OBJECTIVES: To evaluate the cost-effectiveness of testing and treatment for Mycobacterium tuberculosis (Mtb) infection among Asian and Hispanic persons with diagnosed diabetes in the United States. METHODS: We estimated population size and Mtb infection prevalence for Asian and Hispanic persons aged ≥15 years with diagnosed, non-gestational diabetes, by age and US-born-status. We assumed a one-time test for Mtb infection intervention, with positive-testing persons offered treatment. Using a deterministic, transmission-dynamic model of TB in the United States, we estimated costs, TB cases and deaths averted, and quality-adjusted life-years (QALY) gained under the intervention compared to no-intervention. We estimated incremental cost-effectiveness ratios (ICERs), calculated as costs per QALY-gained, from a TB health services perspective, including diagnosis and treatment for TB infection and disease. We also assessed health services and societal perspectives. We estimated 95% uncertainty intervals via probabilistic sensitivity analysis. RESULTS: TB cases averted per 100,000 persons tested ranged from 7.5 (95% uncertainty interval: 6.9-8.1) among US-born Hispanic persons to 238.9 (225.2-254.3) among non-US-born Asian persons. TB deaths averted per 100,000 persons tested ranged from 1.3 (1.2-1.4) among US-born Hispanic persons to 53.7 (51.4-56.1) among non-US-born Asian persons. ICERs for US-born Asian and Hispanic populations were $856,671 ($533,506-$1,234,032) and $1,081,646 ($673,142-$1,551,264), respectively. ICERs for non-US-born Asian and Hispanic populations were lower: $66,664 ($41,456-$93,625) and $68,749 ($43,136-$97,044), respectively. ICERs were 2-19% higher under a societal perspective. CONCLUSIONS: While the intervention produced health benefits for all populations assessed, health benefits were greater-and ICERs more favorable-for non-US-born Asian and Hispanic populations with diagnosed-diabetes.

BACKGROUND: Tuberculosis (TB) notifications and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends. METHODS: We identified four mechanisms potentially contributing to observed TB trends during 2020-2023: immigration, respiratory contact rates, rates of accurate diagnosis and treatment initiation, and mortality rates for persons experiencing TB disease. We employed a Bayesian approach to synthesize evidence on how these mechanisms changed during the pandemic and how they might have combined to produce observed 2020-2023 TB data, using a transmission-dynamic model to link mechanisms to TB outcomes. We also simulated a no-pandemic-counterfactual scenario that assumed mechanisms followed pre-pandemic trends. We estimated TB outcomes associated with the pandemic until 2035 to capture lagged effects. We evaluated additional scenarios to estimate the individual effect of each mechanism. RESULTS: Over 2020-2035, we estimate an additional 2,784 (95% uncertainty interval: 2,164-3,461) TB notifications and 1,138 (1,076-1,201) TB deaths in the United States associated with changes occurring during the COVID-19 pandemic. Mechanisms had offsetting effects - decreases in TB diagnosis rates led to more TB deaths and notifications, while reductions in contact rates reduced TB deaths and notifications. Immigration changes initially reduced TB deaths, but increased deaths and notifications over time. Higher TB mortality rates increased TB deaths, but decreased TB notifications. CONCLUSIONS: While direct impacts of the COVID-19 pandemic occurred between 2020-2023, these changes may continue to influence TB incidence and mortality in future years.

RATIONALE: Individuals surviving TB disease may experience chronic sequelae that reduce survival and quality-of-life. These post-TB sequalae are not generally considered in estimates of the health impact of TB disease. OBJECTIVES: To estimate the TB-attributable reductions in life expectancy and quality-adjusted life expectancy for individuals developing TB disease in the United States, including post-TB sequelae. METHODS: We extracted national surveillance data on individuals diagnosed with TB during 2015-2019, including demographics, vital status at diagnosis, treatment duration, treatment outcome, and co-prevalent conditions. Using a mathematical model we simulated life expectancy and quality-adjusted life-years (QALYs) for the TB cohort, as compared to a no-TB counterfactual (same distribution of age, sex, race/ethnicity, and co-prevalent conditions as the TB cohort but without TB-attributable mortality and disutility). We disaggregated results to report the proportion due to post-TB sequelae, and stratified outcomes by age, sex, and race. MEASUREMENTS AND MAIN RESULTS: Estimated life expectancy after TB diagnosis was 30.3 (95% uncertainty interval: 29.9, 30.7) years for the TB cohort versus 32.3 (31.9, 32.7) without TB, a difference of 2.03 (1.84, 2.21) years and 1.93 (1.69, 2.18) QALYs. Life-years lost were greatest for 65-74-year-olds versus other age groups, for men versus women, and for American Indian or Alaska Native individuals versus persons from other race/ethnicities. Overall, 41% (35, 46) of life-years and 48% (42, 54) of QALYs lost were estimated to result from post-TB sequelae. CONCLUSIONS: In the United States, a substantial fraction of the life-years and QALYs lost from TB are attributable to post-TB sequelae. Evidence is needed on approaches to prevent and repair post-TB lung damage, in the context of frequent co-prevalent health conditions.

BACKGROUND: In the United States, older adults have elevated prevalence of latent tuberculosis infection (LTBI) and incidence of tuberculosis (TB). OBJECTIVE: To estimate the health benefits and cost-effectiveness of LTBI testing and treatment among the Medicare-eligible population. DESIGN: Model-based cost-effectiveness analysis. DATA SOURCES: Nationally representative surveys and published evidence. TARGET POPULATION: Medicare-eligible persons aged 65 years or older with at least 1 of 15 factors associated with elevated TB risk, as identified by guidelines from the U.S. Preventive Services Task Force (USPSTF) and other organizations. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: One-time offer of LTBI testing and treatment versus no intervention. OUTCOME MEASURES: Lifetime TB cases and deaths averted, quality-adjusted life-years (QALYs) gained, costs, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: In 2022, there were an estimated 29.9 million Medicare-eligible persons (95% uncertainty interval [UI], 28.4 to 31.6 million persons) aged 65 years or older with elevated TB risks, including 14.7 million (95% UI, 13.4 to 16.0 million) with USPSTF-recommended factors. In the target population, 4.9 million persons (95% UI, 4.0 to 5.8 million persons) (16.4% [95% UI, 13.9% to 19.1%]) were estimated to have LTBI. Testing and treatment of LTBI was estimated to prevent 10 946 TB cases (95% UI, 4684 to 20 579 cases) and 2579 TB deaths (95% UI, 1106 to 4882 deaths), with 13 234 lifetime QALYs (95% UI, 5343 to 25 519 lifetime QALYs) gained. For the overall target population and for persons with USPSTF-recommended factors, ICERs were $192 000 (95% UI, $92 000 to $503 000) and $155 000 (95% UI, $77 000 to $393 000) per QALY gained, respectively. RESULTS OF SENSITIVITY ANALYSIS: The ICER was $109 000 (95% UI, $49 000 to $285 000) per QALY gained for 65-year-olds newly eligible for Medicare. LIMITATION: Health benefits from averted post-TB sequelae were not estimated. CONCLUSION: Medicare-eligible persons represent approximately one third of all U.S. persons with LTBI. Testing and treatment of LTBI in this population could lead to substantial reductions in TB and TB-related mortality, particularly among 65-year-olds newly eligible for Medicare. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

BACKGROUND: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative. METHODS AND FINDINGS: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available. CONCLUSIONS: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

IMPORTANCE: Despite significant progress made toward tuberculosis (TB) elimination, racial and ethnic disparities persist in TB incidence and case-fatality rates in the US. OBJECTIVE: To estimate the health outcomes and economic cost of TB disparities among US-born persons from 2023 to 2035. DESIGN, SETTING, AND PARTICIPANTS: Generalized additive regression models projecting trends in TB incidence and case-fatality rates from 2023 to 2035 were fit based on national TB surveillance data for 2010 to 2019 in the 50 US states and the District of Columbia among US-born persons. This baseline scenario was compared with alternative scenarios in which racial and ethnic disparities in age- and sex-adjusted incidence and case-fatality rates were eliminated by setting rates for each race and ethnicity to goal values. Additional scenarios were created examining the potential outcomes of delayed reduction of racial and ethnic disparities. The potential benefits of eliminating disparities from differences between baseline and alternative scenario outcomes were quantified. Data were analyzed from January 2010 to December 2019. EXPOSURES: Non-Hispanic American Indian or Alaska Native, non-Hispanic Asian, non-Hispanic Black, Hispanic, non-Hispanic Native Hawaiian or Other Pacific Islander, or non-Hispanic White race and ethnicity. MAIN OUTCOMES AND MEASURES: TB cases and deaths averted, quality-adjusted life years gained, and associated costs from a societal perspective. RESULTS: The study included 31 811 persons with reported TB from 2010 to 2019 (mean [SD] age, 47 [24] years; 20 504 [64%] male; 1179 [4%] American Indian or Alaska Native persons; 1332 [4%] Asian persons; 12 152 [38%] Black persons; 6595 [21%] Hispanic persons; 299 [1%] Native Hawaiian or Other Pacific Islander persons; and 10 254 [32%] White persons). There were 3722 persons with a reported TB death. Persistent racial and ethnic disparities were associated with an estimated 11 901 of 26 203 TB cases among US-born persons (45%; 95% uncertainty interval [UI], 44%-47%), 1421 of 3264 TB deaths among US-born persons (44%; 95% UI, 39%-48%), and an economic cost of $914 (95% UI, $675-$1147) million from 2023 to 2035. Delayed goal attainment reduced the estimated avertable TB outcomes by 505 (95% UI, 495-518) TB cases, 55 (95% UI, 51-59) TB deaths, and $32 (95% UI, $24-$40) million in societal costs annually. CONCLUSIONS AND RELEVANCE: In this modeling study of racial and ethnic disparities of TB, these disparities were associated with substantial future health and economic outcomes of TB among US-born persons without interventions beyond current efforts. Actions to eliminate disparities may reduce the excess TB burden among these persons and may contribute to accelerating TB elimination within the US.

BACKGROUND: For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023. METHODS: Using a mathematical modelling framework, we simulated how US tuberculosis incidence could be affected by changes in tuberculosis services in the countries of origin for future migrants to the USA, as well as changes in tuberculosis services inside the USA. To do so, we used a linked set of transmission dynamic models, calibrated to demographic and epidemiological data for each setting. We constructed intervention scenarios representing improvements in tuberculosis services internationally and within the USA, individually and in combination, plus a base-case scenario representing continuation of current services. We simulated health and economic outcomes until 2100, using a Bayesian approach to quantify uncertainty in these outcomes. FINDINGS: Under the base-case scenario, US tuberculosis incidence was projected to decline to 1·8 cases per 100 000 (95% uncertainty interval [UI] 1·5-2·1) in the total population by 2050. Intervention scenarios produced substantial reductions in tuberculosis incidence, with the combination of all domestic and international interventions projected to achieve pre-elimination by 2033 (95% UI 2031-2037). Compared with the base-case scenario, this combination of interventions could avert 101 000 tuberculosis cases (95% UI 84 000-120 000) and 13 300 tuberculosis deaths (95% UI 10 500-16 300) in the USA from 2025 to 2050. Tuberculosis elimination was not projected before 2100. INTERPRETATION: Strengthening tuberculosis services domestically, promoting the development of more effective technologies and interventions, and supporting tuberculosis programmes in countries with a high tuberculosis burden are key strategies for accelerating progress towards tuberculosis elimination in the USA. FUNDING: US Centers for Disease Control and Prevention.

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 Extremes(Race-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.

About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non-US-born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals. We simulated immigrants with HBV infection arriving to the United States from 2000 to 2070 using models of the 10 countries from which the largest numbers of individuals with HBV infection were born. We estimated costs in the United States among these cohorts using a disease simulation model. We simulated three scenarios: a scenario with no progress in infant vaccination for hepatitis B since 2000 (baseline), current (2020) progress and achieving WHO 2030 goals for hepatitis B vaccination. We estimate current hepatitis B vaccination progress since the 2000 baseline in these 10 countries will lead to 468,686 fewer HBV infections, avoid 35,582 hepatitis B-related deaths and save $4.2 billion in the United States through 2070. Achieving the WHO 2030 90% hepatitis B infant vaccination targets could lead to an additional 16,762 fewer HBV infections, 989 fewer hepatitis B-related deaths and save $143 million through 2070. Global hepatitis B vaccination since 2000 reduced prevalence of HBV infection in the United States. Achieving the WHO 2030 infant vaccination goals globally could lead to over one hundred million dollars in additional savings.

BACKGROUND: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. OBJECTIVE: To quantify trends in racial/ethnic disparities in TB incidence among U.S.-born persons. DESIGN: Time-series analysis of national TB registry data for 2011 to 2021. SETTING: United States. PARTICIPANTS: U.S.-born persons stratified by race/ethnicity. MEASUREMENTS: TB incidence rates, incidence rate differences, and incidence rate ratios compared with non-Hispanic White persons; excess TB cases (calculated from incidence rate differences); and the index of disparity. Analyses were stratified by sex and by attribution of TB disease to recent transmission and were adjusted for age, year, and state of residence. RESULTS: In analyses of TB incidence rates for each racial/ethnic population compared with non-Hispanic White persons, incidence rate ratios were as high as 14.2 (95% CI, 13.0 to 15.5) among American Indian or Alaska Native (AI/AN) females. Relative disparities were greater for females, younger persons, and TB attributed to recent transmission. Absolute disparities were greater for males. Excess TB cases in 2011 to 2021 represented 69% (CI, 66% to 71%) and 62% (CI, 60% to 64%) of total cases for females and males, respectively. No evidence was found to indicate that incidence rate ratios decreased over time, and most relative disparity measures showed small, statistically nonsignificant increases. LIMITATION: Analyses assumed complete TB case diagnosis and self-report of race/ethnicity and were not adjusted for medical comorbidities or social determinants of health. CONCLUSION: There are persistent disparities in TB incidence by race/ethnicity. Relative disparities were greater for AI/AN persons, females, and younger persons, and absolute disparities were greater for males. Eliminating these disparities could reduce overall TB incidence by more than 60% among the U.S.-born population. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

BACKGROUND: In the United States, over 80% of tuberculosis (TB) disease cases are estimated to result from reactivation of latent TB infection (LTBI) acquired more than 2 years previously ("reactivation TB"). We estimated reactivation TB rates for the US population with LTBI, overall, by age, sex, race-ethnicity, and US-born status, and for selected comorbidities (diabetes, end-stage renal disease, and HIV). METHODS: We collated nationally representative data for 2011-2012. Reactivation TB incidence was based on TB cases reported to the National TB Surveillance System that were attributed to LTBI reactivation. Person-years at risk of reactivation TB were calculated using interferon-gamma release assay (IGRA) positivity from the National Health and Nutrition Examination Survey, published values for interferon-gamma release assay sensitivity and specificity, and population estimates from the American Community Survey. RESULTS: For persons aged ≥6 years with LTBI, the overall reactivation rate was estimated as 0.072 (95% uncertainty interval: 0.047, 0.12) per 100 person-years. Estimated reactivation rates declined with age. Compared to the overall population, estimated reactivation rates were higher for persons with diabetes (adjusted rate ratio [aRR] = 1.6 [1.5, 1.7]), end-stage renal disease (aRR = 9.8 [5.4, 19]), and HIV (aRR = 12 [10, 13]). CONCLUSIONS: In our study, individuals with LTBI faced small, non-negligible risks of reactivation TB. Risks were elevated for individuals with medical comorbidities that weaken immune function.

BACKGROUND: Persistent racial and ethnic disparities in tuberculosis incidence exist in the USA, however, less is known about disparities along the tuberculosis continuum of care. This study aimed to describe how race and ethnicity are associated with tuberculosis diagnosis and treatment outcomes. METHODS: In this analysis of national surveillance data, we extracted data from the US National Tuberculosis Surveillance System on US-born patients with tuberculosis during 2003-19. To estimate the association between race and ethnicity and tuberculosis diagnosis (diagnosis after death, cavitation, and sputum smear positivity) and treatment outcomes (treatment for more than 12 months, treatment discontinuation, and death during treatment), we fitted log-binomial regression models adjusting for calendar year, sex, age category, and regional division. Race and ethnicity were defined based on US Census Bureau classification as White, Black, Hispanic, Asian, American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and people of other ethnicities. We quantified racial and ethnic disparities as adjusted relative risks (aRRs) using non-Hispanic White people as the reference group. We also calculated the Index of Disparity as a summary measure that quantifies the dispersion in a given outcome across all racial and ethnic groups, relative to the population mean. We estimated time trends in each outcome to evaluate whether disparities were closing or widening. FINDINGS: From 2003 to 2019, there were 72 809 US-born individuals diagnosed with tuberculosis disease of whom 72 369 (35·7% women and 64·3% men) could be included in analyses. We observed an overall higher risk of any adverse outcome (defined as diagnosis after death, treatment discontinuation, or death during treatment) for non-Hispanic Black people (aRR 1·27, 95% CI 1·22-1·32), Hispanic people (1·20, 1·14-1·27), and American Indian or Alaska Native people (1·24, 1·12-1·37), relative to non-Hispanic White people. The Index of Disparity for this summary outcome remained unchanged over the study period. INTERPRETATION: This study, based on national surveillance data, indicates racial and ethnic disparaties among US-born tuberculosis patients along the tuberculosis continuum of care. Initiatives are needed to reduce diagnostic delays and improve treatment outcomes for US-born racially marginalised people in the USA. FUNDING: US Centers for Disease Control and Prevention.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

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.

BACKGROUND: In the United States, the tuberculosis (TB) disease burden and associated factors vary substantially across states. While public health agencies must choose how to deploy resources to combat TB and latent tuberculosis infection (LTBI), state-level modeling analyses to inform policy decisions have not been widely available. METHODS: We developed a mathematical model of TB epidemiology linked to a web-based user interface - Tabby2. The model is calibrated to epidemiological and demographic data for the United States, each U.S. state, and the District of Columbia. Users can simulate pre-defined scenarios describing approaches to TB prevention and treatment or create their own intervention scenarios. Location-specific results for epidemiological outcomes, service utilization, costs, and cost-effectiveness are reported as downloadable tables and customizable visualizations. To demonstrate the tool's functionality, we projected trends in TB outcomes without additional intervention for all 50 states and the District of Columbia. We further undertook a case study of expanded treatment of LTBI among non-U.S.-born individuals in Massachusetts, covering 10% of the target population annually over 2025-2029. RESULTS: Between 2022 and 2050, TB incidence rates were projected to decline in all states and the District of Columbia. Incidence projections for the year 2050 ranged from 0.03 to 3.8 cases (median 0.95) per 100,000 persons. By 2050, we project that majority (> 50%) of TB will be diagnosed among non-U.S.-born persons in 46 states and the District of Columbia; per state percentages range from 17.4% to 96.7% (median 83.0%). In Massachusetts, expanded testing and treatment for LTBI in this population was projected to reduce cumulative TB cases between 2025 and 2050 by 6.3% and TB-related deaths by 8.4%, relative to base case projections. This intervention had an incremental cost-effectiveness ratio of $180,951 (2020 USD) per quality-adjusted life year gained from the societal perspective. CONCLUSIONS: Tabby2 allows users to estimate the costs, impact, and cost-effectiveness of different TB prevention approaches for multiple geographic areas in the United States. Expanded testing and treatment for LTBI could accelerate declines in TB incidence in the United States, as demonstrated in the Massachusetts case study.

Delays in case reporting are common to disease surveillance systems, making it difficult to track diseases in real-time. “Nowcast” approaches attempt to estimate the complete case counts for a given reporting date, using a time series of case reports that is known to be incomplete due to reporting delays. Modeling the reporting delay distribution is a common feature of nowcast approaches. However, many nowcast approaches ignore a crucial feature of infectious disease transmission—that future cases are intrinsically linked to past reported cases—and are optimized to a single application, which may limit generalizability. Here, we present a Bayesian approach, NobBS (Nowcasting by Bayesian Smoothing) capable of producing smooth and accurate nowcasts in multiple disease settings. We test NobBS on dengue in Puerto Rico and influenza-like illness (ILI) in the United States to examine performance and robustness across settings exhibiting a range of common reporting delay characteristics (from stable to time-varying), and compare this approach with a published nowcasting package. We show that introducing a temporal relationship between cases considerably improves performance when the reporting delay distribution is time-varying, and we identify trade-offs in the role of moving windows to accurately capture changes in the delay. We present software implementing this new approach (R package “NobBS”) for widespread application.Significance Achieving accurate, real-time estimates of disease activity is challenged by delays in case reporting. However, approaches that seek to estimate cases in spite of reporting delays often do not consider the temporal relationship between cases during an outbreak, nor do they identify characteristics of robust approaches that generalize to a wide range of surveillance contexts with very different reporting delays. Here, we present a smooth Bayesian nowcasting approach that produces accurate estimates that capture the time evolution of the epidemic curve and outperform a previous approach in the literature. We assess the performance for two diseases to identify important features of the reporting delay distribution that contribute to the model’s performance and robustness across surveillance settings.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

BACKGROUND: 3 months of weekly rifapentine plus isoniazid (3HP) and 4 months of daily rifampicin (4R) are recommended for tuberculosis preventive treatment. As these regimens have not been compared directly, we used individual patient data and network meta-analysis methods to compare completion, safety, and efficacy between 3HP and 4R. METHODS: We conducted a network meta-analysis of individual patient data by searching PubMed for randomised controlled trials (RCTs) published between Jan 1, 2000, and Mar 1, 2019. Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease. Deidentified individual patient data from eligible studies were provided by study investigators and outcomes were harmonised. Methods for network meta-analysis were used to generate indirect adjusted risk ratios (aRRs) and risk differences (aRDs) with their 95% CIs. FINDINGS: We included 17 572 participants from 14 countries in six trials. In the network meta-analysis, treatment completion was higher for people on 3HP than for those on 4R (aRR 1·06 [95% CI 1·02-1·10]; aRD 0·05 [95% CI 0·02-0·07]). For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 [2·12-4·21]; aRD 0·03 [0·02-0·05]) and for grade 3-4 adverse events (aRR 3·46 [2·09-6·17]; aRD 0·02 [0·01-0·03]). Similar increased risks with 3HP were observed with other definitions of adverse events and were consistent across age groups. No difference in the incidence of tuberculosis disease between 3HP and 4R was found. INTERPRETATION: In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events. Although findings should be confirmed, the trade-off between completion and safety must be considered when selecting a regimen for tuberculosis preventive treatment. FUNDING: None. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

BACKGROUND: Chlamydia remains a significant public health problem that contributes to adverse reproductive health outcomes. In the United States, sexually active women 24 years and younger are recommended to receive annual screening for chlamydia. In this study, we evaluated the impact of estimated current levels of screening and partner notification (PN), and the impact of screening based on guidelines on chlamydia associated sequelae, quality adjusted life years (QALYs) lost and costs. METHODS: We conducted a cost-effectiveness analysis of chlamydia screening, using a published calibrated pair formation transmission model that estimated trends in chlamydia screening coverage in the United States from 2000 to 2015 consistent with epidemiological data. We used probability trees to translate chlamydial infection outcomes into estimated numbers of chlamydia-associated sequelae, QALYs lost, and health care services costs (in 2020 US dollars). We evaluated the costs and population health benefits of screening and PN in the United States for 2000 to 2015, as compared with no screening and no PN. We also estimated the additional benefits that could be achieved by increasing screening coverage to the levels indicated by the policy recommendations for 2016 to 2019, compared with screening coverage achieved by 2015. RESULTS: Screening and PN from 2000 to 2015 were estimated to have averted 1.3 million (95% uncertainty interval [UI] 490,000-2.3 million) cases of pelvic inflammatory disease, 430,000 (95% UI, 160,000-760,000) cases of chronic pelvic pain, 300,000 (95% UI, 104,000-570,000) cases of tubal factor infertility, and 140,000 (95% UI, 47,000-260,000) cases of ectopic pregnancy in women. We estimated that chlamydia screening and PN cost $9700 per QALY gained compared with no screening and no PN. We estimated the full realization of chlamydia screening guidelines for 2016 to 2019 to cost $30,000 per QALY gained, compared with a scenario in which chlamydia screening coverage was maintained at 2015 levels. DISCUSSION: Chlamydia screening and PN as implemented in the United States from 2000 through 2015 has substantially improved population health and provided good value for money when considering associated health care services costs. Further population health gains are attainable by increasing screening further, at reasonable cost per QALY gained.

We appreciate the letter by Drs. Chang and Yew commenting on the Official Guidelines of the American Thoracic Society (ATS)/CDC/European Respiratory Society (ERS)/Infectious Disease Society of America (IDSA) on the treatment of multidrug-resistant tuberculosis (MDR-TB) (1). Three issues are raised in the letter: first, the certainty of the evidence on the use of linezolid and bedaquiline in the management of fluoroquinolone-sensitive and -resistant MDR-TB; second, the risk of resistance to these two drugs with generalized use, suggesting focused use of these drugs in selected patients might limit this hazard and minimize acquisition of resistance and serious adverse events; and third, that with broadening availability of rapid drug susceptibility testing (DST), optimized longer and existing standardized shorter-course regimens still have value.

Due to greater exposure to Mycobacterium tuberculosis infection before migration, migrants moving to low-incidence settings can experience substantially higher tuberculosis (TB) rates than the native-born population. This review describes the impact of migration on TB epidemiology in the United States, and how the TB burden differs between US-born and non-US-born populations. The United States has a long history of receiving migrants from other parts of the world, and TB among non-US-born individuals now represents the majority of new TB cases. Based on an analysis of TB cases among individuals from the top 30 countries of origin in terms of non-US-born TB burden between 2003 and 2015, we describe how TB risks vary within the non-US-born population according to age, years since entry, entry year, and country of origin. Variation along each of these dimensions is associated with more than 10-fold differences in the risk of developing active TB, and this risk is also positively associated with TB incidence estimates for the country of origin and the composition of the migrant pool in the entry year. Approximately 87 000 lifetime TB cases are predicted for the non-US-born population resident in the United States in 2015, and 5800 lifetime cases for the population entering the United States in 2015.

Background: Disparities in the health and economic burden of gonorrhoea have not been systematically quantified. We estimated population-level health losses and costs associated with gonococcal infection and sequelae in the United States. Methods: We used probability-tree models to capture gonorrhoea sequelae and to estimate attributable disease burden in terms of the discounted lifetime costs and quality-adjusted life-years (QALYs) lost due to incident infections acquired during 2015 from the healthcare system perspective. Numbers of infections in 2015 were obtained from a published gonorrhoea transmission model. We evaluated population-level disease burden, disaggregated by sex, age, race/ethnicity, and for men who have sex with men (MSM). We conducted a multivariate sensitivity analysis for key parameters. Findings: Discounted lifetime QALYs lost per incident gonococcal infection were estimated as 0.093 (95% uncertainty interval [UI] 0.022-0.22) for women, 0.0020 (0.0015-0.0024) for heterosexual men, and 0.0015 (0.00070-0.0021) for MSM. Discounted lifetime costs per incident infection were USD 261 (109-480), 169 (88-263), and 133 (50-239), respectively. At the population level, total discounted lifetime QALYs lost due to infections acquired during 2015 were 53,293 (12,326-125,366) for women, 621 (430-872) for heterosexual men, and 1,078 (427-1,870) for MSM. Total discounted lifetime costs were USD 150 million (64-277 million), 54 million (25-92 million), and 97 million (34-197 million), respectively. The highest total burden of both QALYs and costs at the population-level was observed in Non-Hispanic Black women, and highest burden per 1,000 person-years was identified in MSM among men and American Indian/Alaska Native among women. Interpretation: Gonorrhoea causes substantial health losses and costs in the United States. These results can inform planning and prioritization of prevention services. Funding: Centers for Disease Control and Prevention, Charles A. King Trust. © 2022 The Author(s)

BACKGROUND: Effective targeting of latent tuberculosis infection (LTBI) treatment requires identifying those most likely to progress to tuberculosis (TB). We estimated the potential health and economic benefits of diagnostics with improved discrimination for LTBI that will progress to TB. METHODS: A base-case scenario represented current LTBI testing and treatment services in the United States in 2020, with diagnosis via interferon-gamma release assay (IGRA). Alternative scenarios represented tests with higher positive predictive value (PPV) for future TB but similar price to IGRA, and scenarios that additionally assumed higher treatment initiation and completion. We predicted outcomes using multiple transmission-dynamic models calibrated to different geographic areas, and estimated costs from a societal perspective. RESULTS: In 2020, 2.1% (range across model results: 1.1%-3.4%) of individuals with LTBI were predicted to develop TB in their remaining lifetime. For IGRA, we estimated the PPV for future TB as 1.3% (0.6%-1.8%). Relative to IGRA, we estimated a test with 10% PPV would reduce treatment volume by 87% (82%-94%), reduce incremental costs by 30% (15%-52%), and increase quality-adjusted life years by 3% (2%-6%). Cost reductions and health improvements were substantially larger for scenarios in which higher PPV for future TB was associated with greater initiation and completion of treatment. CONCLUSIONS: We estimated that tests with better predictive performance would substantially reduce the number of individuals treated to prevent TB, but would have a modest impact on incremental costs and health impact of TB prevention services, unless accompanied by greater treatment acceptance and completion.

BACKGROUND: Older age is a risk factor for TB in low incidence settings. Using data from the U.S. National TB Surveillance System and American Community Survey, we estimated trends and racial/ethnic differences in TB incidence among US-born cohorts aged ≥50 years. METHODS: 42,000 TB cases among US-born persons ≥50 years were reported during 2001-2019. We used generalized additive regression models to decompose the effects of birth cohort and age on TB incidence rates, stratified by sex and race/ethnicity. Using genotype-based estimates of recent transmission (available 2011-2019), we implemented additional models to decompose incidence trends by estimated recent versus remote infection. RESULTS: Estimated incidence rates declined with age, for the overall cohort and most sex and race/ethnicity strata. Average annual percentage declines flattened for older individuals, from 8.80% (95% confidence interval 8.34-9.23) in 51-year-olds to 4.51% (3.87-5.14) in 90-year-olds. Controlling for age, incidence rates were lower for more recent birth cohorts, dropping 8.79% (6.13-11.26) on average between successive cohort years. Incidence rates were substantially higher for racial/ethnic minorities, and these inequalities persisted across all birth cohorts. Rates from recent infection declined at approximately 10% per year as individuals aged. Rates from remote infection declined more slowly with age, and this annual percentage decline approached zero for the oldest individuals. CONCLUSIONS: TB rates were highest for racial/ethnic minorities and for the earliest birth cohorts and declined with age. For the oldest individuals, annual percentage declines were low, and most cases were attributed to remote infection.

BACKGROUND: Men who have sex with men (MSM) experience high rates of gonococcal infection at extragenital (rectal and pharyngeal) anatomic sites, which often are missed without asymptomatic screening and may be important for onward transmission. Implementing an express pathway for asymptomatic MSM seeking routine screening at their clinic may be a cost-effective way to improve extragenital screening by allowing patients to be screened at more anatomic sites through a streamlined, less costly process. METHODS: We modified an agent-based model of anatomic site-specific gonococcal infection in U.S. MSM to assess the cost-effectiveness of an express screening pathway in which all asymptomatic MSM presenting at their clinic were screened at the urogenital, rectal, and pharyngeal sites but forewent a provider consultation and physical exam and self-collected their own samples. We calculated the cumulative health effects expressed as gonococcal infections and cases averted over five years, labor and material costs, and incremental cost effectiveness ratios (ICER) for express versus traditional scenarios. RESULTS: The express scenario averted more infections and cases in each intervention year. The increased diagnostic costs of triple-site screening were largely offset by the lowered visit costs of the express pathway and, from the end of year 3 onward, this pathway generated small cost savings. However, in a sensitivity analysis of assumed overhead costs, cost savings under the express scenario disappeared in the majority of simulations once overhead costs exceeded 7% of total annual costs. CONCLUSIONS: Express screening may be a cost-effective option for improving multi-site anatomic screening among U.S. MSM.

BACKGROUND: Risk of tuberculosis (TB) declines over time since Mycobacterium tuberculosis infection, but progression to clinical disease is still possible decades later. In the United States, most TB cases result from the progression of latent TB infection acquired over 2 years ago. METHODS: We synthesized evidence on TB natural history and incidence trends using a transmission-dynamic model. For the 2020 US population, we estimated average time since infection and annual, cumulative, and remaining lifetime risks of progression to TB, by nativity and age. RESULTS: For a newly infected adult with no other risk factors for progression to TB, estimated rates of progression declined from 38 (95% uncertainty interval: 33, 46) to 0.38 (0.32, 0.45) per 1000 person-years between the first and 25th year since infection. Cumulative risk over 25 years from new infection was 7.9% (7.0, 8.9). In 2020, an estimated average age of individuals with prevalent infection was 62 (61, 63) for the US-born population, 55 (54, 55) for non-US-born, and 57 (56, 58) overall. Average risks of developing TB over the remaining lifetime were 1.2% (1.0, 1.4) for US-born, 2.2% (1.8, 2.6) for non-US-born, and 1.9% (1.6, 2.2) for the general population. Risk estimates were higher for younger age groups. CONCLUSIONS: Our analysis suggests that, although newly infected individuals face appreciable lifetime TB risks, most US individuals with latent TB infection were infected long ago, and face low future risks of developing TB. Better approaches are needed for identifying recently infected individuals and those with elevated progression risks.

BACKGROUND: In 2016, Namibia had ~ 230,000 people living with HIV (PLHIV) and 9154 new tuberculosis (TB) cases, including 3410 (38%) co-infected cases. TB preventative therapy (TPT), consisting of intensive case finding and isoniazid preventative therapy, is critical to reducing TB disease and mortality. METHODS: Between November 2014 and February 2015, data was abstracted from charts of PLHIV enrolled in HIV treatment. Fifty-five facilities were purposively selected based on patient volume, type and location. Charts were randomly sampled. The primary outcome was to estimate baseline TPT in PLHIV, using nationally weighted proportions. Qualitative surveys were conducted and summarized to evaluate TPT practices and quantify challenges encountered by health care workers (HCW). RESULTS: Among 861 PLHIV sampled, 96% were eligible for TPT services, of which 87.1% were screened for TB at least once. For PLHIV eligible for preventative therapy (646/810; 82.6%), 45.4% (294/646) initiated therapy and 45.7% (139/294) of those completed therapy. The proportion of eligible PLHIV completing TB screening, initiating preventative therapy and then completing preventative therapy was 20.7%. Qualitative surveys with 271 HCW identified barriers to TPT implementation including: lack of training (61.3% reported receiving training on TPT); misunderstandings about timing of TPT initiation (46.7% correctly reported TPT should be started with antiretroviral therapy); and variable screening practices and responsibilities (66.1% of HCWs screened for TB at every encounter). Though barriers were evident, 72.2% HCWs surveyed described their clinical performance as very good, often placing responsibility of difficulties on patients and downplaying challenges like staff shortages and medication stock outs. CONCLUSIONS: In this study, only 1 in 5 eligible PLHIV completed the TPT cascade in Namibia. Lack of training, irregularities with TB screening and timing of TPT, unclear prescribing and recording responsibilities, and a clinical misperception may have contributed to suboptimal programmatic implementation. Addressing these challenges will be critical with continued TPT scale-up.

In the United States, new tuberculosis cases are increasingly concentrated within non-native-born populations. We estimated trends and differences in tuberculosis incidence rates for the non-U.S.-born population, at a resolution unobtainable from raw data. We obtained non-U.S.-born tuberculosis case reports for 2000-2016 from the National Tuberculosis Surveillance System, and population data from the American Community Survey and 2000 U.S. Census. We constructed generalized additive regression models to estimate incidence rates in terms of birth country, entry year, age at entry, and number of years since entry into the United States and described how these factors contribute to overall tuberculosis risk. Controlling for other factors, tuberculosis incidence rates were lower for more recent immigration cohorts, with an incidence risk ratio (IRR) of 10.2 (95 % confidence interval 7.0, 14.7) for the 1950 entry cohort compared to its 2016 counterpart. Greater years since entry and younger age at entry were associated with substantially lower incidence rates. IRRs for birth country varied between 8.86 (6.78, 11.52) for Somalia and 0.02 (0.01, 0.03) for Canada, compared to all non-U.S.-born residents in 2016. IRRs were positively correlated with WHO predicted incidence rate and negatively associated with wealth level for the birth country. Lower country wealth level was also associated with shallower declines in tuberculosis over time. Tuberculosis risks differ by several orders of magnitude within the non-U.S.-born population. A better understanding of these differences will allow more effective targeting of tuberculosis prevention efforts. The methods presented here may also be relevant for understanding tuberculosis trends in other high-income countries.

BACKGROUND: As new drugs are developed for multidrug-resistant tuberculosis (MDR-TB), the role of currently used drugs must be reevaluated. METHODS: We combined individual-level data on patients with pulmonary MDR-TB published during 2009-2016 from 25 countries. We compared patients receiving each of the injectable drugs and those receiving no injectable drugs. Analyses were based on patients whose isolates were susceptible to the drug they received. Using random-effects logistic regression with propensity score matching, we estimated the effect of each agent in terms of standardized treatment outcomes. RESULTS: More patients received kanamycin (n = 4330) and capreomycin (n = 2401) than amikacin (n = 2275) or streptomycin (n = 1554), opposite to their apparent effectiveness. Compared with kanamycin, amikacin was associated with 6 more cures per 100 patients (95% confidence interval [CI], 4-8), while streptomycin was associated with 7 (95% CI, 5-8) more cures and 5 (95% CI, 4-7) fewer deaths per 100 patients. Compared with capreomycin, amikacin was associated with 9 (95% CI, 6-11) more cures and 5 (95% CI, 2-8) fewer deaths per 100 patients, while streptomycin was associated with 10 (95% CI, 8-13) more cures and 10 (95% CI, 7-12) fewer deaths per 100 patients treated. In contrast to amikacin and streptomycin, patients treated with kanamycin or capreomycin did not fare better than patients treated with no injectable drugs. CONCLUSIONS: When aminoglycosides are used to treat MDR-TB and drug susceptibility test results support their use, streptomycin and amikacin, not kanamycin or capreomycin, are the drugs of choice.

The Centers for Disease Control and Prevention attributes only 13% of incident tuberculosis (TB) disease in the United States to recent (≤2 yr) transmission; nearly all of the remaining incident cases of TB disease are believed to occur via reactivation of latent TB infection (LTBI) acquired by individuals earlier in their lives (1). It is estimated that up to 13 million people would test positive on the tuberculin skin test, and 9 (6–15) million people have untreated LTBI in the United States (2, 3). As such, treatment of LTBI is central to the current U.S. TB elimination strategy (4). Treatment regimens such as 3 months of isoniazid and rifapentine (3HP), 4 months of rifampin (4R), and 6–9 months of isoniazid are efficacious in preventing TB disease (5–8), but effectiveness of any LTBI regimen in general populations may be limited by suboptimal levels of treatment initiation and completion (8, 9) and by discontinuation because of adverse effects (AEs) (7, 9). Novel regimens with shorter duration of therapy, such as 6 weeks of daily 600-mg doses of rifapentine (6wP), which is currently being evaluated in a phase III clinical trial, may have important benefits, particularly if determined to be noninferior to 3HP and 9 months of isoniazid with lower discontinuation rates (10).