Tuberculin Skin Test Results Research Articles

Contribution of QuantiFERON-TB Gold-in-Tube to the Diagnosis of Mycobacterium tuberculosis Infection in Young Children in a Low TB Prevalence Country.

Introduction: Interferon Gamma Release Assay (IGRA) has proven to be a useful test to evaluate the immune response to Mycobacterium tuberculosis antigens in children over the age of 5 years as an alternative to tuberculin skin testing (TST). Much less is known about its performance in younger children, who are at higher risk for developing tuberculosis (TB) disease after exposure. We aimed to evaluate the accuracy of using IGRA in TB screening in this population.Methods: Children below the age of 5 years at high risk for TB infection were prospectively enrolled, to compare the performance of TST and the QuantiFERON-TB Gold-In-Tube test (QFT). Children were treated in accordance with the diagnosis made at baseline and followed-up for 12 months.Results: We included a total of 60 children of which 97 blood samples were available for analysis. There was 90.72% agreement between TST and QFT (Kappa test 0.59, moderate agreement). With TST as a reference, the QFT positive predictive value was 0.72 and the negative predictive value 0.93. Discordant results were observed with 6% TST+/QFT– paired tests. When we restricted the comparison of TST and QFT to non-BCG-vaccinated children, the degree of agreement was more substantial (95%, Kappa test 0.75) and the negative predictive value was 0.99. We observed 3% discordant TST–/QFT+ results. All children with active TB disease had concordant positive QFT results, with QFT values above 4.00 IU/ml.Conclusion: In a low TB prevalence country, serial testing of QFT was found to produce a moderate agreement with TST results. False positive QFT results would have been eliminated by using a higher cutoff without misdiagnosing the children with TB disease. Some of the false negative QFT results could be explained by false positive TST results on consecutive testing. For now the most prudent approach would be to consider discordant QFT–/TST+ results as false negative QFT results, taking into account the young age of our population and the potential risk for evolution to active TB disease.

The association between tuberculin skin test result and active tuberculosis risk of college students in Beijing, China: a retrospective cohort study

BackgroundAbout 10% latent tuberculosis infections (LTBI) would progress to active tuberculosis (TB), if left prophylactic therapy. Tuberculin skin test (TST) is the most widely used method for LTBI screening in the school of China. However, for college students, the association between TST reaction size and active TB risk was unclear.MethodsWe conducted a retrospective study to assess whether the TST reaction size would predict active TB during the next two years after TST screening for college students. Multivariable Cox regression was performed to identify the size of TST reaction and other factors associated with active TB risk.ResultsA total of 67292 college students in Beijing, China were included in this study; 8021 (11.92%) individuals were TST positive (≥10 mm), and 3879 (5.76%) of them were strong TST positive (≥15 mm). During the two years of follow-up, 26 active TB cases were reported in 134575 person-years with an incidence rate of 19.32 (95% CI: 12.61–28.32) per 100000 person-years. The adjusted hazard ratios (HR) (95% CI) were 1.094 (0.247~4.846), 3.644 (1.188~11.179), 6.832 (2.436~19.163) and 9.768 (2.203~43.315) of cohorts with the TST reaction size intervals 5~9, 10~14, 15~20 and ≥ 20 mm, respectively, compared to cohort with interval 0~4 mm. Besides, the adjusted HR (95% CI) was 3.593 (1.354~9.537) of males compared to females.ConclusionsThis study indicated that the risk of active TB increased in college students when the TST reaction size was ≥10 mm, and males had a higher risk compared to females.

Radiological Signs of Latent Tuberculosis on Chest Radiography: A Systematic Review and Meta-Analysis.

ObjectiveCurrent guidelines recommend screening for latent tuberculosis infection (LTBI) with a tuberculin skin test (TST) or interferon gamma release assay (IGRA), or both. Many also recommend chest radiography (CXR), although its added value is uncertain. This systematic review assessed the prevalence of abnormalities suggestive of LTBI on CXR (LTBI-CXR lesions) and evaluated the strength of the association.MethodWe searched 4 databases up to September 2017 and systematically reviewed cross-sectional and cohort studies reporting LTBI-CXR lesions in individuals with a positive TST or IGRA, or both, result. Prevalence estimates were pooled using random effects models and odds ratios (ORs) were used to calculate risk estimates.ResultsIn the 26 included studies, the pooled proportion of individuals with LTBI having LTBI-CXR lesions was 0.15 (95% confidence interval [CI], 0.12–0.18]. In 16 studies that reported on individuals with LTBI and uninfected controls, LTBI-CXR lesions were associated with a positive TST result ≥ 5 mm or ≥ 10 mm (OR, 2.45; 95% CI, 1.00–5.99; and OR, 2.06; 95% CI, 1.38–3.09, respectively) and with a positive QuantiFERON result (OR, 1.99; 95% CI, 1.17–3.39) compared to CXR in uninfected controls. Although few studies reported specified lesions, calcified nodules were most frequently reported in individuals with LTBI (proportion, 0.07; 95% CI, 0.02–0.11).ConclusionsLesions on CXR suggestive of previous infection with Mycobacterium tuberculosis were significantly associated with positive tests for LTBI, although the sensitivity was only 15%. This finding may have added value when detection of past LTBI is important but immunodiagnostic tests may be unreliable.

Evaluating a 24-year tuberculosis screening in first-grade elementary schoolers in a low-burden area.

Early diagnosis of tuberculosis infection can significantly contribute to the control of the disease. The aim of the present study was to describe the tuberculin skin test (TST) trends over a 24-year period (1990-2013) and explore the value of universal tuberculosis screening in a low-burden area. All first graders that underwent TST during the 24-year study period (1990-2013) on the island of Crete, Greece, were retrospectively included in the study. A total of 82402 children (92.3% of Greek nationality; 51.0% male) underwent TST, of whom 335 (0.41%, 95% CI 0.37-0.46) were found to have positive TST while 0.27% of the study population had a TST between 5 and 9mm. The tuberculin index declined significantly between 1990-1994 and 2010-2013 (0.67 vs 0.26; RR 2.73, 95% CI 1.82-4.09; p<0.0001). Positive TST result was significantly higher in the immigrant than the native group (0.66% vs 0.24%; RR 3.76 95%, CI 2.89-4.84; p<0.0001). In the last study years, 386 children (488 native; 153 immigrant) should be tested for one to be found TST positive. Our findings question the massive tuberculin testing in low-burden areas and point to selective screening of high-risk groups.

Tuberculosis household accompaniment to improve the contact management cascade: A prospective cohort study.

BackgroundAppropriate management of people exposed in the home to tuberculosis is essential to prevent morbidity. These household contacts, particularly children, should receive preventive therapy to prevent them from falling ill. However, few people receive preventive therapy worldwide. We sought to determine whether a community-based accompaniment intervention could improve tuberculosis contact management.MethodsWe conducted a prospective cohort study of household contacts of tuberculosis patients who initiated treatment during September 2015-June 2016 in Lima, Peru. Enrolled households received an intervention comprising home visits, transport vouchers, assistance coordinating evaluation procedures, and adherence support during preventive therapy. To evaluate the impact of the intervention, we conducted retrospective chart reviews of all patients initiating treatment during 6-month baseline and intervention periods.ResultsWe enrolled 314 household contacts of 109 index patients. Of these, 283 (90%) completed evaluation, and 4 (1%) were diagnosed with tuberculosis. Preventive therapy was prescribed for 35/38 (92%) contacts 0–19 years old who were eligible under Peruvian guidelines. Preventive therapy was also prescribed for 6/26 (23%) contacts with unknown eligibility due to lack of a tuberculin skin test (TST), and 20/69 (29%) who were ineligible either because of a negative TST result or exposure to a drug-resistant or extrapulmonary case. Of the 61 contacts who were prescribed preventive therapy, 57 (93%) initiated treatment, and 51 (91%) completed treatment. The proportion of contacts who completed evaluation increased from 42% during the baseline period to 71% during the evaluation period (risk ratio [RR] = 1.73, 95% confidence interval [95% CI]: 1.41–2.13). The proportion of contacts who initiated preventive therapy increased from 15% to 40% (RR = 2.45, 95% CI: 1.42–4.22).ConclusionAccompaniment of TB patient households greatly improved the evaluation of household contacts for TB and increased the use of preventive therapy.

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital

BackgroundMozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established.MethodsThis study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated.ResultsOf 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35–49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p < 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%.ConclusionsThere is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results.

The role of super-spreading events in Mycobacterium tuberculosis transmission: evidence from contact tracing

BackgroundIn current epidemiology of tuberculosis (TB), heterogeneity in infectiousness among TB patients is a challenge, which is not well studied. We aimed to quantify this heterogeneity and the presence of “super-spreading” events that can assist in designing optimal public health interventions.MethodsTB epidemiologic investigation data notified between 1 January 2005 and 31 December 2015 from Victoria, Australia were used to quantify TB patients’ heterogeneity in infectiousness and super-spreading events. We fitted a negative binomial offspring distribution (NBD) for the number of secondary infections and secondary active TB disease each TB patient produced. The dispersion parameter, k, of the NBD measures the level of heterogeneity, where low values of k (e.g. k < 1) indicate over-dispersion. Super-spreading was defined as patients causing as many or more secondary infections as the 99th centile of an equivalent homogeneous distribution. Contact infection was determined based on a tuberculin skin test (TST) result of ≥10 mm. A NBD model was fitted to identify index characteristics that were associated with the number of contacts infected and risk ratios (RRs) were used to quantify the strength of this association.ResultsThere were 4190 (2312 pulmonary and 1878 extrapulmonary) index TB patients and 18,030 contacts. A total of 15,522 contacts were tested with TST, of whom 3213 had a result of ≥10 mm. The dispersion parameter, k for secondary infections was estimated at 0.16 (95%CI 0.14–0.17) and there were 414 (9.9%) super-spreading events. From the 3213 secondary infections, 2415 (75.2%) were due to super-spreading events. There were 226 contacts who developed active TB disease and a higher level of heterogeneity was found for this outcome than for secondary infection, with k estimated at 0.036 (95%CI 0.025–0.046). In regression analyses, we found that infectiousness was greater among index patients found by clinical presentation and those with bacteriological confirmation.ConclusionTB transmission is highly over dispersed and super-spreading events are responsible for a substantial majority of secondary infections. Heterogeneity of transmission and super-spreading are critical issues to consider in the design of interventions and models of TB transmission dynamics.

Negative tuberculin skin test result predicts all-cause mortality among tuberculosis patients with HIV and diabetes comorbidity

PurposeThe purpose of this study was to determine if a negative tuberculin skin test (TST) result is associated with increased risk of mortality during tuberculosis (TB) treatment. MethodsWe conducted a retrospective cohort study among patients aged ≥15 years with culture-positive TB reported to the Georgia State Electronic Notifiable Disease Surveillance System from 2009 to 2014. TST positivity was defined by the US Centers for Disease Control guidelines. All-cause mortality during TB treatment as well as HIV, diabetes, and end-stage renal disease status were collected from surveillance data. Log-binomial regression was used to estimate adjusted risk ratios and 95% confidence intervals. ResultsAmong 1186 culture-confirmed TB patients, 780 (65.8%) with a valid TST and TB treatment outcomes were eligible. Nearly one-third (242/780) had a negative TST result, and 5.6% died during treatment. The highest risk of death was observed among patients with a negative TST and HIV (12.5%) and a negative TST and diabetes (15.4%). Adjusting for confounders, the risk of death among patients with a negative TST was significantly greater compared with those with a positive TST (adjusted risk ratio 2.33 95% confidence interval 1.23–4.43). ConclusionsA negative TST was associated with more than twice the risk of mortality during TB treatment after adjusting for immunosuppressive conditions.

Comparison of tuberculin skin test and interferon-gamma release assay in the diagnosis of latent tuberculosis infection among indonesian health-care workers

Background: Health-care workers are groups that are close contact with tuberculosis (TB) patients. As an alternative to the tuberculin skin test (TST), there is interferon-gamma release assay (IGRA) for the diagnosis of latent TB infection (LTBI). The objective of this study is to compare TST and IGRA in the diagnosis of LTBI among Indonesian health-care workers. Methods: This study design was a cross-sectional study. TST results are consistent for LTBI if there is induration ≥10 mm in individuals without previous TST, or ≥15 mm in participants with a history of previous TST. Medical history interview, physical examination, chest X-ray, and sputum smear examination were performed to exclude active TB infection. Results: Among 84 healthcare workers, the prevalence of LTBI was 51.2% by IGRA and 29.8% by TST with sufficient agreement (κ = 0.34). Age and low education were significantly correlated with the positive results of IGRA (P

The prevalence of latent tuberculosis infection in patients with inflammatory arthritis and the diagnostic efficacy of different screening methods

Objective: To investigate the prevalence of latent tuberculosis infection (LTBI) in patients with inflammatory arthritis, and to compare the efficacy of tuberculin skin test (TST) and QuantiFERON-TB Gold (QFT) in screening for LTBI in these patients. Method: Medical records of 149 patients with inflammatory arthritis admitted to inpatient of Peking University International Hospital from December 2015 to December 2017 (diagnosis with rheumatoid arthritis, ankylosing spondylitis, sero-negative spondyloarthropathy, psoriatic arthritis, or reactive arthritis) who accepted TST or QFT were collected. The information included gender, age, history of tuberculosis infection, calcifications presence in chest X-ray or chest CT, TST result, QFT result, medication history before test, and biological treatment and all the patients were made a follow-up. Results: The positive rate of TST was 18.2%(14/77) and that of QFT was 27.1%(26/96), and the overall consistency between the two tests was fair. The rate of LTBI diagnosed by QFT was 22.9%(22/96). The positive rate of TST in patients older than 50 years was significantly higher than those younger than 50 years, but there was no significant difference between the two groups screened by QFT. The M-N values in QFT were decreased in both the patients above the age of 50 and in the patients using immunosuppressive agents. A total of 64 patients accepted biological agent therapy, and in those with a positive result of TST or QFT, only 2 cases received anti-LTBI treatment, but the other 14 cases without anti-LTBI treatment. None of them developed active tuberculosis in the following 3-24 months. Conclusion: The prevalence of LTBI in patients with inflammatory arthritis is consistent with that reported in rheumatoid patients, which is higher than in general people. In patients with inflammatory arthritis older than 50 years, especially those accepted immunosuppressive agents therapy, the immunity may be impaired and QFT is more sensitive than TST for screening LTBI.

Good Agreement between an Interferon Gamma Release Assay and Tuberculin Skin Tests in Testing for Latent Tuberculosis Infection among HIV-Infected Patients in Indonesia.

BackgroundLatent tuberculosis infection is a condition where there is a persistent immune response to Mycobacterium tuberculosis without clinical manifestations of tuberculosis. Currently, there is no gold standard to diagnose latent tuberculosis infection. The tuberculin skin test and interferon-gamma release assay are currently used to diagnose latent tuberculosis infection. However, studies have shown inconsistencies regarding the level of agreement between these tests in different settings. In this study, we aimed to evaluate the agreement between these two tests for diagnosing latent tuberculosis infection in human immunodeficiency virus (HIV)-infected individuals.MethodsWe screened HIV patients with no clinical symptoms of tuberculosis, a normal chest X-ray, and no history of tuberculosis or use of antituberculous drugs. Participants were tested with tuberculin skin test (TST) and T-SPOT.TB (an interferon gamma release assay) simultaneously. Participants' HIV stage was determined by measuring the level of CD4+ T-lymphocytes. Tuberculosis status was confirmed by sputum examination using GeneXpert. The level of agreement between the TST and T-SPOT.TB results was measured using Cohen's κ coefficient.ResultsOf the 112 participants, 20 had a positive T-SPOT.TB test result, and 21 had a positive TST result. The TST and T-SPOT.TB test results showed a high level of agreement (κ = 0.648, P < 0.001). Performance of the tests did not vary with CD4+ level. However, in participants with CD4+ < 200 cells/mm3, T-SPOT.TB detected more latent tuberculosis infections than the TST.ConclusionThere was good agreement between the TST and T-SPOT.TB results of latent tuberculosis infection in participants. TST is the preferred test for diagnosing latent tuberculosis infection in HIV-infected patients, especially in resource-limited settings, because it is simple and cost-effective. However, T-SPOT.TB may be useful to rule out latent tuberculosis infection in patients with severe immunodeficiency.

Tuberculin skin test response in patients with juvenile idiopathic arthritis on anti-TNF therapy

The aim of this study is to evaluate the effect of biologic drugs on the tuberculin skin test in patients with juvenile idiopathic arthritis. A total of 234 biologic drug-using juvenile idiopathic arthritis patients and 45 healthy controls were enrolled in the study. The tuberculin skin test results of the patients, which had been routinely provided during follow-up, were obtained from the patient files. Tuberculin skin test values of ≥5 mm were considered to be positive. The mean diameter of tuberculin skin test induration was 4.99 ± 6.84 mm (IQR: 0–10 mm) and 7.83 ± 3.47 mm (IQR: 0–16 mm) in patients and controls, respectively (P < 0.05). Tuberculin skin test positivity (≥5 mm) was found in 96 (41%) and 38 (84.4%) of patients and controls, respectively (P < 0.001). There was no induration in 125 (53.4%) patients and 3 (6.6%) healthy controls, respectively (P < 0.001). In the patients with juvenile idiopathic arthritis who were using biologic drugs, tuberculin skin test induration was significantly lower compared to the control group. Tuberculin skin tests alone seem inadequate for recognition of latent tuberculosis in juvenile idiopathic arthritis patients on anti-TNF therapy.

806. 2013–2015 Nationwide Tuberculosis Contact Investigation in Childcare Centers and Schools in Korea

BackgroundThe Republic of Korea has the highest incidence rate of tuberculosis (TB) among members of the OECD, reported as 78.8/100,000 population in 2016. In response, a state-run intensive contact investigation for TB is being conducted. More effective TB control requires an epidemiologic emphasis on the diagnosis and treatment of latent TB infections in children and adolescents, compared with other age groups. Here we present an analysis of data from the childcare center and school contact investigation by the Korea Centers for Disease Control and Prevention (CDC) in 2013–2015.MethodsData collected from index patients included age, sex, occupation, disease status, results of AFB smear/culture, and chest x-ray. Data collected from contacts included age, sex, results of serial tuberculin skin test (TST), and chest x-ray. Congregate settings included childcare centers, kindergartens, elementary and secondary schools, and age groups were stratified as follows: 0–4 years, 5–12 years, and 13–18 years. TSTs were considered positive if induration ≥10 mm on the first test (TST1) or demonstrated an increase ≥6 mm over the induration of TST1 on repeat testing after 8 weeks (TST2).ResultsOf the 197,801 subjects with data collected, 173,998 were eligible and included in our analysis. TST1 results were available for 159,346 (91.6%) and when results were positive, induration was 10–14 mm in 7.6% and ≥15 mm in 1.5%. TST2 results were available for 119,797 (82.7%) of the 144,904 with negative TST1, and conversion rate was 9.0%. Altogether considering TST1 and TST2, 17.3% contacts had latent TB infections. Positive rates of TST significantly decreased with age: 20.3% in 0–4 years, 18.8% in 5–12 years, 17.1% in 13–18 years.ConclusionIn this 3-year school-setting contact investigation, 17.3% contacts were diagnosed with latent TB infection, as demonstrated by TST reactions. Positive rates of TST significantly but mildly decreased with age.Disclosures All authors: No reported disclosures.

Polymorphisms in TLR4 and TNFA and Risk of Mycobacterium tuberculosis Infection and Development of Active Disease in Contacts of Tuberculosis Cases in Brazil: A Prospective Cohort Study.

The role of genetic polymorphisms in latent tuberculosis (TB) infection and progression to active TB is not fully understood. We tested the single-nucleotide polymorphisms (SNPs) rs5743708 (TLR2), rs4986791 (TLR4), rs361525 (TNFA), rs2430561 (IFNG) rs1143627 (IL1B) as risk factors for tuberculin skin test (TST) conversion or development of active TB in contacts of active TB cases. Contacts of microbiologically confirmed pulmonary TB cases were initially screened for longitudinal evaluation up to 24 months, with clinical examination and serial TST, between 1998 and 2004 at a referral center in Brazil. Data and biospecimens were collected from 526 individuals who were contacts of 177 active TB index cases. TST conversion was defined as induration ≥5 mm after a negative TST result (0 mm) at baseline or month 4 visit. Independent associations were tested using logistic regression models. Among the 526 contacts, 60 had TST conversion and 44 developed active TB during follow-up. Multivariable regression analysis demonstrated that male sex (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1-4.6), as well as SNPs in TLR4 genes (OR: 62.8, 95% CI: 7.5-525.3) and TNFA (OR: 4.2, 95% CI: 1.9-9.5) were independently associated with TST conversion. Moreover, a positive TST at baseline (OR: 4.7, 95% CI: 2.3-9.7) and SNPs in TLR4 (OR: 6.5, 95% CI: 1.1-36.7) and TNFA (OR: 12.4, 95% CI:5.1-30.1) were independently associated with incident TB. SNPs in TLR4 and TNFA predicted both TST conversion and active TB among contacts of TB cases in Brazil.

Interferon-\u03b3 release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study

BackgroundIn developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established.MethodsThis cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI.ResultsAmong 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk (P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI (p < 0.001).ConclusionsCompared to TST, IGRA positivity is consistent with the risk of TB infection and seems to be a better diagnostic tool for LTBI in HIV-infected patients.

Screening for latent tuberculosis infection prior to biologic therapy in patients with chronic immune-mediated inflammatory diseases (IMID): Interferon-gamma release assay (IGRA) versus tuberculin skin test (TST)

BackgroundThe screening for latent tuberculosis infection (LTBI) is mandatory before initiating biologics in patients with chronic immune-mediated inflammatory disease (IMID). The recommendations are based on the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Aim of the workTo evaluate the agreement between the two tests in the diagnosis of LTBI and to identify risk factors associated with positive TST and IGRA results. Patients and methodsMedical records of 105 IMID patients going to receive a biologic agents were extracted in a cross sectional study (2015–2017). No biologics was undertaken before LTBI screening. All patients underwent IGRA and chest radiography. TST was performed in 94 cases. ResultsThe mean age of the patients was 47.7 ± 14.4 years and disease duration of 11.2 ± 7.6 years. Agreement between the 2 tests results was low (κ coefficient = 0.08). The sensitivity of TST and IGRA was equally low but the specificity of IGRA was higher. Replacing TST results by positive IGRA showed that number of patients who would take anti-tuberculous chemoprophylaxis will be significantly reduced by 46.5% (from 40.9% to 21.9%; p = 0.0002). TST results were significantly less positive for patients receiving immunosuppressives than for those receiving no treatment (35.1% vs 42.5%, p = 0.031). IGRA results were associated with absence of Bacilli Calemtte-Guérin vaccination. Age was the only risk factor for LTBI associated with both IGRA and TST positivity (p = 0.031, p = 0.011 respectively). ConclusionsTST and IGRA have a low agreement. Both tests should be included in the strategy to diagnose LTBI prior to biologic therapy in IMID patients.

Screening for active and latent tuberculosis among asylum seekers in Italy: A retrospective cohort analysis.

The World Health Organization conditionally recommends systematic screening of tuberculosis (TB) and Latent Tuberculosis Infection (LTBI) among asylum seekers (AS) from high-burden countries, but the effectiveness of different screening approaches is controversial. We report the results of a retrospective cohort analysis of TB and LTBI screening among consecutive AS in Brescia, Italy during 2015-2016. TB screening was based on symptoms, LTBI screening on the tuberculin skin test (TST). Logistic regression analysis was performed to identify factors associated with screening uptake. Of 2904 registered AS 2567 (88.4%) were evaluated for TB, 62 (2.4%) had symptoms and active TB yield was 155/100,000. Prevalence and incidence TB rates were 545/100,000 persons and 220/100,000 person-years. Questionnaire screening identified 28.6% (4/14) prevalent cases. Of 2303 (89.7%) AS with TST result, the positivity rate was 36.6% (843/2303). Of the 843 candidates for LTBI treatment 413 (49.0%) completed the screening. LTBI treatment was prescribed to 190 (47.9%) of 397 eligible individuals, 10.8% (91) completed treatment. TB prevalence and incidence rates were high in this AS population, but symptom-based screening performed poorly. LTBI cascade losses were significant and mainly attributable to the defragmentation of the health care system.

Results of a population screening intervention for tuberculosis in a Nunavik village, Quebec, 2015-2016.

A small village in Nunavik, Quebec experienced a tuberculosis (TB) outbreak in 2012-2013 and then a resurgence in 2015-2016. Cases were still occurring, despite the fact that contact tracing had already been conducted on one quarter of the population. A decision was taken to conduct large-scale screening of the population for TB. To describe the results of a population-based TB screening intervention designed to identify individuals with latent TB infection (LTBI) or active TB requiring treatment. The history of TB infection (either active TB or LTBI, defined as a positive tuberculin skin test result of at least five mm induration) and treatment (considered adequate if at least 80% of prescribed doses were taken) were determined. Those who were two years of age and older and had not been included in contact tracing after June 1, 2015 were included for TB screening (n=1,026 eligible individuals). Screening included a nurse assessment, tuberculin skin test (TST) for those with previous negative TST or of unknown status and chest X-ray for the others. Of the eligible individuals in the affected village, 1,004 (98%) participated in the screening. Of these, 30% had a history of previous TB infection. A TST screening was administered to 71% of the participants, 10% of whom had positive results. Assessments were performed on 425 participants and 385 underwent a chest X-ray. Fifty-two cases of previously diagnosed active TB and three cases of new active TB were documented. In addition, there were 247 individuals with LTBI who had been previously identified (191 were found to have had adequate LTBI treatment, 56 were found to have had inadequate LTBI treatment) and 69 were identified with de novo LTBI. In addition, 633 participants were found to have no TB infection. There were 125 participants who were referred for LTBI treatment. Follow-up information was available for 120 and 85 (71%) of these completed the treatment. Within this northern village, which had persistent TB transmission despite classic control measures, population-based screening had a high degree of coverage and was an effective way to detect additional cases of individuals with active TB and those with LTBI.

Risk of latent tuberculosis infection among diabetic patients in Azadi Teaching Hospital, Duhok province: a case control study

Diabetes can be linked with impaired host immunity that subsequently increases the rate of various infections including tuberculosis (TB), particularly in developing countries where TB is endemic. The objectives of this case control study were to determine the prevalence and the risk of LTBI among diabetic patients. It is a prospective case control study conducted in Azadi Teaching Hospital from September 2017 until May 2018. The diabetic patients included in this study were randomly selected. The diagnosis of diabetes mellitus (DM) was made according to the American Diabetes Association (ADA). Diabetes mellitus patients and the control participants were offered a voluntary tuberculin skin test (TST). The TST ≥10 mm was considered positive. The results were analyzed by entering the data in SPSS (statistical package for the social sciences, version 16; SPSS Inc., Chicago, Illinois, USA). Two hundred DM patients and 208 control individuals participated in this study. Collectively, 28 patients had positive TST results. Based on the sputum smear microscopy and CXR, none of these patients showed active TB disease. The differences between the DM patients and the control group had no statistical significance apart from previous hospitalization. The prevalence of LTBI was 23.53% in the diabetic group, whereas, it was 9.62% in the control group. The frequency of LTBI in diabetic patients was significantly higher than the control group. When the diabetic group was compared with the control group in terms of diabetic control and the duration of diabetes disease, there was a statistically significant association of diabetes duration ≥ 10 years and TST positivity. In conclusion, the previous hospitalization was a significant risk factor for diabetic patients to acquire TB bacilli. Latent TB infection was more common in diabetics than non diabetics and there was an increased likelihood of having LTBI with the duration of diabetes ≥ 10 years. To avoid the threatening of TB control program, prophylactic treatment of LTBI in diabetic patients is paramount.Asian J. Med. Biol. Res. June 2018, 4(2): 227-232

Prognostic value of interferon-γ release assays and tuberculin skin test in predicting the development of active tuberculosis (UK PREDICT TB): a prospective cohort study

SummaryBackgroundTackling tuberculosis requires testing and treatment of latent tuberculosis in high-risk groups. The aim of this study was to estimate the predictive values of the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs) for the development of active tuberculosis in high-risk groups—ie, people in recent contact with active tuberculosis cases and from high-burden countries.MethodIn this prospective cohort study, we recruited participants from 54 centres (eg, clinics, community settings) in London, Birmingham, and Leicester in the UK. Participants were eligible if they were aged 16 years or older and at high risk for latent tuberculosis infection (ie, recent contact with someone with active tuberculosis [contacts] or a migrant who had arrived in the UK in the past 5 years from—or who frequently travelled to—a country with a high burden of tuberculosis [migrants]). Exclusion criteria included prevalent cases of tuberculosis, and participants who were treated for latent tuberculosis after a positive test result in this study. Each participant received three tests (QuantiFERON-TB Gold-In Tube, T-SPOT.TB, and a Mantoux TST). A positive TST result was reported using three thresholds: 5 mm (TST-5), 10 mm (TST-10), and greater than 5 mm in BCG-naive or 15 mm in BCG-vaccinated (TST-15) participants. Participants were followed up from recruitment to development of tuberculosis or censoring. Incident tuberculosis cases were identified by national tuberculosis databases, telephone interview, and review of medical notes. Our primary objective was to estimate the prognostic value of IGRAs compared with TST, assessed by the ratio of incidence rate ratios and predictive values for tuberculosis development. The study was registered with ClinicalTrials.gov, NCT01162265, and is now complete.FindingsBetween May 4, 2010, and June 1, 2015, 10 045 people were recruited, of whom 9610 were eligible for inclusion. Of this cohort, 4861 (50·6%) were contacts and 4749 (49·4%) were migrants. Participants were followed up for a median of 2·9 years (range 21 days to 5·9 years). 97 (1·0%) of 9610 participants developed active tuberculosis (77 [1·2%] of 6380 with results for all three tests). In all tests, annual incidence of tuberculosis was very low in those who tested negatively (ranging from 1·2 per 1000 person-years, 95% CI 0·6–2·0 for TST-5 to 1·9 per 1000 person-years, 95% CI 1·3–2·7, for QuantiFERON-TB Gold In-Tube). Annual incidence in participants who tested positively were highest for T-SPOT.TB (13·2 per 1000 person-years, 95% CI 9·9–17·4), TST-15 (11·1 per 1000 person-years, 8·3–14·6), and QuantiFERON-TB Gold In-Tube (10·1 per 1000 person-years, 7·4–13·4). Positive results for these tests were significantly better predictors of progression than TST-10 and TST-5 (eg, ratio of test positivity rates in those progressing to tuberculosis compared with those not progressing T-SPOT.TB vs TST-5: 1·99, 95% CI 1·68–2·34; p<0·0001). However, TST-5 identified a higher proportion of participants who progressed to active tuberculosis (64 [83%] of 77 tested) than all other tests and TST thresholds (≤75%).InterpretationIGRA-based or BCG-stratified TST strategies appear most suited to screening for potential disease progression among high-risk groups. Further work will be needed to assess country-specific cost-effectiveness of each screening test, and in the absence of highly specific diagnostic tests, cheap non-toxic treatments need to be developed that could be given to larger groups of people at potential risk.FundingNational Institute for Health Research Health Technology Assessment Programme 08-68-01.