quired to achieve protection against multiple diseases and reduces the number of visits to health care providers, thereby resulting in wider protection of the population (Goldenthal et al., 1995; Rappuoli, 1996; Choo and Finn, 1999). However, researchers continue to investigate whether interactions may decrease the efficacy of the component vaccines (i.e., as manifested in lower seroconversion rates and lower antibody titers) or increase the frequency of adverse effects.

In the United States, multiple vaccinations are routinely given to children, to adults prior to travel to areas of risk, and to military personnel. A number of combination vaccines have been licensed in the United States including: diphtheria–tetanus–pertussis (DTP), measles–mumps–rubella (MMR), 23-valent pneumococcal polysaccharide, and 4-valent meningococcal polysaccharide (Parkman, 1995; Ellis, 1996; CDC, 1999a; Choo and Finn, 1999). Additionally, safety and immunogenicity reports have appeared in the literature for several pediatric combinations including: DTP–hepatitis B (HBV); DTP–IPV (inactivated poliovirus vaccine)–HIB (Haemophilus influenzae type B); and MMR– varicella (Choo and Finn, 1999). Evidence suggests that although some combination vaccines interfere with immunogenicity, others enhance it (Insel, 1995). Short-term follow-up trials have shown these combination vaccines to be safe (Choo and Finn, 1999).

Some sets of vaccines can be administered simultaneously (i.e., on the same day but not at the same anatomical site) including yellow fever and measles; MMR and trivalent oral polio vaccine (OPV); and DTP, OPV, and MMR (CDC, 1994a; Insel, 1995; Parkman, 1995). In general, this practice does not appear to affect immune response to individual vaccines, nor does it result in substantial adverse effects in short-term (2–6 months and occasionally 2 years) follow-up studies (Grabenstein, 1990; CDC, 1994a; Parkman, 1995). The frequency of local and systemic reactions is generally the same as in separate vaccine administrations; however some patients experience greater local tenderness (King and Hadler, 1994). CDC states that simultaneous administration of inactivated vaccines that commonly produce local or systemic reactions, (e.g., cholera, parenteral typhoid, plague) may accentuate the reactions. CDC advises injections on separate days for these vaccines (CDC, 1994a). A study of the safety of the simultaneous administration of several childhood vaccines found that the proportion of MSAEFI (Monitoring System for Adverse Events Following Immunization, the precursor of VAERS) reports that described a set of specific adverse effects remained constant compared to the frequency reported for separate administrations, with one exception: local reactions were more frequent with simultaneous vaccinations (Chen et al., 1995). The MSAEFI system was a passive surveillance system based on reports by people who had been vaccinated, family members, and other individuals.

Toxicology

The intended effect of vaccination is to protect individuals from infection by stimulating the immune response to a particular antigen. Vaccination with



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement