CDC cautious after two deaths among smallpox vaccine recipients

ATLANTA — The CDC is recommending that all individuals with heart disease be deferred from vaccination against smallpox after two deaths due to myocardial infarction were reported in recipients of the vaccine.

Health officials are uncertain if the deaths are a direct result of vaccination against smallpox, but at least three other individuals have reported cardiac-related illnesses after receipt of the vaccine. Among 250,000 military personnel receiving the vaccine for the first time, there have been 14 cases of myocarditis plus one fatal myocardial infarction, according to the CDC. There have been no reports of cardiac disease among 115,000 personnel being revaccinated.

To date, there have been four reports of myocardial infarction after exposure to the vaccine among civilian the population, including one death in a 50-year-old Maryland woman, and a second death in a 57-year-old woman with a history of smoking and hypertension. A third woman to suffer a heart attack after receiving the vaccinia vaccine (Dryvax, Wyeth) was also in her 50s, and all three women had known risk factors for the development of cardiac complications, according to Julie Gerberding, MD, director of the CDC.

In their weekly update on reported adverse events after smallpox vaccination, the CDC reported a fourth myocardial infarction in a 64-year-old male with atherosclerotic coronary artery disease and dyspnea on exertion. The CDC has also received two reports of angina that may be linked to smallpox vaccination, three cases myopericarditis and one myocarditis.

Cardiac sequelae not foreseen

Before the smallpox program began, a CDC advisory board stated that based on past experience with the vaccinia vaccine, vaccination should be contraindicated in patients with compromised immune systems, pregnant women, patients with eczema, as well as household contacts — this because they are at increased risk for serious adverse events, even death.

The screening guidelines made no mention of potential cardiac sequelae. There were case reports of heart inflammation following vaccination against smallpox in the 1960s and 1970s, but the reports did not provide information on whether the patients were at high risk for cardiac complications, CDC officials said.

“In the past vaccination programs for smallpox before eradication, we didn’t have a lot of experience vaccinating older people,” explained Gerberding in a press briefing on March 25. “There is no known association throughout that experience with any kind of cardiac events associated with immunization.”

In addition to the five patients with known cardiac sequelae after vaccination, Gerberding also said the CDC received reports on two other patients with “inflammatory conditions that have affected the heart.” The CDC later identified the two cases as myopericarditis.

One patient with myocarditis was subsequently evaluated and found not to have illness related to vaccination. The other individual, receiving the vaccine for the first time, suffered a mild case of probable pericardial inflammation, “an experience consistent with what we understand might be a condition in other people who are being vaccinated for the first time,” said Gerberding.

Between March 25 and March 30 an additional two cases of myopericarditis have been reported, but no additional information is available on the cases.

At least three of the patients with myocardial infarction and the two with angina had known risk factors for developing coronary artery disease. Even though the link between the vaccine and cardiac complications is not definite, Gerberding said the CDC wants to “err on the side of safety” in limiting vaccination in individuals with known serious heart disease.

Included in the deferral are patients with either coronary artery disease or myocardial disease, a history of heart attack, congestive heart failure and patients with any kind of cardiomyopathy. Individuals with underlying heart disease with or without symptoms, or who have three or more known major risk factors – defined as hypertension, diabetes, hypercholestolemia, heart disease at age 50 in a primary relative or smoking – should be excluded from vaccination, the CDC said.

CDC officials are still investigating whether the deaths are linked to vaccination. Myocardial infarctions occurred two, five, nine and 17 days after vaccination and both angina cases occurred four days after vaccination. Among patients reporting myopericarditis, symptom onset ranged from 12 to 17 days postvaccination.

Although the timing of symptoms is consistent with a causal relationship, no such association between ischemic cardiac events and smallpox vaccination has been established. However, the CDC continues to closely monitor adverse events among recipients of vaccination against smallpox.

Cardiac Events and Smallpox Vaccination Reported cardiac events among 29,584 civilian recipients of smallpox vaccination through March 30, 2003 EVENTS Myocardial infarction Myopericarditis Angina Myocarditis REPORTS 4 3 2 1 Source: CDC

Because of known risks associated with vaccination against smallpox, the CDC set up a monitoring system to track adverse events among vaccinated individuals. Through March 30, the CDC received 26 reports of moderate to severe events, or events that require medical monitoring but are expected to have a good outcome, and 24 reports of other severe events, or events that have been temporarily associated with vaccination but have yet to be verified as causally associated.

Six moderate-to-severe events involved transmission of vaccinia virus from military personnel to civilian contacts. One patient so far has required treatment with vaccinia immune globulin, but there have been no deaths positively associated with the vaccine. The 24 other severe events include reports of four myocardial infarctions, two cases of angina, and four cases of myopericarditis.

The CDC has also received numerous reports of mild adverse events, including soreness at the vaccination site, redness, swelling, fever, rashes and missed days from work or school, but they have largely been self-limiting and resolved with proper care.