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Second, their use of an occlusive dressing may retard scab formation, and the resultant increased cutaneous permeability may foster local bacterial invasion.
Finally, as I reported in ProMED on November 1, 2001 (http://www.fas.org/promed), at our clinic, my colleagues and I have observed the emergence, since January 2001, of cellulitis — a complication of vaccinia vaccination that was previously rare in first-time vaccinees. This same phenomenon was also observed by the Centers for Disease Control and Prevention during their vaccinia-immunization effort in December 2001. There are several possible reasons for the emergence of this complication,6 but its rapid resolution with antibiotic therapy strongly argues for a bacterial cause. At our clinic, the rate of apparent cellulitis as a complication of vaccination jumped from 3.9 percent (in 11 of 279 persons) in 2001 to 10.2 percent (in 12 of 118) after the switch in February 2002 to the IND vaccinia protocol with the use of 15 scratches.
In contrast to the results reported by Frey et al., only 2 of 12 persons at our clinic required one or two days of medical leave. We believe the difference in morbidity rates is primarily due to the fact that we followed the standard procedures for vaccinia vaccination rather than the new procedure.
Michael A. Sauri, M.D., M.P.H.&T.M.
Occupational Health Consultants
Rockville, MD 20850
References
During the course of other investigations,2 we tested the CD8+ T-lymphocyte responses to vaccinia virus in persons who had been recently vaccinated (within the previous five years because of work-related potential exposures), unvaccinated persons, and persons who had been vaccinated 6 to 35 years earlier or more than 35 years earlier. Figure 1 shows the results of intracellular interferon-
staining of CD8+ lymphocytes from persons in each of these groups, as determined by overnight culture with vaccinia-virus–infected, autologous B-lymphocyte cell lines. Vaccinia induces a robust CD8+ T-lymphocyte response in healthy persons, and this response is of long duration. It is striking that the loss of reactivity over a period of more than 35 years was very low — by a factor of less than two in persons with a remote history of vaccination (4 percent of CD8+ T lymphocytes), as compared with recently vaccinated persons (6.5 percent of CD8+ T lymphocytes). The durability of vaccinia-specific CD8+ T-lymphocyte responses is very good, suggesting that those previously vaccinated still have a significant measure of protection.
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Jeffrey A. Frelinger, Ph.D.
Mohammed L. Garba, M.D.
University of North Carolina
Chapel Hill, NC 27599-7290
jfrelin{at}med.unc.edu
References
To the Editor: Dr. Sauri is concerned about the high rate of vaccinia-related adverse events in our studies.1,2 It is true that the current protocol differs from previous methods of administering vaccinia. We used 15 skin punctures, the current recommendation of the Advisory Committee on Immunization Practices,3 in previously unvaccinated subjects rather than the 5 previously used. We also now use semipermeable membrane dressings to provide protection against accidental inoculation with vaccinia. A randomized comparative trial would be required to determine the contribution — if any — of the current methods to adverse events. Our opinion is that the modern clinical-trial design and careful observations of minor as well as major events give us an accurate picture of the common acute viral syndrome associated with infection with vaccinia virus caused by vaccination. Other vaccines are not as reactogenic, and we, as a medical community, have forgotten or never saw vaccine reactions of the frequency reported.
The dose of vaccinia varied by a factor of 100 in one study and by a factor of 10 in the other, yet there was no difference in the frequency of systemic events across groups. There were differences in local inflammation (greater with undiluted vaccinia) and formation of local satellite lesions (greater with diluted vaccinia), and we speculate on the mechanism behind these events in our Discussion section. With 15 skin punctures as compared with 5 skin punctures, the dose would not be expected to vary by a factor of more than three. A comparison of vaccinations with dressings and without dressings has not been undertaken.
We disagree with the assertion that the extensive erythema observed in some vaccinated subjects represents bacterial cellulitis and that an apparent response to antibiotics argues for bacteria as a cause. Even without antibiotic treatment, the commonly observed extensive erythema and induration are short-lived and resolve rapidly, usually in two to three days. Extensive erythema does not appear to be toxic, and affected persons do not have more pain than those without extensive erythema. In addition, maximal erythema is reached on days 10 to 12; erythema due to bacterial cellulitis should develop much sooner. We believe the most likely cause of the erythema is a cellular inflammatory response to vaccinia itself.
Robert B. Belshe, M.D.
Sharon E. Frey, M.D.
Saint Louis University School of Medicine
St. Louis, MO 63110
References
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