ABSTRACT
The occurrence of drug hypersensitivity reactions (DHRs) following administration of low molecular weight (LMW) drugs is an important health concern. However, in vivo animal models which could be used as tools for the prediction of DHRs are lacking. As a result, research has focused on development of in vitro tools for predicting DHRs. In this study a novel human in vitro pre-clinical skin explant test was used to predict T cell-mediated hypersensitivity responses induced by LMW drugs. Responses in the skin explant test for 12 LMW drugs associated with T cell-mediated hypersensitivity in the clinic (abacavir, amoxicillin, carbamazepine, diclofenac, lamotrigine, lapatinib, lumiracoxib, nevirapine, ofloxacin, phenytoin, propranolol, sulfamethoxazole) were compared with responses for 5 drugs with few/no reports of T cell-mediated hypersensitivity reactions (acetaminophen, cimetidine, flecainide, metformin, verapamil). Changes in skin histology following in vitro exposure to the drugs as well as T cell proliferation and interferon gamma (IFNγ) production were studied. The results of the skin explant assays showed a good positive correlation (râ¯=â¯0.77, pâ¯<â¯.001) between the test outcome (prediction of positive or negative) and the clinical classification of the tested drugs. The T cell proliferation assay showed a correlation of râ¯=â¯0.60 (pâ¯<â¯.01) and the IFNγ assay râ¯=â¯0.51 (pâ¯<â¯.04). The data suggest that the skin explant model could be a useful tool to predict the potential of LMW drugs to induce DHRs.
Subject(s)
Drug Hypersensitivity/etiology , Irritants/toxicity , Skin Irritancy Tests/methods , Skin/drug effects , T-Lymphocytes/drug effects , Cell Proliferation/drug effects , Coculture Techniques , Drug Hypersensitivity/immunology , Drug Hypersensitivity/metabolism , Drug Hypersensitivity/pathology , Humans , Interferon-gamma/metabolism , Lymphocyte Activation , Molecular Weight , Reproducibility of Results , Risk Assessment , Skin/immunology , Skin/metabolism , Skin/pathology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Tissue Culture TechniquesABSTRACT
In September and October 1981 six cases of pneumonia occurred among men working in a power station under construction. Three were identified as cases of legionella pneumonia and two others had serology suggestive of legionella infection. In a sample of 92 men from the site 10 had low levels of antibodies to legionella; a similar sample of men working on an adjacent site showed none with positive serology. In a case control study it was found that cases of pneumonia were more likely than controls to have worked on a part of the site where four small capacity cooling towers were located. Legionella pneumophila serogroup 1 was isolated from the water systems of these four towers but was not found in samples from any other cooling towers or hot or cold water outlets on the site. It would appear that there was airborne spread of the organism from these cooling water systems which had not received conventional treatment to inhibit corrosion and organic growth. This is the first outbreak of legionnaires' disease to be recorded in an industrial setting in the United Kingdom. No cases of legionella infection have occurred on the site since the introduction of control measures.
Subject(s)
Disease Outbreaks/epidemiology , Legionnaires' Disease/epidemiology , Occupational Diseases/epidemiology , Power Plants , Antibodies, Bacterial/analysis , England , Humans , Legionella/immunology , Legionella/isolation & purification , Legionnaires' Disease/immunology , Male , Nuclear Reactors , Water MicrobiologyABSTRACT
A person to person outbreak of hepatitis A is described: 90 cases of hepatitis A occurred in a small town in Calabria, southern Italy; all cases were under 18 years of age with the highest age-specific incidence rate in the 6-10 year age group. Transmission was identified by tracing close contacts with other incubating or active cases; only eight out of 90 cases were not identified as having a very probable or possible contact with an infecting case. Transmission was high between family members leading to a secondary family attack rate of 51% in children under 16. An enteric disease educational campaign was carried out together with IgG and no cases of hepatitis A were reported in the two years following the investigation.
Subject(s)
Disease Outbreaks/epidemiology , Hepatitis A/epidemiology , Adolescent , Child , Child, Preschool , Female , Hepatitis A/transmission , Humans , Infant , Infant, Newborn , Italy , MaleABSTRACT
National surveillance of legionnaires' disease in England and Wales identified 588 cases during the years 1979--1982. The majority of cases appeared to be sporadic but 32 clusters of two or more cases were recognised, 24 in association with hotels, seven with hospitals and one with a construction site. Reports (3 published and 3 unpublished) on the investigation and control of six outbreaks are reviewed. All six were found to be common source outbreaks; four hotel associated, one was nosocomial and one was associated with a construction site. Domestic water systems were implicated as sources in the four hotels and the hospital. The most effective control measure was found to be continuous chlorination of the water supply combined with raising the hot water temperature to 60 degrees C or more in the calorifier and at least 55 degrees C to a maximum of 60 degrees C at outlets. Raising hot water temperatures alone was not always completely successful as a control measure. Only in the construction site outbreak was a cooling water system shown to be the principal source of infection.
