal incidence among mothers and infants.ResultsDuring June 2015 to May 2020, we analysed data from 3,026 pregnant women at a median gestational age of 16 weeks (interquartile range [IQR], 13, 18) and followed 2,550 infants. Incidence of laboratory‐confirmed influenza during pregnancy (10.3 episodes per 1,000 person‐months [95% confidence interval {CI} 8.6–11.8]) was twofold higher than in the postpartum period (4.0 [95% CI 2.6–5.5]; p < 0.01). Incidence was significantly higher among human immunodeficiency virus (HIV)‐infected pregnant women (15.6 [95% CI 11.0–20.6] vs. 9.1 [95% CI 7.5–10.8]; p < 0.01). Incidence among young infants was 4.4 (95% CI 3.0–5.9) and similar among HIV‐exposed and HIV‐unexposed infants.ConclusionOur findings suggest a substantial burden of influenza illnesses during pregnancy, with a higher burden among HIV‐infected mothers. Kenyan authorities should consider the value of vaccinating pregnant women, especially if HIV infected.     

Point‐of‐care testing for influenza in a university emergency department: A prospective study

BackgroundSeasonal influenza is a burden for emergency departments (ED). The aim of this study was to investigate whether point‐of‐care (POC) PCR testing can be used to reduce staff sick days and improve diagnostic and therapeutic procedures.ObjectivesThe aim of this study was to investigate whether point‐of‐care (POC) PCR testing can be used to reduce staff sick days and improve diagnostic and therapeutic procedures.MethodsUsing a cross‐over design, the cobas® Liat® Influenza A/B POC PCR test (Liat) was compared with standard clinical practice during the 2019/2020 influenza season. All adult patients (aged ≥ 18 years) with fever (≥38°C) and respiratory symptoms were included. Primary end points were the prevalence of influenza infections in the ED and staff sick days. Secondary end points were frequency of antiviral and antibacterial therapy, time between admission and test result or treatment initiation, patient disposition, ED length of stay (LOS), and for inpatients mortality and LOS. Nurses were interviewed about handling and integration of POC testing. The occurrence of SARS‐CoV‐2 infections coincided with the second half of the study.ResultsA total of 828 patients were enrolled in the study. All 375 patients of the intervention group were tested with Liat, and 103 patients of them (27.6%) tested positive. During the intervention period, staff sick days were reduced by 34.4% (P = .023). Significantly, more patients in the intervention group received antiviral therapy with neuraminidase inhibitors (7.2% vs 3.8%, P = .028) and tested patients received antibiotics more frequently (40.0% vs 31.6%, P = .033). Patients with POC test were transferred to external hospitals significantly more often (5.6% vs 1.3%, P = .01).ConclusionWe conclude that POC testing for influenza is useful in the ED, especially if it is heavily frequented by patients with respiratory symptoms.     

Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City

BackgroundAlthough the burden of influenza is well characterized, the burden of community‐onset non‐influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non‐influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines.MethodsFrom October 2017 to September 2019, a retrospective study was performed in a pre‐defined catchment area to estimate the population‐based incidence of community‐onset respiratory viruses associated with hospitalization. Included patients were ≥18 years old, resided in New York City, were hospitalized for ≥24 hours, and had a respiratory virus detected within 3 calendar‐days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in‐hospital mortality and compared among those with laboratory‐confirmed influenza versus those with laboratory‐confirmed non‐influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus).ResultsDuring the study period, 4232 eligible patients were identified of whom 50.9% were ≥65 years of age. For each virus, the population‐based incidence was highest for those ≥80 years of age. When compared to those with influenza viruses detected, those with non‐influenza respiratory viruses detected (combined) had higher population‐based incidence, significantly more ICU admissions, and higher in‐house mortality.ConclusionsThe burden of non‐influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non‐influenza respiratory viruses, particularly for older adults.     

Amaryllidaceae alkaloids inhibit nuclear‐to‐cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1

Please cite this paper as: He et al. (2013) Amaryllidaceae alkaloids inhibit nuclear‐to‐cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1. Influenza and Other Respiratory Viruses 7(6), 922–931. Background  Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as Lycoris radiata, are a potential source of new antiviral agents. Objective  To test 15 Amaryllidaceae alkaloids isolated from the bulbs of L. radiata in vitro for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178). Methods  Antiviral activities of the compounds were tested in time‐of‐addition assays, hemagglutination inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry inhibition assays using H5N1‐HIV pseudoviruses. Effects of the compounds on localization and activity of the viral ribonucleoprotein (RNP) were determined by immunofluorescence and an RNP minigenome assay, respectively. Results  Among the alkaloids, lycorine (AA1), hippeastrine (AA2), hemanthamine (AA3) and 11‐hydroxy vittatine (AA4) exhibited antiviral activities, with EC₉₀ values of 0·52, 82·07, 4·15, and 13·45 μm, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited the RNP complex in the nucleus at an early stage of a single‐round and multi‐round of replication. Conclusion  Four Amaryllidaceae alkaloids were first determined that could exert anti‐influenza activities after virus entry into cells. Furthermore, AA1 and AA3 could inhibit nuclear‐to‐cytoplasmic export of the RNP complex of virus replication. Thus, these compounds may be developed further as anti‐influenza drug candidates.     

Viral co‐infections are associated with increased rates of hospitalization in those with influenza

BackgroundInfluenza causes significant morbidity and mortality in the United States. Among patients infected with influenza, the presence of bacterial co‐infection is associated with worse clinical outcomes; less is known regarding the clinical importance of viral co‐infections. The objective of this study was to determine rates of viral co‐infections in emergency department (ED) patients with confirmed influenza and association of co‐infection with disease severity.MethodsSecondary analysis of a biorepository and clinical database from a parent study where rapid influenza testing was implemented in four U.S. academic EDs, during the 2014–2015 influenza season. Patients were systematically tested for influenza virus using a validated clinical decision guideline. Demographic and clinical data were extracted from medical records; nasopharyngeal specimens from influenza‐positive patients were tested for viral co‐infections (ePlex, Genmark Diagnostics). Patterns of viral co‐infections were evaluated using chi‐square analysis. The association of viral co‐infection with hospital admission was assessed using univariate and multivariate regression.ResultsThe overall influenza A/B positivity rate was 18.1% (1071/5919). Of the 999 samples with ePlex results, the prevalence of viral co‐infections was 7.9% (79/999). The most common viral co‐infection was rhinovirus/enterovirus (RhV/EV), at 3.9% (39/999). The odds of hospital admission (OR 2.33, 95% CI: 1.01–5.34) increased significantly for those with viral co‐infections (other than RhV/EV) versus those with influenza A infection only.ConclusionPresence of viral co‐infection (other than RhV/EV) in ED influenza A/B positive patients was independently associated with increased risk of hospital admission. Further research is needed to determine clinical utility of ED multiplex testing.     

Epidemiology and outcome of influenza‐associated infections among hospitalized patients with acute respiratory infections,Egypt national surveillance system, 2016‐2019

IntroductionEgypt has established different types of surveillance systems to monitor influenza activities, early detect outbreaks, and tailor efficient prevention and control strategies. This is the first study to describe epidemiology and outcome of influenza‐associated infections among hospitalized patients using the National Electronic Disease Surveillance System (NEDSS) data, 2016‐2019.MethodsData reported from 284 hospitals all over Egypt were extracted from the NEDSS. Data of hospitalized patients with Acute Respiratory Infections (ARI), 2016‐2019, were included in the analysis. Laboratory testing for influenza by RT‐PCR according to US CDC testing protocol was used to confirm influenza type and subtype.ResultsOverall 46 417 patients hospitalized with ARI were identified, their mean age was 30.9 ± 26 and 52.9% were males. Among 41 512 (89.4%) laboratory‐tested patients, 7167 (17.3%) were positive for one or more types of influenza viruses. Influenza viruses circulated in all ages and throughout the year, with higher rates in winter, late childhood, and middle ages. Mortality from influenza was significantly higher than other causes of ARIs (5.0% vs 3.8%, P < .001), and it was associated with older ages, December‐May, delay in hospital admission, residence in urban and frontier governorates and infection with A/H1N1 virus. The distribution of influenza subtype by time shows alternate pattern between A/H1N1 and H3N2, each subtype peaks every other year with a high peak of A/H1N1 in 2016.ConclusionsThe national Egyptian surveillance succeeded to describe the epidemiology of hospitalized patients with ARIs and influenza in Egypt over time. Surveillance with strain‐specific laboratory testing and annual assessment of associated severity might be useful to guide influenza prevention and control strategies including vaccination and case management.     

Overrepresentation of South Asian ethnic groups among cases of influenza A(H1N1)pdm09 during the first phase of the 2009 pandemic in England

BackgroundDuring the first wave of the influenza A(H1N1)pdm09 pandemic in England in 2009, morbidity and mortality were higher in patients of South Asian (Indian, Pakistani or Bangladeshi) ethnic minority groups.ObjectivesThis study aims to provide insights in the representation of this group among reported cases, indicating susceptibility and exposure.MethodsAll laboratory‐confirmed cases including basic demographic and limited clinical information that were reported to the FluZone surveillance system between April and October 2009 were retrieved. Missing ethnicity data were imputed using the previously developed and validated South Asian Names and Group Recognition Algorithm (SANGRA). Differences between ethnic groups were calculated using chi‐square, log‐rank and t tests and rate ratios. Geographic clustering was compared using Ripley''s K functions.ResultsSANGRA identified 2447 (28%) of the total of 8748 reported cases as South Asian. South Asian cases were younger (P < .001), more often male (P = .002) and more often from deprived areas (P < .001) than cases of other ethnic groups. Time between onset of symptoms and laboratory sampling was longer in this group (P < .001), and they were less often advised antiviral treatment (P < .001), however, declined treatment less. The highest cumulative incidence was seen in the West Midlands region (32.7/10 000), London (7.0/10 000) and East of England region (5.7/10 000).ConclusionsPeople of South Asian ethnic groups were disproportionally affected by the first wave of the influenza pandemic in England in 2009. The findings presented contribute to further understanding of demographic, socioeconomic and ethnic factors of the outbreak and inform future influenza preparedness to ensure appropriate prevention and care.     

Antibody titres elicited by the 2018 seasonal inactivated influenza vaccine decline by 3 months post‐vaccination but persist for at least 6 months

BackgroundIn Australia, seasonal inactivated influenza vaccine is typically offered in April. However, the onset, peak and end of a typical influenza season vary, and optimal timing for vaccination remains unclear. Here, we investigated vaccine‐induced antibody response kinetics over 6 months in different age groups.MethodsWe conducted a prospective serosurvey among 71 adults aged 18–50 years, 15 community‐dwelling (‘healthy’) and 16 aged‐care facility resident (‘frail’) older adults aged ≥65 years who received the 2018 southern hemisphere vaccines. Sera were collected at baseline, and 1, 2, 4, and 6 months post‐vaccination. Antibody titres were measured by haemagglutination inhibition or microneutralisation assays. Geometric mean titres were estimated using random effects regression modelling and superimposed on 2014–2018 influenza season epidemic curves.ResultsAntibody titres peaked 1.2–1.3 months post‐vaccination for all viruses, declined by 3 months post‐vaccination but, notably, persisted above baseline after 6 months in all age groups by 1.3‐ to 1.5‐fold against A(H1N1)pdm09, 1.7‐ to 2‐fold against A(H3N2), 1.7‐ to 2.1‐fold against B/Yamagata and 1.8‐fold against B/Victoria. Antibody kinetics were similar among different age groups. Antibody responses were poor against cell‐culture grown compared to egg‐grown viruses.ConclusionsThese results suggest subtype‐specific antibody‐mediated protection persists for at least 6 months, which corresponds to the duration of a typical influenza season.     

Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow‐fill‐seal device in adults: a randomized,active‐controlled study

Please cite this paper as: Sheldon et al. (2013) Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow‐fill‐seal device in adults: a randomized, active‐controlled study. Influenza and Other Respiratory Viruses 7(6), 1142–1150. Background  Influenza B strains from two distinct lineages (Yamagata and Victoria) have cocirculated over recent years. Current seasonal vaccines contain a single B lineage resulting in frequent mismatches between the vaccine strain and the circulating strain. An Ann Arbor strain quadrivalent live attenuated influenza vaccine (Q/LAIV) containing B strains from both lineages is being developed to address this issue. Objectives  The goal of this study was to evaluate whether Q/LAIV administered intranasally as a single dose to a single nostril, using a blow‐fill‐seal (BFS) delivery system had a similar immunogenicity and safety profile compared with the licensed trivalent vaccine delivered using the Accuspray device. Patients/Methods  Adults aged 18–49 years were randomized to receive one intranasal dose of Q/LAIV delivered using a BFS device (Q/LAIV‐BFS; n = 1202) or one of two trivalent live attenuated influenza vaccines (T/LAIV) containing one of the corresponding B strains (total T/LAIV, n = 598). Primary endpoints were the post‐vaccination strain‐specific serum hemagglutination inhibition antibody geometric mean titers for each strain. Secondary immunogenicity endpoints, safety, and acceptability of the BFS device were also assessed. Results  Q/LAIV was immunogenically non‐inferior to T/LAIV for all four influenza strains. Secondary immunogenicity outcomes were consistent with the primary endpoint. Solicited symptoms and AEs were comparable in both groups. Subjects considered the BFS device to be acceptable. Conclusions  Immune responses to vaccination with Ann Arbor strain Q/LAIV‐BFS were non‐inferior to those with T/LAIV. Q/LAIV may confer broader protection against seasonal influenza B by targeting both major influenza B lineages.     

Predicting virologically confirmed influenza using school absences in Allegheny County,Pennsylvania, USA during the 2007‐2015 influenza seasons

BackgroundChildren are important in community‐level influenza transmission. School‐based monitoring may inform influenza surveillance.MethodsWe used reported weekly confirmed influenza in Allegheny County during the 2007 and 2010‐2015 influenza seasons using Pennsylvania''s Allegheny County Health Department all‐age influenza cases from health facilities, and all‐cause and influenza‐like illness (ILI)‐specific absences from nine county school districts. Negative binomial regression predicted influenza cases using all‐cause and illness‐specific absence rates, calendar week, average weekly temperature, and relative humidity, using four cross‐validations.ResultsSchool districts reported 2 184 220 all‐cause absences (2010‐2015). Three one‐season studies reported 19 577 all‐cause and 3012 ILI‐related absences (2007, 2012, 2015). Over seven seasons, 11 946 confirmed influenza cases were reported. Absences improved seasonal model fits and predictions. Multivariate models using elementary school absences outperformed middle and high school models (relative mean absolute error (relMAE) = 0.94, 0.98, 0.99). K‐5 grade‐specific absence models had lowest mean absolute errors (MAE) in cross‐validations. ILI‐specific absences performed marginally better than all‐cause absences in two years, adjusting for other covariates, but markedly worse one year.ConclusionsOur findings suggest seasonal models including K‐5th grade absences predict all‐age‐confirmed influenza and may serve as a useful surveillance tool.     

Using the health belief model to identify barriers to seasonal influenza vaccination among Australian adults in 2019

BackgroundEach year tens of thousands of Australians become ill with influenza, resulting in thousands of severe infections that require hospitalisation. However, only 40% of adults receive the annual influenza vaccine. We surveyed Australian adults to provide up to date, population‐specific data on the predictors and barriers of seasonal influenza vaccination.MethodsWe administered an online survey to a nationally representative sample of Australian adults. We designed survey questions using the theoretical constructs of the health belief model. Using simple and multivariable Poisson regression, we identified attitudes and beliefs associated with influenza vaccination in 2019.ResultsAmong 1,444 respondents, 51.7% self‐reported influenza vaccination in 2019. We estimated vaccine coverage to be 44% for adults under 45, 46% for adults aged 45 to 64 and 77% for adults aged 65 and over. The strongest individual predictors of self‐reported vaccination were believing the vaccine is effective at preventing influenza (APR = 3.71; 95% CI = 2.87‐4.80), followed by recalling their doctor recommending the vaccine (APR = 2.70; 95% CI = 2.31‐3.16). Common perceived barriers that predicted self‐reported vaccination included believing the vaccine could give you influenza (APR = 0.59; 95% CI = 0.52‐0.67), believing the vaccine can make you ill afterwards (APR = 0.68; 95% CI = 0.62‐0.74) and preferring to develop immunity “naturally” (APR = 0.38; 95% CI = 0.32‐0.45).ConclusionAlthough vaccine uptake in 2019 appears to be higher than previous years, there are perceived barriers which may limit uptake among Australians. Tailored interventions are needed to combat widespread influenza vaccine hesitancy, particularly among high‐risk groups.