A Multi-Center Non-inferiority Evaluation of Hain GenoType MTBDRplus Version 2 and Nipro NTM+MDRTB line probe assays for the diagnosis of Rifampin and Isoniazid Resistance
2-phase study conducted in 2 supra-national reference laboratories to allow head-to-head comparisons of 2 new tests
Abstract
Introduction. Under 30% of MDR-TB patients are currently diagnosed due to laboratory constraints. Molecular diagnostics enable rapid and simplified diagnosis. Newer version line probe assays have not been evaluated against the WHO-endorsed GenoType® MTBDRplus (HainV1) for the rapid detection of rifampin (RIF) and isoniazid (INH) resistance.
Methods. A two-phase non-inferiority study was conducted in two supra-national reference laboratories to allow head-to-head comparisons of two new tests (HainV2, Nipro) to HainV1. In phase 1, results for 379 test strains were compared to a composite reference standard using phenotypic DST and targeted sequencing. In phase 2, results for 644 sputum samples were compared to phenotypic DST.
Results. Using a challenging set of strains in phase 1, sensitivity and specificity for HainV1, HainV2 and Nipro for RIF resistance detection were 90.3%/98.5%, 90.3%/98.5% and 92.0%/98.5% respectively and 89.1%/99.4%, 89.1%/99.4% and 89.6%/100.0% for INH resistance detection. Testing of sputa in phase 2 yielded a sensitivity and specificity of 97.1%/97.1%, 98.2%/97.8% and 96.5%/97.5% for RIF and 94.4%/96.4%, 95.4%/98.8% and 94.9%/97.6% for INH. Overall indeterminate rates were low but there was a higher rate of indeterminate results with Nipro compared to HainV1 and V2 in samples with low smear-grade.
Conclusion. Non-inferiority of HainV2 and Nipro to HainV1 was demonstrated for RIF and INH resistance detection in isolates and sputum specimens. These results support WHO endorsement of HainV2 and Nipro assays for MDR-TB detection.
Citation
Nathavitharana, R.R.; Hillemann, D.; Schumacher, S.G.; Schlueter, B.; Ismail, N.; Omar, S.V.; Sikhondze, W.; Havumaki, J.; Valli, E.; Boehme, C.; Denkinger, C.M. A Multi-Center Non-inferiority Evaluation of Hain GenoType MTBDRplus Version 2 and Nipro NTM+MDRTB line probe assays for the diagnosis of Rifampin and Isoniazid Resistance. Journal of Clinical Microbiology (2016) : JCM.00251-16. [DOI: 10.1128/JCM.00251-16]