QuantiFERON-TB Gold Research Articles

Testing for Mycobacterium tuberculosis infection using the QuantiFERON-TB GOLD assay in patients with comorbid conditions in a tertiary care endemic setting

IntroductionThere were 10 million new cases of tuberculosis (TB) in 2017. To eliminate TB, it is necessary to diagnose active TB and latent tuberculosis infection (LTBI). Diagnosis of paucibacillary disease and in extrapulmonary TB (EPTB) remains challenging; low mycobacterial load can be missed by microbiological or molecular based confirmation; EPTB, can be misdiagnosed due to absence of site specific specimens for testing. Interferon gamma release assays (IGRA) use T cell-based Interferon-gamma (IFN-γ) to identify infection with M. tuberculosis (MTB) but cannot discriminate between active and LTBI. We investigated how IGRA was being used in a high burden low resource setting.MethodsWe conducted a retrospective review of 149 consecutive cases received for QuantiFERON-TB Gold In-Tube Assay (QFT-GIT) testing in routine clinical service.ResultsFifty-six cases were QFT-GIT positive and 93 were QFT-GIT negative. Thirty-six per cent of QFT-GIT tested cases had active TB. Of QFT-GIT positive cases, 59% patients had active TB; 10 with pulmonary and 23 with extra-pulmonary TB. The remaining 41% QFT-positive cases were LTBI. Of the QFT-GIT negative cases, 22% had active TB. Co-morbid conditions were present in 37% of QFT-GIT positive and 60% of QFT-GIT negative cases.ConclusionsOur study shows that IGRA is being used as an adjunct test for active TB in this population. It highlights the complexity of interpreting QFT-GIT results particularly for QFT-GIT negative cases when ruling out MTB infection.

Role of CD8 T-cell in immune response to tuberculosis-specific antigen in QuantiFERON-TB Gold Plus

Recent contacts with active TB (tuberculosis) patients were screened for latent tuberculosis infection (LTBI) because of their greater relative risk for developing active TB. QuantiFERON®-TB Gold Plus (QFT-Plus) offers two TB-specific antigen tubes (TB1 and TB2). TB1 elicits CD4 T-cell responses, and TB2 is designed to elicit both CD4 and CD8 T-cell responses. These mechanisms could be useful for estimating the role of CD8 T-cell immune responses to TB-specific antigens. To estimate the QFT-Plus capability to diagnose LTBI, a prospective cross-sectional study was conducted. A total of 412 TB contacts (median age 44 years) were enrolled. The positivity rates of QFT-Plus, TB1 and TB2 were 7.5%, 6.3% and 7.2%, respectively. TB2 showed a higher positivity rate compared to TB1, but without significant difference. The interferon (IFN)-γ productions of TB1 and TB2 were well correlated (r = 0.934, P < 0.001). The ratio of IFN-γ production between TB1 and TB2 showed a median (interquartile range) of IFN-γ[QFT-Plus TB2]/IFN-γ[QFT-Plus TB1] of 1.09 (0.91–1.36). CD8 T-cell immune response to TB-specific antigens varied among subjects. CD8 T-cell potentially boosts IFN-γ productions in QFT-Plus and results in the detection of more persons with LTBI. However, there was no significant difference in the positivity rates of QFT-Plus TB1 and TB2 in our TB contact investigation. The contribution of CD8 T-cells might be small for the diagnosis of LTBI. The analysis of IFN-γ production in both TB1 and TB2 would lead to further analysis of the TB immune response, and especially that caused by CD8 T-cells.

False-positive Results of Quantiferon-Tb-Gold Assay in Children.

We present a pediatric case series describing false-positive QuantiFERON-TB Gold In-tube (QFT-GIT) assay (QIAGEN, Germany) results observed in a tertiary hospital in Spain (2013-2018). During the study period, 7 of 737 test results were considered false-positives: 4 children with chronic medical conditions, 1 Mycobacterium lentiflavum lymphadenitis, 1 infant born to a mother with pulmonary tuberculosis, and 1 child exposed to a noninfectious tuberculosis patient. Data regarding interferon-gamma release assays false-positive results in children are scarce, and more studies are necessary to determine the rates of false-positive results in low-prevalence settings.

Dynamic changes of interferon gamma release assay results with latent tuberculosis infection treatment

ObjectivesUsing QuantiFERON-TB Gold In-Tube (QFT-GIT) for monitoring tuberculosis (TB) and latent TB infection treatment effect is controversial. The present study aimed to evaluate the dynamic changes of interferon gamma (IFN-γ) levels along with latent TB infection treatment via a randomized controlled study. MethodsA total of 910 participants treated with 8 weeks of once-weekly rifapentine plus isoniazid (group A), 890 treated with 6 weeks of twice-weekly rifapentine plus isoniazid (group B) and 818 untreated controls (group C) were followed for 2 years to track active TB development. QFT-GIT tests were repeated three times for all groups: before treatment (T0), at completion of treatment (T1) and 3 months after completion of treatment (T2). ResultsSimilar rates of persistent QFT-GIT reversion were observed in groups A (19.0%, 173/910), B (18.5%, 165/890) and C (20.7%, 169/818) (p 0.512). The dynamic changes of IFN-γ levels were not statistically significant among the three groups. In treated participants, individuals with higher baseline IFN-γ levels showed increased TB occurrence (1.0%, 9/896) compared to those with lower baseline levels (0.2%, 2/904) (p 0.037). A similar but statistically insignificant trend was also observed in untreated controls (1.8% (7/400) vs. 0.5% (2/418), p 0.100). When TB cases were matched with non-TB cases on baseline IFN-γ levels, no significant differences were found with respect to the dynamic changes in IFN-γ levels with time, regardless of whether they received treatment. ConclusionsQFT-GIT reversion or decreased IFN-γ levels should not be used for monitoring host response to latent TB infection treatment.

Impact of Baseline Tuberculin Skin Test and Isoniazid Chemoprophylaxis on Subsequent Quantiferon-TB Gold In-Tube Performance in Young Children Assessed After Tuberculosis Contact in Catalonia.

We investigated the impact of baseline tuberculin skin tests (TSTs) and preventive isoniazid chemoprophylaxis on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) assays performed after a 10- to 12-week window period in 114 children <5 years of age. Previous TSTs and chemoprophylaxis had no impact on the magnitude of subsequent antigen-induced responses in QFT-GIT. Furthermore, previous TSTs did not induce conversion from a negative to a positive QFT-GIT result.

Spot on! evaluation of T-spot.TB following indeterminant quantiferon TB-gold plus in screening for latent tuberculosis

Spot on! evaluation of T-spot.TB following indeterminant quantiferon TB-gold plus in screening for latent tuberculosis

P016 IMPROVING TUBERCULOSIS RE SCREENING IN INFLAMMATORY BOWEL DISEASE PATIENTS RECEIVING BIOLOGIC THERAPY: A SINGLE CENTER QUALITY IMPROVEMENT INITIATIVE.

Abstract Background Biological agents have revolutionized the management of inflammatory bowel disease (IBD). There is a known increased risk of tuberculosis (TB) reactivation with biologic therapy (1). ACG guidelines recommend screening for active and latent TB infection (LTBI) prior to starting certain biologic agents (2). However, there are no consensus guideline on the utility of yearly screening testing in IBD patients without TB risk factors. With a number of patients now receiving the biologic therapy outside their primary care centers it has become increasingly difficult to effectively provide ongoing TB screening. With this quality improvement exercise, we aim to improve TB re-screening in patients receiving biologics by completing a yearly phone screening for exposure history. Method An interdisciplinary team from GI and ID developed a TB risk factor screening questionairre, adapting the California Department of Public Health’s Pediatric TB Risk Assessment tool (3). A list of patients receiving biologics was sorted by month of birth in the EMR. When the current calendar month aligned with the patient’s birth month, a GI RN reviewed the TB questionnaire with the patient (≥18 yo) and/or legal guardian by phone. If one or more TB risk factors were identified, the GI RN would notify the provider and a QuantiFERON-TB Gold (QFT) was ordered to be completed. Results 60 patients were found on biologic therapy (median age 17 yo) (38 males, 22 females) (68% CD, 28% UC, 3.3% IBD-U)(75% IFX, 12% ADA, and 3% other) to be to eligible TB screening between January - July 2019, 48 patients completed the phone screening. All 61 patients had completed TB screening prior to starting biologic therapy, which was reported to be negative. 13 patients were unable to be reached. 6/48 were identified as having at least 1 risk factor for TB. 5/6 patients with a positive screen had a negative QFT. 1 patient was away at college and a request to his adult GI managing his biologic was sent. Conclusion Screening for LTBI is required prior to starting a biologic therapy, though there are no guidelines for routine TB screening following initiation of the biologic. We propose performing an annual phone screening for TB exposure history for IBD patients on biologic therapy. QTF testing remains appropriate in patients with potential risk factors, such as being a health care worker or travel to/living in high endemic TB regions. References

Treatment of latent tuberculosis infection with short-course regimens in potential living kidney donors.

Treatment data for latent tuberculosis infection (LTBI) among potential living kidney donors are scarce. This retrospective study was performed to evaluate the prevalence of positive QuantiFERON-TB Gold In-Tube (QFT-GIT) among potential living kidney donors that were screened from 2009 to 2017. We investigated if there was any difference in the time to donation between QFT-GIT-positive and QFT-GIT-negative donors. We assessed the regimens used to treat LTBI and whether the recipients of QFT-GIT-positive donors developed active tuberculosis (TB). Forty out of 427 (9%) potential living kidney donors had a positive QFT-GIT. QFT-GIT-positive donors were as likely as negative donors to undergo donation (30 [75%] vs 315 [81%], P=.33). The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors (median 221days [range: 4-1139] vs 86days [range: 3-1887], P=.001). Twelve-week rifapentine (RPT)/Isoniazid (INH) was the most common treatment used and was not associated with significant adverse reactions. There was a trend toward longer time to donation among QFT-GIT-positive donors who were treated for LTBI compared with QFT-GIT-positive donors who were not (252days [range: 88-1139] vs 95days [range: 4-802], P=.05). Twenty-nine recipients of QFT-GIT-positive living kidney donors were evaluated. Eleven of these recipients received kidneys from donors that were not treated for LTBI. Two of these recipients were treated with INH post-transplantation. The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors. The short-course regimens appear to be excellent options for LTBI treatment among living kidney donors and avoid delaying organ donation further.

Risk Factors and Prevalence for Latent Tuberculosis Infection among Health Care Workers in Al-Quwayiyah General Hospital Riyadh, KSA

Background: All health care facilities should intensify TB screening and encourage treatment of latent tuberculosis infection (LTBI) among Healthcare workers (HCWs) to prevent progression to tuberculosis (TB) disease.&#x0D; Aim: This study was conducted to determine the prevalence and associated risk factors of LTBI among HCWs in Al Quwayiyah General hospital as well as to compare the performance of QuantiFERON-TB Gold Plus (QFT-Plus) to TST in identifying LTBI.&#x0D; Methods: A cross sectional study and prospective cohort study was performed from January to July 2019 in Al Quwayiyah General hospital involving a total of 718 HCWs. questionnaire with socio-demographic data and work history was filled, and both tests were done TST and QFT test for each Healthcare worker.&#x0D; Results: The study showed that The prevalence of latent tuberculosis diagnosed was 9.05% and 9.19% using QFT-Plus and TST respectively. Only 26 (3.62%) subjects were positive for both tests whereas 131 (18.25%) were positive by either test. Comparing the results of the QFT-Plus with those of the TST, both tests had a significant total agreement of 88.8. Negative concordance comprised 85.37% of the results, and positive concordance comprised 3.62%. However, positive TST but negative QFT-Plus comprised 5.57% of the results, and negative TST but positive QFT-Plus comprised 5.43%. The association between risk factors and QFT-Plus test results in the studied groups showed that the smoking, health status, immunosuppresion, housing, occupation, contact T.B. at work place, past history of TB and diabetes mellitus appear as significant risk factors. The association between the studied risk factors and TST in the studied groups showed sig­nificant difference noted for smoking, BCG vaccination, immunosuppresion, housing, occupation, contact T.B. at work place, past history of TB and diabetes mellitus.&#x0D; Conclusion: The prevalence of latent tuberculosis diagnosed was 9.05% and 9.19% using QFT-Plus and TST respectively. Testing of HCWs at hire and periodically can help in the detection of LTBI Large scale study is recommended to confirm such findings in Saudi Arabia, also the use of Quantiferon for detection of LTBI beside using TST is recommended as it reduce the false positive reports by TST and is not affected by prior BCG status.

Positive conversion of interferon-γ release assay in patients with rheumatic diseases treated with biologics.

The objective of this study is to investigate whether the type of biologics (TNFi or others) or type of rheumatic diseases (RA or AS) influence the conversion rate of initially negative tuberculosis (TB) screening test results. A total of 119 patients with RA or AS who had negative baseline interferon-γ release assay (IGRA) results assessed by QuantiFERON-TB Gold in tube (QTF-GIT) were included. All patients received biologic agents, and rescreening with QTF-GIT was performed after a median of 25.9months from the baseline test. Clinical characteristics and IFN-γ levels were compared between converters and non-converters. Logistic regression analysis was performed to identify factors associated with positive conversion. IGRA conversion was found in 14 of 119 patients (11.8%). The converters were older (53.4 ± 14.2 vs 44.4 ± 15.5years, p = 0.040), had higher baseline TB-specific IFN-γ responses (0.105 [0.018-0.205] vs 0.010 [0.000-0.035] IU/ml, p = 0.001) and higher incidence of active TB (14.3% vs 0.0%, p = 0.013). The number of patients with RA or AS was 9 (64.3%) or 5 (35.7%) in converters, and 45 (42.9%) or 60 (57.1%) in non-converters. In terms of use of biologics, TNFi of monoclonal antibody form was less commonly used in the converters (p = 0.024). In the logistic regression analysis, type of disease and type of biologics used were not associated with IGRA conversion, whereas baseline TB-specific IFN-γ response was significantly associated with IGRA conversion (OR 1.083, 95% CI 1.019-1.151, p = 0.011). Serial monitoring of LTBI with IGRA retesting is needed during biologic treatment, regardless of the type of rheumatic diseases or type biologics used.

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with tuberculosis exposure or tuberculosis disease

Objective: To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children. Methods: A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis. QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test were performed in each patient. Results: Of the 60 children, median age 3.3 years, 17 had tuberculosis and 43 had recent tuberculosis exposure. Overall, 15 (25.0%) children had tuberculin skin test reaction ≥ 10 mm; 8 (13.3%) were positive by QuantiFERON-TB Gold In-Tube test, and 12 (20.0%) by T-SPOT.TB. Nineteen (31.7%) children had at least one positive test. There was a moderate agreement between interferon gamma release assays and tuberculin skin test. Conclusions: The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis, supporting the management strategy without testing in children younger than 5 years.

Latentna tuberkulozna infekcija u zdravstvenih radnika povezana je s alergijama i senzibilizacijom na uobičajene inhalacijske alergene

Health care workers (HCW) are at increased risk of a latent tuberculosis infection (LTBI) due to occupational exposure to Mycobacterium tuberculosis. In order to investigate the mutual influence of a TH1 type immune response caused by LTBI and T helper 2 (TH2) type immune response caused by allergy, we conducted a study examining the prevalence of common inhaled allergen sensitization in the HCW population with different levels of exposure to tuberculosis (high and low). HCW with possible exposure to tuberculosis (TB) were tested with QuantiFERON-TB Gold (QFT-G) and tuberculin skin test (TST), while skin prick test (SPT) was performed for inhaled allergens. The antigen (Ag) response at QFT-G was inversely correlated with participants` allergy anamnesis (p= 0.039). Sensitization to inhaled allergens (positive SPT and number of positive allergens at SPT) was more prominent in the low exposure group (p= 0.006 and p= 0.0065, respectively). Ag response at QFT-G test was significantly higher in participants with no medical history of allergy (p= 0.048). Our results demonstrate that exposure to TB and LTBI are associated with inhaled allergen sensitization in HCW, possibly inhibiting allergic sensitization by mediating the T-helper type 1 (Th1) immune response.

Performance and correlation of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution

Objective: To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods: A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes >25% or >500 cells/mm3 for at least 6 months. QuantiFERON-TB Gold, T-SPOT.TB, and tuberculin skin test were performed in each patient.Results: A total of 50 patients were enrolled with median age of 13.7 years, CD4 counts of 753 (IQR: 587-989) cells/mm3. Among 27 patients with tuberculosis (16) or tuberculosis exposure (11), 8 (29.6%) were positive to at least one test, 2 (7.4%) were positive QuantiFERON-TB Gold, 3 (11.1%) positive T-SPOT.TB, and 7 (25.9%) had tuberculin skin test ≥5 mm. Among 23 patients without history of tuberculosis or exposure, all had negative interferon gamma release assays, while 2 (8.7%) had positive tuberculin skin test.Conclusions: All tests had low sensitivity despite immune reconstitution.

Lichen planus and multifocal choroiditis - A diagnostic dilemma.

A 24-year-old gentleman had a right headache and MFC; for 1 year [Fig. 1a]; being on AKT for 3 weeks with further worsening. Fundus fluorescein angiography (FFA) [Fig. 1b]; optical coherence tomography (OCT), [Fig. 1c] and B-Scan [Fig. 1d] had been done. Serum angiotensin-converting enzyme (ACE), serum uric acid, and QuantiFERON TB Gold Test were normal. Mantoux was 19 mm [48 h/5 tuberculin units (TU)]. Oculus sinister (OS) was normal. On presentation to us, OD had finger counting close to face with congestion; mild relative afferent pupillary defect (RAPD); painful movements; disc edema; peripapillary sub-retinal exudation, and MFC [Fig. 1e]. We did contrast magnetic resonance imaging (MRI) brain/orbit, venereal disease research laboratory (VDRL), antinuclear antibody (ANA), antineutrophil cytoplasmic autoantibody (ANCA), and HIV, which were normal. Paradoxical worsening of TB choroiditis (3 weeks AKT) was considered and intravenous methylprednisolone was used. Repeat history-taking, caused him to recall having skin biopsy-proven LP; treated with oral prednisolone; just prior to ocular symptoms; 1 year back. Pursuing the possibility of flare-up of occult systemic TB; after the use of oral steroids to treat LP, a contrast chest CT was done, which was normal. A previously reported; LP associated intraocular inflammation[1] led us to use of azathioprine. One of the treatment protocols could have been the continuation of AKT, but our physician stopped AKT to avoid hepatotoxicity. Intraocular inflammation resolved within 2 months of azathioprine, [Fig. 1f]; which was continued for 9 months. At 16 months post cessation of azathioprine; he stays in remission.Figure 1: (a) Fundus showing fulminant MFC on treatment with tapering oral steroids for one year. (b) FFA showing late hyperfluorescence; pooling; disc leakage. (c) OCT showing choroidal elevation with macular thickening. (d) B-Scan showing grossly thickened choroid with sub-tenons fluid in macular area. (e) Fundus showing disc edema with peripapillary sub retinal exudation and MFC. (f) Fundus showing resolution of inflammation; 2 months on azathioprineDiscussion Ocular LP is largely extraocular and involves conjunctiva, cornea, and lacrimal drainage system.[2] The role of cellular immunity in LP and retinal vasculitis[34] was believed to be the cause of their once previously reported association.[1] In our patient; there is a diagnostic dilemma of the mere coexistence of LP and MFC with a temporal dissociation (LP occurring just prior to the onset of ocular symptoms) vs possible association between these two otherwise separate immune-mediated clinical entities. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Acknowledgement The authors wish to acknowledge Dr. Avinash Pathengay, for his technical help in the management of this patient.

Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children

IntroductionHIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because...

Introduction of a Borderline Range for the Interpretation of QuantiFERON-TB Gold In-Tube Results in Korean Healthcare Workers

South Korea is the only Organisation for Economic Co-operation and Development (OECD) country with a high incidence of tuberculosis (TB). Healthcare workers (HCWs) have an increased risk of TB infection. QuantiFERON-TB Gold In-Tube (QFT-GIT) testing is performed for occupational health screening to detect latent TB infection (LTBI). We evaluated the introduction of new criteria for borderline ranges for interferon-gamma release assay (IGRA) results in HCWs. The results of QFT-GIT tests in HCWs in 2017 and 2018 were collected, with high-risk HCWs having two serial test results. Existing dichotomous criteria and new criteria with borderline ranges (bor-derline negative [BN], 0.20 - 0.34 IU/mL; borderline positive [BP], 0.35 - 0.99 IU/mL) were applied to each test re-sult. After applying the borderline range, 26.4% of the positive results were classified as BP (4% of total results), while 4.2% of the negative results were classified as BN (3.6% of total results). Among seven HCWs with initial results in the borderline range, two had repeated borderline results while 71.4% had low negative results. We recommend the introduction of borderline ranges in the interpretation of QFT-GIT results to reduce unnecessary TB therapy in HCWs.

Latent tuberculosis infection among patients with type 2 diabetes mellitus

Background Although there is well-proved association between type 2 diabetes mellitus (T2DM) and active tuberculosis, factors involved in the association between T2DM and latent tuberculosis infection (LTBI) are scarcely known. Aim The aim of this study was to study the prevalence and risk factors of LTBI in a cohort of Egyptian adults with T2DM including studying the effect of oral hypoglycemic drugs on this prevalence. Patients and methods All patients with T2DM were recruited from Menoufia University Endocrinology outpatient clinic during the period from June to December 2018. Demographic and clinical data, serum glucose and glycosylated hemoglobin (HbA1c) level, and QuantiFERON-TB Gold In-Tube and tuberculin skin test were assessed. Results In all, 102 patients were recruited, according to the QuantiFERON test; 22 (21.6%) patients were diagnosed with LTBI. Their mean age was 54.91±8.85, mean T2DM duration was 9.82±6.54/year, mean HbA1c% was 10.29±1.59, which is significantly higher than patients without LTBI. Patients on metformin-containing regimens were only 18% (four of 22 cases) among the LTBI patients, and 89.7% of the whole patients with metformin-containing regimen were without LTBI. Multivariant regression showed that age (odds ratio=1.178, P=0.041) and HbA1c% (odds ratio=2.789, P=0.008) were strong predictors for LTBI. Conclusion LTBI is prevalent in patients with T2DM especially among those with older age, longer duration of diabetes mellitus, uncontrolled diabetes mellitus, and on nonmetformin regimens. Age and HbA1c are strong predictors of LTBI in T2DM patients.

Tuberculin Skin Test Versus the Interferon-γ Release Assays: Out With the Old, In With the New

* Abbreviations: BCG — : Bacillus Calmette-Guerin IGRA — : interferon-γ release assay QFT — : QuantiFERON-TB Gold In-Tube TST — : tuberculin skin test The tuberculin skin test (TST) for determining if a person is infected with Mycobacterium tuberculosis has been the dominant test for a century. The interferon-γ release assays (IGRAs) have been available for a decade; dozens of studies have compared the performance of the 2 types of tests in a variety of settings. The advantages of the IGRAs have led some experts to recommend the “retirement” of the TST, even in pediatrics.1 However, the best use of the IGRAs in young children remains controversial because of a paucity of data.2 Both test types depend on the cellular immune response to mycobacterial antigens. Purified protein derivative, the solution used in the TST, has dozens of antigens, some of which are also found on many species of nontuberculous mycobacteria and the Bacillus Calmette-Guerin (BCG) vaccines, leading to low test specificity. The IGRAs use only 2 or 3 antigens that do not cross-react with most nontuberculous mycobacteria and BCG and consistently have higher specificity than the TST.3 Unfortunately, both test types have lower sensitivity in individuals with diminished cellular immunity who are at high risk of having tuberculosis infection progress to disease, and neither test type … Address correspondence to Jeffrey R. Starke, MD, FAAP, Baylor College of Medicine, Texas Children’s Hospital, MC 3-2371, Bates Ave, Houston, TX 77030. E-mail: jstarke{at}bcm.edu

Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain.

PurposeThe prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea.Materials and MethodsPulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed.ResultsStatistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95–100%).ConclusionOur data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.

The use of GeneXpert Mycobacterium tuberculosis/rifampicin assay in diagnosis of pulmonary tuberculosis in children

Introduction Rapid diagno sis of tuberculosis (TB) is essential for early disease management. GeneXpert (GX) test is a novel rapid diagnostic modality. In this study, we aimed to evaluate the diagnostic role of GX test in diagnosing pulmonary tuberculosis (PTB) in children as well as detection of rifampicin (RIF) resistance. Patients and methods This was a cross-sectional study that included 80 patients suspected to have PTB based on clinical data together with at least one of the followings: a positive tuberculin skin test or QuantiFERON-TB Gold In-Tube test result, a positive blood TB PCR result, or a positive Ziehl–Neelsen staining result. Results PTB was more common in older females. Extrapulmonary manifestations and hilar lymphadenopathy were more frequent in younger age. Both positive tuberculin skin test and positive GX were more frequent in older age. Positive GX was found in 30 (37.5%) cases, and RIF resistance was detected in two (6.6%) of them. Positive GX results were more frequent in sputum than gastric aspirate samples. Positive GX results were more frequent with absent Bacillus Calmette–Guerin scar, and with hemoptysis, failure to thrive, cavitary lung lesions, and lower mean hemoglobin. Conclusion GX detects many more cases than blood PCR and Ziehl–Neelsen stain. GX had 70% sensitivity and 95% specificity in diagnosing PTB, with overall diagnostic accuracy of 86.67%, with better performance in older children who could expectorate. RIF resistance was ∼6.6%.