CDC offers clinicians guidance on smallpox vaccination reactions


Jan 28, 2003 (CIDRAP News) – In the years when smallpox vaccine was being used to eradicate the disease, about 50 people out of every million vaccinated suffered life-threatening complications, and another 935 had serious complications. About two thirds of those complications might have been prevented with better screening, according to a new report from the Centers for Disease Control and Prevention (CDC).

The CDC last week released "Smallpox Vaccination and Adverse Reactions: Guidance for Clinicians," a thorough review of the range of vaccinia vaccine complications and their diagnosis and treatment. The 29-page article, issued as a supplement to Morbidity and Mortality Weekly Report, is available online. It comes as states are beginning to vaccinate healthcare and public health workers who will serve on smallpox response teams.

"During the smallpox eradication era, approximately two thirds of complications after smallpox vaccination might have been preventable and might have been avoided with better screening," the report says. "However, screening will not eliminate risk, because the risk factors for certain adverse reactions have not been clearly defined and screening success is subject to recall bias and the participant's willingness to disclose personal information."

In 1968, the report says, a 10-state survey showed that the rate of life-threatening reactions to smallpox vaccination in first-time vaccinees was 52.3 per million vaccinations and the death rate was 1.5 per million. In addition, serious but not life-threatening reactions occurred in 935.3 per million cases.

A national survey conducted the same year showed much lower complication rates: 14.2 life-threatening reactions, 1.1 deaths, and 48.8 serious but not life-threatening reactions per million people vaccinated. But the 10-state survey is probably a better measure, because researchers actively contacted clinicians and urged them to report all adverse reactions, the report states. Data in the national survey came mostly from a Red Cross system for distributing vaccinia immune globulin (VIG), which is used to treat severe complications, and complications that did not warrant treatment with VIG were less likely to be reported, according to the CDC.

Minor but still troublesome reactions to the vaccine are far more common, the report notes. In a recent clinical trial in which 680 adults were vaccinated for the first time, many reported having one or more symptoms in the first 2 weeks. These included fatigue in 50%; headache, 40%; muscle aches and chills, 20%; nausea, 20%; and fever of 100˚F or higher, 10%. About a third of the people were sick enough to have trouble sleeping or to miss school, work, or recreational activities. A CDC database of symptoms among 633 people vaccinated by the CDC in 2001 and 2002 shows similar rates, the report says.

Fever is especially common in children who get the shot for the first time. In one series, about 70% of children had more than 1 day of temperatures higher than 100˚F, and 15% to 20% had temperatures higher than 102˚F, the report says. The rates were much lower after second vaccinations.

But most of the CDC report focuses on the more serious or life-threatening complications of smallpox vaccine, including inadvertent inoculation, ocular vaccinia, generalized vaccinia, eczema vaccinatum, progressive vaccinia, postvaccinia encephalopathy and encephalomyelitis, and fetal vaccinia. People who have an increased risk of serious complications include those who have atopic dermatitis, commonly called eczema, and those whose immune systems have been weakened by cancer treatment, HIV, or other factors.

The risk of inadvertent inoculation—transfer of vaccinia virus from the vaccination site to another site on the vaccinee or to another person—warrants careful prevention steps, the report notes. Vaccinees and their close contacts should not touch the vaccination site until it has healed. After touching the site or changing a dressing, vaccinees and caregivers should wash their hands with warm water and soap or use a hand rub containing at least 60% alcohol. Healthcare workers who provide direct patient care should keep their inoculation site covered with gauze and a semipermeable dressing, the report notes.

Historically, most contact transmission of vaccinia occurred at home, rather than in healthcare settings, the report states. Most cases of inadvertent inoculation were eye infections. The report says most cases of inadvertent inoculation don't require treatment and resolve in about 3 weeks, but it includes a detailed discussion of treatment for complicated eye infections.

Below are some points the CDC makes regarding some of the other major complications:

  • People with a history of atopic dermatitis have an increased risk of eczema vaccinatum, a severe rash often accompanied by fever, "but no data exist to predict the absolute risk for these persons." The condition was fatal in 30% to 40% of cases before VIG became available; afterward the mortality dropped to 7%.
  • Progressive vaccinia, a rare condition that affects people with immune deficiencies, was always fatal before the introduction of VIG. The survival rate improved with VIG treatment, but the condition will probably continue to cause a high rate of mortality.
  • Fewer than 50 cases of fetal vaccinia have been described in the literature. The condition, resulting from vaccinia transmission from mother to fetus, often leads to fetal or neonatal death. Because it is so rare, the risks for fetal vaccinia "cannot be reliably determined," and "vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy."

The report says VIG is effective for treating eczema vaccinatum, progressive vaccinia, and severe cases for generalized vaccinia, but not for postvaccinia central nervous system disease. In the absence of a smallpox outbreak, VIG is not recommended for concomitant use with smallpox vaccination in people who have contraindications to the vaccine.

The report also discusses the antiviral drug cidofovir, normally used for treating cytomegalovirus retinitis in AIDS patients. Under an experimental (investigational new drug) protocol sponsored by the CDC, cidofovir can be used to treat smallpox vaccination complications that do not respond to VIG treatment. Cidofovir causes renal toxicity that is sometimes irreversible.

The report includes phone numbers that civilian and military physicians can use to request VIG or cidofovir from the CDC (877-554-4625) or the US Army Medical Research Institute of Infectious Diseases (301-619-2257).

See also:

Full text of the report

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