Initial Tuberculin Skin Test Research Articles

Boosted Reaction on Two-Step Tuberculin Skin Test among Military Personnel in South Korea, a Setting with an Intermediate Burden of Tuberculosis and Routine Bacille Calmette-Guérin Vaccination

This study was performed to estimate the rate of boosted reaction in the two-step tuberculin skin test (TST) and to evaluate the associated factors among military personnel of South Korea, which has an intermediate burden of tuberculosis (TB) and a routine bacille Calmette-Guérin (BCG) vaccination policy. Two-step TST was performed on 264 military personnel who did not have a history of close contact to TB. Subjects with a negative reaction to the first test of <10 mm had a second TST applied 1 week later on the other forearm. A positive result (≥10 mm) on the initial TST was observed in 126 (48%) of the subjects. A boosted reaction on the second TST developed in 32 (23%) of the 124 subjects with a negative initial TST. In multiple logistic regression analysis, the size of the initial TST reaction was the only factor associated with a boosted reaction on the second TST. The high rate of boosted reaction among healthy adults in South Korea suggests that two-step TST should be performed to assess the baseline TST reactivity in settings with an intermediate burden of TB and routine BCG vaccination policy, especially among subjects with an initial TST reaction that is ≥5 mm.

Comparison of the interferon- γ release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers

Health care workers are at increased risk of Mycobacterium tuberculosis infection. The tuberculin skin test (TST) is frequently false positive in BCG-vaccinated health care workers. QuantiFERON-TB GOLD (QFT-G) is a sensitive and specific interferon-gamma release assay unaffected by BCG vaccination. This study compared TST and QFT-G in the diagnosis of latent TB infection in BCG-vaccinated health care workers. 39 health care workers exposed to a smear-positive TB patient were enrolled. Initial TST was positive in 33 (84.6%) cases, but only 4 (10.2%) cases using QFT-G. TST conversion occurred in 2/6 (33.3%), compared to 4/32(12.5%), cases using QFT-G. A higher proportion of QFT converters was associated with intimate contact, although not reaching statistical significance. Face-to-face contact >1 h was significantly associated with QFT-G conversion >or=0.7 IU/ml (OR 8.63, 95%CI 1.08-69.07, p=0.04). Agreement between TST and QFT-G was 18.0%, (kappa: -0.03). Concordance between TST and QFT (>or=0.35 IU/ml) conversion was 40.0%(kappa=-0.40), and 60.0%(kappa=0.00) if QFT >or=0.7 IU/ml was used. Agreement increased with increasing TST cut-offs. TST is not useful in contact investigation among BCG-vaccinated health care workers, in an area with intermediate burden of TB. QFT may provide additional information for the diagnosis and strategic management of preventive treatment of LTBI in BCG-vaccinated health care workers in a country with intermediate burden of TB.

Evidence for boostingMycobacterium tuberculosis-specific IFN-γ responses at 6 weeks following tuberculin skin testing: Table 1—

To the Editors: We read with great interest the paper by Leyten et al. 1 in the present issue of the European Respiratory Journal , which assessed whether the tuberculin skin test (TST) might affect the results of the QuantiFERON®-TB Gold (QFT-G), a blood-based Mycobacterium tuberculosis -specific interferon-γ release assay (IFNGRA). This is an important topic in the UK with respect to the recently published National Institute for Clinical Excellence (NICE) guidelines 2 for the diagnosis and treatment of tuberculosis (TB). The guidelines state that if a suspected case of TB yields a negative initial TST then the subject should be re-tested at 6 weeks, at which point an IFNGRA may be used in conjunction with the TST. Experts within the field have previously been worried about the potential boosting effect of the TST on IFNGRA responses. However, to …

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.

Boosted tuberculin skin testing in hemodialysis patients

Tuberculosis remains a significant health problem for patients receiving long-term hemodialysis (HD). The tuberculin skin test (TST) is an important method of detecting Mycobacterium tuberculosis infection. Cutaneous anergy decreases the accuracy of the test in these patients. Higher and repeating doses have been mentioned in the immunosuppressed patients. This study examined the significance and frequency of the booster phenomenon in 2-step tuberculin testing of these patients. A total of 106 outpatients in a hospital-based HD center in Turkey were screened with 5 and 10 tuberculin units (TU) and Candida antigen. To determine the frequency of booster phenomenon, patients with <10 mm indurations to the initial TST with 5 TU were given a second test with 10 TU, 7 days later. Forty (37.7%) of 106 patients had a significant tuberculin reaction (>or=10 mm) on the initial TST with 5 TU. The booster effect was detected in 16 (24.3%) of 66 patients who had a negative reaction (<or=10 mm) to the initial test. Overall, 56 (52.8%) patients showed a significant reaction on both tests. Anergy was found in 39 (36.8%) of 106 patients. Even with the high rate of anergy, TST seems to be useful for these patients; also, it is inexpensive and easy to perform. We suggest repeating the test with higher doses in patients with a high risk for tuberculosis. Anergy testing with Candida antigen may be helpful in determining the value of TST.

High Rate of Negative Results of Tuberculin and QuantiFERON Tests Among Individuals With a History of Positive Skin Test Results

To evaluate individuals at high risk for tuberculosis exposure who had a history of a positive tuberculin skin test (TST) result in order to determine the prevalence of unsuspected negative TST results. To confirm these findings with the QuantiFERON-TB test (QFT), an in vitro whole-blood assay that measures tuberculin-induced secretion of interferon-gamma. This survey was conducted from November 2001 through December 2003 at 3 sites where TST screening is regularly done. Detailed histories and reviews of medical records were performed. TSTs were placed and read by 2 experienced healthcare workers, and blood was drawn for QFT. Any subject with a negative result of an initial TST during the study (induration diameter, <10 mm) underwent a second TST and a second QFT. The TST-negative group comprised individuals for whom both TSTs had an induration diameter of <10 mm. The confirmed-negative group comprised individuals for whom both TSTs yielded no detectable induration and results of both QFTs were negative. A total of 67 immunocompetent subjects with positive results of a previous TST were enrolled in the study. Of 56 subjects who completed the TST protocol, 25 (44.6%; 95% confidence interval [CI], 31.6%-57.6%) were TST negative (P<.001). Of 31 subjects who completed the TST protocol and the QFT protocol, 8 (25.8%; 95% CI, 10.4%-41.2%) were confirmed negative (P<.005). A significant proportion of subjects with positive results of a previous TST were TST negative in this study, and a subset of these were confirmed negative. These individuals' TST status may have reverted or may never have been positive. It will be important in future studies to determine whether such individuals lack immunity to tuberculosis and whether they should be considered for reentry into tuberculosis screening programs.

Comparing Interferon- Release Assay with Tuberculin Skin Test Readings at 48-72 Hours and 144-168 Hours with Use of 2 Commercial Reagents

Despite widespread use, the tuberculin skin test (TST) has many limitations, including a requirement for a second visit between 48 and 72 hours. The goal of this study was to determine the reliability of a TST reading between 144 and 168 hours. Tuberculin antigen was applied into both forearms (Aplisol in one arm and Tubersol in the other, from single lots of each product) by the Mantoux method. Blood samples were obtained for interferon- gamma release assay. Subjects were seen at 48-72 hours for the initial (day 2) TST reading and returned at 144-168 hours for a second (day 7) reading. A total of 116 subjects at increased risk for tuberculosis were studied; 25 (22%) had positive results at day 2 with Tubersol and 27 (23%) had positive results at day 2 with Aplisol. Overall agreement between Tubersol and Aplisol at day 2 was 93% (kappa = 0.80) and at day 7 was 94% (kappa = 0.76). Overall agreement between day 2 and day 7 was 89% for Tubersol and 86% for Aplisol. Discordant results between day 2 and day 7 occurred mostly in persons with a history of bacille Calmette-Guerin vaccination. Subjects who fail to present at 48-72 hours for TST reading may still have a reliable TST reading at up to 168 hours. Aplisol and Tubersol reagents produce comparable results when compared with the interferon- gamma release assay.

Predictors of Positive Tuberculin Skin Test (TST) Results after 2‐Step TST among Health Care Workers in Manitoba, Canada

Baseline 2-step tuberculin skin testing (TST) is recommended for health care workers (HCWs) to identify cases of the "boosting phenomenon" (i.e., a negative initial TST result followed by a positive result) and to track the risk of acquiring occupational tuberculosis. However, the 2-step TST has been shown to be insufficient to identify all cases of the booster phenomenon in older adults and refugees. The objective of this study was to identify whether a history of bacille Calmette-Guérin (BCG) vaccination and foreign birth--variables that are known to be associated with the booster phenomenon--remain predictors of a positive TST result in a group of HCWs documented to have negative 2-step TST results (i.e., 2 TSTs done 7-28 days apart with indurations <10 mm in diameter). We performed a retrospective analysis of an employee database in a tertiary care hospital in Winnipeg, Canada. The study population was comprised of 698 HCWs with negative 2-step TST results who underwent a TST 0-2 years after completion of the 2-step procedure. Forty-six HCWs (6.6%) had a positive TST result 0-2 years after the 2-step test. In a multiple logistic regression analysis controlling for age, BCG vaccination, foreign birth, sex, and work setting, only history of BCG vaccination (odds ratio [OR], 8.38; 95% confidence interval [CI], 4.04-17.4), foreign birth (OR, 3.19; 95% CI, 1.53-6.62), and high-risk work setting (OR, 2.93; 95% CI, 1.44-5.95) were associated with a positive TST result. Even for HCWs with negative results of 2-step TST, foreign birth and history of BCG vaccination are associated with a positive result of a future TST. Some positive TST results in such HCWs are related to nonoccupational factors, including delayed boosting, rather than to conversion due to recent tuberculosis contact.

The booster phenomenon in 2-step tuberculin skin testing of patients receiving long-term hemodialysis

Background Tuberculosis remains a significant health problem for patients receiving long-term hemodialysis (HD). The tuberculin skin test (TST) is an important method for detecting Mycobacterium tuberculosis infection. This study examined the significance and frequency of the booster phenomenon in serial TST of HD patients. Method Fifty-three outpatients in a hospital-based HD center in Turkey were screened for tuberculosis with the TST between August and October 1999. To determine the frequency of booster phenomenon, patients with less than 10 mm indurations to the initial TST were given a second test 7 days later. Results Nineteen (35.8%) of 53 patients had a significant tuberculin reaction (≥ 10 mm) on the initial TST. The booster effect was detected in 10 (29.4%) of 34 patients who had a negative reaction (< 10 mm) to the initial test. Overall, 29 (54.7%) patients showed a significant reaction on both tests. Conclusions These results showed significant rates of TST positivity and the booster effect in this HD center.

Incidence of tuberculosis among a cohort of tuberculin-positive refugees in Australia: reappraising the estimates of risk.

Estimates of the lifetime risk of tuberculosis have varied widely and may not be applicable in all current settings. The aim of this study was to measure the incidence of reactivation of latent tuberculosis in a cohort of 15,489 predominantly Southeast Asian refugees aged 12 yr and over who arrived in Sydney, Australia during the period 1984 to 1994 and who had a clear chest X-ray on arrival. Tuberculin skin test (TST) reaction size and the presence of a BCG scar were recorded at entry. Incident cases of tuberculosis, occurring before June 1998, were identified by record linkage analysis with confirmatory review of case notes. There were 122 cases of tuberculosis over an average 10.3 yr of follow-up (crude annual incidence, 76.2/100,000). There was a linear increase in risk with increasing TST reaction size above 10 mm. The risk, and the relation of risk to TST reaction size, were unrelated to BCG scar status. Among those whose initial TST reaction was >/= 15 mm, the annual incidence rate in the first 3 yr was 213 (95% CI, 150 to 300) per 100,000 person-years and in the subsequent 10 yr the rate averaged 122 (95% CI, 90 to 165) per 100,000 person-years. The observed rates are similar to those estimated in the general population of the United States in the 1950s and 1960s. Further data on the prognosis of tuberculosis and the effects of isoniazid preventive therapy in Southeast Asian migrants to Western countries are required to inform policy and practice for the prevention of tuberculosis in this population.

What does tuberculin reactivity after bacille Calmette-Guérin vaccination tell us?

The effect of bacille Calmette-Guérin (BCG) vaccination on tuberculin reactivity is briefly reviewed. BCG vaccination will almost invariably result in tuberculin conversion with a positive tuberculin skin test developing 4-8 weeks after vaccination. However, these tuberculin reactions will wane-rapidly in all individuals who receive the vaccine in the neonatal period and more slowly in those who are vaccinated at an older age such as during the primary-school years. Of BCG vaccine recipients whose initial tuberculin skin test is negative, 10%-25% will have a positive tuberculin skin test if they are retested within 1-4 weeks-the so-called "booster phenomenon. " There is no relationship between tuberculin reactivity after BCG vaccination and the protective efficacy of the vaccine against development of active tuberculosis. Therefore, the ideal BCG vaccine would produce a scar at the site of injection to identify individuals who have been vaccinated but would have no effect on tuberculin reactivity.