title: Diagnosis and follow-up of treatment of latent tuberculosis; the utility of the QuantiFERON-TB Gold In-tube assay in outpatients from a tuberculosis low-endemic country.
abstract: BACKGROUND
  Interferon-gamma (IFN-gamma) Release Assays (IGRA) are more specific than the tuberculosis skin test (TST) in the diagnosis of latent tuberculosis (TB) infection (LTBI). We present the performance of the QuantiFERON-TB Gold In-tube (QFT-TB) assay as diagnostic test and during follow-up of preventive TB therapy in outpatients from a TB low-endemic country.
  
  
  METHODS
  481 persons with suspected TB infection were tested with QFT-TB. Thoracic X-ray and sputum samples were performed and a questionnaire concerning risk factors for TB was filled. Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months.
  
  
  RESULTS
  The QFT-TB test was positive in 30.8% (148/481) of the total, in 66.9% (111/166) of persons with origin from a TB endemic country, in 71.4% (20/28) previously treated for TB and in 100% (15/15) of those diagnosed with active TB with no inconclusive results. The QFT-TB test was more frequently positive in those with TST > or = 15 mm (47.5%) compared to TST 11-14 mm (21.3%) and TST 6-10 mm (10.5%), (p < 0.001). Origin from a TB endemic country (OR 6.82, 95% CI 1.73-26.82), recent stay in a TB endemic country (OR 1.32, 95% CI 1.09-1.59), duration of TB exposure (OR 1.59, 95% CI 1.14-2.22) and previous TB disease (OR 11.60, 95% CI 2.02-66.73) were all independently associated with a positive QFT-TB test. After preventive therapy, 35/40 (87.5%) and 22/26 (84.6%) were still QFT-TB positive after three and 15 months, respectively. IFN-gamma responses were comparable at start (mean 6.13 IU/ml +/- SD 3.99) and after three months (mean 5.65 IU/ml +/- SD 3.66) and 15 months (mean 5.65 IU/ml +/- SD 4.14), (p > 0.05).
  
  
  CONCLUSIONS
  Only one third of those with suspected TB infection had a positive QFT-TB test. Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening. Since most patients remained QFT-TB positive after therapy, the test should not be used to monitor the effect of preventive therapy. Prospective studies are needed in order to determine the usefulness of IGRA tests during therapy.
authors.affiliation: Department of Medicine, Section of Infectious diseases, Haukeland University Hospital, Bergen, N-5021, Norway. adri@helse-bergen.no
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dyrhol-Riise
authors.forename: Gerd
authors.initials: G
authors.lastname: Gran
authors.forename: Tore
authors.initials: T
authors.lastname: Wentzel-Larsen
authors.forename: Bjørn
authors.initials: B
authors.lastname: Blomberg
authors.forename: Christel Gill
authors.initials: CG
authors.lastname: Haanshuus
authors.forename: Odd
authors.initials: O
authors.lastname: Mørkve
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care / Q000379:methods*; D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D002648:Child; D019411:Clinical Laboratory Techniques / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007538:Isoniazid / Q000627:therapeutic use; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D013902:Radiography, Thoracic; D012293:Rifampin / Q000627:therapeutic use; D012307:Risk Factors; D013183:Sputum / Q000382:microbiology; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin