title: Rapid diagnosis of tuberculosis and multidrug resistance by the microscopic-observation drug-susceptibility assay.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Tugela Ferry Care and Research Collaboration, Tugela Ferry, South Africa. ns597@columbia.edu
authors.forename: N Sarita
authors.initials: NS
authors.lastname: Shah
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.forename: Palav
authors.initials: P
authors.lastname: Babaria
authors.forename: Salona
authors.initials: S
authors.lastname: Moodley
authors.forename: Melissa
authors.initials: M
authors.lastname: Ramtahal
authors.forename: Jessica
authors.initials: J
authors.lastname: Richardson
authors.forename: Scott
authors.initials: S
authors.lastname: Heysell
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Anthony
authors.initials: A
authors.lastname: Moll
authors.forename: Gerald
authors.initials: G
authors.lastname: Friedland
authors.forename: A Willem
authors.initials: AW
authors.lastname: Sturm
authors.forename: Neel R
authors.initials: NR
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000453:epidemiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents