# Complementary diagnostic biomarkers of sputum culture-negative TB [R21]

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2022 · $235,007

## Abstract

ABSTRACT
At least 15-30% of symptomatic tuberculosis (TB) is estimated to be culture-negative, of whom
approximately half progress to culture-positive TB. Improved diagnostics for sputum culture-
negative TB thus represents a major opportunity for early intervention to prevent morbidity and
development of transmissible disease. However, there are currently no validated diagnostic
strategies to confirm or screen for culture-negative TB. Only recently, progress in non-sputum
based near-patient diagnostics – including cartridge-based tests of TB host response signatures
and lateral flow assays to detect TB antigen from urine – have provided progressively more
sensitive readouts of TB infection independent of sputum culture. Together, these methods have
unexplored potential as complementary diagnostic biomarkers with an ability to detect TB patients
otherwise missed by slow, inaccessible sputum culture-based methods. With the long-term goal
of developing rapid and feasible diagnostic approach for culture-negative TB, we will evaluate the
latest, most promising urine LAM platforms and TB host response signatures among an existing
cohort of symptomatic but culture-negative individuals who have been clinically and
microbiologically characterized over 12 months. Our central hypothesis is that host-response
signatures and urine LAM detection - alone or combined - will have an AUC ROC of over 70% for
discriminating individuals with “probable” versus “unlikely” culture-negative TB – referenced by
their longitudinal clinical and extended microbiologic signals of TB. We will test our hypothesis
through the following complementary aims:
Aim 1 will compare a panel of previously validated TB host response gene expression signatures
between culture-confirmed TB, TB-negative controls, and the well-characterized cohort of culture-
negative individuals, with the hypothesis that readouts of symptomatic, culture-negative
individuals will fall between that of culture-confirmed TB and TB-negative controls. We will then
evaluate the ability of these signatures to discriminate probable versus unlikely culture negative
TB. In Aim 2, we will follow the same approach to evaluate for presence of TB LAM using existing
and novel high-affinity urine LAM assays between these three cohorts, and evaluate the individual
and combined value of urine LAM and host response signatures for discriminating probable
versus unlikely culture-negative TB.
The expected outcome of this study is the foundation of a diagnostic strategy for culture-negative
TB to facilitate early appropriate treatment, thereby halting development of a significant population
of culture-positive disease with far-reaching impact in preventing TB morbidity and transmission.

## Key facts

- **NIH application ID:** 10433028
- **Project number:** 1R21AI169329-01
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** ABRAHAM PINTER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,007
- **Award type:** 1
- **Project period:** 2022-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433028

## Citation

> US National Institutes of Health, RePORTER application 10433028, Complementary diagnostic biomarkers of sputum culture-negative TB [R21] (1R21AI169329-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10433028. Licensed CC0.

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