# Determinants of TB control, relapse and reinfection

> **NIH NIH U19** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $2,583,322

## Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), continues to be a severe global
health problem. TB is multifaceted, but a central clinical and microbiologic feature of the disease is the ability of
Mtb to resist complete elimination, both by the host immune system and by chemotherapeutic agents with potent
growth inhibitory activity. This persistence in the face of immunologic and antibiotic pressure underlies several
important facets of TB disease, including 1) the existence of latent tuberculosis infection (LTBI) and, in the setting
of immunologic failure of LTBI control, its role in the genesis of active TB and 2) the prolonged course of TB
antibiotic therapy, which requires 6 months of multidrug therapy to achieve reliable clinical cure. Rather than
producing complete bacterial eradication in all treated subjects, cure following TB chemotherapy is now
understood to be an antibiotic induced paucibacillary state in which prevention of relapse depends in part on
poorly understood host factors. The host and bacterial determinants that mediate these two interrelated types of
persistence are only partially understood, a knowledge gap the Tri-I-TBRU aims to fill. We propose a set of 3
intersecting projects and 3 cores all focused on different facets of the problem of paucibacillary TB, both post
treatment and LTBI. The projects will use samples and clinical data from TB cohorts at our clinical site at
GHESKIO in Port Au Prince Haiti, to examine the immunologic, microbiomic, transcriptomic, pharmacokinetic,
and genetic factors that influence or predict the transition points between paucibacillary states of TB disease and
active transmissible infection. These human studies will be compared and contrasted with a new mouse model
of paucibacillary infection that will allow us to test mechanistic hypotheses about the host and bacterial
determinants of paucibacillary disease. This work with be conducted by a team of highly collaborative
investigators who have who have worked well together for several years.

## Key facts

- **NIH application ID:** 10430221
- **Project number:** 5U19AI162568-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** SABINE EHRT
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,583,322
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430221

## Citation

> US National Institutes of Health, RePORTER application 10430221, Determinants of TB control, relapse and reinfection (5U19AI162568-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10430221. Licensed CC0.

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