06 November 2015 - WHO has approved the use of two alternative line probe assays (LPAs), with the capability to detect TB and rifampicin resistance. This follows the 2008 recommendation by WHO on the use of LPAs for the rapid detection of rifampicin resistance. At that time, the evidence assessed was for the LPA technology, Hain Version 1 assay.
Line probe assays are a rapid DNA based test which simultaneously confirm the presence of TB and detect resistance to rifampicin.
The two LPAs are: GenoType® MTBDRplus assay, Hain Lifescience (Hain Version 2 assay)
Hain Lifesciences have developed an updated version of their MTBDRplus line probe assay. The Hain Version 2 assay allows for the identification of M. tuberculosis complex, and incorporates rpoB probes for rifampicin resistance detection as well as katG probes and inhA probes for the determination of isoniazid resistance.
Nipro Assay, Nipro Corporation
Nipro Corporation, Japan has developed an LPA that is similar to that of Hain Lifesciences (Nipro assay). This assay allows for the detection of rifampicin and isoniazid conferring mutations, the identification of M. tuberculosis complex and the identification of some common nontuberculous mycobacteria including M. avium, M. intracellulare and M. kansasii.
FIND study on diagnostic accuracy of the assays
For new versions of technologies that WHO has already recommended, WHO requires a head-to-head comparison with the existing technology. Hain Version 1 assay was used as the head-to-head comparison for the new assays to demonstrate their equivalent performance.
In 2014 and 2015, FIND coordinated a multi-center, blinded cross-sectional study of the diagnostic accuracy of these two newly-available tests, to compare their performance against that of the Hain Version 1 assay. A composite reference standard including phenotypic drug susceptibility testing (DST) and DNA sequencing was used. The study had two phases. Phase 1 was designed to evaluate the performance of the newer assays on a wide range of clinical isolates and Phase 2 to evaluate their performance on sputum specimens from patients with pulmonary TB.
The study demonstrated equivalence of the newer LPA assays (Hain Version 2 and Nipro) with the Hain version 1 assay. These assays showed comparable performance for the detection of M. tuberculosis and rifampicin resistance conferring mutations in acid-fast bacilli (AFB) smear-positive samples and isolates of M. tuberculosis. Details of the study are available here.
Based on the outcomes of the FIND-coordinated study, WHO extends its recommendations for the use of Hain Version 1 assay to the Hain version 2 and Nipro assays, for the rapid detection of rifampicin conferring mutations in AFB smear-positive samples and positive cultures. This recommendation does not apply to other LPAs available on the market. WHO does not recommend the use of LPAs in AFB smear-negative samples.
In 2016, WHO will update current policy recommendations for the use of LPAs and review new evidence about the clinical utility of the Hain Lifescience GenoType MTBDRsl assay in detecting resistance to second-line drugs.
World Health Organization
Global TB Programme
20, Avenue Appia, CH-1211, Geneva, Switzerland
Tel: (+41) 22 791 4695
For more information please go to www.who.int/tb