title: Risk of sensitization in healthy adults following repeated administration of rdESAT-6 skin test reagent by the Mantoux injection technique.
abstract: Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase 1 open clinical trial was to assess the sensitization risk and safety of repeated administration of rdESAT-6 reagent in 31 healthy adult volunteers. Three groups of volunteers received two fixed doses of 0.1 microg rdESAT-6 28, 56 or 112 days apart, respectively. After the second injection, the diameter of induration and/or redness at the injection site was measured and taken as a possible sensitization reaction if >5mm. In vitro interferon gamma (IFN-gamma) responses were measured as supportive evidence. Local adverse reactions at the injection site and adverse events were recorded. One out of 31 (3%) volunteers showed a positive skin reaction (sensitization) upon a second injection of rdESAT-6 after 28days and an increased IFN-gamma response to ESAT-6. For 7 (23%) of the volunteers, local adverse reactions related to the product were registered, but all reactions were mild and predictable. In conclusion, repeated injections of the rdESAT-6 skin test reagent are safe, and sensitization occurs at a low rate, especially if the time span between succeeding doses is wide.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. lillebaek@dadlnet.dk
authors.forename: Troels
authors.initials: T
authors.lastname: Lillebaek
authors.forename: Winnie
authors.initials: W
authors.lastname: Bergstedt
authors.forename: Pernille N
authors.initials: PN
authors.lastname: Tingskov
authors.forename: Birgit
authors.initials: B
authors.lastname: Thierry-Carstensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Aggerbeck
authors.forename: Soeren T
authors.initials: ST
authors.lastname: Hoff
authors.forename: Karin
authors.initials: K
authors.lastname: Weldingh
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Bolette
authors.initials: B
authors.lastname: Soborg
authors.forename: Vibeke O
authors.initials: VO
authors.lastname: Thomsen
authors.forename: Aase B
authors.initials: AB
authors.lastname: Andersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D007428:Intradermal Tests / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma