Advertisement

Typhoid Fever Epidemic in Ancient Athens

  • Manolis J. Papagrigorakis
  • Christos Yapijakis
  • Philippos N. Synodinos

Molecular evidence, resulting from investigation and analysis of ancient DNA, has identified the presence of Salmonella enterica serovar Typhi in victims of the Plague of Athens, thereby incriminating typhoid fever as a likely cause of the epidemic. Current clinical and epidemiological scientific data, related to modern-day typhoid, correlate well to the signs and symptoms of the disease as Thucydides has described them, whereas their apparent differences may be reasonably explained. The most striking hypothesis is that the ancient S. typhi strain may constitute the ancestral original strain of the pathogen, capable of affecting both human and animal hosts. The genomic evolution of the ancient Salmonella typhi strain over time may provide a satisfactory explanation for the diminished morbidity and the varying clinical symptomatology of modern-day typhoid fever. Further investigations, implementing DNA sequencing techniques of the ancient strain of S. enterica, may elucidate its genetically determined differences from its modern counterpart, thus facilitating new approaches to preventing or treating typhoid fever epidemics.

Keywords

Typhoid Fever Dental Pulp Mass Grave Yersinia Pestis Lassa Fever 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aboudharam G, Lascola B, Raoult D, Drancourt M (2000) Detection of Coxiella burnetti DNA in dental pulp during experimental bacteremia. Microb Pathog 28:249–254PubMedCrossRefGoogle Scholar
  2. Baziotopoulou-Valavani EA (2002) Mass burial from the Cemetery of Kerameikos. In: Stamatopoulou M, Yeroulanou M (eds) Excavating classical culture. Recent archaeological discoveries in Greece. Studies in Classical Archaeology I. BAR International Series 1031. Archaeopress, Oxford, pp 187–201Google Scholar
  3. Bhan MK, Bahl R, Sazawal S, Sinha A, Kumar R, Mahalanabis D, Clemens JD (2002) Association between Helicobacter pylori infection and increased risk of typhoid fever. J Infect Dis 186:1857–1860PubMedCrossRefGoogle Scholar
  4. Bhan MK, Bahl R, Bhatnagar S (2005) Typhoid and paratyphoid fever. Lancet 366:749–762PubMedCrossRefGoogle Scholar
  5. Black RE, Cisneros L, Levine MM, Banfi A, Lobos H, Rodriguez H (1985) Case-control study to identify risk factors for paediatric endemic typhoid fever in Santiago, Chile. Bull World Health Organ 63:899–904PubMedGoogle Scholar
  6. Connor BA, Schwartz E (2005) Typhoid and paratyphoid in travelers. Lancet Infect Dis 5:623–628PubMedCrossRefGoogle Scholar
  7. Cooper A, Poinar HN (2000) Ancient DNA: do it right or not at all. Science 289:1139PubMedCrossRefGoogle Scholar
  8. Cunha BA (2004) The cause of the plague of Athens: plague, typhoid, typhus, smallpox or measles? Infect Dis Clin N Am 18:29–43CrossRefGoogle Scholar
  9. Deng W, Liou SR, Plunkett G III, Mayhew GF, Rose DJ, Burland V, Kodoyianni V, Schwartz DC, Blattner FR (2003) Comparative genomics of Salmonella enterica serovar Typhi Strains Ty2 and CT18. J Bacteriol 185:2330–2337PubMedCrossRefGoogle Scholar
  10. Drancourt M, Raoult D (2002) Molecular insights into the history of plague. Microbes Infect 4:105–109PubMedCrossRefGoogle Scholar
  11. Durack DT, Littman RJ, Benitez RM, Mackowiak PA (2000) Hellenic holocaust: a historical clinico-pathologic conference. Am J Med 109:391–397PubMedCrossRefGoogle Scholar
  12. Gasem MH, Dolmans WM, Keuter MM, Djokomoeljanto RR (2001) Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia. Trop Med Int Health 6:484–490PubMedCrossRefGoogle Scholar
  13. Glick M, Trope M, Bagasra O, Pliskin ME (1991) Human immunodeficiency virus infection of fibroblasts of dental pulp in seropositive patients. Oral Surg Oral Med Oral Pathol 71:733–736PubMedCrossRefGoogle Scholar
  14. Hoffner RJ, Slaven E, Perez J, Magana RN, Henderson SO (2000) Emergency department presentations of typhoid fever. J Emerg Med 4:317–321CrossRefGoogle Scholar
  15. Holden C (1996) Athenian plague probe. Science 274:1307CrossRefGoogle Scholar
  16. Holden C (1998) Old dental pulp points to plague. Science 282:619Google Scholar
  17. Holladay AJ (1986) The Thucydides syndrome: another view. N Engl J Med 15:1170–1173Google Scholar
  18. Hook EW (1984) Typhoid fever today. N Engl J Med 310:116–118PubMedGoogle Scholar
  19. House D, Bishop A, Parry CM, Dougan G, Wain J (2001) Typhoid fever: pathogenesis and disease. Curr Opin Infect Dis 14:573–578PubMedGoogle Scholar
  20. Huan DB, DuPont HI (2005) Problem pathogens: extra-intestinal complications of Salmonella enterica serotype typhi infection. Lancet Infect Dis 5:341–348CrossRefGoogle Scholar
  21. Kidgell C, Reichard U, Wain J, Linz B, Torpdahl M, Dougan G, Achman M (2002) Salmonella typhi, the causative agent of typhoid fever, is approximately 50, 000 years old. Infect Genet Evol 2:39–45PubMedCrossRefGoogle Scholar
  22. Kolman CJ, Centurion-Lara A, Lukehart SA, Owsley DW, Tuross N (2000) Identification of Treponema pallidum subspecies pallidum in a 200-year-old skeletal specimen. Infect Dis 180:2060–2063CrossRefGoogle Scholar
  23. Langmuir AD, Worthen TD, Solomon J, Ray CG, Petersen E (1985) The Thucydides syndrome: a new hypothesis for the cause of the plague of Athens. N Engl J Med 313:1027–1030PubMedGoogle Scholar
  24. Lim ML, Wallace MR (2004) Infectious diarrhea in history. Infect Dis Clin N Am 18:261–274CrossRefGoogle Scholar
  25. Littman RJ, Littman ML (1969) The Athenian plague: smallpox. Trans Am Philol Assoc 100:261–275CrossRefGoogle Scholar
  26. Longrigg J (1980) The great plague of Athens. Hist Sci 18:209–225PubMedGoogle Scholar
  27. Luby SP, Faizan MK, Fisher-Hoch SP, Syed A, Mintz ED, Bhutta ZA, McCormick JB (1998) Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan. Epidemiol Infect 120:129–138PubMedCrossRefGoogle Scholar
  28. Luxemburger C, Chau MC, Mai NL, Wain J, Tran TH, Simpson JA, Le HK, Nguyen TTT, White NJ, Farrar JJ (2001) Risk factors for typhoid fever in the Mekong Delta, southern Viet Nam: a case-control study. Trans R Soc Trop Med Hyg 95:19–23PubMedCrossRefGoogle Scholar
  29. McClelland M, Sanderson KE, Spieth J, Clifton SW, Latreille P, Courtney L, Porwollik S, Ali J, Dante M, Du F, Hou S, Layman D, Leonard S, Nguyen C, Scott K, Holmes A, Grewal N, Mulvaney E, Ryan E, Sun H, Florea L, Miller W, Stoneking T, Nhan M, Waterston R, Wilson RK (2001) Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852–856PubMedCrossRefGoogle Scholar
  30. McSherry J, Kilpatrick R (1992) The Plague of Athens. J R Soc Med 85:713PubMedGoogle Scholar
  31. Mermin JH, Villar R, Carpenter J, Roberts L, Samaridden A, Gasanova L, Lomakina S, Bopp C, Hutwagner L, Mead P, Ross B, Mintz ED (1999) A massive epidemic of multidrug-resistant typhoid fever in Tajikistan associated with consumption of municipal water. J Infect Dis 179:1416–1422PubMedCrossRefGoogle Scholar
  32. Nerlich A, Haas CJ, Zink A, Szeimies U, Hagedom HG (1997) Molecular evidence for tuberculosis in an ancient Egyptian mummy. Lancet 350:1404PubMedCrossRefGoogle Scholar
  33. Olson PE, Hames CS, Benenson AS, Genovese EN (1996) The Thucydides syndrome: Ebola deja vu? (or Ebola reemergent?). Emerg Infect Dis 2:155–156PubMedCrossRefGoogle Scholar
  34. Olson PE, Benerson AS, Genovese EN (1998) Ebola/Athens revisited. Emerg Infect Dis 4:134PubMedCrossRefGoogle Scholar
  35. Oscarsson J, Westermark M, Löfdahl S, Olsen B, Palmgren H, Mizunoe Y, Wai SN, Uhlin BE (2002) Characterization of a pore-forming cytotoxin expressed by Salmonella enterica serovars Typhi and Paratyphi A. Infect Immun 10:5759–5769CrossRefGoogle Scholar
  36. Pääbo S (1989) Ancient DNA: extraction, characterization, molecular cloning and enzymatic amplification. Proc Natl Acad Sci USA 86:1939–1943PubMedCrossRefGoogle Scholar
  37. Page DL (1953) Thucydides’ description of the great plague. Classical Q 3:97–119CrossRefGoogle Scholar
  38. Papagrigorakis MI, Yapijakis C, Synodinos PN, Baziotolpoulou-Valavani E (2006a) DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens. Int J Infect Dis 10:206–214PubMedCrossRefGoogle Scholar
  39. Papagrigorakis MI, Yapijakis C, Synodinos PN, Baziotolpoulou-Valavani E (2006b) Insufficient phylogenetic analysis may not exclude candidacy of typhoid fever as a probable cause of the Plague of Athens (reply to Shapiro et al.). Int J Infect Dis 10:335–336CrossRefGoogle Scholar
  40. Papagrigorakis MJ, Synodinos PN, Yapijakis C (2007) Ancient typhoid epidemic reveals possible ancestral strain of Salmonella enterica serovar Typhi. Infect Genet Evol 7:126–127PubMedCrossRefGoogle Scholar
  41. Parkhill J, Dougan G, James KD, Thomson NR, Pickard D, Wain J, Churcher C, Mungall KL, Bentley SD, Holden MT, Sebaihia M, Baker S, Basham D, Brooks K, Chillingworth T, Connerton P, Cronin A, Davis P, Davies RM, Dowd L, White N, Farrar J, Feltwell T, Hamlin N, Haque A, Hien TT, Holroyd S, Jagels K, Krogh A, Larsen TS, Leather S, Moule S, O’Gaora P, Parry C, Quail M, Rutherford K, Simmonds M, Skelton J, Stevens K, Whitehead S, Barrell BG (2001) Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413:848–852PubMedCrossRefGoogle Scholar
  42. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ (2002) Typhoid fever. New Engl J Med 347:1770–1782PubMedCrossRefGoogle Scholar
  43. Perry RD, Fetherston JD (1997) Yersinia pestis: the agent of the plague. Clin Microbiol Rev 10:35–66PubMedGoogle Scholar
  44. Punjabi NH, Hoffman SL, Edman DC, Sukri N, Laughlin LW, Pulungsih SP, Rivai AR, Sututo, Moechtar A, Woodward TE (1988) Treatment of severe typhoid fever in children with high dose dexamethasone. Pediatr Infect Dis J 7:598–600PubMedCrossRefGoogle Scholar
  45. Raoult D, Aboudharam G, Crubézy E, Larroy G, Ludes B, Drancourt M (2000) Molecular identification by suicide PCR of Yersinia pestis as the agent of medieval black death. Proc Natl Acad Sci USA 23:12800–12803CrossRefGoogle Scholar
  46. Raoult D, Dutour O, Houhamdi L, Jankauskas R, Fournier PE, Ardagna Y, Drancourt M, Signoli M, La VD, Macia Y, Aboudharam G (2006) Evidence for louse-transmitted diseases in soldiers of Napoleon’s Grand Army in Vilnius. J Infect Dis 193:112–120PubMedCrossRefGoogle Scholar
  47. Rogerson SJ, Spooner VJ, Smith TA, Richens J (1991) Hydrocortisone in chloramphenicol-treated severe typhoid fever in Papua New Guinea. Trans R Soc Trop Med Hyg 85:113–116PubMedCrossRefGoogle Scholar
  48. Scarrow GD (1988) The Athenian plague: a possible diagnosis. Ancient Hist Bull 2:4–8Google Scholar
  49. Shapiro B, Rambaut A, Gilbert MTP (2006) No proof that typhoid caused the Plague of Athens (a reply to Papagrigorakis et al.). Int J Infect Dis 10:334–335PubMedCrossRefGoogle Scholar
  50. Shrewsbury JDF (1950) The plague of Athens. Bull Hist Med 24:1–24Google Scholar
  51. Soupios MA (2004) Impact of the plague in Ancient Greece. Infect Dis Clin N Am 18:45–51CrossRefGoogle Scholar
  52. Stuart BM, Pullen RL (1946) Typhoid: clinical analysis of three hundred and sixty cases. Arch Intern Med 78:629–661Google Scholar
  53. Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG (1997) Initial genetic characterisation of the 1918 Spanish influenza virus. Science 275:1793–1796PubMedCrossRefGoogle Scholar
  54. Taylor GM, Crossey M, Saldanha JA, Waldron T (1996) Detection of Mycobacterium tuberculosis bacterial DNA in medieval skeletal remains using polymerase chain reaction. J Archeol Sci 23:789–98CrossRefGoogle Scholar
  55. Taylor GM, Goyal M, Legge AJ, Shaw RJ, Young D (1999) Genotypic analysis of Mycobacterium tuberculosis from medieval human remains. Microbiology 145:899–904PubMedCrossRefGoogle Scholar
  56. Thucydides (1919) (Translation by C.F. Smith) History of the Peloponnesian War. Books I & II, 2.47–2.55. Harvard University Press, CambridgeGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Manolis J. Papagrigorakis
    • 1
  • Christos Yapijakis
    • 2
  • Philippos N. Synodinos
    • 3
  1. 1.Department of OrthodonticsUniversity of AthensGreece
  2. 2.Department of NeurologyEginition HospitalGreece
  3. 3.Department of OrthodonticsUniversity of AthensGreece

Personalised recommendations