Influenza-associated Hospitalizations Research Articles

Rates of Severe Influenza-Associated Outcomes Among Older Adults Living With Diabetes-Influenza Hospitalization Surveillance Network (FluSurv-NET), 2012-2017.

Diabetes mellitus (DM) is common among older adults hospitalized with influenza, yet data are limited on the impact of DM on risk of severe influenza-associated outcomes. We included adults aged ≥65 years hospitalized with influenza during 2012-2013 through 2016-2017 from the Influenza Hospitalization Surveillance Network (FluSurv-NET), a population-based surveillance system for laboratory-confirmed influenza-associated hospitalizations conducted in defined counties within 13 states. We calculated population denominators using the Centers for Medicare and Medicaid Services county-specific DM prevalence estimates and National Center for Health Statistics population data. We present pooled rates and rate ratios (RRs) of intensive care unit (ICU) admission, pneumonia diagnosis, mechanical ventilation, and in-hospital death for persons with and without DM. We estimated RRs and 95% confidence intervals (CIs) using meta-analysis with site as a random effect in order to control for site differences in the estimates. Of 31 934 hospitalized adults included in the analysis, 34% had DM. Compared to those without DM, adults with DM had higher rates of influenza-associated hospitalization (RR, 1.57 [95% CI, 1.43-1.72]), ICU admission (RR, 1.84 [95% CI, 1.67-2.04]), pneumonia (RR, 1.57 [95% CI, 1.42-1.73]), mechanical ventilation (RR, 1.95 [95% CI, 1.74-2.20]), and in-hospital death (RR, 1.48 [95% CI, 1.23-1.80]). Older adults with DM have higher rates of severe influenza-associated outcomes compared to those without DM. These findings reinforce the importance of preventing influenza virus infections through annual vaccination, and early treatment of influenza illness with antivirals in older adults with DM.

Improving Influenza Vaccination Rates in an Underserved Primary Care Clinic Using a Simple Educational Tool.

Influenza is a preventable communicable illness that has a significant impact on people of all ages. In 2018, it was estimated that 80 000 people died of influenza-related illnesses. In the 2018-2019 influenza season, only 34.9% of individuals in the 18 to 49 years age group received the influenza vaccine. Despite the low vaccination rate for influenza, the vaccine has multiple evidence-based benefits that demonstrate the importance of improving its uptake among adults. According to data from the Centers for Disease Control and Prevention (CDC), the vaccine prevented around "6.2 million influenza illnesses, 3.2 million influenza-associated medical visits 91 000 influenza-associated hospitalizations, and 5700 influenza-associated deaths" in the 2017-2018 influenza season. In a suburban family medicine clinic, a primary care provider (PCP) observed that greater than 50% of adult patients in his family medicine practice declined influenza vaccine when offered during the 2018-2019 season compared with the site rate of 43.4% and the department rate of 47.9%. The goal of this project was to educate patients who initially decline the vaccine to agree to receive the vaccine and to increase the percentage of patients who get an influenza vaccine from 43.4% to 50% in adult patients at a suburban primary care clinic by having them read the CDC document and asking them after they read the document whether they would like to receive the vaccine. From October 1, 2018, to February 28, 2019, adult patients in a primary care clinic were asked whether they wanted to receive the influenza vaccination and responses were recorded. During this time, 589 patients were questioned, with 56% (n = 330) answering no, or 43% of patients receiving the influenza vaccination. In total, 658 patients were offered the flu shot during the intervention period, representing 27.7% of the patients seen in this clinic. While there was some monthly variation, the PCP was able improve the percentage of patients receiving the influenza vaccination from 43% to 60.9% with this simple educational intervention. The overall clinic rate for this time frame increased from 56.6% to 58.2%. This simple intervention was effective in improving influenza vaccine rates for one provider in a suburban safety-net clinic. It added minimal workload to the provider, and the intervention is easily replicable in other settings.

National FluWatch mid-season report, 2021-2022: Sporadic influenza activity returns.

Surveillance for Canada's 2021-2022 seasonal influenza epidemic began in epidemiological week 35 (the week starting August 29, 2021) during the ongoing coronavirus disease 2019 (COVID-19) global public health emergency. In the 2021-2022 surveillance season to date, there has been a return of persistent sporadic influenza activity, and the first influenza-associated hospitalizations since mid-2020 have been reported. However, as of week 52 (week ending 01/01/2022) activity has remained sporadic, and no influenza-confirmed outbreaks or epidemic activity have been detected. There has been a delay or absence in several traditional seasonal influenza milestones, including the declared start of the influenza season, marked by a threshold of 5% positivity, which historically has occurred on average in week 47. The 429 sporadic detections reported in Canada to date have occurred in 31 regions across seven provinces/territories. Nearly half (n=155/335, 46.3%) of reported cases have been in the paediatric (younger than 19 years) population. Three-quarters of the cases were influenza A detections (n=323/429, 75.3%). Of the subtyped influenza A detections, A(H3N2) predominated (n=83/86, 96.5%). Of the 12 viruses characterized by the National Microbiology Laboratory, 11 were seasonal strains. Among the seasonal strains characterized, only one was antigenically similar to the strains recommended for the 2021-2022 Northern Hemisphere vaccine, though all were sensitive to the antivirals, oseltamivir and zanamivir. Until very recently, seasonal influenza epidemics had not been reported since March 2020. Evidence on the re-emergence of seasonal influenza strains in Canada following the A(H1N1)pdm09 pandemic shows that influenza A(H3N2) and B epidemics ceased through the 2009-2010 season and second wave of A(H1N1)pdm09, but then re-emerged in subsequent seasons to predominate causing epidemics of higher intensity than in the pre-pandemic seasons. When and where seasonal influenza epidemic activity resumes cannot be predicted, but model-based estimates and historical post-pandemic patterns of intensified epidemics warrant continued vigilance through the usual season and for out-of-season re-emergence. In addition, ongoing population preparedness measures, such as annual influenza vaccination to mitigate the intensity and burden of future seasonal influenza epidemic waves, should continue.

Epidemiology and direct healthcare costs of Influenza-associated hospitalizations \u2013 nationwide inpatient data (Germany 2010-2019)

IntroductionDetailed and up-to-date data on the epidemiology and healthcare costs of Influenza are fundamental for public health decision-making. We analyzed inpatient data on Influenza-associated hospitalizations (IAH), selected complications and risk factors, and their related direct costs for Germany during ten consecutive years.MethodsWe conducted a retrospective cost-of-illness study on patients with laboratory-confirmed IAH (ICD-10-GM code J09/J10 as primary diagnosis) by ICD-10-GM-based remote data query using the Hospital Statistics database of the German Federal Statistical Office. Clinical data and associated direct costs of hospital treatment are presented stratified by demographic and clinical variables.ResultsBetween January 2010 to December 2019, 156,097 persons were hospitalized due to laboratory-confirmed Influenza (J09/J10 primary diagnosis). The annual cumulative incidence was low in 2010, 2012 and 2014 (1.3 to 3.1 hospitalizations per 100,000 persons) and high in 2013 and 2015-2019 (12.6 to 60.3). Overall direct per patient hospitalization costs were mean (SD) 3521 EUR (± 8896) and median (IQR) 1805 EUR (1502; 2694), with the highest mean costs in 2010 (mean 8965 EUR ± 26,538) and the lowest costs in 2012 (mean 2588 EUR ± 6153). Mean costs were highest in 60-69 year olds, and in 50-59, 70-79 and 40-49 year olds; they were lowest in 10-19 year olds. Increased costs were associated with conditions such as diabetes (frequency 15.0%; 3.45-fold increase compared to those without diabetes), adiposity (3.3%; 2.09-fold increase) or immune disorders (5.6%; 1.88-fold increase) and with Influenza-associated complications such as Influenza pneumonia (24.3%; 1.95-fold), bacterial pneumonia (6.3%; 3.86-fold), ARDS (1.2%; 10.90-fold increase) or sepsis (2.3%; 8.30-fold). Estimated overall costs reported for the 10-year period were 549.6 Million euros (95% CI 542.7-556.4 million euros).ConclusionWe found that the economic burden of IAH in Germany is substantial, even when considering solely laboratory-confirmed IAH reported as primary diagnosis. The highest costs were found in the elderly, patients with certain underlying risk factors and patients who required advanced life support treatment, and median and mean costs showed considerable variations between single years. Furthermore, there was a relevant burden of disease in middle-aged adults, who are not covered by the current vaccination recommendations in Germany.

Longitudinal, population-based cohort study of prenatal influenza vaccination and influenza infection in childhood

BackgroundInfluenza vaccination is recommended to protect mothers and their infants from influenza infection. Few studies have evaluated the health impacts of in utero exposure to influenza vaccine among children more than six months of age. MethodsWe used probabilistically linked administrative health records to establish a mother–child cohort to evaluate the risk of influenza and acute respiratory infections associated with maternal influenza vaccination. Outcomes were laboratory-confirmed influenza (LCI) and hospitalization for influenza or acute respiratory infection (ARI). Adjusted hazard ratios (aHRs) accounted for child’s Aboriginal status and were weighted by the inverse-probability of treatment. Results14,396 (11.5%) children were born to vaccinated mothers. Maternally vaccinated infants aged < 6 months had lower risk of LCI (aHR: 0.33; 95% CI: 0.13, 0.85), influenza-associated hospitalization (aHR: 0.39; 95% CI: 0.16, 0.94) and ARI-associated hospitalization (aHR: 0.85; 95% CI: 0.77, 0.94) compared to maternally unvaccinated infants. With the exception of an increased risk of LCI among children aged 6 months to < 2 years old following first trimester vaccination (aHR: 2.28; 95% CI: 1.41, 3.69), there were no other differences in the risk of LCI, influenza-associated hospitalization or ARI-associated hospitalization among children aged > 6 months. ConclusionStudy results show that maternal influenza vaccination is effective in preventing influenza in the first six months and had no impact on respiratory infections after two years of age.

Report of the National Influenza Surveillance Scheme, 2011 to 2018.

This report describes influenza surveillance activities in Australia for the period 2011 to 2018. Data were extracted from several sources constituting the National Influenza Surveillance Scheme (NISS). Laboratory-confirmed influenza notification rates (per 100,000 population) increased from 122 in 2011 to 1,021 in 2017, before declining to 235 in 2018. The highest laboratory-confirmed notification rates during the eight-year period were from the smaller jurisdictions (South Australia and the Northern Territory), except in 2016 when Queensland reported the highest rate. Similar trends were observed in community reports of influenza-like illness (ILI), presentations of ILI to sentinel general practice (GP) sites, and influenza hospitalisations. Children aged 14 years or younger, and adults 65 years of age or older, had the highest notification rates of laboratory-confirmed influenza. Adults aged 65 years or older and patients with comorbidities had higher rates of influenza-associated hospitalisations and mortality. Over half of eligible patients admitted to sentinel hospitals (57%) received oseltamivir treatment, with 17% receiving the treatment within 48 hours of symptom onset. Influenza type A predominated over the eight years, except in 2015 when type B predominated. This trend was consistent with Australian World Health Organization Collaborating Centre (WHOCC) data for influenza isolates tested. Of influenza viruses circulating during the reporting period, A(H1N1) viruses were mostly antigenically similar to the vaccine strain A/California/7/2009 (H1N1), except in 2017 and 2018 when they were mostly similar to A/Michigan/45/2015. The A(H3N2) strains varied over the years but included the vaccine strains A/Perth/16/2009, A/Switzerland/9715293/2013, A/Hong Kong/4801/2014, and A/Singapore/INFIMH/2016. The B/Victoria/2/87 lineage (represented by the 2016 vaccine strain B/Brisbane/60/2008) and the B/Yamagata/16/88 lineage (represented by the southern hemisphere 2015 vaccine strain B/Phuket/3073/2013) were the circulating influenza B viruses during the reporting period. Influenza B accounted for just under a third of notifications (32%) from 2011 to 2018. Fifty-four per cent of influenza B viruses characterised by the Australian WHOCC site during the eight-year period were from the Yamagata lineage, although the proportion was higher (67%) when analysing the most recent four years (2015 to 2018). In contrast, during the 2010 season, 99% of all influenza B viruses characterised by the Australian WHOCC site were in the B-Victoria lineage. During the 2018 season the Australian WHOCC site detected, for the first time, swine A(H3N2)v virus from a human patient in Australia, highlighting the need to maintain vigilance for zoonotic infections.

Vaccine Effectiveness Against Influenza Hospitalization and Emergency Department Visits in 2 A(H3N2) Dominant Influenza Seasons Among Children

Studies have shown egg-adaptive mutations in influenza vaccine strains that might have impaired protection against circulating A(H3N2) influenza viruses during the 2016-2017 and 2017-2018 seasons. We used the test-negative design and multivariable models to assess vaccine effectiveness against influenza-associated hospitalization and emergency department visits among children (<18 years old) during the 2016-2017 and 2017-2018 seasons. Effectiveness was 71% (95% confidence interval, 59%-79%), 46% (35%-55%), and 45% (33%-55%) against A(H1N1)pdm09, A(H3N2), and B viruses respectively, across both seasons. During high-severity seasons with concerns for vaccine mismatch, vaccination offered substantial protection against severe influenza outcomes requiring hospitalization or emergency department visits among children.

1178. Sustained Vaccine Effectiveness Against Influenza-Associated Hospitalization in Children: Evidence from the New Vaccine Surveillance Network, 2015-2016 Through 2019-2020

BackgroundAdult studies have demonstrated intra-season declines in influenza vaccine effectiveness (VE) with increasing time since vaccination; however, data in children are limited. MethodsWe conducted a prospective, test-negative study of children ages 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers each season in the New Vaccine Surveillance Network during the 2015-2016 through 2019-2020 influenza seasons. Cases were children with an influenza-positive molecular test; controls were influenza-negative children. Controls were matched to cases by illness onset date using 3:1 nearest neighbor matching. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥ 1 dose of influenza vaccine ≥ 14 days before the onset of illness that resulted in hospitalization among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date during each season were estimated using multivariable logistic regression models.ResultsOf 8,430 hospitalized children (4,781 [57%] male; median age 2.4 years), 4,653 (55%) received ≥ 1 dose of influenza vaccine. On average, 48% and 85% of children were vaccinated by the end of October and December, respectively. Influenza-positive cases (n=1,000; 12%) were less likely to be vaccinated than influenza-negative controls (39% vs. 61%, p< 0.001) and overall VE against hospitalization was 53% (95% CI: 46%, 60%). Pooling data across 5 seasons, the odds of any influenza-associated hospitalization increased 0.96% (95% CI: -0.76%, 2.71%) per week with a corresponding weekly decrease in VE of 0.45% (p=0.275). Odds of hospitalization with time since vaccination increased 0.66% (95% CI: -0.76%, 2.71%) per week in children ≤ 8 years (n=3,084) and 2.16% (95% CI: -1.68%, 6.15%) per week in children 9-17 years (n=771). No significant differences were observed by virus subtype or lineage.Figure 1. Declines in influenza VE over time from 2015-2016 through 2019-2020, overall (a) and by age group (b: ≤ 8 years; c: 9-17 years) ConclusionWe observed minimal intra-season declines in VE against influenza-associated hospitalization in U.S. children. Vaccination following Advisory Committee on Immunization Practices guidelines and current timing of vaccine receipt is the best strategy for prevention of influenza-associated hospitalization in children. Disclosures Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)

Hospital-acquired influenza in the United States, FluSurv-NET, 2011-2012 through 2018-2019.

To estimate population-based rates and to describe clinical characteristics of hospital-acquired (HA) influenza. Cross-sectional study. US Influenza Hospitalization Surveillance Network (FluSurv-NET) during 2011-2012 through 2018-2019 seasons. Patients were identified through provider-initiated or facility-based testing. HA influenza was defined as a positive influenza test date and respiratory symptom onset >3 days after admission. Patients with positive test date >3 days after admission but missing respiratory symptom onset date were classified as possible HA influenza. Among 94,158 influenza-associated hospitalizations, 353 (0.4%) had HA influenza. The overall adjusted rate of HA influenza was 0.4 per 100,000 persons. Among HA influenza cases, 50.7% were 65 years of age or older, and 52.0% of children and 95.7% of adults had underlying conditions; 44.9% overall had received influenza vaccine prior to hospitalization. Overall, 34.5% of HA cases received ICU care during hospitalization, 19.8% required mechanical ventilation, and 6.7% died. After including possible HA cases, prevalence among all influenza-associated hospitalizations increased to 1.3% and the adjusted rate increased to 1.5 per 100,000 persons. Over 8 seasons, rates of HA influenza were low but were likely underestimated because testing was not systematic. A high proportion of patients with HA influenza were unvaccinated and had severe outcomes. Annual influenza vaccination and implementation of robust hospital infection control measures may help to prevent HA influenza and its impacts on patient outcomes and the healthcare system.

Burden of Influenza-Associated Respiratory Hospitalizations, Vietnam, 2014-2016.

Influenza burden estimates are essential to informing prevention and control policies. To complement recent influenza vaccine production capacity in Vietnam, we used acute respiratory infection (ARI) hospitalization data, severe acute respiratory infection (SARI) surveillance data, and provincial population data from 4 provinces representing Vietnam’s major regions during 2014–2016 to calculate provincial and national influenza-associated ARI and SARI hospitalization rates. We determined the proportion of ARI admissions meeting the World Health Organization SARI case definition through medical record review. The mean influenza-associated hospitalization rates per 100,000 population were 218 (95% uncertainty interval [UI] 197–238) for ARI and 134 (95% UI 119–149) for SARI. Influenza-associated SARI hospitalization rates per 100,000 population were highest among children <5 years of age (1,123; 95% UI 946–1,301) and adults >65 years of age (207; 95% UI 186–227), underscoring the need for prevention and control measures, such as vaccination, in these at-risk populations.

Rates of Influenza-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death by Race and Ethnicity in the United States From 2009 to 2019

Racial and ethnic minority groups, such as Black, Hispanic, American Indian or Alaska Native, and Asian or Pacific Islander persons, often experience higher rates of severe influenza disease. To describe rates of influenza-associated hospitalization, intensive care unit (ICU) admission, and in-hospital death by race and ethnicity over 10 influenza seasons. This cross-sectional study used data from the Influenza-Associated Hospitalization Surveillance Network (FluSurv-NET), which conducts population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in selected counties, representing approximately 9% of the US population. Influenza hospitalizations from the 2009 to 2010 season to the 2018 to 2019 season were analyzed. Data were analyzed from October 2020 to July 2021. The main outcomes were age-adjusted and age-stratified rates of influenza-associated hospitalization, ICU admission, and in-hospital death by race and ethnicity overall and by influenza season. Among 113 352 persons with an influenza-associated hospitalization (34 436 persons [32.0%] aged ≥75 years; 61 009 [53.8%] women), 70 225 persons (62.3%) were non-Hispanic White (White), 24 850 persons (21.6%) were non-Hispanic Black (Black), 11 903 persons (10.3%) were Hispanic, 5517 persons (5.1%) were non-Hispanic Asian or Pacific Islander, and 857 persons (0.7%) were non-Hispanic American Indian or Alaska Native. Among persons aged younger than 75 years and compared with White persons of the same ages, Black persons were more likely to be hospitalized (eg, age 50-64 years: rate ratio [RR], 2.50 95% CI, 2.43-2.57) and to be admitted to an ICU (eg, age 50-64 years: RR, 2.09; 95% CI, 1.96-2.23). Among persons aged younger than 50 years and compared with White persons of the same ages, American Indian or Alaska Native persons were more likely to be hospitalized (eg, age 18-49 years: RR, 1.72; 95% CI, 1.51-1.96) and to be admitted to an ICU (eg, age 18-49 years: RR, 1.84; 95% CI, 1.40-2.42). Among children aged 4 years or younger and compared with White children, hospitalization rates were higher in Black children (RR, 2.21; 95% CI, 2.10-2.33), Hispanic children (RR, 1.87; 95% CI, 1.77-1.97), American Indian or Alaska Native children (RR, 3.00; 95% CI, 2.55-3.53), and Asian or Pacific Islander children (RR, 1.26; 95% CI, 1.16-1.38), as were rates of ICU admission (Black children: RR, 2.74; 95% CI, 2.43-3.09; Hispanic children: RR, 1.96; 95% CI, 1.73-2.23; American Indian and Alaska Native children: RR, 3.51; 95% CI, 2.45-5.05). In this age group and compared with White children, in-hospital death rates were higher among Hispanic children (RR, 2.98; 95% CI, 1.23-7.19), Black children (RR, 3.39; 95% CI, 1.40-8.18), and Asian or Pacific Islander children (RR, 4.35; 95% CI, 1.55-12.22). Few differences were observed in rates of severe influenza-associated outcomes by race and ethnicity among adults aged 75 years or older. For example, in this age group, compared with White adults, hospitalization rates were slightly higher only among Black adults (RR, 1.05; 95% CI 1.02-1.09). Overall, Black persons had the highest age-adjusted hospitalization rate (68.8 [95% CI, 68.0-69.7] hospitalizations per 100 000 population) and ICU admission rate (11.6 [95% CI, 11.2-11.9] admissions per 100 000 population). This cross-sectional study found racial and ethnic disparities in rates of severe influenza-associated disease. These data identified subgroups for whom improvements in influenza prevention efforts could be targeted.

Excess respiratory mortality and hospitalizations associated with influenza in Australia, 2007-2015.

Influenza is the most common vaccine-preventable disease in Australia, causing significant morbidity and mortality. We assessed the burden of influenza across all ages in terms of influenza-associated mortality and hospitalizations using national mortality, hospital-discharge and influenza surveillance data. Influenza-associated excess respiratory mortality and hospitalization rates from 2007 to 2015 were estimated using generalized additive models with a proxy of influenza activity based on syndromic and laboratory surveillance data. Estimates were made for each age group and year. The estimated mean annual influenza-associated excess respiratory mortality was 2.6 per 100 000 population [95% confidence interval (CI): 1.8, 3.4 per 100 000 population]. The excess annual respiratory hospitalization rate was 57.4 per 100 000 population (95% CI: 32.5, 82.2 per 100 000 population). The highest mortality rates were observed among those aged ≥75 years (35.11 per 100 000 population; 95% CI: 19.93, 50.29 per 100 000 population) and hospitalization rates were also highest among older adults aged ≥75 years (302.95 per 100 000 population; 95% CI: 144.71, 461.19 per 100 000 population), as well as children aged <6 months (164.02 per 100 000 population; 95% CI: -34.84, 362.88 per 100 000 population). Annual variation was apparent, ranging from 1.0 to 3.9 per 100 000 population for mortality and 24.2 to 94.28 per 100 000 population for hospitalizations. Influenza A contributed to almost 80% of the average excess respiratory hospitalizations and 60% of the average excess respiratory deaths. Influenza causes considerable burden to all Australians. Expected variation was observed among age groups, years and influenza type, with the greatest burden falling to older adults and young children. Understanding the current burden is useful for understanding the potential impact of mitigation strategies, such as vaccination.

Influenza vaccine effectiveness against influenza-associated hospitalization in children in Hong Kong, 2010–2020

BackgroundInfluenza virus infections can cause hospitalizations in children, and annual vaccination of children can provide protection against influenza. MethodsWe analyzed a test-negative design study with data spanning from 2010/11 through 2019/20 to evaluate influenza vaccine effectiveness (VE) against influenza hospitalization in children by age group, influenza type/subtype and time period within each season. We enrolled children admitted to hospital with acute febrile respiratory illnesses. Nasopharyngeal aspirates were tested by culture and/or RT-PCR to determine influenza status, and vaccination status was obtained by interviewing parents or legal guardians and was verified where possible. VE was estimated by conditional logistic regression model adjusting for sex, age and age-squared, matching on week. ResultsInfluenza seasons in Hong Kong are prolonged with influenza-associated hospitalizations occurring in almost every month of the year during the study period. Influenza vaccination was effective in preventing influenza-associated hospitalizations in children of all ages. Influenza VE was higher in younger children than in older children, and higher against hospitalization due to influenza A(H1N1)pdm09 than A(H3N2) and B. ConclusionsThe childhood influenza vaccination program in Hong Kong has prevented influenza-associated hospitalizations particularly in younger children. Our findings support the use of influenza vaccines in children as an effective approach to influenza control and prevention.

Global hospital admissions and in-hospital mortality associated with all-cause and virus-specific acute lower respiratory infections in children and adolescents aged 5–19 years between 1995 and 2019: a systematic review and modelling study

IntroductionThe burden of acute lower respiratory infections (ALRI), and common viral ALRI aetiologies among 5–19 years are less well understood. We conducted a systematic review to estimate global burden of...

Estimating the national burden of hospitalizations for influenza-associated severe acute respiratory infection in the Lao People's Democratic Republic, 2016.

ObjectiveEstimates of the burden of influenza are needed to inform prevention and control activities for seasonal influenza, including to support the development of appropriate vaccination policies. We used sentinel surveillance data on severe acute respiratory infection (SARI) to estimate the burden of influenza-associated hospitalizations in the Lao People's Democratic Republic.MethodsUsing methods developed by the World Health Organization, we combined data from hospital logbook reviews with epidemiological and virological data from influenza surveillance from 1 January to 31 December 2016 in defined catchment areas for two sentinel sites (Champasack and Luang Prabang provincial hospitals) to derive population-based estimates of influenza-associated SARI hospitalization rates. Hospitalization rates by age group were then applied to national age-specific population estimates using 2015 census data.ResultsWe estimated the overall influenza-associated SARI hospitalization rate to be 48/100 000 population (95% confidence interval [CI]: 44–51) or 3097 admissions (95% CI: 2881–3313). SARI hospitalization rates were estimated to be as low as 40/100 000 population (95% CI: 37–43) and as high as 92/100 000 population (95% CI: 87–98) after accounting for SARI patient underascertainment in hospital logbooks. Influenza-associated SARI hospitalization rates were highest in children aged < 5 years (219; 95% CI: 198–241) and persons aged 3 65 years (106; 95% CI: 91–121).DiscussionOur findings have identified age groups at higher risk for influenza-associated SARI hospitalization, which will support policy decisions for influenza prevention and control strategies, including for vaccination. Further work is needed to estimate the burdens of outpatient influenza and influenza in specific high-risk subpopulations.

Effectiveness of Influenza Vaccination in Preventing Hospitalization Due to Influenza in Children: A Systematic Review and Meta-analysis.

This systematic review assesses the literature for estimates of influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalization in children. Studies of any design to June 8, 2020, were included if the outcome was hospitalization, participants were 17 years or younger and influenza infection was laboratory-confirmed. A random-effects meta-analysis of 37 studies that used a test-negative design gave a pooled seasonal IVE against hospitalization of 53.3% (47.2-58.8) for any influenza. IVE was higher against influenza A/H1N1pdm09 (68.7%, 56.9-77.2) and lowest against influenza A/H3N2 (35.8%, 23.4-46.3). Estimates by vaccine type ranged from 44.3% (30.1-55.7) for live-attenuated influenza vaccines to 68.9% (53.6-79.2) for inactivated vaccines. IVE estimates were higher in seasons when the circulating influenza strains were antigenically matched to vaccine strains (59.3%, 48.3-68.0). Influenza vaccination gives moderate overall protection against influenza-associated hospitalization in children supporting annual vaccination. IVE varies by influenza subtype and vaccine type.

Estimating the disease burden of seasonal influenza in China, 2006-2019

Objective: To estimate the health impact and economic burden of seasonal influenza in mainland China. Methods: From systematic literature reviews, we collected the influenza-associated excess influenza-like-illness (ILI) outpatient consultation rates, hospitalization rates of severe acute respiratory infections (SARI) and respiratory excess mortality, 2006-2017. Using these data, as well as demographic data (2019), the number of influenza-associated excess ILI outpatient consultations, SARI hospitalizations and respiratory excess deaths were estimated. Then using per capita economic burden of influenza-associated outpatient consultations and hospitalizations, as well as the productivity loss of influenza-related premature deaths, the annual influenza-associated total economic burden was estimated. All costs were adjusted to 2019 using the consumer price index. Results: The annual influenza-associated excess ILI outpatient consultations, SARI hospitalizations and excess respiratory deaths were 3 million, 2.34 million, 0.09 million, respectively. The total economic burden was 26.38 billion CNY, accounting for 0.266‰ GDP in 2019, of which the hospitalization-related economic burden accounted for the highest proportion (86.4%, 22.79 billion CNY), followed by the outpatient-related economic burden (11.3%, 2.97 billion CNY), and the indirect economic burden of productivity loss of premature deaths was the lowest (2.4%, 0.62 billion CNY). Largest economic burden was observed in East China (10.51 billion CNY) and smallest observed in Northeast China (0.38 billion CNY). Conclusion: The health burden of influenza-related outpatient visits and hospitalizations were substantial. The economic burden of influenza-related SARI hospitalization was higher than that of influenza-related outpatients and pre-mature deaths. The highest economic burden of influenza occurred in the East China.

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

BackgroundInfluenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings.Methods and findingsWe aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996–31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle–Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20–64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%–16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000–46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000–9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000–5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000–44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265–612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources.ConclusionsIn this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Cross-protective potential of a MF59-adjuvanted quadrivalent influenza vaccine in older adults

A decline in humoral and cell-mediated immunity inevitably accompanies the ageing process. The weakened immunity in older people not only makes them more susceptible to natural influenza infections, but also prevents them from developing protective immunity to standard influenza vaccines. 1 McElhaney JE Influenza vaccine responses in older adults. Ageing Res Rev. 2011; 10: 379-388 Crossref PubMed Scopus (121) Google Scholar Besides immunosenescence, this reduced vaccine effectiveness can be associated with immunological responses to repeated vaccination. 2 Sullivan SG Price OH Regan AK Burden, effectiveness and safety of influenza vaccines in elderly, paediatric and pregnant populations. Ther Adv Vaccines Immunother. 2019; 72515135519826481 Crossref Google Scholar Furthermore, the greatest effect of H3N2 influenza on the risk of hospitalisation relative to H1N1 and influenza B strains in the population aged 65 years or older 3 Thompson WW Shay DK Weintraub E et al. Influenza-associated hospitalizations in the United States. JAMA. 2004; 292: 1333-1340 Crossref PubMed Scopus (1733) Google Scholar suggests that a strong anamnestic response to the original infecting strain can be responsible for the disproportionate burden of H3N2 viruses, as this population was born during the era of circulation of H1N1 viruses. 4 Monto AS Malosh RE Petrie JG Martin ET The doctrine of original antigenic sin: separating good from evil. J Infect Dis. 2017; 215: 1782-1788 Crossref PubMed Scopus (68) Google Scholar This vulnerability of adults aged 65 or older underscores the need for effective preventive measures and ongoing efforts to improve the available influenza vaccines for this age group. To date, the most promising approach is to use so-called enhanced influenza vaccines, which either contain a higher dose of the antigen or are formulated with specific adjuvants. A successful example is the MF59 adjuvant that significantly enhanced the immunogenicity of inactivated influenza vaccines in older adults, 5 Gasparini R Pozzi T Montomoli E et al. Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects. Eur J Epidemiol. 2001; 17: 135-140 Crossref PubMed Scopus (97) Google Scholar for whom a switch to a quadrivalent formulation did not affect the overall immunogenicity and safety of the vaccine. 6 Essink B Fierro C Rosen J et al. Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults. Vaccine. 2020; 38: 242-250 Crossref PubMed Scopus (10) Google Scholar However, the question remained regarding to what extent this MF59-adjuvanted quadrivalent influenza vaccine (aQIV) can provide protection for older adults against the disease. Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy studyThe prespecified criterion for showing the efficacy of aQIV in older adults was not met during the influenza seasons with high amounts of vaccine strain mismatch. Vaccine efficacy was higher against influenza cases associated with higher fever, which represent more clinically significant disease. Full-Text PDF

Influenza-associated disease burden in mainland China: a systematic review and meta-analysis

Influenza causes substantial morbidity and mortality. Many original studies have been carried out to estimate disease burden of influenza in mainland China, while the full disease burden has not yet been systematically reviewed. We did a systematic review and meta-analysis to assess the burden of influenza-associated mortality, hospitalization, and outpatient visit in mainland China. We searched 3 English and 4 Chinese databases with studies published from 2005 to 2019. Studies reporting population-based rates of mortality, hospitalization, or outpatient visit attributed to seasonal influenza were included in the analysis. Fixed-effects or random-effects model was used to calculate pooled estimates of influenza-associated mortality depending on the degree of heterogeneity. Meta-regression was applied to explore the sources of heterogeneity. Publication bias was assessed by funnel plots and Egger’s test. We identified 30 studies eligible for inclusion with 17, 8, 5 studies reporting mortality, hospitalization, and outpatient visit associated with influenza, respectively. The pooled influenza-associated all-cause mortality rates were 14.33 and 122.79 per 100,000 persons for all ages and ≥ 65 years age groups, respectively. Studies were highly heterogeneous in aspects of age group, cause of death, statistical model, geographic location, and study period, and these factors could explain 60.14% of the heterogeneity in influenza-associated mortality. No significant publication bias existed in estimates of influenza-associated all-cause mortality. Children aged < 5 years were observed with the highest rates of influenza-associated hospitalizations and ILI outpatient visits. People aged ≥ 65 years and < 5 years contribute mostly to mortality and morbidity burden due to influenza, which calls for targeted vaccination policy for older adults and younger children in mainland China.