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Smallpox is an infectious disease that no longer occurs naturally.

What is smallpox?

Smallpox is a virus from the Orthopoxvirus family. The disease comes in various forms, each identified by the features of its rash. The rash, which develops into characteristic pustules, can leave the skin permanently scarred.

The two most common forms of smallpox were:

  • Variola major – the more severe form and usually kills up to 40% of unvaccinated people infected and 3% of those who are vaccinated. Death usually occurs five to seven days into the illness.
  • Variola minor – less severe; usually kills 1-2% of unvaccinated infected people.

There are also less common and more serious forms of smallpox:

Purpura variolosa (or haemorrhagic-type smallpox) – the most severe form. Sufferers usually experience a severe loss of blood into the skin and internal organs and die before the typical smallpox rash appears. Haemorrhagic smallpox is always fatal.

Flat-type (malignant) smallpox – another rare form of smallpox seen in a small percentage of people. Skin lesions develop more slowly, are never raised above the surface of the skin, and feel soft to the touch. Malignant smallpox is characterised by severe illness and is almost always fatal, but those that survive this form rarely experience severe scarring.

Symptoms and course

The first symptoms of smallpox usually occur within 10 to 12 days after exposure, with the rash appearing two to four days later. The first symptoms could appear, however, as early as six days after exposure, or as late as 22 days.

The initial symptoms of smallpox are flu-like:

  • Headache
  • High fever with rigors (bouts of uncontrollable shivering)
  • Severe muscle aches and backache
  • Abdominal pain and vomiting
  • Delirium (confusion and a lowered level of consciousness)

Two or three days later, the fever drops and a characteristic rash appears all at once all over the body. This is in contrast to the rash of chickenpox that appears in groups or ‘crops’ at the peak of the fever. The smallpox rash starts as flat or slightly thickened spots (known as macules) and progresses to raised spots (known as papules).

The lesions begin in the mucous membranes of the mouth and spread to the face, forearms and hands, where they remain more concentrated, before spreading to the legs and torso. A noticeable feature of the rash is that the palms and soles are not spared and most of the lesions in any given area are in the same stage of development.

These spots grow and become filled with clear fluid. As they continue to enlarge, the fluid inside gradually becomes pus like (around the eighth day of illness), and the spots are then referred to as pustules. During this stage fever is common.

By the second week, the pustules dry up and form scabs. After three weeks, the dried scabs start to fall off the skin, often leaving the skin permanently scarred.

Apart from lesions in the skin, internal organs such as lymph nodes, spleen, liver, bone marrow and lungs are damaged early in the disease. Respiratory problems are very common in smallpox victims. Complications included bone, joint and eye inflammation, the latter sometimes resulting in blindness.

What is the cause of smallpox?

Smallpox is a contagious virus that spreads directly from person to person, primarily by secretions from the nose or mouth and material from scabs or pocks. Contrary to common belief, smallpox spreads quite slowly and requires close personal contact with an infected person. Contaminated clothing or bed linen can also spread the virus.

Smallpox patients are most infectious during the first week of the rash and a person remains contagious until the scabs have fallen off.

Smallpox spreads most readily during the cool, dry winter months but can be transmitted in any climate and in any part of the world.


Smallpox used to be worldwide in scope, but the last known case of naturally occurring smallpox in a human was recorded in Somalia in 1977. There have been a limited number of cases since then, where researchers have become infected from exposures that took place in a laboratory.

In 1980, the World Health Organization announced that smallpox had been eradicated and recommended that all countries cease vaccination.

What are the risk factors?

Today, risk factors for smallpox include being a laboratory worker who handles the virus (rare), or being in the environment where the virus is released as a biological weapon. Although it is potentially a fatal disease in any person, the very young and the elderly are at increased risk. Pregnant women are most at risk for severe disease and death.

How is it treated?

There is no effective antiviral drug to treat smallpox. Treatment is limited to supportive therapy and antibiotics are required for secondary bacterial infections. There is an effective vaccine to prevent smallpox, which played a large part in eradicating the disease. Until the disease was declared eradicated in 1980, the smallpox vaccine was a universal childhood vaccine. The vaccine is also effective in reducing the risk of death if given within three to five days of exposure.

The original smallpox vaccine, a live attenuated viral vaccine containing an attenuated virus called ‘vaccinia’, was, however, sometimes associated with significant complications. The risk of adverse effects, accompanied by the rapid decrease in smallpox around the world in the 1970s, was part of the justification to discontinue routine vaccination. Towards the end of the smallpox eradication campaign, other strains of virus were used in the attenuated smallpox vaccines, including a virus known as ‘modified vaccinia ankara’ or MVA. This recombinant MVA containing vaccine was used safely with very few side effects and forms the basis of some research for an appropriate vehicle or vector for a preventative HIV vaccine.

The only persons currently recommended to receive smallpox vaccine are persons working in a laboratory setting with smallpox or closely related viruses.

In the unlikely event that the diagnosis of smallpox is made, those suspected of being infected should be immediately isolated and all persons in the household and others who have had face-to-face contact with the infected person after the onset of fever should be vaccinated.

How is it diagnosed?

Smallpox can be difficult to diagnose early in the disease because of the non-specific initial symptoms. Very severe disease may result in death even before the rash is fully developed and sometimes, as in haemorrhagic smallpox, haemorrhaging can focus attention on another cause.

Smallpox is often confused with chickenpox, but several features of these diseases are different:

  • The initial symptoms of smallpox are much more severe than those of chickenpox.
  • Smallpox rash is most dense on exposed sections of the body like the face, forearms, palms, legs, feet, and soles – chickenpox is most dense on covered areas of the body (chest and back).
  • Smallpox rash lesions tend to be at the same stage of development, and there is only one eruption – with chickenpox, it is common to have more than one eruption of lesions and these can be in different stages of maturation.
  • Smallpox lesions tend to be deeper in the skin than chickenpox lesions and hard to the touch.

Definitive testing for smallpox is done through a laboratory and involves a sample of vesicular fluid and biopsy of scab material.

How is it prevented?

While smallpox itself creates lifetime immunity, successful vaccination offers high level protection for about five years. Adults given smallpox vaccinations as children before the disease was eradicated in the mid-1970’s, have probably lost their immunity to the highly infectious disease.

Vaccination before exposure or within two to three days after exposure affords almost complete protection against disease. Vaccination as late as four to five days after exposure may protect against death.

Smallpox vaccination is associated with some risk for adverse reactions, including severe ulceration and scarring at the vaccine site, encephalitis and developing a milder smallpox-like illness.

Groups at risk for smallpox vaccination complications include people with eczema or other skin conditions, those with suppressed immune systems, pregnant women and infants.

(Reviewed by Dr Eftyhia Vardas, Faculty of Health Sciences, University of the Witwatersrand)

The information provided in this article was correct at the time of publishing. At Mediclinic we endeavour to provide our patients and readers with accurate and reliable information, which is why we continually review and update our content. However, due to the dynamic nature of clinical information and medicine, some information may from time to time become outdated prior to revision.

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