Rapid diagnosis of sepsis in acutely ill children

Grant ID: EMPJ-378R27-2017

Project Summary

Life threatening bacterial infections such as sepsis are a leading cause of childhood mortality. International authorities recognise the urgent need for better recognition, diagnosis, and management of children with sepsis. Children in regional and remote settings are at particular risk for late or inaccurate diagnosis resulting in worse outcomes.

In this study, the researchers are testing the feasibility, performance, time-to-diagnosis, and cost impact of applying the most advanced genomics-based sepsis diagnostic tools. This could lead to better treatment of infections, reduce unnecessary antibiotic use, shorten hospital length of stay, improve patient outcomes, and allow patients and families to be managed closer to home, with the aim to provide the same care for all children around the state. We are recruiting acutely ill children presenting with suspected sepsis to Emergency Departments, including regional and remote centres in Queensland.

Outcomes

With seed funding from the EMF grant, the research team was able to establish the study and secure further research grants totalling over $3m. This includes a highly competitive 2020 grant from the Medical Research Future Fund (MRFF). Over 1200 children undergoing sepsis evaluation at the Queensland Children's Hospital, Gold Coast University Hospital, Townsville Hospital and Thursday Island Hospital have been recruited, building up a large observational paediatric sepsis cohort. The MRFF grant will enable the research team to recruit up to 1,500 patients in total and to perform further genomic and marker analyses.

The researchers used cutting-edge technology to demonstrate the capacity of gene transcription-based signatures to diagnose sepsis in children. They derived a signature of 10 gene transcripts which performed markedly better than both conventional blood test markers and previously published gene expression-based analyses. Additional analyses were performed comparing the performance of this novel signature to discriminate bacterial versus viral infection. In all of these analyses, the performance of the novel signature was superior to those previously published. These findings - once published - will help develop better tools for rapid sepsis recognition with higher diagnostic yield, and shorter time for test results to reach clinicians, and ultimately to faster and more appropriate care for paediatric patients with sepsis. The team will publish final results once recruitment has been completed.

RAPIDS was the first study in the field of infections in acutely/critically ill children in Queensland and further studies in this field will benefit from this development of a research network across paediatric sites in Queensland. The EMF grant was instrumental for the team to leverage further research funding that has helped boost innovative and translational research in Queensland.

Leveraged Funds

- Medical Research Future Fund, 2020: $2,406,970
- Children’s Hospital Foundation, 2020: $225,000
- Medical Research Future Fund, 2019: $249,937
- National Health and Medical Research Council (NHMRC), 2018: $348,495
- Australian Infectious Diseases Research: 2018, $50,000
- Townsville Hospital and Health Service, 2018: $24,000
- T for Thomas Foundation: 2018, $15,000
- Gold Coast University Hospital Foundation, 2017: $100,000
- Mater Foundation, 2017: $20,000
- Far North Queensland Hospital Foundation, 2017: $5000

Dissemination

- Gelbart, B., Schlapbach, L., Ganeshalingham, A., Ganu, S., Erickson, S., Oberender, F., Hoq, M., Williams, G., George, S. and Festa, M., 2018. Fluid bolus therapy in critically ill children: A survey of practice among paediatric intensive care doctors in Australia and New Zealand. Critical Care and Resuscitation, 20(2), p.131.

- Kawasaki, T., Shime, N., Straney, L., Bellomo, R., MacLaren, G., Pilcher, D. and Schlapbach, L.J., “Paediatric sequential organ failure assessment score (pSOFA): a plea for the world-wide collaboration for consensus”, Intensive care medicine, 2018; 44(6):995-997

- Leclerc, F., Duhamel, A., Leteurtre, S., Straney, L., Bellomo, R., MacLaren, G., Pilcher, D. and Schlapbach, L.J., “Which organ dysfunction scores to use in children with infection?”, Intensive care medicine, 2018; 44(5):697-698

- Schlapbach, L.J., MacLaren, G., Festa, M., Alexander, J., Erickson, S., Beca, J., Slater, A., Schibler, A., Pilcher, D., Millar, J. and Straney, L., 2017. Prediction of pediatric sepsis mortality within 1 h of intensive care admission. Intensive care medicine, 43(8), pp.1085-1096.

Conference presentation:
- ANZICS/ACCCN Intensive Care ASM, Oct 2017