The value of counting BCG scars for interpretation of tuberculin skin tests in a tuberculosis hyperendemic shantytown, Peru.

SETTING: The tuberculin skin test (TST) is widely used as a diagnostic or screening test for Mycobacterium tuberculosis infection and disease. A peri-urban shantytown in the desert hills of south Lima, Peru, highly endemic for tuberculosis, and where bacille Calmette-Guérin (BCG) vaccine had been given in multiple doses until 1995. OBJECTIVE: To analyze the effect of multiple BCG vaccines on TST in a community-based setting. DESIGN: Point-prevalence survey of TST reactions of 572 people aged 6-26 years from 255 households. TST reactions were compared to the observed number of BCG scars and other potential risk factors (age, living with a TST-positive person, and contact with active tuberculosis). RESULT: People with two or more scars had significantly larger reactions, even after adjusting for potential risk factors. The adjusted population attributable fraction of being TST-positive and having two or more BCG scars was 26%. CONCLUSION: There is no demonstrated benefit of repeat BCG vaccination. We therefore recommend that physicians take into consideration the number of BCG scars when interpreting the TST and that programs give no more than one BCG vaccination.     

Tuberculin skin testing in BCG-vaccinated populations of adults and children at high risk for tuberculosis in Taiwan.

SETTING: Various populations at high risk for tuberculosis (TB) infection and with high bacille Calmette-Guérin (BCG) vaccination coverage in eastern Taiwan. OBJECTIVE: To investigate the usefulness of the tuberculin skin test (TST) to diagnose TB in BCG-vaccinated populations. DESIGN: Cross-sectional survey. RESULTS: TST reaction size was recorded for 444 individuals ranging in age from 8 months to 99 years, of whom 94.3% had scars to suggest previous BCG vaccination. The TST-positive (> or =10 mm) rate was increased in all comparisons of higher to lower TB risk, including household contacts (relative risk [RR] 3.52, P < 0.0001) and intermediate risk residents (RR 2.30, P = 0.030) compared to a lower risk control group. Advancing age was generally associated with increases in the TST-positive rate. Gender or the number of BCG vaccinations had no relation to the TST-positive rate. CONCLUSIONS: The results of this survey suggest that in eastern Taiwan a positive TST represents either active or latent TB infection rather than past BCG vaccination. Therefore, high BCG vaccination coverage in this region does not appear to limit the usefulness of the TST as a tool for diagnosing TB.     

Tuberculin reactivity in first‐year schoolchildren in Madagascar

Objective The tuberculin skin test (TST) is an important tool in the diagnosis of tuberculosis infection in children. However, the interpretation of TST may be complicated by prior Bacillus Calmette‐Guerin (BCG) vaccination. We evaluated the effect of vaccination with BCG on TST reactivity in first‐year pupils attending state schools in Antananarivo. Methods STs were performed on 376 first‐year schoolchildren, aged 6 and 7, attending two state primary schools. The relationships between epidemiological information, BCG status (vaccination, BCG scars) and TST reactivity were assessed to compare TST sensitivity between children with and without BCG vaccination and between those with and without a BCG scar. Result The prevalence of positive TST results of ≥5, ≥10 and ≥ 15 mm was 20.2% (76/376), 18.3% (69/376) and 11.4% (43/376), respectively. BCG vaccination was not associated with TST reactivity, whatever the threshold used: ≥5 mm (odds ratio (OR, 1.2; 95% confidence interval (CI), 0.7–2.0); ≥10 mm (OR, 0.9; 95% CI, 0.6–1.7); ≥15 mm (OR, 0.6; 95% CI, 0.3–1.2). Conclusion These results suggest that in Madagascar, a positive TST result indicates TB infection (active or latent) rather than past BCG vaccination. Therefore, high BCG vaccination coverage does not appear to impair the usefulness of the TST as a tool for diagnosing tuberculosis.     

Comparison of tuberculin skin testing and QuantiFERON-TB Gold-In Tube test in health care workers

The purpose of this prospective, cross-sectional observational study was to compare the tuberculin skin testing (TST) with QuantiFERON-TB Gold-In Tube (QTF-GIT) for the detection of latent tuberculosis infection in healthcare workers (HCWs). The study included 78 volunteers who are HCWs at the same tertiary care teaching hospital for chest diseases and tuberculosis. Participants with active tuberculosis, immunodefficiency or malnutrition were not included. The TST was administered by the Mantoux method. Peptides representing ESAT-6, CFP-10 and TB7-7 were used as TB-specific antigens in the whole-blood Interferon-gamma (IFN-g) assay (QTF-GIT). There was a statistically significant relation between the number of Bacillus Calmette-Guerin (BCG) scars and the diameter of TST (p< 0.01). QTF results according to previous BCG vaccinations did not significantly differ (p> 0.05). There was an intermediate concordance between two tests (k: 0.346). QTF-GIT has a sensitivity of 56.14% (both TST and QTF-GIT are positive), specificity of 90.48% (both TST and QTF-GIT are negative); positive predictive value of 94.12% and negative predictive value of 43.18% and accuracy is 65.38%. There was a statistically significant relation between TST diameter and QTF result (p< 0.01). Latent tuberculosis infection prevalance of our study population was 43% according to QTF-GIT test, 73% according to TST and BCG vaccination rate was 87%. In conclusion, TST is affected by previous BCG vaccinations, QTF-GIT is not. We can recommend QTF-GIT test for the detection of latent tuberculosis infection as an alternative to TST in populations with routine BCG vaccination programme.     

QuantiFERON-TB Gold test for screening latent tuberculosis infection in hemodialysis patients

Hemodialysis patients are at increased risk of latent tuberculosis infection (LTBI) compared with the general population. QuantiFERON-TB Gold (QFT-G) for LTBI detection is more promising than tuberculin skin test (TST) in hemodialysis patients. The aim of this study is to determine whether the QFT-G is more sensitive than the TST in hemodialysis patients in LTBI. Eighty nine hemodialysis patients were evaluated for latent tuberculosis infection with the TST and QFT-G. Blood was obtained for QFT-G, and then TST was administered to all patients. Demographic information, laboratory tests, chest radiography results and BCG vaccination status were collected on standardized patient medical files. Forty patients had positive QFT-G results. 56 patients had TST induration above 5 mm, 28 patients above 10 mm. 61 patients had BCG vaccination scar. Statistically significant correlation was detected between TST and QFT-G (p< 0.05). In the BCG non-vaccinated subgroup, TST was positive in 8 (29%) patients and the QFT-G was positive in 11 (39%). Among the 21 non vaccinated patients with results for both tests, the concordance between the TST and QFT-G was 82%, k= 0.61, p= 0.001. We found good agreement between the TST and QFT-G test for LTBI in non vaccinated hemodialysis patients, whereas we found poor agreement in vaccinated patients. Because BCG vaccination is widely used in our country, the QFT-G test might be more useful for the diagnosis of LTBI than TST in hemodialysis patients who are suspected to have LTBI.     

Contact tracing using a new T-cell-based test: better correlation with tuberculosis exposure than the tuberculin skin test.

SETTING: Residential institution for alcoholics in Switzerland. OBJECTIVE: To compare the results of the tuberculin skin test (TST) and the new T-cell-based test for tuberculosis infection (T-SPOT.TB) in subjects exposed to a case of smear-positive pulmonary TB (PTB). DESIGN: After the notification of smear-positive PTB in a resident of an institution for alcoholics, contacts underwent TST and determination of Mycobacterium tuberculosis specific T-cells in blood by T-SPOT.TB. Results were analysed according to age, history of BCG vaccination, and level of exposure to the index case. RESULTS: There was no correlation between the level of exposure and the TST results, but the T-SPOT.TB results were significantly correlated with the level of exposure (P = 0.029, OR 5.00, 95%CI 1.05-23.86). Contacts who had been previously BCG-vaccinated were significantly more likely to have a positive TST than unvaccinated contacts (52% vs. 0%, P = 0.0003), but there was no influence of prior BCG vaccination on T-SPOT.TB results. CONCLUSIONS: T-SPOT.TB test results correlated better than TST with level of exposure to M. tuberculosis and were not confounded by prior BCG vaccination. This test allows better selection of contacts who should receive treatment for latent TB infection.     

BCG vaccination: where are we now?

The bacillus Calmette-Guerin (BCG) vaccine is administered and recommended for the prevention and control of tuberculosis in developing countries with high-risk settings. A new general BCG vaccination programme against tuberculosis has been introduced since 1997 in Turkey. The aim of this study was to evaluate the BCG vaccination status in Düzce and to analyze contributing factors for the vaccination programme. BCG screening were performed in 1100 8th class students from nine primary schools of Düzce city centre and seven counties. BCG scar presence was taken as authoritative for vaccination status. BCG vaccination ratio was 0.94. Of 1100 students, 1030 had BCG scars; 478 had single scar, 536 had two scars and 16 had three scars. The significant negative correlation was observed between the BCG administration ratio and the number of children under age of 15 per health personnel (r= -0.771, p= 0.025). Furthermore, based on some published studies marked regional variation of BCG vaccination status in Turkey was also discussed in this article.     

The frequency profile of tuberculin skin testing among students in nursing school]

The frequency profile of tuberculin skin testing (TST) among students in nursing school was studied. Students received a TST upon matriculation. The TST was done by the method of Mantoux, in which 0.1 ml of PPDs was administered intradermally, and the diameters of skin rash and induration were read by the medical doctor at 48 hours. When TST results are negative--that is, the diameter of skin rash is below 10 mm (in Japan, the TST results are judged by skin rash diameter rather than that of induration)-BCG vaccination is given. Those receiving the BCG vaccination are retested with a TST one year later. When the second TST was also negative both the BCG vaccination and TST were followed for two more years. Those students testing TST-negative are not permitted to take clinical training in the tuberculosis ward. Student's mean age on entrance was 18.6 +/- 2.1 years old, and all but three were female. About 70% of students entering in 1996 to 1998 had a history of previous BCG vaccination. In 14% their positive TSTs could be attributed to probable infection with tuberculosis in childhood. In the remaining 16%, details as to TST and BCG vaccination status are unknown. The frequency distribution of TST results was bimodal, showing one peak at 6 mm and another at 12 mm (skin rash diameter). The percentage of negative and positive reactors are 47.1% and 52.9%, respectively. The TST-negative students entering in 1994 to 1996 were given the BCG vaccination. Twenty-four of 134 students (17.9%) remained negative at the second TST, and 6 students (4.5%) at the third year, even after two repeated BCG vaccinations. The TST results were chronologically observed in the above 6 students after BCG vaccination. The TST results of two students showed positive in September, 1996 and June, 1997. While four students showed positive in September, 1996, all ultimately reverted to negative when retested in June, 1997. Those students had negative results for TST at the initial test in 1998 had the two step-tuberculin skin testing. All eight students with negative TST had the history of BCG vaccination. The second TST showed positive except one student whose scar after BCG vaccination was not observed on the arm. The TST is currently recommended in hospital tuberculosis-control programs. If TST-negative, medical staff and students may not work in the tuberculosis ward. However, after BCG vaccinations is given, and subsequent TST conversion is confirmed, they are then able to work or to have training in the ward. From our results, there is 4.5% non-convertors even after 2 years of repeated BCG vaccinations. However, these non-converters turned positive four months after BCG vaccination, only to revert to negative nine months later. These students are considered to have delayed hypersensitivity to PPD after BCG vaccination. However, their reactivity waned in the short period of nine months after the conversion of their TST's. Therefore, it is concluded that non converters after repeated BCG vaccinations are able to have clinical training in the tuberculosis ward as long as their BCG vaccinations are correctly administered and any immunological deficiencies are ruled out.     

Tuberculin reactivity in a pediatric population with high BCG vaccination coverage.

SETTING: The tuberculin skin test (TST) is often included in diagnostic algorithms for tuberculosis (TB) in children. TST interpretation, however, may be complicated by prior Bacillus Calmette-Guerin (BCG) vaccination. We assessed the prevalence of and risk factors for positive TST reactions in children 3 to 60 months of age in Botswana, a country with high TB rates and BCG coverage of over 90%. METHODS: A multi-stage cluster survey was conducted in one rural and three urban districts. Data collected included demographic characteristics, nutritional indices, vaccination status, and prior TB exposure. Mantoux TSTs were administered and induration measured at 48-72 hours. RESULTS: Of 821 children identified, 783 had TSTs placed and read. Of the 759 children with vaccination cards, 755 (99.5%) had received BCG vaccine. Seventy-nine per cent of children had 0 mm induration, 7% had > or =10 mm induration ('positive' TST), and 2% had > or =15 mm. A positive TST was associated with reported contact with any person with active TB (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.02-3.6), or a mother (OR 5.1; 95% CI 2.1-12.4) or aunt (OR 5.3; 95% CI 2.0-14.0) with active TB. TSTs > or =5 mm (but not > or =10 mm) were associated with presence of a BCG scar. Positive reactions were not associated with age, time since BCG vaccination, clinical signs or symptoms of TB, nutritional status, crowding, or recent measles or polio immunization. CONCLUSION: The TST remains useful in identifying children with tuberculous infection in this setting of high TB prevalence and extensive BCG coverage.     

Detecting a low prevalence of latent tuberculosis among health care workers in Denmark detected by M. tuberculosis specific IFN-gamma whole-blood test

The study was designed to estimate prevalence of tuberculosis infection among health care workers, using the tuberculin skin test (TST) and the new M. tuberculosis specific diagnostic whole-blood test and to identify possible risk factors. Employees at 2 departments of infectious diseases in Copenhagen were invited to enter the study. All attendants completed a questionnaire, had a TST and blood drawn for detection of interferon-gamma produced after stimulation with M. tuberculosis specific antigens ESAT-6 and CFP-10 (QuantiFERON-TB-Gold, Cellestis). 47 of 139 (34%) participants had a positive TST whereas only 2 of 139 (1%) had a positive QuantiFERON TB-Gold test (QFT-TB). 42 of 106 (40%) BCG vaccinated had positive TST (> or =12 mm) compared with 2 of 27 (7%) unvaccinated persons. Among 47 persons with positive TST, 42 (89%) were BCG- vaccinated. The 2 QFT-TB positive participants as well as the remaining 45 TST positive participants showed no sign of active tuberculous disease and were allocated to 6-month clinical follow-up, without medical therapy. Today, 1.5 y later, all remain healthy. The high rate of positive TST among health care workers was most probably due to BCG vaccination and not to infection with M. tuberculosis. The overall transmission rate determined by QFT-TB was found to be very low. The QFT-TB may be useful in distinguishing persons with latent TB infection from persons with positive TST due to BCG vaccination and its use may reduce anxiety.     

Comparison of the QuantiFERON‐TB Gold In‐Tube test with the tuberculin skin test for detecting latent tuberculosis infection in hemodialysis patients

E.C. Seyhan, S. Sökücü, S. Altin, G. Günlüo?lu, S. Trablus, D. Yilmaz, O.K. Koksalan, H. Issever. Comparison of the QuantiFERON‐TB Gold In‐Tube test with the tuberculin skin test for detecting latent tuberculosis infection in hemodialysis patients.
Transpl Infect Dis 2010: 12: 98–105. All rights reserved Background and objectives. Hemodialysis (HD) patients are at increased risk of reactivation of latent tuberculosis (TB) infection (LTBI). LTBI screening of this population is recommended. The QuantiFERON‐TB Gold assay (QFT‐G) may be more accurate than the tuberculin skin test (TST) in the detection of LTBI. We prospectively compared the results of QFT‐G to TST in HD patients. Methods. We examined 100 patients and performed TST and QFT‐G tests. Data obtained from patients and medical records included medical history (past history of TB, Bacillus Calmette–Guerin [BCG] vaccination, history of contact with previous TB cases), radiography reports (chest x‐ray with changes consistent with old TB), and basic laboratory findings. Results. Forty‐three of 100 patients (43%) had a positive QFT‐G test result and 34 (34%) had a positive TST test result. Overall agreement between the QFT‐G and the TST was 65% (concordance [k]=0.26, P=0.01). Discordant test results were seen in 13 TST‐positive/QFT‐G‐negative patients and in 22 TST‐negative/QFT‐G‐positive patients. Before BCG vaccination and radiographic reports (of old TB changes) were associated with discordant test results. On multivariate analysis, a positive QFT‐G test was associated with contact with previous TB cases (P=0.026) and radiographic report (P=0.034), whereas a positive TST test also was associated with a history of BCG vaccination (P=0.015). Conclusions. QFT‐G test results were more closely associated with TB risk factors than were positive TST results. Additionally, the QFT‐G test was not affected by BCG vaccination. We concluded that QFT‐G test is a more useful diagnostic method than TST for detecting LTBI in HD patients.     

The effect of neonatal bacille Calmette-Guérin vaccination on purified protein derivative skin test results in Canadian aboriginal children

BACKGROUND: The effect that neonatal bacille Calmette-Guérin (BCG) vaccination has on tuberculin skin test (TST) results is not well evaluated in preschool children. METHODS: This was a retrospective cohort study of TST results in aboriginal children in Saskatchewan reserve communities. Records from the centralized provincial tuberculosis program were searched for aboriginal children aged 0 to 4 years during the time period 1991 to 1999. Only the first TST result reported as part of infant and preschool screening programs was considered. Children with active tuberculosis and those evaluated as part of a contact-tracing program were excluded. The BCG-vaccinated and unvaccinated groups were compared using wheal size cut points of 5 mm, 10 mm, and 15 mm. RESULTS: Data from 1,086 children with neonatal BCG vaccination and 1,867 unvaccinated children were analyzed. The rate of TST reactions was higher in vaccinated children at all ages, using a cut point of 5 mm. The rate of TST reactions was no different in vaccinated children >or= 1 year old when using a cut point of 15 mm. When using a cut point of 10 mm, the rate of TST reactions was higher at age 1 year but not different at age 4 years in the vaccinated children. CONCLUSION: The rate of TST reactions in preschool aboriginal children living on a reserve who have received neonatal BCG vaccination is affected by the cut point and age. The BCG vaccination status and age should therefore be considered when interpreting TST reactivity in the clinical assessment of aboriginal children participating in a tuberculosis control program.     

Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test.

Bacille Calmette-Guérin (BCG) vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection (LTBI). The TST was compared with a Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay during an outbreak of MTB infection at a police academy in Germany. Participants were grouped according to their risk of LTBI in close (n = 36) or occasional (n = 333) contacts to the index case. For the TST, the positive response rate was 53% (19 out of 36) among close and 16% (52 out of 333) among occasional contacts. In total, 56 TST-positive contacts (56 out of 71 = 78.9%) and 27 TST-negative controls (27 out of 298 = 9.1%) underwent ELISPOT testing. The odds ratio (OR) of a positive test result across the two groups was 29.2 (95% confidence interval (CI) 3.5-245.0) for the ELISPOT and 19.7 (95% CI 2.0-190.2) for the TST with a 5 mm cut-off. Of 369 contacts, 158 (42.8%) had previously received BCG vaccination. The overall agreement between the TST and the ELISPOT was low, and positive TST reactions were confounded by BCG vaccination (OR 4.8 (95% CI 1.3-18.0)). In contrast, use of a 10-mm induration cut-off for the TST among occasional contacts showed strong agreement between TST and ELISPOT in nonvaccinated persons. In bacille Calmette-Guérin-vaccinated individuals, the Mycobacterium tuberculosis-specific enzyme-linked immunospot assay is a better indicator for the risk of latent tuberculosis infection than the tuberculin skin test.     

Effect of BCG vaccination and non-tuberculous Mycobacterium infection on interferon gamma specific assay and a tuberculin skin test among children with a tuberculosis contact in Surabaya, Indonesia

The tuberculin skin test (TST) as a diagnostic tool for tuberculosis (TB) infection is used in many countries, including Indonesia, but lacks specificity. Interferon-gamma is a highly specific assay because it is not influenced by previous BCG vaccination or non-tuberculous mycobacteria (NTM) infections. We aimed to study the effect of BCG vaccination and NTM infection on the results of the interferon-gamma specific assay and TST among children with a TB contact. We carried out a cross-sectional study of children at an outpatient clinic in Surabaya, Indonesia. We studied 37 children aged 1-15 years having a household contact with an acid-fast bacilli positive adult index case. BCG vaccination was determined by the presence of a BCG scar. A PPD RT23 2 tuberculin test was used for the TST. ESAT-6, CFP-10, and TB 7.7(p4) antigens were used for the interferon-gamma assay by ELISA. Gastric aspirates were cultured in Lowenstein-Jensen media. A comparison of the two diagnostic tools among children aged 1-5 years without a BCG scar, revealed high agreement, while children with a BCG scar it revealed disagreement. Among children aged > 5 years with or without a BCG scar the comparisons revealed disagreement. Among children aged > 5-10 years, a comparison of the two diagnostic tools among NTM positive and negative children, there was a disagreement in results. Among children aged 1-5 years, the TST was influenced by a BCG scar. Infection with NTM had no influence on the results of the TST among children aged > 5-10 years, while in children aged 1-5 years and > 10 years the results could not be determined in this study.     

A comparison of an interferon-gamma release assay and tuberculin skin test in refractory inflammatory disease patients screened for latent tuberculosis prior to the initiation of a first tumor necrosis factor α inhibitor

Treatment with TNFα inhibitors increases risk of reactivating a latent tuberculosis\infection (LTBI). Therefore screening, prior to therapy with TNFα inhibitors, has been recommended, even in low-endemic areas such as well-developed Western Europe countries. We evaluated interferon-gamma release assay (IGRA), as opposed to tuberculin skin test (TST), for detection of LTBI in refractory inflammatory disease patients prior to the initiation of a first TNFα inhibitor. In addition, we evaluated the impact of impaired cellular immunity on IGRA. Patients starting on TNFα inhibition were screened for LTBI by TST and IGRA (Quantiferon-TB Gold). Data on tuberculosis exposure and Bacillus Calmette–Guérin (BCG) vaccination were obtained. Cellular immunity was assessed by CD4⁺ T lymphocyte cell count. Nine out of 56 patients (16.1%) tested positive for LTBI. A concordant positive result was present in three patients with a medical history of tuberculosis exposure. Six patients with discordant test results had either: (1) a negative TST and positive IGRA in combination with a medical history of tuberculosis exposure (n = 1) or (2) a positive TST and negative IGRA in combination with BCG vaccination (n = 3) or a medical history of tuberculosis exposure (n = 2). CD4⁺ T lymphocyte cell counts were within normal limits, and no indeterminate results of IGRA were present. IGRA appears reliable for confirming TST and excluding a false positive TST (due to prior BCG vaccination) in this Dutch serie of patients. In addition, IGRA may detect one additional case of LTBI out of 56 patients that would otherwise be missed using solely TST. Immune suppression appears not to result significantly in lower CD4⁺ T lymphocyte cell counts and indeterminate results of IGRA, despite systemic corticosteroid treatment in half of the patients. Confirmation in larger studies, including assessment of cost-effectiveness, is required.     

Tuberculin skin testing of physicians at a midwestern teaching hospital: a 6-year prospective study.

The epidemiology of tuberculin reactivity among physicians practicing in regions of moderate tuberculosis prevalence is unknown. We prospectively assessed the epidemiology of tuberculin skin test (TST) reactivity among physicians in training in St. Louis between 1992 and 1998. Of 1574 physicians who were tested, 267 (17%) had positive TST results. Older age, birth outside of the United States, prior bacille Calmette-Guérin (BCG) vaccination, and practice in the fields of medicine, anesthesiology, or psychiatry were associated with a positive TST result. Among physicians born in the United States, 63 (5.7%) had positive TST results. Among physicians with > or = 2 documented TSTs, 12 had conversion to a positive TST (1.6%; 1.03 conversions per 100 person-years). Physicians in this study had a high rate of tuberculin reactivity, despite a low conversion rate. The relationship between TST conversion and birth outside of the United States and BCG vaccination suggests a booster phenomenon rather than true new TST conversions.     

Use of an interferon-gamma release assay to diagnose latent tuberculosis infection in foreign-born patients

BACKGROUND: The tuberculin skin test (TST) has a low specificity in the setting of bacille Calmette-Guérin (BCG) vaccination. Interferon-gamma release assays (IGRAs) appear to be more specific but have not been validated in this population under routine clinical conditions. We sought to validate the routine clinical use of the T-SPOT.TB test (Oxford Immunotec; Oxford, UK), an IGRA, in a predominantly foreign-born population with a high rate of BCG vaccination. METHODS: We compared the TST and the T-SPOT.TB test in 96 subjects at a New York City Department of Health tuberculosis clinic. We aimed to determine which test better predicted being a close contact of a case of active tuberculosis, a surrogate for latent tuberculosis infection. RESULTS: A positive T-SPOT.TB test result was strongly associated with being a close contact of a case of active tuberculosis after adjustment for potential confounders (adjusted odds ratio, 2.9; 95% confidence interval, 1.1 to 7.3; p = 0.03). A positive TST result was associated with being a contact only in subjects without BCG vaccination (p = 0.02). The T-SPOT.TB test was more specific for being a close contact than the TST (p < 0.001). Specificity in BCG-vaccinated subjects was 3% for the TST compared with 70% for the T-SPOT.TB test (p < 0.001). CONCLUSIONS: The T-SPOT.TB test is superior in routine clinical use to the TST for identifying high-risk individuals among foreign-born populations with high rates of BCG vaccination.     

Comparison of the QuantiFERON‐TB Gold In‐Tube test with the tuberculin skin test for detecting latent tuberculosis infection prior to hematopoietic stem cell transplantation

A total of 244 patients including 100 (41%) autologous hematopoietic stem cell transplant (HCT) recipients and 144 (59%) allogeneic HCT recipients were enrolled over a 28‐month period. During the study period, no prophylaxis for latent tuberculosis (TB) infection was administrated. Of these, 201 (82%) had Bacillus Calmette‐Guérin (BCG) scars or prior histories of BCG vaccination. The tuberculin skin test (TST) and the QuantiFERON‐TB Gold In‐Tube (QFT‐GIT) test were performed simultaneously in all 244 patients. TST indurations were ≥ 5 mm in 39 of these patients (15%), and in 25 (10%) indurations were ≥ 10 mm. In addition, 40 (16%) had positive QFT‐GIT outcomes, and 34 (14%) indeterminate outcomes. If the 34 patients with indeterminate QFT‐GIT results were excluded from the overall agreement analysis, the agreement between the TST results (induration size ≥ 5 mm) and the QFT‐GIT results in the 210 patients with clear QFT results was poor (κ = 0.08, 95% confidence interval [CI] ?0.06 to 0.24), as it was for the patients with indurations ≥ 10 mm (κ = 0.15, 95% CI ?0.004 to 0.31). During follow up, 2 patients developed TB after HCT. The incidence of TB in the patients with positive QFT‐GIT outcomes was 2.80 per 100 person‐years (95% CI 0.07–15.81), whereas among those with positive TST (≥ 5 mm) results, it was 0 per 100 person‐years (95% CI 0–8.00). However, this finding should be cautiously interpreted because of the relatively short follow up and the fact that the sample size of the study cohort did not have adequate power. In conclusion, our data show that, although the frequencies of positive outcomes in the 2 TB screening tests were similar, the overall agreement between the TST and the QFT‐GIT test was poor, regardless of BCG vaccination history.     

Rapid diagnosis of Mycobacterium tuberculosis infection in children using interferon-gamma release assays (IGRAs)

Diagnosis of tuberculosis (TB) in children by the tuberculin skin test (TST) poses a diagnostic challenge for physicians due to its low specificity and cross-reactivity with nontuberculous mycobacteria and bacille Calmette-Guerin (BCG). Although interferon-gamma release assays (IGRAs) have been shown as novel TST alternatives for diagnosis of latent TB infection (LTBI) in adults, their effectiveness is less clear in children. The present study examined QuantiFERON-TB Gold (QFT-G) responses and IFN-gamma production capacity of TST-positive children, younger children ≤5 years. A total of 517 children of whom 434 were TST positive ranging in age from 1 month to 18 years were evaluated by the QFT-G. Of the 517 children, 434 (84%) were TST positive, 25 (5.8%) of whom were found to be QFT-G positive and 25 (5.4%) with an indeterminate response. Of the 517 children, 355 (68.7%) were previously BCG immunized and 310/355 (87.3%) were TST positive including 18/27 (66.7%) QFT-positive children. Adequate IFN-gamma production by purified TB peptides or mitogen was observed in 92.8% of children, 29.6% of whom were <5 years. This study shows that the QFT-G assay is useful for diagnosis of LTBI. The finding of 5.8% positive QFT-G in 434 TST-positive children underscores the superior specificity of the QFT-G than the TST and its greater cost effectiveness in preventing unnecessary and potentially toxic treatment in children. The study suggests that the majority of positive TST in children represent false-positive reactions and supports the use of IGRAs for diagnosis of LTBI in children, including those <5 years of age.