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Case-Control study of Firefighters with documented positive tuberculin skin test results using Quantiferon-TB testing in comparison with Firefighters with negative tuberculin skin test results.

BACKGROUND: Phoenix Firefighters have had abnormally high rates of tuberculin skin test (TBST) results on medical surveillance. The objectives of this study were to evaluate our firefighters using QuantiFERON-TB (QFT), comparing the results to their TBST results. METHODS: Using QFT results obtained during the study, we compared previously positive TBST responders (Cases) to negative responders (Controls). We also compared both groups for QFT results for Mycobacterium avium (MA) exposure. RESULTS: QFT effectively monitored our working population. 12.9% of the 148 cases, and 3.2% of the 220 controls had a positive QFT result. Another 14.8% of cases and 4.5% of controls had conditionally positive QFT results. There was an unusually high rate of MA response on QFT testing in both groups. CONCLUSION: Phoenix Firefighters have a higher than expected TBST and QFT results, which cannot be explained by the increased MA rate. The decreased level of QFT positivity in comparison to TBST results may indicate a considerable false positive TBST rate. The QFT offers many advantages as a surveillance method over TBST in exposed worker populations.

Journal Article↗

Skin test development in leprosy: progress with first-generation skin test antigens, and an approach to the second generation.

One of the most urgent needs from leprosy research is a test for infection. The lepromin test is not suitable as a diagnostic test for leprosy, and neither the Rees nor the Convit soluble antigens has appeared sufficiently specific. Because two new antigens, MLSA-LAM and MLCwA, may not fully meet the requirements for specificity, we have embarked upon the preparation of a second generation of skin test antigens. Size-fractionated cryptozoic proteins were prepared from M. leprae by electroelution from preoperative sodium dodecylsulphate-polyacrylamide gel electrophoresis, and individual fractions were probed with polyclonal and monoclonal antibody reagents to identify both known and novel proteins. In addition, immunological responses were assessed in M. leprae-sensitized guinea pigs against both crude subcellular fractions (cytosol, membrane, and soluble cell wall proteins) and the size-fractionated cytosolic proteins. A particularly promising subcellular fraction is the membrane fraction of M. leprae, which contains many proteins unique to the organism. Clinical trials of the M. leprae membrane proteins are now being planned.

Antigens, Bacterial↗

Latex-specific IgE, skin testing, and lymphocyte transformation to latex in latex allergy.

BACKGROUND: This study was designed to determine the discriminative value of latex-specific IgE tests, latex skin tests, and lymphocyte transformation tests (LTTs) to latex in 38 patients with latex allergy (12 nonatopic and 26 atopic) and 44 control subjects (24 nonatopic and 20 atopic). We also evaluated the recommended positive cutoff (i.e., 0.35 kU/L) of both in vitro latex-IgE tests. METHODS: Latex-specific IgE levels were determined by the Immuno-CAP (Upjohn-Pharmacia) and the ALaSTAT-RIA (Diagnostic Products Corp.) assays. Skin tests and LTFs were performed with a nonammoniated latex extract (DPC). Sensitivities and specificities were defined according to the 95th percentile value of nonatopic control subjects. For the in vitro IgE tests, sensitivity and specificity were also calculated by using the proposed positive threshold of 0.35 kU/L. Sensitivities and specificities of both cutoffs were compared. RESULTS: Compared with a clinical history of latex allergy and according to the 95th percentile value of nonatopic control subjects (0.44 kU/L), latex-specific IgE determined by the Immuno-CAP assay achieved a sensitivity of 97% and a specificity of 86%. For the ALaSTAT-RIA assay, with 0.54 kU/L as the 95th percentile threshold value in nonatopic control subjects, sensitivity was 100%, and specificity was 83%. According to the threshold value of 0.35 kU/L, a sensitivity of 97% and a specificity of 83% for the Immuno-CAP assay and a sensitivity of 100% and a specificity of 33% for the ALaSTAT-RIA assay were observed. The latex skin test reached a sensitivity of 97% and a specificity of 100%. The LTF to latex showed a sensitivity of 39% and a specificity of 95%. No relation between symptoms and latex-specific IgE tests, latex skin tests, or LTTs was found. CONCLUSIONS: Our results confirm that latex skin tests and latex-specific IgE assessments are sensitive and specific methods for establishing the diagnosis of latex allergy, although the specificity of the ALaSTAT-RIA assay was very low when interpreted according to the threshold of 0.35 kU/L. The LTT to nonammoniated latex is too insensitive for diagnosis of allergy to latex. This reemphasizes that in order to evaluate the sensitivity and specificity of diagnostic procedures, one should always include an appropriate control group.

Adolescent↗

Frequency of systematic reactions to penicillin skin tests.

BACKGROUND: Penicillin skin testing is generally considered to be safe when performed sequentially with puncture and intradermal testing although fatalities have been reported. OBJECTIVE: We analyzed the rate of systemic reactions to penicillin skin tests for a period of seven and two-thirds years. METHOD: This retrospective study used a computerized database at the Mayo Clinic. Altogether 1710 patients were skin-tested to penicillin from January 1992 to September 1999. All patients tested had a history of penicillin allergy. Patients were tested with benzylpenicilloyl polylysine (Pre-Pen) (6.0 X 10(-5) M), freshly prepared penicillin G (10,000 units/ml), and penicilloate (0.01 M). Prick tests were done first and if negative then intradermal tests. Systemic reactions were evaluated and treated by physicians. RESULTS: Eighty-six patients had positive penicillin skin tests of which two had systemic reactions. Our systemic reaction rate for all patients tested was 0.12%; and 2.3% for the penicillin skin test-positive group, with no fatalities. CONCLUSION: The incidence of systemic reaction to penicillin skin tests is low. Skin prick tests should always be done first. If there is a history of a previous serious reaction, the skin tests-if done-should be diluted to start with. Those doing penicillin skin tests should be prepared to treat a systemic reaction.

Aged↗

Specificity and sensitivity of skin test reactions to extracts of Toxocara canis and Ascaris suum. I. Skin tests done on infected guinea pigs.

The specificity and sensitivity of adult and larval somatic antigens, and perienteric fluid of Toxocara canis and Ascaris suum were investigated by using intradermal skin tests in guinea pigs. These animals were infected with low doses (0.01, 0.1 or 1.0 egg/g) of these helminths. Toxocara larval antigen (TL) induced larger reactions in Toxocara-infected animals than did the other antigens, suggesting a superior sensitivity for this antigen. In addition, Ascaris perienteric fluid (AP) provoked skin responses in these animals of a magnitude similar to those induced by TL. The reciprocal relationship, i.e., comparable reactivity of AP and TL in Ascaris-infected animals, was not apparent. In general, Ascaris larval antigen and AP elicited larger intradermal reactions than other antigens in Ascaris-infected animals. The results of this study indicated no superiority of adult antigens in differentiating Ascaris and Toxocara infections.

Animals↗

Immuno-biochemical evaluations of phenol and thimerosal as antigen preservatives in Montenegro skin test.

Montenegro skin test (MST) represents the main complementary diagnostic test for tegumentary leishmaniases (TL) in endemic regions. Most antigen formulations used for the MST contain thimerosal as preservative. The Food and Drug Administration (FDA), however, recommended reducing or eliminating thimerosal from vaccines and other biological reagents and the Agência Nacional de Vigilância Sanitária (ANVISA) in Brazil, prohibited the use of mercurial compounds in immunobiologicals. In the search for an alternative stabilizer, phenol and thimerosal were tested as antigen preservatives in MST. Formulations were tested when fresh and after a 12-month storage at 4 degrees C in TL confirmed mice and human patients, and were evaluated for protein constitution by SDS-PAGE, Western blot and anti-gp63 ELISA. In mice, a decrease in the diagnostic effectiveness in merthiolate formulation was observed after a 12-month storage. SDS-PAGE, Western blot and anti-gp63 ELISA analyses showed a degradation of antigen proteins in both formulations after 12-month storage and that phenol-preserved antigen was quantitatively and qualitatively better than the merthiolate-preserved one. In patients, the average of induration diameter was larger in fresh antigens (p<0.05). However, storage time did not jeopardize their diagnostic capacity. No non-specific reactions produced by phenol or merthiolate were observed neither in humans nor in mice. Phenol could be a good alternative to replace the merthiolate in MST, and despite the proteolytic activity, antigens remain viable for at least 12 months.

Animals↗

Evidence of previous infection with Mycobacterium avium-Mycobacterium intracellulare complex among healthy subjects: an international study of dominant mycobacterial skin test reactions.

Skin tests with 0.1 mL of intermediate-strength Mycobacterium tuberculosis purified protein derivative (PPD) and 0.1 mL of Mycobacterium avium sensitin were conducted on 484 healthy subjects from diverse geographic sites. Reactions of > or = 5 mm to one antigen that exceeded the reaction to the other by > or = 3 mm were considered M. avium- or PPD-dominant. PPD-dominant reactions were more frequent at sites where routine Bacille Calmette-Guérin immunization is done or where there are high rates of tuberculosis: New Hampshire, 2%; Boston, 7%; Finland, 14%; Trinidad, 26%; and Kenya, 28%. However, rates of M. avium-dominant reactions ranged from 7% to 12% at all sites. Analysis of dominant reactions based on a more stringent 10-mm minimum reaction size showed similar trends. These data suggest that exposure to MAC is similar in developed and developing countries but that broad mycobacterial immunity is greater in developing countries and may contribute to the lower rates of disseminated MAC infections in AIDS in these areas.

Adult↗

Improvements in skin-testing technique.

Allergy skin testing is the primary modality used in the diagnosis of allergic diseases and guides development of treatment and avoidance plans. The goal of the Allergist is to skin test the appropriate population with a device and technique that minimizes pain while maximizing sensitivity and specificity. The debate involving the use of intradermal versus skin-prick testing in the diagnosis of aeroallergy has been long lasting. Past and present medical literature will be reviewed, establishing the lack of diagnostic use of intradermal testing in the setting of aeroallergy. New skin devices continue to be developed with a trend toward production of multidevices. Performance characteristics of various skin test devices will be reviewed with an emphasis on sensitivity, specificity, and variability of skin-prick testing devices. Significant statistical differences exist between all devices tested and reported in the literature. Whether these statistical differences equate to clinical differences is not known. With this review the practicing allergist should carefully evaluate multiple different devices and choose a device that suits their practice needs. In addition, allergists must ensure that technicians are sufficiently trained on the correct use of their device and should conduct continuing education to ensure that proper skin testing techniques are being used in their practice. Finally, the use of skin testing in pediatrics will be reviewed with a focus on safety. Care should be taken when skin testing infants < or = 6 months of age, especially in the setting of eczema and a family history of atopy.

Humans↗