NEEMA Funded Projects - Tuberculosis

NEEMA 2.0 (2019-2024)

Impact of targeted testing and treatment for tuberculosis (TB) among Asian and Hispanic persons with diabetes

From 2011 to 2020, Asian and Hispanic Americans comprised 34.7% and 28.8% of tuberculosis (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 tuberculosis disease among those with latent tuberculosis infection (LTBI). Employing a TTT intervention for LTBI among Asian and Hispanic Americans with diabetes may have the potential to reduce tuberculosis disease in the United States. This project uses a transmission-dynamic model of tuberculosis in the United States to estimate the impact of TTT among Asian and Hispanic Americans with diabetes at the national level.

Modeling the TB consequences of the COVID-19 pandemic

The COVID-19 pandemic has likely had wide-ranging impact on different determinants of tuberculosis outcomes in the United States. Understanding the different pathways impacted, the relative magnitude, and implications for tuberculosis control strategies is important for continuing progress toward tuberculosis elimination. This project will estimate changes in different epidemiological drivers (immigration, case detection, transmission, competing mortality) in the United States that occurred during 2020 and 2021 as a result of the COVID-19 pandemic, and the impact of these changes on tuberculosis epidemiology and outcomes over the following 15 years, quantified as tuberculosis incidence and tuberculosis-associated mortality in the United States.

Trends in TB incidence and reactivation of latent TB infection (LTBI) in the elderly U.S.-born population

Trends in tuberculosis incidence among the elderly are of programmatic and scientific interest. Much of the older U.S. population has had greater exposure to tuberculosis infection and has a higher prevalence of LTBI compared to younger populations. Tuberculosis incidence rates are also known to be higher in the elderly. It has been hypothesized that the risks of progression to tuberculosis 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 tuberculosis cases in older cohorts are thought to be due to recent infection. This analysis will investigate trends in tuberculosis incidence and reactivation of LTBI among U.S.-born persons aged 50 years and older in the United States. Specifically, the analysis will describe how tuberculosis incidence rates within the older cohort changed from 1993 to 2018, and how trends in earlier birth cohorts compare with those of later birth cohorts.

Estimating rates of LTBI reactivation by population

More than 80% of tuberculosis cases in the United States result from reactivation of LTBI. For this reason, identifying and treating individuals with LTBI is a primary focus of tuberculosis prevention. Evidence suggests that LTBI reactivation rates vary by age and time since infection, as well as the presence of risk factors associated with minor (e.g., smoking, diabetes, under-nutrition) or major (e.g., advanced HIV, end-stage renal disease) 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 as these rates determine the cumulative tuberculosis risk that can be averted by such interventions. Reactivation rates are also important inputs for analyses investigating the current status and future course of population-level tuberculosis epidemiology. Despite their importance, reactivation rate estimates for different population groups are either unavailable or are relatively uncertain. This analysis will use a Bayesian evidence synthesis to estimate the distribution of likely reactivation rates for key populations at increased risk for tuberculosis. Furthermore, these rates will be projected to estimate cumulative lifetime reactivation risks.

Tool for estimating intervention costs and averted TB and LTBI

Information on the costs and health outcomes of tuberculosis services, such as testing and treatment for LTBI to prevent tuberculosis progression, is important for national, state, and local tuberculosis decision-making. Knowing the potential epidemiologic and economic impact of tuberculosis services, including across populations at risk, 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 tuberculosis 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 tuberculosis prevention and the funding required to effectively address the burden of tuberculosis and LTBI. This work will extend the functionality of the existing user-friendly tool, Tabby2, by providing locally tailored results for all 50 states and the District of Columbia and by broadening the functionality of the tool to report future costs and cost-savings associated with tuberculosis and tuberculosis interventions.

Description of large TB outbreaks in the U.S.

While tuberculosis transmission rates have declined nationally in the United States during the last two decades—owing largely to tuberculosis control efforts—responding to tuberculosis outbreaks (which often occur among people experiencing homelessness or incarceration) to prevent further transmission, remains an important priority for tuberculosis control. This project will collaborate closely with the Division of Tuberculosis Elimination (DTBE) and state-level tuberculosis controllers to develop tuberculosis outbreak models in the U.S. These proposed models will focus on large tuberculosis outbreaks and aim to estimate the epidemiological impact and cost-effectiveness of tuberculosis outbreak response in the U.S.

Impact of interventions to reduce TB transmission and outbreaks in disproportionately affected populations

Tuberculosis transmission in the United States is both heterogeneous, with a few cases contributing to a large proportion of recent transmission, and disproportionately burdensome to disadvantaged populations—including racial and ethnic minorities, as well as people experiencing homelessness, who are incarcerated, and who use drugs (injection and non-injection). Public health efforts to reduce tuberculosis transmission have been instrumental in lowering incidence in the U.S. in the last few decades, but these interventions can be resource intensive. This project aims to better understand tuberculosis genotype clusters in the United States and across four key states (CA, FL, NY, TX) in order to identify targeted interventions that are feasible to implement, might be prioritized by tuberculosis controllers and other health officials, and are likely to be impactful in reducing the risk of tuberculosis transmission and outbreaks, especially in disproportionately affected populations.

COVID-19 pandemic as a natural experiment to inform TB elimination efforts

The United States observed a sharp decline in tuberculosis incidence in 2020. Declines were pervasive, observed across almost all states, all age strata, both U.S.- and non-U.S.-born populations, and across all subpopulations disaggregated by race or ethnicity. The COVID-19 pandemic resulted in drastic changes that would be expected to result in short-term declines in tuberculosis notifications – but the implications for tuberculosis control differ tremendously, providing a unique opportunity to better understand how to control tuberculosis in the longer term, irrespective of the pandemic itself. This project will expand a previously developed model-based framework to include mechanisms of change in tuberculosis transmission and epidemiology as a result of COVID-19-related disruptions. Using this updated model, the project aims to offer a better understanding of tuberculosis transmission and notification patterns following COVID-19 disruptions in Calif., Fla. N.Y., and Texas, and to project changes in tuberculosis trends over the next 20 years in these four target states.

Domestic and global approaches for U.S. TB elimination

The majority of tuberculosis cases in the United States arise in the non-U.S.-born population, and many of these tuberculosis cases are due to infections acquired abroad. Rising tuberculosis among non-U.S.-born individuals has slowed the rate of decline in overall U.S. Tuberculosis incidence, and there is concern that trends in non-U.S.-born tuberculosis will impede efforts to achieve long-term tuberculosis elimination goals for the United States. Past studies have demonstrated that: (a) strengthening domestic tuberculosis prevention activities (in particular, expanded access to targeted testing and treatment for LTBI) can substantially decelerate the rate of tuberculosis incidence in the U.S., in addition to providing important individual health benefits; and (b) that improved global tuberculosis control, particularly among the countries that represent a large share of U.S. tuberculosis cases, can also lead to substantial reductions in future U.S. tuberculosis cases. These prior analyses investigated separate mechanisms for accelerating declines in tuberculosis cases in the United States, raising the prospect that coordinated action on both fronts—that is, improvements in global tuberculosis control paired with improvements in domestic tuberculosis prevention—may allow the U.S. to achieve tuberculosis elimination goals over a shorter duration than presumed by earlier analyses. This project aims to analyze the combination of strengthened domestic and international tuberculosis control activities, and what this would mean for future tuberculosis case trends in the United States.

Quantifying the health and economic burden of long-term sequelae among TB survivors

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

Estimating the Medicare population eligible for targeted LTBI testing and treatment

In 2020, the population enrolled in Medicare (Part A and or B) 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 (when compared to the general population due to greater lifetime exposure) and elevated tuberculosis incidence rates (when compared to younger age groups). 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 tuberculosis incidence rates in this population. Doing so could accelerate declines in tuberculosis incidence within the U.S. and prevent tuberculosis disease in a group with higher tuberculosis case fatality rates. This project will support and inform the testing and treatment needs for LTBI among the Medicare population and will also add to the literature on the benefits of LTBI treatment by age, as there are currently no/few estimates of the impact of testing and treating by age group.