To mark the centenary of Franz Kafka’s death from laryngeal tuberculosis at the age of 40 in June 1924, the University of Oxford ran a series of events, including talks, an exhibition and a public reading of the Metamorphosis in the Sheldonian Theatre.
It is believe he lived with tuberculosis for the last 7 years of his life and it likely affected his writings, including works such as The Hunger Artist. In recognition there was a public talk on 5 June 2024 entitled “Tuberculosis: vaccines, diagnostics and experience” with contributions on vaccines by Professor Helen McShane and diagnostics by one of our Unit, Dr Philip Fowler.
The highlight however was hearing the experience of someone who had been diagnosed with tuberculosis about 20 years and how, despite, surviving this ancient disease, it has profoundly affected how she lives day to day.
You can hear the CRyPTIC Principal Investigator, Prof Derrick Crook, talking about the project and its impact on tuberculosis on News Hour on the BBC World Service here. The segment starts about 35 minutes in. You will need a BBC login so this link may not work for everyone.
The CRyPTIC project, which is coordinated by us (Derrick Crook is the Principal Investigator) has released the largest ever global study of tuberculosis aimed at identifying all the genetic variants responsible for antibiotic resistance.
The Comprehensive Resistance Prediction for Tuberculosis International Consortium (CRyPTIC) research project has collected the largest ever global dataset of clinical M. tuberculosis samples from across the world consisting of 15,211 samples from 27 countries on five continents.
Using two key advances: a new quantitative test for drug resistance and a new approach which identifies all the genetic changes in a sample of drug-resistant TB bacteria the researchers have generated a unique dataset which the team has used to quantify how changes in the genetic code of M. tuberculosis reduce how well different drugs kill these bacteria that cause TB. These innovations, combined with ongoing work in the field, promise to profoundly improve how patients with TB are treated in the future.
Tuberculosis kills more people each year than any other bacterium, virus, or parasite, except for SARS-CoV-2. Although it is treatable, drug resistance has emerged as a major problem over the past 3 decades. Testing for mutations in the M. tuberculosis genome to determine which drugs will give a patient the best chance of cure is the most realistic way of getting drug resistance testing to every patient who needs it.
“This innovative, large-scale, international collaboration has enabled us to create possibly the most comprehensive map yet of the genetic changes responsible for drug resistance in tuberculosis.”
Dr. Derrick Crook, Professor of Microbiology at the University of Oxford.
In a series of nine new preprint manuscripts, each documenting a different aspect of how the CRyPTIC project has advanced the field, the researchers reveal:
How individual mutations, and combinations of mutations, can be related not just to blunt measures of ‘resistance’ or ‘susceptibility’, but also to even minor changes in the way a drug kills M. tuberculosis, thereby reducing the effectiveness of treatment with special attention being paid to two novel compounds being used to treat tuberculosis.
These results aim to help improve control of tuberculosis and facilitate the World Health Organisation’s end TB strategy through better, faster and more targeted treatment of drug-resistant tuberculosis via genetic resistance prediction, paving the way towards universal drug susceptibility testing (DST).
“Our ultimate goal is to achieve a sufficiently accurate genetic prediction of resistance to most anti-tuberculosis drugs, so that whole genome sequencing can replace culture-based DST for TB. This will enable rapid-turnaround near-to-patient assays to revolutionise MDR-TB identification and management.”
Professor Derrick Crook
The data, which are now freely available, can be used by the wider scientific community to improve our understanding of drug resistance in TB and how to best treat this important disease.
