Smallpox

Smallpox is a disfiguring and potentially deadly infectious disease caused by the Variola major virus. Few other illnesses have had such a profound effect on human health and history. In the 20^th century alone an estimated 300 million people died of smallpox. Before smallpox was eradicated there were two forms of the disease worldwide: Variola major, the deadly disease, and Variola minor, a much milder form. According to some health experts, over the centuries smallpox was responsible for more deaths than all other infectious diseases combined. The disease spreads in any climate and during all seasons. Although a worldwide immunization program eradicated smallpox disease decades ago, small quantities of smallpox virus officially still exist in two research laboratories in Atlanta, Georgia and in Russia.

The last naturally occurring case of smallpox was reported in 1977. In 1980 the World Health Organization declared that smallpox had been eradicated. Currently there is no evidence of naturally occurring smallpox transmission anywhere in the world.

The microbe. Scientists have not studied Variola virus well because of the hazards associated with potential exposure. In addition, by international agreement smallpox may only be studied at the Centers for Disease Control and Prevention (CDC) high containment facility or one in the former USSR and experiments must be approved in advance by an international committee. Vaccinia virus, however, used to make a smallpox vaccine and closely related to Variola has been studied thoroughly. There is one major difference between the two viruses: Vaccinia can infect several types of living beings, while Variola infects only humans naturally and cynomolgus monkeys under highly artificial laboratory conditions. Researchers are now investigating Vaccinia as a possible way to deliver genes from other viruses to make new vaccines.

Transmission. Smallpox is highly contagious. In most cases people get smallpox by inhaling droplets of saliva which are full of virus during face-to-face contact with an infected person. When someone becomes infected they do not immediately feel sick or shed virus to their household contacts. In addition, they have no symptoms for 10 to 12 days. After the virus has multiplied and spread throughout the body, a rash and fever develop. This is the “illness” portion of the disease and it’s when someone is most infectious. In short, someone who becomes infected is not going to be ill until 10 to 12 days later.

Some risk of transmission lasts, however, until all scabs have fallen off. Contaminated clothing or bed linens also can spread the virus. Those caring for people with smallpox need to use special safety measures to ensure that all bedding and clothing from the infected person are cleaned appropriately with bleach and hot water. Caretakers can use disinfectants such as bleach and ammonia to clean contaminated surfaces.

Symptoms. Symptoms of smallpox infection usually appear within 7 to 17 days after exposure to the virus, and on average appear after 12 days. The first symptoms of smallpox may be difficult to distinguish from other flu-like illnesses and include high fever, tiredness, malaise, headache, and backache. A characteristic rash most prominent on the face, arms, and legs follows 2 to 3 days after the first symptoms. The rash starts with flat red lesions (sores) that develop at the same rate. After a few days, the lesions become filled with pus and they begin to crust early in the second week. Scabs develop and then separate and fall off after about 3 weeks.

There is no proven treatment for smallpox. People with the disease can benefit from intravenous fluids and medicine to control fever or pain as well as antibiotics for any secondary bacterial infections that may occur. If an infected person gets the smallpox vaccine within 4 days after exposure to the virus it may lessen the severity of illness or even prevent it. The majority of people with smallpox recover but death may occur in up to 30 percent of cases. Those who do recover are often left with disfiguring scars.

Getting the vaccine. Health care providers use a hypodermic needle, usually used for vaccinations to give the smallpox vaccine. Instead, they use a tiny, two-pronged needle that is dipped into the vaccine solution. When removed, the needle keeps a droplet of the vaccine. The needle is used to prick the skin, usually in the upper arm, a number of times within a few seconds. The pricking is not deep but it will cause a sore spot and one or two droplets of blood to form. if the vaccination is successful a red and itchy bump develops at the vaccine site in 3 or 4 days. In the first week the bump becomes a large blister, fills with pus, and begins to drain. During the second week the blister begins to dry up and a scab forms. In the third week the scab falls off leaving a small scar. People who get the vaccine for the first time have a stronger reaction than those who are revaccinated.

Reactions and complications. The vaccine often causes fever as well as large skin reactions at the vaccination site. These reactions usually go away leaving only the telltate smallpox vaccine scar. The vaccine, however, can cause several complications, some life-threatening, particularly in people with immune deficiencies and skin disorders. Based on reactions to smallpox vaccines in the past CDC estimates that between 14 and 52 people out of every 1 million people vaccinated for the first time will have potentially life-threatening complications that require medical attention progressive Vaccinia uncontrolled spread of Vaccinia virus to adjacent and underlying tissues resulting in tissue death, postvaccinal encephalitis spread of the Vaccinia virus to the central nervous system that is probably made worse by an over-response by the immune system.

Vaccine supply and strength. Expanding the US smallpox vaccine supply is a high priority of the bioterrorism preparedness plan. Results from an NIAID study show that the existing US supply of smallpox vaccine 15.4 million doses could successfully be diluted up to five times and retain its potency effectively expanding the number of individuals it could protect from the contagious disease. The vaccine called Dryvax had been stored since production stopped in 1983.

The trial compared the full-strength vaccine with fivefold as well as tenfold dilutions in 680 young adults with no history of smallpox vaccination. More than 97 percent of all participants in the trial responded with a vaccine take, a blister-like sore at the injection site that serves as an indirect measure of the vaccine effectiveness. A new study has been conducted to determine how effective the diluted Dryvax is in the people who have been previously vaccinated against smallpox.

Treatment. In collaboration with the US Department of Defense (DoD) NIAID has screened more than 500 compounds against smallpox and related viruses. In addition, NIAID supports studies that evaluate experimental antiviral compounds in a number of mouse models in Vaccinia and cowpox (another member of the orthopoxvirus family). NIAID also supports mouse pox virus and rabbit pox virus models. Compounds that are effective in these small-animal models are given priority for evaluation by DoD researchers in the monkey pox primate model.

In addition to collaborating with DoD scientists, NIAID is working with scientists at other federal agencies such as CDC and the Department of Energy to develop and test at least three antiviral drugs against smallpox and determine whether existing antiviral compounds are those being developed are effective against variola virus. In addition to those treatment studies, NIAID is collaborating on studies to help develop a safer, sterile smallpox vaccine using modern technology; to explore developing a vaccine that can be used safely in all segments of the population; to increase scientific knowledge about the genome of Variola and related viruses.