INTRODUCTION: Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis. Pediatric data comparing the two IGRAs in the United States are very limited. We compared the performance of the two IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cut-off values. METHODS: Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON TB-Gold In-Tube (QFT-GIT) tests were identified from a U.S. multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar's Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results. RESULTS: Among 3,793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, p < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cut-off of 0.35 IU/mL. CONCLUSIONS: In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cut-offs.

BACKGROUND: The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). METHODS: This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. RESULTS: Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. CONCLUSIONS: TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

BACKGROUND: Close contacts infected with Mycobacterium tuberculosis are at high risk of tuberculosis (TB) disease and a priority for preventive treatment. Three tests measure infection: two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). The objective of our study was to assess the association of positive test results in contacts with infectiousness of the presumed TB source case. METHODS: Contacts in a cohort study at 10 United States sites received both IGRAs (QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT)) and TST. We defined test conversion as negative for all tests at baseline and positive for at least one on retest. Risk ratios (RR) and 95% confidence intervals (CI) assessed association of positive test results with increased infectiousness of the TB case-defined as acid-fast bacilli (AFB) on sputum microscopy or cavities on chest radiographs- and contact demographics. RESULTS: Adjusted for contacts' age, nativity, sex, and race, IGRAs (QFT-GIT RR = 6.1, 95% CI 1.7-22.2; T-SPOT RR = 9.4, 95% CI 1.1-79.1), but not TST (RR = 1.7, 95% CI 0.8-3.7), were more likely to convert among contacts exposed to persons with cavitary TB disease. CONCLUSIONS: Because IGRA conversions in contacts are associated with infectiousness of the TB case, their use may improve efficiency of health department contact investigations by focusing efforts on those likely to benefit from preventive treatment in the United States.

OBJECTIVE: Tuberculosis (TB) is a public health problem, especially among people experiencing homelessness (PEH). The Advisory Council for the Elimination of Tuberculosis issued recommendations in 1992 for TB prevention and control among PEH. Our goal was to provide current guidelines and information in one place to inform medical and public health providers and TB programs on TB incidence, diagnosis, and treatment among PEH. METHODS: We reviewed and synthesized diagnostic and treatment recommendations for TB disease and latent TB infection (LTBI) as of 2022 and information after 1992 on the magnitude of homelessness in the United States, the incidence of TB among PEH, the role of public health departments in TB case management among PEH, and recently published evidence. RESULTS: In 2018, there were 1.45 million estimated PEH in the United States. During the past 2 decades, the incidence of TB was >10 times higher and the prevalence of LTBI was 7 to 20 times higher among PEH than among people not experiencing homelessness. TB outbreaks were common in overnight shelters. Permanent housing for PEH and the use of rapid TB diagnostic tests, along with isolation and treatment, reduced TB exposure among PEH. The use of direct observation enhanced treatment adherence among PEH, as did involvement of social workers to help secure shelter, food, safety, and treatment for comorbidities, especially HIV and substance use disorders. Testing and treatment for LTBI prevented progression to TB disease, and shorter LTBI regimens helped improve adherence. Federal agencies and the National Health Care for the Homeless Council have helpful resources. CONCLUSION: Improvements in TB diagnosis, treatment, and prevention among PEH are possible by following existing recommendations and using client-centered approaches.

The COVID-19 pandemic caused disruptions in behavioral health services (BHS), essential for people experiencing homelessness (PEH). BHS changes created barriers to care and opportunities for innovative strategies for reaching PEH. The authors conducted 50 qualitative interviews with behavioral health providers in the USA during August-October 2020 to explore their observations of BHS changes for PEH. Interviews were transcribed and entered into MAXQDA for analysis and to identify salient themes. The largest impact from COVID-19 was the closure or limited hours for BHS and homeless shelters due to mandated "stay-at-home" orders or staff working remotely leading to a disconnection in services and housing linkages. Most providers initiated telehealth services for clients, yielding positive outcomes. Implications for BHS are the need for long-term strategies, such as advances in communication technology to support BHS and homeless services and to ensure the needs of underserved populations are met during public health emergencies.

BACKGROUND: Individuals with both diabetes mellitus (DM) and TB infection are at higher risk of progressing to TB disease.OBJECTIVE: To determine DM prevalence in populations at high risk for latent TB infection (LTBI) and to identify the most accurate point-of-care (POC) method for DM screening.METHODS: Adults aged ≥25 years were recruited at health department clinics in Hawaii and Arizona, USA, and screened for LTBI and DM. Screening methods for DM included self-report, random blood glucose (RBG), and POC hemoglobin A1c (HbA1c). Using HbA1c ≥6.5% or self-reported history as the gold standard for DM, we compared test strategies to determine the most accurate method while keeping test costs low.RESULTS: Of 472 participants, 13% had DM and half were unaware of their diagnosis. Limiting HbA1c testing to ages ≥30 years with a RBG level of 120-180 mg/dL helped identify most participants with DM (sensitivity 85%, specificity 99%) at an average test cost of US$2.56 per person compared to US$9.56 per person using HbA1c for all patients.CONCLUSION: Self-report was insufficient to determine DM status because many participants were previously undiagnosed. Using a combination of POC RBG and HbA1c provided an inexpensive option to assess DM status in persons at high risk for LTBI.

PURPOSE: Contact tracing is intended to reduce the spread of coronavirus disease 2019 (COVID-19), but it is difficult to conduct among people who live in congregate settings, including people experiencing homelessness (PEH). This analysis compares person-based contact tracing among two populations in Salt Lake County, Utah, from March-May 2020. METHODS: All laboratory-confirmed positive cases among PEH (n=169) and documented in Utah's surveillance system were included in this analysis. The general population comparison group (n=163) were systematically selected from all laboratory-confirmed cases identified during the same period. RESULTS: Ninety-three PEH cases (55%) were interviewed compared to 163 (100%) cases among the general population (p<0.0001). PEH were more likely to be lost to follow-up at end of isolation (14.2%) versus the general population (0%; p-value<0.0001) and provided fewer contacts per case (0.31) than the general population (4.7) (p-value<0.0001). Contacts of PEH were more often unreachable (13.0% vs. 7.1%; p-value<0.0001). CONCLUSIONS: These findings suggest that contact tracing among PEH should include a location-based approach, along with a person-based approach when resources allow, due to challenges in identifying, locating, and reaching cases among PEH and their contacts through person-based contact tracing efforts alone.

The fourth generation QuantiFERON test for tuberculosis infection, QuantiFERON-TB Gold Plus (QFT-Plus) has replaced the earlier version, QuantiFERON-TB Gold In-Tube (QFT-GIT). A clinical need exists for information about agreement between QFT-Plus and other tests.We conducted this study to assess agreement of test results for QFT-Plus with those of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT) and the tuberculin skin test (TST).Persons at high risk of LTBI and/or progression to TB disease were enrolled at the 10 sites of the Tuberculosis Epidemiologic Studies Consortium from October 2016 through May 2017; each participant received all four tests. Cohen's kappa (kappa) and Wilcoxon signed rank test compared qualitative and quantitative results of QFT-Plus with the other tests.Test results for 506 participants showed 94% agreement between QFT-Plus and QFT-GIT, with 19% positive and 75% negative results. When the tests disagreed, it was most often in the direction of QFT-GIT negative/QFT-Plus positive. QFT-Plus had similar concordance as QFT-GIT with TST (77% and 77%) and T-SPOT (92% and 91%), respectively.Conclusions: The study showed high agreement between QFT-GIT and QFT-Plus in a direct comparison. Both tests had similar agreement with TST and T-SPOT.

BACKGROUND: Lack of a gold standard for latent TB infection has precluded direct measurement of test characteristics of the tuberculin skin test and interferon-gamma release assays (QuantiFERON Gold In-Tube and T-SPOT.TB). OBJECTIVE: We estimated test sensitivity/specificity and latent TB infection prevalence in a prospective, US-based cohort of 10 740 participants at high risk for latent infection. METHODS: Bayesian latent class analysis was used to estimate test sensitivity/specificity and latent TB infection prevalence among subgroups based on age, foreign birth outside the USA and HIV infection. RESULTS: Latent TB infection prevalence varied from 4.0% among foreign-born, HIV-seronegative persons aged <5 years to 34.0% among foreign-born, HIV-seronegative persons aged >/=5 years. Test sensitivity ranged from 45.8% for the T-SPOT.TB among foreign-born, HIV-seropositive persons aged >/=5 years to 80.7% for the tuberculin skin test among foreign-born, HIV-seronegative persons aged >/=5 years. The skin test was less specific than either interferon-gamma release assay, particularly among foreign-born populations (eg, the skin test had 70.0% specificity among foreign-born, HIV-seronegative persons aged >/=5 years vs 98.5% and 99.3% specificity for the QuantiFERON and T-SPOT.TB, respectively). The tuberculin skin test's positive predictive value ranged from 10.0% among foreign-born children aged <5 years to 69.2% among foreign-born, HIV-seropositive persons aged >/=5 years; the positive predictive values of the QuantiFERON (41.4%) and T-SPOT.TB (77.5%) were also low among US-born, HIV-seropositive persons aged >/=5 years. CONCLUSIONS: These data reinforce guidelines preferring interferon-gamma release assays for foreign-born populations and recommending against screening populations at low risk for latent TB infection. TRIAL REGISTRATION NUMBER: NCT01622140.

OBJECTIVES: To assess latent tuberculous infection (LTBI) treatment completion rates in a large prospective US/Canada multisite cohort and identify associated risk factors. METHODS: This prospective cohort study assessed factors associated with LTBI treatment completion through interviews with persons who initiated treatment at 12 sites. Interviews were conducted at treatment initiation and completion/cessation. Participants received usual care according to each clinic's procedure. Multivariable models were constructed based on stepwise assessment of potential predictors and interactions. RESULTS: Of 1515 participants initiating LTBI treatment, 1323 had information available on treatment completion; 617 (46.6%) completed treatment. Baseline predictors of completion included male sex, foreign birth, not thinking it would be a problem to take anti-tuberculosis medication, and having health insurance. Participants in stable housing who received monthly appointment reminders were more likely to complete treatment than those without stable housing or without monthly reminders. End-of-treatment predictors of non-completion included severe symptoms and the inconvenience of clinic/pharmacy schedules, barriers to care and changes of residence. Common reasons for treatment non-completion were patient concerns about tolerability/toxicity, appointment conflicts, low prioritization of TB, and forgetfulness. CONCLUSIONS: Less than half of treatment initiators completed treatment in our multisite study. Addressing tangible issues such as not having health insurance, toxicity concerns, and clinic accessibility could help to improve treatment completion rates.

BACKGROUND: The utility of Mycobacterium tuberculosis Direct nucleic acid amplification testing (MTD) for pulmonary tuberculosis disease diagnosis in the U.S. has not been well described. METHODS: We analyzed a retrospective cohort of reported patients with suspected active pulmonary tuberculosis in 2008-2010 from Georgia, Hawaii, Maryland, and Massachusetts to assess MTD use, effectiveness, health-system benefits, and cost-effectiveness. RESULTS: Among 2140 patients in whom pulmonary tuberculosis was suspected, 799 (37%) were Mycobacterium-tuberculosis-culture-positive. Eighty percent (680/848) of patients having acid-fast-bacilli-smear-positive specimens had MTD performed; MTD positive-predictive value (PPV) was 98% and negative-predictive value (NPV) was 94%. Nineteen percent (240/1292) of patients having smear-negative specimens had MTD; MTD PPV was 90% and NPV was 88%. Among patients suspected of tuberculosis but not having MTD, smear PPV for lab-confirmed tuberculosis was 77% and NPV 78%. Compared with no MTD, MTD significantly decreased time to diagnosis in patients with smear-positive/MTD(+) specimens, decreased respiratory isolation for patients having smear-positive/MTD(-)/culture-negative specimens, decreased outpatient days of unnecessary tuberculosis medications, and reduced resources expended on contact investigation. While MTD generally cost more than no MTD, incremental cost savings occurred in patients with HIV or homelessness to diagnose or to exclude tuberculosis, and in patients with substance abuse having smear-negative specimens to exclude tuberculosis. CONCLUSIONS: MTD improved diagnostic accuracy and timeliness, and reduced unnecessary respiratory isolation, treatment, and contact investigations. It was cost saving in patients with HIV, homelessness, or substance abuse, but not in others.