TB samples being tested at John Radcliffe Hospital. Image credit: NIHR Oxford Biomedical Research Centre.
UK-led study marks shift towards genetic era in tackling TB
26 Sep 2018
A landmark study, part-funded by the MRC, may herald a quicker, more tailored treatment for the millions of people around the world living with tuberculosis (TB). UK researchers have shown how our understanding of TB’s genetic code is now so detailed that we can predict which commonly used anti-TB drugs are best for treating a patient’s infection and which are not.
The study is by far the largest of its kind, covering over 10,000 TB genomes from 16 equal partner countries around the globe. Its full findings were published Wednesday in the New England Journal of Medicine, and announced at the United Nations General Assembly high-level meeting on tuberculosis.
The study was led by the international CRyPTIC consortium based at the University of Oxford and facilitated by the United Kingdom government’s 100,000 Genomes Project. It revealed a much greater accuracy in predicting the susceptibility of the bacterium to anti-TB drugs than had been expected.
The lead investigator, Dr Tim Walker, Academic Clinical Lecturer in Microbiology and Infectious Diseases at the University of Oxford, said: “This study represents a paradigm shift away from a dependence on testing drugs against bacteria in culture and towards the genetic era.
“With ever-faster and more portable DNA sequencing technologies being developed, this advance means that we are now much closer to delivering tailored therapy to TB patients around the world whose treatments have so far been largely based on a ‘best guess’. Giving the correct drugs to more patients will improve cure rates and help stop the spread of drug-resistant strains.”
Dr Jonathan Pearce, Head of Infections and Immunity at the MRC, said: “The results of this study represent an important step forward for rapid clinical decision-making and antibiotic stewardship for TB treatment, and also provide a potential precedent for a sequencing approach for other pathogens.”
Tuberculosis remains the world’s biggest infectious disease killer, claiming 1.7 million lives in 2016. The number of drug-resistant cases is rising, meaning new strategies and interventions are urgently needed if the World Health Organization’s (WHO) target to end the global TB epidemic by 2035 is to be met.
One of the key interventions for achieving this target – and saving millions of lives - is getting the correct drugs to patients in a timely manner.
Since TB-antibiotics were first introduced 70 years ago, tests to determine which antibiotics will best treat an individual patient have depended on growing the bacteria in a laboratory, a process that takes weeks or even months. These difficult and slow tests remain out of reach for most of the world’s TB patients, leaving many on the wrong combination of drugs and with a reduced chance of cure and survival.
It is estimated that only 22% of an estimated 600,000 patients requiring treatment for multi-drug-resistant tuberculosis received diagnoses and were treated in 2016, which has facilitated the spread of multidrug-resistant strains.
The improved knowledge of the genomic variations of TB should lead to more accurate PCR tests for the disease.
The results of this study have already led to decisions in England, the Netherlands and by the Wadsworth Centre for Public Health, New York State, to reduce reliance on bacterial culture and deliver treatment according to DNA sequencing results alone.
The international research was funded by the MRC, the UK Department of Health and Social Care through the National Institute for Health Research, Public Health England and the 100,000 Genomes Project, MBL's European Bioinformatics Institute (EMBL-EBI), the Wellcome Trust, and the Bill and Melinda Gates Foundation.
This paper is available on Europe PMC.