Epidemiology of influenza
- Raphael Dolin, MD
Raphael Dolin, MD
- Professor of Medicine
- Harvard Medical School
Influenza occurs in distinct outbreaks of varying extent every year. This epidemiologic pattern reflects the changing nature of the antigenic properties of influenza viruses, and their subsequent spread depends upon multiple factors, including transmissibility of the virus and the susceptibility of the population. Influenza A viruses, in particular, have a remarkable ability to undergo periodic changes in the antigenic characteristics of their envelope glycoproteins, the hemagglutinin and the neuraminidase.
Influenza hemagglutinin is a surface glycoprotein that binds to sialic acid residues on respiratory epithelial cell surface glycoproteins. This interaction is necessary for the initiation of infection. After viral replication, progeny virions are also bound to the host cell. Neuraminidase cleaves these links and liberates the new virions; it also counteracts hemagglutinin-mediated self-aggregation entrapment in respiratory secretions.
Among influenza A viruses that infect humans, three major subtypes of hemagglutinins (H1, H2, and H3) and two subtypes of neuraminidases (N1 and N2) have been described. Influenza B viruses have a lesser propensity for antigenic changes, and only antigenic drifts in the hemagglutinin have been described.
The epidemiology of influenza, including morbidity and mortality, will be reviewed here. The clinical manifestations, complications, diagnosis, prevention, and treatment of this infection are discussed separately; the epidemiology of pandemic H1N1 influenza ("swine influenza") and avian influenza are also presented elsewhere. (See "Clinical manifestations of seasonal influenza in adults" and "Seasonal influenza in children: Prevention and treatment with antiviral drugs" and "Seasonal influenza vaccination in adults" and "Diagnosis of seasonal influenza in adults" and "Treatment of seasonal influenza in adults" and "Prevention of seasonal influenza with antiviral drugs in adults" and "Epidemiology of pandemic H1N1 influenza ('swine influenza')" and "Epidemiology, transmission, and pathogenesis of avian influenza" and "Avian influenza A H7N9: Epidemiology, clinical manifestations, and diagnosis".)
DEFINITION OF ANTIGENIC SHIFTS AND DRIFTS
Major changes in the envelope glycoproteins, the hemagglutinin and the neuraminidase, are referred to as antigenic shifts, and minor changes are called antigenic drifts. Antigenic shifts are associated with epidemics and pandemics of influenza A, whereas antigenic drifts are associated with more localized outbreaks of varying extent.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Dolin R. Influenza. In: Harrison's Principles of Internal Medicine, 17, Braunwald E, Fauci AS, Kasper DL, et al (Eds), McGraw Hill, New York 2008. p.1127.
- Webster RG, Wright SM, Castrucci MR, et al. Influenza--a model of an emerging virus disease. Intervirology 1993; 35:16.
- Ellis JS, Alvarez-Aguero A, Gregory V, et al. Influenza AH1N2 viruses, United Kingdom, 2001-02 influenza season. Emerg Infect Dis 2003; 9:304.
- Paget WJ, Meerhoff TJ, Goddard NL, EISS. Mild to moderate influenza activity in Europe and the detection of novel A(H1N2) and B viruses during the winter of 2001-02. Euro Surveill 2002; 7:147.
- Xu X, Smith CB, Mungall BA, et al. Intercontinental circulation of human influenza A(H1N2) reassortant viruses during the 2001-2002 influenza season. J Infect Dis 2002; 186:1490.
- Morens DM, Taubenberger JK, Folkers GK, Fauci AS. Pandemic influenza's 500th anniversary. Clin Infect Dis 2010; 51:1442.
- Taubenberger JK, Reid AH, Krafft AE, et al. Initial genetic characterization of the 1918 "Spanish" influenza virus. Science 1997; 275:1793.
- Masurel N, Marine WM. Recycling of Asian and Hong Kong influenza A virus hemagglutinins in man. Am J Epidemiol 1973; 97:44.
- Kendal AP, Schieble J, Cooney MK, et al. Co-circulation of two influenza A (H3N2) antigenic variants detected by virus surveillance in individual communities. Am J Epidemiol 1978; 108:308.
- Centers for Disease Control and Prevention (CDC). Update: Influenza A (H3N2)v transmission and guidelines - five states, 2011. MMWR Morb Mortal Wkly Rep 2012; 60:1741.
- Centers for Disease Control and Prevention (CDC). Notes from the field: Outbreak of influenza A (H3N2) virus among persons and swine at a county fair--Indiana, July 2012. MMWR Morb Mortal Wkly Rep 2012; 61:561.
- Centers for Disease Control and Prevention. First H3N2 variant virus infection reported for 2012. http://www.cdc.gov/flu/spotlights/h3n2v-variant-utah.htm (Accessed on August 10, 2012).
- Centers for Disease Control and Prevention (CDC). CDC Health Advisory. Variant influenza virus (H3N2v) infections. http://emergency.cdc.gov/HAN/han00351.asp (Accessed on August 17, 2016).
- Finelli L, Swerdlow DL. The emergence of influenza A (H3N2)v virus: what we learned from the first wave. Clin Infect Dis 2013; 57 Suppl 1:S1.
- Epperson S, Jhung M, Richards S, et al. Human infections with influenza A(H3N2) variant virus in the United States, 2011-2012. Clin Infect Dis 2013; 57 Suppl 1:S4.
- Jhung MA, Epperson S, Biggerstaff M, et al. Outbreak of variant influenza A(H3N2) virus in the United States. Clin Infect Dis 2013; 57:1703.
- Schicker RS, Rossow J, Eckel S, et al. Outbreak of Influenza A(H3N2) Variant Virus Infections Among Persons Attending Agricultural Fairs Housing Infected Swine - Michigan and Ohio, July-August 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1157.
- Centers for Disease Control and Prevention. Weekly US influenza surveillance report. 2016-2017 Influenza season week 29 ending July 22, 2017. https://www.cdc.gov/flu/weekly/ (Accessed on July 28, 2017).
- Centers for Disease Control and Prevention. Information on influenza A (H3N2) variant viruses (“H3N2v”). http://www.cdc.gov/flu/swineflu/influenza-variant-viruses-h3n2v.htm#table (Accessed on August 20, 2012).
- Greenbaum A, Quinn C, Bailer J, et al. Investigation of an Outbreak of Variant Influenza A(H3N2) Virus Infection Associated With an Agricultural Fair-Ohio, August 2012. J Infect Dis 2015; 212:1592.
- Skowronski DM, Janjua NZ, De Serres G, et al. Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v). J Infect Dis 2012; 206:1852.
- Webster RG, Kendal AP, Gerhard W. Analysis of antigenic drift in recently isolated influenza A (H1N1) viruses using monoclonal antibody preparations. Virology 1979; 96:258.
- Johnson NP, Mueller J. Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic. Bull Hist Med 2002; 76:105.
- Morens DM, Fauci AS. The 1918 influenza pandemic: insights for the 21st century. J Infect Dis 2007; 195:1018.
- Kobasa D, Takada A, Shinya K, et al. Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature 2004; 431:703.
- Hoft DF, Belshe RB. The genetic archaeology of influenza. N Engl J Med 2004; 351:2550.
- Tumpey TM, Basler CF, Aguilar PV, et al. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005; 310:77.
- Taubenberger JK, Reid AH, Lourens RM, et al. Characterization of the 1918 influenza virus polymerase genes. Nature 2005; 437:889.
- Bresee J, Hayden FG. Epidemic influenza--responding to the expected but unpredictable. N Engl J Med 2013; 368:589.
- US Centers for Disease Control and Prevention. Seasonal Influenza (Flu) - Flu View. http://www.cdc.gov/flu/weekly/ (Accessed on April 05, 2011).
- Su WJ, Shao PL, Liu MT, et al. Low seroprotection against preseasonal influenza local strains in children might predict the upcoming epidemic influenza strains. Clin Infect Dis 2010; 51:171.
- Moura FE. Influenza in the tropics. Curr Opin Infect Dis 2010; 23:415.
- Azziz Baumgartner E, Dao CN, Nasreen S, et al. Seasonality, timing, and climate drivers of influenza activity worldwide. J Infect Dis 2012; 206:838.
- Brownstein JS, Wolfe CJ, Mandl KD. Empirical evidence for the effect of airline travel on inter-regional influenza spread in the United States. PLoS Med 2006; 3:e401.
- Glezen WP, Couch RB. Interpandemic influenza in the Houston area, 1974-76. N Engl J Med 1978; 298:587.
- Monto AS, Kioumehr F. The Tecumseh Study of Respiratory Illness. IX. Occurence of influenza in the community, 1966--1971. Am J Epidemiol 1975; 102:553.
- Huang SS, Banner D, Fang Y, et al. Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets. PLoS One 2011; 6:e27512.
- Su S, Chaves SS, Perez A, et al. Comparing clinical characteristics between hospitalized adults with laboratory-confirmed influenza A and B virus infection. Clin Infect Dis 2014; 59:252.
- Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004; 292:1333.
- Dao CN, Kamimoto L, Nowell M, et al. Adult hospitalizations for laboratory-positive influenza during the 2005-2006 through 2007-2008 seasons in the United States. J Infect Dis 2010; 202:881.
- Zhou H, Thompson WW, Viboud CG, et al. Hospitalizations associated with influenza and respiratory syncytial virus in the United States, 1993-2008. Clin Infect Dis 2012; 54:1427.
- Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep 2010; 59:1057.
- Chaves SS, Aragon D, Bennett N, et al. Patients hospitalized with laboratory-confirmed influenza during the 2010-2011 influenza season: exploring disease severity by virus type and subtype. J Infect Dis 2013; 208:1305.
- Reed C, Chaves SS, Perez A, et al. Complications among adults hospitalized with influenza: a comparison of seasonal influenza and the 2009 H1N1 pandemic. Clin Infect Dis 2014; 59:166.
- Yu X, Tsibane T, McGraw PA, et al. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 2008; 455:532.
- Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis 2006; 42:518.
- Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289:179.
- Fry AM, Shay DK, Holman RC, et al. Trends in hospitalizations for pneumonia among persons aged 65 years or older in the United States, 1988-2002. JAMA 2005; 294:2712.
- Cohen C, Simonsen L, Kang JW, et al. Elevated influenza-related excess mortality in South African elderly individuals, 1998-2005. Clin Infect Dis 2010; 51:1362.
- van Asten L, van den Wijngaard C, van Pelt W, et al. Mortality attributable to 9 common infections: significant effect of influenza A, respiratory syncytial virus, influenza B, norovirus, and parainfluenza in elderly persons. J Infect Dis 2012; 206:628.
- Wu P, Goldstein E, Ho LM, et al. Excess mortality associated with influenza A and B virus in Hong Kong, 1998-2009. J Infect Dis 2012; 206:1862.
- Neuzil KM, Reed GW, Mitchel EF Jr, Griffin MR. Influenza-associated morbidity and mortality in young and middle-aged women. JAMA 1999; 281:901.
- Nichol KL, Nordin J, Mullooly J, et al. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med 2003; 348:1322.
- Simonsen L, Clarke MJ, Schonberger LB, et al. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis 1998; 178:53.
- Taubenberger JK, Morens DM. 1918 Influenza: the mother of all pandemics. Emerg Infect Dis 2006; 12:15.
- Viboud C, Grais RF, Lafont BA, et al. Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a smoldering pandemic. J Infect Dis 2005; 192:233.
- Brundage JF, Shanks GD. Deaths from bacterial pneumonia during 1918-19 influenza pandemic. Emerg Infect Dis 2008; 14:1193.
- Sheng ZM, Chertow DS, Ambroggio X, et al. Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak. Proc Natl Acad Sci U S A 2011; 108:16416.
- DEFINITION OF ANTIGENIC SHIFTS AND DRIFTS
- ANTIGENIC SHIFTS
- Pandemic of 1918
- Other pandemics
- H3N2 variant influenza
- Avian H7N9 influenza
- ANTIGENIC DRIFTS
- CHARACTERISTICS OF INFLUENZA OUTBREAKS
- Time course of an outbreak
- Factors determining the severity of an outbreak
- ANTIBODY RESPONSE TO THE 1918 PANDEMIC STRAIN
- MORBIDITY AND MORTALITY IN ADULTS
- Mortality during influenza pandemics
- RISK FACTORS FOR COMPLICATIONS
- INFLUENZA ACTIVITY
- INFORMATION FOR PATIENTS