Application of rapid nanopore metagenomics sequencing for the diagnosis of prosthetic joint infection (OGradyU16ORUK)
The commonest cause of prosthetic joint failure is aseptic loosening, followed by prosthetic joint infection (PJI). We hypothesise that infection is under-diagnosed in patients undergoing prosthetic joint replacement surgery and that ‘aseptic loosening’ may often be caused by occult microbial infection. The PhD student will use modern molecular diagnostic methods, with a focus on metagenomics, to analyse the synovium, synovial fluid and periprosthetic tissue around implants, replaced due to aseptic loosening, for evidence of infection not detectable by conventional methods. This will provide data on the sensitivity of our methods compared to current microbiological methods and on the commonest occult PJIs. Ultimately, we will develop rapid molecular diagnostics methods for the routine analysis of prosthetic joint failure caused by loosening that comprehensively rule out infection.
1. To develop efficient nucleic acid extraction methods for the detection of microbes in TJA revision diagnostic samples
2. To develop and optimise 16S/18S rRNA and whole genome shotgun metagenomics sequencing methods to detect and identify microorganisms in these samples
3. To prospectively test 150 aseptic loosening samples and controls using the developed molecular methods and define the percentage of loosening cases truly caused by occult microbial infection at the Norfolk and Norwich University Hospital (working with co-supervisor Professor Iain McNamara).
4. To develop the novel molecular methods into routine tests for the investigation of PJI and ‘aseptic loosening’.
The novel diagnostics will ensure that appropriate antibiotic treatment can be administered, improving surgery success rates, reducing patient mortality and reducing hospital stays.
Our labs are situated in the new Norwich Medical School building at UEA where we have state of the art molecular diagnostics and NGS facilities including MinION, PromethION, NextSeq and MiSeq devices. We are currently funded by the NIHR, MRC, ORUK, Rosetrees Trust and industry partners.