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Published Date: 2003-03-27 23:50:00
Subject: PRO> Smallpox vaccination adverse events - USA (08)
Archive Number: 20030327.0772

SMALLPOX VACCINATION ADVERSE EVENTS - USA (08)
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Date: 27 Mar 2003
From: ProMED-mail <promed@promedmail.org>
Source: MMWR 28 Mar 2003 52(12);248-250 [edited]
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5212a2.htm>

Cardiac Adverse Events Following Smallpox Vaccination --- United States, 2003
------------------------
During 24 Jan--21 Mar2003, smallpox vaccine was administered to 25 645
civilian health-care and public health workers in 53 jurisdictions as part
of an effort to prepare the United States in the event of a terrorist
attack using smallpox. 7 cases of cardiac adverse events have been reported
among civilian vaccinees since the beginning of the smallpox vaccination
program. In addition, 10 cases of myopericarditis have been reported among
military vaccinees. This report summarizes data on the 7 cases reported
among civilians and provides background information on recent military
vaccinees. Although a causal association between vaccination and adverse
cardiac events in the civilian population is unproven, as a precautionary
measure, CDC recommends that persons with physician-diagnosed cardiac
disease with or without symptoms (e.g., previous myocardial infarction,
angina, congestive heart failure, or cardiomyopathy) be excluded from
vaccination during this smallpox preparedness program.
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. Cardiac adverse events among civilians and myopericarditis cases
among military vaccinees were reported to CDC from the Vaccine Adverse
Event Reporting System (VAERS) as of 23 Mar 2003. 4 of the civilian cases
were previously reported in MMWR. Reported adverse events are not
necessarily associated causally with vaccination, and some or all of these
events might be coincidental.
The 7 adverse events of cardiac origin among civilian vaccinees include 3
myocardial infarctions, 2 cases of angina, and 2 cases of myopericarditis.
The median age of patients was 50 years (range: 43--60 years), and 5 were
women. 2 of the 3 patients who had a myocardial infarction died. 2 had
previous illnesses consistent with coronary artery disease (CAD); the other
had a history of hypertension, a known risk factor for CAD. Of the two
patients with angina, one had a history of CAD, and the other had no
history of CAD but at cardiac catheterization was discovered to have a
tortuous coronary artery. Both patients with myopericarditis had a history
of hypertension but no history of CAD. The 5 patients with myocardial
infarction and angina had illness onset from 4 to 17 days after
vaccination; the 2 patients with myopericarditis were both aged 45 years
and had onset of illness at 2 and 17 days after vaccination.
Case Reports
Case 1. A woman aged 50 years with a history of hypertension,
hypercholesterolemia, and smoking was vaccinated on 18 Mar 2003. On 22 Mar
2003, she had chest tightness, dizziness, nausea, and vomiting;
approximately 24 hours after onset of these symptoms, she was found
unresponsive and pronounced dead. A preliminary autopsy report indicated
that a myocardial infarction with thrombus of the right coronary artery had
occurred with extensive underlying atherosclerotic disease.
Case 2. On 4 Mar 2003, a woman aged 57 years with a history of smoking and
hypertension reported to an emergency department (ED) and was diagnosed
with an exacerbation of chronic obstructive pulmonary disease and
dehydration 6 days after smallpox vaccination (1). The patient had a
previous cardiac catheterization that was complicated by a transient
ischemic attack during the procedure. In the ED, she was treated with
oxygen, antibiotics, and intravenous fluids and was released. On 16 Mar
2003, the patient was hospitalized again following a sudden cardiopulmonary
arrest at home. Approximately 10--20 minutes elapsed between the time of
the arrest and the arrival of emergency medical personnel. The patient was
admitted to a cardiac intensive care unit with a diagnosis of myocardial
infarction. The patient died on 26 Mar 2003.
Case 3. A woman aged 54 years with a history of poorly controlled diabetes
mellitus, hypertension, obesity, untreated hyperlipidemia, and a recent
history of exertional chest pain was vaccinated on 3 Mar 2003. On 12 Mar
2003, she had onset of chest discomfort and irregular heartbeat. She was
hospitalized with atrial fibrillation and had electrocardiographic changes
and elevated cardiac enzymes consistent with subendocardial myocardial
infarction. Cardiac catheterization indicated severe CAD. Echocardiography
showed no evidence suggestive of myocarditis.
Case 4. On 14 Mar 2003, a woman aged 43 years with no history of heart
disease and no known cardiac risk factors had dizziness and lightheadedness
2 days after vaccination (1). On 16 Mar 2003, she had chest pain and
dyspnea. Subsequent cardiac catheterization identified a tortuous coronary
artery thought to be the cause of her anginal symptoms.
Case 5. A man aged 60 years with a history of hypertension, hyperlipidemia,
exertional chest pain, and a family history of CAD had onset of chest pain
while playing tennis 4 days after smallpox vaccination and reported to an
ED (2). Right coronary artery occlusion was diagnosed, and an angioplasty
was performed. He was discharged after a 2-day hospitalization.
Case 6. A male civilian federal employee aged 45 years, who had a history
of hypertension and who was vaccinated once as a child, was vaccinated on
23 Jan 2003. On 9 Feb 2003, he had fever, chills, malaise, and chest pain.
He was hospitalized for 1 day and treated with nonsteroidal
anti-inflammatory drugs and prednisone. Electrocardiogram indicated ST
segment changes and global J point elevation. His creatinine phosphokinase
was reported as mildly elevated at 223 IU (normal range: 55--170 IU), and
echocardiography and thallium studies were normal. Myopericarditis was
diagnosed. After discharge, the patient was continued on prednisone.
Case 7. On 14 Mar 2003, a woman aged 45 years who was revaccinated on 26
Feb 2003 had myocarditis; the patient had a history of hypertension treated
with an angiotensin converting enzyme (ACE) inhibitor (1). Approximately 2
weeks before vaccination, she had onset of influenza-like illness (ILI)
with fever, chills, myalgia, malaise, cough, and pleuritic chest pain and
missed 1 week of work. On 28 Feb 2003, she had sharp left shoulder pain
followed by nonexertional chest pain that improved but did not resolve
completely with nonsteroidal anti-inflammatory drugs. On 3 Mar 2003, she
complained again of dyspnea and exertional chest pain and was hospitalized
the next day. On 5 Mar 2003, an echocardiogram demonstrated decreased left
ventricular function, left ventricular wall motion abnormality, and a small
pericardial effusion. Cardiac catheterization found no evidence of coronary
artery disease. Myocarditis was diagnosed. On 6 Mar 2003, the patient was
discharged, and her symptoms improved after treatment with an increased
dose of ACE inhibitor, addition of a low-dose beta blocker, and NSAIDS. The
antecedent ILI and chest pain before vaccination suggests a nonvaccinia
infectious etiology.
As of 23 Mar 2003, a total of 10 cases of myocarditis and/or pericarditis
have been identified among approximately 225 000 primary vaccinees in the
military smallpox vaccination program. All had onset of chest pain 6--12
days following vaccination and all had clinical, laboratory,
electrocardiographic, and/or echocardiographic evidence of myocardial
and/or pericardial inflammation. None of the cases was clinically severe,
and all patients recovered fully and returned to active duty. No cases of
myocarditis or pericarditis were detected among approximately 100 000
persons in the military program who were revaccinated.
Editorial Note:
Myocarditis and pericarditis following smallpox vaccination have been
reported (3,4). The majority of reports were from Europe and Australia,
where a more virulent vaccine strain was used, but myopericarditis is not a
well-recognized complication following vaccination with the strain of
vaccinia being used in the United States (i.e., the New York City Board of
Health vaccinia strain, DryVax® [Wyeth Laboratories Inc., Marietta,
Pennsylvania]). Data from the military smallpox vaccination program are
consistent with a causal association between vaccination and
myopericarditis, although this association is not proven.
Other coronary events, including angina and myocardial infarction, have not
been previously associated with smallpox vaccination (5,6). The relation
between smallpox vaccine and the coronary events observed in the civilian
vaccination program is unclear.
The frequency of coronary heart disease in the general population makes it
difficult to determine if a serious coronary event following vaccination is
coincidental or associated with vaccination. The civilian smallpox
vaccination program might differ from historical experience because more
older patients with underlying heart disease and cardiac risk factors
(e.g., hypertension and diabetes mellitus) might be receiving vaccinations.
In addition, because current diagnostic tests, including cardiac enzymes
and echocardiography, are more sensitive for diagnosing myocardial
infarction than previous methods, more events might be detected than were
previously observed.
Cardiac-associated death following smallpox vaccination, although extremely
rare, has been reported in Europe and Australia and has been thought to be
associated with myocarditis (7,8). However, in the United States, a
death-certificate study of vaccinia-associated deaths conducted during
1959--1966 and 1968 did not identify any deaths associated with cardiac
complications (9).
Because of the substantial numbers of persons vaccinated in the civilian
program, a small number of deaths following vaccination are expected to
occur. Of the 25 645 persons vaccinated in the civilian program, age data
are available for 14 438. By using the age distribution for these persons,
using year 2000 age-specific death rates from all causes (10), and assuming
that the age distribution is the same for persons whose age is unknown,
2--3 deaths are expected to occur within 3 weeks of vaccination among
persons aged 45--54 years and an additional 2--3 deaths among vaccinees
aged 55--64 years. Among vaccinees aged 45--64 years, 1--2
cardiac-associated deaths are expected to occur within 3 weeks of vaccination.
Because of the reports of myopericarditis and other cardiac adverse events,
CDC and DoD are issuing a supplement to the smallpox vaccine information
statement, disseminating information to partners and clinicians, and
developing strategies to assess prospectively the incidence and potential
causal association of cardiac events among vaccine recipients.
Because a causal relation between smallpox vaccination and serious cardiac
events cannot be excluded, CDC recommends as a precautionary measure that
persons with known cardiac disease with or without symptoms be excluded
from vaccination. As more information becomes available, this
recommendation might be revised.
Persons receiving smallpox vaccine should be informed that myopericarditis
might be associated with smallpox vaccination and that they should seek
medical attention if they develop chest pain, shortness of breath, or other
symptoms of cardiac disease after smallpox vaccination. For suspected
adverse cardiac events among smallpox vaccine recipients, providers should
consult with a cardiologist to ensure appropriate diagnostic studies are
conducted to facilitate diagnosis and treatment.
Health-care providers needing assistance evaluating a smallpox vaccinee
with a serious adverse event should contact their state health department
or CDC's Clinician Information Line, telephone 877-554-4625. This
information line, staffed by nurses 24 hours a day, 7 days a week, is a
source for general smallpox clinical adverse event information and for
assistance with adverse event reporting.
References
1. CDC. Smallpox vaccine adverse events among civilians---United States,
March 4--10, 2003. MMWR 2003;52:201--3.
Smallpox vaccine adverse events among civilians---United States, February
18--24, 2003. MMWR 2003;52:156--7.
2. Karjalainen J, Heikkila J, Nieminen MS, et al. Etiology of mild acute
infectious myocarditis. Acta Medica Scandinavica 1983;213:65--73.
3. Helle EJ, Koskenvuo K, Heikkila J, Pikkarainen J, Weckstrom P.
Myocardial complications of immunisations. Ann Clin Res 1978;10:280--7.
4. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox
vaccination: national surveillance in the United States, 1968. N Engl J Med
1969;281:1201--7.
5. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox
vaccination, 1968: results of ten statewide surveys. J Infect Dis
1970;122:303--9.
6. Finlay-Jones LR. Fatal myocarditis after vaccination against smallpox:
report of a case. N Engl J Med 1964;270.
7. Feery BJ. Adverse reactions after smallpox vaccination. Med J Aust
1997;2:180--3.
8. Lane JM, Ruben FL, Abrutyn E, Millar JD. Deaths attributable to smallpox
vaccination, 1959 to 1966, and 1968. JAMA 1970;212:441--4.
9. Minino AM, Smith BL. Deaths: preliminary data for 2000. Natl Vital Stat
Rep 2001;49.
--
ProMED-mail
<promed@promedmail.org>
[The occurrence of 10 cases of myocarditis among healthy young vaccinees
(one assumes the vaccinees were born after 1972 when routine vaccination
with smallpox was discontinued in the USA) is of concern. This represents
a rate of 4.4 per 100 000 population, a rate significantly less than
presented in reference 2 above (1 per 10 000). We await more information
on this investigation. - Mod.MPP]

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