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

BACKGROUND : Influenza 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 METHODS AND FINDINGS : We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza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 The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast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. CONCLUSIONS : In 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.S1 Data. CSV-formatted analysis dataset.S1 Fig. Forest plot of individual study estimates included in meta-analysis (all adults).S1 PRISMA Checklist. PRISMA checklist.S1 Table. Literature search methodology and results, by database.S2 Table. Summary of published articles included in the analyses, with reference list.S3 Table. Median number of specimens tested and percent positive for influenza, by age group, study design, and population, among all data sources.S4 Table. Regional estimates of influenza-associated lower respiratory infection (LRI) episodes and hospitalizations, by age group.S5 Table. Sensitivity analyses.Grants from the Foundation for Influenza Epidemiology, grants from Innovative Medicines Initiative, grants from the WHO, personal fees from Bill and Melinda Gates Foundation, grants and personal fees from Sanofi, grants from National Institute of Health Research, personal fees from Janssen and personal fees from AbbVie.https://journals.plos.org/plosmedicine/am2023Medical Virolog

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

Background: Influenza 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 findings: We 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 &lt;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. Conclusions: In 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

Dose effect of influenza vaccine on protection against laboratory-confirmed influenza illness among children aged 6 months to 8 years of age in southern China, 2013/14–2015/16 seasons: a matched case–control study

Background We conducted a matched case–control study in China during the 2013/14–2015/16 influenza seasons to estimate influenza vaccine effectiveness (VE) by dose among children aged 6 months to 8 years. Methods Cases were laboratory-confirmed influenza infections identified through the influenza-like illness sentinel surveillance network in Guangzhou. Age- and sex-matched community controls were randomly selected through the expanded immunization program database. We defined priming as receipt of ≥1 dose of influenza vaccine during the immediate prior season. Results In total, 4,185 case–control pairs were analyzed. Among children 6–35 months, VE for current season dose(s) across the three seasons during 2013/14–2015/16 were 59% (95% Confidence Interval: 44–71%), 12% (−11%,30%), 54% (32–69%); among unprimed children 6–35 months, VE for 1 vs 2 current season doses were 45% (8–67%) vs 65% (46–78%), −2% (−53%,32%) vs 19% (−11%,40%), and 37% (−24%,68%) vs 61% (32–78%). Among children aged 3–8 years, VE for current season dose(s) across study seasons were 62% (36–78%), 43% (22–58%), 32% (1–53%). VE for unprimed children receiving 1 dose only in current season was insignificant or lower than among all children. Conclusion Findings support utility of providing second dose (“booster dose”) of seasonal influenza vaccine to unprimed children aged 6–35 months, and the need to study further dose effect of a booster dose among unprimed children aged 3–8 years in China

Review of the status and challenges associated with increasing influenza vaccination coverage among pregnant women in China

Influenza vaccination coverage in pregnant women in China remains low. In this review, we first provide an overview of the evidence for the use of influenza vaccination during pregnancy. Second, we discuss influenza vaccination policy and barriers to increased seasonal influenza vaccination coverage in pregnant women in China. Third, we provide case studies of successes and challenges of programs for increasing seasonal influenza vaccination in pregnant women from other parts of Asia with lessons learned for China. Finally, we assess opportunities and challenges for increasing influenza vaccination coverage among pregnant women in China

Potential impact of B lineage mismatch on trivalent influenza vaccine effectiveness during the 2015–2016 influenza season among nursery school children in Suzhou, China

Background: We actively followed a cohort of nursery school children in Suzhou, China to assess the impact of vaccination with trivalent influenza vaccine on the prevention of influenza like illness (ILI). Methods: We enrolled children aged 36 to 72 months from 13 nursery schools in Suzhou starting two weeks after vaccination during October 2015-February 2016. Every school-day, teachers reported the names of students with ILI to study clinicians, who collected the student's nasopharyngeal swab or throat swab, either at a study clinic or the child's home. Swabs were sent to the Suzhou Center for Disease Control and Prevention's laboratory for influenza testing by RT-PCR. Results: In total, 3278 children were enrolled; 83 (3%) were lost to follow-up, while 3195 (vaccinated: 1492, unvaccinated: 1703) were followed for 24 weeks. During the study, 40 samples tested positive; 17 in the vaccinated (B Victoria: 12; A(H1N1)pdm09: 5) and 23 in the unvaccinated group (B Victoria: 10; B Yamagata: 2; A(H1N1)pdm09: 11). The VE estimates were: 16% overall (95%CI:-58%,56%), 48% (−47%,84%) for influenza A(H1N1)pdm09, 43% (−650%,98%) for influenza B Yamagata, and −37% (−227%,42%) for influenza B Victoria. Data were analyzed by vaccinated and unvaccinated groups based on enrollees' vaccination records. Conclusions: The VE for A(H1N1)pdm09 was moderate but not significant. Mismatching of B lineage may have compromised trivalent influenza vaccine effectiveness during the 2015–2016 influenza season among nursery school children in Suzhou, China. Additional larger studies are warranted to inform policy related to quadrivalent influenza vaccine licensure in China in the future

Innovations in adult influenza vaccination in China, 2014–2015: Leveraging a chronic disease management system in a community-based intervention

Objectives: To evaluate a community-based intervention that leveraged the non-communicable disease management system to increase seasonal influenza vaccination coverage among older adults in Ningbo, China. Methods: From October 2014 – March 2015, we piloted the following on one street in Ningbo, China: educating community healthcare workers (C-HCWs) about influenza and vaccination; requiring C-HCWs to recommend influenza vaccination to older adults during routine chronic disease follow-up; and opening 14 additional temporary vaccination clinics. We selected a non-intervention street for comparison pre- and post-intervention vaccine coverage. In April 2016, we interviewed a random sample of unvaccinated older adults on the intervention street to ask why they remained unvaccinated. Results: Pre-intervention influenza vaccine coverage among adults aged 60 years and older on both streets was 0.3%. Post-intervention, coverage among adults 60 years and older was 19% (1338/7013) on the intervention street and 0.4% (20/5500) on the non-intervention street (p<0.01). Among vaccinated older adults, 98% reported their main reason for vaccination was receiving a C-HCW's recommendation, 90% were vaccinated at temporary vaccination clinics, and 53% paid for vaccine (10 USD) out-of-pocket. Reasons for not getting vaccinated among 150 unvaccinated adults (response rate = 75%) included: good health (39%); not trusting C-HCWs' recommendations (24%); not knowing where to get vaccinated (17%); and not wanting to pay (9%). Conclusions: Recommending influenza vaccination within a non-communicable disease management system, combined with adding vaccination sites, increased vaccine coverage among older adults in Ningbo, China

A ten-year China-US laboratory collaboration: improving response to influenza threats in China and the world, 2004–2014

Abstract The emergence of severe acute respiratory syndrome (SARS) underscored the importance of influenza detection and response in China. From 2004, the Chinese National Influenza Center (CNIC) and the United States Centers for Disease Control and Prevention (USCDC) initiated Cooperative Agreements to build capacity in influenza surveillance in China. From 2004 to 2014, CNIC and USCDC collaborated on the following activities: 1) developing human technical expertise in virology and epidemiology in China; 2) developing a comprehensive influenza surveillance system by enhancing influenza-like illness (ILI) reporting and virological characterization; 3) strengthening analysis, utilization and dissemination of surveillance data; and 4) improving early response to influenza viruses with pandemic potential. Since 2004, CNIC expanded its national influenza surveillance and response system which, as of 2014, included 408 laboratories and 554 sentinel hospitals. With support from USCDC, more than 2500 public health staff from China received virology and epidemiology training, enabling > 98% network laboratories to establish virus isolation and/or nucleic acid detection techniques. CNIC established viral drug resistance surveillance and platforms for gene sequencing, reverse genetics, serologic detection, and vaccine strains development. CNIC also built a bioinformatics platform to strengthen data analysis and utilization, publishing weekly on-line influenza surveillance reports in English and Chinese. The surveillance system collects 200,000–400,000 specimens and tests more than 20,000 influenza viruses annually, which provides valuable information for World Health Organization (WHO) influenza vaccine strain recommendations. In 2010, CNIC became the sixth WHO Collaborating Centre for Influenza. CNIC has strengthened virus and data sharing, and has provided training and reagents for other countries to improve global capacity for influenza control and prevention. The collaboration’s successes were built upon shared mission and values, emphasis on long-term capacity development and sustainability, and leadership commitment

Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017

We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients

Enhanced environmental surveillance for avian influenza A/H5, H7 and H9 viruses in Guangxi, China, 2017–2019

We conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 2017–2018 and 2018–2019, we collected environmental samples from 14 LPMs, 4 poultry farms, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% − 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology