Journal Article Meta-Analysis Systematic Review Epublish 175 citations
PubMed: 33647033 DOI: 10.1371/journal.pmed.1003550
Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.
PLoS Med 18(3):e1003550
Authors: Kathryn E Lafond, Rachael M Porter, Melissa J Whaley, Zhou Suizan, Zhang Ran, Mohammad Abdul Aleem, Binay Thapa, Borann Sar, Viviana Sotomayor Proschle, Zhibin Peng, Luzhao Feng, Daouda Coulibaly, Edith Nkwembe, Alfredo Olmedo, William Ampofo, Siddhartha Saha, Mandeep Chadha, Amalya Mangiri, Vivi Setiawaty, Sami Sheikh Ali, Sandra S Chaves, Dinagul Otorbaeva, Onechanh Keosavanh, Majd Saleh, Antonia Ho, Burmaa Alexander, Hicham Oumzil, Kedar Prasad Baral, Q Sue Huang, Adedeji A Adebayo, Idris Al-Abaidani, Marta von Horoch, Cheryl Cohen, Stefano Tempia, Vida Mmbaga, Malinee Chittaganpitch, Mariana Casal, Duc Anh Dang, Paula Couto, Harish Nair, Joseph S Bresee, Sonja J Olsen, Eduardo Azziz-Baumgartner, J Pekka Nuorti, Marc-Alain Widdowson
Affiliations
- Influenza Division, US Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
- Health Sciences Unit, Faculty of Social Sciences, Tampere University, Tampere, Finland.
- US Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
- Influenza Division, US Centers for Disease Control and Prevention, Beijing, China.
- Program for Emerging Infections, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
- Royal Centre for Disease Control, Thimphu, Bhutan.
- Centers for Disease Control and Prevention, Phnom Penh, Cambodia.
- Department of Epidemiology, Ministerio de Salud, Santiago, Chile.
- Division of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China.
- School of Population Medicine & Public Health, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
- Institut National d'Hygiène Publique, Abidjan, Côte d'Ivoire.
- Institut National de Recherches Biomédicales, Kinshasa, République Démocratique du Congo.
- Ministerio de Salud, Quito, Ecuador.
- Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
- Influenza Division, US Centers for Disease Control and Prevention, New Delhi, India.
- National Institute of Virology, Pune, India.
- US Centers for Disease Control and Prevention, Jakarta, Indonesia.
- National Institute of Health Research and Development, Jakarta, Indonesia.
- Ministry of Health, Amman, Jordan.
- Influenza Division, US Centers for Disease Control and Prevention, Nairobi, Kenya.
- Department of State Sanitary Epidemiological Surveillance, Bishkek, Kyrgyzstan.
- National Center for Laboratory and Epidemiology, Vientiane, Lao People's Democratic Republic.
- Epidemiological Surveillance Program, Lebanese Ministry of Public Health, Beirut, Lebanon.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
- National Centre for Communicable Disease, Ulaanbaatar, Mongolia.
- Virology Department, Institut National d'Hygiène, Rabat, Morocco.
- Faculty of Medicine, Microbiology RPU, Mohammed V University, Rabat, Morocco.
- Patan Academy of Health Sciences, Lalitpur, Nepal.
- WHO National Influenza Centre, Institute of Environmental Science and Research, Wellington, New Zealand.
- Nigeria Centre for Disease Control, Federal Ministry of Health, Abuja, Nigeria.
- Directorate General of Disease Surveillance and Control, Ministry of Health, Muscat, Oman.
- Ministerio de Salud Publica y Bienestar Social, Asunción, Paraguay.
- National Institute for Communicable Diseases, Johannesburg, South Africa.
- MassGenics, Duluth, Georgia, United States of America.
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Ministry of Health, Dar es Salaam, Tanzania.
- National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
- Arizona Department of Health Services, Phoenix, Arizona, United States of America.
- National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
- Pan American Health Organization, Washington, District of Columbia, United States of America.
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.
- Finnish Institute for Health and Welfare, Helsinki, Finland.
- Division of Global Health Protection, US Centers for Disease Control and Prevention, Nairobi, Kenya.
- Institute of Tropical Medicine, Antwerp, Belgium.
Abstract
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.
MeSH
Hospitalization, Income, Respiratory Tract Infections, Influenza, Human, Viruses, Cost Of Illness, Orthomyxoviridae, Infections
Cited by
- Immune memory shapes human polyclonal antibody responses to H2N2 vaccination. bioRxiv, 2023
- Vaccine or Garlic-Is It a Choice? Awareness of Medical Personnel on Prevention of Influenza Infections. Vaccines (Basel), 2023
- A comparative analysis of influenza and COVID-19: Environmental-ecological impacts, socioeconomic implications, and future challenges. Biosaf Health, 2025
- Bivalent vaccines effectively protect mice against influenza A and respiratory syncytial viruses. Emerg Microbes Infect, 2023
- Incidence of Human Metapneumovirus Among Older Adults in 10 High-Income Countries: A Systematic Literature Review, Meta-analysis, and Modeling Study. Open Forum Infect Dis, 2025
- Influenza A virus NS1 protein represses antiviral immune response by hijacking NF-κB to mediate transcription of type III IFN. Front Cell Infect Microbiol, 2022
- Inference of age-dependent case-fatality ratios for seasonal influenza virus subtypes A(H3N2) and A(H1N1)pdm09 and B lineages using data from the Netherlands. Influenza Other Respir Viruses, 2023
- Myeloid Protease-Activated Receptor-2 Contributes to Influenza A Virus Pathology in Mice. Front Immunol, 2022
- Therapeutic Trends of Cerebrovascular Disease during the COVID-19 Pandemic and Future Perspectives. J Stroke, 2022
- A Randomized Trial of Behavioral Nudges Delivered Through Text Messages to Increase Influenza Vaccination Among Patients With an Upcoming Primary Care Visit. Am J Health Promot, 2023
- Influenza. Lancet, 2022
- LAG-3 Contribution to T Cell Downmodulation during Acute Respiratory Viral Infections. Viruses, 2023
- A single dose of inactivated influenza virus vaccine expressing COBRA hemagglutinin elicits broadly-reactive and long-lasting protection. PLoS One, 2025
- COVID-19 pandemic interventions reshaped the global dispersal of seasonal influenza viruses. Science, 2024
- Influenza Induces Lung Lymphangiogenesis Independent of YAP/TAZ Activity in Lymphatic Endothelial Cells. Res Sq, 2024
- Genetic variants in BAT2 are associated with immune responsiveness to influenza vaccination. Front Genet, 2023
- Viral cardiovascular surgical diseases: global burdens, challenges and opportunities. Future Cardiol, 2024
- A semi-empirical risk panel to monitor epidemics: multi-faceted tool to assist healthcare and public health professionals. Front Public Health, 2024
- Interferons-Implications in the Immune Response to Respiratory Viruses. Microorganisms, 2023
- Safety and Immunogenicity of OVX836, a Nucleoprotein-Based Universal Influenza Vaccine, Co-Administered with Fluarix ® Tetra, a Seasonal Hemagglutinin-Based Vaccine. Vaccines (Basel), 2025