Optimal targeting for individual and population-level TB prevention - PROJECT SUMMARY/ABSTRACT
Within the same community, TB risks can differ by several orders of magnitude due to differences in
infectious exposure and immune competence, and TB control depends heavily on targeting services to
those most at risk. Priority groups described by the CDC and other agencies capture major TB risk
factors, but these broad categories include many individuals with low TB risk, and exclude others who
would benefit from screening. Our long-term objective is to provide individually- and locally-tailored
evidence on TB risks and intervention effects, to optimize TB prevention services. In prior work we have
demonstrated the feasibility of estimating TB risks for small population groups, and in Aim 1 we will
create granular estimates of TB risk for the US population, via a Bayesian evidence synthesis combining
time series data on TB cases and population size, prevalence of latent infection (LTBI), and the fraction
of cases due to recent infection. This analysis will allow us to produce individually-tailored risk predictions
to better target preventive services, and provide patients with quantitative information on the risks they
face. The number of patients to whom this applies is substantial—approximately half of all US residents
have been tested for LTBI, and of those testing positive only half initiate treatment. This represents a
large number of people facing decisions about LTBI testing and treatment. Aim 2 will directly address
these questions, creating highly-disaggregated estimates of the costs, harms, and benefits of LTBI
testing and treatment. To do so we will construct a Markov microsimulation model of LTBI screening and
treatment. Using this model we will estimate long-term patient-level outcomes, including changes in TB
risk, survival, costs, and adverse events. Based on these analyses we will develop a user-friendly web
tool to provide patients and clinicians prompt, validated, and individually-tailored information on possible
treatment outcomes. We will also conduct analyses and develop a companion tool that will report the
impact and cost-effectiveness of LTBI screening for user-defined target groups for the purpose of guiding
program decision-making. To increase the reach and impact of these tools we will adapt them for other
countries with TB incidence below 20 per 100,000. In Aim 3 we will develop a transmission-dynamic
simulation model to predict long-term outcomes for a broad set of TB control options (including but not
limited to LTBI treatment) and risk factor trends. The model will be calibrated for multiple jurisdictions,
and a web-based interface will allow users to specify scenarios and visualize outcomes. By identifying
how current and novel interventions can be most effectively deployed to improve health, this research
addresses the NIH’s highest priority area of health economics research, and responds directly to the
need for computational tools and models to better understand and respond to infectious disease risks.
1