The Xpert MTB/XDR test developed by the Foundation for Innovative New Diagnostics (FIND) and Cepheid Inc. quickly indicates whether a patient has a dangerous – and rapidly increasing – strain of multidrug resistant tuberculosis (TB). The new test enables clinicians to return results in 90 minutes and see immediately whether the pathogen would respond to standard first- or second-line therapies.

TB killed 1.5 million people across the globe last year. Inappropriate treatment has driven a rapid rise in cases of multidrug- (MDR TB) and extensively drug-resistant tuberculosis (XDR TB).

MDR and XDR forms of TB remain relatively rare in the U.S., but they are very costly, with the MDR TB treatment running about $150,000 per case and XDR TB costing more than $482,000 per case, according to the U.S. CDC. For best outcomes, both types require prompt diagnosis. That’s hampered by current tests that can be very complex and may take as long as 16 weeks to return results.

"An ordinary TB diagnosis is awful, but XDR-TB is the worst nightmare of every TB doctor and every patient," said Catharina Boehme, CEO of FIND. "Recent treatment advances are already making a huge impact, but for the best chances of survival, patients need to be able to start on treatment as soon as possible – and the only way for that to happen is through rapid diagnosis. By providing test results in just a few hours, the Xpert MTB/XDR test will save lives."

In 2017, about 558,000 people developed TB that was resistant to first-line drugs, and 82% of those individuals had a strain of MDR TB. About 13,000 people contracted XDR TB in 2018, based on WHO estimates, and some groups of those patients had mortality rates in excess of 40%.

The technology

Xpert MTB/XDR uses Cepheid’s recently developed 10-color technology to detect multiple mutations across several genes from a single sample.

“Adding four novel dyes allows for multiplex detection of 10 independent targets in a single reaction – which compared to splitting the sample to accomplish multiplexing delivers much higher sensitivity,” a Cepheid spokesperson told BioWorld. “Additionally, the upgraded 10-color Genexpert modules enable the use of 10 different fluorescent channels at the same time in a single Xpert cartridge. Thus, the melt-curve analysis in a single cartridge is about to identify mutations in eight different genes associated with drug resistance.”

The test can detect resistance to isoniazid, ethionamide, fluoroquinolones, amikacin, kanamycin and capreomycin, which are considered the key resistances in both forms of TB. To preserve the effectiveness of drugs against MDR and XDR TB, patients must be tested for resistance to fluoroquinolones and second-line injectables prior to initiation of the therapies.

The Xpert test can be run on any Genexpert system with a 10-color module. About 25,000 are currently available worldwide, with a significant percentage in high-burden and rural clinics, according to the Cepheid spokesperson.

Future steps

The Xpert MTB/XDR test has CE mark and launched in Europe in June. Cepheid is working with FIND, as well as David Alland and his team at Rutgers University to prepare data for the test’s dossier for review by WHO. Cepheid hopes to have WHO endorsement by the end of the year.

WHO has set a goal of reducing new cases of TB by 80% and TB deaths by 90% by 2030. As part of its aim to end TB, WHO established 10 priorities, which included testing 90% of new and relapsed patients with WHO-recommended rapid tests at the time of diagnosis and coverage of drug susceptibility testing for all TB patients.

"Rapid testing of resistance to isoniazid and fluoroquinolones is a critical step towards ensuring those who are ill with drug-resistant TB, and in particular XDR-TB, can access treatment and care early – in line with the latest WHO guidelines on the treatment of drug-resistant TB," said Tereza Kasaeva, director of the WHO Global TB Program. "WHO is looking forward to receiving all relevant data on the Genexpert MTB/XDR cartridge from Cepheid and partners to rapidly proceed with an evaluation of the new test."

“If the test is recommended for use by WHO, countries could include it in their national policies and accelerate its scale up – particularly in high-burden tuberculosis countries such as India and China,” Cepheid’s spokesperson noted.

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