Tuberculosis is the leading cause of death by an infectious disease worldwide. Tuberculosis control strategies in low- and middle-income countries (LMICs), which bear the major burden of TB, currently suffer from two major gaps in the scientific evidence on program implementation, which must be overcome to achieve global targets: (1) how to trace the chain of transmission to the major pockets of the population where TB is increasingly concentrated (i.e., populations serving as reservoirs for broader population epidemics); and (2) how to efficiently and cost-effectively screen populations within these concentrated reservoirs. Our preliminary research and those of several other groups has revealed that prisons are likely to be an important reservoir for tuberculosis in many LMICs. Mass screening, as suggested by the World Health Organization, could be an effective means of case detection, but is not widely implemented in LMICs due to high costs and infrastructure requirements. We propose to leverage unique research and tuberculosis surveillance infrastructure in prisons and community settings in Central- Western Brazil to address these critical questions. We will test the following three hypotheses: 1) a major burden of tuberculosis in communities is attributable to transmission in prisons; 2) testing pooled sputum samples using a new, sensitive molecular diagnostic assay (Xpert Ultra) on a mobile diagnostic unit can accurately and efficient detect tuberculosis cases; and 3) prison-based mass screening can cost- effectively reduce the community burden of tuberculosis. This project will utilize a novel statistical modeling approach to infer the directionality of transmission by integrating tuberculosis natural history, exposure and phylogenetic data derived from whole genome sequencing. Additionally, this work will generate an open source tool for comparing the impact of various diagnostic strategies in prisons and other high-burden populations. Overall, this project addresses persistent scientific barriers to tuberculosis control: how to clearly identify the contribution of reservoir populations, and how to screen them efficiently in cost-conscious settings.

Public Health Relevance

Tuberculosis is the leading cause of death by a communicable disease globally. A critical barrier to controlling tuberculosis is its concentration in high-risk settings or populations. This project aims to examine the role of prisons in driving community epidemics of tuberculosis, and to identify novel and efficient diagnosis strategies to reduce the burden of this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI130058-02
Application #
9441709
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Lacourciere, Karen A
Project Start
2017-03-01
Project End
2022-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Correia Sacchi, Flávia Patussi; Tatara, Mariana Bento; Camioli de Lima, Camila et al. (2017) Genetic Clustering of Tuberculosis in an Indigenous Community of Brazil. Am J Trop Med Hyg :