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Multicenter Study of the Accuracy of the BD MAX MDR-TB Assay for Detection of M. tuberculosis Complex and Mutations Associated with Resistance to Rifampin or Isoniazid
Tuberculosis (TB) causes more than 8 million cases and 1.3 million deaths per year. Over 95% of new TB cases and deaths occur in developing countries. Culture is the gold standard for TB detection, but remains restricted to higher levels of the health infrastructure because of expertise and equipment requirements. Furthermore, it takes weeks to obtain a result as to whether M. tuberculosis is present or absent, plus additional weeks to obtain information about drug resistance. Smear microscopy is still the most widely used up-front diagnostic in most countries, but only detects about half of TB cases. Two molecular tests, namely the Xpert® MTB/RIF assay on the GeneXpert platform (Cepheid, Sunnyvale, CA) and the GenoType® MTBDRplus (Hain Lifescience, Nehren, Germany) have been commercialized and are used in some TB-endemic settings, but each of these tests has important limitations in addition to their attributes. The Xpert® MTB/RIF assay is fully integrated and automated and is appropriate for near-care, but has limited throughput and tests for resistance mutations associated only with rifampin but not isoniazid. The GenoType® MTBDRplus test can detect mutations associated with isoniazid and rifampin resistance, but has sub-optimal sensitivity for M. tuberculosis complex detection, is not fully integrated or automated, and has a turn-around time of at least several hours. In the TB diagnostics field there is a need for products that, in aggregate, cover a range of performance profiles suitable for the realities of tiered healthcare systems that include specimen testing at point-of-care as well as in more centralized laboratories.
The BD MAX™ MDR-TB assay, performed on the BD MAX™ System (both from Becton Dickenson), is an automated qualitative in vitro diagnostic test for the direct detection of Mycobacterium tuberculosis complex DNA in raw sputum or concentrated sputum sediments prepared from induced or expectorated sputa. In specimens where M. tuberculosis complex DNA is detected, the BD MAX™ MDR-TB assay also detects mutations of the rpoB gene associated with rifampin resistance as well as mutations in the katG gene and inhA promoter region both of which are associated with isoniazid resistance. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and fluorogenic target-specific hybridization probes to detect M. tuberculosis complex DNA as well as the DNA associated with mutations in the rpoB and katG genes and the inhA promoter region associated with multidrug resistant TB (MDR-TB). The BD MAX™ MDR-TB assay is intended for use with specimens from patients for whom there is clinical suspicion of tuberculosis (TB) and who have not received anti-tuberculosis therapy, or less than three days of anti-tuberculosis therapy in the past six months. The BD MAX™ MDR-TB assay is automated and integrated, and requires a stable source of electricity; 24 specimens can be tested in one run, and turn-around time from the testing start to result is 4 hours. Therefore the BD MAX™ MDR-TB assay is expected to be most suitable for use in central laboratories in which large numbers of specimens are tested and minimal operator hands-on time is desirable.
To evaluate the performance of the BD MAX™ MDR-TB assay for the detection of Mycobacterium tuberculosis complex, and to determine whether M. tuberculosis complex detected is resistant to rifampin and to isoniazid from raw sputum or concentrated sputum sediments prepared from induced or expectorated sputa collected from patients with symptoms of pulmonary tuberculosis (TB) in a clinical setting.
- To estimate the positive and negative predictive values (PPV and NPV) of the BD MAX™ MDR-TB assay.
- To estimate the rate of non-reportable results for the BD MAX™ MDR-TB assay.
- To determine the reproducibility between sites of the BD MAX™ MDR-TB assay.
- To assess end-user experience with the BD MAX™ workflow via a usability survey of study laboratory staff.
This is a multicountry research effort being conducted in India, Kenya, Peru, South Africa, and Uganda.