Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort study.

BACKGROUND: Treatment of latent tuberculosis infection is an important strategy to prevent tuberculosis disease. In the USA, three tests are used to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON). To our knowledge, few large studies have compared all three tests among people at high risk of latent tuberculosis infection or progression to tuberculosis disease. We aimed to assess test agreement between IFN-γ release assays and TST to provide guidance on their use in important risk groups. METHODS: In this observational cohort study, we enrolled participants at high risk of latent tuberculosis infection or progression to tuberculosis disease at ten US sites with 18 affiliated clinics, including close contacts of infectious tuberculosis cases, people born in countries whose populations in the USA have high (≥100 cases per 100 000 people) or moderate (10-99 cases per 100 000 people) tuberculosis incidence, and people with HIV. Participants were interviewed about demographics and medical risk factors, and all three tests were administered to each participant. The primary endpoints for this study were the proportions of positive test results by test type stratified by risk group and test concordance by risk group for participants with valid results for all three test types. The study is registered at ClinicalTrials.gov, NCT01622140. FINDINGS: Between July 12, 2012, and May 5, 2017, 26 292 people were approached and 22 131 (84·2%) were enrolled in the study. Data from 21 846 (98·7%) participants were available for analysis, including 3790 (17·3%) born in the USA and 18 023 (82·5%) born outside the USA. Among non-US-born participants overall, the RR comparing the proportions of TST-positive results (7476 [43·2%] of 17 306 participants) to QuantiFERON-positive results (4732 [26·5%] of 17 882 participants) was 1·6 (95% CI 1·6-1·7). The risk ratio (RR) for the comparison with the proportion of T-SPOT.TB-positive results (3693 [21·6%] of 17 118 participants) was 2·0 (95% CI 1·9-2·1). US-born participants had less variation in the proportions of positive results across all tests. The RRs for the proportion of TST-positive results (391 [10·9%] of 3575 participants) compared with the proportion of QuantiFERON-positive results (445 [12·0%] of 3693 participants) and T-SPOT.TB-positive results (295 [8·1%] of 3638 participants) were 0·9 (95% CI 0·8-1·0) and 1·3 (1·2-1·6), respectively. 20 149 (91·0%) of 21 846 participants had results for all three tests, including 16 712 (76%) non-US-born participants. Discordance between TST and IFN-γ release assay results varied by age among non-US-born participants and was greatest among the 848 non-US-born children younger than 5 years. 204 (87·2%) of 234 non-US-born children younger than 5 years with at least one positive test were TST-positive and IFN-γ release assay-negative. The proportion of non-US-born participants who were TST-negative but IFN-γ release assay-positive ranged from one (0·5%) of 199 children younger than 2 years to 86 (14·5%) of 594 participants aged 65 years and older (ptrend<0·0001). Test agreement was higher between the two IFN-γ release assays than between TST and either IFN-γ release assay, regardless of birthplace. κ agreement was particularly low between TST and IFN-γ release assays in non-US-born children younger than 5 years. INTERPRETATION: Our findings support the preferential use of IFN-γ release assays for the diagnosis of latent tuberculosis in high-risk populations, especially in very young and older people born outside the USA. FUNDING: US Centers for Disease Control and Prevention.

Non-IFNγ Whole Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in HIV-exposed Infants.

BACKGROUND: HIV-exposed uninfected (HEU) infants have increased risk of tuberculosis (TB). Testing for Mycobacterium tuberculosis (Mtb) infection is limited by reduced Quantiferon (QFT) sensitivity in infants and tuberculin skin test (TST) cross-reactivity with Bacillus Calmette-Guérin vaccine. Our objective is to assess if non-IFNγ cytokine responses to Mtb-specific antigens have improved sensitivity in detecting Mtb infection in HEU infants compared with QFT. METHODS: HEU infants were enrolled in a randomized clinical trial of isoniazid preventive therapy (IPT) to prevent Mtb infection in Kenya (N = 300) and assessed at 12 months postrandomization (14 months of age) by TST and QFT-Plus. Non-IFNγ cytokine secretion (IL2, TNF, IP10, N = 229) in QFT-Plus supernatants was measured using Luminex assay. Logistic regression was used to assess the effect of IPT on Mtb infection outcomes in HEU infants. RESULTS: Three of 251 (1.2%) infants were QFT-Plus positive. Non-IFNγ Mtb antigen-specific responses were detected in 12 additional infants (12/229, 5.2%), all TST negative. IPT was not associated with Mtb infection defined as any Mtb antigen-specific cytokine response (odds ratio = 0.7, P = 0.54). Mtb antigen-specific IL2/IP10 responses had fair correlation (τ = 0.25). Otherwise, non-IFNγ cytokine responses had minimal correlation with QFT-Plus and no correlation with TST size. CONCLUSIONS: We detected non-IFNg Mtb antigen-specific T-cell responses in 14-month HEU infants. Non-IFNg cytokines may be more sensitive than IFNg in detecting infant Mtb infection. IPT during the first year of life was not associated with Mtb infection measured by IFNg, IL2, IP10 and TNF Mtb-specific responses.

Phenotype Definition for "Resisters" to Mycobacterium tuberculosis Infection in the Literature-A Review and Recommendations.

Tuberculosis (TB) remains a worldwide problem. Despite the high disease rate, not all who are infected with Mycobacterium Tuberculosis (Mtb) develop disease. Interferon-γ (IFN-γ) specific T cell immune assays such as Quantiferon and Elispot, as well as a skin hypersensitivity test, known as a tuberculin skin test, are widely used to infer infection. These assays measure immune conversion in response to Mtb. Some individuals measure persistently negative to immune conversion, despite high and prolonged exposure to Mtb. Increasing interest into this phenotype has led to multiple publications describing various aspects of these responses. However, there is a lack of a unified "resister" definition. A universal definition will improve cross study data comparisons and assist with future study design and planning. We review the current literature describing this phenotype and make recommendations for future studies.

Interferon-Gamma Release Assay Testing in Children Younger Than 2 Years in a US-Based Health System.

BACKGROUND: Use of interferon-gamma releasing assays (IGRAs) in children <2 years old may derive many of the same advantages, which have led to preference over tuberculin skin test (TST) in older children, but data are limited. Since 2011, we have tested children <2 years old with Quantiferon-TB Gold/Gold Plus (QFT)) in select clinical scenarios at Denver Health, a health system encompassing a TB clinic, refugee and immigrant screening and primary care. METHODS: We identified patients <2 years old tested with QFT between February, 2011 and August, 2019. The primary outcome measure was incident cases of TB among tested patients. Test results and in vitro characteristics were analyzed, as were demographic, epidemiologic and clinical outcomes. RESULTS: We analyzed 116 QFTs ordered in children age 7-23 months. Two were positive, 3 indeterminate, 3 failed/refused phlebotomy and the remainder (93%) were negative. Mitogen tube results were robust. Thirteen patients were TST-positive: 11 were QFT-negative, 1 QFT-positive and 1 failed phlebotomy. Eight patients received some form of TB medication, including 4 QFT-negative patients who were treated for active TB or latent TB infection based on positive TST or clinical findings. Among QFT-negative patients, including 6 TST-positive, not treated for active TB or latent TB infection, no TB disease has been identified over a median follow-up time of 2.96 years. CONCLUSIONS: IGRA use was not limited by barriers of phlebotomy, indeterminate result or gamma-interferon production. The risk of missing an infected but IGRA-negative patient can be reduced by treatment of select patients at higher risk. Current recommendations against IGRA use in children <2 years old could be amended to allow careful introduction, particularly among well-appearing BCG-vaccinated patients.

Comparison Of Positivity Of Tuberculin Skin Test With Diagnostic Bcg In Children Suffering From Tuberculosis.

BACKGROUND: Tuberculosis is major public health problem in Pakistan and it is often unrecognized cause of morbidity and mortality in children living in endemic areas. Children with age less than 5 years, and especially those who are immune compromised, are at higher risk of developing tuberculosis following exposure. Tuberculosis in children is usually difficult to diagnose compare to adult patients due to its atypical presentation. Tuberculin skin test and Bacille Calmette-Guerin (BCG) are widely used as diagnostic tests for tuberculosis. It was a Cross sectional study carried out from May 2017 to Nov 2018 in the department of Paediatrics, Ayub Teaching Hospital Abbottabad.. METHODS: Both BCG and tuberculin skin test were performed at the same time by the same doctor. Personal data like age, gender and address, type of tuberculosis, positivity of tuberculin skin test and positivity of diagnostic BCG were recorded. The induration was read 48- 72 hours after administration. RESULTS: As per frequencies and percentages for positivity of tuberculin skin, 51 (67.10%) patients showed positivity for tuberculin skin while 71 (93.42%) patients showed positive results via BCG Test. CONCLUSIONS: In paediatric age group, diagnostic BCG test has got better diagnostic value over Tuberculin Skin Test in diagnosis of tuberculosis.

Comparison of tuberculin skin test and interferon gamma release assay in pediatric candidates of heart transplantation and a 2-year follow-up.

BACKGROUND: Currently, tuberculin skin test (TST) and interferon gamma release assay (IGRA) are used to find the latent tuberculosis infection (LTBI) cases in the candidates of heart transplantation. Therefore, this study aimed to compare TST and IGRA to diagnose LTBI in pediatric heart transplant candidates. METHODS: This cross-sectional study was performed on 50 children, who were candidates for heart transplantation, of whom 42 cases underwent heart transplantation in Shahid Rajaie Cardiovascular, Medical, and Research center, Tehran, Iran, from 2016 to 2017. RESULTS: Participants of the study included 24 male patients (%48) (p-value = 0.67). The mean age of the patients was 8.18 ± 4.27 years (1-16 years). According to the results, IGRA was negative in all patients, and no indeterminate result was reported, while the purified derivative test (PPD) was positive in three (6%) cases. In comparison with QFT, an accuracy of 94% was achieved for TST to diagnose Mycobacterium tuberculosis infection. CONCLUSIONS: It seems that TST can still be used as an accurate test for screening LTBI in pediatric candidates for heart transplantation.

Reproducibility of the T-SPOT.TB test for screening Mycobacterium tuberculosis infection in Japan.

OBJECTIVES: The interferon-gamma release assay (IGRA) is useful for diagnosing Mycobacterium tuberculosis infections, especially in countries where Bacille Calmette-Guérin vaccinations are performed. However, reproducibility of the IGRA is unclear, as recent data suggest high IGRA conversion and reversion rates in serial tests among healthcare workers. This longitudinal study aimed to evaluate reproducibility of T-SPOT.TB for screening M. tuberculosis infections in Japan. METHODS: Results of T-SPOT.TB tests performed between April 2014 and March 2016 at two hospitals in Yokohama, Japan, where the incidence of tuberculosis was 18.0 per 100,000 population in 2014, were analyzed. RESULTS: In total, 3890 T-SPOT.TB tests were included. Overall, positive and negative test rates were 8.4% and 87.6%, respectively. Among 373 serial tests within two years, conversion and reversion rates were only 1.1% and 12.5%, respectively. Almost all patients who were initially negative (98.9%) remained so. There was no statistically significant difference between the outcomes observed at the two hospitals. CONCLUSIONS: The conversion rate of T-SPOT.TB in Japan is as low as that recently reported in other countries where the incidence of tuberculosis is low. These data indicate that T-SPOT.TB is a reproducible tuberculosis screening tool at local hospitals in areas with a moderate incidence of tuberculosis.

[Comparison of Tuberculin Skin Test (TST) and T-SPOT.TB Tests for Diagnosis of Latent Tuberculosis Infection (LTBI) in HIV-infected Patients]. / HIV ile Enfekte Hastalarda Latent Tüberküloz Enfeksiyonunu (LTBE) Belirlemede Tüberkülin Deri Testi (TDT) ve T-SPOT.TB Testlerinin Karsilastirilmasi.

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most important step in preventing the development of active TB. In our country where TB is moderately endemic, HIV-infected patients should be investigated for LTBI. Tuberculin skin test (TST) and interferongamma release assays (IGRA) are used in the diagnosis of LTBI but there isn't a standard practice. The aim of this study is to compare the TST and T-SPOT.TB test efficiency in the diagnosis of LTBI in HIVinfected patients. Patients who had no previous active TB infection, who were not treated for LTBI and who had no active tuberculosis infection at the time of admission were included in the study. A total of 100 HIV-infected patients who were admitted to the Infectious Diseases and Clinical Microbiology outpatient clinic between June 2015 and March 2016 were evaluated cross-sectionally. CD4+ T lymphocyte counts in the last one month were detected. All patients underwent chest radiography at the time of admission. Patients who are not considered as active TB infection with clinical and laboratory findings and who had no TST within the last one month were included in the study. TST was performed after the blood samples were taken for T-SPOT.TB test. In our study, 87% of the patients were male and the mean age was 40.2. The mean CD4+ T lymphocyte count was 605 cells/mm³ (26-1313). 16% of the patients had a history of encountring a person with tuberculosis and 81% had BCG vaccination scar. TST positivity and T-SPOT.TB positivity were 22.9% and 22%, respectively. The concordance between the two tests was found to be moderate (Kappa= 0.491). It was determined that BCG vaccination and the presence of a contact with a patient with TB did not affect TST and T-SPOT.TB test positivity (p> 0.05). There was a positive correlation between CD4+ T lymphocyte count and TST measurement values (r= 0.3, p= 0.003). Accordingly, as the number of CD4+ T lymphocytes increased, TST positivity increased (p= 0.007). T-SPOT.TB test was not affected by CD4+ T lymphocyte count (p= 0.289). Our study showed that TST was affected by CD4+ T lymphocyte count and patients' compliance with this test was also low. On the contrary T-SPOT.TB test was not affected by CD4+ T lymphocyte count. There was no statistically significant difference between T-SPOT.TB test positivity and CD4+ T lymphocyte count (p= 0.289). The concordance between the two tests was found to be moderate. It is thought that the main reason for the discordance between the tests is due to false negative or false positive results of TST. In conclusion, T-SPOT.TB was found more reliable in the diagnosis of LTBI in HIV-infected individuals. In the light of these findings, especially in HIV-infected patients with low CD4+ T lymphocyte counts, T-SPOT.TB test can be considered for LTBI diagnosis.

Cost-effectiveness of QuantiFERON-TB Gold In-Tube versus tuberculin skin test for diagnosis and treatment of Latent Tuberculosis Infection in primary health care workers in Brazil.

OBJECTIVES: The goal of this study was to perform a cost-effectiveness analysis from the public health system perspective, comparing five strategies for Latent Tuberculosis Infection (LTBI) diagnosis in primary health care workers in Brazil. DESIGN: Analytical model for decision making, characterized by cost-effectiveness analysis. SETTING: Primary Care Level, considering primary health care workers in Brazil. PARTICIPANTS: An analytical model for decision making, characterized by a tree of probabilities of events, was developed considering a hypothetical cohort of 10,000 primary health care workers, using the software TreeAge Pro™ 2013 to simulate the clinical and economic impacts of new diagnostic technology (QuantiFERON®-TB Gold in-Tube) versus the traditional tuberculin skin test. METHODS: This model simulated five diagnostic strategies for LTBI in primary health care workers (HCW) in Brazil: tuberculin skin testing using ≥5 mm cut-off, tuberculin skin testing ≥10 mm cut-off, QuantiFERON®-TB Gold in-Tube, tuberculin skin testing using ≥5 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive, tuberculin skin testing using ≥10 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measures are the number of individuals correctly classified by the test and the number of Tuberculosis cases avoided. RESULTS: The most cost-effective strategy was the tuberculin skin test considering ≥10mm cut-off. The isolated use of the QuantiFERON®-TB Gold In-Tube revealed the strategy of lower efficiency with incremental cost-effectiveness ratio (ICER) of US$ 146.05 for each HCW correctly classified by the test. CONCLUSIONS: The tuberculin skin test using ≥10 mm cut-off was the most cost-effective strategy in the diagnosis of Latent Tuberculosis Infection in primary health care works in Brazil.

Evaluation of the QuantiFERON®-TB Gold In-Tube Assay and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in an Iranian Referral Hospital.

BACKGROUND: Mycobacterium tuberculosis remains as a vital threat to global health and its diagnosis is still complicated. Since there is no gold standard for the diagnosis of latent tuberculosis infection (LTBI), its diagnosis routinely relies on measurement of host immune responses to M. tuberculosis antigens using the Tuberculin Skin Test (TST) and Interferon-Y Release Assays (IGRAs). OBJECTIVE: The aim of this study was to evaluate LTBI among hospitalized children and their parents/ guardians as general populations. METHODS: A cross-sectional study comparing TST and IGRA for the diagnosis of suspected LTBI was performed in children and their guardians (as general population) in Children Medical Center, an Iranian referral hospital. RESULTS: In this study, 81 patients hospitalized in CMC and 102 patient's guardians were included. A total of 57 patients (70.4%) had performed a TST and were interpreted during the study. Among them, 32 (56%) had a positive test result when a cut-off of 10 mm induration. There were fewer positive IGRA test results than positive TST results (33% versus 56%) in children. Among guardians, TST and IGRA were positive in 41% and 40% respectively. The agreement between the IGRA test and the TST among them was 0.7, while this was as slightly lower in children (0.63). CONCLUSION: The results of our study indicate that the IGRA test has a higher specificity than TST, especially in children, while the frequency of positive results with both tests in adults was similar. Considering the false positive results reported with the TST, replacement of the IGRA test with TST in children is recommended.

Utility of tuberculin skin test and IGRA for tuberculosis screening in internationally adopted children: Retrospective analysis from a single center in Florence, Italy.

BACKGROUND: Most of internationally adopted children (IAC) come from countries in which tuberculosis (TB) is endemic. Interpretation of discordant Tuberculin Skin Test (TST) and Quantiferon-Gold In Tube (QFT) results is under debate. METHODS: Children consecutively referred to our IAC Center between 2009-2017 were prospectively evaluated and screened with protocol recommended by the America Academy of Pediatrics, including TST and QFT. TB infection prevalence was evaluated and possible risk factors associated with discordant TST/QFT results were investigated. RESULTS: 1775 IAC were enrolled (median age: 5.8; IQR:3.3-8.2; 1065 [60.0%] males). Most of the children came from a European country (715; 40.3%) and, among them, 428 (59.9%) from Russia. Active pulmonary TB was diagnosed in 7 (0.4%) children while LTBI was diagnosed in 255 (14.4%) children. Concordant TST-/QFT-result was observed in 1520 (85.6%) children, concordant TST+/QFT + result in 63 children (3.5%), while 169 children (9.5%) displayed TST+/QFT-result and the remaining 23 children (1.3%) TST-/QFT+. Factor significantly associated with discordant TST+/QFT-result was BCG vaccination (aOR:2.62; 95%CI. 1.12-6.12; P = 0.026) and age <5 years (aOR: 5.59; 95%CI:2.27-12.18; P < 0001). . No significant association was evidenced with, continent of origin, eosinophilia or gender. CONCLUSIONS: Our data suggest that QFT might be used as unique screening assay in IAC, but further studies are needed at this regard.

Tuberculin skin test reaction depends on type of purified protein derivative: implications for cut-off values.

SETTING: Due to purified protein derivative (PPD) RT23 stock-outs in 2014, PPD-Tubersol and PPD-Bulbio have been used for latent tuberculosis infection (LTBI) testing in the Netherlands.OBJECTIVE: To determine whether PPD-RT23, PPD-Tubersol and PPD-Bulbio were associated with differential indurations and confirmation using interferon-gamma release assays (IGRAs).DESIGN: LTBI surveillance data from 2013 to 2016 were extracted. Regression analyses were used to determine whether IGRA confirmation of TST-positive indurations depended on PPD, controlling for sex, age, incidence in country of origin, and bacille Calmette-Guérin (BCG) status.RESULTS: A total of 20 956 individuals were tested with PPD-RT23: 10 382 with PPD-Tubersol and 18 562 with PPD-Bulbio. Overall, 21% with PPD-Bulbio had an induration of ≥5 mm compared to 12% of those tested with PPD-RT23 and PPD-Tubersol. Compared to PPD-RT23, PPD-Bulbio indurations ≥5 mm were significantly less often IGRA-confirmed among contacts (aOR 1.3, 95% CI 1.1-1.6) and BCG-vaccinated immigrants (PPD-RT23, aOR 2.4, 95% CI 1.4-4.1). Increasing the PPD-Bulbio cut-off from ≥5 to ≥10 mm would save respectively 26%, 42%, and 35% of IGRAs among contacts, health care workers (HCWs) and BCG-vaccinated immigrants, with small absolute numbers of positive IGRAs missed (range 0-55 annually).CONCLUSION: PPD-Bulbio shows larger TST indurations than other PPDs, but is less often IGRA-confirmed. Increasing the TST cut-off from 5 to 10 mm prior to testing with an IGRA in HCWs and immigrants is recommended.

QuantiFERON-TB-GOLD In-Tube in patients with sarcoidosis.

INTRODUCTION: Sarcoidosis and tuberculosis (TB) are the diseases that share many similarities. Mycobacterium tuberculosis (MTB) culture results are the gold standard for the diagnosis of TB, but false positive results are not rare. The aim was to evaluate the utility of QFT in detecting latent TB infection in a group of sarcoidosis patients with negative history of TB and negative culture/BACTEC results, and checking sarcoidosis activity influence on the QFT results. Additionally, we assessed if QFT negative result may strengthen the suspicion that positive culture/BACTEC results are false positive. MATERIAL AND METHODS: 37 culture-negative and 6 culture-positive sarcoidosis patients were enrolled. On the basis of clinical and radiological data TB was considered unlikely (false-positive results). A control group consisted of age-matched subjects with excluded TB (n = 37). QuantiFERON-TB GOLD In-Tube (QIAGEN, USA) was used according to the manual. Test validity was checked basing on the results obtained from a low-risk (n = 21) and active TB group (n = 23). RESULTS: The frequency of positive results tended to be higher in MTB(-) sarcoidosis (24.3% vs. 13.5% for the control group, p = 0.37), but was similar to the general population. None of culture-positive sarcoidosis patients was QFT-positive. The positive results were equally distributed among patients with active and inactive sarcoidosis. CONCLUSIONS: QFT has been found to be the useful test for the detection of latent TB infection in sarcoidosis patients. In addition, we confirm that sarcoidosis activity does not negatively influence the result of QFT. Moreover, QFT would be proposed as a cost-saving diagnostic test providing additional diagnostic information when false positive MTB culture result in the sarcoidosis patient is highly suspected. However, in each case clinical, radiological and epidemiological data should be considered before taking the therapeutic decision.

Bayesian latent class estimation of sensitivity and specificity parameters of diagnostic tests for bovine tuberculosis in chronically infected herds in Northern Ireland.

In the European Union, the recommended ante-mortem diagnostic methods for bovine tuberculosis (bTB) include the single intradermal cervical comparative tuberculin (SICCT) test and the interferon-gamma (IFN-γ) test as an ancillary test. The SICCT test has a moderate sensitivity (Se) and high specificity (Sp), while the IFN-γ test has good Se, but a lower Sp than the SICCT test. A retrospective Bayesian latent class analysis was conducted on 71,185 cattle from 806 herds chronically infected with bTB distributed across Northern Ireland (NI) to estimate the Se and Sp of the common ante-mortem tests and meat inspection. Analyses were also performed on data stratified by farming type and herd location to explore possible differences in test performance given the heterogeneity in the population. The mean estimates in chronically infected herds were: (1) 'standard' SICCT: Se 40.5-57.7%, Sp 96.3-99.7%; (2) 'severe' SICCT: Se 49.0%-60.6%, Sp 94.4-99.4%; (3) IFN-γ(bovine-avian) using a NI optical density (OD) cut-off difference of 0.05: IFN-γ(B-A)NI: Se 85.8-93.0%, Sp 75.6-96.2%; (4) IFN-γ(bovine-avian) using a standard 'commercial' OD cut-off difference of 0.1: IFN-γ(B-A)0.1: Se 83.1-92.1%, Sp 83.1-97.3%; and (5) meat inspection: Se 49.0-57.1% Se, Sp 99.1-100%. Se estimates were lower in cattle from dairy farms than from beef farms. There were no notable differences in estimates by location of herds. Certain population characteristics, such as production type, might influence the ability of bTB tests to disclose truly infected cases.