Smallpox vaccine risks

Smallpox vaccine: Balancing the benefits and the risks

"This is not an innocuous vaccine," said Donald Henderson, MD, director of the Center for Civilian Biodefense Studies at John Hopkins University in Baltimore. He was recently named head of a federal advisory committee to assist the government in deciding when and if to begin another widespread smallpox vaccination program. Dr. Henderson is also known for his work in helping to rid the world of smallpox years ago.

(For a sampling of the medical literature on smallpox vaccine reactions, click here.)

Commentary: Smallpox Vaccine Has Risks

Unfortunately, the smallpox vaccine is just not as safe as any of the other vaccines routinely used in the United States today.

The vaccine injection causes a red, tender and crusting reaction at the vaccination skin site that lasts up to two weeks.

More importantly, one out of 150,000 smallpox vaccination recipients experiences more severe reactions, including overwhelming infection due to the vaccine virus in individuals with abnormal immune systems, encephalitis or brain infection. Another one out of 500,000 individuals will die as a direct cause of the vaccine.

Although the risk of either death or these severe side effects may sound relatively rare, vaccination of the entire U.S. population would result in 600 deaths and 2,000 individuals with serious brain infections. These very real risks must be balanced against what is currently only a theoretical risk of smallpox being introduced by terrorists.

Enforceable, Mandatory Vaccination Seen Necessary in Event of Smallpox Attack 

Prior acknowledged that the potential for federally enforced mandatory vaccinations could arouse anti-government sentiments in some sectors of the American public. Any mass-vaccination policy would also have to take into account the vaccine's side effects. Historically, the smallpox vaccine caused serious reactions in about 1 in every 4,000 persons and death in about 4 per 1 million.

Poll finds bioterror concerns widespread

Among the risks: About 3 in every 1 million people vaccinated would get encephalitis, which can cause permanent brain damage or death. Another 250 would get a smallpox-like rash that also can be fatal if not properly treated.

People with weak immune systems -- patients who have AIDS, cancer or organ transplants or are taking high-dose steroids -- are most at risk for the side effects, as are people with the skin condition eczema.

AMA: Further Smallpox Study Needed

Some doctors said they worry the vaccine itself could kill as many as 300 people if the entire U.S. population were vaccinated. There's also disagreement about whether those already inoculated would need another vaccination to prevent a smallpox infection.

Babies younger than 1 and people with weakened immune systems couldn't withstand smallpox vaccinations, doctors said.

Vaccinia (Smallpox) Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001

Moderate to Severe Adverse Reactions. Moderate and severe complications of vaccinia vaccination include eczema vaccinatum, generalized vaccinia, progressive vaccinia, and postvaccinial encephalitis (Table 2). These complications are rare but occur >10 times more often among primary vaccinees than among revaccinees and are more frequent among infants than among older children and adults (53--55) (Table 3). A study of Israeli military recruits aged >18 years, who were vaccinated during 1991--1996, reported rates of the severe complications progressive vaccinia (i.e., vaccinia necrosum rate: 0/10,000 vaccinees) and postvaccinial encephalitis (rate: 0/10,000 vaccinees) similar to those reported in previous studies (56).

Eczema vaccinatum is a localized or systemic dissemination of vaccinia virus among persons who have eczema or a history of eczema or other chronic or exfoliative skin conditions (e.g., atopic dermatitis) (Figure 5). Usually, illness is mild and self-limited but can be severe or fatal. The most serious cases among vaccine recipients occur among primary vaccinees and are independent of the activity of the underlying eczema (57). Severe cases have been observed also after contact of recently vaccinated persons with persons who have active eczema or a history of eczema (see Contacts of Vaccinees) (Figure 6).

Generalized vaccinia is characterized by a vesicular rash of varying extent that can occur among persons without underlying illnesses (Figure 7). The rash is generally self-limited and requires minor or no therapy except among patients whose conditions might be toxic or who have serious underlying immunosuppressive illnesses (e.g., acquired immunodeficiency syndrome [AIDS]) (58).

Progressive vaccinia (vaccinia necrosum) is a severe, potentially fatal illness characterized by progressive necrosis in the area of vaccination, often with metastatic lesions (Figure 8). It has occurred almost exclusively among persons with cellular immunodeficiency. The most serious complication is postvaccinial encephalitis. In the majority of cases, it affects primary vaccinees aged <1 year or adolescents and adults receiving a primary vaccination (3). Occurrence of this complication was influenced by the strain of vaccine virus and was higher in Europe than in the United States. The principle strain of vaccinia virus used in the United States, NYCBOH, was associated with the lowest incidence of postvaccinial encephalitis (3). Approximately 15%--25% of affected vaccinees with this complication die, and 25% have permanent neurological sequelae (52--54). Fatal complications caused by vaccinia vaccination are rare, with approximately 1 death/million primary vaccinations and 0.25 deaths/million revaccinations (54). Death is most often the result of postvaccinial encephalitis or progressive vaccinia

Contacts of Vaccinees

Transmission of vaccinia virus can occur when a recently vaccinated person has contact with a susceptible person. In a 1968 10-state survey of complications of vaccinia vaccination, the risk for transmission to contacts was 27 infections/million total vaccinations; 44% of those contact cases occurred among children aged <5 years (53). Before the U.S. military discontinued routine smallpox vaccination in 1990, occurrences of contact transmission of vaccinia virus from recently vaccinated military recruits had been reported, including six cases resulting from transmission from one vaccine recipient (59--61).

Approximately 60% of contact transmissions reported in the 1968 10-state survey resulted in inadvertent inoculation of otherwise healthy persons. Approximately 30% of the eczema vaccinatum cases reported in that study were a result of contact transmission (53). Eczema vaccinatum might be more severe among contacts than among vaccinated persons, possibly because of simultaneous multiple inoculations at several sites (54,62). Contact transmission rarely results in postvaccinial encephalitis or vaccinia necrosum.

Precautions and Contraindications

Routine Nonemergency Laboratory and Health-Care Worker Contraindications

The following contraindications to vaccination apply to routine nonemergency use of vaccinia vaccine (see Smallpox Vaccine for Bioterrorism Preparedness for information regarding precautions and contraindications to vaccination during a smallpox outbreak emergency) (Table 4). Before administering vaccinia vaccine, the physician should complete a thorough patient history to document the absence of vaccination contraindications among both vaccinees and their household contacts. Efforts should be made to identify vaccinees and their household contacts who have eczema, a history of eczema, or immunodeficiencies. Vaccinia vaccine should not be administered for routine nonemergency indications if these conditions are present among either recipients or their household contacts.

History or Presence of Eczema or Other Skin Conditions

Because of the increased risk for eczema vaccinatum, vaccinia vaccine should not be administered to persons with eczema of any degree, those with a past history of eczema, those whose household contacts have active eczema, or whose household contacts have a history of eczema. Persons with other acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, or varicella zoster) might also be at higher risk for eczema vaccinatum and should not be vaccinated until the condition resolves.

Pregnancy

Live-viral vaccines are contraindicated during pregnancy; therefore, vaccinia vaccine should not be administered to pregnant women for routine nonemergency indications. However, vaccinia vaccine is not known to cause congenital malformations (63). Although <50 cases of fetal vaccinia infection have been reported, vaccinia virus has been reported to cause fetal infection on rare occasions, almost always after primary vaccination of the mother (64). Cases have been reported as recently as 1978 (55,65). When fetal vaccinia does occur, it usually results in stillbirth or death of the infant soon after delivery.

Altered Immunocompetence

Replication of vaccinia virus can be enhanced among persons with immunodeficiency diseases and among those with immunosuppression (e.g., as occurs with leukemia, lymphoma, generalized malignancy, solid organ transplantation, cellular or humoral immunity disorders, or therapy with alkylating agents, antimetabolites, radiation, or high-dose corticosteroid therapy [i.e., >2 mg/kg body weight or 20 mg/day of prednisone for >2 weeks] [66]). Persons with immunosuppression also include hematopoietic stem cell transplant recipients who are <24 months posttransplant, and hematopoietic stem cell transplant recipients who are >24 months posttransplant but who have graft-versus-host disease or disease relapse. Persons with such conditions or whose household contacts have such conditions should not be administered vaccinia vaccine.

Persons Infected with HIV

Risk for severe complications after vaccinia vaccination for persons infected with HIV is unknown. One case of severe generalized vaccinia has been reported involving an asymptomatic HIV-infected military recruit after the administration of multiple vaccines that included vaccinia vaccine (58). Additionally, a 1991 report indicated that two HIV-infected persons might have died of a progressive vaccinia-like illness after treatment with inactivated autologous lymphocytes infected with a recombinant HIV-vaccinia virus (67). No evidence exists that smallpox vaccination accelerates the progression of HIV-related disease. However, the degree of immunosuppression that would place an HIV-infected person at greater risk for adverse events is unknown. Because of this uncertainty, until additional information becomes available, not vaccinating persons (under routine nonemergency conditions) who have HIV infection is advisable.

Infants and Children

Before the eradication of smallpox, vaccinia vaccination was administered routinely during childhood. However, smallpox vaccination is no longer indicated for infants or children for routine nonemergency indications.

Persons with Allergies to Vaccine Components

The currently available vaccinia vaccine (i.e., Dryvax) contains trace amounts of polymyxin B sulfate, streptomycin sulfate, chlortetracycline hydrochloride, and neomycin sulfate. Persons who experience anaphylactic reactions (i.e., hives, swelling of the mouth and throat, difficulty breathing, hypotension, and shock) to any of these antibiotics should not be vaccinated. Vaccinia vaccine does not contain penicillin. Future supplies of vaccinia vaccine will be reformulated and might contain other preservatives or stabilizers. Refer to the manufacturer's package insert for additional information

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