Oxford leads £10m international study as resistance threatens new TB treatments

Researchers across five high-burden countries will track how resistance to newer drugs is emerging as tuberculosis continues to kill an estimated 1.23 million people a year

Oxford researchers are leading a £10m international programme to investigate growing resistance to some of the newest treatments for drug-resistant tuberculosis.

The RESPECT-TB project will bring together 15 research organisations, public health bodies and national TB programmes in India, Kazakhstan, Mozambique, South Africa and Vietnam.

The five-country study will examine how widespread resistance is to newer drugs used against drug-resistant TB, why it develops and how it affects patients, combining genetic sequencing of the bacteria with laboratory testing and clinical data.

The work comes after the introduction of six-month treatment regimens based on bedaquiline helped push cure rates for drug-resistant TB to around 90 per cent.

Researchers say resistance to the newer medicines is now beginning to emerge in countries with high levels of the disease, threatening gains made in treatment.

Tuberculosis remains the world’s leading infectious disease killer, accounting for an estimated 1.23 million deaths each year.

Professor Timothy Walker, Professor of Infectious Diseases at Oxford and coordinator of RESPECT-TB, said: “The introduction of bedaquiline-based treatment regimens has transformed care for people with drug-resistant tuberculosis but we are now seeing resistance to these medicines emerge in countries with high rates of the disease.

“RESPECT-TB will help us understand where resistance is emerging, how it develops and how we can preserve the effectiveness of these treatments.”

Professor Nazir Ismail, of the University of the Witwatersrand and South Africa’s National Health Laboratory Service, added: “RESPECT-TB is a powerful example of how global collaboration can accelerate our understanding of emerging drug resistance and its clinical impact.

“By bringing together expertise from across multiple regions we can generate critical evidence that guides global policy and helps protect the gains we have made against drug-resistant TB.”

The programme, funded by Wellcome and coordinated by the University of Oxford’s Nuffield Department of Medicine, will also strengthen laboratory facilities, genomic sequencing and surveillance in participating countries so emerging resistance can be identified more quickly.

RESPECT-TB will also create a major open-access collection linking Mycobacterium tuberculosis genomes with information on drug susceptibility and patient outcomes, allowing researchers to investigate why treatment succeeds in some patients and fails in others.

Dr Ana Cehovin, Research Lead at Wellcome, added: “Drug-resistance is continuously undermining decades of progress in tuberculosis treatment, and now threatens the new shorter, more effective bedaquiline-based regimens.”

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_{Main image: Mycobacteria Growth Indicator Tube samples fluoresce under ultraviolet light. The Oxford-led RESPECT-TB programme will combine laboratory drug-susceptibility testing with genomic and clinical data to track emerging resistance in tuberculosis. Credit: Mikael Häggström / Wikimedia Commons / CC0}