13[C]-Urea Breath Test as a Novel Point-of-Care Biomarker for Tuberculosis Treatment and Diagnosis

Autor: Viorel Atudorei, Zachary D. Sharp, Vojo Deretic, Gueno G. Nedeltchev, Graham S. Timmins, Mandeep S. Jassal, William R. Bishai, Jong-Hee Lee, Seong Won Choi
Rok vydání: 2010
Předmět:
medicine.medical_specialty
Tuberculosis
Urease
Point-of-Care Systems
Urea breath test
lcsh:Medicine
Respiratory Medicine/Respiratory Infections
Gastroenterology
Mycobacterium tuberculosis
03 medical and health sciences
Tuberculosis diagnosis
Internal medicine
Bronchoscopy
medicine
Animals
Urea
lcsh:Science
Lung
030304 developmental biology
Breath test
Carbon Isotopes
0303 health sciences
Mycobacterium bovis
Multidisciplinary
medicine.diagnostic_test
biology
030306 microbiology
business.industry
Infectious Diseases/Respiratory Infections
lcsh:R
Isoniazid
biology.organism_classification
medicine.disease
3. Good health
Phenotype
Treatment Outcome
Infectious Diseases/Neglected Tropical Diseases
Breath Tests
Immunology
biology.protein
Immunization
lcsh:Q
Rabbits
business
Biomarkers
Research Article
medicine.drug
Zdroj: PLoS ONE, Vol 5, Iss 8, p e12451 (2010)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0012451
Popis: BACKGROUND:Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeled substrates and detection of labeled products in exhaled breath using portable infrared spectrometers. METHODOLOGY/PRINCIPAL FINDINGS:We tested whether mycobacterial urease activity could be utilized in such a breath test format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent bronchoscopic infection with either Mycobacterium bovis or Mycobacterium tuberculosis. Rabbits were treated with 25 mg/kg of isoniazid (INH) approximately 2 months after infection when significant cavitary lung pathology was present. [(13)C] urea was instilled directly into the lungs of intubated rabbits at selected time points, exhaled air samples analyzed, and the kinetics of delta(13)CO(2) formation were determined. Samples obtained prior to inoculation served as control samples for background (13)CO(2) conversion in the rabbit model. (13)CO(2), from metabolic conversion of [(13)C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15 minutes of administration. Analyses showed a rapid increase in the rate of (13)CO(2) formation both early in disease and prior to treatment with INH. Following INH treatment, all evaluable rabbits showed a decrease in the rate of (13)CO(2) formation. CONCLUSIONS/SIGNIFICANCE:Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of unlabeled urea, which would prevent the delta(13)CO(2) signal from urease-positive gastrointestinal organisms.
Databáze: OpenAIRE
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