Identification Of Latent Tuberculosis Infection Research Articles

Acute Leukemia and Latent Tuberculosis Infection in Italy: Quantiferon-Tb Test Screening in a Low Tuberculosis Incidence Country.

Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. However, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated. QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between October 2019 and August 2023. We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. During the 46 months of observation, no patients developed TB reactivation. Despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in Italy. This finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy.

A-170 Investigation of High Rate of Low Positive Quantiferon-TB Gold Plus Results

Abstract Background Tuberculosis (TB) is a communicable disease, transmitted almost exclusively by cough aerosols carrying pathogens of the M. tuberculosis complex. TB continues to be a major public health threat, causing an estimated 10.4 million new cases and 1.3 million deaths from TB globally in 2016. Many more people may have latent tuberculosis infection (LTBI), which may go undetected without further laboratory investigation. The Quantiferon-TB Gold Plus (QFT-Plus) is an Interferon Gamma Release Assay (IGRA) for the identification of LTBI. It detects the cellular immune response to antigens of M. tuberculosis and represents an indirect marker of M. tuberculosis exposure. In January of 2021, the NorthShore University HealthSystem Core Laboratory transitioned from a reference laboratory ELISA-based QFT-Plus test to an in-house DiaSorin LIAISON® QuantiFERON®-TB Gold Plus test. After implementation, we noticed a higher rate of low positive QFT-Plus results (1.3%–5.4%) in our patient population that we regard as a mixed risk population. The expected percent of low positive results in a mixed risk population is 2%–3%. Objective To determine the potential causes of a higher rate of low positive Quantiferon-TB Gold Plus Results. Methods Forty specimens with Antigen-Nil results between 0.35–1.00 IU/mL using LIAISON® QuantiFERON®-TB Gold Plus reagent from 8/2022–10/2022 were collected for this study. All forty specimens were re-tested using ELISA-based methodology. Patient demographics and medical history were reviewed for any factor that may be responsible for the low positive results. Results Results from the two different methodologies were compared: 28/40 (70%) specimens showed positive results on the DiaSorin LIAISON®-XL platform, but negative results on the ELISA platform. Review of medical history showed that 92% of the sample population had received more than 2 doses of COVID-19 vaccine and 12.5 % had previous COVID-19 infection. 30% had an underlying autoimmune disease, with psoriasis and rheumatoid arthritis being the most common. However, no correlation was found between medical or vaccination history and the QFT-Plus results. Conclusion LIAISON® QuantiFERON®-TB Gold Plus is a Chemiluminescence immunoassay which is more sensitive than ELISA, resulting in an increased number of low positive QFT-Plus results. Physicians need to correlate clinical findings and TB exposure history to the QFT-Plus results when making clinical decisions.

Optimizing tuberculosis screening for immigrants in southern New Brunswick: A pilot study protocol.

Immigrants from high tuberculosis-burdened countries have been shown to have an increased risk of latent tuberculosis infection (LTBI). To reduce the risk of increased tuberculosis cases in Canada, the country has a comprehensive immigration medical examination process that identifies individuals with active tuberculosis using chest X-ray; however, it fails to identify LTBI. The lack of LTBI identification is concerning because immigrants with LTBI are at an increased risk of developing active tuberculosis within their first few years of migration due to stressful experiences common to many immigrants. The goal of this pilot study is to improve the current LTBI screening protocols among immigrants from high tuberculosis incidence countries and to better prevent and manage tuberculosis cases, by introducing an LTBI screening pilot program. The objectives are threefold: 1) to screen LTBI in immigrants from high tuberculosis incidence countries, including immigrants identified as being at risk of LTBI by the NB health care system, using the QuantiFERON-TB Gold Plus interferon-gamma release assay (IGRA); 2) to offer LTBI treatment and supports to those identified as having LTBI; and 3) to assess immigrant and health care providers (HCPs) satisfaction of the LTBI screening pilot program. This cross-sectional study seeks to recruit 288 participants. Participants will be recruited via posters, social media platforms, invitations at immigrant wellness check-ups, presentations to local ethnocultural groups, and by snowball sampling. Consenting participants will be asked to submit a blood sample for LTBI screening; if positive, participants will be assessed and offered treatment for LTBI based on clinical assessment. Participants and HCPs' feedback will be gathered via short questionnaires. For the quantitative portion of the study, descriptive statistics will be used to summarize participant characteristics and feedback. Simultaneous logistic regression will be performed to identify variables associated with the IGRA test outcome and evidence of increased CD8 T-cell immune response among those found to be LTBI-positive. Qualitative results will be analyzed using inductive thematic analysis. The findings from this study will allow us to understand the role of the IGRA LTBI screening assay and its feasibility and acceptability by immigrants and HCPs in New Brunswick. The findings will additionally provide information on the enhancers and barriers of LTBI screening and management useful in determining how best to expand the LTBI screening program if deemed appropriate.

QuantiFERON-TB Gold Plus Test in Diagnostics of Latent Tuberculosis Infection in Children Aged 1-14 in a Country with a Low Tuberculosis Incidence.

The aim of the study was to evaluate the QuantiFERON-TB Gold Plus (QFT-Plus) test usability in the identification of latent tuberculosis infection (LTBI) in children and the determination of features associated with tuberculin skin test (TST) and QFT-Plus-positive results concerning LTBI. Two-hundred thirteen children aged 1–14 were screened for LTBI due to household contact with TB, suspected TB, or were qualified for biological therapy. The objective of this study was to evaluate the QFT-Plus affectivity as a diagnostic test in the absence of a gold standard (GS) test for the diagnosis of LTBI. The children were diagnosed with QFT-Plus, TST, and culture of TB. The QFT-Plus results were analyzed depending on the children’s age, TST size, and type. In children aged 1–4, the positive predictive value of QFT-Plus was 1, the negative predictive value was 0.94, QFT-Plus sensitivity was 75%, and specificity was 100%. It was observed that in children aged 5–14 years, the level of agreement decreased to the substantial, i.e., 87.2%. Moreover, the negative predictive value was 0.83. QFT-Plus sensitivity was 64%, and specificity was 100%. Statistical analysis of QFT-Plus and TST results showed substantial and almost perfect agreements. Our study suggests that QFT-Plus is helpful in a pediatric practice showing good sensitivity and specificity for LTBI. The BCG vaccine, infections, and concomitant morbidities do not affect QFT-Plus results.

Interferon Gamma Release Assay for Identifying Latent Tuberculosis Infection in People With Bacillus Calmette-Guérin Vaccination


 In people who have been vaccinated with Bacillus Calmette-Guérin, the interferon gamma release assay appears to be related to fewer diagnoses for latent tuberculosis infection, fewer prescriptions of preventive tuberculosis therapy, and no difference in the number of active TB cases compared to the tuberculin skin test (findings based on 1 [non-randomized study] of low quality).
 No evidence-based guidelines were found regarding the identification of latent tuberculosis infection in people with previous Bacillus Calmette-Guérin vaccination.

Interferon Gamma Release Assay for the Identification of Latent Tuberculosis Infection in Rural and Remote Settings


 There is a lack of evidence on the clinical utility of the interferon gamma release assay for identifying latent tuberculosis infection in rural and remote settings.
 In remote Indigenous communities with known history of bacillus Calmette-Guérin vaccination, more positive tests results were reported with the tuberculin skin test than with the interferon gamma release assay.

Is interleukin-2 an optimal marker for diagnosing tuberculosis infection? A systematic review and meta-analysis

Background Latent tuberculosis infection (LTBI) is a huge reservoir for the deadlier TB disease. Accurate identification of LTBI is a key strategy to eliminate TB. Therefore, a systematic review and meta-analysis approach was used to assess diagnostic potential of IL-2 for LTBI. Methods PubMed, Web of Science, the Cochrane Library and Embase were searched. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (AUROC) and hierarchical summary receiver operating characteristic curve (HSROC) were estimated by bivariate and HSROC models. Results Twenty-seven studies including 1404 participants and 1986 samples met the inclusion criteria. The pooled sensitivity, specificity, PLR, NLR, DOR and AUROC of IL-2 were separately as 87%, 98%, 34.78, 0.14, 256.41 and 0.98, indicating a very powerful differentiating ability of IL-2 for LTBI from non-TB controls. For differentiating ATB from LTBI, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC of IL-2 were 83%, 76%, 3.41, 0.22, 15.47 and 0.87, respectively, suggesting a good differentiating ability of IL-2. Conclusions These findings showed that IL-2 is a powerful marker for differentiating LTBI from non-TB controls and a good marker for differentiating ATB from LTBI individuals.

Variations of tuberculin skin test in patients with rheumatologic disorders and under anti-TNF treatment

Aim: Nowadays PPD is the most inexpensive and easy to apply modality of test in identification of latent tuberculosis infection. Isoniazid (INH) prophylaxis must be given before usage of anti-TNF-α agents for patients. We aimed to investigate the change in Tuberculin skin test (TST) levels and Isoniazid (INH) prophylaxis rates in patients with inflammatory rheumatic diseases treated with anti-tumor necrosis factor alpha (TNF-α) agents. Methods: A cross-sectional study was planned. Patients with inflammatory rheumatic diseases treated with anti-TNF agents were included in the study. Demographic data, initial TST level and INH prophylaxis had obtained from patient’s files. Control TST tests had done at tuberculosis dispensaries in different time periods such as 1-2 / 2-3 / 3-4 / ≥4 years of anti TNF treatment. INH prophylaxis rates according to initial and control TST tests were compared. The relationship between INH prophylaxis and duration of anti-TNF therapy were examined.Results: A total of 117 patients were included in the study. The mean age of the patients (81 male, 36 female) was 40.4±12.90. The control TST levels was significantly higher than initial TST (p=0.001). INH prophylaxis was given to total 99 (84.6%) of 117 patients (to 63 (53.8%) according to initial and to 36 (30.8%) according to control TST tests). There was no relationship between duration of anti TNF therapy and INH prophylaxis initiation (p=0.180). Conclusion: Anti-TNF treatments may reduce the rates of false-negative TST in patients with rheumatic diseases and latent tuberculosis (LTBI) at any stage of the treatment. Therefore, LTBI, which is not determined with initial TST tests, may be determined with TST test applied in the later stages of anti-TNF treatment, and the risk of active tuberculosis can be reduced by INH prophylaxis in this patients.

Associated Factors of Latent Tuberculosis among Diabetics in Urban Health Clinics

Mycobacterium tuberculosis infection causes significant morbidity and mortality worldwide. Among the risks for tuberculosis is diabetes, which triples the risk of tuberculosis compared to non-diabetics. One of the effective strategy to reduce the transmission, morbidity, and mortality of active disease among diabetic patients is the identification of latent tuberculosis infection (LTBI). This study aimed to determine the prevalence of LTBI and its associated risk factors among diabetic patients in urban health clinics. This cross-sectional study was conducted at three randomly selected urban health clinics in Terengganu. Participants (n=362) were administered with Tuberculin Skin Test (TST) and interviewed to obtain the socio demographic and clinical data. Simple and multivariate logistic regression were applied to test for the significant associated factors of LTBI. The prevalence of LTBI among diabetic patients was 5.8%. This study revealed that the associated factors for LTBI were having higher glycated haemoglobin (HBA1c) (p=0.016, OR=14.23), smoking (p=0.046, OR=3.78), asthma (p=0.049, OR=5.79) and history of TB contact (p= <0.001, OR=6.92). Active screening, infection control measures and glucose controls are recommended in reducing the risk of LTBI and reactivation of LTBI.

Identification of mycobacterial bacterioferritin B for immune screening of tuberculosis and latent tuberculosis infection

ObjectivesIt remains necessary and urgent to search for novel mycobacterial antigens to increase the sensitivity and specificity for tuberculosis (TB) diagnosis and latent TB infection (LTBI) screening. Antigens capable of inducing strong immune responses during Mycobacterium tuberculosis (M.tb) infection would be good candidates. MethodsCellular responses specific to M.tb derived bacterioferritin B (BfrB) were assessed by IFN-γ ELISPOT in three human cohorts, including healthy controls (HCs), LTBI population and pulmonary TB (PTB) patients. Its significance in TB diagnosis and LTBI identification was further analyzed. ResultsBfrB-specific IFN-γ responses in PTB and LTBI groups were significantly higher than that in HCs. However, BfrB-specific IFN-γ release was not as strong as that to ESAT-6 or CFP-10 in PTB patients whereas comparable in LTBI cohort with possible complementary properties to ESAT-6 or CFP-10. More interestingly, there were a considerable number of HCs with high BfrB-specific cellular responses. When HCs with high BfrB-specific cellular responses were subgrouped into ESAT-6/CFP-10hi (SFUs = 3, 4, 5) and ESAT-6/CFP-10lo (SFUs < 3) groups, those who belonged to ESAT-6/CFP-10hi group exhibited higher PPD responsiveness than ESAT-6/CFP-10lo group. ConclusionsPTB and LTBI groups exhibit higher BfrB-specific IFN-γ responses than HCs. Although BfrB is not as immunodominant as ESAT-6/CFP-10 during acute M.tb infection, comparable BfrB-specific cellular immune responses are observed in LTBI population with the potential to increase the sensitivity for LTBI screening. Moreover, strong BfrB-specific IFN-γ release in the healthy cohort is probably cautionary in identifying leaky LTBI from HCs. BfrB might thus be considered as an additional biomarker antigen for LTBI identification.

Comparing interferon-gamma release assays with tuberculin skin test for identifying latent tuberculosis infection that progresses to active tuberculosis: systematic review and meta-analysis

BackgroundTimely and accurate identification of people with latent tuberculosis infection (LTBI) is important for controlling Mycobacterium tuberculosis (TB). There is no gold standard for diagnosis of LTBI. Screening tests such as interferon gamma release assays (IGRAs) and tuberculin skin test (TST) provide indirect and imperfect information. This systematic review compared two types of IGRAs QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB with TST for identification of LTBI by predicting progression to a diagnosis of active TB in three subgroups: children, immunocompromised people, and those recently arrived from countries with high TB burden.MethodsCohort studies were eligible for inclusion. We searched MEDLINE, EMBASE, the Cochrane Library and other databases from December 2009 to June 2015. One reviewer screened studies, extracted data, and assessed risk of bias with cross checking by a second reviewer. Strength of association between test results and incidence of TB was summarised using cumulative incidence ratios (CIRs with 95% CIs). Summary effect measures: the ratio of CIRs (R-CIR) with 95% CIs. R-CIRs, were pooled using a random-effects model. Heterogeneity was assessed using Chi-squared and I2 statistics.ResultsSeventeen studies, mostly of moderate or high risk of bias (five in children, 10 in immunocompromised people, and two in those recently arrived) were included. In children, while in two studies, there was no significant difference between QFT-GIT and TST (≥5 mm) (pooled R-CIR = 1.11, 95% CI: 0.71, 1.74), two other studies showed QFT-GIT to outperform TST (≥10 mm) in identifying LTBI. In immunocompromised people, IGRA (T-SPOT.TB) was not significant different from TST (≥10 mm) for identifying LTBI, (pooled R-CIR = 1.01, 95% CI: 0.65, 1.58). The forest plot of two studies in recently arrived people from countries with high TB burden demonstrated inconsistent findings (high heterogeneity; I2 = 92%).ConclusionsProspective studies comparing IGRA testing against TST on the progression from LTBI to TB were sparse, and these results should be interpreted with caution due to uncertainty, risk of bias, and unexplained heterogeneity. Population-based studies with adequate sample size and follow-up are required to adequately compare the performance of IGRA with TST in people at high risk of TB.

Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

The identification of individuals with latent tuberculosis infection (LTBI) is useful for both fundamental understanding of the pathogenesis of disease and for clinical and public health interventions (i.e., to prevent progression to disease). Basic research suggests there is a pathogenetic continuum from exposure to infection to disease, and individuals may advance or reverse positions within the spectrum, depending on changes in the host immunity. Unfortunately, there is no diagnostic test that resolves the various stages within the spectrum of Mycobacterium tuberculosis infection. Two main immune-based approaches are currently used for identification of LTBI: the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA). TST can use either the conventional purified protein derivative or more specific antigens. Extensive research suggests that both TST and IGRA represent indirect markers of M. tuberculosis exposure and indicates a cellular immune response to M. tuberculosis. The imperfect concordance between these two tests suggests that neither test is perfect, presumably due to both technical and biological reasons. Neither test can accurately differentiate between LTBI and active TB. Both IGRA and TST have low sensitivity in a variety of immunocompromised populations. Cohort studies have shown that both TST and IGRA have low predictive value for progression from infection to active TB. For fundamental applications, basic research is necessary to identify those at highest risk of disease with a positive TST and/or IGRA. For clinical applications, the identification of such biomarkers can help prioritize efforts to interrupt progression to disease through preventive therapy.

PpiA antigen specific immune response is a potential biomarker for latent tuberculosis infection

One third of the world's population is estimated to harbour latent tuberculosis infection (LTBI). Around 10% of them have the life time risk of developing active tuberculosis (PTB). Currently there is no gold standard test for identifying LTBI. Therefore identification of specific markers for LTBI will help as to develop a test specific for LTBI. Earlier, in our immunoproteomic analysis, we found that peptidyl-prolyl cis-trans isomerase A (PpiA) protein-containing fractions induced significantly higher interferon-gamma (IFN-γ) response in LTBI than in PTB. Immunological characterisation of recombinant PpiA protein was carried out in the current study. We have studied 10 cytokines and 2 chemokine responses against PpiA and standard antigens such as early secretory antigenic target-6 (ESAT-6) and culture filtrate antigen-10 (CFP-10). In healthy household contacts (HHC), all the tested antigens induced significantly higher levels of IFN-γ and Interlukin-8 (IL-8) compared with those in PTB. PpiA-specific IL-12p40 response was significantly increased in HHC compared with that in PTB. PpiA antigen-specific IFN-γ and IL-12p40 both showed 86% positivity in HHC, whereas in PTB, they showed 20% and 38% positivity, respectively. In terms of IFN-γ/TNF-α ratio, PpiA displayed 86% (30/35) positivity in HHC and 18% (7/39) positivity in PTB. In summary we found that PpiA-specific IFN-γ and IFN-γ/TNF-α ratio response were specific biomarkers for LTBI identification.

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers.

The Twin Epidemics of Tuberculosis and HIV

The deadly combination of tuberculosis (TB) and human immunodeficiency virus (HIV) currently ravaging the world, taking a toll of about 0.35 million people every year, is one of the major public health crises of the decade. Throughout the course of HIV infection, the risk of acquisition, reactivation, and reinfection of TB keeps increasing substantially as the immune deficiency progresses. TB coinfected patients inadvertently facilitate HIV infection by release of the proinflammatory cytokines and overexpression of coreceptors CXCR4 and CCR5; thereby, the progression of each is facilitated. The difficulties in diagnosing active tuberculosis in HIV-infected individuals poses a great challenge that is further complicated by the challenges in identification of latent TB infection, creating a setback to preventive therapy. Furthermore, prescribing antituberculous therapy and antiretroviral therapy together poses several management challenges, including drug interactions, added toxicities, and TB immune reconstitution inflammatory syndrome. The current approach to diagnosis, prevention, and treatment strategies in TB and HIV coinfected individuals, along with epidemiology and overview of pathogenetic interplay of both microbes, is reviewed here.

Identification of latent tuberculosis infection in rheumatic patients under consideration for treatment with anti-TNF-α agents

IntroductionImmunosuppressive therapy with anti-tumour necrosis factor-α (TNF-α) agents in rheumatic patients modulates the immune system and may increase the risk of reactivating infections that are normally maintained in a latent state, such as tuberculosis. The purpose of this study was to analyse the value of QuantiFERON TB Gold In-Tube (QFT IT) and tuberculin skin test (TST) in BCG vaccinated patients with rheumatoid arthritis and ankylosing spondylitis who were qualified to receive TNF-α blockers.Material and methodsNinety patients with rheumatoid arthritis and ankylosing spondylitis were included in the study. The control group consisted of 20 healthy participants. Chest X-ray, TST and QFT IT were carried out in all persons.ResultsIn rheumatic patients positive results of QFT IT and TST tests were identified in 15 cases (16.7%) whereas negative results of both tests were detected in 56 cases (62.2%). In the group of examined patients, 11 (12.2%) had QFT IT-/TST+ test results. In patients with QFT IT+/TST– status one active tuberculosis case was detected. In the control group QFT IT positive results were found in 4 cases (20%) and TST positive in 11 cases (55%). Treatment with TNF-α blockers was introduced in 26 rheumatology patients with the following test status: 3 with QFT IT+/TST+; 20 with QFT IT-/TST-; 3 with QFT IT-/TST+.ConclusionsIn the BCG vaccinated population the QFT IT assay may potentially improve the identification and selection for therapy for latent TB infection before treatment with anti-TNF agents.

Interferon Gamma Release Assay No Better Than Skin Test for TB Diagnosis in Children

Diagnosis of tuberculosis (TB) in children is challenging because fewer than 50% of children with active TB have positive cultures. Furthermore, identification of latent TB infection with the tuberculin skin test (TST) is poorly standardized, requires a return visit in 2 to 3 days, and results can be confounded by non-TB mycobacterial exposure and prior bacille Calmette-Guerin (BCG) vaccination. Researchers …

Testing for Tuberculosis: The Roles of Tuberculin Skin Tests and Interferon Gamma Release Assays

The identification of latent tuberculosis infection (LTBI) in any individual or population has proven to carry significant importance not only for that person’s health, but also for the control and eventual elimination of tuberculosis (TB) in the United States. Traditionally, the tuberculin skin test (TST) has served as the standard of care for the identification of prior exposure to Mycobacterium tuberculosis (MTB). However, the specificity of a positive test is less than optimal. It is either due to previous vaccination intended to prevent TB or infection with nontuberculous mycobacterium (NTM). Newer tests classified as interferon-gamma release assays (IGRA) possess potential advantages over the TST when used for identifying those with MTB infection. We recently diagnosed a case of pleuropulmonary infection involving an unusual NTM, Mycobacterium interjectum (M. interjectum) , in an immunocompromised man diagnosed 1 year after he had been treated for LTBI based on a reactive TST. A propos this experience, we discuss the beneficial role of IGRAs and review the literature on infection with M. interjectum . * LTBI : latent tuberculosis infection TST : tuberculin skin test MTB : Mycobacterium tuberculosis NTM : nontuberculous mycobacterium IGRA : interferon gamma release assays PPD : purified protein derivative BCG : Bacillus Calmette-Guerin FDA : Food and Drug Administration IFN-γ : interferon-gamma IGRAs : interferon-gamma release assays INH : isoniazid TNF-α : tumor necrosis factor alpha CXR : chest radiograph CT : computerized tomographic AFB : acid-fast bacilli TB : tuberculosis RA : rheumatoid arthritis MTX : methotrexate DMARDs : disease-modifying antirheumatic drugs CDC : Centers for Disease Control and Prevention DTH : delayed-type hypersensitivity QFT : QuantiFERON-TB QFT-G : QuantiFERON-TB Gold QFT-GIT : QuantiFERON-TB Gold In-Tube ELISA : enzyme-linked immunosorbent assay ESAT-6 : early secretory antigenic target-6 CFP-10 : culture filtrate protein-10 ELISpot : enzyme-linked immunospot assay PBMCs : peripheral blood mononuclear cells MOTT : mycobacteria other than tuberculosis

TNF-alpha antagonist therapy modify the tuberculin skin test response

Tumour necrosis factor-alpha (TNF-α) antagonist drugs have been associated with increased risk of tuberculosis (TB). Tuberculin skin test (TST) is the most frequently used tool for identification of latent TB infection. We herein aimed to analyse the effect of TNF-α antagonists on the TST responses in a prospective study. The study group consisted of 182 patients (99 female, 83 male) who received TNF-α antagonists for various rheumatic disorders. All patients were evaluated with TST along with other parameters on the day of referral and on the 12th month visit. For those patients with a response of <5 mm induration at the initial evaluation, the TST was repeated to observe the booster effect. Out of 182 patients, 87 patients (48%) had a negative (0-4 mm) and 95 (52%) had a positive (≥ 5 mm) TST response at initial evaluation. The TST responses were converted from negative at initial visit to positive at 1-year repeat in 26 (30%) patients. A significant increase was observed in the diameters of TST that were repeated on the first year of TNF-α antagonist treatment (9.15 ± 0.55) compared to their initial diameters (6.60 ± 0.51) (P < 0.001). Increased TST responses in patients receiving TNF-α antagonists may be associated with the restoration of suppressed immune reactivity against TB antigens with the decreased disease activity. The meaning of TST conversion in the definition of latent TB infection and the need for chemoprophylaxis in these patients remains to be answered by further studies.

Agreement Between Quantiferon-TB Gold Test and Tuberculin Skin Test in the Identification of Latent Tuberculosis Infection in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

To compare the Quantiferon-TB Gold test (QTF-G) with the tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) among patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), with reevaluation of the patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists in the followup. The study involved 140 consecutive patients, 82 with RA and 58 with AS. Thirty patients were evaluated with QTF-G for detection of LTBI before and after 6 months of TNF-alpha antagonist treatment. QTF-G was also performed on 49 healthy controls. QTF-G results were recorded as positive, negative, or indeterminate. A positive TST was defined as >or= 5 mm for RA and AS. The percentages of positive QTF-G were comparable in RA and AS (37% vs 32%). The rate of positive QTF-G in healthy controls (29%) was also similar to RA and AS. In contrast to QTF-G results, a high rate of TST positivity was observed in AS compared to RA (82% vs 55%; p = 0.02). The total agreement between QTF-G and TST was observed to be 61% (kappa = 0.29) in the whole group, 70% (kappa = 0.42) in RA, and 49% (kappa = 0.14) in AS. After 6 months of treatment with TNF-alpha antagonists, a high rate of QTF-G change was observed in patients with indeterminate results (23% vs 3%; p = 0.03). The comparable prevalence of LTBI among the study groups according to QTF-G supports the view that QTF-G is less susceptible to external factors than TST. Sequential testing for QTF-G in patients with indeterminate or negative results may also be helpful in discriminating LTBI better.