Chapter 4 Part A: Common reactions
and potential serious adverse events following smallpox
vaccination, with Dr. Brett Petersen.
In Chapter 4 of this training video,
we will describe the common reactions
and potential serious adverse events following vaccination,
and the available treatment.
ACAM2000 has been evaluated for safety in 2,983 subjects
who received ACAM2000 in 6 clinical trials.
Overall, these trials showed that ACAM2000 was well-tolerated
and less reactogenic than older smallpox replication-competent
vaccines such as Dryvax.
Adverse events associated
with ACAM2000 were generally predictable and manageable
with the incidence higher among primary vaccinees
than previously vaccinated subjects.
No deaths were reported
and serious adverse events following vaccination were less
than one percent.
Assessment of risks and benefits must be conducted
when deciding whether to vaccinate an individual
with ACAM2000, especially for those individuals
who have a higher risk
for experiencing a serious adverse event.
However, the risk/benefit profile will differ depending
on if a smallpox emergency is in effect,
versus if there is no smallpox emergency in effect.
Report any adverse events with ACAM2000
to the Vaccine Adverse Event Reporting System, or VAERS.
The most common reactions following ACAM2000 vaccination
during the clinical trials were mild
to moderate vaccination site reactions such as pruritus,
erythema, pain, and swelling at the site; lymph node enlargement
and tenderness usually on the same side
where the vaccination had occurred;
constitutional "flu-like" symptoms such as fever, malaise,
myalgia, headaches, rigors, or "feeling hot";
and mild gastrointestinal symptoms
such as nausea and diarrhea.
These common reactions were generally self-limited.
The most common serious adverse events reported following
ACAM2000 vaccination were suspected
or probable myocarditis and pericarditis in subjects
who received ACAM2000 for the first time,
resulting in an estimated incidence
of 5.7 events per thousand vaccinations.
None of the subjects had confirmed myocarditis
or pericarditis and none
of these events occurred among previously vaccinated subjects.
Other serious cardiac events reported include single reports
of atrial fibrillation, chest discomfort, and chest pain
that may have been associated
with ACAM2000 among 3 previously vaccinated subjects.
One primary vaccinee did experience a new-onset
of seizure 8 days after vaccination;
however predisposing factors were contributory.
All serious adverse events resolved
without permanent sequelae.
Five subjects were also identified
to be pregnant 30 days after ACAM2000 vaccination.
There were no reports of fetal vaccinia, congenital anomalies,
or birth defects following delivery.
Post-licensure monitoring for these serious adverse events
after ACAM2000 vaccination remains ongoing.
Because ACAM2000 is derived from the same New York City Board
of Health strain used
to manufacture other older smallpox vaccines
such as Dryvax; and historically serious adverse events have
occurred following vaccination
with these older smallpox vaccines, it is anticipated
that the safety profile of ACAM2000 is probably similar.
Thus, historical data regarding serious adverse events following
smallpox vaccination during the era
of routine smallpox vaccination in 1968 and from the 2000
to 2005 military and civilian smallpox vaccination program are
briefly summarized here.
Serious adverse events that have occurred following smallpox
vaccination have included myocarditis, pericarditis,
postvaccinial encephalitis, eczema vaccinatum,
progressive vaccinia, generalized vaccinia,
severe vaccinial skin infections,
erythema multiforme major,
including Stevens-Johnson syndrome, fetal vaccinia
and fetal death, and ocular complications,
such as keratitis, corneal scarring and blindness,
and inadvertent inoculation that resulted in severe complications
in non-vaccinated contacts.
The risks of these serious adverse events, which may result
in severe disability, permanent neurological sequelae,
and/or death, might be increased in individuals
with certain conditions such as cardiac disease,
eye disease being treated with topical steroids,
immunodeficiency, eczema
or chronic exfoliative skin conditions,
and in young children or pregnant women.
During routine vaccinations with older smallpox vaccines
in the 1960s, myocarditis
and pericarditis were not commonly reported
following vaccination.
However, these events emerged
with increased frequency during the 2002 to 2005 military
and civilian vaccination campaign
of over 770,000 vaccinees.
The pathophysiology of this complication remains unknown
given the absence of viral damage
in the histopathology examination of myocardial tissue
of those with myocarditis.
Enhanced surveillance and better diagnostic testing probably
played a role in the increase of cases reported.
Other cardiac adverse events such as ischemic cardiac events
and non-ischemic, dilated cardiomyopathy were also
reported during the vaccination campaign.
The incidence of these complications does not appear
to significantly exceed expected background rates
and there is currently no evidence
to suggest a causal association of smallpox vaccination
with cardiac ischemia or myocardial infarction.