Yersinia pestis is the bacterium that causes plague. It originated in Asia over 5,000 years ago and was responsible for three major pandemics: the Plague of Justinian in the 6th century, the Black Death in the 14th century, and a third pandemic from 1855-1959. Currently plague remains endemic in parts of Africa, Asia, and the Americas. Madagascar experiences regular outbreaks and had over 275 cases in 2015. Treatment with antibiotics is effective if administered promptly. Plague poses a potential bioterrorism risk if weaponized. Ongoing surveillance and public health responses are needed to combat future outbreaks.

1. Plague – Yersinia pestis
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Mark R O’Donovan
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2. Presentation Outline
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3. Background
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4. Historical origin/impact
Oldest confirmed cases of Y. pestis (Rasmussen et al. 2015)Medieval art inspired by the plague

5. Timeline of Y. pestis
MRCA = most recent common ancestor
[95% Highest Posterior Density interval]
(Rasmussen et al. 2015)
MRCA of Y. pestis &
Y. pseudotuberculosis
54,735 years ago
[34,659–78,803 years]
MRCA of today’s
Y. pestis strains
5,783 years ago
[5,021–7,022 years]
Flea transmission 951 BC
Increasing virulence (mutations)
- Plague of Justinian (542–750 AD)
- Black Death (1346–1353 AD)
- China/World-wide (1855–1959)
Yersinia genus

6. Genetic evolution of Y. pestis
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(Rasmussen et al. 2015)

7. Pandemic 1: Plague of Justinian (542-750 AD)
• Severely weakened Eastern Roman (Byzantine) Empire
• 25-50 million deaths; 25-30% of Empire
• 5000 deaths a day in Constantinople!
Expansion of the Byzantine Empire. Plague strain originated in Asia and probably entered via Africa (Harbeck et al. 2013)

8. Pandemic 2: Black Death (1346-1353 AD)
• Devastated Europe (inc. Ireland)
• 50 million deaths
• 60% European population!
Spread of the Black death through Europe (Benedictow, 2005)
Plague strain originated in Asia (Harbeck et al. 2013)

9. Pandemic 3: China/World-wide (1855-1959)
• Mostly China, India, and Indonesia
• Spread globally in 1894 from Hong Kong
• About 15 million deaths!
Originated in China,
spread via Hong Kong
(Achtman, 2012)

10. African Outbreaks
Plague (Yersinia pestis); 1954-2015

11. African Plague
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12. Current situation
2010 2011 2012 2013 2014 2015
Dem Rep of Congo 152 (11) 152 (19) 131 (15) 55 (5) 78 (12) 18 (5)
Madagascar 324 (30) 392 (93) 256 (60) 675 (118) 482 (112) 275 (63)
Uganda 14 (1) 14 (2) 22 (6) 13 (3) 6 (0) 3 (0)
Utd Rep of Tanzania 9 (2) 9 (1) 7 (0) _ 31 (1) 5 (3)
Most recent data on cases (and deaths) from Y. pestis in Africa (WHO, 2016)

13. History of the plague in Madagascar
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14. 2016 Madagascar

15. 6 December 2016 – Madagascar
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16. 27th December 2016-Madagascar
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17. Madagascar
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18. 29th December 2016-Madagascar
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19. Public Health Response
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20. Key response activities implemented included:
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21. WHO Advice
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22. Asian Outbreaks
Plague (Yersinia pestis); 1954-2015

23. China
2009 (July-August)
Ziketan, Qinghai province
12 people infected, 3 died
Response
Delayed treatment
Isolated 332 close contacts
Info pamphlets/supplies
wild
marmot
dog
32 year old
herdsman

24. India
1994; Surat, Gujarat State
876 cases? 54 deaths
Economic loss – US$1.7 billion.
2002 (Feb); Hatkoti village, Himachal Pradesh
16 cases; 4 deaths
2004 (Oct); Dangud village, Uttar Kashi
8 cases; 3 deaths

25. Vietnam
1965-67: ≈15,000 cases!
Military movement
Defoliation
Climate
1997-2002: 472 cases
2010-2015: 0 cases
(Cavanaugh et al. 1968)

26. Others
Burma
1974: perhaps 700 cases
1977: 14 cases, with 2 deaths
Indonesia
1968: 102 cases (Boyolali mountains, Java)
No medical facilities available, 35% fatality
Mongolia
1940-2008: 521 cases; 70% fatality

27. Others
Kazakhstan
1990-2002: 19 cases; 6 died
Kyrgyzstan
2 cases in 2013 (0 since 1981)
Russia
1 case in 2014 (0 since 1961)
Kazakhstan – infected gerbil locations (Heier et al. 2011)

28. Current situation
2010 2011 2012 2013 2014 2015
China 5 (1) 1 (1) 1 (0) _ 3 (3) _
Russian Federation _ _ _ _ 1 (0) _
Kyrgyzstan _ _ _ 1 (1) _ _
Mongolia _ 1 (0) _ _ 1 (0) 3 (2)
Most recent data on cases (and deaths) from Y. pestis in Asia (WHO, 2016)

29. North American Outbreaks
Plague (Yersinia pestis); 1954-2015

30. North America; USA:
Impact on population:
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31. Frequency and geographic distribution of human
plague cases in the United States, 1900–2012:
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32. Introduction of antibiotics:
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35. Plague outbreak:
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37. Current practice in the US:
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38. Current situation
2010 2011 2012 2013 2014 2015
USA 2 (0) 3 (0) 4 (0) 4 (1) 10 (0) 16 (4)
Most recent data on cases (and deaths) from Y. pestis in North America (WHO, 2016)

39. South American Outbreaks
Plague (Yersinia pestis); 1954-2015

40. Current situation
2010 2011 2012 2013 2014 2015
Bolivia 1 (1) _ _ _ 2 (1) _
Peru 27 (4) 1 (0) 6 (0) 24 (2) 8 (1) _
Most recent data on cases (and deaths) from Y. pestis in South America (WHO, 2016)

41. South America
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42. Historic information of the presence of human
cases of plague in Latin America, 1899–2012
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43. Timeframe and presence of plague
history, Latin America.
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44. When?
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45. How was it managed and efforts to protect
public health
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46. Number of human cases of plague, by country, Latin
America, 2000–2012.
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47. Public Health Impact
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48. Terrorist threat – weaponization!
• By Tartar force in the Siege of Caffa (in Ukraine, 1346).
• Japanese army, Unit 731, (WW2) – experiments, tested on
populations in China and Manchuria
• Former Soviet Union have successfully weaponized it
• 1970 report by WHO on biological threats!
Riedel, 2005

49. Recommendations

50. Recommendations
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51. Recommendations Contd.
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52. Conclusion

53. Global Comparison (2010-2015)
Cases Deaths Mortality rate
Africa 3123 562 18%
Asia 17 8 47%
North America 39 5 13%
South America 69 9 13%
Total 3248 584 18%
Most recent global data on cases and deaths from Y. pestis (WHO, 2016)

54. Conclusion:
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55. Conclusion (contd.):
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56. To Finish…
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57. References - images
• Yersinia pestis bacterium - http://www.sciencephoto.com/media/11357/view
• “Dance of Death” - http://www.historytoday.com/ole-j-benedictow/black-death-greatest-catastrophe-ever
• Plague of Justinian (2 images) - http://www.romeacrosseurope.com/?p=5893#sthash.X4C6fOXW.dpbs
• Black Death doctor - http://www.health24.com/Medical/infectious-diseases/News/Bubonic-Plague-15-facts-20130318
• Black death map - http://www.historytoday.com/ole-j-benedictow/black-death-greatest-catastrophe-ever
• Third pandemic map - https://www.ucc.ie/en/about/uccnews/archive/2010pressreleases/fullstory-109689-en.html
• Madagascar map -
https://www.google.ie/search?q=madagascar&biw=1242&bih=602&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjC9JTYsq7SAhWIKcAKHdERAksQ_AUIBigB#tbm=isch&q=madagascar+plague&*&
imgrc=lTou3aS4XetDtM
• Map image (China) - https://commons.wikimedia.org/wiki/File:China_(%2Bclaims_hatched),_administrative_divisions_-_de_-_colored.svg
• Map image (India) - http://www.mapsofindia.com/maps/india/large-color.html
• Map image (Indonesia) - http://www.pariwisataboyolali.com/2008/12/boyolali-map.html
• Flea Cycle (CDC) https://www.cdc.gov/dpdx/fleas/modules/fleaslifecycle.gif [removed content]
• Wild rodent cycle http://www.columbia.edu/itc/cerc/danoff-burg/invasion_bio/inv_spp_summ/Yersinia_pestis_files/image006.jpg [removed content]
• Plague doctors - https://themedicinemaker.com/fileadmin/issues/16-09/images/0916-206-img.png
• Global prevalence maps (1954-2015 and 2010-2015) created using Microsoft Paint and a blank world map from Dr. Odd website - http://www.drodd.com/html7/blank-world-map.html

58. References (contd.)
• Achtman, M., 2012. Insights from genomic comparisons of genetically monomorphic bacterial pathogens. Philosophical Transactions of the Royal Society of London B: Biological
Sciences, 367(1590), pp.860-867.
• Aikimbajev, A., Meka-Mechenko, T., Temiralieva, G., Bekenov, J., Sagiyev, Z., Kaljan, K. and Mukhambetova, A.K., 2002. Plague in Kazakhstan at the present time. Przeglad epidemiologiczny, 57(4),
pp.593-598.
• Akiev, A.K., 1982. Epidemiology and incidence of plague in the world, 1958-79. Bulletin of the World Health Organization, 60(2), p.165.
• Benedictow, O.J., 2005. The Black Death: the greatest catastrophe ever. History Today, 55(3), p.42.
• Butler, T., 1983. Plague and other Yersinia infections. Springer Science & Business Media.
• Butler, T., 2009. Plague into the 21st century. Clinical Infectious Diseases, 49(5), pp.736-742.
• Cavanaugh, D.C. and MARSHALL JR, J.D., 1972. The influence of climate on the seasonal prevalence of plague in the Republic of Vietnam. Journal of Wildlife Diseases, 8(1), pp.85-94.
• Cavanaugh, D.C., Dangerfield, H.G., Hunter, D.H., Joy, R.J., Marshall Jr, J.D., Quy, D.V., Vivona, S. and Winter, P.E., 1968. Some observations on the current plague outbreak in the Republic of
Vietnam. American Journal of Public Health and the Nations Health, 58(4), pp.742-752.
• Centers for Disease Control and Prevention, 1996. Prevention of Plague: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Available at:
https://www.cdc.gov/mmwr/preview/mmwrhtml/00044836.htm
• Centers for Disease Control and Prevention, 2015. Plague. Available at: https://www.cdc.gov/plague/faq/
• Centers for Disease Control and Prevention, 2015. “Prevention ”Centers For Disease Control and Prevention.2015. https://www.cdc.gov/plague/prevention/index.html
• Centers for Disease Control and Prevention, 2016. Maps and Statistics. https://www.cdc.gov/plague/maps/index.html
• Dikid, T., Jain, S.K., Sharma, A., Kumar, A. and Narain, J.P., 2013. Emerging & re-emerging infections in India: An overview. Indian Journal of Medical Research, 138(1), p.19.
• ECDC, 2014. “Rapid Risk Assessment, plague outbreak ”ECDC.2014. http://ecdc.europa.eu/en/publications/Publications/plague-madagascar-rapid-risk-assessment-4-December-2014.pdf
• Echenberg, M.J., 2002. Pestis redux: The initial years of the third bubonic plague pandemic, 1894-1901. Journal of World History, 13(2), pp.429-449.
• Galdan, B., Baatar, U., Molotov, B. and Dashdavaa, O., 2010. Plague in mongolia. Vector-borne and zoonotic diseases, 10(1), pp.69-75.
• Harbeck, M., Seifert, L., Hänsch, S., Wagner, D.M., Birdsell, D., Parise, K.L., Wiechmann, I., Grupe, G., Thomas, A., Keim, P. and Zöller, L., 2013. Yersinia pestis DNA from skeletal remains from the 6
th century AD reveals insights into Justinianic Plague. PLoS Pathog, 9(5), p.e1003349.
• Heier, L., Storvik, G.O., Davis, S.A., Viljugrein, H., Ageyev, V.S., Klassovskaya, E. and Stenseth, N.C., 2011. Emergence, spread, persistence and fade-out of sylvatic plague in Kazakhstan. Proceedings
of the Royal Society of London B: Biological Sciences, 278(1720), pp.2915-2923.

59. References (contd.)
• Horgan, J. “Justinian's Plague (541-542 CE),” Ancient History Encyclopedia. Last modified December 26, 2014. http://www.ancient.eu/article/782/
• Kiersten J. Kugeler, J. Erin Staples, Alison F. Hinckley, Kenneth L. Gage, and Paul S. Mead 2015. Epidemiology of Human Plague in the United States, 1900–2012. PubMed.
• Mittal, V., Rana, U.V., Jain, S.K., Kumar, K., Pal, I.S., Arya, R.C., Ichhpujani, R.L., Lal, S. and Agarwal, S.P., 2004. Quick control of bubonic plague outbreak in Uttar Kashi, India. The Journal of
communicable diseases, 36(4), pp.233-239.
• Pham, H.V., Dang, D.T., Minh, N.N.T., Nguyen, N.D. and Nguyen, T.V., 2009. Correlates of environmental factors and human plague: an ecological study in Vietnam. International Journal of
Epidemiology, p.dyp244.
• Rasmussen, S., Allentoft, M.E., Nielsen, K., Orlando, L., Sikora, M., Sjögren, K.G., Pedersen, A.G., Schubert, M., Van Dam, A., Kapel, C.M.O. and Nielsen, H.B., 2015. Early divergent strains of Yersinia
pestis in Eurasia 5,000 years ago. Cell, 163(3), pp.571-582.
• Riedel, S., 2005, April. Plague: from natural disease to bioterrorism. In Baylor University Medical Center. Proceedings (Vol. 18, No. 2, p. 116). Baylor University Medical Center.
• SchneideM. C., Najera, P., Aldighieri, S., Galan, D. I., Bertherat, E., Ruiz, A., Dumit, E., Gabastou, J. M. and Espinal, M. A. (2014) 'Where Does Human Plague Still Persist in Latin America?' in Vinetz, J.
M., ed., PLoS Negl Trop Dis, San Francisco, USAr,.
• Stenseth, N.C., Atshabar, B.B., Begon, M., Belmain, S.R., Bertherat, E., Carniel, E., Gage, K.L., Leirs, H. and Rahalison, L., 2008. Plague: past, present, and future. PLoS Med, 5(1), p.e3.
• Tamara Ben Ari, Alexander Gershunov, Kenneth L Gage, Tord Snäll, Paul Ettestad, Kyrre L Kausrud, Nils Chr Stenseth,2008. Human plague in the USA: the importance of regional and local climate.
Royal Society.
• Thaung, U., Kyi, K.M., Maung, S.M., San Myint, D., Sein, W.U., Hein, R. and Khai, M.C., 1978. An outbreak of plague in Hlegu, Burma in 1977. The Southeast Asian journal of tropical medicine and
public health, 9(3), pp.390-397.
• World Health Organization. 2017 “Emergencies preparedness, response” World Heath Organisation. 2017. http://www.who.int/csr/don/archive/disease/plague/en/
• World Health Organization, 2016. “Plague ” World Health Organization.2015. http://www.who.int/mediacentre/factsheets/fs267/en/
• World Health Organization, 2016. Weekly Epidemiological Record, 26 February 2016, vol. 91, 8 (pp. 89–104).

60. Thank you! Questions?
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