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Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality
logic suppression from simultaneous administration of more than one vaccine or vaccine component. Exposure to multiple foreign antigens is a common part of normal extrauterine life. During a single episode of upper respiratory viral infection, humans are exposed, depending on the particular virus involved, to between 4 and 10 foreign proteins, and during a routine ''strep throat'' infection, to between 25 and 50. Moreover, acquisition of a single new bacterium in the gastrointestinal tract, a common and normal event in consumption of everyday foods, or acquisition of one of the apparently harmless bacteria that inhabit the mouth and nose exposes the immune system to at least 50 potential antigens (Goldblatt et al., 1990). Each one of these foreign molecules typically contains numerous epitopes (antigenic determinants), each of which evokes a separate immune response. Moreover, each of the proteins is broken down in the body to expose still other epitopes, which may be antigenic depending on the genetic background of the host. The normal child may not respond to each of these proteins/epitopes, but in the case of Branhamella catarrhalis, a bacterium that inhabits the nasopharynxes of all normal children, antibodies to 17 different proteins can be detected after colonization (Goldblatt et al., 1990).
Infants, since they are born out of a germ-free environment into a world replete with microorganisms, undergo constant exposure to foreign antigens as their mucosal surfaces are populated with normal bacterial flora and as they are exposed to potentially more pathogenic microorganisms in the environment. During such encounters, the microorganisms would be expected to shed large amounts of their antigens for a period of days. The gradual rise in the levels of circulating immunoglobulins represents one part of the total immunologic response to this onslaught.
In the face of these normal events, it seems unlikely that the number of separate antigens contained in childhood vaccines, whether given orally or by injection, would represent an appreciable added burden on the immune system that would be immunosuppressive. Nevertheless, it is theoretically possible that some vaccine constituent might predispose an individual to infection through its action as an antigen or some other means. The combination of diphtheria-pertussis-tetanus vaccine has been the object of some research, in this regard, in part because pertussis toxin modulates certain immune functions in experimental animals. Fears that four deaths from bacterial infection after a trial of acellular pertussis vaccine in Sweden might have been due to the vaccine were allayed by a subsequent study (Storsaeter et al., 1988) that failed to find an increase in the number of patients hospitalized with bacterial infections after receipt of the vaccine. A report from Israel described an increase in minor infectious illnesses in the 30 days after administration of diphtheria and tetanus toxoids and pertussis vaccine (DPT) (Jaber et al., 1988). However, it is not possible to evaluate these results because of a combination of reporting bias, learning effect, and