Smallpox natural history

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

The natural history and outcome of smallpox depend on the form of disease. The common progress will start with flu-like symptoms followed by a skin rash that generally progresses in a typical fashion, leading to the formation of scabs that will fall off, leaving a scar. The complications may include respiratory conditions, from bronchitis to pneumonia, but may also involve the joints, bones and/or eyes. The overall fatality rate for the variola major form was about 30%.

Smallpox, considered eradicated since 1980 by the WHO, affected mainly children, young adults and family members of infected patients. Symptoms depended on the form of the disease. For the most common form, the ordinary smallpox, symptoms usually developed according to the following sequence:^[1]

• Duration approximately 12 – 14 days
• Noncontagious
• Asymptomatic

• Duration approximately 2 – 4 days
• Sometimes contagious
• Fever
• Malaise
• Muscle pain and headache
• Vomiting

• Duration approximately 4 days
• Most contagious stage
• Rash as small red spots in the mouth
• Rash turns into sores releasing the virus
• Rash appears on the skin, starting on the face, moving towards arms and hands, eventually spreading to the rest of the body within 24 hours
• At this time, fever usually falls and the person feels better
• At the 3rd day of rash, it turns into raised bumps
• At the 4th day of rash, bumps are filled with fluid, with a central depression
• Fever will then raise again, until scabs are formed

• Duration approximately 5 days
• Contagious
• Bumps turn into pustules

• Duration approximately 5 days
• Contagious
• Pustules first form a crust and than a scab

• Duration approximately 6 days
• Scabs start to fall leaving scars not the skin
• Contagious, until all scabs have fallen
• Most scabs will have fallen 3 weeks after start of rash

• All scabs have fallen off
• Person is no longer contagious

Common complications of smallpox include:

• Respiratory complications (viral or bacterial):

• Bronchitis
• Fatal pneumonia

• Secondary bacterial skin infection
• Encephalitis – 1 in 500 patients, commonly in adults
• Permanent pitted scars
• Eye problems – 2% of all cases; pustules can form on the eyelid, conjunctiva, and cornea, leading to:

• Conjunctivitis
• Keratitis
• Corneal ulcer
• Iritis
• Iridocylcitis
• Optic atrophy
• Blindness – occurs in 35% to 40% of eyes affected with keratitis and corneal ulcer
• Subconjunctival and retinal hemorrhages.

• Osteomyelitis – lesions are symmetrical, most common in the elbows, tibia, and fibula
• Arthritis may lead to limb deformities
• Ankylosis

The prognosis of smallpox depends on the form of the disease:

• Fatality rate about 10% for patients with discrete lesions and 60% for those with confluent lesions^[2]
• In fatal cases, death usually occurs between the 10th and 16th days of illness
• Unclear cause of death
• Infection often affected multiple organs
• Possible contributors include:

• Circulating immune complexes
• Severe viremia
• Uncontrolled immune response

• Fatality rate about 90%
• Cause of death commonly included: loss of fluids, electrolytes and protein, as well as severe sepsis

• Fatality rate near 100%, usually between 6th and 7th day after the beginning of fever
• Cause of death was often heart failure, or in late cases intense viremia, with severe platelet loss and weak immune response

• Fatality rate about ≤1%

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