Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 77 Records) |
Query Trace: Menzies H[original query] |
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Disparities in tuberculosis incidence by race and ethnicity among the U.S.-born population in the United States, 2011 to 2021 : An analysis of national disease registry data
Li Y , Regan M , Swartwood NA , Barham T , Beeler Asay GR , Cohen T , Hill AN , Horsburgh CR Jr , Khan A , Marks SM , Myles RL , Salomon JA , Self JL , Menzies NA . Ann Intern Med 2024 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. |
Estimated rates of progression to tuberculosis disease for persons infected with Mycobacterium tuberculosis in the United States
Ekramnia M , Li Y , Haddad MB , Marks SM , Kammerer JS , Swartwood NA , Cohen T , Miller JW , Horsburgh CR , Salomon JA , Menzies NA . Epidemiology 2024 35 (2) 164-173 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. |
Racial and ethnic disparities in diagnosis and treatment outcomes among US-born people diagnosed with tuberculosis, 2003-19: an analysis of national surveillance data
Regan M , Li Y , Swartwood NA , Barham T , Asay GRB , Cohen T , Hill AN , Horsburgh CR , Khan A , Marks SM , Myles RL , Salomon JA , Self JL , Menzies NA . Lancet Public Health 2024 9 (1) e47-e56 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. |
2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis
England BR , Smith BJ , Baker NA , Barton JL , Oatis CA , Guyatt G , Anandarajah A , Carandang K , Chan KK , Constien D , Davidson E , Dodge CV , Bemis-Dougherty A , Everett S , Fisher N , Fraenkel L , Goodman SM , Lewis J , Menzies V , Moreland LW , Navarro-Millan I , Patterson S , Phillips LR , Shah N , Singh N , White D , AlHeresh R , Barbour KE , Bye T , Guglielmo D , Haberman R , Johnson T , Kleiner A , Lane CY , Li LC , Master H , Pinto D , Poole JL , Steinbarger K , Sztubinski D , Thoma L , Tsaltskan V , Turgunbaev M , Wells C , Turner AS , Treadwell JR . Arthritis Rheumatol 2023 75 (8) 1299-1311 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. |
Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment
Winters N , Schnitzer ME , Campbell JR , Ripley S , Winston C , Savic R , Ahmad N , Bisson G , Dheda K , Esmail A , Gegia M , Monedero I , Dalcolmo MP , Rodrigues D , Singla R , Yim JJ , Menzies D . PLoS One 2023 18 (10) e0292106 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. |
Tabby2: a user-friendly web tool for forecasting state-level TB outcomes in the United States
Swartwood NA , Testa C , Cohen T , Marks SM , Hill AN , Beeler Asay G , Cochran J , Cranston K , Randall LM , Tibbs A , Horsburgh CR Jr , Salomon JA , Menzies NA . BMC Med 2023 21 (1) 331 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. |
Nowcasting by Bayesian Smoothing: A flexible, generalizable model for real-time epidemic tracking (preprint)
McGough SF , Johansson MA , Lipsitch M , Menzies NA . bioRxiv 2019 663823 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. |
2022 American College of Rheumatology Guideline for exercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis
England BR , Smith BJ , Baker NA , Barton JL , Oatis CA , Guyatt G , Anandarajah A , Carandang K , Chan KK , Constien D , Davidson E , Dodge CV , Bemis-Dougherty A , Everett S , Fisher N , Fraenkel L , Goodman SM , Lewis J , Menzies V , Moreland LW , Navarro-Millan I , Patterson S , Phillips LR , Shah N , Singh N , White D , AlHeresh R , Barbour KE , Bye T , Guglielmo D , Haberman R , Johnson T , Kleiner A , Lane CY , Li LC , Master H , Pinto D , Poole JL , Steinbarger K , Sztubinski D , Thoma L , Tsaltskan V , Turgunbaev M , Wells C , Turner AS , Treadwell JR . Arthritis Care Res (Hoboken) 2023 75 (8) 1603-1615 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. |
Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis
Winters N , Belknap R , Benedetti A , Borisov A , Campbell JR , Chaisson RE , Chan PC , Martinson N , Nahid P , Scott NA , Sizemore E , Sterling TR , Villarino ME , Wang JY , Menzies D . Lancet Respir Med 2023 11 (9) 782-790 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. |
Costs, health benefits, and cost-effectiveness of chlamydia screening and partner notification in the United States, 2000-2019: A mathematical modeling analysis
Rönn MM , Li Y , Gift TL , Chesson HW , Menzies NA , Hsu K , Salomon JA . Sex Transm Dis 2023 50 (6) 351-358 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. |
Reply to Chang and Yew
Sotgiu G , Battista Migliori G , Menzies D , Mase S , Chorba T , Seaworth B , Nahid P . Am J Respir Crit Care Med 2020 202 (5) 778-779 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. |
The impact of migration on tuberculosis in the United States
Menzies NA , Hill AN , Cohen T , Salomon JA . Int J Tuberc Lung Dis 2018 22 (12) 1392-1403 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. |
Estimated costs and quality-adjusted life-years lost due to N. gonorrhoeae infections acquired in 2015 in the United States: A modelling study of overall burden and disparities by age, race/ethnicity, and other factors
Li Y , Rönn MM , Tuite AR , Chesson HW , Gift TL , Trikalinos TA , Testa C , Bellerose M , Hsu K , Berruti AA , Malyuta Y , Menzies NA , Salomon JA . Lancet Reg Health Am 2022 16 100364 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) |
The health and economic benefits of tests that predict future progression to tuberculosis disease
Menzies NA , Shrestha S , Parriott A , Marks SM , Hill AN , Dowdy DW , Shete PB , Cohen T , Salomon JA . Epidemiology 2021 33 (1) 75-83 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. |
Trends, mechanisms, and racial/ethnic differences of tuberculosis incidence in the US-born population aged 50 years or older in the United States
Kim S , Cohen T , Horsburgh CR , Miller JW , Hill AN , Marks SM , Li R , Kammerer JS , Salomon JA , Menzies NA . Clin Infect Dis 2021 74 (9) 1594-1603 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. |
Modeling the Cost-Effectiveness of Express Multi-Site Gonorrhea Screening among Men Who Have Sex with Men in the United States
Earnest R , Rönn MM , Bellerose M , Menon-Johansson AS , Berruti AA , Chesson HW , Gift TL , Hsu KK , Testa C , Zhu L , Malyuta Y , Menzies NA , Salomon JA . Sex Transm Dis 2021 48 (11) 805-812 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. |
Time since infection and risks of future disease for individuals with Mycobacterium tuberculosis Infection in the United States
Menzies NA , Swartwood N , Testa C , Malyuta Y , Hill AN , Marks SM , Cohen T , Salomon JA . Epidemiology 2021 32 (1) 70-78 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. |
Evaluation of the uptake of tuberculosis preventative therapy for people living with HIV in Namibia: a multiple methods analysis
Roscoe C , Lockhart C , de Klerk M , Baughman A , Agolory S , Gawanab M , Menzies H , Jonas A , Salomo N , Taffa N , Lowrance D , Robsky K , Tollefson D , Pevzner E , Hamunime N , Mavhunga F , Mungunda H . BMC Public Health 2020 20 (1) 1838 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. |
High-resolution estimates of tuberculosis incidence among non-U.S.-born persons residing in the United States, 2000-2016
Hill AN , Cohen T , Salomon JA , Menzies NA . Epidemics 2020 33 100419 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. |
Aminoglycosides and capreomycin in the treatment of multidrug-resistant tuberculosis: Individual patient data meta-analysis of 12 030 patients from 25 countries, 2009-2016
Cegielski JP , Chan PC , Lan Z , Udwadia ZF , Viiklepp P , Yim JJ , Menzies D . Clin Infect Dis 2020 73 (11) e3929-e3936 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. |
Estimated population-level impact of using a six-week regimen of daily rifapentine to treat latent tuberculosis infection in the United States
Shrestha S , Parriott A , Menzies NA , Shete PB , Hill AN , Marks SM , Dowdy DW . Ann Am Thorac Soc 2020 17 (12) 1639-1642 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). |
Exploring how epidemic context influences syphilis screening impact: a mathematical modeling study
Tuite AR , Testa C , Rönn M , Bellerose M , Gift T , Fridge J , Molotnikov L , Desmarais C , Berruti A , Menzies N , Malyuta Y , Hsu K , Salomon JA . Sex Transm Dis 2020 47 (12) 798-810 BACKGROUND: The current syphilis epidemic in the United States is concentrated in gay, bisexual, and other men who have sex with men (MSM), but substantial heterosexual transmission is reported in some parts of the country. Using the U.S. states of Louisiana and Massachusetts as case studies, we investigated how epidemic context influences the impact of population screening approaches for syphilis control. METHODS: We constructed a compartmental metapopulation model parameterized to describe observed patterns of syphilis transmission. We estimated the impact of different approaches to screening, including perfect adherence to current U.S. screening guidelines in MSM. RESULTS: In Louisiana, where syphilis cases are more evenly distributed among MSM and heterosexual populations, we projected that screening according to guidelines would contribute to no change or an increase in syphilis burden, compared to burden with current estimated screening coverage. In Massachusetts, which has a more MSM-focused outbreak, we projected that screening according to guidelines would be as or more effective than current screening coverage in most population groups. CONCLUSIONS: MSM-focused approaches to screening may be insufficient for control when there is substantial transmission in heterosexual populations. Epidemic characteristics may be useful when identifying at-risk groups for syphilis screening. |
An evaluation of 6-month versus continuous isoniazid preventive therapy for M. tuberculosis in adults living with HIV/AIDS in Malawi
Hsieh YL , Jahn A , Menzies NA , Yaesoubi R , Salomon JA , Girma B , Gunde L , Eaton JW , Auld A , Odo M , Kiyiika CN , Kalua T , Chiwandira B , Mpunga JU , Mbendra K , Corbett L , Hosseinipour MC , Cohen T , Kunkel A . J Acquir Immune Defic Syndr 2020 85 (5) 643-650 BACKGROUND: To assist the Malawi Ministry of Health to evaluate two competing strategies for scale-up of isoniazid preventive therapy (IPT) among HIV-positive adults receiving ART. SETTING: Malawi. METHODS: We used a multi-district, compartmental model of the Malawi TB/HIV epidemic to compare the anticipated health impacts of 6-month versus continuous IPT programs over a 12-year horizon, while respecting a US$10.8 million constraint on drug costs in the first three years. RESULTS: The 6-month IPT program could be implemented nationwide while the continuous IPT alternative could be introduced in 14 (out of 27) districts. By the end of year 12, the continuous IPT strategy was predicted to avert more TB cases than the 6-month alternative, although not statistically significantly (2368 additional cases averted; 95%PI, -1459, 5023). The 6-month strategy required fewer person-years of IPT to avert a case of TB or death than the continuous strategy. For both programs, the mean reductions in TB incidence among PLHIV by year 12 were expected to be <10%, and the cumulative numbers of IPT-related hepatotoxicity to exceed the number of all-cause deaths averted in the first three years. CONCLUSION: With the given budgetary constraint, nationwide implementation of 6-month IPT would be more efficient and yield comparable health benefits than implementing continuous IPT program in fewer districts. The anticipated health effects associated with both IPT strategies suggested a combination of different TB intervention strategies would likely be required to yield greater impact on TB control in settings like Malawi, where ART coverage is relatively high. |
Mathematical modeling study of school-based chlamydia screening: potential impact on chlamydia prevalence in intervention schools and surrounding communities
Rönn MM , Dunville R , Wang LY , Bellerose M , Malyuta Y , Menzies NA , Aslam M , Lewis F , Walker-Baban C , Asbel L , Parchem S , Masinter L , Perez E , Gift TL , Hsu K , Barrios LC , Salomon JA . BMC Public Health 2020 20 (1) 1363 BACKGROUND: Chlamydia screening in high schools offers a way to reach adolescents outside of a traditional clinic setting. Using transmission dynamic modeling, we examined the potential impact of high-school-based chlamydia screening programs on the burden of infection within intervention schools and surrounding communities, under varying epidemiological and programmatic conditions. METHODS: A chlamydia transmission model was calibrated to epidemiological data from three different settings. Philadelphia and Chicago are two high-burden cities with existing school-based screening programs. Rural Iowa does not have an existing program but represents a low-burden setting. We modeled the effects of the two existing programs to analyze the potential influence of program coverage and student participation. All three settings were used to examine a broader set of hypothetical programs with varying coverage levels and time trends in participation. RESULTS: In the modeled Philadelphia program, prevalence among the intervention schools' sexually active 15-18 years old population was 4.34% (95% credible interval 3.75-4.71%)after 12 program years compared to 5.03% (4.39-5.43%) in absence of the program. In the modeled Chicago program, prevalence was estimated as 5.97% (2.60-7.88%) after 4 program years compared to 7.00% (3.08-9.29%) without the program. In the broader hypothetical scenarios including both high-burden and low-burden settings, impact of school-based screening programs was greater in absolute terms in the higher-prevalence settings, and benefits in the community were approximately proportional to population coverage of intervention schools. Most benefits were garnered if the student participation did not decline over time. CONCLUSIONS: Sustained high student participation in school-based screening programs and broad coverage of schools within a target community are likely needed to maximize program benefits in terms of reduced burden of chlamydia in the adolescent population. |
Implementation and evaluation of a Project ECHO telementoring program for the Namibian HIV workforce
Bikinesi L , O'Bryan G , Roscoe C , Mekonen T , Shoopala N , Mengistu AT , Sawadogo S , Agolory S , Mutandi G , Garises V , Pati R , Tison L , Igboh L , Johnson C , Rodriguez EM , Ellerbrock T , Menzies H , Baughman AL , Brandt L , Forster N , Scott J , Wood B , Unruh KT , Arora S , Iandiorio M , Kalishman S , Zalud-Cerrato S , Lehmer J , Lee S , Mahdi MA , Spedoske S , Zuber A , Reilley B , Ramers CB , Hamunime N , O'Malley G , Struminger B . Hum Resour Health 2020 18 (1) 61 BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation. |
Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis
Bisson GP , Bastos M , Campbell JR , Bang D , Brust JC , Isaakadis P , Lange C , Menzies D , Migliori GB , Pape JW , Palmero D , Baghei P , Tabarsi P , Viiklepp P , Vilbrun S , Walsh J , Marks SM . Lancet 2020 396 (10248) 402-411 BACKGROUND: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. METHODS: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. FINDINGS: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. INTERPRETATION: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America. |
Policy implications of mathematical modeling of latent tuberculosis infection testing and treatment strategies to accelerate tuberculosis elimination
Marks SM , Dowdy DW , Menzies NA , Shete PB , Salomon JA , Parriott A , Shrestha S , Flood J , Hill AN . Public Health Rep 2020 135 38s-43s Tuberculosis (TB) disease is the leading cause of death globally from a single infectious organism.1 However, TB is both curable and preventable. In the United States during the past 2 decades, a national coordinated multi-agency policy response implemented in 1992, along with other influences (eg, new federal and state funding), led to a decrease in the number of TB cases reported in the United States, from 26 673 in 1992 to 9105 in 2017, a 65.9% decline.2,3 The 1992 national policy response was launched as a result of multidrug-resistant TB outbreaks that occurred during 1985-1992. That response included support for improved TB diagnostics, infection control, monitoring of TB treatment, and investigation of persons who had recent contact with persons who had infectious TB.4 Mathematical modeling of TB during 1995-2014 in the United States estimated that approximately 145 000 to 319 000 TB cases were averted, yielding societal benefits (in 2014 US dollars) of $3.1 billion to $14.5 billion.4 |
Impact of effective global tuberculosis control on health and economic outcomes in the United States
Menzies NA , Bellerose M , Testa C , Swartwood N , Malyuta Y , Cohen T , Marks SM , Hill AN , Date AA , Maloney SA , Bowden SE , Grills AW , Salomon JA . Am J Respir Crit Care Med 2020 202 (11) 1567-1575 RATIONALE: Most United States residents who develop tuberculosis were born abroad, and US TB incidence is increasingly driven by infection risks in other countries. OBJECTIVES: To estimate the potential impact of effective global TB control on health and economic outcomes in the United States. METHODS: We estimated outcomes using linked mathematical models of TB epidemiology in the United States and migrants' birth countries. A base-case scenario extrapolated country-specific TB incidence trends. We compared this to scenarios in which countries achieve 90% TB incidence reductions between 2015 and 2035, as targeted by the Global End TB Strategy ("effective global TB control"). We also considered pessimistic scenarios of flat TB incidence trends in individual countries. MEASUREMENTS AND MAIN RESULTS: We estimated TB cases, TB deaths, costs, and the total economic burden of TB in the US. Compared to the base-case, effective global TB control would avert 40,000 (95% uncertainty interval: 29,000-55,000) TB cases in the United States over 2020-2035. TB incidence rates in 2035 would be 43% (34-54) lower than the base-case, and 49% (44-55) lower than in 2020. Summed over 2020-2035, this represents $0.8 (0.6-1.0) billion dollars in averted healthcare costs and $2.5 (1.7-3.6) billion in productivity gains. The total US economic burden of TB (including the value of averted TB deaths) would be 21% (16-28) lower ($18 (8-32) billion). CONCLUSIONS: In addition to producing major health benefits for high-burden countries, strengthened efforts to achieve effective global TB control could produce substantial health and economic benefits for the United States. |
Potential for point-of-care tests to reduce chlamydia-associated burden in the United States: A mathematical modeling analysis
Ronn MM , Menzies NA , Gift TL , Chesson HW , Trikalinos TA , Bellerose M , Malyuta Y , Berruti A , Gaydos CA , Hsu KK , Salomon JA . Clin Infect Dis 2020 70 (9) 1816-1823 BACKGROUND: Point-of-care testing (POCT) assays for chlamydia are being developed. Their potential impact on the burden of chlamydial infection in the United States, in light of suboptimal screening coverage, remains unclear. METHODS: Using a transmission model calibrated to data in the United States, we estimated the impact of POCT on chlamydia prevalence, incidence, and chlamydia-attributable pelvic inflammatory disease (PID) incidence, assuming status quo (Analysis 1) and improved (Analysis 2) screening frequencies. We tested the robustness of results to changes in POCT sensitivity, the proportion of patients getting treated immediately, the baseline proportion lost to follow-up (LTFU), and the average treatment delay. RESULTS: In Analysis 1, high POCT sensitivity was needed to reduce the chlamydia-associated burden. With a POCT sensitivity of 90%, reductions from the baseline burden only occurred in scenarios in which over 60% of the screened individuals would get immediate treatment and the baseline LTFU proportion was 20%. With a POCT sensitivity of 99% (baseline LTFU 10%, 2-week treatment delay), if everyone were treated immediately, the prevalence reduction was estimated at 5.7% (95% credible interval [CrI] 3.9-8.2%). If only 30% of tested persons would wait for results, the prevalence reduction was only 1.6% (95% CrI 1.1-2.3). POCT with 99% sensitivity could avert up to 12 700 (95% CrI 5000-22 200) PID cases per year, if 100% were treated immediately (baseline LTFU 20% and 3-week treatment delay). In Analysis 2, when POCT was coupled with increasing screening coverage, reductions in the chlamydia burden could be realized with a POCT sensitivity of 90%. CONCLUSIONS: POCT could improve chlamydia prevention efforts if test performance characteristics are significantly improved over currently available options. |
Population-level benefits of extragenital gonorrhea screening among men who have sex with men: An exploratory modeling analysis
Earnest R , Ronn MM , Bellerose M , Gift TL , Berruti AA , Hsu KK , Testa C , Zhu L , Malyuta Y , Menzies NA , Salomon JA . Sex Transm Dis 2020 47 (7) 484-490 BACKGROUND: Men who have sex with men (MSM) are disproportionately burdened by gonorrhea and face high rates of extragenital (rectal and pharyngeal) infection, which is mostly asymptomatic and often missed by urogenital-only screening. Extragenital screening likely remains below CDC-recommended levels. Since increasing screening coverage is often resource-intensive, we assessed whether improved extragenital screening among men already presenting at clinics could lead to substantial reductions in prevalence and incidence. METHODS: We calibrated an agent-based model of site- and race-specific gonorrhea infection in MSM to explicitly model multi-site infection within an individual and transmission via anal, orogenital, and ororectal sex. Compared to current screening levels, we assessed the impact of increasing screening at 1) both extragenital sites, 2) only the rectal site, and 3) only the pharyngeal site among men already being urogenitally screened. RESULTS: All scenarios reduced prevalence and incidence, with improved screening at both extragenital sites having the largest effect across outcomes. Extragenitally screening 100% of men being urogenitally screened reduced site-specific prevalence by an average of 42% (black MSM) and 50% (white MSM), with these values dropping by approximately 10% and 20% for each race group when targeting only the rectum and only the pharynx, respectively. However, increasing only rectal screening was more efficient in terms of the number of screens needed to avert an infection as this avoided duplicative screens due to rectum/pharynx multi-site infection. CONCLUSIONS: Improved extragenital screening substantially reduced site-specific gonorrhea prevalence and incidence, with strategies aimed at increasing rectal screening proving the most efficient. |
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