What is Smallpox?

Smallpox is a serious and contagious disease caused by the variola virus. The virus got its name from the Latin word for “spotted” and refers to the raised bumps that appear on the face and body of a person with the disease (Figure 10). There is currently no effective treatment for this disease (9, 47, 62). 

Smallpox was eradicated from the world following a worldwide vaccination program started by the World Health Organization in 1967. The vaccine used in that program contained another virus closely related to Variola called the vaccinia virus. This vaccination program was successful because;

The last case of smallpox in the United States was in 1949. The last naturally occurring case was in Somalia in 1977. On May 8, 1980, the World Health Assembly declared the world free of smallpox. 

Currently, vaccination involves the use of the Vaccinia virus. In most people it only causes a skin lesion  at the site of the vaccination. The skin lesion starts as a papule then develops into a pustule. The pustule breaks open and then the lesion scabs over. When the scab falls off a scar remains at the lesion site. Those that develop the skin lesion are protected from getting the severest forms of smallpox. Evidence of a successful vaccination can easily be documented because of the scar that occurs following vaccination. In people with compromised immune systems serious and sometimes fatal side effects can occur following vaccination.  Side effects include infection and inflammation of the brain (encephalitis) and infection that causes a severe and damaging lesion at the site of the vaccination (Vaccinia Necrosum). Eventually, the risk of severe vaccine side effects became greater than the risk of getting the disease itself. Therefore, vaccination of the general public stopped in1972 in the U.S. 

The World Health Organization during the 1980's designated two official repositories for storage of smallpox strains. One at CDC in Atlanta Georgia and the other in Novosibirsk, Russia. They instructed others that had smallpox strains to either transfer their virus stocks to the two official repositories or destroy them. Currently, almost one half of the population in the U.S. has not been vaccinated and has no immunity to Vaccinia or Variola. The remainder of the population was vaccinated 30 or more years ago and may have partial protection from the disease. 

There are two basic strains of the Variola virus; Variola major and Variola minor (62).  

Variola major is the strain of the virus that causes the most severe disease and is also the most common form of smallpox. It causes an extensive rash (Figure 10) and high fever. There are four types of Variola major smallpox: ordinary (90% or more of cases); modified (a mild form that occurred in vaccinated people); flat (rare, severe and deadly); and hemorrhagic (rare, severe and deadly). Variola major had an overall death rate of about 30%. Flat and hemorrhagic smallpox were nearly 100% fatal. 

Variola minor is the strain of the Variola that caused a less severe disease and was less common than Variola major. Death rates with this virus type were less than 1%.  

Generally, direct and prolonged face-to-face contact is required to spread smallpox from person-to-person. Usually the virus spreads from person-to-person in the air via aerosols. Inhaling only 10-100 Variola viruses can result in smallpox. Smallpox can also be spread through direct contact with the scabs or pus from the skin lesions caused by Variola. It can also be acquired by contact with infected body fluids or contaminated objects such as bedding or clothing but this route of transmission is less common.  

Rarely, smallpox has been spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. Humans are the only natural hosts of Variola; insects and animals can not transmit smallpox. 

Once the Variola virus is inhaled it lands on and infects the cells that cover the mouth, throat and respiratory tract. All viruses must infect a cell to reproduce. Macrophages infected by the Variola virus then take the virus to the lymph nodes in the head and neck. By day three of the infection the virus gets into the bloodstream. This is called the primary or first viremia (virus in the blood). The Variola virus then invades more macrophages and the cells that cover the inside surfaces of the blood vessels (endothelial cells) in the liver, spleen, lymph nodes and bone marrow. During this time, which can last from 7-17 days, the person will appear to be healthy with no signs of the Variola virus infection. 

The viruses reproduce to such an extent that another viremia will occur. During this second viremia the person will suddenly develop a high fever, severe headache, pharyngitis, nausea and backache. The fever will be quite high; 101-104o F and they will be too ill to carry on with normal activities.  The viruses will also get into the skin at this time. This phase of the disease is called the prodrome. Just before the appearance of the skin rash some red sores (enanthems) are oftentimes observed in the roof of the person’s mouth, on their tongue and at the back of their throat.

Meanwhile, the viruses in the skin will cause a skin rash to develop. In ordinary Variola major the rash starts out as irregularly shaped red spots (macules). The first spots are usually seen on the face and neck and will then develop on the hands, wrists, forearms, feet, ankles, and lower leg. These spots will also develop on the chest and abdomen but are much less numerous than those seen on the head, neck and limbs. These macules will all appear within 24 hours. Usually the person’s fever will go down and they will feel better. The red spots will all at the same time develop into red bumps (papules) after about three days. By the fourth day, the all the papules will fill with a thick, opaque fluid and have a depression in the center. These skin lesions are now called pustules. Their fever will rise again at this time and remain high until scabs form.  In time all the pustules will break open and a crust will form over the skin lesions followed by a scab. On day 14 of the rash the skin lesions will scab over. 

All the skin lesions will go from macule, to papule, to pustule, to crust, to scab at the same time and it will take about 17 days for this to occur. People with smallpox are infectious to others until all the scabs have fallen off.  When the scabs fall off they leave marks on the skin that eventually become pitted scars. The skin rash takes about three weeks to complete (macule to last scab falling off).  

People with the hemorrhagic form of Variola major do not develop the same rash as in ordinary Variola major. Following the prodrome the skin on the chest and abdomen will turn a purplish red (dusky erythema). The capillaries in the skin will then leak blood into the skin. It will start out as small dots (petechiae) that will get larger (purpura) and larger (ecchymoses). Nearly everyone with this form of Variola major will die. 

The flat form of Variola major was also nearly always fatal. After the prodrome the skin would develop a dusky erythema that would then slowly become papules. Sometimes the papules would become blisters. The fever in the prodrome does not go away as in ordinary Variola major. The skin lesions do not crust or scab over but rather the skin will peel away in sheets. Usually death occurred during the second week of the illness. 

Why is smallpox an attractive BW?

The Variola virus is highly infectious with a death rate of 30%. Even if the person does not die they are very ill for a couple of weeks. Less than 10 viruses are needed to start an infection. Those viruses are most likely to result in disease when inhaled. Aerosol exposure of less than 15 minutes is sufficient to cause an infection. Symptoms of infection do not start for 7-17 days. Person-to-person transmission of this disease is common and many more people would be infected. An aerosol of the organism would be very effective way of infecting many people at one time. 

The virus is not very hardy. It will only last a couple of hours at high temperatures and high humidity. Most state/nonstate actor releases would have to be conducted in indoor environments. Yet, even indoors the virus only lasts for about 2 days. Occupying an area contaminated with smallpox would not require decontamination as long as those occupying the area waited until all the virus had become inactivated.

Laboratory Diagnosis

Vaccinated healthcare providers usually swab the patient's pharynx and/or open skin lesions (eg, pustule contents, material from the base of the scab). These swabs will then need to be sent to a laboratory that is prepared to handle this very hazardous sample. The swab can be examined for the presence of virions using an electron microscope, techniques to look for small amounts of Variola DNA (polymerase chain reaction; PCR), or by using antibodies specific for the virus to detect it or by growing the virus on live cell cultures. Blood samples may be obtained to look for antibodies to the Variola virus. 


Initial treatment involves isolating the person from others and maintaining that isolation for at least 17 days. If given early within 3-4 days of exposure to the virus, vaccination can significantly lower the severity of or prevent smallpox disease. Diligent supportive care should consist of adequate nutrition and hydration, eye care, and treatment to prevent secondary bacterial skin infections. 

Cidofovir is an antiviral drug that may be beneficial if given in the early stages of illness, although the effectiveness of this treatment has not been proven in humans. Infections of the cornea of the eye may be treated with topical idoxuridine. Antibody to the Vaccinia virus called Vaccinia immune globulin does not appear to offer a survival benefit when given to patients during the incubation or active-disease stages of smallpox. 


The only effective means of preventing smallpox infection and disease is by vaccination. The vaccine contains the live Vaccinia virus. The virus when placed into the skin will start replicating in the skin cells. It will not cause smallpox but rather a smallpox-like skin lesion. Vaccinia virus vaccine (Dryvax) is delivered by the scarification method, which involves dipping a bifurcated needle (a needle with two points at the end; Figure 11) into the vaccine and poking the tip of the needle into the skin many times. Successful vaccination is marked by the typical Vaccinia (Jennerian or major) reaction, which consists of a visible papule by day 3 that becomes blister-like by day 5-6 and pustule by day 7-10. The pustule resolves with scab separation by day 21. Maximal redness and swelling associated with vaccination usually occurs at days 8-12. Local lymph nodes may swell and the person may have a low fever, and feel tired. 

This is a live virus vaccine and some people should not be given this vaccine. This is especially the case for people that are immunocompromised. Examples of patient who should not get the vaccine are AIDS patients; people with certain skin conditions (eczema and atopic dermatitis), chemotherapy cancer patients, organ transplant recipients and pregnant women. 

The Vaccinia vaccine if given within 3-4 days following exposure to the Variola virus will reduce the chances a person exposed to smallpox will become ill by 2-3 fold. The Vaccinia vaccine is not 100 percent effective in preventing smallpox. However in those vaccinated that get smallpox the vaccine can reduce the mortality rate by 50%. 

The vaccine is most protective during the first 10 years after vaccination and slowly wanes thereafter. Those vaccinated several times are likely to have longer-lasting immunity. Some say protection from smallpox could last as long as 30 years in people vaccinated several times. 

In 2001 following the anthrax-laced letter attacks an inventory of the U.S.’s smallpox vaccine supply was performed. Only 20 million doses of the vaccine existed and it was all over 20 years old. By 2002 the government had contracted with four different companies to provide the U.S. with more vaccine. There are about 290 million doses of the vaccine currently stockpiled by the government (47). 

No vaccination program for the general U.S. population is being conducted because of the adverse reactions associated with the vaccine. Serious non-lethal reactions occur in about 1000 persons for every 1 million people vaccinated. These serious reactions include inadvertent autoinoculation of the vaccinia virus to other parts of the body, generalized vaccinia, and a toxic or allergic rash called erythema multiforme. Between 14 and 54 per 1 million vaccinated will have life-threatening reactions, which include eczema vaccinatum, progressive vaccinia, and postvaccinal encephalitis. It is estimated that 1-2 out of 1 million vaccinated will die (47). 

The current U.S. strategy is to ask healthcare professionals to voluntarily be vaccinated and following a BW release of smallpox to only vaccinate those exposed to known cases of smallpox. Vaccinating only those exposed to smallpox was developed during 1966 in Nigeria when a Dr. William H. Foege and his colleagues faced a critical vaccine shortage. They found this method of vaccination was effective in eliminating the smallpox epidemic in Nigeria and was called “Ring Vaccination”.

Ring vaccination was used worldwide in 1967 to help eradicate smallpox disease. Ring vaccination involves finding people who were exposed to a person with smallpox. The smallpox vaccine is then given to those people who had been, or could have been, exposed to an infected person. This approach creates a "ring" of vaccinated people around the smallpox victims and has been shown to stop the spread of smallpox.


© 2005 Neal Chamberlain. All rights reserved. 
Site Last Revised 5/13/05
Neal Chamberlain, PhD. A. T. Still University of Health Sciences/Kirksville College of Osteopathic Medicine.

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