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SMALLPOX
VACCINATION CAN LEAD TO NEUROLOGIC COMPLICATIONS
HONOLULU—Under the new government initiative to offer smallpox vaccinations to persons who would be providing initial emergency care in the aftermath of a large-scale bioterrorist attack, about 27,000 of the approximately 450,000 eligible civilian “first responders” have opted for the vaccine. For many of those who have decided against it, fear of vaccine-related complications may well have been a factor in their decision.
Such complications are already occurring among current vaccinees at rates that one would expect based on data from previously immunized populations. Some of the complications will be neurologic, stressed Diane E. Griffin, MD, PhD, at the 55th Annual Meeting of the American Academy of Neurology.
COMPLICATION FREQUENCY AND SEVERITY
The frequency of smallpox vaccine–related complications varies with the strain of the vaccine virus, the age of the vaccinee, and any underlying medical problems. The overall rates of hospitalization and death due to complications in recipients of the vaccine are estimated to be one in 100,000 and one in 1,000,000, respectively.
When they occur, neurologic complications such as postvaccinial encephalomyelitis (PVEM) and encephalopathy (PVE), altered mental status, lethargy, seizures, and coma typically appear during or a few days after the maximum skin reaction to the vaccine. Onset is usually abrupt, with exacerbation of fever, nuchal rigidity, obtundation, and multifocal signs.
“The neurologic complications are severe, can cause death, and are not as clearly age-dependent as some of the other complications,” related Dr. Griffin, Professor and Chair of the Department of Molecular Microbiology and Immunology at the Johns Hopkins University Bloomberg School of Public Health in Baltimore. “Mortality rates from 10% to 40% have been reported,” she added.
PVEM AND PVE—VARIABLE INCIDENCE, CONSISTENT DANGER
Histopathologic features of PVEM include perivenous demyelination and limited cerebral edema. Microglial proliferation occurs in demyelinated areas with lymphocytic infiltration. Estimated rates of PVEM are highly variable. For example, follow-up of smallpox vaccine recipients in the United States from 1958 to 1968 suggested a one in 300,000 incidence of PVEM, while the rate in a Dutch smallpox vaccination campaign was far higher: one in 63. “This suggests that particular strains of vaccinia virus are more likely to induce encephalomyelitis than others,” Dr. Griffin remarked.
PVEM has shown some tendency to affect individuals ages 2 and older; it occurs more often after primary vaccination, although revaccination following a long latency since childhood may be a risk factor for adults. In the US cohort from the 1950s and 1960s, PVEM accounted for all of the deaths among smallpox vaccinees older than 20, Dr. Griffin pointed out.
Unlike PVEM, PVE seems to occur somewhat more often in children younger than 2. Generalized cerebral edema, mild lymphocytic meningeal infiltration, and widespread ganglion degeneration are among the histopathologic changes associated with PVE. Neurologic sequelae in survivors of PVEM and PVE can be severe and may include cerebral impairment, hemiplegia, and substantial personality changes.
No clinical criteria, radiographic findings, or laboratory tests are specific for PVEM or PVE. The only way to diagnose either complication is through the exclusion of other infectious or toxic etiologies.
PATHOGENESIS AND TREAMTENT OF NEUROLOGIC COMPLICATIONS
The pathogenesis of smallpox vaccine–related neurologic complications has not been evaluated with modern techniques and thus remains poorly understood. In particular, whether these complications result from vaccine virus invasion of the central nervous system or induction of autoimmune disease, akin to disseminated encephalomyelitis, is unclear.
The vaccine virus in the cerebrospinal fluid of up to one half of smallpox vaccinees with neurologic complications is a small bit of evidence to support the first possibility but may result from virus in the blood, Dr. Griffin noted. The pathogenesis of smallpox vaccine–induced autoimmune disease may be similar to that of chickenpox, measles, or a variety of respiratory diseases that cause acute disseminated encephalomyelitis, she suggested.
There is no known predictor of the neurologic complications of smallpox vaccination. “That is very concerning when you are talking about immunizing a large number of people,” emphasized Dr. Griffin.
Furthermore, there is no specific therapy, only supportive care, anticonvulsants, and possibly intensive care. “Vaccinia immune globulin is not indicated because it is highly unlikely that the virus per se is directly causing the changes,” Dr. Griffin said. The role of antivirals is unclear as the clinical symptoms of PVEM and PVE are not believed to result from replicating vaccinia virus.
NR
—Timothy Begany
Suggested Reading
Booss J, Davis LE. Smallpox and smallpox vaccination: neurological implications. Neurology. 2003;60:1241-1245.
Cono J, Casey CG, Bell DM, Centers for Disease Control and Prevention. Smallpox vaccination and adverse reactions: guidance for clinicians. MMWR Recomm Rep. 2003;52(RR-4):1-28.
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