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BACKGROUND: Despite an overall decline in tuberculosis incidence and mortality in the USA in the past two decades, racial and ethnic disparities in tuberculosis outcomes persist. We aimed to examine the extent to which inequalities in health and neighbourhood-level social vulnerability mediate these disparities. METHODS: We extracted data from the US National Tuberculosis Surveillance System on individuals with tuberculosis during 2011-19. Individuals with multidrug-resistant tuberculosis or missing data on race and ethnicity were excluded. We examined potential disparities in tuberculosis outcomes among US-born and non-US-born individuals and conducted a mediation analysis for groups with a higher risk of treatment incompletion (a summary outcome comprising diagnosis after death, treatment discontinuation, or death during treatment). We used sequential multiple mediation to evaluate eight potential mediators: three comorbid conditions (HIV, end-stage renal disease, and diabetes), homelessness, and four census tract-level measures (poverty, unemployment, insurance coverage, and racialised economic segregation [measured by Index of Concentration at the ExtremesRace-Income]). We estimated the marginal contribution of each mediator using Shapley values. FINDINGS: During 2011-19, 27 788 US-born individuals and 57 225 non-US-born individuals were diagnosed with active tuberculosis, of whom 27 605 and 56 253 individuals, respectively, met eligibility criteria for our analyses. We did not observe evidence of disparities in tuberculosis outcomes for non-US-born individuals by race and ethnicity. Therefore, subsequent analyses were restricted to US-born individuals. Relative to White individuals, Black and Hispanic individuals had a higher risk of not completing tuberculosis treatment (adjusted relative risk 1·27, 95% CI 1·19-1·35; 1·22, 1·11-1·33, respectively). In multiple mediator analysis, the eight measured mediators explained 67% of the disparity for Black individuals and 65% for Hispanic individuals. The biggest contributors to these disparities for Black individuals and Hispanic individuals were concomitant end-stage renal disease, concomitant HIV, census tract-level racialised economic segregation, and census tract-level poverty. INTERPRETATION: Our findings underscore the need for initiatives to reduce disparities in tuberculosis outcomes among US-born individuals, particularly in highly racially and economically polarised neighbourhoods. Mitigating the structural and environmental factors that lead to disparities in the prevalence of comorbidities and their case management should be a priority. FUNDING: US Centers for Disease Control and Prevention National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention Epidemiologic and Economic Modeling Agreement.

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OBJECTIVE: Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment. STUDY DESIGN AND SETTING: We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regression, we estimated associations and their 95% confidence intervals (CI) between the outcome of individual deviation in treatment duration (in months) from the mean duration of their treatment site and patient characteristics, drug resistance, and treatments used. RESULTS: Overall, 6702 patients with successful treatment outcomes from 84 treatment sites were included. We found that factors commonly associated with poor treatment outcomes were also associated with longer treatment durations, relative to the site mean duration. Use of bedaquiline was associated with a 0.51 (95% CI: 0.15, 0.87) month decrease in duration of treatment, which was consistent across subgroups, while MDR/RR-TB with fluoroquinolone resistance was associated with 0.78 (95% CI: 0.36, 1.21) months increase. CONCLUSION: We describe a method to assess associations between clinical factors and treatment duration in observational studies of MDR/RR-TB patients, that may help identify patients who can benefit from shorter treatment.

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We estimated direct costs of a 4-month or 6-month regimen for drug-susceptible pulmonary tuberculosis treatment in the United States. Costs were $23,000 per person treated. Actual treatment costs will vary depending on examination and medication charges, as well as expenses associated with directly observed therapy.

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U.S. clinical practice guidelines recommend directly observed therapy (DOT) as the standard of care for tuberculosis (TB) treatment (1). DOT, during which a health care worker observes a patient ingesting the TB medications, has typically been conducted in person. Video DOT (vDOT) uses video-enabled devices to facilitate remote interactions between patients and health care workers to promote medication adherence and clinical monitoring. Published systematic reviews, a published meta-analysis, and a literature search through 2022 demonstrate that vDOT is associated with a higher proportion of medication doses being observed and similar proportions of cases with treatment completion and microbiologic resolution when compared with in-person DOT (2-5). Based on this evidence, CDC has updated the recommendation for DOT during TB treatment to include vDOT as an equivalent alternative to in-person DOT. vDOT can assist health department TB programs meet the U.S. standard of care for patients undergoing TB treatment, while using resources efficiently.

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On May 5, 2021, CDC's Tuberculosis Trials Consortium and the National Institutes of Health (NIH)-sponsored AIDS Clinical Trials Group (ACTG) published results from a randomized controlled trial indicating that a 4-month regimen containing rifapentine (RPT), moxifloxacin (MOX), isoniazid (INH), and pyrazinamide (PZA) was as effective as the standard 6-month regimen for tuberculosis (TB) treatment (1). On the basis of these findings, CDC recommends the 4-month regimen as a treatment option for U.S. patients aged ≥12 years with drug-susceptible pulmonary TB and provides implementation considerations for this treatment regimen.

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Rationale: A central strategy of tuberculosis (TB) control in the United States is reducing the burden of latent TB infection (LTBI) through targeted testing and treatment of persons with untreated LTBI. Objectives: The objective of the study was to provide estimates of and risk factors for engagement in LTBI care in the overall U.S. population and among specific risk groups. Methods: We used nationally representative data from 7,080 participants in the 2011-2012 National Health and Nutrition Examination Survey. Engagement in LTBI care was assessed by estimating the proportion with a history of testing, diagnosis, treatment initiation, and treatment completion. Weighted methods were used to account for the complex survey design and to derive national estimates. Results: Only 1.4 million (10%) of an estimated 14.0 million individuals with an LTBI had previously completed treatment. Of the 12.6 million who did not complete LTBI treatment, 3.7 million (29%) had never been tested and 7.2 million (57%) received testing but had no history of diagnosis. High-risk groups showed low levels of engagement, including contacts of individuals with TB and persons born outside the United States. Conclusions: There is a reservoir of more than 12 million individuals in the United States who may be at risk for progression to TB disease and potential transmission. TB control programs and community providers should consider focused efforts to increase testing, diagnosis, and treatment for LTBI.

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Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States.The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence).These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93-e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens.In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.

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Rationale: Mathematical modeling is used to understand disease dynamics, forecast trends, and inform public health prioritization. We conducted a comparative analysis of tuberculosis (TB) epidemiology and potential intervention effects in California, using three previously developed epidemiologic models of TB.Objectives: To compare the influence of various modeling methods and assumptions on epidemiologic projections of domestic latent TB infection (LTBI) control interventions in California.Methods: We compared model results between 2005 and 2050 under a base-case scenario representing current TB services and alternative scenarios including: 1) sustained interruption of Mycobacterium tuberculosis (Mtb) transmission, 2) sustained resolution of LTBI and TB prior to entry of new residents, and 3) one-time targeted testing and treatment of LTBI among 25% of non-U.S.-born individuals residing in California.Measurements and Main Results: Model estimates of TB cases and deaths in California were in close agreement over the historical period but diverged for LTBI prevalence and new Mtb infections-outcomes for which definitive data are unavailable. Between 2018 and 2050, models projected average annual declines of 0.58-1.42% in TB cases, without additional interventions. A one-time LTBI testing and treatment intervention among non-U.S.-born residents was projected to produce sustained reductions in TB incidence. Models found prevalent Mtb infection and migration to be more significant drivers of future TB incidence than local transmission.Conclusions: All models projected a stagnation in the decline of TB incidence, highlighting the need for additional interventions including greater access to LTBI diagnosis and treatment for non-U.S.-born individuals. Differences in model results reflect gaps in historical data and uncertainty in the trends of key parameters, demonstrating the need for high-quality, up-to-date data on TB determinants and outcomes.

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BACKGROUND: A single 2-year National Health and Nutrition Examination Survey (NHANES) cycle is designed to provide accurate and stable estimates of conditions with prevalence of at least 10%. Recent NHANES-based estimates of a tuberculin skin test (TST) ≥10 mm in the noninstitutionalized US civilian population are at most 6.3%. METHODS: NHANES included a TST in 1971-1972, 1999-2000, and 2011-2012. We examined the robustness of NHANES-based estimates of the US population prevalence of a skin test ≥10 mm with a bias analysis that considered the influence of non-US birth distributions and within-household skin test results, reclassified borderline-positive results, and adjusted for TST item nonresponse. RESULTS: The weighted non-US birth distribution among NHANES participants was similar to that in the overall US population; further adjustment was unnecessary. We found no evidence of bias due to sampling multiple participants per household. Prevalence estimates changed 0.3% with reclassification of borderline-positive TST results and 0.2%-0.3% with adjustment for item nonresponse. CONCLUSIONS: For estimating the national prevalence of a TST ≥10 mm during these three survey cycles, a conventional NHANES analysis using the standard participant weights and masked design parameters that are provided in the public-use datasets appears robust. See video abstract at, http://links.lww.com/EDE/B636.

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Although considerable progress has been made in reducing US tuberculosis incidence, the goal of eliminating the disease from the United States remains elusive. A continued focus on preventing new tuberculosis infections while also identifying and treating persons with existing tuberculosis infection is needed. Continued vigilance to ensure ongoing control of tuberculosis transmission remains key.

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We describe characteristics of US healthcare personnel (HCP) diagnosed with tuberculosis (TB). Among 64,770 adults with TB during 2010-2016, 2,460 (4%) were HCP. HCP with TB were more likely to be born outside of the United States, and less likely to have TB attributed to recent transmission, than non-HCP.

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The association between chronic kidney disease (CKD) and tuberculosis disease (TB) has been recognized for decades. Recently CKD prevalence is increasing in low- to middle-income countries with high TB burden. Using data from the required overseas medical exam and the recommended US follow-up exam for 444,356 US-bound refugees aged ≥ 18 during 2009-2017, we ran Poisson regression to assess the prevalence of TB among refugees with and without CKD, controlling for sex, age, diabetes, tobacco use, body mass index ( kg/m2), prior residence in camp or non-camp setting, and region of birth country. Of the 1117 (0.3%) with CKD, 21 (1.9%) had TB disease; of the 443,239 who did not have CKD, 3380 (0.8%) had TB. In adjusted analyses, TB was significantly higher among those with than without CKD (prevalence ratio 1.93, 95% CI: 1.26, 2.98, p < 0.01). Healthcare providers attending to refugees need to be aware of this association.

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OBJECTIVES: To assess changes in US tuberculosis (TB) incidence rates by age, period, and cohort effects, stratified according to race/ethnicity and nativity. METHODS: We used US National Tuberculosis Surveillance System data for 1996 to 2016 to estimate trends through age-period-cohort models. RESULTS: Controlling for cohort and period effects indicated that the highest rates of TB incidence occurred among those 0 to 5 and 20 to 30 years of age. The incidence decreased by age for successive birth cohorts. There were greater estimated annual percentage decreases among US-born individuals (-7.3%; 95% confidence interval [CI] = -7.5, -7.1) than among non-US-born individuals (-4.3%; 95% CI = -4.5, -4.1). US-born individuals older than 25 years exhibited the largest decreases, a pattern that was not reflected among non-US-born adults. In the case of race/ethnicity, the greatest decreases by nativity were among US-born Blacks (-9.3%; 95% CI = -9.6, -9.1) and non-US-born Hispanics (-5.7%; 95% CI = -6.0, -5.5). CONCLUSIONS: TB has been decreasing among all ages, races and ethnicities, and consecutive cohorts, although these decreases are less pronounced among non-US-born individuals.

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We used tuberculosis genotyping results to derive estimates of prevalence of latent tuberculosis infection in the United States. We estimated <1% prevalence in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This method for estimating prevalence could be applied in any jurisdiction with an established tuberculosis surveillance system.

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Treatment of latent tuberculosis infection (LTBI) is critical to the control and elimination of tuberculosis disease (TB) in the United States. In 2011, CDC recommended a short-course combination regimen of once-weekly isoniazid and rifapentine for 12 weeks (3HP) by directly observed therapy (DOT) for treatment of LTBI, with limitations for use in children aged <12 years and persons with human immunodeficiency virus (HIV) infection (1). CDC identified the use of 3HP in those populations, as well as self-administration of the 3HP regimen, as areas to address in updated recommendations. In 2017, a CDC Work Group conducted a systematic review and meta-analyses of the 3HP regimen using methods adapted from the Guide to Community Preventive Services. In total, 19 articles representing 15 unique studies were included in the meta-analysis, which determined that 3HP is as safe and effective as other recommended LTBI regimens and achieves substantially higher treatment completion rates. In July 2017, the Work Group presented the meta-analysis findings to a group of TB experts, and in December 2017, CDC solicited input from the Advisory Council for the Elimination of Tuberculosis (ACET) and members of the public for incorporation into the final recommendations. CDC continues to recommend 3HP for treatment of LTBI in adults and now recommends use of 3HP 1) in persons with LTBI aged 2-17 years; 2) in persons with LTBI who have HIV infection, including acquired immunodeficiency syndrome (AIDS), and are taking antiretroviral medications with acceptable drug-drug interactions with rifapentine; and 3) by DOT or self-administered therapy (SAT) in persons aged ≥2 years.

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Telephone triage (TT) is a method whereby medical professionals speak by telephone to patients to assess their symptoms or health concerns and offer advice. These services are often administered through an electronic TT system, which guides TT professionals during the encounter through the use of structured protocols and algorithms to help determine the severity of the patients' health issue and refer them to appropriate care. TT is also an emerging data source for public health surveillance of infectious and noninfectious diseases, including influenza. We calculated Spearman correlation coefficients to compare the weekly number of US Department of Veterans Affairs (VA) TT calls with other conventional influenza measures for the 2011-2012 through 2014-2015 influenza seasons, for which there were a total of 35 666 influenza-coded TT encounters. Influenza-coded calls were strongly correlated with weekly VA influenza-coded hospitalizations (0.85), emergency department visits (0.90), influenza-like illness outpatient visits (0.92), influenza tests performed (0.86), positive influenza tests (0.82), and influenza antiviral prescriptions (0.89). The correlation between VA-TT and Centers for Disease Control and Prevention (CDC) national data for weekly influenza hospitalizations, influenza tests performed, and positive influenza tests was also strong. TT correlates well with VA health care use and CDC data and is a timely data source for monitoring influenza activity.

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OBJECTIVE: To evaluate TB test usage and associated direct medical expenditures from 2013 private insurance claims data in the United States (US). METHODS: We extracted outpatient claims for TB-specific and nonspecific tests from the 2013 MarketScan® commercial database. We estimated average expenditures (adjusted for claim and patient characteristics) using semilog regression analyses and compared them to the Centers for Medicare and Medicaid Services (CMS) national reimbursement limits. RESULTS: Among the TB-specific tests, 1.4% of the enrollees had at least one claim, of which the tuberculin skin test was most common (86%) and least expensive ($9). The T-SPOT® was the most expensive among the TB-specific tests ($106). Among nonspecific TB tests, the chest radiograph was the most used test (78%), while chest computerized tomography was the most expensive ($251). Adjusted average expenditures for the majority of tests (≈74%) were above CMS limits. We estimated that total United States medical expenditures for the employer-based privately insured population for TB-specific tests were $53.0 million in 2013, of which enrollees paid 17% ($9 million). CONCLUSIONS: We found substantial differences in TB test usage and expenditures. Additionally, employer-based private insurers and enrollees paid more than CMS limits for most TB tests.

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Chronic hepatitis B virus (HBV) infection screening usually includes only HBV surface antigen (HBsAg) testing; HBV core and surface antibody (anti-HBc, anti-HBs) assays, indicating resolved infection and immunity, are not routinely performed. Yet, serum HBV DNA is measurable in approximately 10% of HBsAg-negative/anti-HBc-positive cases, representing occult HBV infection (OBI). Patient blood samples from 2 Veterans Affairs medical center look-back investigations were screened for HBV infection using HBsAg enzyme immunoassays. Supplementary testing included anti-HBc and anti-HBs enzyme immunoassays. For anti-HBc-positive samples, HBV DNA testing was performed. Background OBI prevalence was further estimated at these 2 facilities based on HBV serology testing results from 1999-2012. Finally, a literature review was performed to determine OBI prevalence in the published literature. Of 1887 HBsAg-negative cohort patients, 98 (5.2%) were anti-HBc positive/anti-HBs negative; and 175 (9.3%), anti-HBc positive/anti-HBs positive. Six of 273 were HBV DNA positive, representing 0.3% of the total tested and 2.2% who were anti-HBc positive/anti-HBs negative or anti-HBc positive/anti-HBs positive. Among 32,229 general population veterans at these 2 sites who had any HBV testing, 4/108 (3.7%) were HBV DNA positive, none of whom were part of the cohort. In 129 publications with HBsAg-negative patients, 1817/1,209,426 (0.15%) had OBI. However, excluding blood bank studies with greater than 1000 patients, the OBI rate increased to 1800/17,893 (10%). OBI is not rare and has implications for transmission and disease detection. HBsAg testing alone is insufficient for detecting all chronic HBV infections. These findings may impact blood donation, patient HBV screening, follow-up protocols for patients assumed to have cleared the infection, and initiation of immunosuppression in patients with distant or undetected HBV.

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