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

BackgroundInterferon-gamma (IFN-γ) 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.Methods481 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.ResultsThe 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 ≥ 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-γ 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).ConclusionOnly 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.

Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens

“…The macaque develops a variety of lesion types, and it may be that some granuloma types respond to INH more quickly than other lesion types and these lesion types are more prominent in rabbits. In a similar fashion, early (at 1 to 3 months) and transient increases in blood gamma interferon responses have been observed during treatment of both latent and active TB with regimens that include INH (32)(33)(34)(35).…”

Persistently Retained Interferon-Gamma Responsiveness in Individuals with a History of Pulmonary Tuberculosis

“…Some studies have shown declining responses during and after the treatment (Kobashi et al 2009a;Connell et al 2010;Lee et al 2010b), whereas other reports described persistent, fluctuating, or increasing responses (Ferrand et al 2005;Pai et al 2006;Dyrhol-Riise et al 2010). These discrepancies were attributed to variations in incubation periods, antigens, and assay formats (Pai et al 2006).…”

Rapid diagnosis of Mycobacterium tuberculosis infection in children using interferon-gamma release assays (IGRAs)

“…9,14 -16 Several studies performed primarily in adults indicate that both tests are more specific than the TST and are not confounded by previous BCG vaccination or by infection with most nontuberculous bacteria. 9,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Powell et al 30 recommend that with unusual IFN-␥ measurements, not only should the QFT-G and QFT-GIT be repeated with another blood sample to avoid erroneous diagnosis of M. tuberculosis infection and interpreted with caution if they recur but also encourage more meticulous recognition of these unusual IFN-␥ measurements that may be a predictive marker of inaccurate results. In the study by Pareek et al, 24 the use of screening by QFT-GIT in the UK for latent TB in immigrant populations was found to be cost-effective, thereby preventing substantial numbers of future cases of active TB.…”