Tuberculosis

Click on a project title to learn more about PPML's work on Tuberculosis.

Past Projects

• Transmission Modeling of TB in the U.S.
• Targeted Testing and Treatment of Latent TB Infection Among High-Risk Populations in the U.S.
• Impact of International TB Control Efforts on TB Elimination in the U.S.
• Model Comparison Activities for Unified Framework for Modeling Domestic TB Elimination
• Modeling Enhanced Domestic TB Control Interventions at the Local, State, and National Level

Tool for Estimating Intervention Costs and Averted TB and Latent TB Infection Burden

Information on the costs and health outcomes of TB services, such as testing and treatment for latent TB infection (LTBI) to prevent TB progression, is important for national, state, and local TB decision-making. Knowing the potential epidemiologic and economic impact of TB services allows agencies to allocate resources to maximize health impact and to target interventions across risk populations. Locally tailored evidence on the short- and long-term costs of TB and LTBI, as well as interventions to address these conditions, would also help local areas communicate to local officials, media, and community members the importance of TB prevention and the funding required to effectively address the burden of TB and LTBI. 

Tabby2 extends the functionality of the existing user-friendly tool by providing locally tailored results for all 50 states and the District of Columbia, broadening the functionality of the tool to report future costs and cost-savings associated with TB and TB interventions.

Associated Publications and Tools

• Tabby2 Web Application
• Swartwood NA, Testa C, Cohen T, Marks SM, Hill AN, Asay GB, Cochran J, Cranston K, Randall LM, Tibbs A, Horsburgh CR, Salomon JA, Menzies NA. Tabby2: A user-friendly web tool for forecasting state-level TB outcomes in the United States. BMC Med. 2023;21:331. doi:10.1186/s12916-023-02785-y

Rates of Latent TB Infection Reactivation by Population

More than 80% of TB cases in the United States result from reactivation of LTBI. Identifying and treating individuals with LTBI is a primary focus of TB prevention. Evidence suggests that LTBI reactivation rates vary by age, time since infection, and the presence of risk factors associated with immune suppression. Estimates of current and future LTBI reactivation rates among at-risk populations are critical inputs for cost-effectiveness analyses of LTBI testing and treatment to determine the cumulative TB risk averted by interventions. Reactivation rates are also important inputs for investigating the current and future course of population-level TB epidemiology. 

Reactivation rate estimates for different population groups are either unavailable or relatively uncertain. This analysis uses Bayesian evidence synthesis to estimate the distribution of likely reactivation rates for key populations at increased risk for TB. Rates are projected to estimate cumulative lifetime reactivation risks.

Associated Publication

• Ekramnia M, Li Y, Haddad MB, Marks SM, Kammerer JS, Swartwood NA, Cohen T, Miller JW, Horsburgh CR, Salomon JA, Menzies NA. Estimated rates of progression to tuberculosis disease for persons infected with Mycobacterium tuberculosis in the United States. Epidemiology. 2024;35(2):164-173. doi:10.1097/EDE.0000000000001707

Trends in TB Incidence and Reactivation of Latent TB Infection in the Elderly U.S.-Born Population

Much of the elderly U.S. population has had greater exposure to TB infection and has a higher prevalence of LTBI compared to younger populations. TB incidence rates are also known to be higher in the elderly. It has been hypothesized that the risks of progression to TB from prior LTBI increase with older age, due to either immunosenescence or incidence of known medical risks, such as diabetes or cancer, arising later in life. Only a small percentage of TB cases in older cohorts are thought to be due to recent infection. 

This analysis investigates trends in TB incidence and reactivation of LTBI among U.S.-born persons aged 50 years and older. The analysis describes how TB incidence rates within the older cohort changed from 1993 to 2018 and how trends in earlier birth and later birth cohorts compare.

Associated Publication

• Kim S, Cohen T, Horsburgh CR, Miller JW, Hill AN, Marks SM, Li R, Kammerer JS, Salomon JA, Menzies NA. Trends, mechanisms, and racial/ethnic differences of tuberculosis incidence in the US-born population aged 50 years or older in the United States. Clinical Infectious Diseases. 2022;74(9):1594-1603. doi:10.1093/cid/ciab668

Reducing Racial/Ethnic Disparities in Syphilis, TB, Hepatitis C and B in the United States

Despite advances in prevention and treatment, significant disparities exist in rates of sexually transmitted infections (STI), tuberculosis (TB), and viral hepatitis in the United States. Multiple causes, many rooted in social determinants of health, increase risks of exposure, reduce access to preventive services such as testing, and delay linkages to care and treatment for underserved populations. Disparities are expressed in worse health outcomes, and reduced prevention effectiveness also may result in higher care and treatment expenditures. This is a cross-cutting project evaluating and quantifying the potential health and economic impacts of addressing the strategies, goals, and indicators, as defined by the STI, Viral Hepatitis, and TB National Strategic Plans to reduce racial and ethnic disparities. 

Associated Publication

• Regan M, Li Y, Swartwood N, Barham T, Beeler Asay GR, Cohen T,  Hill AN, Horsburgh CR, Khan A, Marks SM, Myles RL, Salomon JA, Self JL, Menzies NA. Racial and ethnic disparities in diagnosis and treatment outcomes among US-born people diagnosed with tuberculosis, 2003–19: An analysis of national surveillance data. Lancet Public Health. 2024;9(1):e47-e56. doi:10.1016/S2468-2667(23)00276-1

Racial and Ethnic Disparities in TB Incidence and Outcomes

Although there has been a steady decline in TB incidence and mortality in the United States, disparities have remained constant or increased for some minority groups. Prior PPML work found that U.S.-born non-Hispanic Black, Hispanic, and American Indian/Alaska Native patients had a higher risk of mortality and failure to complete treatment, relative to non-Hispanic White patients. 

This analysis conceptualizes race/ethnicity as a social construct that affects exposure to downstream risk factors, such as socioeconomic status, access to health care, and structural and interpersonal racism. Adjusting for these risk factors in observational analyses could obscure mechanisms through which these racial/ethnic disparities exist. Analyses that reveal the impact of these mechanisms are needed to develop effective intervention strategies to reduce and eliminate observed disparities.

This project uses mediation analysis and quasi-experimental approaches to examine the extent to which downstream risk factors contribute to racial/ethnic disparities in TB incidence and adverse TB outcomes.

Optimal Domestic and Global Approaches for U.S. TB Elimination

Most TB cases in the United States arise in the non-U.S.-born population, and many of these cases are due to infections acquired abroad. Rising TB among non-U.S.-born individuals has slowed the rate of decline in overall U.S. TB incidence, and there is concern that this trend will impede efforts to achieve long-term TB elimination goals in the United States. 

Past studies have demonstrated that:

• Strengthening domestic TB prevention activities, such as expanded access to targeted testing and treatment for LTBI, can substantially accelerate the rate of decline in TB incidence in the United States
• Improving global TB control, particularly among the countries that represent a large share of domestic TB cases, can lead to substantial reductions in the United States 

While prior analyses investigated separate mechanisms for accelerating declines in TB cases, coordinated efforts may allow the United States to achieve TB elimination goals over a shorter duration. This project analyzes the combination of strengthened domestic and international TB control activities and the impact on future TB case trends in the United States.

Associated Publications

• 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. Impact of effective global tuberculosis control on health and economic outcomes in the United States. Am J Respir Crit Care Med. 2020;202(11):1567-1575. doi:10.1164/rccm.202003-0526OC

Quantifying the Health and Economic Burden of Long-Term Sequelae Among TB Survivors

Many individuals who survive TB disease experience extended morbidity. Observational studies have estimated substantially higher all-cause mortality rates among post-TB individuals compared to their matched controls. However, there is less U.S.-based evidence on the economic effects of TB during and after the disease episode. Estimating the causal impact of TB on long-term outcomes is challenging, as individuals who develop TB have a higher prevalence of other risk factors for mortality and ill health that are not causally attributable to TB. Therefore, naïve comparisons of TB survivors with TB-free controls can overestimate the health risks due to TB. Nevertheless, available evidence suggests these health risks are substantial. 

This project summarizes evidence quantifying the causal effect of TB on healthcare utilization, morbidity, and mortality of TB patients after their initial diagnosis, including consideration of comorbid conditions.

Expanding Eligibility for TB Screening and Treatment to the Medicare-Eligible Population

In 2020, the population enrolled in Medicare was 62.8 million, of which 54.5 million were eligible due to being aged 65 or over. This older population represents 17% of the U.S. general population and includes individuals with higher average LTBI prevalence and elevated TB incidence rates. Expanding access to LTBI testing and treatment with no cost-sharing for the Medicare population could identify and treat persons living with LTBI and reduce TB incidence rates in this population. Doing so could accelerate declines in TB incidence within the U.S. and prevent TB disease in a group with higher TB case fatality rates. 

This project supports and informs the testing and treatment needs for LTBI among the Medicare population. It also adds to the literature on the benefits of LTBI treatment by age, as there are currently few estimates of the impact of testing and treating by age group.

National Modeling of the TB Consequences of the COVID-19 Pandemic

The COVID-19 pandemic has likely had a wide-ranging impact on different determinants of TB outcomes in the United States. Understanding the different pathways impacted, the relative magnitude, and implications for TB control strategies is important for continuing progress toward TB elimination. 

This project estimates changes in different epidemiological drivers (immigration, case detection, transmission, competing mortality) in the United States that occurred during 2020 and 2021 due to the COVID-19 pandemic, and the impact of these changes on TB epidemiology and outcomes over the following 15 years, quantified as TB incidence and TB-associated mortality in the United States.

Impact of Target Testing and Treatment Efforts Specifically Among Asian and Hispanic Persons with Diabetes

From 2011 to 2020, Asian and Hispanic Americans comprised 34.7% and 28.8% of TB cases in the United States, respectively. Both populations are at an elevated risk of diabetes when compared to non-Hispanic White Americans. Diabetes has been shown to elevate the risk of developing TB disease among those with LTBI. Employing a target testing and treatment (TTT) intervention for LTBI among Asian and Hispanic Americans with diabetes may have the potential to reduce TB disease in the United States. 

This project uses a transmission-dynamic model of TB to estimate the impact of TTT among Asian and Hispanic Americans with diabetes at the national level.

Modeling the Potential Impact of Interventions to Improve TB Outcomes Among Marginalized Racial/Ethnic Populations

Compared to Non-Hispanic White populations, minority racial-ethnic populations have elevated TB incidence. Mathematical modeling is used to evaluate the potential impact of strengthening TB services in geographic areas with high TB incidence rates and substantial populations of racial-ethnic minorities, with the goal of targeting services to areas with the greatest potential benefit and reducing racial-ethnic disparities in TB incidence.

This project assesses the potential impact of actions to provide expanded LTBI screening and treatment and strengthen prompt and high-quality TB treatment services in geographic areas with documented high TB incidence rates and a high fraction of racial-ethnic minority populations.

Modeling the Impact and Cost-Effectiveness of Voluntary Pre-Entry LTBI Testing and Treatment for Individuals Entering the United States Under the U.S. Refugee Program

Most TB cases in the United States arise among the non-U.S.-born population and the risk of TB is highest in the years immediately after immigration. For several visa classes, current technical instructions mandate screening for TB disease. However, many individuals with TB infection will go on to TB disease in the years following immigration. Providing testing and treatment of TB infection for individuals planning to enter the United States under the U.S. Refugee Program could reduce TB incidence rates among non-U.S.-born individuals in the United States.

This project considers the potential impact and cost-effectiveness of actions to offer or require LTBI screening and treatment prior to U.S. entry for individuals planning to enter the United States under the United States Refugee Program.

Past Projects

Transmission Modeling of TB in the United States

A key outcome to achieving TB control in the United States is time to elimination. While TB incidence in the United States has mostly been in decline for several decades, elimination is many years away. Simple statistical calculations of years until elimination masks important dynamics of transmission, such as the effects of high-risk populations and immigration. The relationship between types of risk, different available interventions, and transmission/achievement of elimination cannot easily be represented in statistical models or that do not account for transmission dynamics.

This work elaborated on population characteristics, TB natural history and epidemiology, and a refined approach to calibrating the model to observed epidemiologic data to inform guidelines on the detection and treatment of active cases, as well as interventions on the prevalence and outcomes of latent infection to change the trajectory of the TB epidemic in the United States.

This project developed a transmission model of tuberculosis in the United States to assess the impact, costs, and cost-effectiveness of certain interventions at the population level.

Associated Presentations and Publications

• Presented at The Union North America Region and the National Tuberculosis Controllers Association Joint 20th Annual Conference, 2016. The poster can be viewed here.
• Menzies NA, Cohen T, Hill AN, Yaesoubi R, Galer K, Wolf E, Marks SM, Salomon JA. Prospects for tuberculosis elimination in the United States: Results of a transmission dynamic model. Am J Epidemiol. 2018;187(9):2011-2020. doi:10.1093/aje/kwy094
• Menzies NA, Wolf E, Connors D, Bellerose M, Sbarra AN, Cohen T, Hill AN, Yaesoubi R, Galer K, White PJ, Abubakar I, Salomon JA. Progression from latent infection to active disease in dynamic tuberculosis transmission models: a systematic review of the validity of modelling assumptions. Lancet Infect Dis. 2018;18(8):e228-e238. doi:10.1016/S1473-3099(18)30134-8
• Menzies NA, Swartwood N, Testa C, Malyuta Y, Hill AN, Marks SM, Cohen T, Salomon JA. Time since infection and risks of future disease for individuals with mycobacterium tuberculosis infection in the United States. Epidemiology. 2021;32(1):70-78. doi:10.1097/EDE.0000000000001271
• Menzies NA, Cohen T, Salomon JA. Evidence sources on the natural history of latent tuberculosis infection. Lancet Infect Dis. 2018;18(8):834-835. doi:10.1016/S1473-3099(18)30406-7

Targeted Testing and Treatment of Latent TB Infection Among High-Risk Populations in the U.S.

Accelerating TB elimination requires reductions in TB disease through both rapid identification and treatment, and appropriately targeted diagnosis and treatment of LTBI to prevent progression to TB in high-risk populations.

This project developed models of targeted testing and treatment of LTBI among various populations based in the United States who are at high risk for TB disease. Since population-based testing and treatment of LTBI is not feasible on a country-wide level, data-driven models inform strategies for targeting this intervention in high-risk populations.

PPML evaluated strategies, considering different populations for targeting testing strategies and LTBI treatment regimens.

Associated Publications and Presentations

• Presented at the American Thoracic Society International Conference, 2016. The poster can be viewed here.
• Tasillo A, Salomon JA, Trikalinos TA, Horsburgh CR, Marks SM, Linas BP. Cost-effectiveness of testing and treatment for latent tuberculosis infection in residents born outside the United States with and without medical comorbidities in a simulation model. JAMA Intern Med. 2017;177(12):1755-1764. doi:10.1001/jamainternmed.2017.3941

Impact of International TB Control Efforts on TB Elimination in the U.S.

The national TB epidemic is increasingly being sustained by new TB cases among recent migrants, with 64% of new cases in the United States coming from this foreign-born population. The trajectory of this trend will depend on several factors, such as updated screening procedures, which impact both latent and active prevalence among migrants, including many beyond U.S. borders.

This project extended PPML’s TB transmission model to include immigration data, including TB control scenarios in migrant sender countries, changes in immigration policy and screening procedures, and epidemiological trends in sender countries.

Associated Publications

• Hill AN, Cohen T, Salomon JA, Menzies NA. High-resolution estimates of tuberculosis incidence among non-U.S.-born persons residing in the United States, 2000-2016. Epidemics. 2020;33:100419. doi:10.1016/j.epidem.2020.100419
• Menzies NA, Hill AN, Cohen T, Salomon JA. The impact of migration on tuberculosis in the United States. Int J Tuberc Lung Dis. 2018;22(12):1392-1403. doi:10.5588/ijtld.17.0185
• 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. Impact of effective global tuberculosis control on health and economic outcomes in the United States. Am J Respir Crit Care Med. 2020;202(11):1567-1575. doi:10.1164/rccm.202003-0526OC

Model Comparison Activities for Unified Framework for Modeling Domestic TB Elimination

The user-friendly tool, Tabby, allows users to investigate national-level TB outcomes for a set of pre-specified policy options and scenarios. This project expanded several dimensions:

• Adapted the model to allow state-level policy projections
• Collaborated with TB modeling groups to coordinate and compare model inputs, methods, and results
• Expanded the range of outcomes projected by the model
• Continued adapting the model as needed to allow state-level projections and examine a wider range of policy scenarios

Learn more about the updated version of this tool, Tabby2.

Associated Publications

• Menzies NA, Parriott A, Shrestha S, Dowdy DW, Cohen T, Salomon JA, Marks SM, Hill AN, Winston CA, Asay GR, Barry P, Readhead A, Flood J, Kahn JG, Shete PB. Comparative modeling of tuberculosis epidemiology and policy outcomes in California. Am J Respir Crit Care Med. 2020;201(3):356-365. doi:10.1164/rccm.201907-1289OC
• Menzies NA, Parriott A, Shrestha S, Dowdy DW, Cohen T, Salomon JA, Marks SM, Hill AN, Winston CA, Asay GR, Barry P, Readhead A, Flood J, Kahn JG, Shete PB. Comparative modeling of tuberculosis epidemiology and policy outcomes in California. Am J Respir Crit Care Med. 2020;201(3):356-365. doi:10.1164/rccm.201907-1289OC

Modeling Enhanced Domestic TB Control Interventions at the Local, State, and National Levels

This project developed a set of novel and improved TB control interventions standardized to be comparable across TB modeling and examined the impact of these interventions for a set of mutually agreed outcomes. Interventions included:

• TB vaccine
• Gold standard/high-performing LTBI diagnostic tests
• Enhanced contact investigation
• Active case finding in high-priority groups 

This analysis utilized PPML’s existing dynamic TB transmission model and integrated new interventions to be examined.

Associated Publications

• Shrestha S, Parriott A, Menzies NA, Shete PB, Hill AN, Marks SM, Dowdy DW. Estimated population-level impact of using a six-week regimen of daily Rifapentine to treat latent tuberculosis infection in the United States. Ann Am Thorac Soc. 2020;17(12):1639-1642. doi:10.1513/AnnalsATS.202005-574RL
• Menzies NA, Shrestha S, Parriott A, Marks SM, Hill AN, Dowdy DW, Shete PB, Cohen T, Salomon JA. The health and economic benefits of tests that predict future progression to tuberculosis disease. Epidemiology. 2022;33(1):75-83. doi:10.1097/EDE.0000000000001418