Serious adverse reactions to smallpox vaccine appear to be limited

December 06, 2005

There was a low rate of life-threatening adverse reactions to the smallpox vaccine administered to potential first responders to a bioterrorism incident, possibly attributable to rigorous vaccine safety screening and educational programs, according to a study in the December 7 issue of JAMA.

Routine childhood immunization against smallpox in the United States ceased in 1971, according to background information in the article. Although the World Health Organization declared in 1980 that smallpox had been eradicated worldwide, there is concern that smallpox virus may exist outside the World Health Organization−designated repository laboratories and may be used as a bioweapon. Detection of a smallpox case could represent an intentional bioterrorism event requiring an immediate, coordinated response by public health, medical, and law enforcement personnel to control the outbreak and protect the public.

In January 2003, the U.S. Department of Health and Human Services (DHHS) implemented a voluntary civilian smallpox vaccination program, in which vaccine was administered to federal, state, and local volunteers who might be first responders during a bioterrorism event.

Christine G. Casey, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues examined the vaccine safety profile among civilians who received smallpox vaccine between January 24 and October 31, 2003. The researchers evaluated adverse events reported via the Vaccine Adverse Event Reporting System (VAERS) and the Centers for Disease Control and Prevention.

A total of 37,901 volunteers in 55 jurisdictions received at least 1 dose of smallpox vaccine. VAERS received 822 reports of adverse events following smallpox vaccination (overall reporting rate, 217 per 10,000 vaccinees). A total of 590 adverse events (72 percent) were reported within 14 days of vaccination. Nonserious adverse events (n = 722) included multiple signs and symptoms of mild and self-limited local reactions. One hundred adverse events (12 percent) were designated as serious, resulting in 85 hospitalizations, 2 permanent disabilities, 10 life-threatening illnesses, and 3 deaths. Among the serious adverse events, 21 cases were classified as myocarditis (inflammation of the muscular tissue of the heart) and/or pericarditis (inflammation of a membrane that surrounds the heart) and 10 as ischemic cardiac events that were not anticipated based on historical data. Two cases of generalized vaccinia (a skin eruption in reaction to vaccination) and 1 case of postvaccinial encephalitis (inflammation of the brain) were detected. No preventable life-threatening adverse reactions, contact transmissions, or adverse reactions that required treatment with vaccinia immune globulin were identified. Serious adverse events were more common among older revaccinees than younger first-time vaccinees.

"The absence of preventable serious adverse reactions provides indirect evidence of effective vaccination screening and education, as well as attentive vaccination site care and monitoring," the authors write.

"This comprehensive smallpox vaccine safety monitoring and response system can serve as an effective model for vaccine campaigns that may occur in response to public health emergencies. Unique aspects included rapid detection, investigation, and response to rare and potentially serious adverse events. Our report highlights the success of education, screening, and clinical investigations and reviews in augmenting a robust safety monitoring system to minimize preventable adverse events. Additional reduction of overall vaccinia adverse events might be achievable through study of cardiac and dermatological risk factors, a better understanding of vaccinia host-pathogen interaction, and development of a less reactogenic vaccinia vaccine," the researchers conclude.
(JAMA.2005; 294:2734-2743. Available pre-embargo to the media at

Editor's Note: All financial and material support for the surveillance efforts was conducted as part of the CDC and state health department public health response. No additional funding was sought to support these activities.

Neurologic Adverse Events From Smallpox Vaccine Generally Mild

In a related study in this issue of JAMA, adverse neurologic reactions from smallpox vaccination were generally mild and the rate of specific syndromes did not exceed baseline estimates.

Rare adverse events causally associated with smallpox vaccination include neurologic syndromes such as central nervous system (CNS) and peripheral nervous system (PNS) complications, according to background information in the article. The most common CNS complication after smallpox vaccination is encephalitis (postvaccinial encephalomyelitis - inflammation of the brain and spinal cord). Other infrequent events can include headache, Guillain-Barré syndrome (a temporary inflammation of the nerves, causing pain, weakness, and paralysis in the extremities), Bell palsy (paralysis of the facial muscles), and myelitis (inflammation of the spinal cord).

James J. Sejvar, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues assessed reports of postvaccinial encephalomyelitis and other neurologic adverse events between December 16, 2002, and March 11, 2004, among DHHS and DoD smallpox vaccinees, to clinically characterize them and assess their frequency. Information on the events was obtained through active case reporting and review of data submitted to the Vaccine Adverse Event Reporting System among 665,000 persons vaccinated against smallpox by the Departments of Defense (n = 590,400) and Health and Human Services (n = 64,600) during the 2002-2004 U.S. Smallpox Vaccination Program.

The researchers found that there were 214 neurologic adverse events temporally associated with smallpox vaccination; 111 reports involved DHHS and 103 involved DoD vaccinees. Fifty-four percent of these events occurred within 1 week of vaccination, and 53 percent were among primary vaccinees. The most common neurologic adverse event was headache (95 cases), followed by nonserious limb paresthesias (n = 17) or pain (n = 13) and dizziness or vertigo (n = 13). Serious neurologic adverse events included 13 cases of suspected meningitis, 3 cases of suspected encephalitis or myelitis, 11 cases of Bell palsy, 8 seizures (including 1 death), and 3 cases of Guillain-Barré syndrome. Among these 39 events, 27 (69 percent) occurred in primary vaccinees and all but 2 occurred within 12 days of vaccination.

"Our findings identified many milder neurologic adverse events temporally but not necessarily causally associated with smallpox vaccination. They suggest that such events are generally self-limited, nonserious, and not associated with severe morbidity or mortality when screening defers persons with high-risk conditions," the authors write.

"Smallpox vaccine was given to healthy people, which creates a low tolerance for associated risk. Risks associated with vaccines are best identified through population-based assessments. New, possibly less reactogenic smallpox vaccines are currently under development. Continued monitoring for neurologic events is needed to assess the safety of smallpox vaccines and to better characterize the spectrum of neurologic illness associated with them," the researchers conclude.

(JAMA.2005; 294:2744-2750. Available pre-embargo to the media at

Editor's Note: This study was supported by the CDC and the U.S. Department of Defense.

The JAMA Network Journals

Related Public Health Articles from Brightsurf:

COVID-19 and the decolonization of Indigenous public health
Indigenous self-determination, leadership and knowledge have helped protect Indigenous communities in Canada during the coronavirus disease 2019 (COVID-19) pandemic, and these principles should be incorporated into public health in future, argue the authors of a commentary in CMAJ (Canadian Medical Association Journal)

Public health consequences of policing homelessness
In a new study examining homelessness, researchers find that policy such a lifestyle has massive public health implications, making sleeping on the street even MORE unhealthy.

Electronic health information exchange improves public health disease reporting
Disease tracking is an important area of focus for health departments in the midst of the COVID-19 pandemic.

Pandemic likely to cause long-term health problems, Yale School of Public Health finds
The coronavirus pandemic's life-altering effects are likely to result in lasting physical and mental health consequences for many people--particularly those from vulnerable populations--a new study led by the Yale School of Public Health finds.

The Lancet Public Health: US modelling study estimates impact of school closures for COVID-19 on US health-care workforce and associated mortality
US policymakers considering physical distancing measures to slow the spread of COVID-19 face a difficult trade-off between closing schools to reduce transmission and new cases, and potential health-care worker absenteeism due to additional childcare needs that could ultimately increase mortality from COVID-19, according to new modelling research published in The Lancet Public Health journal.

The Lancet Public Health: Access to identification documents reflecting gender identity may improve trans mental health
Results from a survey of over 20,000 American trans adults suggest that having access to identification documents which reflect their identified gender helps to improve their mental health and may reduce suicidal thoughts, according to a study published in The Lancet Public Health journal.

The Lancet Public Health: Study estimates mental health impact of welfare reform, Universal Credit, in Great Britain
The 2013 Universal Credit welfare reform appears to have led to an increase in the prevalence of psychological distress among unemployed recipients, according to a nationally representative study following more than 52,000 working-age individuals from England, Wales, and Scotland over nine years between 2009-2018, published as part of an issue of The Lancet Public Health journal on income and health.

BU researchers: Pornography is not a 'public health crisis'
Researchers from the Boston University School of Public Health (BUSPH) have written an editorial in the American Journal of Public Health special February issue arguing against the claim that pornography is a public health crisis, and explaining why such a claim actually endangers the health of the public.

The Lancet Public Health: Ageism linked to poorer health in older people in England
Ageism may be linked with poorer health in older people in England, according to an observational study of over 7,500 people aged over 50 published in The Lancet Public Health journal.

Study: Public transportation use linked to better public health
Promoting robust public transportation systems may come with a bonus for public health -- lower obesity rates.

Read More: Public Health News and Public Health Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to