of myo/pericarditis (CDC, 2003f). By March 21, 2003, the military program had documented 10 cases of myo/pericarditis in addition to the heart attack noted above (CDC, 2003f; Connolly, 2003c). Recent and historical evidence supported an association between myo/pericarditis and smallpox vaccination (CDC, 2003k). The Department of Defense (DoD) identified a likely causal association between smallpox vaccination and myo/pericarditis (Halsell et al., 2003); the evidence of a causal association in the civilian population remained unclear (ACIP, 2003b).
Concern about cardiac complications associated with smallpox vaccine caused apprehension in people planning to be vaccinated and led many states to temporarily suspend vaccination and wait for CDC guidance (Connolly, 2003c; Kuhles and Ackman, 2003). The Advisory Committee on Immunization Practices (ACIP) and the ACIP Working Group on Smallpox Vaccination—created in February 2003 to monitor vaccination program communication, surveillance, and research activities (ACIP, 2003a)—held an emergency meeting on March 28, 2003, to make recommendations to CDC about medical screening of potential vaccinees and follow-up of persons with cardiovascular risk factors after vaccination (CDC, 2003h). The working group recommended the deferral of volunteers who had known cardiac disease, those who had three or more risk factors (for example, smoking, high blood pressure, and high blood cholesterol concentrations) for heart disease, and those over 50 years old (Neff, 2003a). ACIP accepted the first two recommendations but not the last, because of concerns that it would exclude a substantial proportion of potential civilian vaccinees likely to be older and previously vaccinated (and therefore considered less vulnerable to vaccine complications) (Neff, 2003b). ACIP also looked at historical evidence about myo/pericarditis, found largely in the context of military vaccination among young Finnish men (Helle et al., 1978; Kanjalainen et al., 1983). U.S. data from the 1960s were limited to pediatric vaccination, in which myo/pericarditis could have been missed (CDC, 2003h). Finally, ACIP recommended to CDC the following exclusion criteria: known underlying heart disease with or without symptoms and the presence of three or more of the known major cardiac risk factors (CDC, 2003a, 2003h). CDC accepted ACIP’s recommendations and moved rapidly to revise the vaccination information package, screening materials, and informed consent form.
Myo/pericarditis, the cardiac complication not previously recognized among expected adverse events of smallpox vaccination, constituted a major safety finding and was later identified in the context of clinical trials of a second-generation smallpox vaccine. The pharmaceutical company Acambis in April 2004 temporarily suspended volunteer recruitment for the ACAM2000 clinical trials of cell-culture smallpox vaccine because of the occurrence of at least three cases of myo/pericarditis (Roos, 2004a). In