4 tables omitted
During January 24–March 28, 2003, smallpox vaccine was administered
to 29,584 civilian health-care and public health workers in 54 jurisdictions
as part of an effort to prepare the United States for a terrorist attack using
smallpox virus. This report summarizes data on ten cases of cardiac adverse
events reported among civilian vaccinees since the beginning of the smallpox
vaccination program, including three new cardiac adverse events reported to
CDC from the Vaccine Adverse Event Reporting System (VAERS) during March 24-30.
Fourteen cases of myocarditis and one fatal myocardial infarction have been
reported among military personnel. This report summarizes data on the three
new cases of cardiac adverse events, updates data on seven previously reported
cases among civilian vaccinees,1 summarizes selected cases of cardiac
adverse events among military vaccinees, and updates information on all adverse
events reported in the civilian vaccination program as of March 30.
CDC, the Food and Drug Administration, and state health departments
are conducting surveillance for vaccine-associated adverse events among civilian
vaccinees; the Department of Defense (DoD) is conducting surveillance for
vaccine-associated adverse events among military vaccinees. In the first stage
of the civilian program, active surveillance is being conducted for any adverse
events after vaccination that require medical care. In the military vaccination
program, military personnel receive medical care primarily in a network of
linked clinics, which report adverse events to medical headquarters and VAERS.
The three new cases of cardiac adverse events among civilians during
March 24-30 include two cases of myopericarditis and one case of myocardial
Case 1. A man aged 56 years with a history
of mild hypertension and hypertriglyceridemia was revaccinated on March 4.
On March 16, he had onset of influenza-like illness (ILI), chest discomfort
while lying flat, and pleuritic pain during inspiration; a clinical examination
revealed tachycardia. During the next 7 days, he had chest pain, dyspnea on
exertion, fever, chills, pallor, and left knee pain. All symptoms and signs
had resolved 17 days after vaccination. On day 23 post vaccination, an electrocardiogram
(ECG) indicated low R waves in the anterior leads, and borderline first-degree
AV block (PR interval: 0.21 msec). Echocardiogram revealed widening of the
pericardial space with minimal fluid collection, a normal ejection fraction,
and normal ventricular wall function. Chest radiograph demonstrated left basilar
atelectasis. The patient had normal troponin I, creatine kinase myocardial
band (CK-MB), C-reactive protein levels, and a normal erythrocyte sedimentation
rate. These findings are consistent with mild myopericarditis. The patient
recovered; a follow-up exercise cardiac perfusion scan was normal.
Case 2. A woman aged 32 years with no history
of cardiac disease or major risk factors for coronary artery disease was vaccinated
for the first time on January 31. On February 16, she had fever, crushing-type
chest pain, and shortness of breath, which prompted a visit to the emergency
department (ED). An ECG indicated nonspecific ST-T wave changes; cardiac enzymes
were normal. A repeat ECG several days later was normal. After 5-6 days, her
symptoms resolved completely, and she was able to resume normal activities.
Six weeks after vaccination, a nuclear stress test was normal. Her clinical
course and ECG findings were consistent with myopericarditis.
Case 3. An active man aged 64 years with a
history of dyspnea on exertion and productive cough for 3 months and eight
previous smallpox vaccinations was revaccinated on March 21. On March 23,
he sought medical care for chest "fullness" and dizziness. Blood tests indicated
elevated troponin I and CK-MB levels. ECG demonstrated inferior ST segment
depression and T wave inversion. Echocardiography indicated moderate inferior
wall hypokenesis with a normal ejection fraction. Coronary arteriography showed
three-vessel atherosclerotic disease with development of some collateral circulation.
The patient underwent cardiac catheterization with ballon atherotomy, and
two coronary artery stents were placed. The clinical course and laboratory
findings are consistent with acute myocardial infarction in a patient with
chronic coronary artery disease. He returned to work on March 31.
On March 23, a woman aged 55 years with a history of hypertension, hypercholesterolemia,
and smoking died 5 days after smallpox vaccination.1 Autopsy showed
extensive atherosclerotic disease, with right coronary artery thrombosis and
lateral wall softening. Preliminary testing, including real-time polymerase
chain reaction (PCR) and immunohistochemistry, showed evidence of vaccinia
virus only at the vaccination site; limited analyses of other tissues, including
heart and other visceral tissue, were negative for vaccinia virus by real-time
PCR and immunohistochemistry.
On March 26, a woman aged 57 years with a history of smoking, hypertension,
transient ischemic attack, and carotid endarterectomy died 22 days after smallpox
vaccination.1 Autopsy showed extensive atherosclerosis of the coronary
arteries, and a large healing infarct involving the posterior wall of the
left ventricle and intraventricular septum. Histopathologic evaluation revealed
no evidence of myocarditis or pericarditis. Preliminary analysis using real-time
PCR tests showed evidence of vaccinia virus DNA at the vaccination site but
not in affected myocardium and other viscera.
During March 25-31, four cases of myocarditis and/or pericarditis were
identified, totaling 14 cases among approximately 250,000 personnel who received
smallpox vaccination for the first time. No cases of myocarditis and/or pericarditis
were identified among approximately 115,000 service members who were revaccinated.
Among the approximately 365,000 vaccinated military service members, one death
has been reported.
The 14 patients with myocarditis and/or pericarditis ranged in age from
21 to 33 years. Severity ranged from mild (no ECG or echocardiogram changes)
to severe (congestive heart failure), with onset 7 to 19 days after vaccination.
All military patients were hospitalized, and all survived. As of April 2,
the patient with the most severe case has been hospitalized for 6 days. All
other hospitalized patients have been discharged; they have either returned
to duty or are on short-term convalescent leave. Following are two cases that
represent the spectrum of clinical presentations of myopericarditis and a
report of a fatal case of myocardial infarction.
Case 1. On March 18, a man aged 22 years sought
medical care at a military health clinic for chest pain 12 days after primary
smallpox vaccination. He was treated with nonsteroidal anti-inflammatory agents
for presumed costochondritis. When laboratory tests revealed elevated cardiac
enzymes levels, he was referred to a university hospital emergency department
(ED) for further evaluation. Cardiac enzymes levels remained elevated, but
an ECG, echocardiogram, and cardiac stress test were normal. Myopericarditis
was diagnosed, and he was released that day in good condition.
Case 2. A man aged 29 years had ILI symptoms
during the same week of primary smallpox vaccination. At the time of smallpox
vaccination on March 8, he also received five other inactivated vaccines;
19 days after vaccination, he sought treatment at an ED for dyspnea while
lying flat. On March 28, he was hospitalized and had myopericarditis diagnosed
based on ECG findings and elevated troponin I and CK-MB. The next day, he
had pulmonary edema with a pulmonary artery wedge pressure of 38 mm Hg that
responded well to several doses of intravenous diuretics. Serial echocardiograms
showed ejection fractions as low as 25% that subsequently improved to 45%
(normal: >55%). Endomyocardial biopsy revealed active myocarditis with a mixed
infiltrate of lymphocytes and eosinophils and evidence of eosinophilic degranulation
in proximity to myocyte necrosis. PCR testing of myocardial tissue was negative
for vaccinia virus DNA, varicella-zoster virus DNA, and herpes simplex virus
DNA; reverse transcriptase PCR was negative for enterovirus RNA. As of April
2, he remained hospitalized but was stable and improving.
Case 3. On March 25, an Army National Guardsman
aged 55 years with a history of smoking and treatment for hyperlipidemia was
found unresponsive in a vehicle 5 days after receiving smallpox vaccine and
two other inactivated vaccines. He was resuscitated but died the next day.
Autopsy showed acute thrombosis of the right anterior descending coronary
artery, three-vessel coronary artery disease with 75%-80% occlusion, left
ventricular hypertrophy, and cardiomegaly. Histopathology of left ventricular
myocardium revealed no evidence of myocarditis or pericarditis. Virologic
testing of myocardium is pending. The cause of death was acute myocardial
As of March 30, no cases of several potentially life-threatening adverse
events associated historically with smallpox vaccination (i.e., progressive
vaccinia, eczema vaccinatum, post-vaccinial encephalitis, or encephalomyelitis)
have been reported among civilians. In addition, no cases of vaccinia transmission
from civilians have been reported. This includes no transmission from 18,344
members of health-care teams, 6,655 of whom have been followed for >1 month.
During March 11-30, six cases of generalized vaccinia, 14 cases of inadvertent
inoculation (nonocular), and four cases of myopericarditis were reported.
During the same period, 12 other serious adverse events were reported. Of
these, four were myocardial infarctions, and two were cases of angina. The
remaining six other new serious adverse events had hospital discharge diagnoses
of pancreatic cancer, urinary tract infection, herpes zoster virus infection,
headache, and facial paralysis with paresthesias. Among the 192 vaccinees
with reported other nonserious adverse events during January 24–March
30, the most common signs and symptoms were fever (n = 42), rash (n = 39),
headache (n = 34), and pruritus (n = 32). All of these commonly reported events
are consistent with mild expected reactions after receipt of smallpox vaccine.
Some vaccinees reported multiple signs and symptoms. During March 11-30, no
vaccinia immune globulin was released for civilian vaccinees.
Surveillance for adverse events during the civilian and military smallpox
vaccination programs is ongoing; regular surveillance reports will be published
Smallpox vaccine adverse events coordinators. Military Vaccine Agency,
Army Medical Command, U.S. Dept of Defense. National Center for Infectious
Diseases. National Immunization Program.
New reports of myopericarditis following smallpox vaccination are consistent
with previous reports describing a potential causal association between vaccination
and myopericarditis.1 One new case of myocardial infarction among
civilian vaccinees and one death from myocardial infarction among military
vaccinees have been reported, but any association between smallpox vaccine
and ischemic heart disease remains unclear.
Myopericarditis is often asymptomatic or mild, but can be severe. Symptomatic
patients report chest pain, fatigue, fever, palpitations, and dyspnea on exertion.
The patient with myopericarditis and congestive heart failure reported by
DoD illustrates the potential severity of the condition, which can lead to
severe cardiac dysfunction or dysrhythmia. In addition, rare fatal cases of
myocarditis after smallpox vaccination have been reported in Europe and Australia.2,3 Evaluation and follow-up guidelines are being developed by CDC to
assist health-care providers in managing vaccinees with cardiac adverse events.
Preliminary autopsy findings for the three patients with myocardial
infarction who died showed no evidence of disseminated vaccinia infection
or myopericarditis. Although virologic testing of myocardial tissue is pending
for one patient and is limited for the other two, these findings suggest the
ischemic events in these patients did not result from vaccinia-associated
myocarditis. The number of reported deaths from cardiac disease among civilians
and military personnel is consistent with expected background rates.1 However, it is not known whether smallpox vaccination could contribute
to these events through another mechanism.
On the basis of the civilian and military cases, and guidance from the
Advisory Committee on Immunization Practices4 and an independent
group of cardiology consultants, CDC revised its recommendations for screening
and exclusion of potential smallpox vaccine recipients. Persons should be
excluded from the pre-event smallpox vaccination program if they have had
heart disease or any type of ischemic cardiovascular disease diagnosed, with
or without symptoms (e.g., previous myocardial infarction, angina, congestive
heart failure, cardiomyopathy, stroke or transient ischemic attack, or other
heart conditions under the care of a doctor). Persons also should be excluded
if they have three or more risk factors: hypertension, diabetes, hypercholesterolemia,
smoking, or an immediate family member who had onset of a heart condition
before age 50. To date, five of the six vaccinated civilians with cardiac
adverse events indicative of ischemic heart disease met these exclusion criteria.
References: 4 available
Update: Adverse Events Following Smallpox Vaccination—United
States, 2003. JAMA. 2003;289(16):2060-2063. doi:10.1001/jama.289.16.2060