Comparative accuracy of the REBA MTB MDR and Hain MTBDRplus line probe assays for the detection of multidrug-resistant tuberculosis: A multicenter, non-inferiority study.
BACKGROUND
Despite recent diagnostic advances, the majority of multidrug-resistant tuberculosis (MDR-TB) cases remain undiagnosed. Line probes assays (LiPAs) hold great promise to curb the spread of MDR-TB as they can rapidly detect MDR-TB even when laboratory infrastructure is limited, yet few of these assays are currently widely available or supported by World Health Organization (WHO) policy.


METHODS
The aim of this prospective, blinded, non-inferiority study was to compare the performance of YD Diagnostics REBA MTB MDR LiPA (YD) to the WHO-endorsed Hain MTBDRplus V1 LiPA (Hain V1) for the detection of rifampicin and isoniazid resistance. In phase 1, YD and Hain V1 diagnostic performance was assessed with selected culture isolates and results were compared to phenotypic drug susceptibility testing (DST) results and targeted sequencing data. In phase 2, both assays were tested on processed sputum samples and results were compared to phenotypic DST results.


RESULTS
In phase 1, YD did not achieve non-inferiority to Hain V1. For isoniazid resistance detection, Hain V1 had a sensitivity of 89% (95%CI 83.8-93%) and specificity of 99.4% (95%CI 96.9-100%). While YD had a similar sensitivity of 92% (95%CI 87.3-95.4%), the specificity was inferior at 92.6% (95%CI 87.6-96%). For rifampicin resistance detection, Hain V1 had a sensitivity of 90.2% (95%CI 84.8-94.2%) and specificity of 98.5% (95%CI 95.7-99.7%) while YD had an inferior sensitivity of 72.4% (95%CI 65.1-78.9%) and a comparable specificity of 98% (95%CI 95-99.5%). Similar results were observed in phase 2. For MDR-TB detection, the sensitivity and specificity of Hain V1 was 93.4% (95%CI 88.2-96.2%) and 96.2% (95%CI 88.2-96.8%), respectively, compared to 75.7% (95%CI 68-82.2%) and 92% (95%CI 88.2-94.9%) for YD.


CONCLUSIONS
YD did not achieve non-inferiority with Hain V1. Further improvements and repeat evaluation of YD is necessary prior to recommending its use for clinical settings.
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Joshua
J
Havumaki
National Reference Laboratory for Mycobacteria, Forschungszentrum Borstel, Borstel, Germany.
Doris
D
Hillemann
Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa.
Nazir
N
Ismail
Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa.
Shaheed Vally
SV
Omar
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Sophia B
SB
Georghiou
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Samuel G
SG
Schumacher
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Catharina
C
Boehme
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Claudia M
CM
Denkinger
D000995:Antitubercular Agents / Q000627:therapeutic use*; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D012293:Rifampin / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy
D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin