The World Health Organization supports the use of targeted sequencing, including a test under development from Oxford Nanopore, to detect drug resistance in tuberculosis

The rapid test being developed by Oxford Nanopore, in collaboration with the Quadram Institute Bioscience (QIB), is one of three sequencing-based tests for TB supported by the WHO in a significant step in the global fight against infectious disease.

The World Health Organization (WHO) has announced that a rapid sequencing solution being developed by Oxford Nanopore meets the class-based performance criteria to detect drug resistance after TB diagnosis, to guide clinical decision-making for drug-resistant TB treatment. This is among the first sequencing-based tests to be supported by the WHO in the field of TB – and a significant milestone in the fight against one of the most persistent threats in public health globally.

Drug-resistance remains a major barrier in global efforts to curb the spread of TB, which was the world’s second leading infectious killer after COVID-19 in 2021, according to the WHO. Today, TB remains one of the deadliest diseases in the world, with an estimated 10 million reported new cases in 2020, 1.5 million deaths and three million undiagnosed patients.

The lack of rapid, accessible, and information-rich tests for drug-resistant TB (DR-TB) has stymied progress in combatting the disease by making it harder to successfully control and treat. Major healthcare organisations and non-profits have identified sequencing-based drug resistance tests as a priority.

In 2019, the Foundation for Innovative New Diagnostics (FIND), a global non-profit, launched the Seq&Treat programme, funded by Unitaid and in collaboration with WHO, to investigate whether DR-TB detection could be improved by introducing and accelerating the uptake of targeted next-generation sequencing solutions in clinical settings.

The FIND study investigated Oxford Nanopore’s rapid, end-to-end sequencing test (in development), which identifies mutations associated with drug-resistance across the TB genome in DNA extracted from sputum within as little as five hours. The test, which allows flexible sample batching and can be performed rapidly, includes worldwide exclusively licensed technology from the Quadram Institute Bioscience (QIB). The evaluation was carried out in two phases, culminating in the successful completion of Phase II in May which included clinical samples in India, South Africa and Georgia.

Success in this final stage of the Seq&Treat study and support from the WHO confirms that the Oxford Nanopore sequencing solution meets the diagnostic performance criteria outlined in the NGS Target Product Profile (TPP) established by FIND/WHO for clinical diagnosis of drug resistant TB.

The Oxford Nanopore sequencing test is in active development on a pathway to pursuing regulatory approval. In April, Oxford Nanopore announced a strategic partnership with bioMérieux, a world leader in the field of in vitro diagnostics, to develop innovative infectious disease diagnostics. This includes collaboration on market access and deployment of the TB Drug Resistance assay.

Once complete (and consistent with WHO guidelines and applicable law) this test is anticipated to offer countries in which TB remains a persistent public health threat a faster, accessible option to detect drug resistance in patients. Rapid and comprehensive detection of resistance directly from patient samples is required to initiate appropriate therapy, thereby improving patient outcomes and reducing the spread of DR-TB.

Gordon Sanghera, CEO Oxford Nanopore Technologies, commented:

“For the first time, a sequencing-based test has been supported by the WHO in the field of TB. This is a watershed moment in the fight against a serious threat to public health and, over time, could stop the spread of drug-resistant TB through faster, more accessible diagnostics. We’re excited to receive the WHO’s support, and we look forward to working with our partners to bring this test to market.”

Professor Ian Charles, Director of Quadram Institute Bioscience, commented:

"The growth of drug resistant TB is a major global public health concern and innovative and accurate solutions that deliver benefits at the point of care are needed urgently. It’s very satisfying to see the results of these Phase II trials and to see how licensed technology from research undertaken at the Quadram Institute has supported the development of this new diagnostic tool to combat TB. We look forward to seeing its deployment in those areas of the world where it will deliver real life-saving impact.”

Results of the FIND Study

• The nanopore-based targeted sequencing solution succeeded in the Phase II analytical evaluation by reaching or surpassing the FIND’s main performance criteria, including:

• Sensitivity (>94%) and specificity (>99%) for detection of Tier 1 drug resistance

• A very low failure rate, providing results for almost 80% of smear negative cases

• The WHO supports the targeted next generation sequencing (tNGS) as a new class of rapid test for DR-TB detection.

• Out of three tests assessed, the Oxford Nanopore solution is one of two tests supported within this tNGS class for testing resistance to Tier 1 drugs (rifampicin, isoniazid, fluoroquinalones), amikacin, linezolid and streptomycin.

Drug Resistant TB – fast facts

• Today, TB remains one of the deadliest diseases in the world, with an estimated 10 million reported new cases in 2020, 1.5 million deaths and three million undiagnosed patients.

• Multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) are a major threat to TB control as they represent roughly 10% of diagnosed cases

• Only about one in three people with drug DR-TB accessed treatment in 2020 leaving the majority of DR-TB patients without access to appropriate care and treating affected patients is 50 to 200 times more expensive than patients with drug sensitive TB.

The WHO ‘Use of targeted next-generation sequencing to detect drug-resistant tuberculosis’ is available here.