tified in case reports occur in exposed populations at a rate that exceeds the background rate in unexposed populations.

The case reports relating to AVA come primarily from the Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system that collects reports on adverse events following the use of any vaccine licensed in the United States (see Chapter 5). A subset of the committee reviewed each of 120 VAERS reports on serious adverse events associated with AVA. The committee also heard testimony regarding adverse events following vaccination with AVA. These statements, some of which concerned cases reported to VAERS, added valuable insight into the conditions that some military personnel are experiencing.

In evaluating the epidemiologic studies of adverse events following receipt of AVA (see Chapter 6), the committee gave additional weight to those that (1) used active surveillance rather than self-reports of post-immunization events; (2) included sufficiently large numbers of subjects; (3) had clearly specified, objective criteria for the definition of adverse events; and (4) had sufficiently long postimmunization follow-up intervals to allow identification of later-onset events. Those studies that included a suitable unimmunized comparison group or in which evaluators were blinded to vaccination status were especially useful to the committee.

Substantial data are now available from VAERS, epidemiologic studies with data from the Defense Medical Surveillance System (DMSS), and other epidemiologic studies for assessments of the health outcomes following vaccination with AVA. Immediate-onset health events are observable within hours or days following vaccination; later-onset events would be observable only months or years following vaccination.

Epidemiologic studies that have used either active surveillance (Brachman et al., 1962; Pittman, 2001b,c; Pittman et al., 1997, 2002, in press) or passive surveillance (Hoffman et al., submitted for publication; Pittman, 2001a; Pittman et al., 2001a,b; Wasserman, 2001) have consistently found local injection-site reactions, including redness, induration, edema, itching, or tenderness (see Table 6-1 for details). Systemic events, such as fever, malaise, and myalgia, are also associated with vaccination with AVA but are generally less common than injection-site reactions. The types of local and systemic reactions associated with AVA and the rates at which they were observed are comparable to those observed with other vaccines regularly administered to adults, such as diphtheria and tetanus toxoids and influenza vaccines (Treanor, 2001). Although these immediate-onset health effects can result in brief limitation of activities or the loss of time from work (Hoffman et al., submitted for publication; Wasserman,

Front Matter (R1-R22)

Executive Summary (1-32)

1 Introduction (33-39)

2 Background (40-55)

3 Anthrax Vaccine Efficacy (56-82)

4 Safety: Introduction (83-101)

5 Safety: Case Reports (102-117)

6 Safety: Epidemiologic Studies (118-179)

7 Anthrax Vaccine Manufacture (180-197)

8 Future Needs (198-210)

Appendix A Statement of Task (211-213)

Appendix B Biographical Sketches (214-217)

Appendix C Information-Gathering Meeting Agendas (218-226)

Appendix D Anthrax Vaccine Adsorbed Package Inserts (227-238)

Appendix E Vaccine Adverse Event Reporting System (VAERS) Form (239-242)

Appendix F Anthrax Vaccine Expert Committee (AVEC) Case Assessment Form (243-244)

Appendix G DMSS Analyses Requested by the IOM Committee to Assess the Safety and Efficacy of the Anthrax Vaccine (245-252)

Appendix H An Assessment of the Safety of the Anthrax Vaccine: A Letter Report (253-266)