Open Access Research article

Evaluation of microscopic observation drug susceptibility assay for diagnosis of multidrug-resistant Tuberculosis in Viet Nam

Dang Thi Minh Ha12*, Nguyen Thi Ngoc Lan1, Marcel Wolbers2, Vo sy Kiet2, Hoang Thi Thanh Hang2, Nguyen Hong Duc1, To My Huong1, Vuong Minh Bach1, Nguyen Thi Phuong Thao1, Tran Van Quyet1, Nguyen Thi Bich Tuyen1, Vo Thi Ha1, Nguyen Thi Nho1, Dai Viet Hoa1, Phan Thi Hoang Anh1, Nguyen Huy Dung1, Jeremy Farrar2 and Maxine Caws2

Author affiliations

1 Pham Ngoc Thach Hospital, 120 Hung Vuong, District 5, Ho Chi Minh City, Viet Nam

2 Wellcome Trust Major Overseas Programme and Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, District 5, Ho Chi Minh City, Viet Nam

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Citation and License

BMC Infectious Diseases 2012, 12:49  doi:10.1186/1471-2334-12-49

Published: 1 March 2012

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.

Conclusion

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.

Keywords:
MDR-TB; Tuberculosis; MODS; Diagnosis