# Exploring the Early Tuberculosis Spectrum Through Highly-Sensitive Mtb DNA Detection

> **NIH NIH K22** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $27,681

## Abstract

ABSTRACT
Tuberculosis (TB, Mtb) remains one of the leading infectious disease killer globally,
despite the availability of curative treatment for most individuals. The ability to identify
TB which has progressed beyond bacterial containment associated with latency but not
yet reached the burden of culture-positive, symptomatic active disease could have far-
reaching impact in thwarting transmission and decreasing individual morbidity and
mortality. The global scale-up of ultra-sensitive Mtb DNA detection assays, such as the
WHO-recommended GeneXpert MTB/RIF Ultra (Ultra), presents a critical opportunity to
identify this incipient, pre-cultivatable disease stage. We hypothesize that sputum Mtb
DNA-positive/culture-negative individuals are more likely to have incipient TB than Mtb
DNA-negative/culture-negative (TB-negative) individuals. To test this hypothesis, we
initiated a substudy to an R01-funded Ultra diagnostic accuracy study of adults in Africa
with signs/symptoms of TB to evaluate the biology and natural history Ultra Mtb DNA-
positive/culture-negative individuals. In Aim 1, we will characterize host clinical and
demographic factors associated with sputum Mtb DNA-positive/culture-negative status
and characterize these individuals on the spectrum of Mtb infection using pre-validated
blood transcriptional signatures predictive of progression to active TB. In Aim 2, we will
evaluate and compare microbiologic indicators of TB disease between Mtb DNA
positive/culture negative and TB-negative individuals. Specifically, we propose to
investigate the presence of Mtb mRNA from sputum and evaluate for differentially
culturable Mtb from extended incubation and culture supplemented with growth
promoting factors. Finally, we will evaluate the natural history of Mtb DNA-
positive/culture-negative individuals with respect to TB-negative controls using
longitudinal clinical, microbiologic, and host transcriptional data collected over a 12-
month follow-up period in the parent study. Together, these proposed studies will inform
the utility of ultrasensitive Mtb DNA detection tests for early TB risk stratification and
characterize the natural history and biomarkers of culture-negative TB.

## Key facts

- **NIH application ID:** 10419579
- **Project number:** 3K22AI137320-02S1
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Yingda Linda Xie
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $27,681
- **Award type:** 3
- **Project period:** 2021-09-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419579

## Citation

> US National Institutes of Health, RePORTER application 10419579, Exploring the Early Tuberculosis Spectrum Through Highly-Sensitive Mtb DNA Detection (3K22AI137320-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10419579. Licensed CC0.

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