# M. tuberculosis exosome detection for pediatric TB diagnosis

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $696,418

## Abstract

PROJECT SUMMARY/ABSTRACT
Over one million new cases of tuberculosis (TB) and 239,000 TB-related deaths occur in children each year.
Young children, especially those with HIV, are more likely to present with disseminated or extrapulmonary TB
and paucibacillary disease, often missed by respiratory sampling. Non-sputum, biomarker-based diagnostic tools
for rapid TB detection and treatment response in children, using easily obtained specimens are urgently needed.
Exosomes are small (30-100 nm) membranous extracellular vesicles (EVs) originating from endosomal cell
compartments; those secreted by M. tuberculosis (Mtb) or Mtb-infected macrophages appear to play a significant
role in Mtb pathogenesis. Our collaborators have developed a rapid and sensitive nanoplasmon-enhanced
scattering (nPES) assay which directly detects Mtb-exosomes (Mtb-EVs) from as little as 1 L of serum. Proof-
of-concept nPES assays performed with Mtb markers LpqH (19-kDa Mtb lipoprotein) and LAM distinguished
adult TB from at-risk patients and normal controls, and among pediatric TB cases (including HIV+) and controls
with high sensitivity and specificity.
We propose using archived specimens and clinical data from the Pediatric Urgent Start of HAART (PUSH) Study
(NCT02063880) and a new proposed prospective cohort of children suspected of TB with high HIV prevalence
to evaluate performance of nPES detected Mtb-EVs for pediatric TB diagnosis (Aim 1), treatment response (Aim
2), and evaluation of a point-of-care platform (Aim 3). In addition to assessing conventional diagnostic
performance measures, we propose to use advanced epidemiologic methods (Bayesian latent class analysis)
given the context of an imperfect reference. Additional evaluation in adult TB patients and healthy controls
including household contacts (adults and children) and recently BCG-vaccinated infants without TB is proposed.
We hypothesize nPES detected Mtb-EVs will 1) have similar diagnostic performance to the reference of
Xpert/culture among children with confirmed TB without the need for sputum, and identify additional children
missed by respiratory sample, 2) will provide a useful surrogate marker of treatment response with decline in
quantitative levels during successful treatment, and 3) will maintain performance with a point-of-care platform.
Using cryopreserved samples from a well-characterized cohort of children with HIV who underwent intensive TB
evaluation and a prospective cohort of children suspected of TB with high HIV prevalence provides opportunity
for efficient evaluation of a novel diagnostic with potential for clinical impact to improve pediatric TB diagnosis.

## Key facts

- **NIH application ID:** 10325946
- **Project number:** 1R01AI162152-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sylvia LaCourse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $696,418
- **Award type:** 1
- **Project period:** 2021-06-21 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10325946

## Citation

> US National Institutes of Health, RePORTER application 10325946, M. tuberculosis exosome detection for pediatric TB diagnosis (1R01AI162152-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10325946. Licensed CC0.

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