title: Evaluation of microscopic observation drug susceptibility assay for diagnosis of multidrug-resistant tuberculosis in Viet Nam.
abstract: BACKGROUND
  Early diagnosis of tuberculosis (TB) and multidrug resistant tuberculosis (MDR TB) is important for the elimination of TB. We evaluated the microscopic observation drug susceptibility (MODS) assay as a direct rapid drug susceptibility testing (DST) method for MDR-TB screening in sputum samples
  
  
  METHODS
  All adult TB suspects, who were newly presenting to Pham Ngoc Thach Hospital from August to November 2008 were enrolled into the study. Processed sputum samples were used for DST by MODS (DST-MODS) (Rifampicin (RIF) 1 μg/ml and Isoniazid (INH) 0.4 μg/ml), MGIT culture (Mycobacterial Growth Indicator Tube) and Lowenstein Jensen (LJ) culture. Cultures positive by either MGIT or LJ were used for proportional DST (DST-LJ) (RIF 40 μg/ml and INH 0.2 μg/ml). DST profiles on MODS and LJ were compared. Discrepant results were resolved by multiplex allele specific PCR (MAS-PCR).
  
  
  RESULTS
  Seven hundred and nine TB suspects/samples were enrolled into the study, of which 300 samples with DST profiles available from both MODS and DST-LJ were analyzed. Cording in MODS was unable to correctly identify 3 Mycobacteria Other Than Tuberculosis (MOTT) isolates, resulting in 3 false positive TB diagnoses. None of these isolates were identified as MDR-TB by MODS. The sensitivity and specificity of MODS were 72.6% (95%CI: 59.8, 83.1) and 97.9% (95%CI: 95.2, 99.3), respectively for detection of INH resistant isolates, 72.7% (95%CI: 30.9, 93.7) and 99.7% (95%CI: 98.1, 99.9), respectively for detecting RIF resistant isolates and 77.8% (95%CI: 39.9, 97.1) and 99.7% (95%CI: 98.1, 99.9), respectively for detecting MDR isolates. The positive and negative predictive values (PPV and NPV) of DST-MODS were 87.5% (95%CI: 47.3, 99.6) and 99.3% (95%CI: 97.5, 99.9) for detection of MDR isolates; and the agreement between MODS and DST-LJ was 99.0% (kappa: 0.8, P < 0.001) for MDR diagnosis. The low sensitivity of MODS for drug resistance detection was probably due to low bacterial load samples and the high INH concentration (0.4 μg/ml). The low PPV of DST-MODS may be due to the low MDR-TB rate in the study population (3.8%). The turnaround time of DST-MODS was 9 days and 53 days for DST-LJ.
  
  
  CONCLUSIONS
  The DST-MODS technique is rapid with low contamination rates. However, the sensitivity of DST-MODS for detection of INH and RIF resistance in this study was lower than reported from other settings.
authors.affiliation: Pham Ngoc Thach Hospital, 120 Hung Vuong, District 5, Ho Chi Minh City, Viet Nam. hadtm@oucru.org
authors.forename: Thi Minh Ha
authors.initials: TM
authors.lastname: Dang
authors.forename: Thi Ngoc Lan
authors.initials: TN
authors.lastname: Nguyen
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Sy Kiet
authors.initials: SK
authors.lastname: Vo
authors.forename: Thi Thanh Hang
authors.initials: TT
authors.lastname: Hoang
authors.forename: Hong Duc
authors.initials: HD
authors.lastname: Nguyen
authors.forename: My Huong
authors.initials: MH
authors.lastname: To
authors.forename: Minh Bach
authors.initials: MB
authors.lastname: Vuong
authors.forename: Thi Phuong Thao
authors.initials: TP
authors.lastname: Nguyen
authors.forename: Van Quyet
authors.initials: VQ
authors.lastname: Tran
authors.forename: Thi Bich Tuyen
authors.initials: TB
authors.lastname: Nguyen
authors.forename: Thi Ha
authors.initials: TH
authors.lastname: Vo
authors.forename: Thi Nho
authors.initials: TN
authors.lastname: Nguyen
authors.forename: Viet Hoa
authors.initials: VH
authors.lastname: Dai
authors.forename: Thi Hoang Anh
authors.initials: TH
authors.lastname: Phan
authors.forename: Huy Dung
authors.initials: HD
authors.lastname: Nguyen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Maxine
authors.initials: M
authors.lastname: Caws
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry; D024901:Drug Resistance, Multiple, Bacterial; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008403:Mass Screening / Q000379:methods; D008826:Microbial Sensitivity Tests / Q000379:methods; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis*; D014744:Vietnam
chemical_list: D000995:Antitubercular Agents; D003470:Culture Media; D007538:Isoniazid; D012293:Rifampin