Oxford Biomedical Research Centre

Antimicrobial Resistance and Modernising Microbiology Theme of the Biomedical Research Centre

Introduction

Antimicrobial resistance (AMR) is recognised to be a major threat to modern medicine. Better and faster diagnostic tests are key to improved treatment of infections. By accurately identifying whether a bacteria or virus (pathogen) is present, we can identify whether antibiotics should be used. Sequencing the DNA from the bacteria or virus allows for quick identification of the pathogen causing the disease and provides information on whether it can be treated or not and if it is similar to other pathogens that have been seen previously.

The BRC is supporting our activities in developing time- and cost-saving methodologies to isolate bacterial or viral DNA directly from a clinical sample, rather than waiting for it to grow. Once DNA is obtained we use whole genome sequencing methods (WGS) to accurately “read” the genetic code of the pathogen. This code is then compared to a database containing changes, or mutations, which are known to cause resistance to certain drugs. Comparing our DNA of interest to the catalogue determines whether any of those mutations are present and therefore whether certain drugs would kill the bacterial or virus and thus successfully treat the infection. Our group is developing and improving computer programs to look at WGS quickly and accurately and also expanding the databases containing mutations that cause resistance to drugs for certain pathogens. This work will lead to new, quicker and innovative ways to diagnose and treat infection within a clinical setting.

We are also establishing the use of computers to look at health records and sequence data. Combining sequence data with electronic health records can revolutionise the treatment and management of infectious diseases in the National Health Service (NHS) and help England’s health system monitor what infectious diseases are present (national surveillance). We have demonstrated this by investigating the epidemiology and impact of COVID-19 in Oxford University Hospitals NHS Foundation Trust.

For more information please see the Oxford BRC website.

A comparison of clinical sample collection methods to detect Influenza virus and other respiratory pathogens using whole genome sequencing

A feasibility study to evaluate different clinical samples for their potential for sequencing to diagnose influenza virus and other respiratory viruses

Diagnosis of influenza (“flu”), which is a virus that causes respiratory (chest) infections, has traditionally relied on a patient providing a nose and/or throat swab that is collected in a special fluid to preserve the virus while it is transported to the laboratory. The hospital laboratory then tests this fluid by looking for small parts of the genetic material that make up the virus (a method called PCR). Diagnosis of other respiratory viruses then requires several different, and sometimes expensive, tests. New technology allows all the genetic material in a sample to be tested using a method called whole genome sequencing, enabling us to identify both flu and other viruses using the same test. The information that the new test provides can also tell us other information that is important for providing clinical care, such as whether anti-viral drugs will be effective as treatment, and detecting whether viruses are spreading between people.

The primary goal of our original study was to investigate whether a new sample, a saliva sample, is suitable to diagnose flu by comparing the results from sequencing with the standard laboratory tests and results, as described above. Our secondary goal was to determine whether the saliva sample is suitable to identify all respiratory viruses using one test, and to investigate the ways we can use this genetic information about the virus to identify whether anti-viral treatments will work and to investigate how viruses are spreading in the community. This might also provide information that helps us to understand the extent to which flu infection can be prevented by vaccination. In the long term, results of this study will contribute to better and quicker diagnosis of chest infections like flu, and therefore help the correct treatment choices to be made promptly. It will also provide insights into the spread of flu, and may help to inform improvements in vaccines so that we can protect more people from flu infections.

We stopped flu study recruitment in March 2020 (3 months after study start) because of the onset of the SARS-CoV-2 (Covid) pandemic. The seasonal pattern of respiratory virus infections, including flu, was also completely changed as a result of Covid and changing public health policy (because many people were in lockdown for long periods of time), with very few flu-positive cases noted locally or nationally in 2020-2022, which made our original recruitment targets unfeasible.

As a result we changed the study design to focus on diagnosing Covid infections, mostly to rapidly support the development of novel Covid tests, including lateral flow tests for national roll-out, and the development of a new test method using a very powerful microscope that can "see” viruses labelled with fluorescent markers directly in clinical samples. This test can identify different types of common virus that cause chest infections, including Covid and flu, and is being expanded to identify different types of germ that cause disease, such as bacteria. 

Please click on the link for the Flu Detection Clinical Sample Protocol