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The world’s last case of smallpox, which was due to infection with variola major virus, occurred in 1978. This disease is ancient and played many roles in the course of history. For example, many members of various royal families, including Louis XV of France, died of this illness. The global elimination of smallpox by vaccination remains a major historical and medical milestone. Routine vaccination against smallpox was discontinued in the United States in 1972.1-4 There was a brief resurrection of use of vaccine in the United States during the early 2000s when there was fear that the virus might be used as an agent of bioterrorism.5,6 The smallpox vaccine contains live vaccinia virus, which confers protection against infection from variola virus, the cause of smallpox. Vaccinia virus can be transmitted from a vaccine recipient to other persons through direct (skin-to-skin) contact via material from the unhealed vaccination site or through indirect contact by means of fomites. This can result in eczema vaccinatum, a life-threatening complication of vaccinia virus infection (eFig. 322.1) no longer seen since use of the vaccine was discontinued. This brief chapter is included in this textbook to mark the momentous medical event of disease elimination and to remind medical personnel of the disease that once existed and, it is hoped, will remain forever gone.

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eFigure 322.1.
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Eczema vaccinatum rash with umbilicated lesions in a 28 month old boy exposed following his father's smallpox vaccination.

(From http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5619a4.htm)

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Smallpox is caused by variola virus, a member of the Poxvirus family. It is one of the largest and most complex DNA viruses. For this reason it is easily identified by electron microscopy. This virus is, however, highly contagious and quite stable. It is not a virus to be easily reckoned with. Related viruses include monkeypox, vaccinia, and cowpox.3,4

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Smallpox begins with symptoms such as high fever, malaise, pain (typically in the back, abdomen, and head), and prostration. About 24 hours before onset of rash, an enanthem occurs on the oral mucosa. The rash begins on the face and is centrifugal in distribution (in contrast to varicella, with which it used to be confused). Rash is often present on the palms and soles. Rash progresses from macules to papules and pustules, some of which may become umbilicated. Rash lesions are all in the same stage of development, in contrast to varicella in which macules, papules, and pustules coexist in one area of skin. Smallpox is highly contagious while the rash is evolving, and its evolution may take several weeks. Untreated, unvaccinated patients who develop smallpox have a fatality rates as high as 30%, with highest mortality rates in infants and adults.3

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Diagnosis can be made rapidly by viewing vesicular lesions with electron microscopy. Patients in whom the diagnosis of smallpox is seriously being ...

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