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Chapter: Medical Microbiology: An Introduction to Infectious Diseases: Poxviruses

Variola (Smallpox)

Two virus types are known: variola major and variola minor (alastrim).



Two virus types are known: variola major and variola minor (alastrim). Although the viruses are indistinguishable antigenically, their fatality rates differ considerably ( 1% for variola minor, 3–35% for variola major). They are also difficult to distinguish in the labo-ratory; however, variola major has slightly greater virulence in embryonated hen’s eggs.


Smallpox  is  an  acute  infection  in  which  the  dominant  feature  is  a  uniform papulovesicular rash that evolves to pustules over 1 to 2 weeks. The potential for spread and mortality is significant, particularly in a nonimmune population.

Smallpox has played a significant role in world history with respect to both the seri-ous epidemics recorded since antiquity and the sometimes dangerous measures taken to prevent infection. Smallpox virus is highly contagious and can survive well in the extra-cellular environment. Acquisition of infection by infected saliva droplets or by exposure to skin lesions, contaminated articles, and fomites has been well documented.

In 1967, the World Health Organization (WHO) launched an ambitious program aimed at eradication of smallpox. This goal was considered realistic for two major rea-sons: (1) no extrahuman reservoir of the virus was known to exist, and (2) asymptomatic carriage apparently did not occur. The basic approach included intensive surveillance for clinical cases of smallpox, prompt quarantine of such patients and their contacts, and im-munization of contacts with vaccinia virus (vaccination) to prevent further spread. A tremendous amount of effort was involved, but the results were astonishing: the last recorded case of naturally acquired smallpox occurred in Somalia in 1977. Global eradi-cation of smallpox was confirmed in 1979 and accepted by the WHO in May 1980. Since then, the virus has been solely secured in two WHO-restricted laboratories: one at the United States Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the other at a similar facility in Moscow, Russia.

Unfortunately, the dramatic world events that occurred in 2001 have raised the chilling possibility that clandestine virus stocks may exist elsewhere and could be effectively used for major bioterrorist attacks. Reasons for such concern include (1) known high infectivity among humans; (2) high susceptibility among populations (routine vaccination against smallpox ended in 1972, and current vaccine supplies are limited); (3) risk that health care providers may not promptly recognize and respond to early cases; and (4) absence of spe-cific antiviral treatment. A response plan and guidelines for such threats is posted on a CDC website(www.cdc.gov/nip/smallpox)and is updated at regular intervals.

Continuing surveillance also includes studies of poxviruses of animals (eg, buffalopox, monkeypox) that are antigenically somewhat similar to smallpox. Some virologists remain legitimately concerned that an animal poxvirus, such as monkeypox, could mutate to become highly virulent to humans—a further reminder that complacency could be dangerous.


The orthopoxviruses as a group cause a dramatic effect on host cell macromolecular func-tion, leading to a switch from cellular to viral protein synthesis, changes in cell mem-brane permeability and cytolysis. Eosinophilic inclusions, called Guarnieri’s bodies, can be seen in the cytoplasm. Multiple viral proteins, such as complement regulatory protein and other factors that can interfere with induction or activities of multiple host mononu-clear cell cytokines, are also synthesized; this serves to impair the host defenses that are important in early control of infection.

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