A new metagenomic test developed by researchers at UCL and Great Ormond Street Hospital for Children (GOSH) is providing clinical teams around the country with vital information about rare infections - allowing for patients to access targeted treatments they desperately need.
The test was developed as a collaboration between researchers at UCL, the GOSH Microbiology department and clinical teams at GOSH, led by Professor Judith Breuer (UCL Great Ormond Street Institute of Child Health and GOSH). It is delivered through the GOSH Metagenomics Service.
Its success has been highlighted as the team were able to identify a bacterial infection in a patient's eye that had been plaguing her for over five years.
All previously available testing had been unable to identify a cause for Ellie's eye problems, leaving her considering having her eye removed. However, thanks to the test, the GOSH metagenomics team were able to identify a rare bacterial infection.
And, after a course of targeted antibiotics, Ellie's symptoms began to clear - restoring her eyesight in time for her wedding earlier this year.
Ellie said: "I will never be able to thank the teams that continued to fight to find answers for me enough. Metagenomics has truly been game-changing for me. I spent Boxing Day of 2023 in hospital, thinking about whether it was time to have my eye removed.
"Now, I can't even imagine being back in that place, I am able to get back to focusing on my life - being able to have that for my wedding day is a priceless gift."
Metagenomics is a cutting-edge sequencing genomic technique that allows for the identification of bacteria and other types of infections, and viruses directly from patient samples.
Metagenomics is untargeted, meaning it can look for all types of infections, rather than specific infections.
The testing service, led by Professor Breuer, is the first in the UK to receive accreditation from the UK Accreditation Service (UKAS). It was established to investigate the benefits of this type of sequencing in infections within 'sterile sites' where infectious agents are normally not present - such as the brain, the central nervous system, the liver or, as in Ellie's case, in the fluid behind the eye.
Professor Breuer said: "We have been developing our metagenomics service at GOSH and UCL for over 10 years now and we are incredibly proud to be the first UK accredited service.
"We are now able to offer this vital genomic testing to patients around the country, and it is amazing to see the impact it is already having for patients like Ellie."
The team have worked collaboratively with clinicians at GOSH and across the country to develop a diagnostic standard of test ensuring it is available to patients. Currently, the service is used as a final test, when clinicians suspect an infection, but traditional diagnostic techniques have not been able to identify the pathogen. Even where no pathogen is identified, a negative test gives the clinical team confidence to stop antimicrobials or administer strong drugs to suppress inflammation.
Dr Julianne Brown (GOSH) said: "Being part of the GOSH metagenomics service, since its origins, has meant I have had the privilege of watching it grow from research to an established, accredited clinical service that tests 6 samples a week for patients across the country. It is only thanks to the collaboration between dedicated scientists and clinical teams that a service like this is possible."
Ellie first began experiencing problems with her right eye in early 2019, whilst a medical student.
After initial tests she was diagnosed with uveitis, a condition that causes inflammation of the eye. Initially this was felt to be autoimmune, whereby the body's own immune system mistakenly attacks the eye. As such Ellie was initiated on immunosuppressant medications to try and reduce the inflammation.
Despite continued treatment, Ellie's symptoms continued to worsen. The inflammation and steroid treatment resulted in her developing a cataract in her affected eye which required surgery. At its worst she was having monthly infusions, daily tablets and was having to apply hourly steroid eye drops. Her condition was not behaving as expected but all tests looking for any infections had come back negative.
She said: "I had really just reached my breaking point; my team had tried every test to find a cause and the intensive treatments and multiple appointments were severely impacting my life. I had got to the point that I began to discuss with my team my wish to have the affected eye removed."
After learning about the metagenomic sequencing available, her clinical team at Moorfields Eye Hospital NHS Foundation Trust (Moorfields), worked with the metagenomics team to have a sample from Ellie's eye tested. The sequencing revealed Ellie had a very specific strain of Leptospirosis, a bacterial infection, in her eye which was the cause of all her inflammation.
Ellie was given a 3-week course of antibiotics and the infection completely cleared, she was able to begin weening herself off her steroid eye drops and in March was able to celebrate her wedding day - eye drop and infection free.
Ellie said: "I remember the moment so vividly; it was a Thursday evening and I had multiple calls from my team at Moorfields. This was so close to the end of the line for me, I never expected to get a positive result and so when they told me they had found a treatable infection it really changed my life. No words can express my gratitude to the teams who helped me get the answers I needed and never gave up on me."
While the metagenomics service at GOSH now provides diagnostic testing that can be used as part of a clinical pathway, its establishment was only possible due to continued research investment and the close connection between Professor Breuer's research team at UCL Great Ormond Street Institute of Child Health and the clinical teams within GOSH.
Early work setting up the service was supported by Great Ormond Street Hospital Charity, the Reuben foundation and a Wellcome Trust fellowship to Dr Sofia Morfopoulou (UCL Great Ormond Street Institute of Child Health), and the research has benefited from continuous support from the National Institute for Health and Care Research GOSH and University College London Hospital Biomedical Research Centres.
The teams at UCL and GOSH are working in nationwide collaborations, which are at the forefront of using metagenomics in innovative ways, such as in critical care and immune responsiveness in central nervous system infections.
For example, Professor Breuer and her team are also working closely with colleagues at Guy's and St Thomas' NHS Foundation Trust (GSTT), who are leading a national programme to introduce metagenomics sequencing to identify respiratory infections and support national surveillance of outbreaks and future pandemics.
The test, initially developed and piloted at GSTT, can identify the cause of respiratory infections in under seven hours, allowing for earlier and more personalised treatment. With funding from the Office of Life Sciences, the test is now being deployed at up to 30 sites across the UK, including GOSH.
