Smallpox: Then & Now

Lisa Louise Brailey, MD

History of Medicine, PATH 214

February 23, 2000

Smallpox Family TreeFamily: PoxviridaeSubfamily: ChordopoxvirinaeGenus: OrthopoxvirusSpecies: variolaSubspecies: major and minorRelated Species: vaccinia

cowpoxmonkeypoxectromeliacamelpoxtaterapoxraccoonpoxUasin Gishu

Related Genera: AvipoxvirusCapripoxvirusLeporipoxvirusParapoxvirusSuipoxvirusTanapoxMolluscum contagiosum

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

Smallpox Virion

-transmitted by respiratoryaerosol, direct contact withlesions, contact via fomites

-virus enters upper respiratorytract, causes primary viremia

-then infects internal organs, causes secondary viremia

-spreads to skin; rash is causedby viral replication

-incubation period of 7-14 daysfrom infection to symptoms

Smallpox: Clinical features

Smallpox: Clinical features

-prodrome of feverand malaise

-skin rash proceedingfrom macules topapules to vesicles topustules to crustsover the course of2-3 weeks

-lifelong immunity, though vaccinationconfers ~10 yearsimmunity

Variola minorA less virulent form ofthe variola virus existed.Its existence may have hindered the eradicationprocess, because peoplewere less likely to beconcerned about a more minor disease and were, therefore, less likely to report an infection.

This woman continued hernormal daily activitiesthroughout her illness.

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.

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 eruptionson the lower face. Also noteskin folds possibly due toswelling.

Pattern of Spread in Africa

History of Smallpox

~100 BC: probable mention in Susruta Samhita in India

Spread to Middle East, Far East, and Europe

48-49: introduced into China from the southwest450: Bishop Nicaise of Rheims recovers from smallpox622: smallpox described by Ahrun of Alexandria583: spread from China to Korea585: spread from Korea to Japan700s: Arabs carry to Spain900s: Arabs carry to western Africa

Al-Razi describes smallpoxChinese intranasal variolationJapanese describe “red treatment”

1000-1100: spread by Crusaders

1200s: cutaneous variolation by Mamelukes in Egyptintroduction of smallpox to Iceland from Denmark

1438: major Paris epidemic1507: introduction to Caribbean1520: to Mexico1524: to Peru1555: to Brazil1617: epidemic in Massachusetts1623: first account in Russia1630: Siberia1713: South Africa; destruction of Hottentots1724: variolation in Siberia1744: variolation in Japan1776: Quebec; next year Washington variolates continental army1789: Australian aborigines

History of Smallpox

History of Smallpox

1600s: nasal variolationregularly practiced in China

This Chinese drawing portraysinsufflation of powderedsmallpox scabs.

Spread of Smallpox During Colonialization

History of Smallpox

History of Smallpox

1798: Edward Jenner describes vaccination1800s: Native American pandemics1802: vaccination in India1805: in India1840: in Siam1849: in Japan1845: systematic production of vaccine in cows, Negri in Naples1863: President Lincoln develops smallpox1890s: Variola minor described in South Africa1896: Variola minor in Florida; spreads through US in 4 years

History of Smallpox

1863: Abraham Lincolncontracted smallpox

This portrait was takeneleven days before theGettysburg Address. Lincolndeveloped smallpox just hours after the Address, so this photograph may have been taken on the day he wasinitially infected.

History of Smallpox

1798: Edward Jennerdescribes vaccination

Edward Jenner (1749-1823)

A pastel portrait by J.R.Smithfrom 1800 cleverly portraysJenner with a cow and milkmaid in the background.

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 materialfrom a presumed cowpox lesion on the hand of Sarah Nelmes

-found that those vaccinated were resistant both to variolationand to smallpox infection

History of Smallpox

1801: Jenner prophesizes the eventual eradication ofsmallpox

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 ofinoculation.

Average Life Expectancy at Birth (in years)France

1795 1817-31Male 23 38Female 27 41

This effect is presumed to be primarily due to the introductionof vaccination. Vaccination was the only major public health program implemented during the first part of the nineteenth century.

History of Smallpox

1914: epidemic in Russia due to WWI1951: eliminated from North America, Central America1953: eliminated from Europe1950s: eliminated from Mediterranean Africa1955: 8thWorld Health Assembly rejects concept of eradication

as unrealistic1959: at urging of Viktor Zhdanov, 12th WHA undertakes

global eradication of smallpox1960s: eliminated from China1966: Intensified Smallpox Eradication Programme

Eradication by Vaccination Facilitated by Five Critical Factors

Smallpox:

1. has a single stable serotype2. has no animal reservoir3. causes a prompt antibody response4. is easily recognized clinically5. does not cause subclinical infections or carrier states

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

History of Smallpox

1966: intensification of effortsto wipe out smallpox, despitewidespread discreditation ofthe concept of eradication(Failures to eradicate yellow fever and malaria left doubts regarding the possibility ofultimate success.)

WHO smallpox identificationcard, shown to people to help them identify local cases ofsmallpox.

History of Smallpox

Rahima Banu, who hadthe world’s last case of naturally occurring Variola major (Bangladesh)

1975: eradication from Asia

History of Smallpox

Ali Maow Maalin, whohad the world’s lastcase of naturallyoccurring smallpox(Somalia)

1977: eradication ofsmallpox from theentire world

History of Smallpox

But…August 27,1978, Birmingham, England

Janet Parker, a 40 year old medical photographer, developedelectron microscopically proven smallpox, probably throughan air duct connected to the smallpox laboratory at the University of Birmingham. She died of renal failure associatedwith her illness.Her father died on September 5 of a myocardial infarction.The professor who ran the microbiology laboratory committedsuicide 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.

We, the members of theglobal commission for certification of smallpoxeradication, certify that smallpox has beeneradicated from the world.

GenevaDecember 9, 1979

Official parchment certifying global eradication

History of Smallpox

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.

History of Smallpox

As of 1988, two laboratories were known to have variola virusstocks:

Moscow Research Institute for Viral PreparationsCenters for Disease Control, Atlanta

BibliographyBaxby, 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 HealthOrganization, 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 theClassics 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.