QuantiFERON-TB Gold Research Articles

Prevalence and factors associated with tuberculosis infection in India

BackgroundThe risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection. MethodsIndividuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated. ResultsOf the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 −25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29–1.73), being male (aRR:1.26; 95%CI: 1.18–1.34), residing in urban location (aRR:1.58; 95%CI: 1.03–2.43) and past history of TB (aRR:1.49; 95%CI: 1.26–1.76). ConclusionAbout one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India.

Low performance of interferon gamma release assay Quantiferon-TB gold coupled or not with Pst1/3/lipoglycan humoral detection to predict Mycobacterium tuberculosis complex disease in a low-burden area

Whole T cell interferon gamma release assays such as QuantiFERON-TB Gold Plus (QTF-TB) are used to evaluate Mycobacterium tuberculosis complex (MTC) exposure but fail to discriminate latent tuberculosis infection (LTBI) from active disease. In this study conducted in a low-burden area, 1215 patients presenting MTC risk and tested both for QTF-TB and mycobacterial infection (microscopy, culture, and/or PCR) were selected, as well as 1298 controls screened with QTF-TB before medical recruitment. The humoral response (LIODetect®TB-ST) was further evaluated in 199 selected patients. In patients with active disease, MTC positivity (culture and/or PCR with species identification) was associated with QTF-TB positivity (45/56, 80.4 %). Although QTF-TB1/TB2 peptides were not suitable for discriminating against active MTC disease from LTBI, the cut-off value of 4.4 IFN-γ IU/mL produced the best diagnostic performance for MTC detection. Lower levels of QTF-TB were reported among patients with isolated active pulmonary MTC as compared to a lymph-nodal location and a disseminated form. Next, antibodies were detected in 4/55 (7.3 %) active MTC disease cases, while negative in cases of LTBI and indeterminate/negative QTF-TB. In conclusion, the added value to combine cellular (QTF-TB) and humoral (LIODetect®TB-ST) assays to predict an active MTC disease is limited.

SAT245 Hips Don’t Lie: A Case Of Peri-Prosthetic Pseudotumor Leading To Hypercalcemia After Total Hip Replacement.

Abstract Disclosure: F. Sotomayor: None. H. Whitlatch: None. Background: Peri-prosthetic pseudotumors are well described, yet rare complications of total hip replacement. They can present as destructive or granulomatous lesions. We present the first documented case of 1,25 vitamin D-mediated severe hypercalcemia caused by a periprosthetic granuloma. Case: A 62-year-old man with a history of osteoporosis, ankylosing spondylitis presented with hypercalcemia (calcium 12.2 mg/dL) on routine laboratory testing. He had a history of bilateral cement hip arthroplasty in 1981 followed by multiple bilateral revisions - three revisions of left hip arthroplasty, one revision of right hip arthropasty. Biochemical evaluation included PTH 5 pg/mL (8 - 54 pg/mL), PTHrP 2.7 pmol/L (0.0 - 2.3 pmol/L), vitamin D-25 59 ng/mL (20-80 ng/mL), a negative Quantiferon TB Gold, and normal serum protein electrophoresis. 1,25 Vitamin D was elevated at 280.5 pg/mL (19.9-79.3 pg/mL). During investigation of 1,25 vitamin D-mediated hypercalcemia, he received a dose of zoledronic acid with transient improvement in hypercalcemia. ACE was negative and CT chest and abdomen was without evidence of granulomatous disease. A whole-body PET scan showed increased metabolic activity surrounding the right femoral and acetabular components with a broad zone of osteolysis in the proximal femur and increased metabolic activity surrounding the left greater trochanter. These findings were concerning for inflammatory granuloma formation. He was prescribed prednisone 30 mg daily with rapid normalization of serum calcium. Prednisone was gradually tapered to 10 mg daily with maintenance of normocalcemia. Discussion: Pseudotumors are an uncommon complication of total hip arthroplasty. These are described as non-infectious and non-neoplastic adverse soft tissue reactions to implants. They manifest as destructive or granulomatous periprosthetic lesion. They cause osteolysis, erosions, pathological fractures, and dislocations. Their formation is due to foreign body reaction to polyethylene, methylmethacrylate, cement or metal adjacent to the joint implant. Associated inflammation leads to macrophage activation, prostaglandin release, and osteolysis. Histologically, they are characterized by the presence of macrophages, extensive coagulation necrosis, lymphocytes, eosinophilic infiltration and granulomatous reaction. While non-malignant, they can cause extensive bony destruction and may require complex revision surgery. To date, this is the first reported case of hypercalcemia due to excess 1,25 vitamin D caused by a periprosthetic granuloma. Conclusion: Hypercalcemia is a well-described complication of granulomatous diseases, including sarcoidosis, mycobacterium infection, and lymphoma. In patients with a history of arthroplasty, we recommend adding peri-prosthetic pseudotumors to the differential diagnosis of 1,25 vitamin D mediated hypercalcemia. Presentation: Saturday, June 17, 2023

FRI696 Endocrine Shades Of Silicone Fillers: A Case Of Calcitriol-mediated Hypercalcemia

Abstract Disclosure: M.S. Martinez Cruz: None. T.G. Lozovoy Madsen-Barbosa: None. C.J. Haas: None. Introduction: In rare cases, foreign body granuloma (FBG) reaction is so vast that it leads to severe systemic disease, including increased granuloma-mediated production of calcitriol. Case Description: A 42-year-old woman was referred to the ED due to elevated serum calcium and worsening GFR on routine blood work. She endorsed a two-week of generalized weakness, myalgias, polyuria, polydipsia, and intermittent constipation with prior episodes of such symptomatology. On her first presentation, severe hypercalcemia (13.8 mg/dL), acute-on-chronic renal disease, a normal TSH, an appropriately low PTH, elevated PTHrP, a low 25-hydroxy vitamin D, and a normal 1,25 dihydroxy-vitamin D were noted. She was treated with IV fluids and zoledronic acid 4mg IV one time with subsequent normalization of calcium levels. Six months later, she was re-admitted with similar complaints. Additional blood workup was unremarkable, including urine and serum protein electrophoresis and kappa/lambda ratio. She once again presented with similar complaints; additional workup revealed a normal 25-hydroxy vitamin D, mildly elevated serum angiotensin-converting enzyme, and a negative QuantiFERON-TB gold, but a marked elevation of 1,25 dihydroxy-vitamin D (138 pg/mL). She admitted to subcutaneous silicone filler injections in the lips, cheeks, and hips applied by a non-healthcare provider six years ago. She described that one year after the injections, she had noted intermittently indurated erythematous areas in the skin of the hips and upper lateral thighs that were notably tender to palpation. Diagnostic imaging included a whole-body PET-CT that demonstrated moderate FDG uptake within the subcutaneous adipose tissue of the lateral aspect of bilateral gluteal regions extending from the iliac crests to the upper thighs. She was diagnosed with silicone filler injection-induced hypercalcemia secondary to granulomatous inflammation and initiated on prednisone 20 mg PO daily with progressive normalization in her hypercalcemia (9.7 mg/dl) a month after initiation of treatment. Unique features/Teaching points: FBG reactions occur more commonly against permanent fillers like silicone, especially if injected in larger volumes and highly vasculature areas like hips or buttocks. These reactions may occur years after the initial injection. In rare cases, significant granulomatous immune response leads to the overactivity of 1-alpha-hydroxylase in activated macrophages, resulting in uncontrolled overproduction of calcitriol and, subsequently, hypercalcemia. FBG reactions may also cause increased levels of PTHrP, further contributing to hypercalcemia. Treatment focuses on general hypercalcemia management and FBG remission, most effectively achieved with anti-inflammatory corticosteroid doses. Further studies are needed to evaluate long-term treatment efficacy. Presentation: Friday, June 16, 2023

Case Report: Bilateral optic disc swelling in a patient with tuberculoma

BACKGROUND: In children, tuberculosis of the central nervous system most usually manifests as tubercular meningitis, hydrocephalus post-tubercular meningitis, and, in rare cases, space-occupying lesions known as tuberculoma. We address the diagnostic difficulty in an adult patient with mainly ocular symptoms who was diagnosed with tuberculoma. A 19-year-old young man came with painless bilateral blurring of vision. Bilateral optic disc swelling and bilateral sixth cranial nerve palsy were present. METHODS: Brain imaging revealed ring-enhancing lesions in the cerebellar vermis, left cerebellar hemisphere and left middle cerebral peduncle with surrounding extensive perilesional edema causing effacement of fourth ventricle leading to obstructive hydrocephalus suggestive of tuberculoma. RESULTS: He had a high erythrocyte sedimentation rate and a positive Mantoux test. His Quantiferon-TB Gold test result was positive. The examination of cerebrospinal fluid suggested a high opening pressure. Following anti-tubercular medication along with systemic steroids, his vision improved due to decreased optic disc swelling. CONCLUSION: We wish to highlight that visual loss and grave consequences of tuberculoma can be averted with early recognition and treatment.

Predicting stringent QuantiFERON-TB Gold Plus conversions in contacts of tuberculosis patients.

To assess associations between disease severity in index TB patients and QuantiFERON-TB Gold Plus (QFT-Plus) results in contacts, and predictors for QFT-Plus conversion in contacts over 6-12 months. TB patients (n=295) and the contacts (n=1051) were enrolled during 2018-2021 with QFT-Plus performed at baseline and months 6 and 12. A strong CD8 response was defined as TB2 interferon gamma (IFN-γ) response minus TB1 >0.6 IU/ml and stringent conversion as change from QFT-plus negative to high-positive QFT-Plus (TB1 or TB2 IFN-γ responses >0.7 IU/ml). Contacts with index TB patients with sputum smear >1+ was associated with positive QFT-Plus compared to those without (p<0.001). Contacts with index TB patients with bilateral lung disease were more likely to have strong CD8 responses than those without (p=0.038). QFT-Plus stringent conversion occurred in 9.7% of contacts over 6-12 months. A TB1 IFN-γ response ≥0.03 IU/ml combined with a TB2 ≥0.06 IU/ml was predictive of a 19-fold increased risk for QFT-Plus stringent conversion in contacts (odd ratio 19.565 [8.484-45.116], p<0.001). Bacterial burden and bilateral lung disease of index TB patients were associated with positive QFT-Plus and strong CD8 responses in contacts. TB1 and TB2 IFN-γ responses were synergistically predictive of stringent conversion in contacts.

Prevalence and risk factors of M tuberculosis infection in young people across 14 communities in Zambia and South Africa.

From 2018-2021 the TB Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) project took place in 21 Zambian and South African communities. The TREATS Incidence of TB Infection Cohort Study was conducted in adolescents and young people (AYP), aged 15-24 years in 14 communities. We describe the baseline prevalence and risk factors of Mycobacterium tuberculosis (M. tuberculosis) infection among this cohort and explore the quantitative QFT-Plus interferon gamma (IFN-γ) responses. A random sample of approximately 300 AYP per community were recruited and information on TB/HIV risk factors, TB symptoms and social mixing patterns collected. QuantiFERON TB Gold Plus assay (QFT-Plus) was used to detect M. tuberculosis infection, following manufacturer's instructions. Logistic regression was used to determine factors associated with infection. 5577 eligible AYP were invited to participate across both countries, with 4648 enrolled. QFT-Plus results were available for 4529: 2552(Zambia) and 1977(South Africa). Overall, 47.6% (2156/4529) AYP had positive QFT-Plus results, the prevalence of infection in South Africa being twice that in Zambia (64.7% (1280/1977) vs 34.3% (867/2552) p<0.001). Infection was associated with age, household contact with TB and alcohol in Zambia but showed no associations in South Africa. The antigen tube differential (TB2-TB1>0.6 IU/ml) of the assay at baseline showed no evidence of association with recent TB exposure. The high prevalence of infection in AYP warrants urgent action to address TB control, especially in South Africa. Further research is required to delineate antigen tube responses of the QFT-Plus assay more precisely to fully realise the benefit of the additional TB2 tube in high TB/HIV burden settings.

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.

B-036 Multi-Biomarker Approach to Latent Tuberculosis Diagnosis Using Microring Resonator Sensors

Abstract Background Tuberculosis (TB) is an infectious disease that induces a complex response from the host immune system. Most carriers of the bacteria experience the asymptomatic, non-infectious phase, latent tuberculosis infection (LTBI), but have the potential to reactivate to active, contagious TB infection. Current diagnostics for TB are not sufficient for LTBI and are focused on using one biomarker, interferon-gamma (IFN-g). To build better diagnostics for the complex disease, multi-biomarker approaches to profile the immune system, coupled with machine learning algorithms, are necessary to diagnose LTBI and determine patients' risks of reactivation to active TB. We aim to use a multiplexed silicon photonic microring resonator sensing platform to profile thirteen biomarkers in patients with LTBI infection and use machine learning data analysis to identify biomarkers relevant for diagnosing LTBI and predicting reactivation risk. Methods We employed microring resonators coupled with a sandwich-style detection format to simultaneously detect thirteen cytokines and chemokines in plasma in under 40 minutes. Chip-integrated silicon photonic microrings are small in size and easily multiplexed with up to sixteen different capture agents. Biomolecular binding events are measured by monitoring the resonant wavelength within the sensing cavity, which shifts as binding events occur. Quantitation of each biomarker is possible with calibration curves that correlate standard protein concentrations to wavelength shifts. The multiplexed assay has been optimized for each individual biomarker, tested for cross-reactivity, and calibrated in the plasma matrix of interest. The LODs vary, depending on biomarker and matrix dilution, but range from 4.9 pg/mL to 691 pg/mL. The patient plasma samples are left over from the TB screening IFN-g release assay, QuantiFERON-TB Gold Plus (QFT), putting this method within the current clinical workflow. We use precision normalization approaches from the four QFT stimulations to account for immunologic differences among the subjects. The biomarker concentrations are evaluated using a random forest machine learning model to identify which biomarkers are important for identifying patients with LTBI and predicting their reactivation risk. Results We used this sensor method to profile 42 patients, 24 LTBI negative controls and 18 LTBI positive controls, with 13 being considered at high risk of reactivation. Using a precision normalization approach, a combination of nine normalized conditions using five of the thirteen biomarkers (CCL4, CCL8, IP-10, IL-2, IL-17) discriminated between LTBI positive and negative subjects with a ROC AUC of 0.90. Additionally, eight normalized conditions using four of the same biomarkers discriminated between high and low-risk subjects with an AUC of 0.83. Currently, we have expanded the sample cohort to include an additional 72 subjects, 25 LTBI positive and 47 LTBI negative. Preliminary analysis shows CCL8, IL-2, and IP-10 alone are able to distinguish between LTBI status (P values &amp;lt;0.01) using raw target concentrations prior to precision normalization. Conclusion Overall, we show the importance of multi-biomarker approaches to develop diagnostic and prognostic tools for a complex disease, such as TB. Further work to use the initial machine learning algorithm with the expanded cohort to validate biomarker importance is underway.

Comparison of the Standard E TB-Feron ELISA and QuantiFERON-TB Gold PLUS assays: the advantageous use of whole recombinant protein antigens for latent tuberculosis diagnosis.

The laboratory diagnosis of latent tuberculosis is often performed using interferon-gamma release assays. Here, we compared two enzyme-linked immunosorbent assay-based interferon-gamma release assays, namely, the newly developed Standard E TB-Feron enzyme-linked immunosorbent assay (STFE) and the QuantiFERON-TB Gold PLUS assay (QFT-GP), using samples from 155 participants. The STFE is based on using whole EAST6 and CFP10 recombinant antigens for latent tuberculosis diagnosis. The participants were classified into four groups and screened using both assays per the manufacturers' instructions. Thereafter, two statistical analyses were conducted to compare the obtained results. First, the STFE results were compared with the QTF-GP results (used as the gold standard) to calculate the total concordance, sensitivity, and specificity of STFE. Second, positivity and negativity concordances were calculated to differentiate healthy participants from participants with tuberculosis. The STFE showed 97% and 94% sensitivity and specificity, respectively. Furthermore, its positivity and negativity concordances were 91% and 98%, respectively. These results indicate the coordinated clinical performance of STFE in detecting latent tuberculosis and its improved performance in targeting tuberculosis-infected participants. Based on the comparison of the latent tuberculosis diagnostic abilities of STFE and QFT-GP, we establish the suitability and superior performance of STFE as a diagnostic tool.

Comparative performance evaluation of QIAreach QuantiFERON-TB and tuberculin skin test for diagnosis of tuberculosis infection in Viet Nam

Current WHO-recommended diagnostic tools for tuberculosis infection (TBI) have well-known limitations and viable alternatives are urgently needed. We compared the diagnostic performance and accuracy of the novel QIAreach QuantiFERON-TB assay (QIAreach; index) to the QuantiFERON-TB Gold Plus assay (QFT-Plus; reference). The sample included 261 adults (≥ 18 years) recruited at community-based TB case finding events. Of these, 226 underwent Tuberculin Skin Tests and 200 returned for interpretation (TST; comparator). QIAreach processing and TST reading were completed at lower-level healthcare facilities. We conducted matched-pair comparisons for QIAreach and TST with QFT-Plus, calculated sensitivity, specificity and area under a receiver-operating characteristic curve (AUC), and analyzed concordant-/discordant-pair interferon-gamma (IFN-γ) levels. QIAreach sensitivity and specificity were 98.5% and 72.3%, respectively, for an AUC of 0.85. TST sensitivity (53.2%) at a 5 mm induration threshold was significantly below QIAreach, while specificity (82.4%) was statistically equivalent. The corrected mean IFN-γ level of 0.08 IU/ml and corresponding empirical threshold (0.05) of false-positive QIAreach results were significantly lower than the manufacturer-recommended QFT-Plus threshold (≥ 0.35 IU/ml). Despite QIAreach’s higher sensitivity at equivalent specificity to TST, the high number of false positive results and low specificity limit its utility and highlight the continued need to expand the diagnostic toolkit for TBI.

Exploration and improvement of QuantiFERON-TB assay in patients with indeterminate results in clinical practice: A head-to-head study

BackgroundWe implemented the QuantiFERON-TB Gold In-Tube (QFT-GIT) based on peripheral blood mononuclear cells (QFT-PBMCs) and QFT Gold Plus (QFT-Plus) in patients with indeterminate results, and use Mit-Nil value to identify false negatives and impaired cellular immunity. MethodsOne hundred seventy-one out of 2480 patients who had a QFT-GIT test were prospectively recruited and classified as high Nil (n = 35), low Mit (n = 75) and control (n = 61) cohorts. Head-to-head comparisons, i.e., QFT-PBMCs vs. QFT-GIT in high Nil cohort, QFT-Plus vs. QFT-GIT in low Mit cohort, and QFT-PBMCs vs. QFT-GIT in controls, were performed. Lymphocyte subsets counts were conducted in low Mit and control cohorts. ResultsA significant reduction of positive rate only occurred in Mit-Nil < 6 IU/ml (p < 0.001). QFT-PBMCs yielded 100 % valid results and had a significant Nil decline in high Nil cohort (0.98 ± 1.06 vs. 9.55 ± 0.64 IU/ml, p < 0.0001), while correlated well with QFT-GIT for qualitative (Cohen’s k = 0.93) and quantitative (TB–Ag [R2 = 0.91] and Mit [R2 = 0.94]) analyses. QFT-Plus produced 61.3 % valid results and had a significant Mit increase in low Mit cohort (0.82 ± 0.95 vs. 0.17 ± 0.11 IU/ml, p < 0.0001). Mit-Nil value significantly correlated with lymphocyte subsets counts (R:0.49–0.56, p < 0.0001), separately corresponding to thresholds of 4.26, 5.33, 5.55 and 5.81 IU/ml for predicting decreased total lymphocyte, T lymphocyte, CD4+ and CD8+ cells. ConclusionsQFT that replacing whole blood with PBMCs should be recommended to handle high Nil samples, and QFT-Plus can declined the frequency of low Mit results. In addition, Mit-Nil < 6 and 5.81 IU/ml are potential thresholds to identify the risk of false negatives and impaired cellular immunity, respectively.

P-472 Evaluation of the usefulness of the QuantiFERON-TB gold in-tube test for the detection of latent mycobacterium tuberculosis infections in patients underwent autologous stem cell transplantation

P-472 Evaluation of the usefulness of the QuantiFERON-TB gold in-tube test for the detection of latent mycobacterium tuberculosis infections in patients underwent autologous stem cell transplantation

Reversions of QuantiFERON-TB Gold Plus in tuberculosis contact investigation: A prospective multicentre cohort study.

Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments.

Nomogram to determine predictive risk for active tuberculosis based on the QuantiFERON-TB Gold In-Tube test.

Interferon-γ release assay (IGRA) is a widely used blood test for detecting TB infection. However, a positive result of IGRA cannot differentiate active tuberculosis (ATB) infection from inactive tuberculosis (IATB). In this study, we established a nomogram model for predictive risk of ATB, differentiated from IATB, based on the concentration of interferon-γ (IFN-γ) of QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and clinical characteristics. Participants with a positive QFT-GIT result were recruited and divided into a training and validation cohort according to hospitalisation date. The nomogram model for the differential diagnosis of ATB from IATB was established according to gender, age, pleural effusion (PE), and the concentration of IFN-γ in the Nil, TB antigen, and mitogen tube of QFT-GIT in the training cohort by logistic regression and validated in the validation cohort, and then combined with adenosine deaminase (ADA) to evaluated the performance value in ATB cases with PE. The area under receiver operating characteristic curve (AUC) of the diagnostic nomogram model, which we called the NSMC-ATB model for ATB diagnosis was 0.819 (95% CI 0.797-0.841), with sensitivity 73.16% and specificity 75.95% in training cohort, and AUC was 0.785 (95% CI 0.744-0.827), with sensitivity 67.44% and specificity 75.14% in validation cohort. A combination of the NSMC-ATB model and ADA performed better than the NSMC-ATB model and ADA alone in predicting ATB cases with PE, as AUC was 0.903 (95% CI 0.856-0.950) with sensitivity 78.63% and specificity 87.50%. We established an effective diagnostic nomogram model, called the NSMC-ATB model to differentiate ATB from IATB. Meanwhile, the combination of the NSMC-ATB model and ADA improved the performance value of ATB with PE.

Latent tuberculosis infection in the outpatient general medicine clinic: Efficacy of a nurse-run electronic directly observed treatment program

Tuberculosis (TB) is a leading cause of infectious death worldwide, with nearly 2 billion currently infected globally. While the largest burden of active TB resides in low to middle-income countries, the US contributes to the global epidemic and can play a significant role in interrupting the spread of TB by recognizing and treating latent TB infection (LTBI). The vast majority of active TB in the US originates from the reactivation of LTBI.This cross-sectional study examines the prevalence of LTBI in a general medicine practice and explores the efficacy of a primary care nurse-run electronic directly observed therapy (eDOT) treatment program. 1221 patients were screened for the presence of historical risk factors for LTBI. Of those screened, 192 were offered QuantiFERON-TB Gold Plus (QFT-Plus) testing and a CXR if indicated, resulting in 35 being offered treatment for LTBI. After an initial provider visit to decide on the treatment regimen, patients received weekly nurse calls to verify adherence, assess for side effects and answer additional patient questions. Provider follow-up appointments occurred at the midpoint and completion of treatment.33 (94%) of patients with LTBI completed treatment. Patients found the nurse calls very helpful to reassure them about their treatment and to address treatment concerns.Primary care providers are particularly well-positioned to identify and treat LTBI. Screening is simple and treatment is generally well tolerated. Utilization of a nurse-run eDOT) program can be quite helpful in facilitating adherence and treatment completion.

Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies.

This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

Association of Mycobacterium tuberculosis infection test results with risk factors for tuberculosis transmission

BackgroundClose contacts infected with Mycobacterium tuberculosis are at high risk of tuberculosis (TB) disease and a priority for preventive treatment. Three tests measure infection: two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). The objective of our study was to assess the association of positive test results in contacts with infectiousness of the presumed TB source case. MethodsContacts in a cohort study at 10 United States sites received both IGRAs (QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT)) and TST. We defined test conversion as negative for all tests at baseline and positive for at least one on retest. Risk ratios (RR) and 95% confidence intervals (CI) assessed association of positive test results with increased infectiousness of the TB case—defined as acid-fast bacilli (AFB) on sputum microscopy or cavities on chest radiographs— and contact demographics. ResultsAdjusted for contacts’ age, nativity, sex, and race, IGRAs (QFT-GIT RR = 6.1, 95% CI 1.7–22.2; T-SPOT RR = 9.4, 95% CI 1.1–79.1), but not TST (RR = 1.7, 95% CI 0.8–3.7), were more likely to convert among contacts exposed to persons with cavitary TB disease. ConclusionsBecause IGRA conversions in contacts are associated with infectiousness of the TB case, their use may improve efficiency of health department contact investigations by focusing efforts on those likely to benefit from preventive treatment in the United States.

Smoking is a Factor in Discordance Between QuantiFERONTB Gold Assay and Tuberculosis Etiology: Especially in Older Patients.

Exploring whether smoking is an influencing factor for the inconsistency between QuantiFERONTB Gold assay (QFT-GIT) and tuberculosis etiology. The clinical data of patients who were confirmed positive for Mycobacterium tuberculosis (MTB) after undergoing QFT-GIT testing from September 2017 to August 2021 were retrospectively analyzed. Chi-square and rank-sum tests were used to compare the differences in characteristics between smokers and non-smokers. Logistic regression was used to adjust for confounding factors affecting smoking. Propensity score matching (PSM) was used to verify the above conclusions again. Positive results of tuberculosis etiology were adopted as the standard, the incidence of inconsistent results between QFT-GIT and tuberculosis etiology was 8.90% (108/1213), of which the false negative rate was 6.27% (76/1213) and the indeterminate rate was 2.64% (32/1213). In the overall population, the smokers had a lower level of basal IFN-γ (Z=-2.079, P=0.038). Among 382 elderly (≥65 years old) patients, the smokers had lower levels of antigen-stimulated IFN-γ (Z=-2.838, P=0.005). After performing BOX-COX transformation on all non-normally distributed data, logistic stepwise regression was used to adjust confounding factors. The results showed that smoking was an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiology results (OR=1.69, P=0.020). Using PSM for 1:2 matching, the results showed that smoking was still an independent risk factor for the inconsistent results of QFT-GIT and tuberculosis etiology (OR= 1.95, P=0.019). Age-stratified analysis showed that smoking was an independent risk factor in discordance between QFT-GIT and tuberculosis etiology in patients aged ≥65 years (OR=2.40, P=0.005), but not in patients aged <65 years (P > 0.05). Smoking can reduce the body's IFN-γ release ability, and smoking (especially the elderly) is an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiological results.

Prevalence of Latent Tuberculosis Infection (LTBI) in Mexican Patients With Rheumatoid Arthritis (RA).

Patients with rheumatoid arthritis (RA) are at increased risk of developing tuberculosis, and even more so if they receive biological agents. In Mexico, the prevalence of latent tuberculosis infection (LTBI) in RA diagnosed by interferon-gamma release assay (IGRA) is largely unknown. The objective was to determine LTBI prevalence and the associated risk factors in rheumatoid arthritis patients. A cross-sectional study was performed comprising 82 patients with RA who attended the rheumatology service at a second-level hospital. Demographic characteristics, comorbidity, Bacillus Calmette-Guerin (BCG) vaccination and smoking history, type of treatment, disease activity and functional capacity were investigated. The Disease Activity Score 28 and the Health Assessment Questionnaire-Disability Index were applied for the estimate of RA activity and functional capacity. Further information was compiled from the electronic medical records and personal interviews. LTBI was determined by QuantiFERON TB Gold Plus (QIAGEN, Germantown, USA). Prevalence of LTBI was 14% (95% confidence interval (CI): 8.6% to 23.9%). Factors associated with LTBI were history of smoking (odds ratio (OR) = 6.63 95% CI 1.01 to 43.3) and disability score (OR = 7.19 95%CI 1.41 to 36.6). The prevalence of LTBI in Mexican patients with RA was 14%. Our results suggest prevention of smoking and functional incapacity could reduce the risk of LTBI. Further research could endorse our results.