A Perspective of Influenza Pandemics


The dates of global influenza pandemics are well known as 1848, 1889, 1918, 1957, 1968 and 2009. Less well explored are the so‐called pseudopandemics of 1976 and 1977. Each of these pandemics uncovered a uniqueness either of the virus, the infection, the longevity of human protective immune memory or the scientific and community response. Thus, persons born before 1848 had long‐term immunity from a presumed infection with an H1N1 virus to protect them in 1918. Similarly, older persons were protected from the 2009 H1N1 pandemic because they had immunity from a variant of the (H1N1) virus circulating in the 1950s.

Three of these pandemics had geographically different origins: the 1889 pandemic started in Russia, the 1918 outbreak possibly in France and the 2009 pandemic in Mexico. Little is known about the origin of the 1848 pandemic. These geographical observations do not perturb the published genetic analysis, which suggests Asian origins of both epidemic and pandemic viruses.

Extra research is now directed towards Universal Influenza Vaccines, host proteins as targets for new inhibitory drugs and simple but possibly effective interventions using hygiene, cough etiquette and social distancing.

Against all predictions we are still unable to deduce from total virus genome sequencing whether a newly emerged influenza virus will be extra virulent and indeed be able to spread from person to person. However, recent laboratory experiments have identified as few as four mutations of bird flu (H5N1), which potentially allow spread amongst animals and we can deduce and calculate that such mutants, at least with H5N1 virus, already exist in nature.

It would be wise to revisit pandemic plans immediately and at the same time to increase surveillance at the interface between birds, pigs and humans where too few viruses are analysed. The World Health Organization has published new guidance and plannings.

In the author's opinion it is quite possible that the next pandemic could arise as early as 2018, the anniversary of the Great Spanish Pandemic of 1918 and it would be sensible to have such a date as a target for completeness of pandemic plans.

Key Concepts:

  • The scientific community is continually revisiting the 1918 pandemic to estimate mortality (now revised upwards and approaching 100 million) and also the genetic determinants of virulence. The extensive postmortem lung samples of 1918 patients in pathology museums in the USA and England, exceeding those of all subsequent pandemics are important for this research.

  • As with the 1918 pandemic, the global mortality figures of the influenza A (H1N1) pdm09 pandemic have been reestimated upwards from approximately 18 000–575 500.

  • New studies of bird influenza (H5N1) show that only four mutations could allow this avian pathogen to spread between mammals and hence by deduction to evolve into a significant human pathogen.

  • Pandemics can start anywhere in the world, although generation of genetic diversity is highest in the tropical regions of the world. Such viruses move in travelling individuals, mainly by aeroplane to the two ‘sinks’ of the Northern and Southern Hemisphere.

  • Spread of old and new pandemic viruses in the community is governed by Darwin's evolutionary theory of ‘Survival of the Fittest’ whereby ‘new’ viruses, to which no person has immunity, have the greatest potential to spread.

  • The lung pathology of victims is remarkably similar in pandemics of 1918, 1957, 1968 and 2009. In each pandemic there was a high incidence of coinfections with bacteria.

  • Preparation for the next pandemic, including stockpiling of antibiotics, antivirals, pneumococcus vaccines and influenza vaccines to influenza A (H5N1), (H2N2) and (H7N9) is underway.

  • Pandemic plans need to be updated continually and to have flexibility to cope with virus virulence ranging from mild to severe. Such plans in large corporations, for example, are being tested in the USA at the present time. WHO has recently issued a new guidance for countries ‘pandemic influenza risk management’.

  • A new generation of universal influenza vaccines, broad spectrum antivirals and rapid molecular diagnostics will assist during a new pandemic.

  • Pandemic virus surveillance at the interface between birds, animals and humans is extremely sparse globally given that domestic chickens outnumber humans by three to one. There needs to be a huge expansion in this important endeavour.

  • The proper use of hand hygiene, cough etiquette and personal social distancing has been a focus of recent attention.

Keywords: influenza; virulence; pandemic; epidemic; vaccines; Tamiflu; disinfectants; social distancing; Spanish influenza; masks; pandemic planning; pathology


Abrahams A , Hallow N and French H (1919) A further investigation into influenza pneumococcal and influenza‐streptococcal septicaemia and epidemic influenzal pneumonia of highly fatal type and its relation to purulent bronchitis. Lancet 1: 1–9.

Abrahams A , Hallow NF , Eyre JWH et al. (1917) Purulent bronchitis, its influenza and pneumococcal bacteriology. Lancet 2: 377–380.

Arguedos A , Soley C and Lindert K (2013) Responses to 2009 H1N1 vaccine in children 3 to 17 years of age. New England Journal of Medicine 362: 370–372.

Barry JM (2004) The Great Influenza. USA: Viking. p. 534.

Butler D (2012) Flu surveillance lacking. Nature 483: 520.

Chan PKS , Lee N , Zaman M et al. (2012) Determinants of antiviral effectiveness in influenza virus A subtype H5N1. Journal of Infectious Diseases 206: 1359–1366.

Chertow DS and Memoli MJ (2013) Bacterial co‐infection in influenza: A grand rounds review. Journal of the American Medical Association 309(3): 275–282.

Collier L , Kellam P and Oxford JS (2011) Human Virology, 4th edn. Oxford: Oxford University Press.

Cowling BJ , Chan KH , Fang VJ et al. (2009) Facemasks and hand hygiene to prevent influenza transmission in households. Annals of Internal Medicine 151: 437–446.

Cowling BJ , Jin L , Lau EHY et al. (2013) Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population‐based study of laboratory‐confirmed cases. Lancet 13: 61171.

Crosby AW (1989) Forgotten Pandemic: The Influenza of 1918. Cambridge: Cambridge University Press.

Davies J (2009) Swine flu vaccines: reaching the finish line. Cell 139: 449–451.

Davis JL , Heginbottom JA , Annan AP et al. (2000) Ground penetrating radar surveys to locate 1918 Spanish flu victims in permafrost. Journal of Forensic Science 20: 68–76.

Dawood FS , Iuliano D , Reed C et al. (2012) Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infectious Diseases 12: S1473–S3099.

Dowdle WR (1997) The 1976 experience. Journal of Infectious Diseases: 176(suppl. 1): S69–S72.

Downie JC and Laver WG (1973) Isolation of type A influenza virus from an Australian pelagic bird. Virology 51: 259.

Dunn FL (1958) Pandemic influenza in 1957: a review of international spread of a new Asian strain. Journal of the American Medical Association 166: 1140–1148.

Everitt A , Clare S , Pertel T et al. (2012) IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484: 519–525.

Fouchier RA , Schneeberger PM , Rozendaal FW et al. (2004) Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proceedings of the National Academy of Sciences of the USA 101: 1356–1361.

Galbraith A and Oxford JS (1984) The anti influenza virus activity of amantadine. Viral Chemotherapy 1: 169–252.

Garcia‐Sastre A (2012) The neuraminidase of bat influenza viruses is not a neuraminidase. Proceedings of the National Academy of Sciences of the USA 46: 18635–18636.

Gibson GH and Bowman FB (1919) The etiology of influenza: a filterable virus as the cause with some notes on the culture of the virus by the method of Noguchi. Medical Research Council studies of influenza in hospitals of the British Armies in France 1918, London HMSO.

Gill D and Putkowski J (1995) The British Base Camp at Etaples 1914–1918. p. 80. Etaples: Musée Quentovic.

Greaves K , Oxford JS , Price CP et al. (2003) The prevalence of myocarditis and skeletal muscle injury during acute viral infection in adults: measurement of cardiac troponins I and T in 152 patients with acute influenza infection. Archives of Internal Medicine 163(2): 165–168.

Hammond JAR , Rolland W and Shore THG (1917) Purulent bronchitis a study of cases occurring amongst the British troops at a base in France. Lancet 2: 41–45.

Herfst S , Schrauwen EJ , Linster M et al. (2012) Airborne transmission of influenza A/H5N1 virus between ferrets. Science 337: 1534–1541.

Huang Y , Zaas AK , Rao A et al. (2012) Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza A infection. PLoS Genetics 7: e1002234.

Imai M , Watanabe T , Hatta M et al. (2012) Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486: 420–428.

Itoh Y , Shinya K , Kiso M et al. (2009) In vitro and in vivo characterisation of new Swine origin H1N1 influenza viruses. Nature 460: 1021–1025.

Kilbourne ED (1975) The Influenza Viruses and Influenza, p. 309. London: Academic Press.

Killingley B , Enstone J , Booy R et al. (2011) Potential role of human challenge studies for investigation of influenza transmission. Lancet Infectious Diseases 11(11): 879–886.

Langford C (2002) The age pattern of mortality in the 1918–1919 influenza pandemic: an attempted explanation based on data for England and Wales. Medical History 46: 1–20.

Laver G (2002) Influenza virus surface glycoproteins, haemagglutinin and neuraminidase: a personal account. In: Potter CW (ed.) Influenza, pp. 33–47. Amsterdam: Elsevier.

Laver WG and Webster RG (1979) Ecology of influenza virus in animals and birds. British Medical Bulletin 35: 29.

Leneva R , Russell Y , Boriskin Y et al. (2009) Characteristics of arbidol‐resistant mutants of influenza virus: implications for the mechanism of anti‐influenza action of arbidol. Antiviral Research 81: 132–140.

Lvov DK , Zhdanov VM , Sazonov AA et al. (1978) Comparison of influenza viruses isolated from man and from whales. Bulletin of the World Health Organisation 56(6): 923–930.

MacIntyre CR , Ridda I , Seale H et al. (2012) Respiratory viruses transmission from children to adults within a household. Vaccine 30: 3009–3014.

Markel H , Lipman HB , Navarro JA et al. (2012) Non‐pharmaceutical interventions implemented by US cities during the 1918–1919 influenza pandemic. Journal of the American Medical Association 298(6): 644–654.

Morens DM , Taubenberger JK , Fauci AS et al. (2009) The persistent legancy of the 1918 influenza virus. New England Journal of Medicine 361: 225–229.

Mulder J and Hers JF (1972) Ph. Influenza. Groningen: Wolters Noordhoff Publishing.

Octaviani CP , Ozawa M , Yamada S et al. (2010) High genetic compatibility between swine‐origin H1N1 and highly pathogenic avian H5N1 influenza viruses. Journal of Virology 84(20): 10918–10922.

Oseasohn R , Adelson L and Kaji M (1964) Clinical pathological study of 33 fatal cases of Asian influenza. New England Journal of Medicine 260: 510–518.

Oxford JS (2000) Influenza A pandemics of the 20th century with Special Reference to 1918: Virology, Pathology and Epidemiology. Reviews of Medical Virology 10: 119–133.

Oxford JS (2002) The so‐called Great Spanish Influenza Pandemic of 1918 may have originated in France in 1916. Philosophical Transactions of the Royal Society 356: 1857–1859.

Oxford JS (2013) Towards a universal influenza vaccine: volunteer virus challenge studies in quarantine to speed the development and subsequent licensing. British Journal of Clinical Pharmacology 76: 210–216.

Oxford JS and Oxford JR (2012) Clinical, scientific and ethnographic studies of influenza in quarantine. Expert Review of Vaccines ( 8): 929–937.

Oxford JS , Sefton A , Jackson R et al. (2002) World War I may have allowed the emergence of “Spanish” influenza. Lancet Infectious Diseases 2: 111–114.

Phillips H and Killingray D (eds) (2003). The Spanish Influenza Pandemic of 1918–1919: New Perspectives. Social History of Medicine Series. London: Routledge.

Poehling CA , Edwards KM , Weinberg GA et al. (2006) The under recognised burden of influenza in young children. New England Journal of Medicine 355: 31–40.

Potter CW (1998) Chronicle of influenza pandemics. In: Nicholson KG , Webster RG and Hay AJ (eds) Textbook of Influenza, pp. 3–18. Oxford: Blackwell Science.

Qi L , Davis S , Jagger BW et al. (2012) Analysis by single gene reassortant demonstrates that the 1918 influenza virus is functionally compatible with a low‐pathogenicity avian influenza virus in mice. Journal of Virology 86(17): 9211–9220.

Reichert TA , Sugaya N , Fedson DS et al. (2001) The Japanese experience with vaccinating school children against influenza. New England Journal of Medicine 344: 889–896.

Reid AH , Fanning TG , Hultin JV et al. (1999) Origin and evolution of the 1918 Spanish influenza virus haemagglutinin gene. Proceedings of the National Academy of Sciences of the USA 96: 1651–1656.

Reid AH , Janczewski TA , Greif R et al. (2003) 1918 influenza pandemic caused by highly conserved viruses with two receptor‐binding variants. Emerging Infectious Diseases 10: 1249–1253.

Sachedina N and Donaldson LJ (2010) Paediatric mortality related to pandemic influenza A H1N1 infection in England: an observational population‐based study. Lancet 376: 1846–1852.

Salathe M , Clark C , Freifield MS et al. (2013) Influenza A (H7N9) and the importance of digital epidemiology. New England Journal of Medicine 368: 1862–1864.

Scholtissek C (2002) Pandemic influenza: antigenic shift. In: Potter CW (ed.) Influenza, pp. 87–100. Amsterdam: Elsevier.

Simmerman JM , Suntarattiwong P , Levy J et al. (2010) Influenza virus contamination of common household surfaces during the 2009 influenza A (H1N1) pandemic in Bangkok, Thailand: implications for contact transmission. Clinical Infectious Diseases 51(9): 1053–1061.

Simpson CR , Ritchie LD , Robertson C et al. (2012) Effectiveness of H1N1 vaccine for the prevention of pandemic influenza in Scotland, UK: a retrospective observational cohort study. Lancet Infectious Diseases 12: 696–702.

Sleeman K , Mishin VP , Deyde VM et al. (2010) In vitro antiviral activity of favipiravir (T‐705) against drug resistant influenza A and 2009 (H1N1) viruses. Antimicrobial Agents and Chemotherapy 54: 2517–2524.

Smith JR (2010) Oseltamivir in humans avian influenza infection. Journal of Antimicrobial Chemotherapy 65: ii25–ii33.

Smith W , Andrewes CH and Laidlaw PP (1933) A virus obtained from influenza patients. Lancet 2: 66.

Stuart‐Harris CH , Schild GC and Oxford JS (1985) Influenza: The Virus and The Disease, London: Edward Arnold.

Taubenberger JK and Reid AH (2002) The 1918 ‘Spanish’ influenza pandemic and characterisation of the virus that caused it. In: Potter CW (ed.) Influenza, pp. 101–122. Amsterdam: Elsevier.

Toback SL , Ambrose CS , Eaton A et al. (2013) A postlicensure evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 24–59 months of age. Vaccine 31: 1812–1818.

Triana‐Baltzer GB , Gubareva LV , Nicholls JM et al. (2008) Novel pandemic influenza A (H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein. PLoS One 4: 7788.

Vandermeer ML , Thomas AR , Kamimoto L et al. (2012) Association between use of statins and mortality among patients hospitalised with laboratory‐confirmed influenza virus infections: a multistate study. Journal of Infectious Diseases 205(1): 13–19.

Vesikari T , Knuf M , Wutzler P et al. (2013) Oil‐in‐water emulsion adjuvant with influenza vaccine in young children. New England Journal of Medicine 365: 1406–1416.

Welliver R , Monto AS , Carewitc O et al. (2001) Effectiveness of oseltamivir in preventing influenza in household contacts. Journal of the American Medical Association 285: 748–754.

Wharton SA , Weis W , Skehel JJ and Whiley DC (1989) Structure, function and antigenicity of the haemagglutinin. In: Krug RM (ed.) The Influenza Viruses, pp. 153–173. New York: Plenum Press.

Wilkinson T , Li CKF , Chui CSC et al. (2011) Pre existing influenza specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nature Medicine 18: 247–280.

Winternitz MC , Wason IM and McNamara FP (1920) The Pathology of Influenza. New Haven, Connecticut: Yale University Press.

Yu H , Cowling BJ , Feng L et al. (2013) Human infection with avian influenza A H7N9 virus: an assessment of clinical severity. Lancet 382: 138–145.

Yu H , Liao Q , Yuan Y et al. (2010) Effectiveness of oseltamivir in patients with mild pandemic 2009 influenza H1N1 opportunistic retrospective study of medical charts in China. British Medical Journal, 341: c4779.

Yuen KY , Chan PK , Peiris M et al. (1998) Clinical features and rapid viral diagnostic of human disease associated with avian influenza A H5N1 virus. Lancet 351: 467–471.

Zaman M , Ashraf S , Dreyer NA et al. (2011) Human infection with avian influenza virus, Pakistan, 2007. Emerging Infectious Diseases 17(6): 1056.

Further Reading

Dawood R (2012) Travellers Health. How to stay healthy abroad, 5th edn, p. 530. Oxford: Oxford University Press.

Oxford JS (2012a) Hygiene. In: Antier HK and Juergensmeyer M (ed.) Encyclopedia of Global Studies 2, pp. 838–844. Los Angeles: SAGE Publications Inc.

Oxford JS (2012b) Viruses and Disease, Emerging. In: Antier HK and Juergensmeyer M (ed.) Encyclopedia of Global Studies 4, pp. 1743–1749. Los Angeles: SAGE Publications Inc.

Pandemic Influenza Risk Management (2013) WHO Interim Guidance, p. 56. Geneva: WHO.

Taubenberger JK and Morens DM (2006) 1918 influenza: the mother of all pandemics. Emerging Infectious Diseases 12: 15–22.

Tyrrell D and Fielder M (2002) Cold Wars, the Fight Against the Common Cold, p. 253. Oxford: Oxford University Press.

Viloud C , Alonso WJ and Simonsen L (2006) Influenza in tropical regions. PLoS Medicine 3: 89.

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Oxford, John S(Jan 2014) A Perspective of Influenza Pandemics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023618]