14 November 2012

Bacterial DNA sequence used to map an infection outbreak

Researchers use genome sequencing to dissect and control an MRSA outbreak

Video resource: Controlling MRSA by DNA Sequencing

For the first time, researchers have used DNA sequencing to help bring an infectious disease outbreak in a hospital to a close.

Researchers from the Wellcome Trust Sanger Institute, the University of Cambridge and Cambridge University Hospitals used advanced DNA sequencing technologies to confirm the presence of an ongoing outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a Special Care Baby Unit in real time. This assisted in stopping the outbreak earlier, saving possible harm to patients. This approach is much more accurate than current methods used to detect hospital outbreaks.

Using this technology, the team revealed that the outbreak had extended into the wider community, a conclusion that could not be reached with available methods. They also used sequencing to link the outbreak to an unsuspecting carrier, who was treated to eradicate MRSA.

"We are always seeking ways to improve our patient care and wanted to explore the role that the latest sequencing technologies could play in the control of infections in hospitals," says Dr Nick Brown, author, consultant microbiologist at the Health Protection Agency and infection control doctor at Addenbrooke's Hospital, Cambridge. "Our aim is to prevent outbreaks, and in the event that they occur to identify these rapidly and accurately and bring them under control.

"What we have glimpsed through this pioneering study is a future in which new sequencing methods will help us to identify, manage and stop hospital outbreaks and deliver even better patient care."

Over a six month period, the hospital infection control team used standard protocols to identify 12 patients who were carrying MRSA. However, this standard approach alone could not give enough information to confirm or refute whether or not an ongoing outbreak was actually taking place.

In this study, the researchers analysed MRSA isolates from these 12 patients with DNA sequencing technology and demonstrated clearly that all the MRSA bacteria were closely related and that this was an outbreak. They also revealed that the outbreak was more extensive than previously realised, finding that over twice as many people were carrying or were infected with the same outbreak strain. Many of these additional cases were people who had recent links to the hospital but were otherwise healthy and living in the community when they developed a MRSA infection.

" Our study highlights the power of advanced DNA sequencing used in real time to directly influence infection control procedures. "

Dr Julian Parkhill

While this sequencing study was underway, the infection control team identified a new case of MRSA carriage in the Special Care Baby Unit, which occurred 64 days after the last MRSA-positive patient had left the same unit. The team used advanced DNA sequencing to show in real time that this strain was also part of the outbreak, despite the lack of apparent links between this case and previous patients. This raised the possibility that an individual was unknowingly carrying and transmitting the outbreak MRSA strain.

The infection control team screened 154 healthcare workers for MRSA and found that one staff member was carrying MRSA. Using DNA sequencing, they confirmed that this MRSA strain was linked to the outbreak. This healthcare worker was quickly treated to eradicate their MRSA carriage and thus remove the risk of further spread.

"Our study highlights the power of advanced DNA sequencing used in real time to directly influence infection control procedures," says Dr Julian Parkhill, lead author from the Wellcome Trust Sanger Institute. "There is a real health and cost burden from hospital outbreaks and significant benefits to be gained from their prevention and swift containment. This technology holds great promise for the quick and accurate identification of bacterial transmissions in our hospitals and could lead to a paradigm shift in how we manage infection control and practice."

In this instance, DNA sequencing was a key step in bringing the outbreak to a close, saving possible harm to patients and potentially saving the hospital money.

"Our study indicates the considerable potential of sequencing for the rapid identification of MRSA outbreaks," says Professor Sharon Peacock, lead author from the University of Cambridge and clinical specialist at the Health Protection Agency. "What we need before this can be introduced into routine care is automated tools that interpret sequence data and provide readily understandable information to healthcare workers. We are currently working on such a system.

"If we have a robust system of this type in operation when the outbreaks occur, we predict that we will be able to stop them after the first few cases, as we will rapidly find clear connections."

In their next step, the team will study all MRSA carriers and infected patients over the next year in Addenbrooke's Hospital and surrounding hospitals and the community to understand transmission events with the aim of improving infection management.

Sir Mark Walport, Director of the Wellcome Trust, says: "This is a dramatic demonstration that medical genomics is no longer a technology of the future - it is a technology of the here and now. By collaborating with NHS doctors, geneticists have shown that sequencing can have extremely important applications in healthcare today, halting an outbreak of a potentially deadly disease."

Notes to Editors

Perhaps one in one hundred people carry MRSA on their skin or in their nostrils without apparent harm or symptoms and can be unaware that they do so: some carry MRSA for hours or days, but others can carry MRSA for weeks or months. They don't know that they carry MRSA because they have no symptoms and it does not harm them. Approximately 1% of people carry MRSA at any one time.

Publication details

  • Using whole genome sequencing to dissect the cause and effect of a meticillin-resistant Staphylococcus aureus outbreak: a descriptive study?

    Simon R. Harris, Edward J.P. Cartwright, M. Estée Török, Matthew T.G. Holden, Nicholas M. Brown, Amanda L. Ogilvy-Stuart, Matthew J. Ellington, Michael A. Quail, Stephen D. Bentley, Julian Parkhill, Sharon J. Peacock

    Lancet Infectious Diseases 2012

Funding

The study was supported by UKCRC Translational Infection Research Initiative, Wellcome Trust, Health Protection Agency, and the NIHR Cambridge Biomedical Research Centre.

Participating Centres

  • Department of Medicine, University of Cambridge
  • Department of Pathology, University of Cambridge
  • Wellcome Trust Sanger Institute
  • Health Protection Agency
  • Cambridge University Hospitals NHS Foundation Trust

Cambridge University Hospitals (CUH)

Cambridge University Hospitals (CUH) is one of the largest and best known hospitals in the country. As well as delivering care through Addenbrooke's and the Rosie, it is also:

  • a leading national centre for specialist treatment for rare or complex conditions
  • a government-designated biomedical research centre
  • one of only five academic health science centres in the UK
  • a university teaching hospital with a worldwide reputation
  • a partner in the development of the Cambridge Biomedical Campus

CUH's vision is to be one of the best academic healthcare organisations in the world.

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University of Cambridge

The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK's most generous bursary schemes. The University of Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.

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The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

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The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.

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