The Clinical Usefulness of Tuberculin Skin Test versus Interferon-Gamma Release Assays for Diagnosis of Latent Tuberculosis in HIV Patients: A Meta-Analysis

BackgroundAccurate diagnosis of latent tuberculosis infection (LTBI) is becoming increasingly concerning due to the increasing the HIV epidemic, which have increased the risk for reactivation to active tuberculosis (TB) infection. LTBI is diagnosed by tuberculin skin test (TST) and interferon-gamma release assays (IGRAs).ObjectivesThe aim of the present study was to conduct a meta-analysis of published papers on the agreement (kappa) between TST and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests for diagnosis of LTBI in HIV patient.MethodsElectronic databases including PubMed/Medline, Elsevier/Scopus and Embase/Ovid were reviewed up Jan. 2016. We performed a random effect model meta-analysis for estimation of pooled Kappa between the two methods of diagnosis. Meta regression was used for assessing potential heterogeneity and Egger’s test was used for assessing small study effect and publication bias.ResultsThe initial search strategy produced 6744 records. Of them, 23 cross-sectional studies met the inclusion criteria and 20 studies entered in meta-analysis. The pooled kappa was and prevalence-adjusted and bias-adjusted kappa (PABAK) were 0.37 (95% CI: 0.28, 0.46) and 0.59 (0.49, 0.69). The discordance of TST-/QFT-GIT+ was more than TST+/QFT-GIT-. Kappa estimate between two tests was linearly associated with age and prevalence index and inversely associated with bias index.ConclusionFair agreement between TST and QFT-GIT makes it difficult to know whether TST is as useful as the QFT-GIT in HIV-infected patients. The higher discordance of TST-/QFT-GIT+ in compared to TST+/QFT-GIT- can induce the higher sensitivity of QFT-GIT for diagnosis LTBI in HIV patients. Disagreement between two tests can be influenced by error in measurements and prevalence of HIV.     

Tuberculin Skin Testing and Treatment Modulates Interferon-Gamma Release Assay Results for Latent Tuberculosis in Migrants

Background

Identifying latent tuberculosis infection (LTBI) in people migrating from TB endemic regions to low incidence countries is an important control measure. However, no prospective longitudinal comparisons between diagnostic tests used in such migrant populations are available.

Objectives

To compare commercial interferon (IFN)-gamma release assays (IGRAs) and the tuberculin skin test (TST) for diagnosing LTBI in a migrant population, and the influence of antecedent TST and LTBI treatment on IGRA performance.

Materials and Methods

This cohort study, performed from February to September 2012, assessed longitudinal IGRA and TST responses in Nepalese military recruits recently arrived in the UK. Concomitant T-SPOT.TB, QFT-GIT and TST were performed on day 0, with IGRAs repeated 7 and 200 days later, following treatment for LTBI if necessary.

Results

166 Nepalese recruits were prospectively assessed. At entry, 21 individuals were positive by T-SPOT.TB and 8 individuals by QFT-GIT. There was substantial agreement between TST and T-SPOT.TB positives at baseline (71.4% agreement; κ = 0.62; 95% CI:0.44–0.79), but only moderate concordance between positive IGRAs (38.1% agreement; κ = 0.46; 95% CI:0.25–0.67). When reassessed 7 days following TST, numbers of IGRA-positive individuals changed from 8 to 23 for QFT-GIT (p = 0.0074) and from 21 to 23 for T-SPOT.TB (p = 0.87). This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88). Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5%) provided a positive IGRA and of these 13 were TST negative. Two hundred days after the study commenced and three months after treatment for LTBI was completed by those who were given chemoprophylaxis, 23 and 21 participants were positive by T-SPOT.TB or QFT-GIT respectively. When individual responses were examined longitudinally within this population 35% of the day 7 QFT-GIT-positive, and 19% T-SPOT.TB-positive individuals, were negative by IGRA. When the change in the levels of secreted IFN-γ was examined after chemoprophylaxis the median levels were found to have fallen dramatically by 77.3% from a pre-treatment median concentration of IFN-γ 2.73 IU/ml to a post-treatment median concentration IFN-γ 0.62 (p = 0.0002).

Conclusions

This study suggests differences in the capacity of commercially available IGRAs to identify LTBI in the absence of antecedent TST and that IGRAs, in the time periods examined, may not be the optimal tests to determine the success of chemoprophylaxis for LTBI.     

Interferon-Gamma Assay in Combination with Tuberculin Skin Test Are Insufficient for the Diagnosis of Culture-Negative Pulmonary Tuberculosis

Objective

Early diagnosis of infectious cases and treatment of tuberculosis (TB) are important strategies for reducing the incidence of this disease. Unfortunately, traditional TB diagnostic methods are time-consuming and often unreliable. This study compared the accuracy and reliability of the tuberculin skin test (TST) and interferon (IFN)-γ-based assay (IGRA) for the diagnosis of active pulmonary TB Polish cases that could or could not be confirmed by M. tuberculosis (M.tb) culture.

Methods

In total, 126 adult patients with clinically active TB or non-mycobacterial, community-acquired lung diseases (NMLD) hospitalised at the Regional Specialised Hospital of Tuberculosis, Lung Diseases and Rehabilitation in Tuszyn, Poland were enrolled in the present study. Sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and analytic accuracy (Acc) of TST and IGRA testing for the diagnosis of culture-positive and culture-negative TB patients were calculated. The quantities of IFN-γ produced in the response to M.tb specific antigens (TB Ag – Nil) in the cultures of blood from patients with active TB and NMLD patients were also analysed.

Results

The IGRA sensitivity in culture-positive and culture-negative TB patients was similar, measuring 65.1% and 55.6%, respectively. The sensitivity of TST did not differ from the parameters designated for IGRA, measuring 55.8% in culture-positive and 64.9% in culture-negative TB. The sensitivity of TST and IGRA was age-dependent and decreased significantly with the age of the patients. No differences in the frequency or intensity of M.tb-stimulated IFN-γ production, as assessed by IGRA testing between culture-positive and culture-negative TB were noticed. Significantly lower concentrations of IFN-γ were observed in patients with advanced TB forms compared with those with mild or moderate TB pathologies.

Conclusions

Our results do not show that a combination of IGRA and TST might be a step forward in the diagnosis of culture-negative TB cases. However, M. tuberculosis-stimulated IFN-γ levels might help to assess the extent of pulmonary TB lesions.     

Evaluation of Interferon-Gamma Release Assays in the Diagnosis of Recent Tuberculosis Infection in Health Care Workers

Background

Health care workers (HCWs) are a group at risk of latent tuberculosis infection (LTBI). The aims of this study were to determine IFN-γ response by QuantiFERON-TB GOLD In Tube (QFN-G-IT) and T-SPOT.TB in HCWs, comparing the results with tuberculin skin test (TST); and to analyze the capacity of IFN-γ tests to detect recent versus remote LTBI with a prolonged stimulation test (PST).

Methodology/Principal Findings

A total of 147 HCWs were enrolled; 23 of whom were BCG vaccinated. 95 HCWs (64.6%) had a previous positive TST and were not retested; and 52 HCWs had a previous negative TST or were tested for the first time. When we analysed individuals without previous positive TST, the number of positive results for T-SPOT.TB was 12/52 (23.1%); and for QFN-G-IT, 9/52 (17.3%). The global concordance (κ) between T-SPOT.TB and QFN-G-IT with TST was 0.754 and 0.929 respectively. Of individuals with previous positive TST, T-SPOT.TB and QFN-G-IT were negative in 51.6% (49/95) and 62.1% (59/95) respectively, decreasing the concordance to 0.321 and 0.288, respectively. In non-BCG vaccinated HCWs with previous positive TST a positive IFN-γ test was associated with degree of exposure and diameter of TST. PST was performed in 24 HCW with previous positive TST and negative IFN-γ tests. PST was developed in 3 cell cultures stimulated with medium alone, ESAT-6 and CFP-10, respectively. In the third and sixth day of incubation period, part of the supernatants were replaced with complete medium supplemented with (rIL)-2. On day 9, ELISPOT assay was performed. In 14 samples PST was not valid due to not having enough cells. In 8 cases, the response was negative, and in 2 cases positive, suggesting that these patients were infected with Mycobacterium tuberculosis in some point in the past.

Conclusions

Both IFN-γ tests showed a similar number of positive results, and concordance between the tests was excellent. None of the tests was affected by prior BCG vaccination. IFN-γ tests are a useful tool for detecting recent infection in HCW population.     

Comparison of the Tuberculin Skin Test and Interferon Gamma Release Assay for the Screening of Tuberculosis in Adolescents in Close Contact with Tuberculosis TB Patients

Background

The tuberculin skin test (TST) frequently yields false positive results among BCG-vaccinated persons thereby limiting its diagnostic value particularly in settings with high BCG vaccination rate. We determined the agreement between IGRA and TST using 2 cutoff values and identified possible relationships between the results of these tests and the development of active tuberculosis.

Methodology

Adolescents aged 11–19 years in close contact with smear-positive tuberculosis cases and with normal chest radiographs were recruited from middle and high schools in South Korea. The TST was conducted by trained nurses, and blood was drawn for the QuantiFERON-TB Gold In-Tube (QFT-GIT). Participants were followed up for 2 years to check for incidence tuberculosis.

Results

A total of 2,982 subjects were included in the study, the average age was 15.1 years (SD 1.3), 61% had BCG vaccination scars. The agreement of QFT-GIT and the TST was low (κ = 0.38, 95% CI 0.32 to 0.42) using 10 mm cutoff; however, when the 15 mm cutoff was used, the agreement was intermediate (κ = 0.56, 95% CI 0.50 to 0.61). The odds ratio (OR) for the development of active tuberculosis was 7.9 (95% CI 3.46 to 18.06) for QFT-GIT positive patients, 7.96 (95% CI 3.14-20.22) for TST/QFT-GIT+ and the OR 4.62 (95% CI 2.02 to 10.58) and 16.35 (95% CI 7.09 to 37.71) for TST 10 mm and 15 mm cutoff respectively.

Conclusions

The results of this study suggest that the TST cutoff point for patients aged 11–17 years would be 15 mm in other study. The OR of QFT-GIT for the development of active tuberculosis and its intermediate agreement with TST using 15 mm cutoff demonstrates its role as an adjunct diagnostic tool to current clinical practice. Positive responders to both TST and QFT-GIT at the outset may benefit from chemoprophylaxis.     

Tuberculin Test in Children with Malnutrition

Tuberculin tests with Heaf''s multiple-puncture method, as well as intradermal tests with varying strengths of old tuberculin, were carried out on 402 children with severe malnutrition. From the radiological and bacteriological findings 51 children (12.5%) were considered to have active tuberculosis. The Heaf test was positive in only 11 of these children, but the intradermal test using 100 tuberculin units was positive in a further 18. This confirms previous findings that tuberculin sensitivity is impaired in malnourished children, and suggests that a higher dose of tuberculin is more likely to elicit a positive response.     

TB Screening in Canadian Health Care Workers Using Interferon-Gamma Release Assays

Background

While many North American healthcare institutions are switching from Tuberculin Skin Test (TST) to Interferon-gamma release assays (IGRAs), there is relatively limited data on association between occupational tuberculosis (TB) risk factors and test positivity and/or patterns of test discordance.

Methods

We recruited a cohort of Canadian health care workers (HCWs) in Montreal, and performed both TST and QuantiFERON-TB Gold In Tube (QFT) tests, and assessed risk factors and occupational exposure.

Results

In a cross-sectional analysis of baseline results, the prevalence of TST positivity using the 10 mm cut-off was 5.7% (22/388, 95%CI: 3.6–8.5%), while QFT positivity was 6.2% (24/388, 95%CI: 4–9.1%). Overall agreement between the tests was poor (kappa = 0.26), and 8.3% of HCWs had discordant test results, most frequently TST−/QFT+ (17/388, 4.4%). TST positivity was associated with total years worked in health care, non-occupational exposure to TB and BCG vaccination received after infancy or on multiple occasions. QFT positivity was associated with having worked as a HCW in a foreign country.

Conclusions

Our results suggest that LTBI prevalence as measured by either the TST or the QFT is low in this HCW population. Of concern is the high frequency of unexplainable test discordance, namely: TST−/QFT+ subjects, and the lack of any association between QFT positivity and clear-cut recent TB exposure. If these discordant results are indeed false positives, the use of QFT in lieu of TST in low TB incidence settings could result in overtreatment of uninfected individuals.     

Comparison of Mantoux and Tine Tuberculin Skin Tests in BCG-Vaccinated Children Investigated for Tuberculosis

Background

Tuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result.

Methodology/Principal Findings

1512 South African children younger than 5 years of age who were investigated for tuberculosis (TB) during a Bacille Calmette Guerin (BCG) trial were included in this analysis. Children underwent both Mantoux and Tine tests. A positive test was defined as Mantoux ≥15 mm or Tine ≥ Grade 3 for the binary comparison. Agreement was evaluated using kappa (binary) and weighted kappa (hierarchical). Multivariate regression models identified independent risk factors for TST positivity. The Mantoux test was positive in 430 children (28.4%) and the Tine test in 496 children (32.8%, p<0.0001), with observed binary agreement 87.3% (kappa 0.70) and hierarchical agreement 85.0% (weighted kappa 0.66). Among 173 children culture-positive for Mycobacterium tuberculosis, Mantoux was positive in 49.1% and Tine in 54.9%, p<0.0001 (kappa 0.70). Evidence of digit preference was noted for Mantoux readings at 5 mm threshold intervals. After adjustment for confounders, a positive culture, suggestive chest radiograph, and proximity of TB contact were risk factors for a positive test using both TST methods. There were no independent associations between ethnicity, gender, age, or over-crowding, and TST result.

Conclusions/Significance

The Tine test demonstrated a higher positive test rate than the Mantoux, with substantial agreement between TST methods among young BCG-vaccinated children. TB disease and exposure factors, but not demographic variables, were independent risk factors for a positive result using either test method. These findings suggest that the Tine might be a useful screening tool for childhood TB in resource-limited countries.     

Tuberculosis Contact Investigation Using Interferon-Gamma Release Assay with Chest X-Ray and Computed Tomography

Between September 2009 and January 2010, 6 members of the Japanese Eastern Army, who had completed the same training program, were diagnosed with active tuberculosis (TB) on different occasions. The Ministry of Defense conducted a contact investigation of all members who had come into contact with the infected members. The purpose of this study was to verify the efficacy of the TB screening protocol used in this investigation. A total of 884 subjects underwent interferon-gamma release assay (IGRA) and chest X-ray. The 132 subjects who were IGRA positive or with X-ray findings suggestive of TB subsequently underwent chest computer tomography (CT). Chest CT was performed for 132 subjects. Based on CT findings, 24 (2.7%) subjects were classified into the active TB group, 107 (12.1%) into the latent tuberculosis infection (LTBI) group, and 753 (85.2%) into the non-TB group. The first 2 groups underwent anti-TB therapy, and all 3 groups were followed for 2 years after treatment. Although one subject in the active TB group experienced relapse during the follow-up period, no patient in the LTBI or non-TB groups developed TB. IGRA and chest X-ray, followed by chest CT for those IGRA positive or with suspicious X-ray findings, appears to be an effective means of TB contact screening and infection prevention.     

Interferon-Gamma Release Assay Performance of Pleural Fluid and Peripheral Blood in Pleural Tuberculosis

Background

The diagnosis of pleural tuberculosis (TB) remains to be difficult. Interferon-gamma release assay (IGRA) is a promising method for diagnosing TB in low TB burden countries. The release of interferon-gamma (IFN-γ) by T lymphocytes increases at a localized site of infection with Mycobacterium tuberculosis antigen. This study aimed to examine the clinical accuracy of T-SPOT.TB on pleural fluid and peripheral blood for the diagnosis of pleural TB in high TB burden country.

Methods

168 subjects with pleural effusion were enrolled prospectively and examined with T-SPOT.TB on pleural fluid and peripheral blood samples simultaneously.

Results

The receiver operating characteristic (ROC) curve and cut-off value of pleural fluid T-SPOT.TB was established according to spot forming cells (SFC) between culture/biopsy-confirmed pleural TB group and no pleural TB group. The sensitivity of pleural fluid T-SPOT.TB and peripheral blood T-SPOT.TB was similar (96.3% and 92.7%, respectively) (P= 0.691). In contrast, the specificity of pleural fluid T-SPOT.TB (94.5%) was significantly higher than that of peripheral blood T-SPOT.TB (76.1%) (P=0.002). 2% (2/98) of pleural fluid T-SPOT.TB results were indeterminate.

Conclusion

The diagnostic accuracy of peripheral blood T-SPOT.TB is low in high TB burden countries due to latent tuberculosis infection. Pleural fluid T-SPOT.TB is a relatively useful and supplementary test to explore pleural TB in high TB burden countries, but its diagnostic accuracy needs to be validated in further large scale research.     

Performance of the Interferon Gamma Release Assays in Tuberculosis Disease in Children Five Years Old or Less

Interferon Gamma Release Assays (IGRAs) were developed for the indirect or immunologic diagnosis of tuberculosis infection; however, they have also been used to assist in difficult to diagnose cases of tuberculosis disease in adults, and to a lesser extent, in children, especially in those under 5 years old. We evaluated the utility of using an IGRA in pediatric tuberculosis in younger children in a hospital setting. The diagnostic accuracy of T-SPOT.TB and TST was assessed in 117 children with active tuberculosis and 413 children with respiratory tract infection. Sensitivity and specificity were calculated for the tests used individually and together. Concordance was also calculated. Sensitivity of T-SPOT.TB (82.9%) was higher than TST (78.6% using a 5mm cut-off), especially in children confirmed to have TB. T-SPOT.TB was more specific than TST using a 5mm cut-off (96.1% vs. 70.9%). Combining T-SPOT.TB and TST results improved the sensitivity to 96.6%. In conclusion, the results of the current study indicate that T-SPOT.TB has good sensitivity and specificity, supporting its use among patients of this age. A combination of IGRA and TST would be useful additions to assist in the diagnosis of childhood TB.     

Role of QuantiFERON-TB Gold,Interferon Gamma Inducible Protein-10 and Tuberculin Skin Test in Active Tuberculosis Diagnosis

Background

The measurement of Interferon gamma or Interferon gamma inducible protein (IP)-10 in antigen stimulated blood samples is suggested as an alternative method for latent tuberculosis (TB) diagnosis. Nonetheless, their role in active TB diagnosis, particularly in TB endemic settings is yet to be defined. In this study, the sensitivities and specificities of Interferon gamma release assay (IGRA), IP-10 assay and tuberculin skin test (TST) in detecting active TB cases were assessed in human immunodeficiency virus (HIV) sero-negative TB patients and healthy controls respectively.

Methods/Principal Findings

A total of 177 adult TB patients and 100 healthy controls were included for this study. QuantiFERON-TB Gold In-tube (QFT-IT) method was used to analyze the sensitivity and specificity of IGRA. QFT-IT, IP-10 and TST yielded the diagnostic sensitivities of 90.6% (95%CI: 86.3%–94.9%), 92.5% (95%CI: 88.6%–96.4%) and 68.9% (95%CI: 60.6%–77.2%) and specificities of 55% (95% CI: 35.2%–54.8%), 48% (95% CI: 38.2%–57.8%) and 75.5% (95% CI: 66.8%–84.2%), respectively. The extent of pulmonary involvement or presence of diabetes mellitus did not appear to influence the sensitivities of any of these tests. The combination of any of the two tests among QFT-IT, IP-10 and TST showed >98% sensitivity among smear negative cases and particularly the combination of IP-10, TST and smear microscopy showed 100% sensitivity, however, the specificity was decreased to 44.8%.

Conclusions/Significance

QFT-IT and IP-10 were highly sensitive in detecting active TB cases. The combination with TST improved the sensitivity of QFT-IT and IP-10 significantly. Although the higher sensitivity of combination of QFT-IT/IP-10 and TST may be useful in active TB diagnosis, they are limited by their poor specificity due to the high prevalence of latent TB in our settings.     

The Feasibility of the Interferon Gamma Release Assay and Predictors of Discordance with the Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in a Remote Aboriginal Community

Background

The tuberculin skin test (TST) is the standard test used to screen for latent TB infection (LTBI) in the northern Canadian territory of Nunavut. Interferon gamma release assays (IGRA) are T cell blood-based assays to diagnose LTBI. The Bacillus Calmette-Guerin (BCG) vaccine is part of the routine immunization schedule in Nunavut. The objective of this study was to test the feasibility, and predictors of discordance between the Tuberculin Skin Test (TST) and the IGRA assay in a medically under-serviced remote arctic Aboriginal population.

Methods

Both the TST and QuantiFERON-TB Gold (Qiagen group) IGRA tests were offered to people in their homes as part of a public health campaign aimed at high TB risk residential areas in Iqaluit, Nunavut, Canada. Feasibility was measured by the capacity of the staff to do the test successfully as measured by the proportion of results obtained.

Results

In this population of predominantly young Inuit who were mostly BCG vaccinated, the use of IGRA for the diagnosis of LTBI was feasible. IGRA testing resulted in more available test results reaching patients (95.6% vs 90.9% p = 0.02) but took longer (median 8 days (IGRA) vs 2 days (TST), p value <0.0001). 44/256 participants (17.2%) had discordant results. Multivariable regression analysis suggested that discordant results were most likely to have received multiple BCG vaccinations (RR 20.03, 95% CI, 3.94–101.82)), followed by BCG given post infancy (RR 8.13, 95% CI, 2.54–26.03)) and then to a lesser degree when BCG was given in infancy (RR 6.43, 95% CI, 1.72–24.85).

Interpretation

IGRA is feasible in Iqaluit, Nunavut, a remote Arctic community. IGRA testing results in more test results available to patients compared to TST. This test could result in fewer patients requiring latent TB treatment among those previously vaccinated with BCG in a region with limited public health human resources.     

A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children

Background

A Tuberculin skin test (TST) survey was conducted to assess the prevalence of latent TB Infection (LTBI) and to estimate the annual risk of M. tuberculosis infection (ARTI) in Gambian school children. The results are expected to contribute to understanding of Tuberculosis epidemiology in The Gambia.

Methods

This was a nationwide, multi-cluster survey in children aged 6–11 years. Districts, 20 of 37, were selected by probability proportional to size and schools by simple random sampling. All TST were performed using the Mantoux method. Height and weight measurements were obtained for all participants. We calculated prevalence of LTBI using cut-off points of 10mm, the mirror and mixture modelling methods.

Results

TST readings were completed 13,386 children with median age of 9 years (interquartile range [IQR] 8–10 years). Mixture analysis yielded a cut-off point of 12 mm, and LTBI prevalence of 6.9% [95%CI 6.47–7.37] and the ARTI was 0.75% [95%CI 0.60–0.91]. LTBI was associated gender and urban residence (p <0.01). Nutritional status was not associated with non-reactive TST or sizes of TST indurations. ARTI did not differ significantly by age, gender, BCG vaccination or residence.

Conclusions

This estimates for LTBI prevalence and ARTI were low but this survey provides updated data. Malnutrition did not affect estimates of LTBI and ARTI. Given the low ARTI in this survey and the overlapping distribution of indurations with mixture modelling, further surveys may require complementary tests such as interferon gamma release assays or novel diagnostic tools.     

Neutrophil-to-Lymphocyte Ratio Is Associated with Impaired Interferon-Gamma Release to Phytohemagglutinin

ObjectiveThe neutrophil-to-lymphocyte ratio (NLR) has been shown to predict adverse outcomes in several pathologic conditions. The majority of indeterminate interferon (IFN)-γ release assays were due to inadequate IFN-γ response to the phytohemagglutinin. We sought to study the value of NLR to predict an indeterminate result of QuantiFERON-TB Gold In-Tube (QFT-GIT) performed in routine laboratory practice.MethodsResults from 2,773 QFT-GIT assays were analyzed. Data collection included demographic data, the level of IFN-γ to nil, mitogen, and TB antigen of QFT-GIT, total WBC, and a differential count. We calculated the absolute neutrophil count, lymphocyte count, and NLR.ResultsOf the total, 224 (8.1%) indeterminate results were observed. Twelve (1.8%) showed indeterminate results in the NLR range from 1.71 to 2.84, but 132 (19.2%) had indeterminate results in NLR≥5.18 (p<0.0001). The likelihood ratio for indeterminate results were 2.70 (95% CI, 2.36-3.08) in NLR ≥5.18 and 1.93 (95% CI, 1.64-2.27) in lymphocyte count ≤1050/μL. NLR and neutrophil count were independent predictors for indeterminate QFT-GIT result in multiple regression analysis. The IFN-γ response to PHA was negatively associated with NLR (r=-0.33, p<0.001).ConclusionWe showed that the NLR is an independent predictor of indeterminate QFT-GIT result. Low frequency of indeterminate results in group with normal NLR may imply the importance of a balance between two cellular compartments in physiological and pathological conditions.     

Tuberculin Skin Test Distribution following a Change in BCG Vaccination Policy

Background

Epidemiologic data regarding tuberculin skin test (TST) responses are an important basis for TB control strategies. This study analyzed TST responses in Korea, which experienced a rapid change in BCG vaccination status.

Methods

TST responses in young adults were examined over 5 years. Participants with active TB lesions were excluded.

Results

A total of 5,552 participants were enrolled with median age of 21 years. When an induration diameter ≥10 mm was used as the criterion for a positive test, TST positivity fell (from 28.0% in 2005 to 15.3% in 2009); however, they remained steady when the criterion was ≥15–20 mm. A positive TST was associated with a personal or family of TB, the presence of a Bacille Calmette-Guérin (BCG) scar, and age (odds ratio [95% confidence interval] = 4.03 [2.61–6.22], 2.91 [1.80–4.71], 1.50 [1.31–1.72], and 1.15 [1.09–1.20], respectively). Among these factors, the decrease of participants with BCG scars was the most prominent change, which appeared to be associated with the change of TST positivity rate.

Conclusion

Overall, the rate of TST positivity in Korea decreased. However, this trend seems associated with the change of BCG vaccination strategy rather than successful control of LTBI. This study showed that change in BCG vaccination strategy can have great impact on TB epidemiologic survey based on TST.     

Tuberculin Skin Test Result and Risk of Death among Persons with Active TB

Background

Although the tuberculin skin test (TST) is frequently used to aid in the diagnosis of tuberculosis (TB) disease and to identify persons with latent TB infection, it is an imperfect test and approximately 10–25% of persons with microbiologically confirmed TB disease have a negative TST. Previous studies have suggested that persons with a negative TST are more likely to present with severe TB disease and have an increased rate of TB-related death.

Methods

We analyzed culture-confirmed TB cases captured in US TB surveillance data from 1993 to 2008 and performed multivariate logistic regression analysis to determine the association between TST result and death.

Results

Of 284,866 cases of TB reported in the US, 58,180 persons were eligible for inclusion in the analysis and 3,270 of those persons died after initiating TB treatment. Persons with a negative TST accounted for only 14% of the eligible cases but accounted for 42% of the deaths. Persons with a TST≥15 mm had 67% lower odds of death than persons with a negative TST (adjusted odds ratio 0.33, 95% confidence interval 0.30–0.36).

Conclusions

A negative TST is associated with an increased risk of death among persons with culture-confirmed TB disease, even after adjustment for HIV status, site of TB disease, sputum smear AFB status, drug susceptibility, age, sex, and origin of birth. In addition to indicating risk of developing disease, the TST may also be a marker for increased risk of death.     

Increase in the Number of Tuberculosis Cases Treated following Tuberculin Skin Testing in First-Year Schoolchildren in Madagascar

Background

Tuberculosis continues to cause unacceptably high levels of disease and death worldwide. Active preventive strategies are required to improve tuberculosis control and to increase the number of cases treated in developing countries. The aim of this study was to evaluate the utility of the tuberculin skin test (TST) in first-year schoolchildren as a means of increasing the number of tuberculosis cases detected through the screening of close contacts.

Methods

All members of the households of 90 schoolchildren assigned to three groups on the basis of TST category (≤5 mm, [5–15)mm, ≥15 mm) were screened for sputum smear-positive pulmonary tuberculosis. The percentage detection of tuberculosis in close contacts was compared between TST categories.

Results

We identified 433 close contacts of the 90 schoolchildren, who were then evaluated for tuberculosis. We identified 11 cases of pulmonary tuberculosis among the close contacts (7 already on treatment and 4 previously undiagnosed): 0 in TST category ≤5 mm, 3 in TST category [5–15) mm and 8 in TST category ≥15 mm). This approach increased the detection of tuberculosis cases by a factor of 1.6 in first-year schoolchildren of the TST ≥5 mm group.

Conclusion

TST in first-year schoolchildren is a potentially effective method for improving the detection of tuberculosis in close contacts.