Rapid diagnosis of tuberculosis and multidrug resistance by the microscopic-observation drug-susceptibility assay

Am J Respir Crit Care Med. 2011 May 15;183(10):1427-33. doi: 10.1164/rccm.201009-1449OC. Epub 2011 Feb 4.


Rationale: Mortality is exceedingly high and rapid among patients infected with HIV and tuberculosis (TB), in part because of limited access to appropriate TB diagnostics. The microscopic observation drug-susceptibility (MODS) assay is a simple, rapid, low-cost test for TB and multidrug-resistant (MDR) TB, but data in individuals infected with HIV and in Africa are limited.

Objectives: To evaluate the MODS assay in a high-HIV-prevalence setting.

Methods: We performed a prospective diagnostic accuracy study of consecutive adults suspected to have TB from outpatient and inpatient settings at a district hospital in rural South Africa. Sputum was tested by concentrated smear microscopy; agar (Middlebrook 7H11) and liquid (mycobacterial growth indicator tube) culture; and the MODS assay. Drug-susceptibility testing (DST) was by indirect 1% proportion method and MODS. Reference standard for Mycobacterium tuberculosis detection was growth on Middlebrook or mycobacterial growth indicator tube culture; 1% proportion was the reference standard for isoniazid and rifampin DST.

Measurements and main results: Among 534 adults enrolled, 388 (73%) were HIV-positive, with a median CD4 count of 161 cells/mm(3) (interquartile range [IQR]: 72-307). TB was diagnosed by the reference standard culture in 113 (21%). MODS sensitivity was 85% (95% confidence interval [CI], 78-92%), and specificity was 97% (CI, 95-99%). MODS test performance did not differ by patients' HIV status (sensitivity 88% vs. 90%, specificity 97% vs. 100% for HIV-positive versus HIV-negative, respectively). For MDR-TB diagnosis (n = 11), sensitivity was 100% (one-sided CI, 68-100%) and specificity was 94% (CI, 82-98%). Median turnaround time for MDR-TB diagnosis was 7 days (IQR: 6-9) with MODS versus 70 days (IQR: 49-96) with indirect proportion method (P < 0.001).

Conclusions: Among adult TB suspects predominantly infected with HIV, MODS provided high sensitivity and specificity for rapid diagnosis of TB and MDR-TB. Given the high mortality from TB and MDR-TB and prolonged opportunity for TB transmission before diagnosis, the MODS assay warrants serious consideration for use in similar high-HIV-prevalence, resource-limited settings.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / pharmacology
  • Female
  • HIV Infections / epidemiology
  • Humans
  • Male
  • Microbial Sensitivity Tests / methods*
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Prospective Studies
  • Reproducibility of Results
  • Sensitivity and Specificity
  • South Africa / epidemiology
  • Sputum / microbiology
  • Tuberculosis / diagnosis*
  • Tuberculosis / epidemiology
  • Tuberculosis / microbiology
  • Tuberculosis, Multidrug-Resistant / diagnosis
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / microbiology


  • Antitubercular Agents