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Updated: Aug 20, 2026

Vaccinia Reporter Viruses for Quantifying Viral Function at All Stages of Gene Expression
Published on: May 15, 2014
Superinfection following smallpox vaccination (Vaccinia), United States: surveillance January 2003 through January
Claudia Vellozzi1, Francisco Averhoff, J Michael Lane
1National Immunization Program, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. bno1@cdc.gov
Background:
Superinfection is an adverse event following smallpox vaccination. The clinical presentation is similar to that of a large normal vaccine reaction or "robust take," and the frequency is unknown.
Methods:
We retrospectively reviewed all reported severe local reactions consistent with superinfection among United States civilian smallpox vaccinees from January 2003 through January 2004. We applied a standard case definition and estimated the frequency of superinfection following smallpox vaccination.
Results:
We identified 48 reported cases for further review among 39,350 [corrected] smallpox vaccinees. Two (4%) of the 48 reported cases met the case definition for superinfection; neither of the patients had a pathogenic organism isolated from their infection site. Both were treated with antibiotics and resolved their infection. Of the 46 cases determined not to be superinfection, 41 (89%) were temporally consistent with a large normal vaccine reaction. Thirty (75%) of 40 reported case patients for whom data were available received antibiotic therapy.
Conclusions:
Superinfection following smallpox vaccination is rare. Most of the reported superinfection cases were probably large normal smallpox vaccine reactions. Educating providers about the normal response to smallpox vaccine may decrease the overdiagnosis of superinfection and the unnecessary use of antimicrobials.
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