Interferon-γ release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States.

RATIONALE: IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs). OBJECTIVES: Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs. METHODS: A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011. MEASUREMENTS AND MAIN RESULTS: A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later. CONCLUSIONS: Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Acceptability of interferon-gamma release assays among healthcare workers who receive routine employee tuberculosis testing.

BACKGROUND: Healthcare workers (HCWs) undergo annual testing for latent tuberculosis infection (LTBI). OBJECTIVE: Compare acceptability of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) among HCWs. METHODS: HCWs at four medical centers in the US were administered an acceptability questionnaire including a brief objective description of both tests and eliciting attitudes regarding TST and IGRAs, confidence in results, and likelihood of taking LTBI treatment. RESULTS: Of 406 participants, 75% had never heard of IGRAs. IGRAs were preferred to TST. Belief in accuracy of hypothetical positive results of TST or IGRA and willingness to accept LTBI treatment were similar across tests. When presented with hypothetical discordant results, HCWs expressed more confidence in IGRAs. Perceived accuracy of results was the most important factor in test preferences. CONCLUSIONS: Although HCWs preferred and indicated more confidence in IGRAs, the likelihood that HCWs would believe LTBI diagnosis and initiate treatment based on positive results was similar for TST and IGRAs.

Poor concordance between interferon-gamma release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals.

BACKGROUND: A new generation of diagnostic tests, the interferon-gamma release assays (IGRAs), have been developed for the detection of latent tuberculosis infection (LTBI). Limited data are available on their use in HIV-infected persons. METHODS: A cross-sectional study was carried out at 2 HIV clinics in Atlanta to assess the utility of two IGRA tests (T-SPOT.TB [TSPOT] and QuantiFERON-TB Gold in Tube [QFT-3G]) compared to the tuberculin skin test (TST). RESULTS: 336 HIV-infected persons were enrolled. Median CD4 count was 335 cells/microl and median HIV viral load was 400 copies/ml. Overall, 27 patients (8.0%) had at least 1 positive diagnostic test for LTBI: 7 (2.1%) had a positive TST; 9 (2.7%) a positive QFT-3G; and 14 (4.2%) a positive TSPOT. Agreement between the 3 diagnostic tests was poor: TST and TSPOT, [kappa = 0.16, 95% CI (-0.06, 0.39)], TST and QFT-3G [kappa = 0.23, 95% CI (-0.05, 0.51)], QFT-3G and TSPOT [kappa = 0.06, 95% CI (-0.1, 0.2)]. An indeterminate test result occurred among 6 (1.8%) of QFT-3G and 47 (14%) of TSPOT tests. In multivariate analysis, patients with a CD4 < or = 200 cells/microl were significantly more likely to have an indeterminate result [OR = 3.6, 95% CI (1.9, 6.8)]. CONCLUSION: We found a low prevalence of LTBI and poor concordance between all 3 diagnostic tests. Indeterminate test results were more likely at CD4 counts < or = 200 cells/microl. Additional studies among HIV-infected populations with a high prevalence of TB are needed to further assess the utility of IGRAs in this patient population.

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities.

Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

Latent TB infection treatment acceptance and completion in the United States and Canada.

BACKGROUND: Treatment of latent TB infection (LTBI) is essential for preventing TB in North America, but acceptance and completion of this treatment have not been systematically assessed. METHODS: We performed a retrospective, randomized two-stage cross-sectional survey of treatment and completion of LTBI at public and private clinics in 19 regions of the United States and Canada in 2002. RESULTS: At 32 clinics that both performed tuberculin skin testing and offered treatment, 123 (17.1%; 95% CI, 14.5%-20.0%) of 720 subjects tested and offered treatment declined. Employees at health-care facilities were more likely to decline (odds ratio [OR], 4.74; 95% CI, 1.75-12.9; P = .003), whereas those in contact with a patient with TB were less likely to decline (OR, 0.19; 95% CI, 0.07-0.50; P = .001). At 68 clinics starting treatment regardless of where skin testing was performed, 1,045 (52.7%; 95% CI, 48.5%-56.8%) of 1,994 people starting treatment failed to complete the recommended course. Risk factors for failure to complete included starting the 9-month isoniazid regimen (OR, 2.08; 95% CI, 1.23-3.57), residence in a congregate setting (nursing home, shelter, or jail; OR, 2.94; 95% CI, 1.58-5.56), injection drug use (OR, 2.13; 95% CI, 1.04-4.35), age >or= 15 years (OR, 1.49; 95% CI, 1.14-1.94), and employment at a health-care facility (1.37; 95% CI, 1.00-1.85). CONCLUSIONS: Fewer than half of the people starting treatment of LTBI completed therapy. Shorter regimens and interventions targeting residents of congregate settings, injection drug users, and employees of health-care facilities are needed to increase completion.

The scope and impact of treatment of latent tuberculosis infection in the United States and Canada.

RATIONALE: The scope of treatment of latent tuberculosis infection (LTBI) in the United States and Canada is unknown. Identifying the types of clinics that administer such treatment and patients who receive it could guide resource utilization and improve treatment initiation and completion. OBJECTIVES: Estimate the number of persons started on LTBI treatment; describe the types of clinics that treat LTBI. METHODS: The Tuberculosis Epidemiologic Studies Consortium, consisting of 19 United States and 2 Canadian sites, conducted a survey among clinics that initiated LTBI treatment for>or=10 patients in 2002. RESULTS: Study catchment areas from the 19 United States sites represented 8.6% of the United States population and 12.7% of all tuberculosis cases in 2000. An estimated 37,857 patients started LTBI treatment during 2002 at 244 clinics surveyed. Of these treatment starts, 29,970 (79%) occurred at general public health clinics; immigrant/refugee clinics (2,409; 6.4%) and correctional/detention facilities (2,325; 6.1%) were the next most common sites. Based on these data, United States tuberculosis case rates, and United States population data, the estimated total number of LTBI treatment starts in the United States was 291,000-433,000. When the 37,145 persons who initiated LTBI treatment in the United States were extrapolated to the entire United States population, with a 5% lifetime risk of tuberculosis without treatment, and 20-60% treatment effectiveness, approximately 4,000-11,000 tuberculosis cases were prevented in the United States. CONCLUSIONS: LTBI treatment is initiated among a substantial number of persons in the United States and Canada, primarily in the public sector. Treatment of LTBI can significantly decrease the tuberculosis burden.