A non-invasive "liquid-biopsy" for Kingella kingae infections in children using cell-free DNA

PhD Scholarship
KATHARINA WOLF

 

Katharina Wolf v3
Principal Investigator
Katharina Wolf
University of Otago
Public Contact
Kim Thomas
teniwhacomms@otago.ac.nz
Project Timeframe/Status
-
In Process

Whakarāpopoto Rangahau Summary of Research

Acute osteoarticular infections (OAI) pose a significant threat to Australasian children with reported infections rates higher than in other OECD countries. Improved culture techniques and sensitive nucleic acid amplification assays have resulted in recognizing Kingella kingae as the leading cause in young children. Early identification of the disease-causing pathogen improves patient prognosis and reduces treatment duration and the possibility of long term sequalae. About 1/3 of cases have no microbiological diagnosis with current gold standard polymerase chain reaction (PCR) and culture. Blood cultures are routinely performed but less sensitive compared to culture from joint aspirates, however these are not routinely carried out due to their invasiveness.  

Our group are developing a liquid biopsy assay to detect K. kingae cell-free DNA (cfDNA) in a patient’s blood and urine. Pathogenic cfDNA can be concentrated from urine using K. kingae specific probes coupled to magnetic beads. The captured cfDNA can then be amplified and quantified with real-time PCR. This novel diagnostic assay can be routinely implemented leading to more targeted antibiotic treatment for OAI patients. It also has the potential to be a foundation for the detection of other infectious diseases, following development of specific primers and probes for different pathogenic microorganisms. 

Te Hiranga a Rangahau Research Impact

The overall impact of this project will be to improve the diagnosis of currently hard-to-diagnose infections. Both platforms can be used within a laboratory setting without disrupting current workflows. The platforms will allow for faster diagnosis which will improve antimicrobial stewardship as doctors may not need to start empirical treatment. The ability for these two platforms to be utilised in remote areas either within Aotearoa or in the Pacific is promising. A non-invasive diagnostic platform will be a significant advance, especially in diagnosing disease in tamariki where obtaining invasive samples can be very difficult.

Te Niwha

Kairangahau Research Personnel

Dr Amy Scott-Thomas
Department of Pathology and Biomedical Science - University of Otago | Primary Supervisor
Professor Stephen Chambers
Department of Pathology and Biomedical Science - University of Otago | Supervisor
Professor Tony Walls
Department of Paediatrics - University of Otago | Supervisor
Trevor Anderson
Microbiology Department - Canterbury Health Laboratories | Supervisor