̽��ֱ�� of Cambridge - Ewan Harrison

Genomic study shows that England’s travel quarantine measures were effective – up to a limit

cjb250 — Wed, 23 Feb 2022 10:00:17 +0000

In July 2020, following the first months of the pandemic, the UK government established new rules for travellers to and from England, in order to reduce the number of COVID-19 cases being imported into the country. Between 4 July 2020 and 1 February 2021, it established ‘travel corridors’ to countries deemed to be low risk for COVID-19, meaning that travellers returning from these countries did not need to quarantine. However, the majority of people returning from countries outside these corridors were required to quarantine for 14 days at home.

In research published today in Nature Communications, a team of scientists from the ̽��ֱ�� of Cambridge, Wellcome Sanger Institute, COVID-19 Genomics UK (COG-UK) consortium and UKHSA (formerly Public Health England) examined the effectiveness of this policy by analysing contact-tracing data from NHS Test and Trace and genome sequences made available through COG-UK.

̽��ֱ��team compared the number of contacts reported per case prior to a COVID-19 diagnosis between individuals returning from a country with a requirement to quarantine and those who did not need to quarantine on return. They tracked the spread of genomes from imported cases.

̽��ֱ��researchers identified 4,207 positive COVID-19 cases in England between 27 May 2020 and 13 September 2020 related to international travel – with more than half (51%) of all imported cases coming from just one of three countries, Greece, Croatia, and Spain.

Travellers with COVID-19 returning from countries that required them to quarantine had fewer contacts than those returning from countries within the travel corridors, and so were less likely to pass on the infection to others. Using mathematical modelling, they estimate that individuals travelling from a country requiring quarantine had an average (mean) of 3.5 contacts, 40% fewer than someone returning from a country that did not require quarantine measures (who had an average of 5.9 contacts).

̽��ֱ��number of contacts per case was greatest in the 16-20 age group who had travelled to countries with no requirement for quarantine, with a mean of 9.0. When quarantine was required, this fell to 4.7, similar to that of other age groups.

Genomic sequencing allowed a number of unique imported SARS-CoV-2 genomes to be identified that could be monitored to see how widely they had spread. ̽��ֱ��cluster size – that is, the number of related cases of onward transmission – for genomes imported from a country without a requirement to quarantine on return was significantly higher than for those related to countries with mandatory quarantine in place.

Dr Dinesh Aggarwal from the Department of Medicine at the ̽��ֱ�� of Cambridge, the study’s first author, said: “Although the pandemic now looks very different to how it was in 2020 – with the emergence of new variants offset by increased vaccination – there are still important lessons that can be learned about the effectiveness of quarantine, in particular for future pandemic preparedness.

“Our study shows that while travel restrictions are effective in reducing the number of imported COVID-19 cases, they do not eliminate them entirely. It’s likely that one of the main reasons that quarantine measures helped is that they put people off travelling during this period.”

For the most common destinations – barring Spain – the number of imported cases dropped when the government removed a country from the ‘safe’ list and reintroduced mandatory quarantine.

̽��ֱ��majority of importations from Greece came at the end of August and continued into September, a period during which there was no requirement to quarantine for travellers returning from the county – this was the source of greatest imported SARS-CoV-2 cases during the study period.

Dr Ewan Harrison from the Wellcome Sanger Institute, senior author, added: “Genomics has proven to be an invaluable tool in monitoring how the coronavirus spreads and helping inform infection control measures. By applying it to travel-related cases, it could help governments rapidly refine their travel policies and consider if any quarantine measures are appropriate.”

̽��ֱ��research was supported by Wellcome, UK Research and Innovation, and the COVID-19 Genomics UK (COG-UK) Consortium

Dr Aggarwal is a PhD student at Churchill College.

Reference
Aggarwal, D, Page, AJ, Schaefer et al. Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission. Nat Comms; 23 Feb 2022: DOI: 10.1038/s41467-022-28371-z

Fourteen-day quarantine measures imposed on incoming travellers returning to England in summer 2020 helped prevent the spread of the SARS-CoV-2 virus, particularly among 16-20 year olds, say a team led by Cambridge scientists.

Although the pandemic now looks very different to how it was in 2020 – with the emergence of new variants offset by increased vaccination – there are still important lessons that can be learned about the effectiveness of quarantine

Dinesh Aggarwal

Jerry Zhang

Airplane wing

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MRSA arose in hedgehogs long before antibiotic use

jg533 — Tue, 04 Jan 2022 11:07:30 +0000

Staphylococcus aureus first developed resistance to the antibiotic methicillin around 200 years ago, according to a large international collaboration including the ̽��ֱ�� of Cambridge, the Wellcome Sanger Institute, Denmark’s Serum Statens Institut and the Royal Botanic Gardens, Kew, which has traced the genetic history of the bacteria.

They were investigating the surprising discovery - from hedgehog surveys from Denmark and Sweden - that up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA. ̽��ֱ��new study also found high levels of MRSA in swabs taken from hedgehogs across their range in Europe and New Zealand.

̽��ֱ��study is published today in the journal Nature.

̽��ֱ��researchers believe that antibiotic resistance evolved in Staphylococcus aureus as an adaptation to having to exist side-by-side on the skin of hedgehogs with the fungus Trichophyton erinacei, which produces its own antibiotics.

̽��ֱ��resulting methicillin-resistant Staphylococcus aureus is better known as the superbug MRSA. ̽��ֱ��discovery of this centuries-old antibiotic resistance predates antibiotic use in medical and agricultural settings.

“Using sequencing technology we have traced the genes that give mecC-MRSA its antibiotic resistance all the way back to their first appearance, and found they were around in the nineteenth century,” said Dr Ewan Harrison, a researcher at the Wellcome Sanger Institute and ̽��ֱ�� of Cambridge and a senior author of the study.

He added: “Our study suggests that it wasn’t the use of penicillin that drove the initial emergence of MRSA, it was a natural biological process. We think MRSA evolved in a battle for survival on the skin of hedgehogs, and subsequently spread to livestock and humans through direct contact.”

Antibiotic resistance in bugs causing human infections was previously thought to be a modern phenomenon, driven by the clinical use of antibiotics. Misuse of antibiotics is now accelerating the process, and antibiotic resistance is rising to dangerously high levels in all parts of the world.

Since almost all the antibiotics we use today arose in nature, the researchers say it is likely that resistance to them already exists in nature too. Overuse of any antibiotic in humans or livestock will favour resistant strains of the bug, so it is only a matter of time before the antibiotic starts to lose its effectiveness.

“This study is a stark warning that when we use antibiotics, we have to use them with care. There’s a very big wildlife ‘reservoir’ where antibiotic-resistant bacteria can survive – and from there it’s a short step for them to be picked up by livestock, and then to infect humans,” said Professor Mark Holmes, a researcher in the ̽��ֱ�� of Cambridge’s Department of Veterinary Medicine and a senior author of the report.

In 2011, previous work led by Professor Holmes first identified mecC -MRSA in human and dairy cow populations. At the time it was assumed the strain had arisen in the cows because of the large amount of antibiotics they are routinely given.

MRSA was first identified in patients in 1960, and around 1 in 200 of all MRSA infections are caused by mecC-MRSA. Due to its resistance to antibiotics, MRSA is much harder to treat than other bacterial infections. ̽��ֱ��World Health Organization now considers MRSA one of the world’s greatest threats to human health. It is also a major challenge in livestock farming.

̽��ֱ��findings are not a reason to fear hedgehogs, say the researchers: humans rarely get infections with mecC-MRSA, even though it has been present in hedgehogs for more than 200 years.

”It isn’t just hedgehogs that harbour antibiotic-resistant bacteria - all wildlife carries many different types of bacteria, as well as parasites, fungi and viruses,” said Holmes.

He added: “Wild animals, livestock and humans are all interconnected: we all share one ecosystem. It isn’t possible to understand the evolution of antibiotic resistance unless you look at the whole system.”

This research was funded by the Medical Research Council.

Reference
Larsen, J et al: ‘Emergence of methicillin resistance predates the clinical use of antibiotics.’ Nature, January 2022, DOI: 10.1038/s41586-021-04265-w

Scientists have found evidence that a type of the antibiotic-resistant superbug MRSA arose in nature long before the use of antibiotics in humans and livestock, which has traditionally been blamed for its emergence.

We think MRSA evolved in a battle for survival on the skin of hedgehogs, and subsequently spread to livestock and humans through direct contact

Ewan Harrison

Pia B Hansen

Hedgehog

At a glance

Hedgehogs carry a fungus and a bacteria on their skin, and the two are locked in a battle for survival
̽��ֱ��fungus secretes antibiotics to kill the bacteria, but in response the bacteria has evolved antibiotic resistance – becoming Methicillin-resistant Staphylococcus aureus, or MRSA
Up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA, which causes 1 in 200 of all MRSA infections in humans
Natural biological processes, not antibiotic use, drove the initial emergence of this superbug on hedgehogs around 200 years ago

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Cambridge to spearhead £20million alliance to map spread of COVID-19 coronavirus

cjb250 — Mon, 23 Mar 2020 00:01:10 +0000

Through a £20 million investment administered by the ̽��ֱ��, the COVID-19 Genomics UK Consortium – comprised of the NHS, Public Health Agencies, Wellcome Sanger Institute, and numerous academic institutions – will deliver large-scale, rapid sequencing of the cause of the disease and share intelligence with hospitals, regional NHS centres and the Government.

Samples from patients with confirmed cases of COVID-19 will be sent to a network of sequencing centres which currently includes Belfast, Birmingham, Cambridge, Cardiff, Edinburgh, Exeter, Glasgow, Liverpool, London, Norwich, Nottingham, Oxford and Sheffield.

̽��ֱ�� ̽��ֱ��, together with the Wellcome Sanger Institute, one of the world’s most advanced centres of genomes and data, will coordinate the collaboration between expert groups across the UK to analyse the genetic code of COVID-19 samples circulating in the UK and in doing so, give public health agencies and clinicians a unique, cutting-edge tool to combat the virus.

By looking at the whole virus genome in people who have had confirmed cases of COVID-19, scientists can monitor changes in the virus at a national scale to understand how the virus is spreading and whether different strains are emerging. This will help clinical care of patients and save lives.

Business Secretary Alok Sharma said: “At a critical moment in history, this new consortium will bring together the UK’s brightest and best scientists to build our understanding of this pandemic, tackle the disease and ultimately, save lives.

“As a Government we are working tirelessly to do all we can to fight COVID-19 to protect as many lives and save as many jobs as possible.”

Whole genome sequencing involves reading the entire genetic code of the virus. It will help scientists understand COVID-19 and its spread. It can also help guide treatments in the future and help monitor the impact of interventions.

Government Chief Scientific Adviser, Sir Patrick Vallance said: “ ̽��ֱ��UK is one of the world’s leading destinations for genomics research and development, and I am confident that our best minds, working as part of this consortium, will make vital breakthroughs to help us tackle this disease.”

̽��ֱ��UK Consortium, supported by the Government, including the NHS, Public Health England, UK Research and Innovation (UKRI), and Wellcome, will enable clinicians and public health teams to rapidly investigate clusters of cases in hospitals, care homes and the community, to understand how the virus is spread and implement appropriate infection control measures.

̽��ֱ��Consortium Director will be Professor Sharon Peacock, Chair of Public Health and Microbiology at the ̽��ֱ�� of Cambridge and Director of the National Infection Service, Public Health England.

“This virus is one of the biggest threats our nation has faced in recent times and crucial to helping us fight it is understanding how it is spreading,” said Professor Peacock. “Harnessing innovative genome technologies will help us tease apart the complex picture of coronavirus spread in the UK, and rapidly evaluate ways to reduce the impact of this disease on our society.”

Dr Ewan Harrison from the Department of Medicine will serve as the Scientific Project Manager. Professor John Danesh from the Department of Public Health and Primary Care will serve on the consortium’s Steering Committee

“We are delighted to be leading this important national programme,” said Professor Ken Smith, Director of the Cambridge Institute of Therapeutic Immunology & Infectious Disease. “It builds on years of work on pathogen genomics by Professor Peacock and her group, and synergises with other major COVID-19 programmes being driven from Cambridge. ̽��ֱ��size and reach of this study across many centres in the UK will provide unprecedented insight into the biology of COVID-19 and its impact on the population. It will be essential for understand how this virus spreads and why it causes disease, and for monitoring how it evolves, particularly looking at whether it becomes more or less dangerous.”

Professor Sir Mike Stratton, Director of the Wellcome Sanger Institute, added: “Samples from substantial numbers of confirmed cases of COVID-19 will be whole genome sequenced and, employing the Sanger Institute’s expertise in genomics and surveillance of infectious diseases, our researchers will collaborate with other leading groups across the country to analyse the data generated and work out how coronavirus is spreading in the UK. This will inform national and international strategies to control the pandemic and prevent further spread.”

Sir Jeremy Farrar, Director of Wellcome, said: “Rapid genome sequencing of COVID-19 will give us unparalleled insights into the spread, distribution and scale of the epidemic in the UK. ̽��ֱ��power of 21st century science to combat this pandemic is something that those going before us could not have dreamt of, and it is incumbent on us to do everything we can to first understand, and then limit, the impact of COVID-19.”

Professor Fiona Watt, Executive Chair of the Medical Research Council, part of UK Research and Innovation said: “ ̽��ֱ��UK is a leader in cutting-edge genome sequencing science. We are now applying specialist expertise in our fight to slow the spread of Coronavirus and accelerate treatments for those affected.

“ ̽��ֱ��ambitious and coordinated response of our research community to the COVID-19 challenge is remarkable. This investment and the findings from the consortium will help prepare the UK and the world for future pandemics.”

How you can support Cambridge's COVID-19 research effort

Donate to support COVID-19 research at Cambridge

̽��ֱ�� ̽��ֱ�� of Cambridge is to take a leading role in a major national effort to help understand and control the new coronavirus infection (COVID-19) announced today by the Government and the UK’s Chief Scientific Adviser.

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Coronavirus COVID-19

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Widely-available antibiotics could be used in the treatment of ‘superbug’ MRSA

cjb250 — Mon, 24 Jun 2019 11:33:23 +0000

Since the discovery of penicillin, the introduction of antibiotics to treat infections has revolutionised medicine and healthcare, saving millions of lives. However, widespread use (and misuse) of the drugs has led some bacteria to develop resistance, making the medicines less effective. With few new antibiotics in development, antibiotic resistance is widely considered a serious threat to the future of modern medicine, raising the spectre of untreatable infections.

One of the most widely used and clinically important groups of antibiotics is the family that includes penicillin and penicillin derivatives. ̽��ֱ��first type of penicillin resistance occurred when bacteria acquired an enzyme, known as a beta-lactamase, which destroys penicillin. To overcome this, drug manufacturers developed new derivatives of penicillin, such as methicillin, which were resistant to beta-lactamase.

In the escalating arms race, one particular type of bacteria known as Methicillin-resistant Staphylococcus aureus – MRSA – has developed widespread resistance to this class of drugs. MRSA has become a serious problem in hospital- and community-acquired infections, forcing doctors to turn to alternative antibiotics, or a cocktail of different drugs which are often less effective, and raises concerns that even these drugs will in time become ineffective.

In previous research, a team of researchers in Cambridge identified an isolate of MRSA (a sample grown in culture from a patient’s infection) that showed susceptibility to penicillin in combination with clavulanic acid. Clavulanic acid is a beta-lactamase inhibitor, which prevents the beta-lactamase enzyme destroying penicillin; it is already used as a medicine to treat kidney infections during pregnancy.

In a study published today in Nature Microbiology, a team of scientists from the UK, Denmark, Germany, Portugal, and USA used genome sequencing technology to identify which genes make MRSA susceptible to this combination of drugs. They identified a number of mutations (changes in the DNA sequence) centred around a protein known as a penicillin-binding protein 2a or PBP2a.

PBP2a is crucial to MRSA strains as it enables them to keep growing in the presence of penicillin and other antibiotics derived from penicillin. Two of these mutations reduced PBP2a expression (the amount of PBP2a produced), while two other mutations increased the ability of penicillin to bind to PBP2a in the presence of clavulanic acid. Overall the effect of these mutations means that a combination of penicillin and clavulanic acid could overcome the resistance to penicillin in a proportion of MRSA strains.

̽��ֱ��team then looked at whole genome sequences of a diverse collection of MRSA strains and found that a significant number of strains – including USA300 clone, the dominant strain in the United States – contained both mutations that confer susceptibility. This means that one of the most widespread strains of MRSA-causing infections could be treatable by a combination of drugs already licensed for use.

Using this knowledge, the researchers used a combination of the two drugs to successfully treat MRSA infections in moth larvae and then mice. Their next step will be to conduct the further experimental work required for a clinical trial in humans.

Dr Mark Holmes from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, a senior author of the study, says: “MRSA and other antibiotic-resistant infections are a major threat to modern medicine and we urgently need to find new ways to tackle them. Developing new medicines is extremely important, but can be a lengthy and expensive process. Our works suggests that already widely-available medicines could be used to treat one of the world’s major strains of MRSA.”

First author Dr Ewan Harrison, from the Wellcome Sanger Institute and the ̽��ֱ�� of Cambridge, adds: “This study highlights the importance of genomic surveillance – collecting and sequencing representative collections of bacterial strains. By combining the DNA sequencing data generated by genomic surveillance with laboratory testing of the strains against a broad selection of antibiotics, we may find other unexpected cracks in the armour of antibiotic-resistant bacteria that might give us new treatment options.”

̽��ֱ��research was funded by the Medical Research Council (MRC), Wellcome and the Department of Health.

Dr Jessica Boname, Head of Antimicrobial Resistance at the MRC, says: “This study demonstrates how a mechanistic understanding of resistance and access to clinical data can be used to find new ways to contain and control infections with existing resources.”

Reference
Harrison, EM et al. Genomic identification of cryptic susceptibility to penicillins and β-lactamase inhibitors in methicillin-resistant Staphylococcus aureus. Nature Microbiology; 24 June 2019; DOI: 10.1038/s41564-019-0471-0

Some MRSA infections could be tackled using widely-available antibiotics, suggests new research from an international collaboration led by scientists at the ̽��ֱ�� of Cambridge and the Wellcome Sanger Institute.

MRSA and other antibiotic-resistant infections are a major threat to modern medicine and we urgently need to find new ways to tackle them

Mark Holmes

NIAID

Scanning electron micrograph of a human neutrophil ingesting MRSA (yellow)

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̽��ֱ�� of Cambridge - Ewan Harrison

Genomic study shows that England’s travel quarantine measures were effective – up to a limit

MRSA arose in hedgehogs long before antibiotic use

Hedgehogs carry a fungus and a bacteria on their skin, and the two are locked in a battle for survival

̽��ֱ��fungus secretes antibiotics to kill the bacteria, but in response the bacteria has evolved antibiotic resistance – becoming Methicillin-resistant Staphylococcus aureus, or MRSA

Up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA, which causes 1 in 200 of all MRSA infections in humans

Natural biological processes, not antibiotic use, drove the initial emergence of this superbug on hedgehogs around 200 years ago

Cambridge to spearhead £20million alliance to map spread of COVID-19 coronavirus

How you can support Cambridge's COVID-19 research effort

Widely-available antibiotics could be used in the treatment of ‘superbug’ MRSA

**̽��ֱ��fungus secretes antibiotics to kill the bacteria, but in response the bacteria has evolved antibiotic resistance – becoming Methicillin-resistant Staphylococcus aureus, or MRSA**