Variola (the virus that causes smallpox) is the most notorious of the poxviruses. Smallpox was an important cause of illness and death in the developing world until recent times. In 1980, the World Health Organization (WHO) declared that smallpox had been completely wiped out. The last case was noted in Somalia in 1977.

Variola represents a significant threat as a biological warfare agent. Variola is highly infectious and is associated with a high death rate and secondary spread. Currently, the majority of the US population has no immunity, vaccine is in short supply, and no effective treatment exists for the disease. Two WHO-approved and inspected repositories remain: One is at the Centers for Disease Control and Prevention in the United States; the other at Vector Laboratories in Russia. It is widely believed that clandestine stockpiles exist in other countries such as Iraq and North Korea.

Variola virus is highly infectious when released into the air. It is environmentally stable and can retain its ability to infect people for long periods. Infection through contaminated objects such as clothing is infrequent. After a person is exposed to aerosolized virus, the virus multiplies in the person’s respiratory tract. After a period of 7-17 days, variola is spread through the bloodstream to lymph nodes where it continues to multiply.

Variola then moves into smaller blood vessels near the surface of the skin where the inflammatory changes occur. The classic smallpox rash then begins. Two types of smallpox generally are recognized.

  • Variola major, the most severe form, may cause death in up to 30% of unvaccinated people who develop it. (3% of people vaccinated people may also develop variola major).
  • Variola minor, a milder form of smallpox, produces death in 1% of unvaccinated people.

Signs and symptoms

The symptoms of variola major occur after a 7- to 17-day incubation period. They begin acutely with high fever, headache, chills, aches, vomiting, abdominal and back pain. During the initial phase, 15% of people develop delirium (hallucinations), and 10% of light-skinned people may develop a fleeting rash.

After 2-3 days, the rash develops on the face, hands, and forearms and extends gradually to the trunk and lower part of the body. The sores progress all at once into fluid-filled sacs. The distribution of the rash is important in making the diagnosis of smallpox. A greater number of lesions will appear on the face arms and legs compared to the trunk. People with smallpox are most infectious on days 3-6 after the fever begins. Virus is spread to others through coughing and sneezing or by direct contact.

With the milder form of smallpox, variola minor, the skin sores are similar but smaller and fewer in number. People are not as ill as those who have variola major.

Diagnosis

Most doctors have never seen a case of smallpox and may have difficulty diagnosing it. Other viral illnesses with rash, such as chickenpox or allergic contact dermatitis, can look similar. Smallpox is different from chickenpox because of the distribution of the lesions and because they are all at the same stage of development everywhere on the body. With chickenpox, sores may be forming while others are scabbing over.

The failure to recognize mild cases of smallpox in people with partial immunity permits rapid person-to-person transmission. Exposed people may shed virus through coughing without ever showing the signs and symptoms of the disease.

The doctor may look at scrapings of tissue under a microscope but will be unable to tell the difference between smallpox and monkeypox or cowpox. Advanced PCR techniques have been developed and may provide for more accurate diagnosis in the near future.

Treatment

People with smallpox are usually isolated from people without smallpox for 17 days. Anyone exposed to either weaponized variola or people infected with smallpox must be vaccinated immediately; this may lessen or prevent the illness if done within 4 or 5 days of infection.

Treatment of smallpox is mainly to help relieve symptoms. The antiviral agent, cidofovir, may be effective in treating symptoms.

Prevention

Smallpox vaccine is used to prevent people from getting smallpox. The vaccine is given as a type of shot, but a 2-pronged needle is used to place the medication into the skin. This leaves a permanent scar, which many adults may still have from smallpox inoculations given to them when they were babies.

Once the shot is given, a small fluid-filled pimple usually appears 5-7 days later. A scab forms over the site during the next 1-2 weeks. Common side effects include low-grade fever and swollen lymph glands. People with weakened immune systems should not have the smallpox vaccination. This includes people with HIV, anyone with a history of eczema, and pregnant women.