Chapter 16 : History of Smallpox and Its Spread in Human Populations

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Smallpox, the infectious disease caused by species of the variola virus (VARV), is probably one of the most terrible diseases to have affected human populations over the past hundreds of years. Its dissemination was significantly related to global population growth and the movement of people across regions and continents. The geographical origin of the disease remains a matter of debate; hypotheses suggest the Indus Valley or Egypt and the Near East, regions that had high population densities 3,000 to 4,000 years ago ( ). The latter hypothesis was recently refined by Babkin and Babkina ( ), who suggested that the initial spread of the virus in humans could have occurred in the Horn of Africa (Kingdom of the Queen of Sheba). In this region, active trade expeditions overlapped with the distribution areas of several animal poxvirus hosts (including the naked-soled gerbil) and the introduction of the domesticated camel as a new potential host. The disease spread from these regions to the west and east, with historical reports suggesting epidemics in China and Europe as early as the 1st or 2nd century CE, with a subsequent progressive emergence of the virus in western Africa ( ). During the 16th century, smallpox was a significant cause of death in Europe. The smallpox agent was also exported to South America during this time and passed over both American continents ( ). As noted by Fenner et al., smallpox was a major global endemic disease by the mid-18th century, with the exception of Australia ( ). Only the variolation and vaccination campaigns initiated more than two centuries ago reduced dramatically the spread and impact of the disease in contemporary populations.

Citation: Thèves C, Crubézy E, Biagini P. 2016. History of Smallpox and Its Spread in Human Populations, p 161-172. In Drancourt M, Raoult D (ed), Paleomicrobiology of Humans. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PoH-0004-2014
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Figure 1

(Left) A young mummified woman from the Arbre Chamanique multiple burial; lung tissues were studied by microscopy and DNA analysis. (Courtesy of Patrice Gérard, CNRS.) (Top right) The lung tissue structure was identified. It exhibited numerous scattered, black-pigmented deposits, potentially the pigment of black lung disease (coal worker’s pneumoconiosis). Hematoxylin and eosin coloration, ×50. Courtesy of Catherine Cannet, IML, Strasbourg.) (Bottom right) A significant amount of iron was found in the lung parenchyma and may correspond to important bleeding. Perls coloration, × 100. Courtesy of Catherine Cannet, IML, Strasbourg.)

Citation: Thèves C, Crubézy E, Biagini P. 2016. History of Smallpox and Its Spread in Human Populations, p 161-172. In Drancourt M, Raoult D (ed), Paleomicrobiology of Humans. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PoH-0004-2014
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Image of Figure 2
Figure 2

Phylogenetic analysis of concatenated sequences of an ancient Siberian smallpox virus (PoxSib) and representative strains identified in humans and animals. Phylogeny suggests that the 300-year-old viral sequence did not belong to the cluster of strains sequenced from the 20th century (1947 to 1975). Strains identified in humans: Guin69, Guinea 1969; SierL69, Sierra Leone 1969; BenDH68, Benin 1968; BrazGar66 and Braz66, Brazil 1966; Syr72, Syria 1972; Pak69, Pakistan 1969; Ind64, India 1964; Sarf65, South Africa 1965; Bots72, Botswana 1972; Ethio72, Ethiopia 1972; Bangla75, Bangladesh 1975; Sum70, Sumatra 1970; ChinHorn48, China 1948; Kor47, Korea 1947; Jap51, Japan 1951; Tanz65, Tanzania 1965; Cng70, Congo 1970. Strains identified in animals: CMLV M96, camelpox virus M96; CPXV FIN, cowpox Finland 2000; CPXV GER, cowpox GER91-3; CPXV GRI, cowpox GRI-90; HPXV, horsepox virus 76; MPXV Z96, monkeypox Zaire-96; VACV, vaccinia virus Copenhagen-derived clone 1990. (Derived from Fig. 1B in reference . Reproduced with permission.)

Citation: Thèves C, Crubézy E, Biagini P. 2016. History of Smallpox and Its Spread in Human Populations, p 161-172. In Drancourt M, Raoult D (ed), Paleomicrobiology of Humans. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PoH-0004-2014
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Figure 3

Phylogenetic tree built with central conserved regions of diverse orthopoxvirus genomes (maximum credibility tree, Bayesian method) ( ). Mutation accumulation rates are shown (substitutions/site/year). Numbers on nodes indicate the time to the most recent common ancestor of the clades (in years). Gray bars: 95% highest probability density intervals; the posterior probabilities of all clades are >90% except the node marked with an asterisk. Strains: VARV, variola virus; TATV, taterapox virus; CMLV, camelpox virus; CPXV, cowpox virus; HPXV, horsepox virus; MPXV, monkeypox virus; MA VARV, variola minor alastrim strains; WA VARV, West African variola virus strains; WA MPXV, West African monkeypox virus strains. (Legend derived from Fig. 2 in reference ; figure reproduced from Fig. 2 in reference with permission.)

Citation: Thèves C, Crubézy E, Biagini P. 2016. History of Smallpox and Its Spread in Human Populations, p 161-172. In Drancourt M, Raoult D (ed), Paleomicrobiology of Humans. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PoH-0004-2014
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