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

ABSTRACT

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.