Tuberculosis sufferers will be able get drug treatment sooner thanks to a new whole genome sequencing technique to determine for the first time which drugs to give sufferers, researchers in Oxford have reported.
University of Oxford researchers at the John Radcliffe Hospital have developed a genetic test – details of which are published online in the Lancet Infectious Diseases – that can detect which drugs will effectively treat people with the disease and those that will not.
Tuberculosis sufferers will be able get drug treatment sooner thanks to a new whole genome sequencing technique to determine for the first time which drugs to give sufferers, researchers in Oxford have reported.
University of Oxford researchers at the John Radcliffe Hospital have developed a genetic test – details of which are published online in the Lancet Infectious Diseases – that can detect which drugs will effectively treat people with the disease and those that will not.
From 1948, the only way to test for drug resistance was to run laboratory tests on sufferers’ sputum, a process which could take up to six weeks, delaying potentially lifesaving treatment.
In the last two decades genetic tests targeted at small sections of the TB DNA have been able to tell doctors what drugs to rule out.
However, medics would still carry out time-consuming laboratory test to be sure of their results. The new test studied the whole TB genome – its entire DNA code – to identify mutations that cause drug resistance and those that don’t.
It means doctors will be able to rule out but also, for the first time, rule in which drugs to give to sufferers without the need for a lengthy laboratory culture test. This will speed up diagnosis of sufferers, particularly in developing countries where TB rates are highest, so they get the right drugs sooner. The test is being trialled in the Midlands by Public Health England and, if successful, it is hoped it will be rolled out across the country.
The new technique also means new mutations in TB DNA can be identified and added to an ever expanding catalogue of mutations that have been characterised as either causing drug resistance or not.
The two and a half year study is the biggest ever of its kind and comprised more than 3,600 samples from the UK, including Oxford, Germany, Uzbekistan, Sierra Leone and South Africa.
It was led by the NIHR Oxford Biomedical Research Centre (BRC), based at Oxford’s Churchill Hospital; Public Health England; the German Centre for Infection Research in Borstel, and the South African National Institute for Communicable Diseases.
Most patients with TB live in low-income countries where the basic laboratory facilities required to perform culture are often lacking.
Misdiagnosing drug resistance risks onward transmission and patient deaths but there are hopes the test can be developed into an affordable, hand-held device for use around the world.
Lead investigator Professor Tim Peto, of the Oxford BRC and a consultant in infectious diseases at the Churchill and John Radcliffe Hospital, said: “This is the beginning of the end for routine laboratory culture for TB drug resistance.
“We are moving from 130 years of culturing TB to a new digital era in microbiology. It is particularly exciting for low-income settings where the lack of laboratories currently leads to under diagnosis of drug resistance. These results pave the way for mobile genetic sequencing technologies to bypass such obstacles to better patient care.”
“This work provides the foundation for a new era in TB diagnostics.”
Co-investigator Prof. Stefan Niemann, leading the Molecular Mycobacteriology Unit at theResearch Center Borstel, described the findings as “a paramount change opening the way to treat multi-drug resistant TB patients better”.
There are about nine million global TB cases each year and 1.5-million deaths. There were 7,892 UK cases in 2013 with up to 334 deaths in 2012.
A multi-drug resistant strain of the disease affects about 480,000 people globally, for which treatment can last two years and lead to side effects including nausea, deafness, liver toxicity and psychosis.
The World Health Organization (WHO) aims to stop TB by 2035, a target that will not be met without improvements in the diagnosis of drug resistance.
