Smallpox: Then & Now

1. Smallpox: Then & Now Lisa Louise Brailey, MD History of Medicine, PATH 214 February 23, 2000

2. Smallpox Family Tree Family: Poxviridae Subfamily: Chordopoxvirinae Genus: Orthopoxvirus Species: variola Subspecies: major and minor Related Species: vaccinia cowpox monkeypox ectromelia camelpox taterapox raccoonpox Uasin Gishu Related Genera: Avipoxvirus Capripoxvirus Leporipoxvirus Parapoxvirus Suipoxvirus Tanapox Molluscum contagiosum

3. Smallpox Virion -large, complex virus -“brick-shaped” particle -linear double-stranded DNA -disk-shaped core -double membrane -lipoprotein envelope -replicates in cytoplasm -single, stable serotype

4. Smallpox: Clinical features -transmitted by respiratory aerosol, direct contact with lesions, contact via fomites -virus enters upper respiratory tract, causes primary viremia -then infects internal organs, causes secondary viremia -spreads to skin; rash is caused by viral replication -incubation period of 7-14 days from infection to symptoms

5. Smallpox: Clinical features -prodrome of fever and malaise -skin rash proceeding from macules to papules to vesicles to pustules to crusts over the course of 2-3 weeks -lifelong immunity, though vaccination confers ~10 years immunity

6. Variola minor A less virulent form of the variola virus existed. Its existence may have hindered the eradication process, because people were less likely to be concerned about a more minor disease and were, therefore, less likely to report an infection. This woman continued her normal daily activities throughout her illness.

7. Case-Fatality Rates Variola major: ~20-50% depending on population Variola minor: 1% There were several clinical forms of smallpox identified: usual, discrete, confluent, hemorrhagic, flat, and probably more. Both the subtype of smallpox and individual and population variation would affect mortality rates.

8. History of Smallpox 2000-1000 BC: possible smallpox in Egyptian mummies This is the mummy of Ramses V, who died in 1157 BC. Note the eruptions on the lower face. Also note skin folds possibly due to swelling.

9. Pattern of Spread in Africa

10. History of Smallpox ~100 BC: probable mention in Susruta Samhita in India Spread to Middle East, Far East, and Europe

11. 48-49: introduced into China from the southwest 450: Bishop Nicaise of Rheims recovers from smallpox 622: smallpox described by Ahrun of Alexandria 583: spread from China to Korea 585: spread from Korea to Japan 700s: Arabs carry to Spain 900s: Arabs carry to western Africa Al-Razi describes smallpox Chinese intranasal variolation Japanese describe “red treatment” 1000- 1100: spread by Crusaders

12. History of Smallpox 1200s: cutaneous variolation by Mamelukes in Egypt introduction of smallpox to Iceland from Denmark 1438: major Paris epidemic 1507: introduction to Caribbean 1520: to Mexico 1524: to Peru 1555: to Brazil 1617: epidemic in Massachusetts 1623: first account in Russia 1630: Siberia 1713: South Africa; destruction of Hottentots 1724: variolation in Siberia 1744: variolation in Japan 1776: Quebec; next year Washington variolates continental army 1789: Australian aborigines

13. History of Smallpox 1600s: nasal variolation regularly practiced in China This Chinese drawing portrays insufflation of powdered smallpox scabs.

14. History of Smallpox Spread of Smallpox During Colonialization

15. History of Smallpox 1798: Edward Jenner describes vaccination 1800s: Native American pandemics 1802: vaccination in India 1805: in India 1840: in Siam 1849: in Japan 1845: systematic production of vaccine in cows, Negri in Naples 1863: President Lincoln develops smallpox 1890s: Variola minor described in South Africa 1896: Variola minor in Florida; spreads through US in 4 years

16. History of Smallpox 1863: Abraham Lincoln contracted smallpox This portrait was taken eleven days before the Gettysburg Address. Lincoln developed smallpox just hours after the Address, so this photograph may have been taken on the day he was initially infected.

17. History of Smallpox 1798: Edward Jenner describes vaccination Edward Jenner (1749-1823) A pastel portrait by J.R.Smith from 1800 cleverly portrays Jenner with a cow and milkmaid in the background.

18. Edward Jenner -born May 17, 1749 -third son of Reverend Stephen Jenner -apprenticed to an apothecary at age 13 -private house-student of John Hunter in 1770 -studied angina pectoris, cuckoos, manure, ophthalmology, bird migration, tuberculosis -violinist, poet, artist -apparently became interested in vaccination when told by a country girl that she was immune from smallpox because she’d had cowpox -vaccinated an 8 year old boy, James Phipps, in 1796 with material from a presumed cowpox lesion on the hand of Sarah Nelmes -found that those vaccinated were resistant both to variolation and to smallpox infection

19. History of Smallpox 1801: Jenner prophesizes the eventual eradication of smallpox

20. Comparison of Variolation and Vaccination Variolation caused a more severe skin eruption, but one much less severe than full-blown smallpox. Vaccination generally caused a single pustule at the site of inoculation.

21. Average Life Expectancy at Birth (in years) France 1795 1817-31 Male 23 38 Female 27 41 This effect is presumed to be primarily due to the introduction of vaccination. Vaccination was the only major public health program implemented during the first part of the nineteenth century.

22. History of Smallpox 1914: epidemic in Russia due to WWI 1951: eliminated from North America, Central America 1953: eliminated from Europe 1950s: eliminated from Mediterranean Africa 1955: 8thWorld Health Assembly rejects concept of eradication as unrealistic 1959: at urging of Viktor Zhdanov, 12th WHA undertakes global eradication of smallpox 1960s: eliminated from China 1966: Intensified Smallpox Eradication Programme

23. Eradication by Vaccination Facilitated by Five Critical Factors Smallpox: 1. has a single stable serotype 2. has no animal reservoir 3. causes a prompt antibody response 4. is easily recognized clinically 5. does not cause subclinical infections or carrier states

24. Eradication Strategies -mass vaccination programs -surveillance with outbreak containment -reward programs for identifying cases -smallpox recognition cards and pamphlets -development of heat stable vaccines total expenditure of $97,969,737 from 1967 to 1979

26. History of Smallpox 1966: intensification of efforts to wipe out smallpox, despite widespread discreditation of the concept of eradication (Failures to eradicate yellow fever and malaria left doubts regarding the possibility of ultimate success.) WHO smallpox identification card, shown to people to help them identify local cases of smallpox.

27. History of Smallpox 1975: eradication from Asia Rahima Banu, who had the world’s last case of naturally occurring Variola major (Bangladesh)

28. History of Smallpox 1977: eradication of smallpox from the entire world Ali Maow Maalin, who had the world’s last case of naturally occurring smallpox (Somalia)

29. History of Smallpox But… August 27,1978, Birmingham, England Janet Parker, a 40 year old medical photographer, developed electron microscopically proven smallpox, probably through an air duct connected to the smallpox laboratory at the University of Birmingham. She died of renal failure associated with her illness. Her father died on September 5 of a myocardial infarction. The professor who ran the microbiology laboratory committed suicide and died on September 7. Her mother developed a mild case of smallpox on September 8, recovered and was released from quarantine on September 22. This latter was the last known case of smallpox in the world.

30. History of Smallpox We, the members of the global commission for certification of smallpox eradication, certify that smallpox has been eradicated from the world. Geneva December 9, 1979 Official parchment certifying global eradication

31. Potential Sources for a Return of Smallpox -wildlife reservoir -material stored by variolators -laboratory stocks -secret stocks for possible biological warfare -reactivation of latent virus -preservation on scabs, clothing, gravesites -transformation of another species of orthopoxvirus All are generally viewed as highly unlikely.

32. History of Smallpox As of 1988, two laboratories were known to have variola virus stocks: Moscow Research Institute for Viral Preparations Centers for Disease Control, Atlanta

33. Bibliography Baxby, Derrick. Jenner’s Smallpox Vaccine: The Riddle of Vaccinia Virus and its Origin. Heinemann Educational Books, London, 1981. Fenner, F. et al. Smallpox and its Eradication. World Health Organization, Geneva, 1988. Hopkins, Donald. Princes and Peasants: Smallpox in History. University of Chicago Press, Chicago, 1983. Jenner, Edward. The Causes and Effects of the Variolae Vaccinae. Sampson Low, London, 1798 (privately reprinted for the Classics of Medicine Library, 1978). Levinson, Warren and Jawetz, Ernest. Medical Microbiology and Immunology. Appleton and Lange, Norwalk, Connecticut, 1994. Shurkin, Joel. The Invisible Fire: The Story of Mankind’s Victory Over the Ancient Scourge of Smallpox. G.P. Putnam, New York, 1979.