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