Occurrence Of Hypersensitivity Reactions Research Articles

Undesired consequences of vaccination and faults in vaccination

Different diseases in domestic animals require the application of different methods of immunological protection, depending on the type of vaccine manner of application and type of adjuvant. The objective of the work was to consider general principles and the basic requirements for efficient vaccination. It points out existing faults in practice which lead to the occurrence of mistakes made during vaccination and the appearance of resulting undesired consequences. There are many reasons why vaccination cannot achieve adequate protection of immunity in the organism. In most cases, this occurs due to the inadequate manner of application of the vaccine or subdosage. Mistakes can occur due to inadequate storage conditions which is an essential factor for maintaining vaccine viability. A special problem is vaccination of pregnant animals and young animals, the vaccination of immunodeficient animals. Risks which follow the implementation of vaccines are existing residual virrulence and toxicity the occurrence of hypersensitivity reactions which tend to appear when inactivated vaccines are applied, the occurrence of diseases in immunodeficient animals. Under certain conditions, vaccines can activate an autoimmune response, but the precise pathogenesis of this syndrome is unclear.

Antigenicity and immunogenicity of sulphamethoxazole: demonstration of metabolism-dependent haptenation and T-cell proliferation in vivo.

Sulphamethoxazole has been associated with the occurrence of hypersensitivity reactions. There is controversy as to whether the immune response is metabolism-dependent or -independent. We have therefore investigated the site of antigen formation and the nature of the drug signal presented to the immune system in vivo. Male Wistar rats were dosed with sulphamethoxazole, sulphamethoxazole hydroxylamine or nitroso sulphamethoxazole. Antigen formation on cell surfaces was determined by flow cytometry using a specific anti-sulphamethoxazole antibody. Immunogenicity was determined by assessment of ex vivo T-cell proliferation. Administration of nitroso sulphamethoxazole, but not sulphamethoxazole or sulphamethoxazole hydroxylamine, resulted in antigen formation on the surface of lymphocytes, splenocytes and epidermal keratinocytes, and a strong proliferative response of splenocytes on re-stimulation with nitroso sulphamethoxazole. Rats dosed with sulphamethoxazole or sulphamethoxazole hydroxylamine did not respond to any of the test compounds. CD4+ or CD8+ depleted cells responded equally to nitroso sulphamethoxazole. The proliferative response to nitroso sulphamethoxazole was seen even after pulsing for only 5 min, and was not inhibited by glutathione. Responding cells produced IFN-gamma, but not IL-4. Haptenation of cells by sulphamethoxazole hydroxylamine was seen after depletion of glutathione by pre-treating the rats with diethyl maleate. Splenocytes from the glutathione-depleted sulphamethoxazole hydroxylamine-treated rats responded weakly to nitroso sulphamethoxazole, but not to sulphamethoxazole or sulphamethoxazole hydroxylamine. Dosing of rats with sulphamethoxazole produced a cellular response to nitroso sulphamethoxazole (but not to sulphamethoxazole or its hydroxylamine) when the animals were primed with complete Freund's adjuvant. These studies demonstrate the antigenicity of nitroso sulphamethoxazole in vivo and provide evidence for the role of drug metabolism and cell surface haptenation in the induction of a cellular immune response in the rat.

Detection and evaluation of adverse drug reactions

Adverse drug reactions (ADRs) occur in about 5% of drug-treated patients. Hospital admissions are caused by ADRs in 5% of patients and roughly 2% of hospitalized patients will experience an ADR. The economic burden of ADRs can only be estimated. Type A reactions can be explained by the pharmacological action of the drugs, and are preventable in many cases. However, Type B reactions involving the immune system and/or idiosyncratic reactions occur rarely and most of them are not fully understood. Genotyping represents an elegant method to explain the presence of abnormal enzyme activities and allows prediction of adverse drug effects in individual cases. Typical time frames have been identified for the occurrence of hypersensitivity reactions, although definite causality assessment is often impeded due to the absence or unavailability of specific laboratory tests and the impossibility of rechallenge. Diagnosis of an ADR is often difficult due to comorbidity and polypharmacy, thus causality assessment is often divergent even between specialists. In Germany, ADRs are reported preferably to the manufacturer of the suspicious drug and then collected and evaluated at the Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM. However, total number and quality of reported ADRs could be improved.

Dialyzer Hypersensitivity Syndrome: Possible Role of Allergy to Ethylene Oxide

The occurrence of hypersensitivity reactions in patients dialyzed on artificial kidneys is well recognized in the dialysis community, but has received little attention in the medical literature. We report 4 cases of dialyzer hypersensitivity reactions and review the previously reported cases. Dialyzer hypersensitivity syndrome presents as an acute anaphylactoid reaction, the symptoms of which may range from mild to life threatening in severity. The cause of this syndrome is unknown, but affected patients appear to have a high incidence of positive radioallergosorbent tests to a conjugate of human serum albumin and ethylene oxide, suggesting that ethylene oxide, a substance used to dry sterilize artificial kidneys, may be an offending allergen.

Predictive evaluation in animals of the contact allergenic potential of medically important substances

Results of the optimization method and of other methods used to assess contact allergy in laboratory animals were compared with known epidemiological data on the occurrence of hypersensitivity reactions in man. Tests were performed with preservatives (formalin, ethylenediamine and sorbic acid), drugs (penicillin G, Benzocaine and sulphathiazole) and other contactants belonging to widely different chemical classes (p-phenylenediamine, triclosan, pyrazole derivatives, nickel and chrome salts, eugenol, isoeugenol and mercaptobenzothiazole). The degree of sensitization achieved in guinea pigs by the optimized procedure (intradermal test with adjuvant combination) and the maximization procedure was invariably superior to that produced by the epidermal method using prior irritation of the site of application. Both the optimized procedure and the maximization test seem to be capable of identifying contact allergens that cause hypersensitivity reactions in as few as 1 in 10,000 of the human population as a whole. The optimization test merits consideration as a standardized and efficiently predictive procedure.

Reactions to Antibiotics

To the Editor.— A retrospective chart review was undertaken at the University of Florida in an attempt to determine the relative incidence of nephritis caused by methicillin, oxacillin, ampicillin, and penicillin. As only a single case of nephritis was suspected from data available in 489 charts, this goal could not be realized. However, another interesting fact did emerge. Of the 489 charts selected for review, 130 contained sufficient data at appropriate time intervals to allow a conclusion regarding the occurrence of hypersensitivity reactions including eosinophilia, skin rash, drug fever, positive Coombs test, and nephritis. The overall incidence of such reactions was 31% in 45 patients receiving methicillin, 0% in 10 patients receiving oxacillin, 39% among 36 patients receiving ampicillin, and 44% in 39 patients receiving penicillin therapy. Single cases of nephritis and positive Coombs test occurred among patients receiving methicillin; a rash developed in one patient in the penicillin group;