Usefulness of Ifn-Gamma Release Assays in Clinical Management of Difficult TB Cases: Evidence from Clinical Practice

Abstract

Performance of T-SPOT.TBTM (TS-TB) and QuantiFERON TB Gold-In tube (QFT-IT) assays was evaluated for detection of M. tuberculosis (Mtb) infection in patients with suspected extra-pulmonary or smear-negative pulmonary tuberculosis (TB) in a low prevalence country. Twenty-one out of 35 patients were affected by active TB. Mtb culture isolation was achieved in 76% of cases. Tuberculin skin testing (TST), TS-TB, and QFT-IT yielded a positive result in 67%, 95% and 81% of cases, respectively. Agreement of interferon-y release assays and TST was 70% (K=0.18 for TS-TB; K=0.46 for QFT-IT). Increased sensitivity of blood assays (>80%) improved diagnostic evaluation of difficult TB cases.Successful control of tuberculosis (TB) relies on prompt detection and treatment of active disease. While smear-positive pulmonary TB is readily diagnosed, bacteriological confirmation is often not possible in smear-negative cases. Conventional staining for acid-fast bacilli (AFB) and M tuberculosis (Mtb) culture are insensitive or time-consuming (l). In addition, nucleic acid amplification procedures, while providing quick and specific results, are considerably less sensitive than culture in AFB-negative cases (l). The IOO-yr old tuberculin skin test (TST) remains the most widely used tool in clinical practice in the evaluation of TB infection despite its poor sensitivity and specificity (l). Advances in scientific knowledge have recently led to the development of blood tests based on the principle of detecting the release of interferon (IFN)-y by memory effector T cells upon in vitro stimulation with two Mtbspecific RD (region of difference )-1 encoded antigens, ESAT (early secretory antigen)-6 and CFP (culture filtrate protein)-IO (2). These assays are more specific than TST, as RD-l genes are not shared by most environmental mycobacteria and M bovis BCG, correlate better with Mtb exposure, and are more sensitive in detecting active TB cases, at least in low prevalence settings (3-5). The aim of the present note is to address the usefulness of two IGRAs, i.e., T-SPOT.TB™ (TS-TB, Oxford Immunotech, Abingdon, UK) and QuantiFERON-TB GOLD In tube (QFT-IT), as surrogate tools for detection of Mtb infection in difficult-to-manage TB cases in clinical practice in a referral center in a low prevalence setting.

Cholesterol, Cytokines and Diseases

“…The effect on plaque stability is explained by the observation that blockade of IL-12 may diminish the recruitment ofT cells into the plaque (80)(81)(82)(83).…”

Psychological Stress and Cancer

“…Cellular-mediated and humoral-mediated responses are affected in general psychiatry traumatic disorders, as is the production of cytokines (13)(14)(15). The hypothalamic-pituitaryadrenal axis responds to several compounds, such as inflammatory cytokines: tumor necrosis factor (TNF)-u, interleukin-I (lL-I) alpha and beta, interleukin-18, interleukin-33 and interleukin-6 (16)(17)(18)(19)(20)(21)(22). Several studies proved the correlation between stress and progression of various types of cancer and cancer recurrence, in humans (23)(24)(25).…”

Cholesterol: An Inflammatory Compound

“…CD40L as well as IL-I produced by T cells induce macrophages to release interstitial collagenases, including MMP-I, -8, and -13 (14-17). The shoulder region of plaques as well as areas of foam cell accumulation contain MMP-9, a member of the gelatinase class of the rnetalloproteinase family (18)(19)(20)(21)(22). Human plaque analysis has revealed that MMP-9 is catalytically active and may thus contribute to the dysregulation of extracellular matrix that leads to plaque rupture during the complication of atherothrombosis (23)(24)(25)(26).…”