December 17, 2002

Although smallpox no longer occurs, the smallpox virus (variola virus) still exists. It is not known whether or not smallpox virus has been obtained by persons who might use it to cause intentional infections. In order to provide a measure of protection in case smallpox were to be used in a biological attack, on December 13, 2002, the Bush administration announced a National Smallpox Vaccination Plan for the U.S.

In the absence of a smallpox attack, who will be vaccinated?

In stage 1 of the plan, teams of acute care hospital and public health workers with specific skills are to be voluntarily vaccinated in order to form smallpox response teams to provide hospital care for the initial suspected or confirmed smallpox cases and to conduct public health disease control activities. The rationale for this is that having teams of health care and public health workers vaccinated and designated to perform specific roles in response to the first smallpox cases will allow a more effective response to a smallpox outbreak while minimizing exposure of large numbers of people to the vaccine. Also in stage 1, the US military will begin using smallpox vaccine. The timing for stage 1 has not been announced, but may begin as early as January 2003. Public Health is currently working on stage 1 activities with hospitals in King County in collaboration with Washington State Department of Health. Health care workers interested in volunteering for hospital-based smallpox health care teams should contact their hospital administration or infection control team.

In stage 2, smallpox vaccine will be available to additional health care workers and other first responders such as police, fire, and other public safety responders. The timing for stage 2 has not been announced, but would be expected to follow completion of stage 1. The vaccine to be used in stages 1 and 2 is the same licensed, undiluted smallpox vaccine as was previously used in the U.S. when smallpox vaccination was routine, over 30 years ago. The vaccine has been preserved by the federal government.

Stage 3 of the plan will make smallpox vaccine available to the general public on a voluntary basis after a new version of the vaccine is produced and licensed (expected in 2004), or before that time under study protocols. If a smallpox outbreak does occur before that time, sufficient amounts of vaccine are available to immunize the public. Because the risk of smallpox occurring is low and because the smallpox vaccine has serious side effects, including death, smallpox vaccine is not recommended or available for the general public at this time.

GENERAL INFORMATION ON SMALLPOX AND SMALLPOX VACCINE

What is smallpox?

• Smallpox is a severe rash illness with fever caused by variola virus.
  
• Smallpox vaccine is made from vaccinia, a related virus.
  
• After the successful global vaccination-based smallpox elimination program, the World Health Organization declared smallpox eradicated from the earth in 1980.
• Routine vaccination for smallpox in the U.S. stopped in 1972. Because protection from the vaccine decreases with time, virtually all persons in the U.S. are considered susceptible to smallpox today.
  
• Smallpox is of current concern because of its theoretical potential use as a biological weapon, although there is currently no way to predict the likelihood of this actually occurring.

Symptoms

• A febrile illness (prodrome) occurs 1-4 days before rash onset consisting of fever >102º F and at least one of the following: patient looks and feels severely ill, headache, backache, chills, vomiting, or severe abdominal pain.
• After 1-4 days, classic smallpox lesions appear in the mouth and throat followed by the face, hands, and forearms and spread over 7 days to the lower extremities and the trunk. Lesions progress slowly over about a week from macules to vesicles to pustules to scabs, and subsequently over another 1-2 weeks to separation of scabs. Lesions are deep, firm/hard, round, and well-circumscribed.
• Lesions are in same stage of development on any one part of the body (e.g., face or arm).

Smallpox can be differentiated from varicella (chickenpox) by differences in lesion progression and distribution, illness course and presence of a febrile prodrome.

Transmission of smallpox

• Smallpox is primarily transmitted from person-to-person by respiratory droplets (like chickenpox and influenza). Less commonly, transmission occurs through infectious aerosols, followed by direct contact with smallpox lesions. Smallpox is less easily transmitted than measles, chickenpox or influenza.
• Smallpox is most contagious from the onset of rash until day 7-10 of the rash.. The ability to spread the virus decreases with scab formation and ceases with separation of scabs.
• Secondary cases occur primarily in household, hospital, & other close contacts and severely ill or coughing patients are mot infectious.
• Smallpox can remain infectious for prolonged periods on contaminated clothing and bedding.
• Infection control recommendations include both droplet and aerosol precautions.

Diagnosis of smallpox

Clinical diagnosis is made by evaluation of clinical symptoms and rash using the CDC diagnostic criteria for smallpox, and is confirmed with laboratory testing at CDC.

Smallpox vaccine

Smallpox vaccine is made from vaccinia virus, which is closely related to the smallpox virus, variola. The smallpox vaccine provides the best available protection from exposure to the smallpox virus. However, smallpox vaccine can cause serious side effects, including death. For that reason, smallpox vaccination is voluntary and persons receiving the vaccine must be carefully screened to avoid complications. People who have received smallpox vaccine in the past without complications and who are currently healthy have a lower risk for serious side effects and are the best candidates for voluntary smallpox vaccination at this time.

• Decision-making for vaccine use in general balances the risk of disease against the side effects of the vaccine. Smallpox vaccine is associated with potentially severe adverse effects.
• Smallpox vaccine is made from live vaccinia virus, which is similar to but different from smallpox (variola) virus.
• Vaccine is administered by poking the skin 15 times with a bifurcated (two-pronged) needle, which causes a localized vaccinia infection.
• Six to eight days after vaccination, a scab or ulcer develops at the vaccine site. This reaction is called a "take" and means that immunity has developed.
• A permanent scar will result at the injection site. If this reaction does not occur, the vaccination should be repeated.
• Routine smallpox vaccination in the U.S. stopped in 1972. Since 1980 vaccinia vaccine has been recommended only to protect laboratory workers from infection with orthopoxviruses.
• Immunity from the vaccine wanes with time; therefore in a present-day release of variola virus, most people are considered susceptible to infection.
• There is no recommendation to resume routine smallpox vaccination at this time. In addition to voluntary vaccination of health care and emergency responders as described above, the current CDC strategy for control of a smallpox outbreak is "ring vaccination" of contacts of cases following report of a smallpox case. This involves isolation of confirmed & suspected smallpox cases, vaccination & close surveillance of contacts, and vaccination of contacts of the contacts. More widespread community vaccination could be used if necessary to control an outbreak.

People who should not get the vaccine include anyone who is allergic to the vaccine or any of its components; pregnant women; women who are breastfeeding; anyone under 12 months of age; people who have, or have had, skin conditions (especially eczema and atopic dermatitis); and people with weakened immune systems, such as those who have received a transplant, are HIV positive, are receiving treatment for cancer, or are taking medications (like steroids) that suppress the immune system. The Advisory Committee on Immunization Practices advises against non-emergency use of smallpox vaccine in anyone under 18 years of age. These people should not receive the vaccine unless they have been exposed to smallpox.

In order to work, the smallpox vaccine causes an infection in the person vaccinated that can spread to other close contacts and cause serious reactions. For that reason, any person who has household members with any of the conditions above should NOT receive the smallpox vaccine.

Vaccine Side Effects

Most people experience reactions that include a sore arm, fever, and body aches. These side effects are usually not serious. In recent tests, one in three people felt bad enough to miss work, school, or recreational activity or had trouble sleeping after receiving the vaccine. In the past, about 1,000 people for every 1 million people vaccinated for the first time experienced reactions that, while not life-threatening, were serious.

Severe reactions to the vaccine are less common. In the past, between 14 and 52 people per 1 million vaccinated experienced potentially life-threatening reactions, including eczema vaccinatum, progressive vaccinia (or vaccinia necrosum), or postvaccinal encephalitis. Based on past experience, it is estimated that between 1 and 2 people out of every 1 million people vaccinated will die as a result of life-threatening reactions to the vaccine.

The overall risks of serious complications of vaccinia vaccination are low, but not insignificant. Complications occur more frequently in persons receiving their first dose of vaccine, and among young children. The rates of complications following primary vaccination listed below are taken from the June 22, 2001 issue of MMWR [50(RR10);1-25]: Vaccinia (Smallpox) Vaccine - Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001 and are derived from observations made when smallpox vaccine was in routine use in the U.S. over 30 years ago. Higher rates of vaccine complications would likely occur today given the increased number of persons with medical conditions or medications causing immune system compromise.

The most frequent serious complications of vaccination are:

• Encephalitis (brain inflammation) -- (12.3 per million). This complication is fatal in 25% of cases, and causes neurological sequelae in 23%.
  
• Vaccinia necrosum (progressive destruction of skin and other tissues at the vaccination site that spreads throughout the body) -- (1.5 per million doses). This complication has been limited to recipients who have abnormalities of their immune system, for whom pre-exposure administration of vaccine in contraindicated.
• Eczema vaccinatum (severe infection of skin caused by vaccinia virus in persons with eczema or other chronic skin disorder) -- (38.5 per million doses). This complication has been limited to recipients who have eczema or other chronic skin conditions, for whom pre-exposure administration of vaccine is contraindicated.
• Fetal vaccinia - rare

Other less serious complications include:

• Generalized vaccinia (spread of vaccinia virus to other parts of the body) -- 241.5 per million doses. Generalized vaccinia in persons without underlying illness (such as immune deficiency) is generally self-limited although approximately 10% of cases are severe
• Inadvertent transfer (autoinoculation) of vaccinia from the vaccination site to other parts of the body causing localized vaccinia infections - 529.2 per million doses (30% in one study were contacts). Inadvertent transfer of vaccinia from the vaccination site to other parts of the body can be prevented by careful handwashing after touching the vaccination site and keeping the site covered.

Because the vaccinia virus is present at the vaccination site, other persons can become infected if they come in direct contact with the vaccinee's lesions. Vaccinees can also transfer virus from the vaccination site to another person by touching the lesion and then touching the other person. The exact risk of infection by such routes of transmission is unknown; however, virus can be cultured from the vaccination site until the skin heals. Most instances of contact transmission of vaccinia do not lead to serious illness in the contact. However, persons at high-risk of severe adverse events (persons with immune system compromise) can develop serious infection with vaccinia virus through inadvertent contact with vaccinees.

People with the following conditions are at increased risk of developing severe complications following vaccination with vaccinia vaccine and should not be immunized in the absence of a smallpox exposure or outbreak:

• Diseases or conditions which cause immunodeficiency, such as HIV, AIDS, leukemia, lymphoma, generalized malignancy, agammaglobulinemia, or chemotherapy, radiation or high doses of corticosteroids.
• History of eczema, even if the condition is mild or not presently active.
• Pregnancy or planning to become pregnant within a month after vaccination.
• Other acute or chronic skin conditions such as atopic dermatitis, burns, impetigo, or varicella zoster (shingles).
• Life-threatening allergy to polymixin B, streptomycin, tetracycline, or neomycin.

In addition, because of the risk of transferring vaccinia from vaccinees to susceptible contacts, people who have household, sexual or other close contact with a person who has one of the above conditions should not be vaccinated in the absence of a smallpox outbreak or release.

Adverse reactions

Successful vaccination, particularly in persons receiving their first dose of vaccine, is associated with tenderness, redness, swelling, and a lesion at the vaccination site, and may cause fever for a few days. The lymph nodes in the armpit of the vaccinated arm may become enlarged and tender. These symptoms are more common in persons receiving their first dose of vaccine (15%-20%) than in persons being revaccinated (5%-10%).

The overall risks of serious complications of vaccinia vaccination are low, but not insignificant. Complications occur more frequently in persons receiving their first dose of vaccine, and among young children. The rates of complications following primary vaccination listed below are taken from the June 22, 2001 issue of MMWR [50(RR10);1-25]: Vaccinia (Smallpox) Vaccine - Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001 and are derived from observations made when smallpox vaccine was in routine use in the U.S. over 30 years ago. Higher rates of vaccine complications would likely occur today given the increased number of persons with medical conditions or medications causing immune system compromise.

The most frequent serious complications of vaccination are:

• Encephalitis (brain inflammation) -- (12.3 per million). This complication is fatal in 25% of cases, and causes neurological sequelae in 23%.
• Vaccinia necrosum (progressive destruction of skin and other tissues at the vaccination site that spreads throughout the body) -- (1.5 per million doses). This complication has been limited to recipients who have abnormalities of their immune system, for whom pre-exposure administration of vaccine in contraindicated.
• Eczema vaccinatum (severe infection of skin caused by vaccinia virus in persons with eczema or other chronic skin disorder) -- (38.5 per million doses). This complication has been limited to recipients who have eczema or other chronic skin conditions, for whom pre-exposure administration of vaccine is contraindicated.
• Fetal vaccinia - rare

Other less serious complications include:

• Generalized vaccinia (spread of vaccinia virus to other parts of the body) -- 241.5 per million doses. Generalized vaccinia in persons without underlying illness (such as immune deficiency) is generally self-limited although approximately 10% of cases are severe.
• Inadvertent transfer (autoinoculation) of vaccinia from the vaccination site to other parts of the body causing localized vaccinia infections - 529.2 per million doses (30% in one study were contacts). Inadvertent transfer of vaccinia from the vaccination site to other parts of the body can be prevented by careful handwashing after touching the vaccination site and keeping the site covered.

Because the vaccinia virus is present at the vaccination site, other persons can become infected if they come in direct contact with the vaccinee's lesions. Vaccinees can also transfer virus from the vaccination site to another person by touching the lesion and then touching the other person. The exact risk of infection by such routes of transmission is unknown; however, virus can be cultured from the vaccination site until the skin heals. Most instances of contact transmission of vaccinia do not lead to serious illness in the contact. However, persons at high-risk of severe adverse events (persons with immune system compromise) can develop serious infection with vaccinia virus through inadvertent contact with vaccinees.

WHERE CAN I GET MORE INFORMATION ABOUT SMALLPOX AND VACCINIA (SMALLPOX) VACCINE?

If you have questions about vaccinia vaccination, you can discuss with your health care provider or call Public Health at 206-296-4774, or visit the Centers for Disease Control and Prevention website at www.bt.cdc.gov/Agent/Smallpox/SmallpoxGen.asp

Detailed information Health Advisories & Resources is available at: www.bt.cdc.gov/agent/smallpox/reference/resource-kit.asp

Additional references:

• CDC Advisory Committee on Immunization Practices (ACIP). " Vaccinia (Smallpox) Vaccine -- Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR [50(RR10);1-25]; June 22, 2001. This statement is available on-line at www.cdc.gov/mmwr/preview/mmwrhtml/rr5010a1.htm
  
  
• Infectious Diseases Society of America: www.idsociety.org
  
  
• Henderson D., Moss B. (1999) Smallpox and Vaccinia. In: Plotkin S, Orenstein W. Vaccines. 3rd ed. Philadelphia, PA: W.B. Saunders Co.