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Tackling drug-resistant infections in seriously ill children

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What did the project achieve?

“We have developed faster, more accurate testing for detecting drug-resistant viral strains in children with potentially life-threatening infections, enabling doctors to personalise their treatment,” says Professor Breuer of University College London and Great Ormond Street Hospital.

Children with weakened immune systems, such as those who are undergoing a transplant, receiving cancer treatment or who have HIV, are at an increased risk of developing dangerous infections.

Two of the biggest threats are cytomegalovirus (CMV) and adenovirus (AdV), both of which can kill or cause lifelong health complications. Resistance to anti-viral drugs presents a major challenge when caring for children with these infections, as drugs may continue to be given when they are no longer effective or be stopped too soon before they have had the chance to work.

Professor Breuer is developing the use of state-of-the-art DNA sequencing technologies to improve testing for anti-viral drug resistance in seriously ill children.

“We dramatically reduced the time between testing and reporting results back to their doctor – from three months to six days – and we know this could be done even faster if there is a strong clinical need,” says Professor Breuer. “This will enable more informed and timely decisions about a child’s treatment, potentially sparing them from the side-effects of ineffective drugs.”

They also found that their approach improved the sensitivity for detecting drug-resistant CMV so that children can be tested earlier during their infection, allowing more rapid treatment adjustments if required.

“We are now seeking the appropriate accreditation for these sequencing methods, so they can be more widely used in clinical practice and benefit more patients in the future,” says Professor Breuer.

This research was completed on

Some of the most vulnerable children in our hospitals may one day benefit from research by Professor Judy Breuer of University College London and Great Ormond Street Hospital. Professor Breuer aims to help children with weakened immune systems. This includes children who are undergoing transplants, are having treatment for cancer or have HIV. Viral infections that are normally harmless can be life threatening for these children, particularly if the virus becomes resistant to drug treatment. Professor Breuer is developing a way to spot problematic drug resistance sooner, so doctors can adjust children’s treatment earlier and boost children’s chances of making a good recovery.

Action Medical Research and Great Ormond Street Hospital Children's Charity are jointly funding this research.​

How are children’s lives affected now?

“Around three in every 10 children we see at Great Ormond Street Hospital have weakened immune systems, which puts them at risk of developing life-threatening viral infections,” says Professor Breuer.1

“In this project, we’re concentrating on cytomegalovirus (CMV), and adenovirus (AdV) infections,” adds Professor Breuer. “These infections can make children with weakened immune systems seriously ill. Sadly, some children lose their lives and those who survive can develop lifelong disabilities, such as vision loss.”

Resistance of viruses to drug treatments presents a major challenge when caring for children with these infections.

“Inadequacies of existing tests mean doctors can’t normally tell for sure, particularly early on, whether a child’s infection is becoming resistant to the drug they’re taking and whether they should switch to another drug,” says Professor Breuer. “This means drugs may be continued when they’re no longer useful, or withdrawn when they’re working, but doing so only slowly.”

How could this research help?

Professor Breuer’s team is developing new blood tests that will reveal early on whether a child’s CMV or AdV infection is starting to develop some resistance to drug treatment. The team is also trying to find ways to use the results of the blood tests to predict how a child’s illness might progress and how they’re likely to respond to different drugs.

Professor Breuer explains: “Earlier detection of drug resistance in children with CMV or AdV infections could help doctors to decide which drug to give a child and to act quickly if they need to switch treatments. Better treatment decisions like this could boost children’s chances of making a good recovery.”

“The tests we’re developing could also provide an early warning if drug resistant infections are being spread within a hospital,” continues Professor Breuer. “This would allow hospitals to take urgent action when necessary, by closing wards and deep cleaning them.”

References

1. Data supplied by Professor Judith Breuer, Department of Infection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health and Great Ormond Street Hospital, University of London

 

 

 

Project Leader Professor Judith Breuer MBBS MD FRCPath
Project Team Dr Charlotte Houldcroft BA PhDDr Joe F Standing BSc MRPharmS PhD
Project Location Department of Infection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health University College London and Great Ormond Street Hospital
Project duration 1 year
Date awarded 20 July 2015
Project start date 1 November 2015
Project end date 31 October 2016
Grant amount £62,911
Grant code GN2424

 

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