Evaluation of the Latent Tuberculosis Care Cascade Among Public Health Clinics in the United States.

BACKGROUND: Tuberculosis (TB) elimination within the United States will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), although gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions. METHODS: We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the United States. Data were abstracted on individuals receiving LTBI care during 2016-2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion. RESULTS: Among 23 885 participants tested by LHDs, 46% (11 009) were male with a median age of 31 (interquartile range [IQR] 20-46). A median of 35% of participants were US-born at each site (IQR 11-78). Overall, 16 689 (70%) received a tuberculin skin test (TST), 6993 (29%) received a Quantiferon (QFT), and 1934 (8%) received a T-SPOT.TB; 5% (1190) had more than one test. Among those tested, 2877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US-born, P < .01). Of 2515 (11%) of the total participants diagnosed with LTBI, 1073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis). CONCLUSIONS: Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.

Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007.

To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease.

Importance: Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. Objective: To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. Design, Setting, and Participants: This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. Exposures: At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Main Outcomes and Measures: Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. Results: A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). Conclusions and Relevance: In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Interferon-γ Release Assays in Children <15 Years of Age.

OBJECTIVES: The tuberculin skin test (TST) has been preferred for screening young children for latent tuberculosis infection (LTBI) because of concerns that interferon-γ release assays (IGRAs) may be less sensitive in this high-risk population. In this study, we compared the predictive value of IGRAs to the TST for progression to tuberculosis disease in children, including those <5 years old. METHODS: Children <15 years old at risk for LTBI or progression to disease were tested with TST, QuantiFERON-TB Gold In-Tube test (QFT-GIT), and T-SPOT.TB test (T-SPOT) and followed actively for 2 years, then with registry matches, to identify incident disease. RESULTS: Of 3593 children enrolled September 2012 to April 2016, 92% were born outside the United States; 25% were <5 years old. Four children developed tuberculosis over a median 4.3 years of follow-up. Sensitivities for progression to disease for TST and IGRAs were low (50%-75%), with wide confidence intervals (CIs). Specificities for TST, QFT-GIT, and T-SPOT were 73.4% (95% CI: 71.9-74.8), 90.1% (95% CI: 89.1-91.1), and 92.9% (95% CI: 92.0-93.7), respectively. Positive and negative predictive values for TST, QFT-GIT, and T-SPOT were 0.2 (95% CI: 0.1-0.8), 0.9 (95% CI: 0.3-2.5), and 0.8 (95% CI: 0.2-2.9) and 99.9 (95% CI: 99.7-100), 100 (95% CI: 99.8-100), and 99.9 (95% CI: 99.8-100), respectively. Of 533 children with TST-positive, IGRA-negative results not treated for LTBI, including 54 children <2 years old, none developed disease. CONCLUSIONS: Although both types of tests poorly predict disease progression, IGRAs are no less predictive than the TST and offer high specificity and negative predictive values. Results from this study support the use of IGRAs for children, especially those who are not born in the United States.

Opportunities for tuberculosis diagnosis and prevention among persons living with HIV: a cross-sectional study of policies and practices at four large Ryan White Program-Funded HIV clinics.

OBJECTIVE: We describe the frequency and attributes of tuberculosis testing and treatment at four publicly-funded HIV clinics. METHODS: We abstracted medical records from a random sample of 600 HIV-infected patients having at least one clinic visit in 2009 at four clinics in New York and Los Angeles Metropolitan Statistical areas. We described testing and treatment for tuberculosis infection (TBI), 2008-2010, and estimated adjusted odds ratios (aORs). We interviewed key informants and described clinic policies and practices. RESULTS: Of 600 patients, 500 were eligible for testing, and 393 (79%) were tested 2008-2010; 107 (21%) did not receive at least one tuberculin skin test or interferon gamma release assay. Results were positive in 20 (5%) patients, negative in 357 (91%), and unknown in 16 (4%). Fourteen (70%) of 20 patients with TBI initiated treatment at the clinics; only three were documented to have completed treatment. Three hundred twenty three (54%) patients had chest radiography, 346 (58%) had tuberculosis symptom screening, and three had tuberculosis disease (117 per 100,000 person-years, 95% confidence interval (CI) = 101-165). Adjusting for site, non-Hispanic ethnicity (aOR = 4.9, 95% CI = 2.6-9.5), and employment (aOR = 1.9, 95% CI = 1.0-3.4) were associated with TBI testing; female gender (aOR = 2.0, 95% CI = 1.4-3.3), non-black race (aOR = 1.7, 95% CI = 1.3-2.5), and unemployment (aOR = 1.5, 95% CI = 1.1-2.1) were associated with chest radiography. Clinics evaluated TBI testing performance annually and identified challenges to TB prevention. CONCLUSIONS: Study clinics routinely tested patients for TBI, but did not always document treatment. In a population with a high TB rate, ensuring treatment of TBI may enhance TB prevention.

Transmission of multidrug-resistant tuberculosis in the USA: a cross-sectional study.

BACKGROUND: Multidrug-resistant (MDR) tuberculosis is a potential threat to tuberculosis elimination, but the extent of MDR tuberculosis disease in the USA that is attributable to transmission within the country is unknown. We assessed transmission of MDR tuberculosis and potential contributing factors in the USA. METHODS: In a cross-sectional study, clinical, demographic, epidemiological, and Mycobacterium tuberculosis genotype data were obtained during routine surveillance of all verified cases of MDR tuberculosis reported from eight states in the USA (California from Jan 1, 2007, to Dec 31, 2009; Texas from Jan 1, 2007, to March 31, 2009; and the states of Colorado, Maryland, Massachusetts, New York, Tennessee, and Washington from Jan 1, 2007 to Dec 31, 2008). In-depth interviews and health-record abstraction were done for all who consented to ascertain potential interpersonal connections. FINDINGS: 168 cases of MDR tuberculosis were reported in the eight states during our study period. 92 individuals (55%) consented to in-depth interview. 20 (22%) of these individuals developed MDR tuberculosis as a result of transmission in the USA; a source case was identified for eight of them (9%). 20 individuals (22%) had imported active tuberculosis (ie, culture-confirmed disease within 3 months of entry into the USA). 38 (41%) were deemed to have reactivation of disease, of whom 14 (15%) had a known previous episode of tuberculosis outside the USA. Five individuals (5%) had documented treatment of a previous episode in the USA, and so were deemed to have relapsed. For nine cases (10%), insufficient evidence was available to definitively classify reason for presentation. INTERPRETATION: About a fifth of cases of MDR tuberculosis in the USA can be linked to transmission within the country. Many individuals acquire MDR tuberculosis before entry into the USA. MDR tuberculosis needs to be diagnosed rapidly to reduce potential infectious periods, and clinicians should consider latent tuberculosis infection treatment-tailored to the results of drug susceptibility testing of the putative source case-for exposed individuals. FUNDING: Centers for Disease Control and Prevention.