QuantiFERON-TB Gold In-Tube Research Articles

Tuberculosis infection among close contacts of patients with pulmonary tuberculosis in China: a population-based, multicentered study

ObjectivesLimited information is currently available on the prevalence of and risk factors for tuberculosis infection (TBI) among close contacts of patients with pulmonary TB (PTB) in China. In this study, we estimated the burden of TBI among close contacts using QuantiFERON-TB Gold In-Tube assay (QFT) and identified factors associated with TB transmission among this high-risk population. MethodsFrom January 1, 2018 to August 31, 2020, we identified laboratory-confirmed patients with PTB from a population-based, multicentered, cluster-randomized control trial for tuberculosis preventive treatment. Close contacts of these patients were identified, interviewed, and tested using the QFT assay. We estimated TBI prevalence and calculated ORs and 95% CIs for TBI risk factors. ResultsA total of 3138 index cases and 8117 close contacts were identified. Of these contacts, 36 had PTB (a prevalence of 443.51 cases/100 000 population). Among the remaining 7986 close contacts; 3124 (39.12%) reported a positive QFT result. QFT positivity was significantly associated with older age (adjusted OR, 1.77; [95% CI, 1.27–2.47], 2.20; [95% CI, 1.59–3.05], and 2.74; [95% CI, 1.96–3.82]) for age groups: 35–44, 45–54, and 55–64, respectively) when compared with a younger age group: 5–14; longer contact duration (adjusted OR, 1.44; 95% CI, 1.22–1.69); and sharing of a bedroom (adjusted OR, 1.39; 95% CI, 1.18–1.65). DiscussionOur findings indicate a high TBI burden among the close contacts of PTB. The results also highlighted that contact tracing and investigation for TBI are necessary and beneficial, particularly for those who are older, have had a longer contact duration, and share a bedroom.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease

Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Tuberculosis infection and hypertension: prevalence estimates from the US National Health and Nutrition Examination Survey

ObjectivesTuberculosis infection (TBI) is marked by dynamic host–pathogen interactions with persistent low-grade inflammation and is associated with increased risk of cardiovascular diseases (CVD) including acute coronary syndrome, myocardial infarction and...

CD8+ T cell response in QuantiFERON-TB Gold Plus testing was associated with tuberculosis recurrence: a 2-year prospective study

Background Recurrence posed an important challenge to pulmonary tuberculosis (PTB) control in China. The prospective study aimed to identify potential risk factors and to explore the value of QuantiFERON-TB Gold Plus (QFT-Plus) in identifying at-risk individuals with treated prior PTB history. Methods All eligible individuals aged ≥18 years who had been diagnosed with PTB before 2016 in Zhongmu County, where with an average level of TB prevalence in China, were included and received baseline survey including chest radiography, QuantiFERON-TB Gold In-Tube (QFT-GIT) and QFT-Plus, then PTB recurrence was tracked through a 2-year follow-up. Results Half of 1068 (52.34%, 559/1068) included eligible participants were QFT-Plus positive at baseline and 21 of them recurred active TB in 2-year follow-up. Individuals aged ≥ 60 years, who had a recent history of TB and smokers were associated with increased risk of TB recurrence with an adjusted odds ratio (aOR) of 3.97 (95% confidence interval (CI): 1.29–12.24), 7.71 (95% CI: 1.74–34.25) and 4.56 (95% CI: 1.62–12.83), respectively. Compared to QFT-Plus negatives, those who were TB2+/TB1- (aOR = 15.34) exhibited stronger association with the risk of TB recurrence than those who were TB1+/TB2+ (aOR = 6.06). A dose response relationship was also found between the risk of TB recurrence with the baseline level of TB2-TB1 (p for trend < 0.001). Conclusions High burden of TB infection and high risk of PTB recurrence were observed in the study population. Those with recent onset of prior TB, elderly smokers and QFT-Plus positives especially with TB2 single positive deserved further attention in active TB surveillance.

Tuberculous peritonitis: an analysis of case series of 49 consecutive patients

Objectives: The incidence of tuberculous peritonitis has been reported between 0.1% and 0.7% among all tuberculosis types. This study, it was aimed to evaluate the cases with tuberculous peritonitis, which has an important place in the differential diagnosis of patients with ascites, clinically, biochemically, microbiologically, and histopathologically. Methods: : Forty-nine patients with a definite clinical, radiological, and histopathological diagnosis of tuberculous peritonitis, which formed the basis of our study, were analyzed retrospectively. Results: The mean age of patients with tuberculous peritonitis was found to be 39.45 ± 19.02 years. Purified-protein derivative (PPD) was positive in 23 (72%) of 32 patients with tuberculous peritonitis whose PPD results were recorded, in 9 (28%) PPD results were evaluated as anergic or negative. QuantiFERON-TB Gold In-Tube (QFT-GIT) test was sent in 10 of the patients, the result was positive in 9 (90%) patients and negative in 1 (10%) patient. There were 32 patients in whom tuberculosis polymerase chain reaction (PCR) was studied from ascitic fluid, 7 (22%) of the patients were PCR positive and 25 (78%) negative. Mycobacterium tuberculosis culture positivity was found in 18 (69%) of 26 patients who were biopsied. In total, 29 (59%) of the patients had M. tuberculosis culture positivity. Conclusions: Tuberculous peritonitis constitutes a public health problem in endemic regions of the world and tuberculous peritonitis should be considered in patients presenting with ascites. Despite all diagnostic difficulties, necessary tests, especially peritoneal biopsy, should be performed for early diagnosis, and it should not be forgotten that early initiation of treatment is very important in terms of morbidity and mortality of the disease.

Interferon-Gamma Release Assay Combined with Renal Indicators to Reduce the False-Negativity of Latent Tuberculosis Infection in End-Stage Renal Disease with Hemodialysis Patients.

Tuberculosis (TB) is still the main cause of mortality due to a single transfectant, Mycobacterium tuberculosis (MTB). Latent tuberculosis infection (LTBI) is a condition characterized by the presence of tuberculosis (TB) that is not clinically apparent but nonetheless shows a sustained response to MTB. Presently, tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are mainly used to detect LTBI via cell-mediated immunity of T-cells. For people with end-stage renal disease (ESRD), the diagnosis of patients infected with MTB is difficult because of T-cell dysfunction. To get more accurate diagnosis results of LTBI, it must compensate for the deficiency of IGRA tests. Sixty-seven hemodialysis (HD) patients and 96 non-HD patients were enrolled in this study and the study population is continuously included. IFN-γ levels were measured by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Kidney function indicators, blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR) were used to compensate for the declined IFN-γ levels in the IGRA test. In individuals who were previously undetected, the results of compensation with serum Cr increased by 10.81%, allowing for about 28% more detection, and compensation with eGFR increased by 5.41%, allowing for approximately 14% more detectable potential among them and employing both of them could enhance the prior shortcomings of IGRA tests. when both are used, the maximum compensation results show a sensitivity increase rate of 8.81%, and approximately 23% of patients who were previously undetectable may be found. Therefore, the renal function markers which are routine tests for HD patients to compensate for the deficiency of IGRA tests could increase the accuracy of LTBI diagnosis.

Psoriasis'te Biyolojik Tedavi Öncesi Latent Tüberküloz Enfeksiyonunun Değerlendirilmesi: Web Tabanlı Yorumlayıcı ile Yeni Bir Tanı Yaklaşımı

Purpose: The use of biological agents, particularly anti-TNF-alpha treatments, is associated with an elevated risk of tuberculosis (TB). Hence, a comprehensive assessment of latent tuberculosis infection (LTBI) before biologic therapies is imperative. The objective of this study was to evaluate the utility of an online tuberculin skin test (TST)/ interferon-γ release assay (IGRA) interpreter (OI-TST/IGRA) in assessing the risk of LTBI prior to initiating biological therapies in psoriasis patients.&#x0D; Materials and methods: 116 psoriasis patients who were previously evaluated for TB by a pulmonologist before being treated with a biologic agent were re-evaluated retrospectively with OI-TST/IGRA (tstin3d.com). Mean positive predictive value (PPV), mean annual risk of development of active tuberculosis (ARDATB), and mean cumulative risk of active tuberculosis (CRATB) values were calculated with OI-TST/IGRA and compared with previous results. Chi-square, Fisher-Freeman-Halton exact tests, Cohen's Kappa, and Mann-Whitney U-test were used in comparisons of groups. &#x0D; Results: The PPV of the LTBI-positive group was significantly higher than the LTBI-negative group. The PPV, ARDATB and CRATB values of the TST size of &gt;15 mm group were significantly higher than the TST size of 5-9 mm and TST size of 10-15 mm groups. The PPV, ARDATB, and CRATB values of the QuantiFERON-TB Gold In-tube test (QFT-GIT)-positive group were significantly higher than the QFT-GIT-negative group. And the same values of the chest X-ray (CXR)-positive group were significantly higher than the CXR-negative group. The PPV, ARDATB, and CRATB values were positively correlated with QFT-GIT and CXR results. In addition, the PPV was positively correlated with previous LTBI decisions and TSTs.&#x0D; Conclusion: OI-TST/IGRA in which many factors are questioned and PPV, ARDATB, and CRATB values are evaluated together, may be a valuable tool for assessing the risk of active TB in psoriasis patients and preventing overdiagnosis and unnecessary prophylaxis.

Interferon-gamma release assay for screening of tuberculosis infection in children

BackgroundInterferon-gamma release assay (IGRA) is the main tool for the diagnosis of latent tuberculosis (TB) infection (LTBI). However, the indeterminate results were more frequent in children, and the underlying reasons were largely speculative. We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) with X.DOT-TB (XDOT) for diagnosing LTBI, and to identify the risk factors associated with indeterminate results in children.MethodsA retrospective study for children<18 years old, at risk for LTBI or progression to TB disease, received either QFT-GIT or X.DOT-TB tests was performed at Beijing Children’s Hospital from August 2019 to August 2022.ResultsA total of 33,662 children were recruited, including 15,129 (44.9%) tested with X.DOT-TB and 18,533 (55.1%) with QFT-GIT. Proportion of positive and indeterminate results in children with respiratory disease was significantly higher than did that with other diseases, respectively (P < 0.001). The indeterminate rate of X.DOT-TB and QFT-GIT results decreased with increasing age (P < 0.001). Proportion of QFT-GIT indeterminate results was higher than that of X.DOT-TB across age groups. Male, age and disease classification all presented a statistically significant association with indeterminate IGRA results.ConclusionsThe positive rates of X.DOT-TB and QFT-GIT in children were 3.1% and 1.8%, respectively. The X.DOT-TB assay performed better than QFT-GIT in children, and male, age and underlying diseases were associated with an increased risk of indeterminate IGRA results.

Fitness for Work in the Long Journey of Tuberculosis Infection to Chronic Posttuberculosis Disease Case Report and Literature Review

Abstract The long journey of tuberculosis (TB) from exposure to latent or progressive TB infection, from primary stage to second stage of illness with or without infectious status, and then to chronic post-TB sequelae is very complex and still unclear, including a various spectrum of stages and manifestations. A case report of a 55 year-old woman with personal history of pleural effusion, in her youth, 2 previous episodes of COVID-19 infections, having no exposure to active smoking but occupational exposure to wood dust, hot steam, barbeque smoke, was admitted to Constanta Clinical Pneumology Hospital in October 2022 for hemoptysis and fatigue. Clinical and paraclinical investigations highlighted an acute evolutive episode of Pulmonary TB with metastatic bilateral nodular pattern, negative smears, positive cultures and positive QuantiFERON TB Gold in Tube (QFT-GIT). TB standard regimen of therapy was started, based on QFT-GIT positivity, and after it ended, chronic obstructive pulmonary disease was detected by spirometry and small airways dysfunction by impulse oscillometry. TB illness does not stop after directly observed therapy ends. So, systematical screening of pulmonary, bronchial or pleural sequelae should be performed and identified syndromes need to be treated, as well as reintegration in the job process by a careful monitoring.

Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial

Vitamin D supplementation has been shown to increase total hip areal bone mineral density in healthy children and adolescents. We aimed to investigate whether supplementing schoolchildren living in Mongolia with weekly vitamin D3 for 3 years affected fracture risk. We did a multicentre, double-blind, randomised, placebo-controlled trial across 18 public schools in Ulaanbaatar, Mongolia. Schoolchildren were eligible if they were aged 6-13 years at screening, had a negative QuantiFERON-TB Gold In-tube assay (QFT) result, were not hypersensitive to vitamin D or immunocompromised, did not use vitamin D supplements, did not have clinical signs of rickets, and had no intention of leaving Ulaanbaatar within 3 years. Participants were randomly assigned (1:1) to receive either vitamin D (oral dose of 14 000 international units [IU] vitamin D3, once per week) or placebo for 3 years using permuted block randomisation stratified by school of attendance. Participants, care providers, and all trial staff were masked to group assignment during the intervention. Prespecified secondary outcomes were incidence of fractures and adverse events, ascertained using questionnaires. The fracture and safety analyses included participants who completed at least one follow-up fracture questionnaire. We estimated adjusted risk ratios (RRs) and 95% CIs using generalised linear models with binomial distribution and a log link function with adjustment for school of attendance. The trial is registered with ClinicalTrials.gov, NCT02276755, and the intervention ended in May, 2019. Between Sept 2, 2015, and March 20, 2017, 11 475 children were invited to participate in the study and 8851 were recruited and randomly assigned to receive either vitamin D (n=4418) or placebo (n=4433). 8348 participants were included in the fracture and safety analyses (4176 [94·5%] in the vitamin D group and 4172 [94·1%] in the placebo group). Of these, 4125 (49·4%) were female, 4223 (50·6%) were male, and 7701 (92·2%) were of Khalkh ancestry. Median age was 9·2 years (IQR 8·0-10·7) and 7975 (95·5%) participants had baseline serum 25-hydroxyvitamin D concentrations less than 50 nmol/L. During a median follow-up of 3·0 years (IQR 2·9-3·1), 268 (6·4%) participants in the vitamin D group and 253 (6·1%) in the placebo group reported one or more fractures (adjusted RR 1·10, 95% CI 0·93-1·29; p=0·27). Incidence of adverse events did not differ between study groups. Oral vitamin D supplementation at a dose of 14 000 IU/week for 3 years was safe, but did not influence fracture risk in schoolchildren living in Mongolia who had a high baseline prevalence of vitamin D deficiency. US National Institutes of Health.

Increased rates of indeterminate results in QuantiFERON-TB gold in-tube during the COVID-19 epidemic in Hunan province, China

Increased rates of indeterminate QuantiFERON-TB Gold In-Tube (QFT-GIT) results have been reported since the COVID-19 epidemic in Hunan Province, China. The indeterminate result (ITR) rate of QFT increased from an average of 5.2% to 12.4%, paralleling the first COVID-19 pandemic wave in the region. QFT-GIT results of 243 hospitalized patients with COVID-19 from January 2022 to April 2023 at Xiangya Hospital of Central South University were analyzed. Of the 243 patients, 71 (29.2%) had ITRs due to reduced interferon-gamma production in the positive control. Multiple factors are associated with ITRs, such as disease severity, respiratory failure incidence, immunosuppressant use, and prognosis. Additionally, interferon-gamma (Mitogen-Nil) levels differed significantly depending upon disease severity, prognosis, immunosuppressant use, sepsis symptoms, respiratory failure, or hyperlipidemia. An abnormal increase in the ITR rate in the QFT was observed after the COVID-19 pandemic, and an optimal machine learning predictive model for indeterminate QFT results was established.

Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context.

Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh.

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.

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.

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.

Performance of two interferon-gamma release assays for tuberculosis infection screening in Kawasaki children before immunosuppressive therapy.

We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) and X.DOT-TB for screening latent tuberculosis infection (LTBI) in kawasaki patients, and to identify the risk factors associated with indeterminate IGRA results. We conducted a retrospective study on children with KD, who were screened for mycobacterium tuberculosis (Mtb) infection by either ELISA-based QFT-GIT or ELISPOT-based X.DOT-TB tests, admitted in Department of Cardiology, Beijing Children's Hospital from July 2019 to April 2022. A total of 1327 cases were included. Among them, 932 cases were tested by QFT-GIT and 395 cases by X.DOT-TB. The positive rate of children was 0.1% and 0.2%, and the indeterminate rate was 68.2% and 6.1% for QFT-GIT and X.DOT-TB, respectively. Patients with hypoproteinemia had a higher risk of indeterminate X.DOT-TB result. Female, critical ill, shock or hypoproteinemia presented statistically significant associations with an increased risk of indeterminate QFT-GIT result. High-dose of IVIG inhibited the release of IFN-γ by more than 90%, which might account for the high indeterminate incidence. It is recommended to perform X.DOT-TB rather than QFT-GIT to screen LTBI in patients with high level of the mitogen that can inhibit IFN-γ release. For KD children with positive IGRA results, it has a higher risk of activation TB infection when treated with immunosuppressive therapy in the future. Children with KD aged <5 years old had higher frequency of indeterminate IGRA results.

Examining Test Cutoffs to Optimize Diagnosis of Latent Tuberculosis Infection in People Born Outside the United States.

Rationale: Detection of latent tuberculosis infection (LTBI) in persons born in high tuberculosis (TB) incidence countries living in low TB incidence countries is key to TB elimination in low-incidence countries. Optimizing LTBI tests is critical to targeting treatment. Objectives: To compare the sensitivity and specificity of tuberculin skin test (TST) and two interferon-γ release assays at different cutoffs and of a single test versus dual testing. Methods: We examined a subset (N = 14,167) of a prospective cohort of people in the United States tested for LTBI. We included non-U.S.-born, human immunodeficiency virus-seronegative people ages 5 years and older with valid TST, QuantiFERON-TB Gold-in-Tube (QFT), and T-SPOT.TB (TSPOT) results. The sensitivity/specificity of different test cutoffs and test combinations, obtained from a Bayesian latent class model, were used to construct receiver operating characteristic (ROC) curves and assess the area under the curve (AUC) for each test. The sensitivity/specificity of dual testing was calculated. Results: The AUC of the TST ROC curve was 0.81 (95% credible interval (CrI), 0.78-0.86), with sensitivity/specificity at cutoffs of 5, 10, and 15 mm of 86.5%/61.6%, 81.7%/71.3%, and 55.6%/88.0%, respectively. The AUC of the QFT ROC curve was 0.89 (95% CrI, 0.86-0.93), with sensitivity/specificity at cutoffs of 0.35, 0.7, and 1.0 IU/mL of 77.7%/98.3%, 66.9%/99.1%, and 61.5%/99.4%. The AUC of the TSPOT ROC curve was 0.92 (95% CrI, 0.88-0.96) with sensitivity/specificity for five, six, seven, and eight spots of 79.2%/96.7%, 76.8%/97.7%, 74.0%/98.6%, and 71.8%/99.5%. Sensitivity/specificity of TST-QFT, TST-TSPOT, and QFT-TSPOT at standard cutoffs were 73.1%/99.4%, 64.8%/99.8%, and 65.3%/100%. Conclusion: Interferon-γ release assays have a better predictive ability than TST in people at high risk of LTBI.

Evaluation of the Diagnostic Efficacy of EC-Test for Latent Tuberculosis Infection in Ambulatory People Living with HIV.

Latent tuberculosis infection (LTBI) co-infected with human immunodeficiency virus (HIV) is more likely to develop into active tuberculosis (ATB), recombinant Mycobacterium tuberculosis fusion protein (ESAT6/CFP10, EC) Test is a latest developed method for LTBI. Compared with the interferon γ release test assays (IGRAs), the diagnostic performance of EC-Test to LTBI screening in HIV needs to be evaluated. A population-based multicenter prospective study was conducted in Guangxi Province, China. The baseline data was collected and LTBI were measured by QuantiFERON-TB Gold In-Tube (QFT-GIT), EC-Test and T-cell spot of the TB assay (T-SPOT.TB). A total of 1478 patients were enrolled. when taking T-SPOT.TB as reference, the value of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency that EC-Test to diagnosis LTBI in HIV is 40.42%, 97.98%, 85.26%, 85.04% and 85.06% respectively; when taking QFT-GIT as reference, the value is 36.00%, 92.57%, 55.10%, 85.09% and 81.13%, respectively. When the CD4+ <200 /μl, the accuracy of EC-Test to T-SPOT.TB and QFT-GIT were 87.12% and 88.89%, respectively; when the 200 ≤ CD4+ ≤ 500 /μl, the accuracy of EC-Test were 86.20% and 83.18%, respectively; when the CD4+ >500/μl, the accuracy of EC-Test were 84.29% and 77.94%, respectively. The incidence of adverse reactions in EC-Test is 34.23% and the serious adverse reactions is 1.15%. EC-Test has good consistency compared with IGRAs in detecting LTBI in HIV no matter in different immunosuppression status or different regions, and the safety of EC-Test is also well, suitable for LTBI screening in HIV in high prevalence settings.

Evaluation of ESAT6-CFP10 Skin Test for Mycobacterium tuberculosis Infection among Persons Living with HIV in China.

Recent global guidelines recommend Mycobacterium tuberculosis antigen-based skin tests, such as the ESAT6-CFP10 (EC) skin test, as acceptable alternatives to the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube test (QFT). However, the diagnostic value of these tests among persons living with HIV (PLHIV) is unknown. We aimed to assess the diagnostic accuracy of the EC among a cohort of PLHIV in China. We recruited PLHIV in Jiangsu Province, China, to assess sensitivity and specificity of the EC test. Participants were tested with the QFT, TST, and EC skin test. Results were stratified by age, M. tuberculosis BCG vaccination, and CD4 count. The sensitivity and specificity of the EC skin test was assessed using distinct cutoffs of the QFT and TST. Of 350 PLHIV enrolled in the study, 58 (16.6%), 89 (25.4%), and 59 (16.9%) tested positive with the EC test, the QFT, and the TST, respectively. Positivity increased with CD4 count; however, these trends were similar across tests. At a 5-mm cutoff, EC skin test specificity was high (99.6%, 95% confidence interval [CI] 95% CI = 97.7 to 100.0); however, sensitivity was moderate (81.4%; 95% CI = 66.6 to 91.6). After stratifying by BCG, the sensitivity and specificity were 86.4% (95% CI = 65.1 to 97.1) and 99.1% (95% CI = 95.0 to 100.0) among vaccinated PLHIV and 76.2% (95% CI = 52.8 to 91.8) and 100.0% (95% CI = 97.2 to 100.0) among unvaccinated PLHIV, respectively. Among PLHIV, the diagnostic value of the EC skin test remained high, regardless of BCG vaccination or CD4 count. The EC skin test performed comparably to TST and may be a valid alternative diagnostic test to use in settings or populations with high HIV prevalence and BCG vaccination. To our knowledge, this is the first study to evaluate the novel ESAT6-CFP10 skin test among PLHIV. Among 350 PLHIV, the test displayed high specificity and sensitivity, a finding which did not markedly differ based on BCG vaccination and CD4 count.