Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 32 Records) |
Query Trace: Menzies NA[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. |
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. |
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. |
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. |
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. |
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). |
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. |
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. |
Nowcasting by Bayesian smoothing: A flexible, generalizable model for real-time epidemic tracking
McGough SF , Johansson MA , Lipsitch M , Menzies NA . PLoS Comput Biol 2020 16 (4) e1007735 Achieving accurate, real-time estimates of disease activity is challenged by delays in case reporting. "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 one or two applications, 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 software package while investigating the features of each approach that contribute to good or poor performance. 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 and provide practical guidance on implementation. |
The potential population-level impact of different gonorrhea screening strategies in Baltimore and San Francisco: an exploratory mathematical modeling analysis
Ronn MM , Testa C , Tuite AR , Chesson HW , Gift TL , Schumacher C , Williford SL , Zhu L , Bellerose M , Earnest R , Malyuta Y , Hsu KK , Salomon JA , Menzies NA . Sex Transm Dis 2019 47 (3) 143-150 BACKGROUND: Baltimore and San Francisco represent high burden areas for gonorrhea in the United States. We explored different gonorrhea screening strategies and their comparative impact in the two cities. METHODS: We used a compartmental transmission model of gonorrhea stratified by sex, sexual orientation, age, and race/ethnicity, calibrated to city-level surveillance data for 2010-2017. We analyzed the benefits of 5-year interventions which improved retention in care cascade or increased screening from current levels. We also examined a 1-year outreach screening intervention of high-activity populations. RESULTS: In Baltimore, annual screening of population aged 15-24 was the most efficient of the five-year interventions with 17.9 additional screening tests (95% Credible Interval [CrI] 11.8-31.4) needed per infection averted while twice annual screening of the same population averted the most infections (5.4%, 95%CrI 3.1-8.2%) overall with 25.3 (95%CrI 19.4-33.4) tests per infection averted. In San Francisco, quarter-annual screening of all men who have sex with men was the most efficient with 16.2 additional (95%CrI 12.5-44.5) tests needed per infection averted and it also averted the most infections (10.8%, 95%CrI 1.2-17.8%). Interventions that reduce loss to follow-up after diagnosis improved outcomes. Depending on the ability to of a short-term outreach screening to screen populations at higher acquisition risk, such interventions can offer efficient ways to expand screening coverage. CONCLUSIONS: Data on gonorrhea prevalence distribution and time trends locally would improve the analyses. More focused intervention strategies could increase the impact and efficiency of screening interventions. |
Comparative modelling of tuberculosis epidemiology and policy outcomes in California
Menzies NA , Parriott A , Shrestha S , Dowdy DW , Cohen T , Salomon JA , Marks SM , Hill AN , Winston CA , Asay G , Barry P , Readhead A , Flood J , Kahn JG , Shete PB . Am J Respir Crit Care Med 2019 201 (3) 356-365 Rationale Mathematical modelling is used to understand disease dynamics, forecast trends, and inform public health prioritization. We conducted a comparative analysis of tuberculosis (TB) epidemiology and potential intervention effects in California, using three previously developed epidemiologic models of TB. Measurements and Methods We compared model results between 2005 and 2050 under a base case scenario representing current TB services, and alternative scenarios including: (i) sustained interruption of Mycobacterium tuberculosis (Mtb) transmission, (ii) sustained resolution of latent TB infection (LTBI) and TB prior to entry of new residents, and (iii) one-time targeted testing and treatment of LTBI among 25% of non-US-born individuals residing in California. Results Model estimates of TB cases and deaths in California were in close agreement over the historical period but diverged for LTBI prevalence and new Mtb infections-outcomes for which definitive data are unavailable. Between 2018 and 2050, models projected average annual declines of 0.58-1.42% in TB cases, without additional interventions. A one-time LTBI testing and treatment intervention among non-US-born residents was projected to produce sustained reductions in TB incidence. Models found prevalent Mtb infection and migration to be more significant drivers of future TB incidence than local transmission. Conclusions All models projected a stagnation in the decline of TB incidence, highlighting the need for additional interventions including greater access to LTBI diagnosis and treatment for non-US-born individuals. Differences in model results reflect gaps in historical data and uncertainty in the trends of key parameters, demonstrating the need for high-quality, up-to-date TB determinant and outcome data. |
The impact of screening and partner notification on chlamydia in the United States, 2000-2015: Evaluation of epidemiologic trends using a pair-formation transmission model
Ronn MM , Tuite AR , Menzies NA , Wolf EE , Gift TL , Chesson HW , Torrone E , Berruti A , Mazzola E , Galer K , Hsu K , Salomon JA . Am J Epidemiol 2019 188 (3) 545-554 Population-level effects of chlamydia control strategies on chlamydia transmission dynamics are difficult to quantify. In this study, we calibrated a novel sex- and age-stratified pair-formation transmission model of chlamydial infection to epidemiological data in the United States for 2000-2015. We used sex- and age-specific prevalence estimates from the National Health and Nutrition Examination Surveys, case report data from national chlamydia surveillance, and survey data from the Youth Risk Behavior Survey on the proportion of sexually active 15-18 year-old population. We were able to reconcile national prevalence estimates and case report data by allowing for changes over time in screening coverage and reporting completeness. In retrospective analysis, we found that in the absence of chlamydia screening and partner notification, chlamydia prevalence would be approximately twice as great in 2015 as currently estimated levels. Although chlamydia screening and partner notification were both found to reduce chlamydia burden, the relative magnitude of their estimated impact varied in our sensitivity analyses. The variation in the model predictions highlights the need for further data collection and research to improve our understanding of the natural history of chlamydia and the pathways through which prevention strategies affect transmission dynamics. |
Estimated impact of screening on gonorrhea epidemiology in the United States: insights from a mathematical model
Tuite AR , Ronn MM , Wolf EE , Gift TL , Chesson HW , Berruti A , Galer K , Menzies NA , Hsu K , Salomon JA . Sex Transm Dis 2018 45 (11) 713-722 BACKGROUND: The burden of gonorrhea infections in the United States is high. There are marked disparities by race/ethnicity and sexual orientation. We quantified the impact of screening and treatment on gonorrhea rates in the US population aged 15-39 years for the time period 2000 to 2015 and estimated the impact that alternative screening strategies might have had over the same time period. METHODS: We developed a national-level transmission model that divides the population by race/ethnicity, preferred sex of sex partners, age, sex, and sexual activity level. We compared our fitted model ('base case') to four alternative strategies: (i) no screening; (ii) full adherence to current screening guidelines; (iii) annual universal screening; or (iv) enhanced screening in groups with the highest infection burden. Main outcomes were incidence, infections averted, and incidence rate ratios by race/ethnicity. Mean values and 95% credible intervals (CrI) were calculated from 1000 draws from parameter posterior distributions. RESULTS: The calibrated model reproduced observed trends in gonorrhea, including disparities in infection burden by race/ethnicity. We estimated that screening for gonorrhea from 2000-2015 averted 30% (95% CrI: 18-44%) of total infections that would otherwise have occurred. All alternative active screening strategies were estimated to further reduce, but not eliminate, gonorrhea infections relative to the base case, with differential impacts on the subpopulations of interest. CONCLUSIONS: Our model results suggest that screening has reduced gonorrhea incidence in the US population. Additional reductions in infection burden may have been possible over this time period with increased screening, but elimination was unlikely.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
Prospects for tuberculosis elimination in the United States: Results of a transmission dynamic model
Menzies NA , Cohen T , Hill AN , Yaesoubi R , Galer K , Wolf E , Marks SM , Salomon JA . Am J Epidemiol 2018 187 (9) 2011-2020 We estimated long-term tuberculosis (TB) trends in the US population and assessed prospects for TB elimination. We used a detailed simulation model allowing for changes in TB transmission, immigration, and other TB risk determinants. We evaluated 5 hypothetical scenarios from 2017 to 2100: 1) maintain current TB prevention and treatment activities (base-case), 2) provision of latent TB infection testing and treatment for new legal immigrants, 3) increased uptake of latent TB infection screening and treatment among high-risk populations, including a 3-month isoniazid-rifapentine regimen, 4) improved TB case detection, 5) improved TB treatment quality. Under the base-case, we estimate that by 2050 TB incidence will decline to 14 cases per million, a 52% (95% interval: 35, 67) reduction from 2016, and 82% (78, 86) of incident TB will be among non-US-born persons. Intensified TB control could reduce incidence by 77% (66, 85) by 2050. By 2100, we predict TB may be eliminated in the US-born but not the non-US-born. Results were sensitive to numbers entering the US with latent or active TB, and robust to alternative interpretations of epidemiologic evidence. TB elimination in the US remains a distant goal. However, strengthening TB prevention and treatment could produce important health benefits. |
Progression from latent infection to active disease in dynamic tuberculosis transmission models: a systematic review of the validity of modelling assumptions
Menzies NA , Wolf E , Connors D , Bellerose M , Sbarra AN , Cohen T , Hill AN , Yaesoubi R , Galer K , White PJ , Abubakar I , Salomon JA . Lancet Infect Dis 2018 18 (8) e228-e238 Mathematical modelling is commonly used to evaluate infectious disease control policy and is influential in shaping policy and budgets. Mathematical models necessarily make assumptions about disease natural history and, if these assumptions are not valid, the results of these studies can be biased. We did a systematic review of published tuberculosis transmission models to assess the validity of assumptions about progression to active disease after initial infection (PROSPERO ID CRD42016030009). We searched PubMed, Web of Science, Embase, Biosis, and Cochrane Library, and included studies from the earliest available date (Jan 1, 1962) to Aug 31, 2017. We identified 312 studies that met inclusion criteria. Predicted tuberculosis incidence varied widely across studies for each risk factor investigated. For population groups with no individual risk factors, annual incidence varied by several orders of magnitude, and 20-year cumulative incidence ranged from close to 0% to 100%. A substantial proportion of modelled results were inconsistent with empirical evidence: for 10-year cumulative incidence, 40% of modelled results were more than double or less than half the empirical estimates. These results demonstrate substantial disagreement between modelling studies on a central feature of tuberculosis natural history. Greater attention to reproducing known features of epidemiology would strengthen future tuberculosis modelling studies, and readers of modelling studies are recommended to assess how well those studies demonstrate their validity. |
The use of mathematical models of chlamydia transmission to address public health policy questions: A systematic review
Ronn MM , Wolf EE , Chesson H , Menzies NA , Galer K , Gorwitz R , Gift T , Hsu K , Salomon JA . Sex Transm Dis 2017 44 (5) 278-283 BACKGROUND: Mathematical models of chlamydia transmission can help inform disease control policy decisions when direct empirical evaluation of alternatives is impractical. We reviewed published chlamydia models to understand the range of approaches used for policy analyses and how the studies have responded to developments in the field. METHODS: We performed a literature review by searching Medline and Google Scholar (up to October 2015) to identify publications describing dynamic chlamydia transmission models used to address public health policy questions. We extracted information on modeling methodology, interventions, and key findings. RESULTS: We identified 47 publications (including two model comparison studies), which reported collectively on 29 distinct mathematical models. Nine models were individual-based, and 20 were deterministic compartmental models. The earliest studies evaluated the benefits of national-level screening programs and predicted potentially large benefits from increased screening. Subsequent trials and further modeling analyses suggested the impact might have been overestimated. Partner notification has been increasingly evaluated in mathematical modeling, whereas behavioral interventions have received relatively limited attention. CONCLUSIONS: Our review provides an overview of chlamydia transmission models and gives a perspective on how mathematical modeling has responded to increasing empirical evidence and addressed policy questions related to prevention of chlamydia infection and sequelae. |
Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models
Eaton JW , Menzies NA , Stover J , Cambiano V , Chindelevitch L , Cori A , Hontelez JA , Humair S , Kerr CC , Klein DJ , Mishra S , Mitchell KM , Nichols BE , Vickerman P , Bakker R , Bärnighausen T , Bershteyn A , Bloom DE , Boily MC , Chang ST , Cohen T , Dodd PJ , Fraser C , Gopalappa C , Lundgren J , Martin NK , Mikkelsen E , Mountain E , Pham QD , Pickles M , Phillips A , Platt L , Pretorius C , Prudden HJ , Salomon JA , van de Vijver DA , de Vlas SJ , Wagner BG , White RG , Wilson DP , Zhang L , Blandford J , Meyer-Rath G , Remme M , Revill P , Sangrujee N , Terris-Prestholt F , Doherty M , Shaffer N , Easterbrook PJ , Hirnschall G , Hallett TB . Lancet Glob Health 2014 2 (1) e23-34 BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. METHODS: We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. FINDINGS: In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. INTERPRETATION: Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. FUNDING: Bill & Melinda Gates Foundation, WHO. |
The determinants of HIV treatment costs in resource limited settings
Menzies NA , Berruti AA , Blandford JM . PLoS One 2012 7 (11) e48726 BACKGROUND: Governments and international donors have partnered to provide free HIV treatment to over 6 million individuals in low and middle-income countries. Understanding the determinants of HIV treatment costs will help improve efficiency and provide greater certainty about future resource needs. METHODS AND FINDINGS: We collected data on HIV treatment costs from 54 clinical sites in Botswana, Ethiopia, Mozambique, Nigeria, Uganda, and Vietnam. Sites provided free HIV treatment funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), national governments, and other partners. Service delivery costs were categorized into successive six-month periods from the date when each site began HIV treatment scale-up. A generalized linear mixed model was used to investigate relationships between site characteristics and per-patient costs, excluding ARV expenses. With predictors at their mean values, average annual per-patient costs were $177 (95% CI: 127-235) for pre-ART patients, $353 (255-468) for adult patients in the first 6 months of ART, and $222 (161-296) for adult patients on ART for >6 months (excludes ARV costs). Patient volume (no. patients receiving treatment) and site maturity (months since clinic began providing treatment services) were both strong independent predictors of per-patient costs. Controlling for other factors, costs declined by 43% (18-63) as patient volume increased from 500 to 5,000 patients, and by 28% (6-47) from 5,000 to 10,000 patients. For site maturity, costs dropped 41% (28-52) between months 0-12 and 25% (15-35) between months 12-24. Price levels (proxied by per-capita GDP) were also influential, with costs increasing by 22% (4-41) for each doubling in per-capita GDP. Additionally, the frequency of clinical follow-up, frequency of laboratory monitoring, and clinician-patient ratio were significant independent predictors of per-patient costs. CONCLUSIONS: Substantial reductions in per-patient service delivery costs occur as sites mature and patient cohorts increase in size. Other predictors suggest possible strategies to reduce per-patient costs. |
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