Tuberculin Skin Test Test Research Articles

Repeated tuberculin skin testing following therapy with TNF-alpha inhibitors

To determine the rate of true tuberculin skin test (TST) response in a cohort of patients with rheumatic disease treated with tumor necrosis factor inhibitors (TNFi). The study population included consecutive patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) treated with TNFi for at least 3 months. Patients with a positive TST at screening who began Tb prophylaxis before the beginning of TNFi therapy were excluded. All patients underwent a second TST. True TST response was defined as an increase of 6 mm of induration between the screening test and the second test. Forty patients (12 men and 28 women) were included. Mean age was 51.2 years. Of them, 27 (67.5%) had RA, eight (20%) had PsA, and five patients (12.5%) had AS. At pre-treatment TST, 15 patients had a TST > or = 5 mm. A significantly higher percent of patients with TST > or = 5 mm was seen among men compared with women (75% vs. 21%, p = 0.012) and patients with PsA compared with patients with RA (75% vs. 22%, p = 0.014). At the second test, eight (20%) had an increase of 6 mm between readings with four having an increase of 10 mm or more. Four patients received infliximab and the other four were treated with etanercept. Seven of these eight patients had RA and one was a patient with PsA. Patients with true TST response were significantly older and non-smokers with elevated sedimentation rate and a higher rate of anemia. Nationality, comorbid conditions, treatment with immunosuppressives, and BCG vaccination status had no significant influence on the TST response. Serial TST testing in patients receiving TNFi is indicated to identify patients with reactivation of latent tuberculosis infection or those exposed to mycobacterium.

The Tuberculin Skin Test Increases the Responses Measured by T Cell Interferon‐Gamma Release Assays

RUTI is a vaccine consisting of Mycobacterium tuberculosis bacilli grown in stress conditions that is fragmented, detoxified and liposomed. RUTI was designed to shorten the treatment of latent tuberculosis infection (LTBI) with isoniazid from 9 months to just 1 month, by additional treatment with two inoculations of RUTI 4 weeks apart. During the validation process for monitoring the immunogenicity of administration of RUTI in a Phase I clinical trial, the question arose whether to introduce the tuberculin skin test (TST) in the screening of non-LTBI volunteers. This study was designed to evaluate the effect of TST on subsequent different T-cell interferon-gamma release assay (TIGRA) responses, using a spectrum of M. tuberculosis-related antigens (ESAT-6, CFP-10, 16 kDa, 19 kDa, MPT64, Ag 85B, 38 kDa, hsp65, PPD and BCG). The results showed an increase in post-TST response even in non-LTBI subjects for most antigens tested, as measured both by whole blood assay (WBA) and ELISPOT. Increased ELISPOT response decreased toward pre-TST levels within 1 month whereas the WBA response did not. Taking into account that there is no definitive correlation between TST and TIGRA tests to diagnose LTBI and the feasibility that TST might alter the immune monitoring included in clinical trials, these data suggest that TST determination should be carefully planned to avoid any interference with TIGRA.

Predictive Value of a Whole Blood IFN-γ Assay for the Development of Active Tuberculosis Disease after Recent Infection with Mycobacterium tuberculosis

Numerous studies have been published on the new Mycobacterium tuberculosis (MTB)-specific IFN-gamma release assays. However, their prognostic value for progression from latent tuberculosis infection (LTBI) to active TB has yet to be established. To compare the QuantiFERON-TB Gold In-Tube assay (QFT) with the tuberculin skin test (TST) in recently exposed close contacts of active TB cases with respect to their development of TB disease within 2 years. Close contacts (n = 601) of MTB-positive source cases underwent both TST and QFT testing and were subsequently observed for 103 (+/-13.5) weeks. Risk factors for MTB infection were evaluated by multivariate analysis. For the TST, 40.4% (243/601) of contacts were positive at a 5-mm cutoff, whereas only 66 (11%) were QFT positive. QFT positivity, but not TST, was associated with exposure time (P < 0.0001). Six contacts progressed to TB disease within the 2-year follow-up. All were QFT positive and had declined preventive treatment, equating to a progression rate of 14.6% (6/41) among those who were QFT positive. The progression rate for untreated TST-positive subjects was significantly lower (P < 0.003), at 2.3% (5 of 219), and one subject who progressed was TST negative. Results suggest that QFT is a more accurate indicator of the presence of LTBI than the TST and provides at least the same sensitivity for detecting those who will progress to active TB. The high rate of progression to active TB of those who are QFT positive (14.6%), which is far greater than the 2.3% found for those who are TST positive, has health and economic implications for enhanced TB control, particularly if this higher progression rate is seen in studies of other at-risk populations.

Comparison of a whole blood Interferon-γ assay and A tuberculin skin test for detecting latent tuberculosis infection in children

Purpose : Surveillance for detecting and managing latent tuberculosis infection (LTBI) is a key component of tuberculosis control. The classic surveillance tool, the tuberculin skin test (TST), may have some limitations when used in the Bacillus Calmette-Guerin (BCG)-vaccinated population. The object was to perform a blood test QuantiFERON®-TB Gold In Tube (QFT-G IT) based on the detection of interferon-γ (IFN-γ) released by T cells in response to Mycobacterium tuberculosis-specific antigens, and to compare the efficacy of this new diagnostic tool for LTBI with that of TST. Methods : For six months, between October 1, 2006 and April 30, 2007, data were collected from 111 patients under 15 years of age at Severance Children's Hospital. TST and QFT-G IT tests were performed with children with or without contact histories of tuberculosis. In addition to these tests, we examined comparative data from 29 adults who had tuberculosis, to detect false negative rates in the QFT-G IT method. Results : Thirty-three children had household contact histories. In this group, 15% and 42% of cases were found to be positive using the QFT-G IT assay and TST, respectively. Agreement was low between these two tests (κ=0.39). In the adult active tuberculosis group, the QFT-G IT false negative rate defined as a positive culture and a negative QFT-G IT result was 12.5%. Conclusion : In diagnosing LTBI in children, the usefulness of a whole-blood IFN-γ assay employing TB-specific antigens will be revealed only by examining additional longitudinal clinical data; this study serves as a starting point in that process.

The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort

BackgroundAssuming a higher risk of latent tuberculosis (TB) infection in the population of Rio de Janeiro, Brazil, in October of 1998 the TB Control Program of Clementino Fraga Filho Hospital (CFFH) routinely started to recommend a two-step tuberculin skin test (TST) in contacts of pulmonary TB cases in order to distinguish a boosting reaction due to a recall of delayed hypersensitivity previously established by infection with Mycobacterium tuberculosis (M.tb) or BCG vaccination from a tuberculin conversion. The aim of this study was to assess the prevalence of boosted tuberculin skin tests among contacts of individuals with active pulmonary tuberculosis (TB).MethodsRetrospective cohort of TB contacts ≥ 12 years old who were evaluated between October 1st, 1998 and October 31st 2001. Contacts with an initial TST ≤ 4 mm were considered negative and had a second TST applied after 7–14 days. Boosting reaction was defined as a second TST ≥ 10 mm with an increase in induration ≥ 6 mm related to the first TST. All contacts with either a positive initial or repeat TST had a chest x-ray to rule out active TB disease, and initially positive contacts were offered isoniazid preventive therapy. Contacts that boosted did not receive treatment for latent TB infection and were followed for 24 months to monitor the development of TB. Statistical analysis of dichotomous variables was performed using Chi-square test. Differences were considered significant at a p < 0.05.ResultsFifty four percent (572/1060) of contacts had an initial negative TST and 79% of them (455/572) had a second TST. Boosting was identified in 6% (28/455). The mean age of contacts with a boosting reaction was 42.3 ± 21.1 and with no boosting was 28.7 ± 21.7 (p = 0.01). Fifty percent (14/28) of individuals whose test boosted met criteria for TST conversion on the second TST (increase in induration ≥ 10 mm). None of the 28 contacts whose reaction boosted developed TB disease within two years following the TST.ConclusionThe low number of contacts with boosting and the difficulty in distinguishing boosting from TST conversion in the second TST suggests that the strategy of two-step TST testing among contacts of active TB cases may not be useful. However, this conclusion must be taken with caution because of the small number of subjects followed.

Usefulness of QuantiFERON TB-2G, a Diagnostic Method for Latent Tuberculosis Infection, in a Contact Investigation of Health Care Workers

To evaluate the usefulness of QuantiFERON TB-2G (QFT-2G) for detecting latent tuberculosis infection (LTBI) in a contact investigation of health care workers. The investigated subjects were 190 subjects among the health care workers who were examined between January 2005 and June 2006. Background information, including a past history of tuberculosis (TB) or tuberculin skin test (TST) or BCG vaccination, and contact score (infectivity x contact duration) were investigated. The TST and QFT-2G test were performed on all subjects. In 109 subjects with a negative TST history, the TST results were converted to positive in 38 subjects. While the TST was positive in 48 subjects (25%), the QFT-2G test was positive in only five subjects (3%). The correlation of the QFT-2G with TST results was not significant. There was no relationship between contact score and the TST result. Twenty-nine subjects had TST positive responses (22%), but there were no QFT-2G positive responses in subjects with a mild contact score. Sixteen subjects had TST positive responses (31%), but two subjects showed positive QFT-2G results (4%) in the moderate contact score group. However, the positive response rate of the TST and QFT-2G test was the same percentage in the severe contact score group (33%). The QFT-2G test showed a significant relationship with the contact score when compared with the TST. If the subjects with LTBI in the moderate contact score group were selectively excluded, the contact investigation in the mild contact score group may not be necessary. If there would have been many subjects with the QFT-2G positive responses in the moderate contact score group, we think that the QFT-2G test must be performed even in the mild contact score group.

Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

BackgroundBCG-vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection.MethodsWe compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON®-TB-Gold In Tube; QFT-G) during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany.ResultsDuring a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years) from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8%) had received BCG vaccination and 84 (27.2%) had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000). For the TST, the positive response rate was 44.3% (137/309), whilst only 31 (10%) showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23), and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5). In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68), increasing to 0.68 (95% CI 0.46–0.81), if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany.ConclusionThe QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

The Value of Serum Antilipoarabinomannan Antibody Detection in the Diagnosis of Latent Tuberculosis in Hemodialysis Patients

The risk for tuberculosis (TB) reactivation in hemodialysis (HD) patients is increased, and screening for latent TB is recommended. The tuberculin skin test (TST) is inaccurate because of the high incidence of anergy in skin testing in HD patients and its inability to differentiate latent from eradicated TB infection. In this study, use of serum antilipoarabinomannan (anti-LAM) antibody detection for the diagnosis of latent TB in a dialysis population was evaluated. Seventy-four HD patients never treated for TB composed the first group. Forty-eight healthy volunteers never treated for TB served as controls. Twenty-one TST-positive renal transplant candidates on dialysis therapy who had completed preventive anti-TB treatment formed a third group. The TST (using the Mantoux method) and anti-LAM test (using an immunochromatographic assay) were performed in all subjects participating in the study. In the first group, a strong association was detected between results of the TST and anti-LAM test (P < 0.0001, chi-square test). A similar association was found in the second group. In the group of HD patients treated for TB, a positive TST result and negative anti-LAM test result was a constant finding. The association between the TST and anti-LAM test in HD patients suggests that the anti-LAM test could be a useful tool for diagnosing latent TB. The absence of anti-LAM antibodies in anti-TB-treated HD patients suggests that immune response to lipoarabinomannan lacks long-lasting memory. A negative anti-LAM test result might reflect the absence of latent TB, even in patients with a positive TST result.

Tuberculosis infection in children who are contacts of immigrant tuberculosis patients

The present study aimed to determine what proportion of children who are in close contact with immigrant tuberculosis (TB) patients are infected with Mycobacterium tuberculosis. For 1.5 yrs, 14 municipal health services in The Netherlands collected data from all non-Dutch TB patients and their contacts. Close contacts aged < 16 yrs received a tuberculin skin test (TST). A positive TST was defined as an induration of > or = 10 mm among nonvaccinated children, and > or = 16 mm among bacille Calmette-Guérin-vaccinated children. In total, 244 patients had 359 close contacts aged < 16 yrs. Nine out of the 359 (2.5%) had TB. A TST test was given to 298 out of the 359 (83%). Of the 115 contacts of 44 extrapulmonary TB patients, three (3%) had a positive TST. Of the 186 contacts of 58 positive pulmonary TB patients, 30 (16%) had a positive TST. Contacts of sputum smear-positive patients significantly more often had a positive TST (25%), compared with the contacts of sputum smear-negative patients (7%). Children born abroad significantly more often had a positive TST (20%) than children born in The Netherlands (5%). In conclusion, the prevalence of active tuberculosis and latent tuberculosis infection among children who are close contacts of immigrant tuberculosis patients is high and warrants an expansion of contact investigation.

A survey of tuberculosis control programs in seventeen Minnesota hospitals: Implications for policy development

Background: Generation of proposed policies directed at interrupting the transmission of Mycobacterium tuberculosis resulted in a need for data establishing health care worker (HCW) tuberculosis (TB) transmission risk and control programs that were in place before 1992. Methods: A voluntary sample of 18 Minnesota health care facilities was surveyed retrospectively for the years 1989 to 1991. The survey was designed to establish the frequency of positive tuberculin skin test (TST) results, the rate of positive results during routine screening, the incidence of positive TST results identified through exposure follow-up, the type of respiratory protection (mask) used, and ventilation patterns of TB isolation rooms. The TST testing program, including name of product used, method of application, and reading/documentation behaviors, was requested. Results: Data were analyzed from 17 hospitals (one long-term facility was deleted). Three hospitals screened all HCWs annually; the remaining hospitals screened HCWs at varying intervals. Forty-eight positive TST results were identified in routine screening. The rate per 10,000 HCWs screened was 5.8 in 1989; 15.9 in 1990; and 14.8 in 1991. An upward trend was noted in positive TST results only in metropolitan teaching/public hospitals. Intercomparisons of TST screening data demonstrated that employees located in Greater Minnesota were more likely to have positive TST results than employees at facilities in the metropolitan area. Hospitals in Greater Minnesota were more likely than metropolitan area hospitals to use tuberculin skin test material. HCWs screened with tuberculin purified protein derivative were more likely to have positive test results than HCWs screened with tuberculin purified protein derivative. Unisolated patients with communicable TB accounted for 445 patient days of probable risk of exposure for HCWs, without demonstration of a trend by calendar year. There were a total of 33 exposure events. Ten of 1031 HCWs screened after an exposure event were declared to be TST positive, for an overall conversion rate of 9.7 per 1000 employees screened. All hospitals used surgical masks for respiratory protection. Seventy-six percent of the hospitals had isolation rooms with negative ventilation; 12% reported isolation rooms with neutral pressure. Conclusion: The practice in Minnesota hospitals surveyed was reasonably consistent with the critical elements defined in the 1990 CDC guidelines for an effective TB control program. The rate of positive TST results was low, with programs in place before 1992. Unified TST programs permitting evaluation of programs are endorsed. Respiratory protection should be protective, not excessive. Engineering controls of isolation rooms should be ensured. Policy development should be driven by the prevalence and incidence of disease in the HCW's place of employment.