Detection of Mycobacterium Tuberculosis Transrenal DNA in Urine Samples Among Adult Patients in Peru

Abstract

Diagnosis of tuberculosis (TB) relies on a sputum sample, which cannot be obtained from all symptomatic patients. Mycobacterium tuberculosis (Mtb) transrenal DNA (trDNA) has been detected in urine, an easily obtainable, noninvasive, alternative sample type. However, reported sensitivities have been variable and likely depend on collection/assay procedures and aspects of trDNA biology. We analyzed three serial urine samples from each of 75 adults with culture-confirmed pulmonary TB disease in Lima, Peru for detection of trDNA using short-fragment real-time PCR. Additionally, we examined host, urine, and sampling factors associated with detection. Overall sample sensitivity was 38% (95% Confidence Interval [CI] 30–45%). On a patient level (i.e., any of three samples positive), sensitivity was 73% (95% CI: 62-83%). Sensitivity was highest among samples from patients with smear-positive TB, 92% (95% CI: 62-100%). Specificity from a single sample from each of 10 healthy controls was 100% (95% CI: 69-100%). Adjusting our assay positivity threshold increased patient-level sensitivity to 88% (95% CI: 78-94%) overall without affecting the specificity. We did not find associations between Mtb trDNA detection and either patient characteristics or urine sample characteristics. Overall, our results support the potential of trDNA detection for TB diagnosis.

Note:
Funding Declaration: This work was supported by the National Institutes of Allergy and Infectious Disease of the National Institutes of Health under award numbers U19AI109755 and R03AI153554. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of Interests: None.

Ethical Approval: Study participants provided written informed consent. All experiments were performed in accordance with the Declaration of Helsinki. All study procedures were approved by the Ethics Committee of Peru’s National Institute of Health (OEE-039-14) and the Office of Human Research Administration at Harvard TH Chan School of Public Health (IRB 13-2754).

Keywords: cell-free DNA, tuberculosis, diagnostics, diagnosis