The Effects on Human Health of Subtherapeutic Use of Antimicrobials in Animal Feeds (1980) / Chapter Skim
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Appendix J: Immunological Consequences of Antimicrobials in Animal Feeds
Appendix J: Immunological Consequences of Antimicrobials in Animal Feeds
Pages 301-316
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From page 301... ...
PREVALENCE OF ALLERGIC SENSITIVITY TO PENICILLINS AND TETRACYCLINES Penicillins display remarkably little toxicity even in high doses. Most adverse reactions are attributed to "allergy." Allergic reactions to penicillin range from anaphylactic shock, which can be life-threatening and even fatal,-to mild evanescent skin rashes of little clinical consequence.
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From page 302... ...
302 TABLE 1 Immunopathological Reactions to Penicillin Gell and Examples of Adverse Coombs Type Description Penicillin Reaction I Anaphylact ic Acut e anaphylaxi s · (IgE-mediated injury) Urticaria II C '-dependent cytolysis Hemolytic anemias Thrombocytopenia Interstitial nephritis III Immune complex damage Serum sicknes s Drug feve r Cutaneous erupt ion s IV " Delayed " or c el lular Contac t de rmat iti s hype rsens itivit aImmunopathogenesis of cutaneous eruptions is not clear.
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From page 303... ...
This spontaneous loss of allergic sensitivity is likely to occur for other less serious types of allergic reactions as well, judging from the fact that it is often possible to treat previously allergic individuals safely (Biennan et al., 1972 ; Levine, 1972 ~ . Tetracyclines are infrequently implicated in allergic reactions.
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From page 304... ...
It is now well established that preformed penicilloyl-protein complexes are much more efficient than the unconjugated penicillin molecule at both stimulating an immune response and eliciting an allergic reaction in a previously sensitized individual (Siegel, 1959; Stewart, 1967~. Immunologically, the antibiotic "residue" of prime importance is the penicilloylprotein complex rather than the free penicillin molecules.
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From page 305... ...
4 -- -- NH-CH C 11 o panicilloyl - protein MAJOR ANTIGENIC DETFRMINANT MINOR ANTIGENIC DETERMINANTS FIGURE 1. Major pathways of penicillin-protein interactions.
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From page 306... ...
Dosage Requirements for Sensitization From immunological studies of laboratory animals and humans it is clear that the dose of any immunogenic substance required for initiating an immune response is appreciably greater than that required to elicit an allergic reaction of the type I variety. The optimal immunizing dose and the minimal dose for eliciting an acute allergic reaction may differ by several orders of magnitude.
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From page 307... ...
The threshold dose for provoking an allergic reaction depends upon the degree of allergic sensitivity of the individual ingesting the antibiotic residues. Clinical observations were made by Walzer and Siegel in 1956 (Siegel, 1959~.
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From page 308... ...
The elimination of her symptoms by the addition of penicillinase to her milk may be taken as evidence that preformed penicilloyl-milk protein complexes were not a major contributor to the elicitation of her allergic reactions. Stricter governmental enforcement of FDA regulations concerning penicillin-contaminated milk has reduced considerably the occult intake of penicillin by the general population over the past two decades.
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From page 309... ...
Thus, the existence of allergies in humans that are attributable to penicillin-contaminated milk can be considered irrelevant to the substantive issue before the committee, namely, the health hazards of subtherapeutic doses of antibiotics. However, these cases of allergy induced by penicillin-contaminated milk provide useful information regarding minimal threshold doses required for provoking allergic symptoms in highly sensitive patients.
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From page 310... ...
, the widespread antibiotic residues in edible meats as late as 1970 suggest that antibiotics were used frequently in therapeutic doses and/or that required periods for withdrawal from antibiotic-enriched feeds were being widely ignored. More recent surveys have reported that penicillin residues were found infrequently in edible meats except when the animals had received injections of penicillins (Food and Drug Administration, 1978~.
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From page 311... ...
First, it seems highly unlikely that a sizable proportion of those individuals ingesting foodstuffs containing trace quantities of antibiotic residues will become sensitized to a clinically significant degree. This assertion is based on three facts: · There is no evidence that such primary sensitization occurred, even after ingestion of penicillin-contaminated milk.
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From page 312... ...
This analytical approach leads one to the tentative conclusion that antibiotic-contaminated foodstuffs can provoke allergic reactions in highly sensitive individuals, but these reactions appear to occur only rarely. Thus, the admittedly sparse data indicate that there appears to be no reason to implicate antibiotic residues in animal foods as a significant source of allergic disease, either potential or actual, for the public at large.
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From page 313... ...
Epidemiological studies of the incidence of penicillin antibodies among populations frequently ingesting foods with penicillin residues versus similar populations not regularly consuming such antibiotic residues. Careful attention would have to be given to matching the exposure to therapeutically administered penicillin in both groups.
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From page 314... ...
One source clandestine de reactions allergiques par sensibilisation a la penicilline: La pollution des aliments.
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From page 315... ...
1971b. The public health hazards associated with the nonmedical and animal health usage of antimicrobial drugs.
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From page 316... ...
1957-1958. Penicillinase treatment of fifty-two patients with allergic reactions to penicillin.
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