Following infection with smallpox virus,
- asymptomatic viraemia develops on the 3rd or 4th day followed by dissemination and replication in the spleen, bone marrow and lymphoid tissues
- secondary viraemia begins around the 8th day and is associated with onset of a characteristic illness around 12 days following exposure (1)
There are two clinical forms of the disease
- variola major- results in a severe disease
- around 90% of cases of variola major in non-immune individuals would present with the following: - sudden onset of high fever with malaise, prostration, headache and backache
- a macular rash develops 1 to 3 days later,- firstly the rash appears on the oral and pharyngeal mucosa, spreading to the face and forearms, trunk and legs
 
- this becomes papular after 1 to 2 days and then vesicular after a further 1 to 2 days- the vesicular rash is typically more prominent on the face and extremities than on the trunk (centrifugal distribution)
 
- these vesicles become pustules after a further 2 to 3 days - pustules are round, tense and deep in the dermis
- they may affect the palms of the hands and soles of the feet
- the pustules form scabs after 5 to 8 days
- the scabs gradually separate leaving characteristic pitted scarring. The scars are most evident on the face
 
 
 
- variola minor
Atypical presentation of the disease.
In addition to the typical presentation, two other rare forms are seen in some cases:
- haemorrhagic smallpox - observed in all ages and in both sexes with pregnant women appearing to be unusually susceptible
- haemorrhage in to the mucous membranes and the skin accompanied the rash
- may be misdiagnosed as meningococcal septicaemia or acute leukaemia.
 
- malignant smallpox - characterised by lesions that did not develop to the pustular stage but remained soft and flat.
- flat-type smallpox was seen in around 6% of cases and was more common in children.
- commonly misdiagnosed as haemorrhagic chickenpox
 
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