Journal of Neural Transmission

, Volume 116, Issue 2, pp 143–150 | Cite as

Encephalitis lethargica and influenza. I. The role of the influenza virus in the influenza pandemic of 1918/1919

  • Paul Bernard FoleyEmail author
Parkinson's Disease and Allied Conditions - Original Article


An investigation of the characteristics of influenza epidemics in the nineteenth and early twentieth centuries was undertaken, principally in order to analyze the role of the 1918/1919 influenza pandemic in the etiology of encephalitis lethargica. Expectations regarding a future influenza pandemic derive principally from experiences in the 1918 epidemic. It is proposed that this pandemic was atypical with respect to many of its features, and that these have not been appropriately regarded in mapping expectations and responses of a future pandemic. Both a longer historical viewpoint (incorporating knowledge from all major nineteenth and twentieth century epidemics) and closer examination of individual epidemics at the town level is essential for producing an accurate picture of the challenge.


Encephalitis lethargica Epidemic encephalitis Influenza History of the neurosciences 



My investigation of encephalitis lethargica was supported by Australian Research Council through a Discovery Grant (DP0451188) and an Australian Postdoctoral Fellowship.


  1. Abrahams A, Hallows NF, Eyre JWH, French H (1917) Purulent bronchitis: its influenzal and pneumococcal bacteriology. Lancet 190:377–382CrossRefGoogle Scholar
  2. Althaus J (1892) Influenza: its pathology, symptoms, complications, and sequels; its origin and mode of spreading; and its diagnosis, prognosis, and treatment, 2nd edn. Longmans & Co., LondonGoogle Scholar
  3. Andreasen V, Viboud C, Simonsen L (2008) Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies. J Infect Dis 197:270–278PubMedCrossRefGoogle Scholar
  4. Barry JM, Viboud C, Simonsen L (2008) Cross-protection between successive waves of the 1918–1919 influenza pandemic: epidemiological evidence from US Army Camps and from Britain. J Infect Dis 198:1427–1434PubMedCrossRefGoogle Scholar
  5. Blay A, Bessler H, Lahad A, Waitman DA, Djaldetti M (2007) Does pneumococcal vaccine reduce influenza morbidity in humans? Vaccine 25:1071–1075PubMedCrossRefGoogle Scholar
  6. Brundage JF, Shanks GD (2008) Deaths from bacterial pneumonia during 1918–19 influenza pandemic. Emerg Infect Dis 14:1193–1199PubMedCrossRefGoogle Scholar
  7. Burnet FM, Clark E (1942) Influenza: a study of the last 50 years in the light of modern work on the virus of epidemic influenza. Macmillan, MelbourneGoogle Scholar
  8. Christian HA (1918) Incorrectness of the diagnosis of death from influenza. Presence of bronchopneumonia in practically all persons severely ill with influenza. J Am Med Assoc 71:1565–1566Google Scholar
  9. Cliff AD, Haggett P, Smallman-Raynor M (2008) An exploratory method for estimating the changing speed of epidemic waves from historical data. Int J Epidemiol 37:106–112PubMedCrossRefGoogle Scholar
  10. Collins SD, Lehmann L (1953) Excess deaths from influenza and pneumonia and from important chronic diseases during epidemic periods, 1918–51. Public health monographs no. 10, public health service publication no. 213. United States Government Printing Office, WashingtonGoogle Scholar
  11. Crookshank FG (1920) A note on the history of epidemic encephalomyelitis. Boston Med Surg J 182:34–45Google Scholar
  12. Crookshank FG (1922) Influenza: essays by several authors. William Heinemann (Medical Books), LondonGoogle Scholar
  13. Cruchet R, Moutier F, Calmettes A (1917) Quarante cas d’encéphalo-myélite subaiguë. Bull Mém Soc Méd Hôp Paris 41:614–616Google Scholar
  14. Davenport F (1977) Reflections on the epidemiology of myxovirus infections. Med Microbiol Immunol (Berl) 164:69–76CrossRefGoogle Scholar
  15. Earn DJD, Dushoff J, Levin SA (2002) Ecology and evolution of the flu. Trends Ecol Evol 17:334–340CrossRefGoogle Scholar
  16. Eberling G (1892) Influenza-Psychosen (thesis: Berlin). Schade, BerlinGoogle Scholar
  17. von Economo C (1917) Encephalitis lethargica. Wr klin Wschr 30:581–585Google Scholar
  18. Forbes J, Conolly J (1839) Schweich, Gluge, Blakiston, and Streeten, on the influenza. Br Foreign Med Rev 7:95–114Google Scholar
  19. Hall MW (1928) Inflammatory diseases of the respiratory tract (bronchitis; influenza; bronchopneumonia; lobar pneumonia). In: Siler JF (ed) Communicable and other diseases (Lynch C, Weed FW, McAfee L, eds). The Medical Department of the United States Army in the World War. The Official History Series, vol IX. U.S. Army Surgeon General’s Office, Washington, pp 61–169Google Scholar
  20. Hammond JAB, Rolland W, Shore THG (1917) Purulent bronchitis. A study of cases occurring amongst the British troops at a base in France. Lancet 190:41–46CrossRefGoogle Scholar
  21. Hampson AW, Mackenzie JS (2006) The influenza viruses. Med J Aust 185:S39–S43PubMedGoogle Scholar
  22. Hope-Simpson RE (1986) Andrewes versus influenza: discussion paper. J Royal Soc Med 79:407–411Google Scholar
  23. Jordan EO (1922) Interepidemic influenza. Am J Hygiene 2:325–345Google Scholar
  24. Kash JC, Tumpey TM, Proll SC, Carter V, Perwitasari O, Thomas MJ, Basler CF, Palese P, Taubenberger JK, García-Sastre A, Swayne DE, Katze MG (2006) Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Nature 443:578–581PubMedGoogle Scholar
  25. Kobasa D, Jones SM, Shinya K, Kash JC, Copps J, Ebihara H, Hatta Y, Hyun Kim J, Halfmann P, Hatta M, Feldmann F, Alimonti JB, Fernando L, Li Y, Katze MG, Feldmann H, Kawaoka Y (2007) Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 445:319–323PubMedCrossRefGoogle Scholar
  26. Leichtenstern O (1912) Influenza, 2nd edn. Alfred Hölder, ViennaGoogle Scholar
  27. Levinthal W, Kuczynski MH, Wolff E (1921) Ätiologie, Epidemiologie, pathologische Morphologie und Pathogenese der Grippe. Ergeb Allgem Pathol Pathol Anat 19, 2. Abt. 848–1163Google Scholar
  28. Leyden E, Guttmann S (1892) Die Influenza-Epidemie 1889/90. Im Auftrage des Vereins für Innere Medicin in Berlin. J. F. Bergmann, WiesbadenGoogle Scholar
  29. MacNalty AS (1927) Epidemic diseases of the central nervous system. Faber & Gwyer (The Scientific Press), LondonGoogle Scholar
  30. Maurizi CP (1989) Influenza caused epidemic encephalitis (encephalitis lethargica): the circumstantial evidence and a challenge to the naysayers. Med Hypotheses 28:139–142PubMedCrossRefGoogle Scholar
  31. McCullers JA (2006) Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev 19:571–582PubMedCrossRefGoogle Scholar
  32. Morens DM, Fauci AS (2007) The 1918 influenza pandemic: insights for the 21st century. J Infect Dis 195:1018–1028PubMedCrossRefGoogle Scholar
  33. Morens DM, Taubenberger JK, Fauci AS (2008) Predominant role of bacterial pneumonia as a cause of death in pandemic ifluenza: implications for pandemic influenza preparedness. J Infect Dis 198:962–970PubMedCrossRefGoogle Scholar
  34. Okamoto S, Kawabata S, Nakagawa I, Okuno Y, Goto T, Sano K, Hamada S (2003) Influenza A virus-infected hosts boost an invasive type of Streptococcus pyogenes infection in mice. J Virol 77:4104–4112PubMedCrossRefGoogle Scholar
  35. Ozanam JAF (1817–1823) Histoire médicale générale et particulière des maladies épidémiques, contagieuses et épizootiques qui ont règne en Europe depuis les temps les plus reculés et notamment depuis le 14. siècle jusqu’à nos jours, Méquignon-Marvis, ParisGoogle Scholar
  36. Pappas C, Aguilar PV, Basler CF, Solorzano A, Zeng H, Perrone LA, Palese P, García-Sastre A, Katz JM, Tumpey TM (2008) Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus. Proc Natl Acad Sci 105:3064–3069PubMedCrossRefGoogle Scholar
  37. Paton RT, Armstrong WG, Dick R, Smith HA, Cleland JB (1920) Report of the Director-General of Public Health, New South Wales, for the year ended 31st December, 1919. Section V. Report on the influenza epidemic in New South Wales in 1919. William Applegate Gullick, Government Printer, SydneyGoogle Scholar
  38. Pfeiffer R (1892) Vorläufige Mittheilungen über den Erreger der Influenza. Dtsch Med Wschr 18:28Google Scholar
  39. Pfeiffer R (1893) Die Ätiologie der Influenza. Zschr Hyg Infektionskrankh 13:357–386CrossRefGoogle Scholar
  40. Sahli H (1913) Lehrbuch der klinischen Untersuchungs-Methoden für Studierende und praktische Ärzte. I. Band, 6th edn. Franz Deuticke, LeipzigGoogle Scholar
  41. Sahli H (1919) Über die Influenza. Korresp-Blatt f Schweiz Aerzte 49:1–18; 193–210Google Scholar
  42. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y (2006) Avian flu: influenza virus receptors in the human airway. Nature 440:435–436PubMedCrossRefGoogle Scholar
  43. Shope RE (1931) Swine influenza. J Exp Med 54:349–385CrossRefGoogle Scholar
  44. Smil V (2005) The next 50 years: fatal discontinuities. Popul Dev Rev 31:201–236CrossRefGoogle Scholar
  45. Smith W, Andrewes CH, Laidlaw PP (1933) A virus obtained from influenza patients. Lancet 222:66–68CrossRefGoogle Scholar
  46. Taubenberger JK (2005) The virulence of the 1918 pandemic influenza virus: unraveling the enigma. In: Peters CJ, Calisher CH (eds) Infectious diseases from nature: Mechanisms of viral emergence and persistence (Arch Virol Suppl 19). Springer, Vienna, pp 101–115CrossRefGoogle Scholar
  47. Taubenberger JK, Morens DM (2008) The pathology of influenza virus infections. Ann Rev Path Mech Dis 3:499–522CrossRefGoogle Scholar
  48. Thomson D, Thomson R (1933) St. Paul’s Hospital. Picket-Thompson Research Laboratory Monograph XVI. Influenza (Part I), with special reference to the part played by Pfeiffer’s bacillus, streptococci, pneumococci, etc., and the virus theory, Baillière, Tindall & Cox, London; Williams and Wilkins, BaltimoreGoogle Scholar
  49. Webster RG, Laver WG (1971) Antigenic variation in influenza virus. Biology and chemistry. Prog Med Virol 13:271–338PubMedGoogle Scholar
  50. Witte W (2006) Erklärungsnotstand. Die Grippe-Epidemie 1918–1920 in Deutschland unter besonderer Berücksichtigung Badens, Centaurus, HerbolzheimGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Prince of Wales Medical Research InstituteRandwickAustralia

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