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Am J Trop Med Hyg. 2018 Aug;99(2):310-316. doi: 10.4269/ajtmh.18-0004. Epub 2018 Apr 19.

Diagnostic and Treatment Monitoring Potential of A Stool-Based Quantitative Polymerase Chain Reaction Assay for Pulmonary Tuberculosis.

Author information

1
Internal Medicine-Infectious Diseases, Baylor College of Medicine, Houston, Texas.
2
The Global TB Program, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.
3
The Baylor-Swaziland Children's Foundation, Mbabane, Swaziland.
4
Ministry of Health, Mbabane, Swaziland.
5
Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, Texas.
6
The National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas.

Abstract

A quantifiable, stool-based, Mycobacterium tuberculosis (Mtb) test has potential complementary value to respiratory specimens. Limit of detection (LOD) was determined by spiking control stool. Clinical test performance was evaluated in a cohort with pulmonary tuberculosis (TB) (N = 166) and asymptomatic household TB child contacts (N = 105). Stool-quantitative polymerase chain reaction (qPCR) results were compared with sputum acid-fast bacilli (AFB) microscopy, GeneXpert MTB/RIF (Xpert MTB/RIF), and cultures. In Mtb stool-spiking studies, the LOD was 96 colony-forming units/50 mg of stool (95% confidence interval [CI]: 84.8-105.6). Among specimens collected within 72 hours of antituberculosis treatment (ATT) initiation, stool qPCR detected 22 of 23 (95%) of culture-positive cases. Among clinically diagnosed cases that were Xpert MTB/RIF and culture negative, stool qPCR detected an additional 8% (3/37). Among asymptomatic, recently TB-exposed participants, stool PCR detected Mtb in two of 105 (1.9%) patients. Two months after ATT, the Mtb quantitative burden in femtogram per microliters decreased (Wilcoxon signed-rank P < 0.001) and persistent positive stool PCR was associated with treatment failure or drug resistance (relative risk 2.8, CI: 1.2-6.5; P = 0.012). Stool-based qPCR is a promising complementary technique to sputum-based diagnosis. It detects and quantifies low levels of stool Mtb DNA, thereby supporting adjunct diagnosis and treatment monitoring in pulmonary TB.

PMID:
29692304
PMCID:
PMC6090360
[Available on 2019-08-01]
DOI:
10.4269/ajtmh.18-0004

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