Estimated Costs of 4-Month Pulmonary Tuberculosis Treatment Regimen, United States.

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.

Recommendations for Use of Video Directly Observed Therapy During Tuberculosis Treatment - United States, 2023.

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.

Self-reported Engagement in Care among U.S. Residents with Latent Tuberculosis Infection: 2011-2012.

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.

Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020.

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.

Robustness of NHANES Estimates of the US Prevalence of a Positive Tuberculin Skin Test.

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.

Comparative Modeling of Tuberculosis Epidemiology and Policy Outcomes in California.

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.

Epidemiology of Tuberculosis in the United States.

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.

Tuberculosis among healthcare personnel, United States, 2010-2016.

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.

Prevalence of Tuberculosis Disease Among Adult US-Bound Refugees with Chronic Kidney Disease.

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.

Age-Period-Cohort Analyses of Tuberculosis Incidence Rates by Nativity, United States, 1996-2016.

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.

Simple Estimates for Local Prevalence of Latent Tuberculosis Infection, United States, 2011-2015.

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.

Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection.

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.

Enhanced Influenza Surveillance Using Telephone Triage and Electronic Syndromic Surveillance in the Department of Veterans Affairs, 2011-2015.

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.

Tuberculosis Test Usage and Medical Expenditures from Outpatient Insurance Claims Data, 2013.

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.

Are current screening protocols for chronic hepatitis B virus infection adequate?

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.

Abrupt Decline in Tuberculosis among Foreign-Born Persons in the United States.

While the number of reported tuberculosis (TB) cases in the United States has declined over the past two decades, TB morbidity among foreign-born persons has remained persistently elevated. A recent unexpected decline in reported TB cases among foreign-born persons beginning in 2007 provided an opportunity to examine contributing factors and inform future TB control strategies. We investigated the relative influence of three factors on the decline: 1) changes in the size of the foreign-born population through immigration and emigration, 2) changes in distribution of country of origin among foreign-born persons, and 3) changes in the TB case rates among foreign-born subpopulations. Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined TB case counts, TB case rates, and population estimates, stratified by years since U.S. entry and country of origin. Regression modeling was used to assess statistically significant changes in trend. Among foreign-born recent entrants (<3 years since U.S. entry), we found a 39.5% decline (-1,013 cases) beginning in 2007 (P<0.05 compared to 2000-2007) and ending in 2011 (P<0.05 compared to 2011-2014). Among recent entrants from Mexico, 80.7% of the decline was attributable to a decrease in population, while the declines among recent entrants from the Philippines, India, Vietnam, and China were almost exclusively (95.5%-100%) the result of decreases in TB case rates. Among foreign-born non-recent entrants (≥3 years since U.S. entry), we found an 8.9% decline (-443 cases) that resulted entirely (100%) from a decrease in the TB case rate. Both recent and non-recent entrants contributed to the decline in TB cases; factors contributing to the decline among recent entrants varied by country of origin. Strategies that impact both recent and non-recent entrants (e.g., investment in overseas TB control) as well as those that focus on non-recent entrants (e.g., expanded targeted testing of high-risk subgroups among non-recent entrants) will be necessary to achieve further declines in TB morbidity among foreign-born persons.

Coding of Electronic Laboratory Reports for Biosurveillance, Selected United States Hospitals, 2011.

Objective Electronic laboratory reporting has been promoted as a public health priority. The Office of the U.S. National Coordinator for Health Information Technology has endorsed two coding systems: Logical Observation Identifiers Names and Codes (LOINC) for laboratory test orders and Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) for test results. Materials and Methods We examined LOINC and SNOMED CT code use in electronic laboratory data reported in 2011 by 63 non-federal hospitals to BioSense electronic syndromic surveillance system. We analyzed the frequencies, characteristics, and code concepts of test orders and results. Results A total of 14,028,774 laboratory test orders or results were reported. No test orders used SNOMED CT codes. To describe test orders, 77% used a LOINC code, 17% had no value, and 6% had a non-informative value, "OTH". Thirty-three percent (33%) of test results had missing or non-informative codes. For test results with at least one informative value, 91.8% had only LOINC codes, 0.7% had only SNOMED codes, and 7.4% had both. Of 108 SNOMED CT codes reported without LOINC codes, 45% could be matched to at least one LOINC code. Conclusion Missing or non-informative codes comprised almost a quarter of laboratory test orders and a third of test results reported to BioSense by non-federal hospitals. Use of LOINC codes for laboratory test results was more common than use of SNOMED CT. Complete and standardized coding could improve the usefulness of laboratory data for public health surveillance and response.

Practical comparison of aberration detection algorithms for biosurveillance systems.

National syndromic surveillance systems require optimal anomaly detection methods. For method performance comparison, we injected multi-day signals stochastically drawn from lognormal distributions into time series of aggregated daily visit counts from the U.S. Centers for Disease Control and Prevention's BioSense syndromic surveillance system. The time series corresponded to three different syndrome groups: rash, upper respiratory infection, and gastrointestinal illness. We included a sample of facilities with data reported every day and with median daily syndromic counts ⩾1 over the entire study period. We compared anomaly detection methods of five control chart adaptations, a linear regression model and a Poisson regression model. We assessed sensitivity and timeliness of these methods for detection of multi-day signals. At a daily background alert rate of 1% and 2%, the sensitivities and timeliness ranged from 24 to 77% and 3.3 to 6.1days, respectively. The overall sensitivity and timeliness increased substantially after stratification by weekday versus weekend and holiday. Adjusting the baseline syndromic count by the total number of facility visits gave consistently improved sensitivity and timeliness without stratification, but it provided better performance when combined with stratification. The daily syndrome/total-visit proportion method did not improve the performance. In general, alerting based on linear regression outperformed control chart based methods. A Poisson regression model obtained the best sensitivity in the series with high-count data.