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

Andrew R. DiNardo, Alexander W. Kay, Gugu Maphalala, Nadine M. Harris, Celia Fung, Godwin Mtetwa, Pilar Ustero, Sindisiwe Dlamini, Ngan Ha, Edward A. Graviss, Rojelio Mejia, Anna M. Mandalakas

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume99
Issue number2
Early online dateApr 23 2018
DOIs
StatePublished - 2018

Keywords

  • Journal Article

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Virology

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