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Smallpox Vaccine Safety
Three studies provide somewhat reassuring data on adverse events in smallpox vaccinees and a fourth suggests that even a diluted vaccine could be effective.
A principal concern in the fall of 2002 regarding a national smallpox vaccination program was the safety of the vaccine in the setting of a largely unimmunized population. Four reports arising from the NIH and U.S. military smallpox vaccination programs provide partial, but relatively reassuring, news on the safety and efficacy of the vaccine.
Grabenstein and Winkenwerder describe the overall experience in the first 6 months of the U.S. military smallpox vaccination program, through which 450,293 individuals were vaccinated between December 2002 and May 2003. All individuals were screened for potential contraindications, and eligible individuals received the licensed full-strength smallpox vaccine containing the New York City Board of Health vaccinia strain. Between 11% and 34% (depending on the military unit) of screened individuals were believed to have contraindications. The median age of vaccinees was 26 years; 70.5% received a primary vaccination. Temporary mild symptoms, including malaise, myalgias, and headache, occurred commonly, but only 3% of carefully followed individuals took sick leave, for an average duration of 1 day; sick leave was more common among primary vaccinees than revaccinees. There were 144 serious adverse events: 36 cases of mild generalized vaccinia, 37 cases of myopericarditis, 48 cases of inadvertent self-inoculation, 21 cases of vaccinia transfer to others, and 1 case each of encephalitis and erythema multiforme. Ten individuals with unrecognized HIV were vaccinated without adverse effects. Vaccinated healthcare workers were not furloughed, and no transmissions to patients were noted during 19,461 worker-months.
Halsell and colleagues provide additional information on the first 18 cases of probable vaccine-associated myopericarditis in U.S. military vaccinees. In contrast to the experience in civilian vaccinees (see JWID Jun 20 2003), all military cases were in primary vaccinees. Disease onset was 7 to 19 days after vaccination. The incidence in primary vaccinees was 7.8 cases per 100,000 during the 30 days following vaccination, compared with an expected incidence in this population of 2.2 cases. No other potential etiologies were identified for any cases; however, no standardized protocol for evaluating etiologies was used. All individuals have recovered.
Using data from an NIH-supported, dose-ranging smallpox vaccine trial, Talbot and colleagues provide detailed information on generalized papulovesicular rashes following primary vaccination. Of 148 healthy volunteers, 4 developed a generalized follicular papulovesicular rash, and 7 others developed a morphologically similar localized rash. The generalized rash appeared 9 to 11 days following vaccination, with simultaneously present lesions at various stages of development. The lesions resolved without scarring, and all patients were afebrile. No vaccinia virus was isolated from any of the 17 lesions tested.
Given the concern that the smallpox vaccine supply remains limited, Frey and colleagues assessed the efficacy of 3 different dilutions of vaccine in 80 previously vaccinated individuals and in 10 previously unvaccinated controls. Overall, initial vaccination was successful in 64 of 80 revaccinees and in all 10 controls. Rates of successful vaccination in revaccinees were 95% for undiluted vaccine, 90% for 1:3.2 vaccine, 81% for 1:10 vaccine, and 53% for 1:32 vaccine. Repeat vaccination of nonresponders with the same dilution 1 week later increased the total success rate to 86% for the 1:10 dilution recipients and 68% for the 1:32 recipients. Size of the vaccination reaction, incidence of fever, and level of viral shedding were lower in revaccinees than in controls. However, vaccinia antibody titers rose faster and higher in revaccinees than in controls.
Comment: These studies suggest that -- if the need arises -- we should be able to immunize much of the healthy U.S. population safely and effectively, even with a diluted vaccine product. As noted in an accompanying editorial, the rate of adverse reactions noted in the military population was comparable to or lower than that noted in studies of the vaccine in the 1960s. Additionally, the risk of inadvertent transmission of vaccinia in the healthcare setting from vaccinated healthcare workers appears to be negligible. Individuals at risk for adverse reactions were excluded from all of the vaccine trials; thus, concern remains about adverse reactions in these populations in the event that vaccinating the general public becomes necessary. It is notable that a small number of HIV-infected individuals tolerated vaccination without difficulty.
— Richard T. Ellison III, MD
Published in Journal Watch Infectious Diseases July 28, 2003
Citation(s):
Grabenstein JD and Winkenwerder W Jr. US military smallpox vaccination program experience. JAMA 2003 Jun 25; 289:3278-82.
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Halsell JS et al. Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel. JAMA 2003 Jun 25; 289:3283-9.
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- Medline abstract (Free)
Talbot TR et al. Focal and generalized folliculitis following smallpox vaccination among vaccinia-naive recipients. JAMA 2003 Jun 25; 289:3290-4.
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Frey SE et al. Response to smallpox vaccine in persons immunized in the distant past. JAMA 2003 Jun 25; 289:3295-9.
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Wright ME and Fauci AS. Smallpox immunization in the 21st century: The old and the new. JAMA 2003 Jun 25; 289:3306-8.
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- Medline abstract (Free)