Global Burden Of Influenza-Associated Lower Respiratory Tract Infections And Hospitalizations Among Adults: A Systematic Review And Meta-Analysis

Author summaryWhy was this study done?Every year, millions of people become infected with influenza viruses, which infect the airways and cause symptoms that include a fever, tiredness and weakness, general aches and pains, sore throat, and cough.Most infected individuals recover quickly, but some develop more severe illness such as pneumonia, and may require hospitalization.Influenza vaccination can prevent infections and severe disease, but decisions on how to prioritize risk groups, particularly in limited-resource settings, require a robust evidence base, including global, regional, and local data.What did the researchers do and find?We conducted a systematic review to identify published articles on influenza-associated respiratory disease in hospitalized adults.We then aggregated the data from these articles with data collected by hospital-based influenza surveillance, to calculate a pooled estimate of the proportion of adults hospitalized with respiratory disease who are positive for influenza.Through this approach, we estimated that influenza was associated with 14% of acute respiratory hospitalizations among adults worldwide.This equates to over 5 million influenza-associated hospitalizations per year, with the highest rates among those 65 years and older.What do these findings mean?Estimating the disease burden of influenza allows researchers and policymakers to better understand its global impact across different target groups and allows comparisons with other causes of morbidity and mortality.As global populations age, the importance of vaccinating adults, particularly older adults, is likely to increase.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particularly in lower-income settings.Methods and findingsWe aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza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.