G is for Greyhound
By amb206 from News feed generator. Published on Jul 15, 2015.
The fabulous architecture of King’s College Chapel is not just about piety. Its gravity-defying fan vaulting, decorative sculpture and stunning windows are an assertion of legitimacy by a royal family under pressure. The Tudors faced many threats – from other claimants to the throne (both dynastic rivals and pretenders) as well as from disease and infertility.
The chapel was constructed over a period of 70 years (1446-1515) under the instructions of four English kings: Henry VI, Richard III, Henry VII and Henry VIII. All four were obsessed by questions of succession; the provision of a healthy male heir was vital to carrying the family line forward.
Henry VII (the first Tudor king) was responsible for the phase of building which saw the creation of the interior that today draws thousands of visitors. Henry VII’s master mason John Wastell and chief carver Thomas Stockton were tasked with creating a chapel ablaze with the emblems of royal dynasties that were sometimes warring, sometimes united.
In Carving in King’s Chapel, a booklet published in 1970, the historian John Saltmarsh wrote that the antechapel at King’s represented “the most lavish display of worldly pomp to be found anywhere in English Gothic”. One of the most eye-catching features of the stone ornamentation of the antechapel is its imposing Tudor armorials – great stone badges.
Saltmarsh described how “over and over again the arms of Henry VII are repeated with his dragon and his greyhound, the crowned Tudor rose, the crowned portcullis which was the badge of his mother’s house of Beaufort, and the crowned fleur de lis for his titular kingship of France”.
Each shield (or escutcheon) is flanked by heraldic ‘supporters’: a dragon on the left and a greyhound on the right. Carved from pale limestone, the slender greyhounds have collars set with jewels, marking them out as favoured members of a wealthy household. All the shields have holes in their left-hand corners. This is a reference to jousting: a knight would pass his lance through the hole in the shield in order to defend himself while tilting at his opponent.
“The Renaissance sculptor skilfully reveals the physical characteristics of the greyhounds which stand on their long thin legs and with their front legs both against, and in front of, the vertical architectural framework structuring the walls, thus placing the animal both inside, and in front of, the three- dimensional space of the heraldic devices,” says Professor Jean Michel Massing, Fellow in History of Art at King’s and co-author of a recent book about King’s Chapel.
“The elongated bodies of the slim-built animals are elegant, with their broad chests, while their alertness is emphasised by their heads which are turned to catch the gaze of the viewers, with ears pricked and elongated muzzles.“
The greyhound is the symbol of the Beaufort family; the dragon is the emblem of the Tudors. Henry VII’s mother was Margaret Beaufort, Countess of Richmond, and his father Edmund Tudor. Margaret was just 13 years old when she gave birth to Henry. Edmund died before his son was born. Margaret, who went on to marry a further three times, founded two Cambridge colleges: St John’s and Christ’s.
As a symbol of celebrity and loyalty, the greyhound is etched into the visual identity of not just one but several powerful families, making its presence in King’s Chapel even more potent. The animal was the emblem of the Richmond family as well as the Beaufort family. Edmund Tudor, First Earl of Richmond and father of Henry VII, was granted a white greyhound as a heraldic supporter by his half-brother Henry VI.
“The greyhound is both a Lancastrian emblem and a Tudor one – and thus very handy as a heraldic expression of the dynastic right of the Tudors to the English throne,” says Peter Jones, the librarian at King’s College. “In this way the dynastic badges in the Chapel are all about legitimacy, a right to rule inherited from the Chapel’s founder, Henry VI, by the Tudors.”
The lean forms of dragon and greyhound can also be spotted in carving on the wooden rood screen that divides the antechapel from the choir stalls and altar. The carvings are in the Renaissance manner and made by foreign craftsman. “The carvings feature the linked initials of Henry VIII and Anne Boleyn, who was executed that year,” says Professor Paul Binski, Professor of Medieval Art and author of Gothic Wonder. “The screen and stalls at King’s display some of the earliest Renaissance detailing in England and show how influential courts were in changing taste.”
Built for hunting, coursing and lolling beside open fires, greyhounds feature in art as far back as 5,000 years.
Considered one of the world’s oldest breeds, greyhounds are the world’s second fastest mammals (cheetahs are marginally faster) and their large ribcages contain big hearts and lungs. The animals achieve their famously high speeds by arching and then contracting their spines like an arching spring.
When it became apparent to vets that greyhounds suffer markedly more than other breeds from bone cancer (osteosarcoma), it was suggested that the disease may result from the stress they experience when they are raced competitively. But preliminary investigation soon showed that greyhounds which never race, and are simply kept as pets, also have a high incidence of the disease with the likelihood of bone cancer increasing as the dogs grow older.
Professor Matthew Allen and his colleagues at the Department of Veterinary Medicine are developing new ways to diagnose and treat bone cancer in dogs. “Greyhounds and other larger breeds, including the Rottweiler, are significantly more likely to develop bone cancer than small dogs,” says Allen. “Environmental factors may make a contribution but it’s clear from the data that genetics play a key role in the development of osteosarcoma. Our research has recently identified five genes that are associated with spread (metastasis) of osteosarcoma in dogs, opening up possibilities for better diagnosis and treatment.”
The dog is an excellent translational model which will help scientists to diagnose and treat humans with bone cancer. Osteosarcoma eats away healthy bone tissue, leaving weaker, damaged bone which can break easily, even with normal activity. In dogs, the disease typically first develops between the ages of five and seven, a stage of life that is ‘middle age’ for dogs. The treatment most commonly offered by vets is amputation followed by chemotherapy and perhaps radiation therapy.
“Amputation seems drastic but dogs manage well with three legs – even greyhounds. But removing the affected leg doesn’t cure the animal. In combination with chemotherapy, it can provide good quality of life for an average of 14 months,” says Allen. “Our work into gene expression in canine osteosarcoma will enable us to better predict which dogs are most at risk of developing metastasis, and should allow us to design better therapies for these patients. Perhaps most importantly, given the close similarities between canine and human osteosarcoma, the work should have direct and tangible benefits to the diagnosis and treatment of humans with this disease.”
Humans are some ten times less likely to develop bone cancer than dogs. But osteosarcoma is notoriously hard to treat in people. It often develops during the late teen years and progresses fast, spreading to other parts of the body with devastating results. “In humans, physicians do everything they can do to save the limb that is affected using therapeutic treatments and implants to replace the damaged bone,” says Allen. “But, especially if the cancer has spread beyond the bone, the long term prognosis can be poor, with five-year survival rates hovering around 50%.”
In addition to collaborating with physicians who treat human osteosarcoma, Allen and colleagues will be working with a network of veterinary practices to reach owners of greyhounds and other large breeds throughout the country. The goal of this programme will be to collect samples of tumours from dogs with primary and metastatic osteosarcoma and to determine whether the genes identified in the research to date can be used to discriminate between tumours with different levels of aggressive behaviour.
“In our experience, the general public is keen to help,” says Allen. “Owners have an opportunity to transform a terrible situation – a diagnosis of osteosarcoma in their dog – into hope for the future by contributing to research that will help to understand and treat the disease in dogs and, ultimately, in humans.”
Next in the Cambridge Animal Alphabet: H is for an animal whose model teeth can be found in the Whipple Museum, which dominate the frieze adorning the Parthenon, and which played a central role in the rise of many great civilisations.
Inset images: Greyhounds on King's College Chapel (Mike Dixon © 2011 King's College, Cambridge); 'Interior of a hall - detail', by Nicolaes de Gyselaer (Fitzwilliam Museum); Osteosarcoma in the dog, showing the significant bone destruction that is typical of this tumour (top). In this dog, the tumour was successfully removed and the bone replaced with a metal implant (lower panel), in a procedure known as limb-sparing surgery (Matthew Allen).
The Cambridge Animal Alphabet series celebrates Cambridge's connections with animals through literature, art, science and society. Here, G is for Greyhound – as heraldic symbols of the Tudors' right to rule, and as part of important research into treatments for osteosarcoma in dogs and humans.
MRSA contamination found in supermarket sausages and minced pork
By cjb250 from News feed generator. Published on Jun 18, 2015.
In February, a team of researchers funded primarily by the Medical Research Council bought and analysed a total of 103 (52 pork and 51 chicken) pre-packaged fresh meat products, labelled as being of UK farm origin, from supermarkets in five different locations across in England.
All of the meat products were frozen at -20 °C and sent to the Department of Veterinary Medicine at the University of Cambridge for testing. After thawing, researchers disinfected the exterior packaging before removing the meat. They then tested a 10g sample of meat from each packet and screened for MRSA. Two of the pork samples – one from sausages, one from minced pork – tested positive for MRSA; the sausage sample contained two strains of the bacteria.
In collaboration with the Wellcome Trust Sanger Institute an analysis of the genetic make-up of the bacteria and confirmed the presence of antibiotic resistant genes. The analysis showed that the bacteria belonged to a type of MRSA known as LA-MRSA CC398, which has emerged over the last few years in continental Europe, particularly in pigs and poultry, but was not previously believed to be widely distributed in the UK.
In many countries, LA-MRSA CC398 represents an occupational risk for those in close contact with livestock, particularly pigs and veal calves. Humans in contact with pigs (farm workers, abattoir workers and veterinarians, etc.) have significantly higher rates of the bacteria in their nasal carriage, according to epidemiological studies, for example. Other studies have revealed an association between clinical disease resulting from LA-MRSA CC398 infection and recent contact with pigs or pig farms. As with other MRSA, this type may be responsible for serious illness following wound or surgery site infections, although many people will carry MRSA on their skin or in their noses without showing signs of disease.
The researchers stress that adequate cooking (heating above 71°C) and hygienic precautions during food preparation should minimise the likelihood of transmission to humans via contaminated pork. However, they argue that the discovery of MRSA in pork identifies a potential way that the bacteria can spread from farms to the wider population.
While human contamination of carcasses or meat products in the abattoir or at the meat packing plant may occur, there is good evidence that these isolates are of animal origin – possibly through the use of antibiotics to treat or control infection in livestock.
As the tests use a highly sensitive method of detection of bacterial contamination, the numbers of MRSA bacteria present may be low. The researchers say that as the two infected samples contained processed pork (sausages and minced pork), they cannot rule out that the meat packing plants from which the MRSA from this study originated also handle imported meat. If this were the case, it is conceivable that cross-contamination might have occurred between non-UK to UK sourced meat.
Dr Mark Holmes from the Department of Veterinary Medicine at the University of Cambridge says: “This is the first time that MRSA has been detected in retail meat products in the UK. The public should not be overly worried by this as sensible food precautions and good hygiene should prevent its spread. It’s also usually pretty harmless and only causes health problems if it infects someone in poor health or gets into a wound.
“However, this does suggest that MRSA is established in our pig farms and provides a possible route of transmission from livestock, through those in direct contact with pigs, into the wider population.”
Dr Des Walsh, Head of Infections and Immunity at the MRC, added: “Studies like this are crucial not just to reveal concerns to human health through contaminated livestock, but to show resistance to antibiotics is a problem growing far beyond just humans. To win the fight against antimicrobial resistance, we need an all hands on deck approach, and that’s why we’ve teamed up with leading experts in biological, social and others sciences in a joint initiative designed to find new solutions, fast.”
The research was funded by the Medical Research Council, with additional support from the Alliance to Save our Antibiotics. The results of the study are published in the online journal Eurosurveillance.
Dr Holmes was recently awarded a further £1.58 million from the MRC to look into the effects of antibiotic use on the entire population of animal gut flora, not just the disease causing bacteria. His work, using research in pigs, will help scientists understand the evolution of antibiotic resistance and help to make better choices about how to reduce the spread of antimicrobial resistance on farms.
Hadjirin, NF et al. Detection of livestock-associated methicillin-resistant Staphylococcus aureus CC398 in retail pork, United Kingdom, February 2015. Eurosurveillance
A survey carried out earlier this year has found the first evidence of the ‘superbug’ bacteria Methicillin-Resistant Staphylococcus Aureus (MRSA) in sausages and minced pork obtained from supermarkets in the UK. However, researchers stress that this does not pose a significant immediate risk to the public.
C is for Chicken (and Campylobacter)
By amb206 from News feed generator. Published on Jun 17, 2015.
Poultry is an important source of protein; almost half the meat we eat in the UK is chicken. And the popularity of chicken is rising: it’s convenient, tasty and cheap. On average we eat around 190g per person per week. Poultry, however, harbours a hidden problem. Around two-thirds of raw chicken sold by British retailers is infected with bacteria called Campylobacter.
Campylobacter is ubiquitous in the environment. All chicken flocks, large or small, factory-farmed or free range, are susceptible to infection. The bacteria have the ability to survive the production chain from farm to fork.
Adequate cooking, however, kills the bacteria and makes chicken safe to eat. Consumers are advised not to wash chicken before cooking and to follow basic hygiene rules when handling raw chicken.
If Campylobacter is ingested by humans, it can lead to diarrhoea. Four out of five cases of food poisoning in the UK can be traced to poultry; sickness from Campylobacter costs the economy an estimated £900 million each year. Recovery can take a week or more, and infection with the bacteria is also associated with serious complications – including reactive arthritis and Guillain-Barré Syndrome.
These facts are the driving force behind research being undertaken by microbiologists Dr Andrew Grant, Professor Duncan Maskell and their groups at the Department of Veterinary Medicine. “Campylobacter is the leading source of bacterial gastroenteritis, affecting half a million people and killing an estimated 100 people each year in the UK,” says Grant. “This is why it’s a major target for research efforts.”
Poultry is big business. Production units supplying the major supermarkets can house 50,000 birds or more. Even when stringent biosecurity measures are taken, incursions occur when barriers are broken. “It takes just a couple of bacteria, or perhaps even one, entering a unit for a flock of thousands of birds to be infected in less than a week,” says Grant. “The chicken gut is the ideal vessel for Campylobacter to flourish. Transmission is guaranteed by a continual process of consumption and excretion known as coprophagy.”
There are no vaccines – either for poultry or humans – to protect against Campylobacter. The ubiquity and resilience of Campylobacter jejuni (the strain that colonises poultry and causes most gastroenteritis in humans) have prompted a government-led push to reduce the level of infection by developing ways in which to contain, and ultimately eliminate, its presence in the nation’s most popular meat.
“We need to look at the problem both on an industry-wide scale and on a microbial scale. The first approach involves working hand-in-hand with producers and processors and the second working in the lab to understand the structure and behaviour of Campylobacter,” says Grant.
“Working with the industry, we’re building a picture of the highly dynamic process of transmission from one bird to another and also at the ways in which Campylobacter is spread during slaughtering and processing. In the lab we’re looking at how we can manipulate Campylobacter so that it can’t spread – essentially we’re trying to identify and target its Achilles heel.”
One avenue being explored is the identification of the Campylobacter genes required for chicken colonisation, which could make good targets for therapeutic intervention. Another approach is to disarm Campylobacter by altering its characteristic shape from spiral to rod-shaped. Once rod shaped it loses its ability to colonise chickens and cause disease in humans.
Scientists working on Campylobacter face formidable challenges. Highly successful in the environments where it thrives best, the bug is difficult to culture in the lab where scientists need to work with live bacteria.
In the food production and retailing sectors, a reluctance to take ownership of the problem has led to lack of investment in measures to address an issue that each sector sees as the other’s problem. The profit margins made by farmers are tiny – as low as one or two pence per bird produced. The onus therefore is seen to lie with processors and retailers to invest in intervention and control strategies.
There is a mounting sense of urgency in the drive to eliminate Campylobacter from the nation’s food chain. Incidents of Campylobacter food poisoning are continuing to rise. Around 75,000 cases per year are ‘culture confirmed’ and, due to under-reporting, the true total is estimated to be equivalent to at least 460,000, and possibly 750,000, cases.
“Campylobacter found in raw chicken sold to consumers is generally on the surface of the birds, which means that adequate cooking quickly destroys the bacteria. But we now think that it might be entering chickens’ muscle tissue and internal organs,” says Grant.
“Infection by Campylobacter is considered to be the most prevalent cause of bacterial diarrhoeal disease worldwide. Compared to many other pathogens we know comparatively little about the bacteria and there are still many more questions than answers. There is a need for alternative strategies to reduce Campylobacter in chickens and Campylobacter-induced disease burden in humans.”
Next in the Cambridge Animal Alphabet: D is for a creature that prowls the Museum of Archaeology and Anthropology, confronts students in the Department of Anglo-Saxon, Norse and Celtic, and was a fertile symbol for medieval poets.
Inset images: Raw chicken in a pot (eltpics); Campylobacter jejuni (Andrew Grant).
The Cambridge Animal Alphabet series celebrates Cambridge's connections with animals through literature, art, science and society. Here, C is for Chicken – a popular source of protein that carries a hidden hazard in the form of Campylobacter.
Novel Thoughts #2: Clare Bryant on AS Byatt’s Possession
By lw355 from News feed generator. Published on Jun 12, 2015.
Professor Clare Bryant from Cambridge’s Department of Veterinary Medicine explains how reading AS Byatt’s Possession at a crucial point in her early career reminded her of the excitement of research and persuaded her not to turn her back on her life as a scientist.
Here she talks about this favourite book as part of ‘Novel Thoughts’, a series exploring the literary reading habits of eight Cambridge scientists. From illustrated children’s books to Thomas Hardy, from Star Wars to Middlemarch, we find out what fiction has meant to each of the scientists and peek inside the covers of the books that have played a major role in their lives.
‘Novel Thoughts’ was inspired by research at the University of St Andrews by Dr Sarah Dillon (now a lecturer in the Faculty of English at Cambridge) who interviewed 20 scientists for the ‘What Scientists Read’ project. She found that reading fiction can help scientists to see the bigger picture and be reminded of the complex richness of human experience. Novels can show the real stories behind the science, or trigger a desire in a young reader to change lives through scientific discovery. They can open up new worlds, or encourage a different approach to familiar tasks.
Is there a novel that has inspired you? Let us know! #novelthoughts
New film series Novel Thoughts reveals the reading habits of eight Cambridge scientists and peeks inside the covers of the books that have played a major role in their lives. In the second film, Professor Clare Bryant talks about how AS Byatt’s Possession inspired her not to turn her back on her life as a scientist.
Virus evolution and human behaviour shape global patterns of flu movement
By cjb250 from News feed generator. Published on Jun 08, 2015.
In the study, an international team of researchers led by the University of Cambridge and the Fred Hutchinson Cancer Research Center, and including all five World Health Organization (WHO) Influenza Collaborating Centres, reports surprising differences between the various types of seasonal flu virus, which they show to be due to the rate at which the different viruses evolve.
There are four types of influenza viruses that cause seasonal flu in humans: two influenza A viruses (H3N2 and H1N1) and two influenza B viruses (Yamagata and Victoria). While H3N2 viruses are the most common of the seasonal influenza viruses, H1N1 and B viruses also cause epidemics worldwide each year, hence the WHO selects representative strains of all four A and B viruses for inclusion in the seasonal influenza vaccine each year.
Importantly, all four of the viruses cause indistinguishable symptoms and evolve by similar mechanisms to escape immunity induced by prior infections and vaccinations. This ‘antigenic’ evolution is part of why people get influenza multiple times over the course of their lives.
In 2008, an international team led by scientists from the University of Cambridge, writing in the journal Science, showed that H3N2 viruses circulate continuously in east and southeast Asia throughout the year, spreading to the rest of the world each year to cause seasonal flu epidemics. Given the fundamental similarities between H3N2, H1N1, and B infection it was thought that they would also emerge from east and southeast Asia to cause yearly epidemics worldwide. However, the work published today in Nature shows that in fact, H1N1 and B viruses behave very differently from H3N2 viruses.
Senior author Dr Colin Russell, from the Department of Veterinary Medicine at the University of Cambridge, UK, says: “While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide. This continuous circulation gives rise to a huge diversity in H1N1 and B viruses circulating globally.”
Interestingly, the researchers found that sometimes new H1N1 and B variants emerge from outside east and southeast Asia and are subsequently seeded into Asia, while in other cases H1N1 and B variants circulate in Asia for years without spreading globally.
“It’s really surprising to find that the H3N2 viruses are unique among the seasonal influenza viruses,” adds first author Dr Trevor Bedford from the Fred Hutchinson Cancer Research Center in Seattle, USA. “It’s almost as surprising to find that the differences among viruses are associated with a simple phenomenon: how quickly the viruses evolve antigenically.”
The Nature study finds that the rate of global movement of each virus, and its ability to circulate continuously between epidemics, is shaped by how quickly that virus changes its coat to escape immunity in the human population. Viruses that evolve quickly, in particular H3N2, spread around the world rapidly, but die out quickly between epidemics. Viruses that evolve more slowly, like H1N1 and B viruses, spread around the world more slowly but are also better at circulating continuously between epidemics.
The key element about global movement is who is getting infected: faster evolving viruses, like H3N2, can infect adults, who tend to travel more frequently than children, providing more opportunities for the virus to spread. Conversely, more slowly evolving viruses, such as H1N1 and B viruses, primarily infect children. Children get sick with all four seasonal flu viruses, but H3N2 evolves faster so it infects adults more often. This leads to a greater proportion of adult infections with H3N2 relative to H1N1 and B viruses, and faster spread of H3N2 viruses.
“Ultimately, this means that we can look at the viruses circulating in Asia to get a good idea of which H3N2 virus might spread worldwide, but for H1N1 and B it’s tremendously variable and the dominant variant can vary from one region of the world to another,” says Dr Russell.
The Nature study also sheds important light on the role of India in the global spread of seasonal influenza viruses. Scientists and public health officials had long known that China and Southeast Asia were important for the evolution and spread of seasonal influenza viruses. However, based on the analysis of an extensive collection of viruses from India, it is now clear that India may be as central as China to the ongoing evolution of seasonal influenza viruses.
“The focus of influenza research in the past has been on China and southeast Asia, but it seems obvious now that surveillance and public health in India, home to over one sixth of the world’s population, should be a high priority for further development to help safeguard India and the world against seasonal flu,” says Dr Mandeep Chadha of the National Institute of Virology, Pune, India.
The research was primarily funded by the Royal Society and US National Institutes of Health with extensive involvement of the World Health Organization’s Global Influenza Surveillance and Response System.
Bedford, T et al. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature; 8 June 2015.
The global movement patterns of all four seasonal influenza viruses are illustrated in research published today in the journal Nature, providing a detailed account of country-to-country virus spread over the last decade and revealing unexpected differences in circulation patterns between viruses.
Pig-borne disease jumped into humans when rearing practices changed
By cjb250 from News feed generator. Published on Mar 31, 2015.
Almost every pig carries harmless strains of the S. suis bacterium – such strains are known as ‘commensal’ strains. However, a more virulent group of strains of the bacteria also exist, which cause disease in pigs worldwide and are a major driver of antibiotic use for prevention. Increasingly, this group of strains is also implicated in serious human diseases such as meningitis and septicaemia.
In order to understand the genetic basis of disease in S. suis, an international study, led by the Bacterial Respiratory Diseases of Pigs-1 Technology (BRaDP1T) consortium, examined the genomes of 375 clinical samples from pigs and humans from the UK and Vietnam and combined these with data already published on 15 S. suis genome sequences and draft genomes from around the world. They found that the commensal strains and disease-causing strains differed genetically; in particular, the disease-causing strains have between 50 and 100 fewer genes than the commensal strains.
Dr Lucy Weinert from the Department of Veterinary Medicine at the University of Cambridge, first author of the study, says: “It seems that the loss of genes is associated with causing disease. This is something we see quite often in bacteria, but for reasons that are unclear. One possibility is that the missing genes are those that hinder the function of newly-acquired virulence factors in the genomes.”
By examining the S. suis’s ‘tree of life’ – which looks at how the bacteria have evolved over time – the researchers were able to show that the emergence of a group of strains causing meningitis in pigs and the human form of the disease dates back to the 1920s, when pig production was intensified with the introduction of wide-scale indoor rearing of meat-producing pigs in larger groups, supported by government schemes that favoured larger producers with regular throughput. However, despite having jumped the species barrier from pig to human, the bacteria do not appear to have adapted to infect humans.
“A group of more virulent strains seem to have emerged at around the time the pig industry changed, and it is these strains that mostly cause disease in pigs and humans,” says Professor Duncan Maskell, Head of the School of the Biological Sciences at Cambridge.
“Human S. suis disease in the West is extremely rare, but is seen more frequently in south east Asia. It is most likely spread to humans through poor food hygiene practices or other environmental factors. This emphasises the importance of monitoring such practices and putting policies in place to reduce the risk of the spread of infections between species.”
The study was primarily funded by the Biotechnology and Biological Sciences Research Council.
Weinert, LA et al. Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis. Nature Communications; 31 March 2015
The most virulent strains of Streptococcus suis, the leading cause of bacterial meningitis in adult humans in parts of southeast Asia and in pigs around the world, are likely to have evolved and become widespread in pigs at the same time as changes in rearing practices, according to research from an international consortium published today in the journal Nature Communications.
Minimising ‘false positives’ key to vaccinating against bovine TB
By cjb250 from News feed generator. Published on Feb 19, 2015.
Using mathematical modelling, researchers at the University of Cambridge and Animal & Plant Health Agency, Surrey, show that it is the specificity of the test – the proportion of uninfected animals that test negative – rather than the efficacy of a vaccine, that is the dominant factor in determining whether vaccination can provide a protective economic benefit when used to supplement existing controls.
Bovine TB is a major economic disease of livestock worldwide. Despite an intensive, and costly, control programme in the United Kingdom, the disease continues to persist. Vaccination using the human vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) offers some protection in cattle, but is currently illegal within the European Union (EU) due to its interference with the tuberculin skin test. This test is the cornerstone of surveillance and eradication strategies and is used to demonstrate progress towards national eradication and as the basis of international trade in cattle.
The current tuberculin skin test has a very high estimated specificity of over 99.97%, which means that less than three animals in 10,000 will test falsely positive. The test as carried out in Great Britain is thought to have at best an 80% sensitivity – a measure of how many infected animals will correctly test positive – missing around 1 in 5 bovine TB-infected cattle. It is used to determine if animals, herds and countries are officially free of bovine TB.
Vaccinated animals that test positive have to be treated as infected animals. Under European law, if an animal tests positive, it must be slaughtered. The remaining herd is put under movement restrictions and tested repeatedly using both the skin test and post-mortem examinations until it can be shown to be officially clear of infection. The duration of movement restrictions is important due to the considerable economic burden they place on farms. The cost to the UK government alone, which depends on the number of visits to farms by veterinarians, tests carried out and compensation for the slaughter of infected animals, is estimated to be up to £0.5 billion pounds over the last ten years.
For vaccination to be feasible economically and useful within the context of European legislation, the benefits of vaccination must be great enough to outweigh any increase in testing. A new generation of diagnostic tests, known as ‘Differentiate Vaccinated from Infected Animals’ (DIVA) tests, opens up the opportunity for the use of BCG within current control programmes.
The EU has recently outlined the requirements for changes in legislation to allow cattle vaccination and a recent report from its European Food Safety Authority emphasized the importance of demonstrating that BCG is efficacious and that DIVA tests can be shown to have a comparable sensitivity to tuberculin testing in large-scale field trials. However, a key factor overlooked in this report was that the currently viable DIVA tests have a lower specificity than tuberculin testing; this could lead to vaccinated herds being unable to escape restrictions once a single test-positive animal has been detected, as the more times the herd is tested, the more likely the test is to record a false positive.
In the study published today, the researchers from Cambridge and the Animal & Plant Health Agency used herd level mathematical models to show that the burden of infection can be reduced in vaccinated herds even when DIVA sensitivity is lower than tuberculin skin testing – provided that the individual level protection is great enough. However, in order to see this benefit of vaccination the DIVA test will need to achieve a specificity of greater than 99.85% to avoid increasing the duration and number of animals condemned during breakdowns. A data set of BCG vaccinated and BCG vaccinated/experimentally M. bovis infected cattle suggests that this specificity could be achievable with a relative sensitivity of the DIVA test of 73.3%.
However, validating a test to such a high specificity will likely prove a challenge. Currently, there is no gold standard test to diagnose TB in cattle. Cattle that test positive are slaughtered immediately and therefore have rarely developed any physical signs – in fact, only around a half of animals examined post-mortem show physical signs of infection even if they are, indeed, infected.
Dr Andrew Conlan from the Department of Veterinary Medicine at the University of Cambridge says: “In order for vaccination to be viable, we will need a DIVA test that has extremely high specificity. If the specificity is not good enough, the test will find false positives, leading to restrictions being put in place and a significant financial burden for the farmer.
“But validating a test that has a very high specificity will in itself be an enormous challenge. We would potentially need to vaccinate, test and kill a large number of animals in order to be confident the test is accurate. This would be very expensive.”
The need for a better DIVA test was acknowledged by the Government at the end of last year. In a written statement to the House of Commons noting data from the University of Cambridge and Animal Health and Veterinary Laboratories Agency, the Rt Hon Elizabeth Truss, Secretary of State for Environment, Food and Rural Affairs, said: “An independent report on the design of field trials of cattle vaccine and a test to detect infected cattle among vaccinated cattle (DIVA) shows that before cattle vaccination field trials can be contemplated, we need to develop a better DIVA test.”
The study was funded by the Department for Environment, Food and Rural Affairs (Defra) in the UK.
Conlan, AJK et al. Potential benefits of cattle vaccination as a supplementary control for bovine tuberculosis. PLOS Comp Biol; 19 Feb 2015
New diagnostic tests are needed to make vaccination against bovine tuberculosis (bovine TB) viable and the number of false positives from these tests must be below 15 out of every 10,000 cattle tested, according to research published today in the journal PLOS Computational Biology.
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Lassa fever controls need to consider human to human transmission and the role of ‘super spreaders’, say researchers
By Anonymous from News feed generator. Published on Jan 15, 2015.
Lassa fever is an acute viral haemorrhagic illness caused by Lassa virus. First identified in the village of Lassa, Nigeria, in 1969, the disease is thought to be transmitted to humans from contact with food or household items contaminated with rat urine or faeces. There have also been recorded cases of human-to-human transmission within hospital settings, but until now the risk – or mode – of transmission has not been clear. Understanding the different modes of transmission and how they are affected by factors such as people’s interaction with their environment is crucial for understanding the link between Lassa and changes in the ecosystem, and has important implications for public health strategies.
“Given the many competing health priorities in West Africa – exacerbated by the current Ebola epidemic – it is essential that we know the relative risk of human-to-human transmission of other potentially deadly diseases, such as Lassa fever,” says first author Dr Gianni Lo Iacono from the Department of Veterinary Medicine at the University of Cambridge. “That way, public health officials can decide where to focus their public health campaigns and how to prevent or respond to potential outbreaks.”
The researchers, part of the Dynamic Drivers of Disease in Africa Consortium, used mathematical modelling to analyse data from outbreaks known to be due to human-to-human chains of transmission, and calculated the ‘effective reproductive number’. This number represents the number of secondary infections from a typical infected individual – for an outbreak to take hold, this number needs to be greater than one. They compared data from hundreds of Lassa infected patients from Kenema Government Hospital, in Sierra Leone, who could have been infected either by rodents or humans, with the data from human-to-human chains. By considering the effective reproductive numbers, they inferred the proportion of patients infected by humans rather than rodents.
The researchers estimated that around one in five cases (20%) of infection is caused by human-to-human transmission. However, the study also highlighted the disproportionate number of infections that could be traced back to a small number of people, whom the researchers describe as ‘super-spreaders’ – rather than passing their infection on to just one other person (if at all), these individuals infected multiple others. It is not clear what makes them a super-spreader – their physiology, the environment in which they live, their social interactions or probably a combination of these factors.
Dr Donald Grant, chief physician at the Lassa ward in Kenema Government Hospital and co-author of the research, said: "Simple messages to the local people could change their perceptions of risk and hopefully make the difference. For example, making people aware that the virus can remain in urine for several weeks during the recovery period, could promote improved hygienic practices.
“What’s more, measures to target human-to-human spread of Lassa virus can be bundled in with prevention interventions for diseases with similar transmission routes, such as Ebola and even Hepatitis B.”
Professor James Wood, Head of the Department of Veterinary Medicine and senior author on the study, says: “The idea of super-spreaders in infectious diseases is not new. We’ve known about them since the notorious case of ‘Typhoid Mary’ in the early twentieth century and they’ve been documented for other diseases including TB, measles and SARS.
“Although we don’t understand what makes someone a ‘super-spreader’, it highlights the importance of strict hygiene measures in preventing infection. In the case of Lassa fever, we now know that whilst the chance of transmission between humans is much lower than it is from rodents, it is still a very real risk.”
Further progress has been hampered by the Ebola outbreak, which has resulted in the death of key collaborators in Kenema Government Hospital, which was used to nurse Ebola patients, in particular Dr Sheik Humarr Khan, who played such a key role in establishing and furthering the Lassa fever research programme.
The Dynamic Drivers of Disease in Africa Consortium, a multidisciplinary research project considering the linkages between zoonoses, ecosystems, health and wellbeing, is supported the UK Government through the Ecosystem for Poverty Alleviation (ESPA) research programme.
G. Lo Iacono, A. A. Cunningham, E. Fichet-Calvet, R. F. Garry, D. S. Grant, S. H. Khan, M. Leach, L. M. Moses, J. S. Schieffelin, J. G. Shaffer, C. T. Webb, J. L. N. Wood. Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of Lassa fever. PLOS NTD; January 2015.
One in five cases of Lassa fever – a disease that kills around 5,000 people a year in West Africa – could be due to human-to-human transmission, with a large proportion of these cases caused by ‘super-spreaders’, according to research published today in the journal PLOS Neglected Tropical Diseases.
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Scientists ‘must not become complacent’ when assessing pandemic threat from flu viruses
By cjb250 from News feed generator. Published on Oct 15, 2014.
Influenza pandemics arise when a new virus strain – against which humans have yet to develop widespread immunity – spreads in the human population. There have been five such pandemics in the past 100 years, the worst of which – the 1918 Spanish Flu – cost 50 million lives worldwide. Of these pandemics, three are thought to have spread from birds and one from pigs. However, pandemic influenza strains represent only a tiny fraction of the total diversity of influenza viruses that exist in nature; the threats posed by the majority of these viruses are poorly understood. Assessing which viruses pose the greatest risk of causing the next human pandemic is an enormous challenge.
Steven Riley from Imperial College London, an author of the study, says: “There are too many strains of influenza viruses out there in non-human hosts to make it feasible to make preparations against each one. Instead, we need to get better at assessing the pandemic risks so that we know where best to focus our efforts. At the moment, this assessment is largely driven by a simple idea: animal viruses that cause sporadic human infections pose a greater risk than viruses that have not been documented to infect humans. But in fact, none of the viruses that caused the major pandemics of the last century were detected in humans before they emerged in their pandemic form.”
Writing in the journal eLife, the scientists set out the steps that they consider necessary to increase our ability to assess pandemic risk. As influenza virus genome sequencing becomes cheaper, faster and more readily available, the data it generates has the potential to transform the research community’s ability to predict the pandemic risk. However, it remains extremely difficult to predict just from a virus’s genome what symptoms it will elicit in its host – and hence how deadly the virus is. The researchers call for better integration of experimental data, computational methods and mathematical models, in conjunction with refinements to surveillance methodology.
However, they say that scientific insights into non‐human influenza viruses must not give way to complacency that the most substantial threats have been identified and characterized. They point out that several recent strains including the 2009 H1N1 “swine flu” pandemic virus and the recently emerged H7N9 viruses in China highlight the importance of remaining vigilant against as-yet unrecognized high risk viruses and the value of surveillance for influenza viruses in humans.
“No one can say with anything close to a hundred percent certainty when or where the next pandemic will start or which virus will cause it,” says Dr Colin Russell from the Department of Veterinary Medicine at the University of Cambridge. “We are getting much better at identifying and assessing potential threats, but we must be vigilant about surprises lurking around the corner.
“We need to be prepared for a swift response, with coordinated action, to help mitigate the spread of the next pandemic virus. Without developing this ability to respond, we will have spent billions building systems just for watching the next pandemic unfold.”
The research was supported in part by the Research and Policy for Infectious Disease Dynamics program of the US Department of Homeland Security and the National Institutes of Health.
Russell, CA et al. Improving pandemic influenza risk assessment. eLife; 15 Oct 2015
As our ability to assess the pandemic risk from strains of influenza virus increases with the latest scientific developments, we must not allow ourselves to become complacent that the most substantial threats have been identified, argue an international consortium of scientists.
The text in this work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page. For image rights, please see the credits associated with each individual image.
Understanding the bushmeat market: why do people risk infection from bat meat?
By cjb250 from News feed generator. Published on Oct 09, 2014.
The Straw-Coloured Fruit Bat, Eidolon helvum, is widely hunted and eaten in Ghana, but carries a risk of infection with ‘zoonotic’ pathogens – diseases transmitted from animal to man. Hunting, butchering and consuming wild animals for food can potentially transmit these infections through bites, scratches, bodily fluids, tissue and excrement. Bats in particular appear to host more zoonotic viruses per species than any other group of mammals, yet very little is known about how humans and bats interact, how people perceive bats and their accompanying disease risk, or who is most at risk.
Dr Olivier Restif from the Department of Veterinary Medicine at the University of Cambridge explains: “Knowing who eats bush meat and why, as well as how they perceive the risks, is important for informing both disease and conservation management plans. This requires a close-knit collaboration between epidemiologists, ecologists and social anthropologists. That is why we have teamed up with the Zoological Society of London and the University of Ghana to develop this research programme.”
Dr Alexandra Kamins, a Gates Cambridge scholar alumna working with Dr Restif, adds: “All too often, local community voices go unheard, despite representing those most at risk of spillover and often shouldering negative impacts arising from intervention measures. That is why it was important for us to listen to them.”
Dr Kamins and colleagues interviewed 577 people across southern Ghana, including hunters, vendors and consumers of bat meat. Of these, the majority (551) were interviewed using a general survey whilst the rest were interviewed in-depth through focus groups.
The researchers found that hunters used a variety of means to capture bats, including shooting, netting and scavenging, and that all of the hunters reported handling live bats, coming into contact with bat blood and getting scratched or bitten. None of the hunters reported using protective measures, such as gloves. Scavenged bats were collected alive, usually when a branch broke and bats fell to the ground, but this too carried risks: four interviewees explained how people would fight over the bats when a large branch fell, sometimes even lying down on top of bats to prevent others from taking them, often sustaining bites and scratches.
The bats were prepared and cooked in a number of ways, the most common methods being to smoke the bats before preparing food and using the bats in soup. At odds with reports from other countries, the survey in South East Ghana revealed few uses of bat bushmeat associated with traditional beliefs or medical practices. In Ghana, bat bushmeat seems to function as both subsistence and luxury food. The large number of hunters who hunt for themselves or who keep some of their catch suggests that bats provide a readily available source of animal protein. At the same time, high taste ratings among consumers and relatively high prices suggest that bat meat is seen as a ‘luxury food’ in Ghana.
Hunters, vendors and consumers of bat meat all tended to be older than those people with no connection to the practice - on average seven to ten years older. The researchers believe this could imply a number of scenarios, the most likely being a decrease in youth interest in bat bushmeat.
They found a strong association between gender and roles in the bat-bushmeat commodity chain, with hunters primarily being male and vendors female, consistent with the cultural norms of rural Ghanaian society. This could mean that disease risk was also different between the sexes. The researchers also found that those people living in urban environments and those who were more educated were less likely to participate in bat bushmeat activities. Although this suggests that increased urbanisation and improvements in education could reduce the use of bats as bushmeat, it is possible that increased household income could lead to increased bushmeat consumption, particularly as the meat appears to be seen as a luxury item.
Using focus groups, the researchers carried out more in-depth interviews to understand participants’ likely reactions to interventions regarding bat bushmeat. They found that regulations by themselves are not effective solutions: laws and fines alone are unlikely to induce change. While only some of our respondents would be willing to risk paying fines if they continued to earn enough from selling bat bushmeat, essentially no one knew of the existing hunting laws in Ghana, suggesting that enforcement is a major issue.
Possible health risks appeared to be more of a deterrent than fines; some respondents suggested that disease risk could motivate them to stop. However, the risk of disease from bat bushmeat was considered to be greatest by those who did not consume the meat and lowest by those who hunted or sold the bats. This finding supports previous research suggesting that people can readily perceive risk and even intellectually acknowledge desire to reduce that risk, but actual behaviour might not change.
Professor James Wood, who leads the research programme at the University of Cambridge, says: “Understanding both actual and perceived risk factors is vital. If a bat-borne zoonotic disease outbreak were to occur in Ghana, our information could prove invaluable in helping target those groups at greatest risk and in planning disease control measures.”
Dr Marcus Rowcliffe from ZSL adds: “Unfortunately, there may not be a simple way to minimise the risks of zoonotic spillover from bats. For example, bat hunting is a highly seasonal occupation and, like all bushmeat hunting, can be started and dropped at will, whereas rearing domestic animals – one possible sustainable solution for reducing bushmeat hunting – requires continuous activity throughout the year on a daily basis.
“Although many programmes suggest economic opportunity as the major motivation behind livelihood choices and success of alternatives, it may not be enough on its own. We found people in Ghana to be responsive to education pieces about the disease risk from bushmeat but also the ecological role of bats in pollination and seed dispersal. Working with local communities to help them find effective and sustainable solutions in line with their economic needs must be a long-term commitment.”
Kamins, AO et al. Characteristics and Risk Perceptions of Ghanaians Potentially Exposed to Bat-Borne Zoonoses through Bushmeat. Ecohealth; 30 Sept 2014
Ebola, as with many emerging infections, is likely to have arisen due to man’s interaction with wild animals – most likely the practice of hunting and eating wild meat known as ‘bushmeat’. A team of researchers led by the University of Cambridge and the Zoological Society of London (ZSL) has surveyed almost six hundred people across southern Ghana to find out what drives consumption of bat bushmeat – and how people perceive the risks associated with the practice.