# Direct quantitation of the circulating Mtb-peptidome for pediatric TB management

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2022 · $386,773

## Abstract

ABSTRACT
Conventional methods for adult and pediatric tuberculosis (TB) diagnosis and treatment monitoring rely heavily
on time-consuming bacterial culture or unquantifiable DNA assays to detect the presence of small numbers of
bacteria. Pediatric TB management is particularly difficult because current organism-based methods for
diagnosis and treatment monitoring are resource-intensive, invasive and inadequately sensitive for children,
who tend to have paucibacillary disease. Due their immunological immaturity, young children are at high risk of
rapid disease TB progression, with significant morbidity and mortality. Assessment of their treatment response
relies on subjective measures, limiting children's access to much needed shorter and safer TB regimens. More
rapid and rigorous methods of TB diagnosis and treatment monitoring are thus critically needed for children. In
order to address current limitations in pediatric TB management, we propose to develop a rapid diagnostic
method, independent of mycobacterial isolation, that quantifies the low molecular-weight M. tuberculosis (Mtb)
antigens (CFP-10 and ESAT-6) and the TB-associated host marker IP-10 in patient blood samples. ESAT-6
and CFP-10 are ideal biomarkers to detect active TB and its treatment response, and addition of IP-10 to this
Mtb-specific proteomic pattern will provide an integrated profile of patients' pathophysiological changes during
anti-TB treatment, while also improving diagnostic sensitivity. Our strategy utilizes hollow, energy-focusing
TiO2 NanoShells functionalized with custom antibodies specific for Mtb CFP-10 and ESAT-6 and host IP-10
peptides with high-throughput mass spectrometry (MS) to increase diagnostic sensitivity and specificity. We
evaluated an Mtb-antigen-only version of this NanoShell-MS platform (no anti-IP-10 NanoShells) with 292 adult
and 102 pediatric patients and controls chosen from five highly relevant cohorts (adult, pediatric and latent TB,
HIV/TB co-infection, and non-TB mycobacterial infection), from our global collaborators. NanoShell-MS
sensitivity and specificity for active TB (bacteriologically confirmed and clinically diagnosed) were, respectively,
90.7% / 97.7% in adults and 88.2% / 100% in children, with 78.6% sensitivity in culture-negative pediatric TB
patients, greatly exceeding the WHO's published 4-15% Xpert sensitivity in this cohort. NanoShell-MS results
can be obtained within one hour of sample collection compared to 4-6 weeks for conventional culture, and
detected decreases in blood Mtb antigen levels within four days of anti-TB treatment initiation. In this proposal
we aim to 1) use NanoShell-MS profiling to develop a quantitative prediction model for active TB diagnosis in
large, well-described prospective pediatric TB cohorts and 2) determine the utility of our approach for rapid
evaluation of treatment efficacy. Our NanoShell-MS assay platform has the advantage that it uses accurate,
high-throughput mass spectrometry, which has...

## Key facts

- **NIH application ID:** 10372903
- **Project number:** 5R01HD090927-06
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Christopher J Lyon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,773
- **Award type:** 5
- **Project period:** 2019-08-09 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372903

## Citation

> US National Institutes of Health, RePORTER application 10372903, Direct quantitation of the circulating Mtb-peptidome for pediatric TB management (5R01HD090927-06). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10372903. Licensed CC0.

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