Microscopic-Observation Drug-Susceptibility Assay for the Diagnosis of TB

TLDR

Rapid, sensitive detection of tuberculosis and multidrug‑resistant tuberculosis in sputum is urgently needed, and proof‑of‑principle studies have shown that the microscopic‑observation drug‑susceptibility (MODS) assay can achieve this by examining broth cultures microscopically for characteristic growth. The MODS assay was evaluated in Peru by comparing it head‑to‑head with automated mycobacterial culture and Löwenstein‑Jensen medium, using broth cultures examined microscopically to detect growth. In 3,760 sputum samples, MODS achieved 97.8 % sensitivity versus 89.0 % for automated culture and 84.0 % for Löwenstein‑Jensen, with median culture positivity times of 7, 13, and 26 days and susceptibility results in 7, 22, and 68 days, respectively, and showed 100 % agreement for rifampin and >95 % agreement for other drugs, confirming its rapid, accurate performance.

Abstract

New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid, sensitive detection of tuberculosis and multidrug-resistant tuberculosis in sputum has been demonstrated in proof-of-principle studies of the microscopic-observation drug-susceptibility (MODS) assay, in which broth cultures are examined microscopically to detect characteristic growth.In an operational setting in Peru, we investigated the performance of the MODS assay for culture and drug-susceptibility testing in three target groups: unselected patients with suspected tuberculosis, prescreened patients at high risk for tuberculosis or multidrug-resistant tuberculosis, and unselected hospitalized patients infected with the human immunodeficiency virus. We compared the MODS assay head-to-head with two reference methods: automated mycobacterial culture and culture on Löwenstein-Jensen medium with the proportion method.Of 3760 sputum samples, 401 (10.7%) yielded cultures positive for Mycobacterium tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89.0% for automated mycobacterial culture, and 84.0% for Löwenstein-Jensen culture (P<0.001); the median time to culture positivity was 7 days, 13 days, and 26 days, respectively (P<0.001), and the median time to the results of susceptibility tests was 7 days, 22 days, and 68 days, respectively. The incremental benefit of a second MODS culture was minimal, particularly in patients at high risk for tuberculosis or multidrug-resistant tuberculosis. Agreement between MODS and the reference standard for susceptibility was 100% for rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined results for multidrug resistance), 95% for ethambutol, and 92% for streptomycin (kappa values, 1.0, 0.89, 0.93, 0.71, and 0.72, respectively).A single MODS culture of a sputum sample offers more rapid and sensitive detection of tuberculosis and multidrug-resistant tuberculosis than the existing gold-standard methods used.