Use Of Interferon-gamma Release Assays Research Articles

Test and treat approach for tuberculosis infection amongst household contacts of drug-susceptible pulmonary tuberculosis, Mumbai, India.

Mumbai is one of the most densely populated areas in the world and is a major contributor to the tuberculosis (TB) epidemic in India. A test and treat approach for TB infection (TBI) amongst household contacts (HHC) is part of the national policy for TB preventive treatment (TPT). However, in practice, the use of interferon-gamma release assay (IGRA) tests for infection are limited, and prevalence of TBI in Mumbai is not known. We conducted a cross-sectional study among HHCs exposed to persons with microbiologically-confirmed, drug-susceptible pulmonary TB that were notified for antituberculosis treatment in Mumbai, India during September-December, 2021. Community-based field workers made home visits and offered IGRA (QuantiFERON-TB® Gold In-Tube Plus) tests to HHC aged 5 years and older. After ruling out active TB disease, HHC with IGRA-positive test results were referred for TPT. All HHC were monitored for at least 24 months for progression to active TB disease. Among 502 HHCs tested, 273 (54%) had IGRA-positive results. A total of 254 (93%) were classified as TBI and were eligible for TPT, of which 215 (85%) initiated TPT, and 194 (90%) completed TPT successfully. There was substantial variation in rates of TBI per household. In 32% of households, all HHC (100%) were IGRA positive and in 64% of households >50% of HHC were infected. In all, 22 HHCs (4%; 22/558) were diagnosed with TB disease; of these, five HHC were diagnosed during follow up, of which three were IGRA positive and had no evidence of disease at initial screening but chose not to initiate TPT. A test and treat strategy for HHC resulted in the detection of a substantial proportion of TBI and secondary TB cases. Home-based IGRA testing led to high participation rates, clinical evaluations, TPT initiation, and early diagnoses of additional secondary cases. A community-focused, test and treat approach was feasible in this population and could be considered for broader implementation.

Interferon Gamma Release Assay Results and Testing Trends Among Patients Younger Than 2 Years Old at Two US Health Centers.

Interferon-gamma release assays (IGRAs) are approved for children ≥2 years old to aid in diagnosis of Mycobacterium tuberculosis (TB) infection and disease. Tuberculin skin tests (TSTs) continue to be the recommended method for diagnosis of TB infection in children <2 years, in part due to limited data and concern for high rates of uninterpretable results. We performed a retrospective cohort study of IGRA use in patients <2 years old in 2 large Boston healthcare systems. The primary outcome was the proportion of valid versus invalid/indeterminate IGRA results. Secondary outcomes included concordance of IGRAs with paired TSTs and trends in IGRA usage over time. A total of 321 IGRA results were analyzed; 308 tests (96%) were valid and 13 (4%) were invalid/indeterminate. Thirty-seven IGRAs were obtained in immunocompromised patients; the proportion of invalid/indeterminate results was significantly higher among immunocompromised (27%) compared with immunocompetent (1%) patients ( P < 0.001). Paired IGRAs and TSTs had a concordance rate of 64%, with most discordant results in bacille Calmette-Guérin-vaccinated patients. The proportion of total TB tests that were IGRAs increased over the study period (Pearson correlation coefficient 0.85, P < 0.001). The high proportion of valid IGRA test results in patients <2 years of age in a low TB prevalence setting in combination with the known logistical and interpretation challenges associated with TSTs support the adoption of IGRAs for this age group in certain clinical scenarios. Interpretation of IGRAs, particularly in immunocompromised patients, should involve consideration of the broader clinical context.

Increasing Use Of Interferon Gamma Release Assays Among Children ≥2 Years of Age in a Setting With Low Tuberculosis Prevalence.

US guidelines recommend interferon gamma release assays (IGRAs) for diagnosis of tuberculosis infection in children. In this retrospective cohort study, IGRA use in children 2-17 years of age increased substantially between 2015 and 2021. Testing in inpatient/subspecialty settings (vs. primary care), public (vs. private) insurance, lower age and non-English preferred language were associated with increased odds of receiving an IGRA.

Interferon gamma release assays for diagnosis of osteoarticular tuberculosis: A systematic review and meta-analysis.

BackgroundAlthough the Interferon Gamma Release Assays (IGRA) is often used to identify latent tuberculosis, it also plays a crucial role in diagnosing active extrapulmonary tuberculosis. Some studies have assessed the use of IGRA as a biomarker for osteoarticular tuberculosis (OATB), which is elevated following TB infection. Still, conclusive results about its effectiveness have not been reported.MethodWe searched PubMed, Embase, and Cochran databases. We obtained literature related to the diagnosis of OATB by IGRA, and the retrieval period was from the establishment of the database to June 2021. The bivariate random effect model was used to summarize the sensitivity, specificity, and accuracy of other indicators in diagnosing OATB by IGRA, and the forest plot and receiver operating characteristic (ROC) curve were used for testing.ResultsWe included seven studies involving 643 subjects in diagnosing OATB by IGRA. The comprehensive sensitivity and specificity were 0.84 (95% CI, 0.70–0.92) and 0.78 (95% CI, 0.66–0.87), respectively. The area under the curve (AUC) was 0.87.ConclusionIn blood samples, the diagnostic accuracy of IGRAS is poor in patients with suspected OAT. We conclude that IGRA may not be appropriate for patients with OATB.

646. Increasing Use of Interferon-Gamma Release Assay to Test for Pediatric Tuberculosis in a Low-Burden Setting

BackgroundThe American Academy of Pediatrics recommends tuberculin skin tests (TSTs) or interferon gamma release assays (IGRAs) to test for tuberculosis (TB) infection in children ≥2 years old, and prioritizes IGRA testing in Bacille Calmette-Guérin vaccine recipients due to cross-reactivity. TSTs require a return visit, which frequently results in loss to follow up. Growing evidence supports accuracy of IGRA testing in pediatric patients, including young children, leading to calls for preferential use of IGRA over TST. We sought to evaluate trends in IGRA use in children over time. MethodsWe identified all TB infection tests conducted in children 5-17 years old at 2 academic medical systems in Boston from October 2015–January 2021. TSTs were identified using medication administration records, and IGRAs were identified using laboratory records. We computed the proportion of tests per month that were IGRA and TST. We used Pearson correlation to determine the association between month of testing and proportion of tests that were IGRAs. Results21,471 TB infection tests were obtained from 16,778 patients during our timeframe. Median age of testing was 13.4 years (IQR 9.2 – 16.2 years). During the study period, there was a significant increase in the monthly proportion of TB infection tests that were IGRAs (Pearson correlation coefficient 0.92, P < 0.001). The total number of tests performed per month also increased, with seasonal increases in testing in late summer and early fall and a substantial decline in testing early in the COVID-19 pandemic. Tuberculosis infection tests and proportion IGRA. Total number of tuberculosis infection tests per month and proportion of tests that were interferon gamma release assays, from October 2015 - January 2021.ConclusionUse of IGRAs among patients age 5-17 years of age increased significantly overall and compared to TST in two large Boston healthcare systems over a 5-year period. These results suggest a shift towards blood-based TB infection testing in a low-burden setting, which may improve completion of the pediatric TB infection care cascade. Future research is needed to determine reasons for changing testing modalities, and similar patterns in other settings.Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

655. Patterns of Interferon-Gamma Release Assay (IGRA) Testing for Tuberculosis in Patients Less Than 2 Years Old

BackgroundThe American Academy of Pediatrics recommends use of Interferon-Gamma Release Assays (IGRAs) to diagnose tuberculosis (TB) infection in patients ≥2 years old. However, IGRAs are not currently recommended in younger patients due to limited data and concerns of invalid/indeterminate test results, which occur if there is a positive or negative control failure. We sought to characterize the patterns of IGRA use in clinical practice and results of IGRAs in patients < 2 years old. MethodsWe conducted a retrospective cohort study of children < 2 years old at two large health systems in the Boston area who had IGRA and/or tuberculin skin test (TST) performed from October 1, 2015 – January 31, 2021. We reviewed medical records to determine IGRA test type, IGRA result (positive, negative, invalid/indeterminate) and location of testing (outpatient primary care, outpatient subspecialty, inpatient). We summarized test interpretability, location, and changes in proportion of IGRA vs. TST. ResultsWe identified 330 IGRA (268 T-SPOT.TB, 62 QuantiFERON Gold) and 2029 TST results among 1982 patients who were < 2 years old (range: 11 days – 1.9 years). Monthly proportion of IGRAs among all TB tests ordered increased from 2015 to 2021 (Figure 1) (Pearson correlation coefficient 0.85, P < 0.001). Among IGRA results, 314 (95%) were negative, 3 (1%) were positive, and 13 (4%) were invalid/indeterminate (11 T-SPOT.TB, 2 QuantiFERON Gold). Of 324 IGRA tests for which testing location was known, 233 (72%) and 91 (28%) were ordered in outpatient and inpatient settings, respectively. Of tests in outpatient settings, 132 (57%) were ordered in primary care offices, 53 (23%) were ordered in subspecialist offices, and 48 (21%) were obtained in outpatient labs of unidentified clinics. Tuberculosis infection tests and proportion IGRA. Total number of tests and proportion of IGRA:TST obtained by month, from October 2015-January 2021.ConclusionWhile most TB infection tests in this age group were TSTs, the monthly proportion of tests that were IGRAs increased over time between 2015-2021. IGRAs were obtained in varied clinical settings. In this low-burden setting, rates of invalid/indeterminate IGRAs were low among children < 2 years old, which suggests that IGRAs are reasonable TB testing options for patients < 2 years old, and may be preferred given limitations of TSTs.Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

Tuberculosis Infection in Children and Adolescents: Testing and Treatment

Tuberculosis (TB) remains an important problem among children in the United States and throughout the world. There is no diagnostic reference standard for latent tuberculosis infection (also referred to as tuberculosis infection [TBI]). The tuberculin skin test (TST) has many limitations, including difficulty in administration and interpretation, the need for a return visit by the patient, and false-positive results caused by cross-reaction with Mycobacterium bovis-bacille Calmette-Guerin vaccines and many nontuberculous mycobacteria. Interferon-gamma release assays (IGRAs) are blood tests that use antigens specific for M tuberculosis; as a result, IGRAs yield fewer false-positive results than the TST. Both IGRAs and the TST have reduced sensitivity in immunocompromised children, including children with severe TB disease. Both methods have high positive predictive value when applied to children with risk factors for TBI, especially recent contact with a person who has TB disease. The advantages of using IGRAs and diminished experience with the placement and interpretation of the TST favor expanded use of IGRAs in children in the United States. There are now several effective and safe regimens for the treatment of TBI in children. For improved adherence to therapy, the 3 rifamycin-based regimens are preferred because of their short duration. Daily isoniazid can be used if there is intolerance or drug interactions with rifamycins. A TB specialist should be involved when there are questions regarding testing interpretation, selection of an appropriate treatment regimen, or management of adverse effects.

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Utility of the Interferon-Gamma Release Assay for Latent Tuberculosis Infection Screening among Indian Health-Care Workers.

Background:The utility of interferon-gamma release assays (IGRAs) for latent tuberculosis infection (LTBI) screening among health-care workers (HCWs) in low- and middle-income countries (LMICs) remains unclear.Methods:This was a prospective cohort study among HCW trainees undergoing annual LTBI screening via tuberculin skin test (TST) and QuantiFERON® TB Gold Test-in-tube (QFT-GIT) in Pune, India. TST induration ≥ 10 mm and QFT-GIT ≥ 0.35 IU/ml were considered positive. Test concordance was evaluated at entry among the entire cohort and at 1 year among baseline TST-negative participants with follow-up testing. Overall test agreement was evaluated at both timepoints using the kappa statistic: fair (k < 0.40), good (0.41 ≥ k ≤0.60), or strong (k > 0.60).Results:Of 200 participants, prevalent LTBI was detected in 42 (21%) via TST and 45 (23%) via QFT-GIT; QFT-GIT was positive in 27/42 (64%) TST-positive and 18/158 (11%) TST-negative trainees. Annual TST conversion was 28% (40/142) and included 11 trainees with baseline TST-/IGRA+; QFT-GIT was positive in 17/40 (43%) TST-positive and 5/102 (5%) TST-negative trainees. Overall test concordance was 84% (k = 0.52; 95% confidence interval [CI]: 0.38–0.66) and 80% (k = 0.44; 95% CI: 0.29–0.59) at baseline and 12 months, respectively.Conclusions:We observed good overall agreement between TST and QFT-GIT, and QFT-GIT detected additional LTBI cases among TST-negative trainees with possible early detection of LTBI conversion. Overall, our results support the use of IGRA for annual LTBI screening among HCWs in a high burden LMIC setting.

Intra-vitam Diagnosis of Tuberculosis in Pigs: Concordance Between Interferon-Gamma Release Assay and Comparative Tuberculin Skin Test.

The role of pigs in the maintenance of bovine tuberculosis caused by Mycobacterium bovis has been demonstrated in many settings; however, the current control programs usually do not state any intra-vitam diagnostic procedure in this species, as for the cattle. Carcass inspection has shown to be insufficient to detect infection in swine; thus, the assessment of intradermal tuberculin test and interferon-gamma release assay (IGRA) in this species is mandatory. The current study compares the performances of the single intradermal comparative cervical tuberculin (SICCT) test and IGRA. A total of 628 Nebrodi Black pigs raised in free-roaming farms were subjected to the two tests simultaneously. Besides, 124 animals underwent postmortem examination for the detection of tuberculous lesions and isolation of mycobacteria from target organs. The two tests showed a concordance of 94.42% with a Cohen's k coefficient of 0.786 and McNemar chi-square of 4.83 (P = 0.03). Slightly lower levels of concordance (90.32%) between SICCT and IGRA were obtained in the group of 124 animals, with a Cohen's k = 0.797 and McNemar chi-squared value of 0.69 with a non-significant P = 0.41. Moreover, the results showed how IGRA tends to result positive in higher rates, mostly when non-tuberculous mycobacteria (NTM) were isolated, suggesting a possible impairment of specificity in the event of coinfections in the swine. In conclusion, the results obtained support the possibility of the strategic use of IGRA or SICCT in combination or alternatively one to the other, particularly IGRA which showed lower specificity but has evident advantages over SICCT.

Interferon gamma release assay tests are associated with persistence and completion of latent tuberculosis infection treatment in the United States: Evidence from commercial insurance data.

Risk-targeted testing and treatment of latent tuberculosis infection (LTBI) is a critical component of the United States' (US) tuberculosis (TB) elimination strategy, but relatively low treatment completion rates remain a challenge. Both treatment persistence and completion may be facilitated by diagnosing LTBI using interferon gamma release assays (IGRA) rather than tuberculin skin tests (TST). We used a national sample of administrative claims data to explore associations diagnostic test choice (TST, IGRA, TST with subsequent IGRA) and treatment persistence and completion in persons initiating a daily dose isoniazid LTBI treatment regimen in the US private healthcare sector between July 2011 and March 2014. Associations were analyzed with a generalized ordered logit model (completion) and a negative binomial regression model (persistence). Of 662 persons initiating treatment, 327 (49.4%) completed at least the 6-month regimen and 173 (26.1%) completed the 9-month regimen; 129 (19.5%) persisted in treatment one month or less. Six-month completion was least likely in persons receiving a TST (42.2%) relative to persons receiving an IGRA (55.0%) or TST then IGRA (67.2%; p = 0.001). Those receiving an IGRA or a TST followed by an IGRA had higher odds of completion compared to those receiving a TST (aOR = 1.59 and 2.50; p = 0.017 and 0.001, respectively). Receiving an IGRA or a TST and subsequent IGRA was associated with increased treatment persistence relative to TST (aIRR = 1.14 and 1.25; p = 0.027 and 0.009, respectively). IGRA use is significantly associated with both higher levels of LTBI treatment completion and treatment persistence. These differences are apparent both when IGRAs alone were administered and when IGRAs were administered subsequent to a TST. Our results suggest that IGRAs contribute to more effective LTBI treatment and consequently individual and population protections against TB.

How are high burden countries implementing policies and tools for latent tuberculosis infection? A survey of current practices and barriers.

Background and aimsDespite the World Health Organization (WHO)'s updated guidelines on tuberculosis (TB) preventive treatment, the scale‐up of TB preventive therapy remains low in many high‐burden countries (HBCs). We conducted a survey to better understand the current status of policy implementation and barriers for scale‐up.MethodsSurvey questions pertained to HBCs' current latent TB infection (LTBI) screening and treatment strategies, and the availability of LTBI tests and newer treatments (eg, isoniazid/rifapentine [3HP]). The 19‐question survey was piloted and sent out via email in June 2019 as a protected Microsoft Word document to contacts [National TB Program (NTP) staff, researchers, and health officials] in the 30 TB HBCs. Responses were accepted until February 2020.ResultsThirty‐seven completed surveys from 24 HBCs were received. Respondents from five countries (Brazil, Lesotho, Mozambique, Russia, Zambia) reported having LTBI guidelines that are fully implemented. Among respondents who indicated their country currently has no LTBI guideline implementation (Angola, China, DRC, India, Indonesia, Kenya, Myanmar), the most often cited barrier to implementation was the prioritization of active TB over LTBI management (n = 5, Angola, China, DRC, India, Kenya). Of the 16 countries in which respondents reported using purified protein derivative (PPD), 9 reported having experienced a PPD shortage within the past year (from time of survey). Respondents from six countries reported currently using Interferon‐gamma Release Assays (IGRAs) in their NTP, and 13 cited high cost as a barrier to IGRA use. Lastly, rifapentine was stated not be available in 8 HBCs.ConclusionThis survey indicates limited implementation of WHO LTBI guidelines in HBCs and provides some insight into barriers to implementation, including shortage of products (eg, PPD), high costs (eg, IGRAs), and lack of regulatory approval of newer treatments (eg, rifapentine). Thus, we should work towards price reductions for LTBI tests and treatments, and the development of tests that can be more easily implemented at peripheral healthcare levels.

Can Interferon-γ Release Assays Be Useful for Monitoring the Response to Anti-tuberculosis Treatment?: A Systematic Review and Meta-analysis.

The number of studies which evaluated interferon-gamma release assays (IGRAs) results after anti-tuberculosis (TB) treatment has been rapidly increasing. The aim of this study was to investigate the potential use of IGRAs (QFT-GIT, T-SPOT.TB, QFT-Plus) in assessing the response to anti-TB treatment. We searched all studies in English language published from 1 October 2011 to 18 November 2018 in PubMed, Web of Science, and Scopus. Our search included the term "tuberculosis treatment AND interferon-γ release assay". We included studies evaluating the performance of commercial IGRAs (including QFT-GIT, T-SPOT.TB and QFT-Plus) before and after the anti-TB treatment. We performed subgroup analysis based on the age (children, adults), type of TB (active, latent, active and latent, and contacts exposed to MDR defined as MDR LTBI), type of IGRAs (QFT-GIT and T-SPOT.TB), and follow-up interval (2, 3, 4, 6, 9months). Of the 18 included studies, 12 used QFT-GIT for assessment of IGRA performance after therapy, 1 used T-SPOT.TB, and 3 used both QFT-GIT and T-SPOT.TB. Since then, only two studies have assessed the QFT-Plus performance during therapy. According to the results of the meta-analysis, the pooled rate of positive IGRAs (QFT-GIT and T-SPOT.TB) following anti-TB therapy was estimated at 76% [95% CI 70-81%] and no difference was found compared to the pooled positive rate of IGRAs before initiation of therapy which was 76% [95% CI 60-89%]. The subgroup analysis showed that the pooled rate of positive IGRAs (QFT-GIT and T-SPOT.TB) after anti-TB therapy was significantly higher in monitoring active TB subjects [80% (95% CI 74-88%)] than LTBI [71% (95% CI 70-81%)]. Available data are now sufficient to suggest that monitoring changes in the IGRAs (QFT-GIT and T-SPOT.TB) response during anti-TB treatment may have limited use in evaluating the effectiveness of treatment, while the monitoring changes in QFT-Plus during anti-tubercular treatment are recommended to determine treatment efficacy or for treatment monitoring. Further research is needed to establish the efficacy of this new assay as marker on a larger scale for treatment monitoring.

Diagnostic performance of interferon-gamma release assay for diagnosis of tuberculous pericarditis: A meta-analysis.

The diagnosis of tuberculous pericarditis is difficult to set, not only for its non-specific clinical presentation, but also for the lack of useful diagnostic tests. We comprehensively evaluate the overall diagnostic accuracy of Interferon-gamma release assays (IGRA) upon tuberculous pericarditis by meta-analysis. We searched PubMed, Embase and Cochrane Library database from the earliest available date of indexing through April 30, 2019. The study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS2) checklist. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-) and constructed summary receiver operating characteristic curves parameters. Across six results from five studies (415 patients), the pooled sensitivity for IGRA methods was 0.94 (95% confidence interval [CI]; 0.87-0.98) with heterogeneity (χ2 =69.9, P=.01) and a pooled specificity of 0.94 (95% CI; 0.75-0.94) without heterogeneity (χ2 =41.1, P=.13). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 16.8 (95% CI; 8.0-35.4) and negative likelihood ratio (LR-) of 0.06 (95% CI; 0.03-0.13). The pooled diagnostic odds ratio was 278 (95% CI; 114-6806). Interferon-gamma release assays demonstrated good sensitivity and specificity for diagnosis of tuberculous pericarditis. At present, the literature regarding remains the use of IGRA for diagnosis of tuberculous pericarditis still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of IGRA test for the diagnosis of tuberculous pericarditis.

1377. Use of Interferon-Gamma Release Assays (IGRAs) Reduced Latent Tuberculosis Infection (LTBI) Diagnosis in Refugee and Immigrant Children

BackgroundFor foreign-born children from countries with high tuberculosis (TB) burden, positive tuberculin skin test (TST) results, associated with Bacillus Calmette Guerin (BCG) vaccination, paradoxically increase the risk for overdiagnosis and overtreatment of latent TB infection (LTBI) during immigration. The higher specificity of interferon-gamma release assays, such as QuantiFERON-TB (QFT), may help distinguish LTBI from positive TSTs due to BCG or non-TB Mycobacteria. However, data on QFT usage in pediatric populations, particularly refugee and immigrant children, are sparse. Our objective was to assess the impact of QFT on LTBI diagnosis and treatment in the vulnerable child refugee and immigrant population.MethodsWe initiated a retrospective study of children (≤15 years) seen in Santa Clara County Refugee/Immigrant Clinic for post-immigration TB re-evaluation in 2017. We collected information from the Electronic Disease Notification system and post-immigration clinic records, including laboratory studies, imaging, and clinical impression. The primary outcome was post-immigration LTBI diagnosis in patients with positive pre-immigration TB screening. Patients with prior active TB or LTBI treatment were excluded.Results102/135 clinic encounters examined to date were post-immigration encounters. Median age was 9 years (range 14mo to 15y). Most (82.5%) were from Asia, primarily the Philippines (n = 48), Afghanistan (n = 10), Iran (n = 9), and Vietnam (n = 8). Sixty-six (64.7%) had documented BCG vaccination. Among 102 encounters, 71 (69.6%) were of children diagnosed pre-immigration with LTBI based on positive TST and normal chest radiograph. After post-immigration evaluation with retesting by QFT, 13/71 (18%) were diagnosed with LTBI (Table 1). There were no active TB cases among 102 patients, though long-term follow-up varied (mean 5.5 ± 6.5 months).ConclusionQFT use for post-immigration LTBI re-evaluation reduced LTBI diagnosis by 82% in children as young as 2 years old. Preliminary data suggest the preferential use of QFT over TST in non-United States-born children, in accordance with new California Department of Public Health TB screening recommendations for children ≥2 years, could reduce unnecessary diagnosis and treatment of LTBI in refugee and immigrant children. Disclosures All authors: No reported disclosures.

Tests for latent tuberculosis in candidates for solid organ transplantation: A systematic review and meta-analysis.

Reactivation of latent tuberculosis following solid organ transplantation has serious consequences for the recipient. The most useful diagnostic test for latent TB is not clear. We conducted a systematic review and meta-analysis to assess the relative test performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) in people undergoing solid organ transplantation. The clinical or radiological risk factors were used as the proxy reference standard. Test performance was expressed as an odd ratio (OR). We identified 24 studies (N=7811), 12 studies compared IGRAs with TST directly, nine studies evaluated only TST and three studies only IGRAs. Direct comparison between tests and clinical risk factors indicated both tests were strongly associated with the presence of clinical risk factors for TB (TST: OR 3.17; 95%CI 1.55-6.48, IGRA: OR 2.78; 95%CI 1.55-5.01), and radiological evidence of past TB (TST: OR 3.26; 95%CI 1.85-5.73, IGRA: OR 3.85; 95%CI 2.16-6.86). Relative comparison indicated IGRAs positivity was more strongly associated with presence of radiological evidence of TB than TST (relative OR: 3.24; 95%CI 1.10-9.56). While there is no strong evidence in supporting use of IGRAs over TST for diagnosing latent TB, IGRAs positivity is more associated with the presence of radiological evidence of previous TB.

Tuberculose oculaire

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients.

Predictors of latent tuberculosis infection treatment completion in the US private sector: an analysis of administrative claims data

BackgroundFactors that affect latent tuberculosis infection (LTBI) treatment completion in the US have not been well studied beyond public health settings. This gap was highlighted by recent health insurance-related regulatory changes that are likely to increase LTBI treatment by private sector healthcare providers. We analyzed LTBI treatment completion in the private healthcare setting to facilitate planning around this important opportunity for tuberculosis (TB) control in the US.MethodsWe analyzed a national sample of commercial insurance medical and pharmacy claims data for people ages 0 to 64 years who initiated daily dose isoniazid treatment between July 2011 and March 2014 and who had complete data. All individuals resided in the US. Factors associated with treatment completion were examined using multivariable generalized ordered logit models and bivariate Kruskal-Wallis tests or Spearman correlations.ResultsWe identified 1072 individuals with complete data who initiated isoniazid LTBI treatment. Treatment completion was significantly associated with less restrictive health insurance, age < 15 years, patient location, use of interferon-gamma release assays, non-poverty, HIV diagnosis, immunosuppressive drug therapy, and higher cumulative counts of clinical risk factors.ConclusionsPrivate sector healthcare claims data provide insights into LTBI treatment completion patterns and patient/provider behaviors. Such information is critical to understanding the opportunities and limitations of private healthcare in the US to support treatment completion as this sector’s role in protecting against and eliminating TB grows.

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A systematic review of economic evaluations of interventions to tackle tuberculosis in homeless people.

ABSTRACTObjectiveTo analyze economic evaluations of interventions related to tuberculosis (TB) diagnostics/screening, treatment, and prevention in homeless people.MethodsA systematic review was conducted. The eligibility criteria were original studies reporting economic evaluation results. The search was not restricted by language or year. A critical appraisal approach was used.ResultsA total of 142 studies were identified, including five research articles (three full economic evaluations and two partial) that were selected for the final review. Most of the studies were conducted in the United States, adopted a public health perspective, and analyzed active TB. Interventions related to diagnostics/screening (the use of interferon-gamma release assay (IGRA) and mobile screening units), treatment (incentives for continuing treatment, and housing programs), and prevention (with the Bacillus Calmette–Guérin (BCG) vaccine) were identified.ConclusionsNo high-quality data were found on cost-effectiveness of interventions on TB diagnostics/screening, treatment, or prevention in homeless people. However, active searching for cases via mobile screening, and financial incentives, could help increase treatment adherence, and the use of IGRA helps boost detection. TB in homeless people is neglected worldwide, especially in developing countries, where this disease tends to afflict more people made vulnerable by their precarious living conditions. Public funding mechanisms should be created to develop cross-sectoral actions targeting homeless people, as the complex dynamics of this group tend to hamper prevention and diagnosis of TB and the completion of TB treatment.