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Pig-borne disease jumped into humans when rearing practices changed

By cjb250 from News feed generator. Published on Mar 31, 2015.

Pigs head at market in Vietnam

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.

Reference
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.

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
Duncan Maskell
Pig Head

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Minimising ‘false positives’ key to vaccinating against bovine TB

By cjb250 from News feed generator. Published on Feb 19, 2015.

Cows in a field

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.

Reference
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.

Validating a test... 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
Andrew Conlan
Cows

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Lassa fever controls need to consider human to human transmission and the role of ‘super spreaders’, say researchers

By from News feed generator. Published on Jan 15, 2015.

Housing in Kenema, Sierra Leone

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.

Reference
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.

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.
Dr Gianni Lo Iacono
Housing in Kenema, Sierra Leone

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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.

Tamiflu antiviral drugs

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.

Reference
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.

We are getting much better at identifying and assessing potential threats, but we must be vigilant about surprises lurking around the corner
Colin Russell
New influenza viruses (cropped)

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Understanding the bushmeat market: why do people risk infection from bat meat?

By cjb250 from News feed generator. Published on Oct 09, 2014.

Straw coloured fruit bat

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.”

Reference
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.

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
Olivier Restif
Straw coloured fruit bat (edit)

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Why live vaccines may be most effective for preventing Salmonella infections

By cjb250 from News feed generator. Published on Sep 18, 2014.

Salmonella bacteria

The BBSRC-funded researchers used a new technique that they have developed where several populations of bacteria, each of which has been individually tagged with a unique DNA sequence, are administered to the same host (in this case, a mouse). This allows the researchers to track how each bacterial population replicates and spreads between organs or is killed by the immune system. Combined with mathematical modelling, this provides a powerful tool to study infections within the host. The findings are published today in the journal PLOS Pathogens.

“We effectively ‘barcode’ the bacteria so that we can see where in the body they go and how they fare against the immune system,” explains Dr Pietro Mastroeni from the Department of Veterinary Medicine at the University of Cambridge, who led the study. “This has provided us with some important insights into why some vaccines are more effective than others.”

The multidisciplinary research team led by Dr Mastroeni used the new technique to look at the effectiveness of vaccines against infection by the bacterium Salmonella enterica, which causes diseases including typhoid fever, non-typhoidal septicaemia and gastroenteritis in humans and animals world-wide. Current measures to control S. enterica infections are limited and the emergence of multi-drug resistant strains has reduced the usefulness of many antibiotics. Vaccination remains the most feasible means to counteract S. enterica infections.

There are two main classes of vaccine: live attenuated vaccines and non-living vaccines. Live attenuated vaccines use a weakened form of the bacteria or virus to stimulate an immune response – however, there are some concerns that the weakened pathogen may become more virulent when used in patients with compromised immune systems, for example people infected with HIV, malaria or TB. Non-living vaccines, on the other hand, are safer as they usually use inactive bacteria or viruses, or their fragments – but these vaccines are often less effective. Both vaccines work by stimulating the immune system to recognise a particular bacterium or virus and initiate the fight back in the event of future infection.

Using their new technique, Dr Mastroeni and colleagues showed that live Salmonella vaccines enhance the ability of the immune system to prevent the bacteria from replicating and spreading to other organs. They can also prevent the spread of the bacteria into the bloodstream, which causes a condition known as bacteraemia, a major killer of children in Africa.

They also found that the antibody response induced by live vaccines enhances the ability of immune cells known as phagocytes to kill bacteria in the very early stages of infection, but that a further type of immune cell known as the T-cell – again stimulated by the live vaccine – is subsequently necessary for control and clearance of the bacteria from the blood and tissues. The killed vaccine, whilst able to boost the phagocyte response via the production of antibodies, did not stimulate a protective form of T-cell immunity and was unable to prevent the subsequent bacterial growth in infected organs or the development of bacteraemia, and was unable to control the spread of the bacteria in the body.

Dr Chris Coward, first author on the study, says: "We have used a collaboration between experimental science and mathematical modelling to examine how vaccines help the immune system control infection. We found that, for Salmonella infections, the immune response induced by a killed vaccine initially kills a proportion of the invading bacteria but the surviving bacteria then replicate resulting in disease. The live vaccine appears superior because it induces a response that both kills the bacteria and restrains their growth, leading to elimination of the infection."

Dr Mastroeni adds: “There is a big push towards the use of non-living vaccines, which are safer, particularly in people with compromised immune systems – and many of the infections such as Salmonella are more prevalent and dangerous in countries blighted by diseases such as HIV, malaria and TB. But our research shows that non-living vaccines against Salmonella may be of limited use only and are not as effective as live vaccines. Therefore more efforts are needed to improve the formulation and delivery of non-living vaccines if these are to be broadly and effectively used to combat systemic bacterial infections. We have used Salmonella infections as a model, but our research approaches can be extended to many pathogens of humans and domestic animals.”

The research was carried out Dr Mastroeni, Dr Coward and colleagues Dr Andrew Grant, Dr Oliver Restif, Dr Richard Dybowski and Professor Duncan Maskell. It was funded by the Biotechnology and Biological Sciences Research Council, which has recently awarded Dr Mastroeni funding  to extend this research to the study of how antibiotics work. The new research aims to optimise treatments and reduce the appearance of antibiotic resistance.

Professor Melanie Welham, BBSRC’s Science Director, said: "To protect our health and the health of animals we rely on, such as livestock, effective vaccines are needed against disease. This new technique provides unique insights that will help us compare vaccines produced in different ways to ensure the best disease prevention strategies."

Reference
Coward, C et al. The Effects of Vaccination and Immunity on Bacterial Infection Dynamics In Vivo. PLOS Pathogens; 18 Sept 2014

Vaccines against Salmonella that use a live, but weakened, form of the bacteria are more effective than those that use only dead fragments because of the particular way in which they stimulate the immune system, according to research from the University of Cambridge published today.

We effectively ‘barcode’ the bacteria so that we can see where in the body they go and how they fare against the immune system
Piero Mastroeni
Salmonella bacteria invade an immune cell

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Global snapshot of infectious canine cancer shows how to control the disease

By cjb250 from News feed generator. Published on Sep 03, 2014.

Sleeping dogs

The survey of veterinarians across the world confirmed that Canine Transmissible Venereal Tumour (CTVT) has a global reach. Researchers from the University of Cambridge found that the countries and areas with the lowest rates of the disease also had strong dog control policies. These include managing the number of street dogs; spay and neuter practices; and quarantine procedures for imported dogs.

CTVT first originated as a tumour in a single dog that lived thousands of years ago, and by becoming transmissible, this cancer has become the oldest, most widespread and prolific cancer known in nature. It causes tumours of the genitals, and is spread by the transfer of living cancer cells between dogs during sex. CTVT is one of only two known transmissible cancers – the other has ravaged the wild Tasmanian devil population.

Until now, no systematic global survey of the disease had been performed. To understand the global distribution and prevalence of the disease, the scientists sent a questionnaire to 645 veterinarians and animal health workers around the world. The replies showed that CTVT is endemic in dogs in at least 90 of 109 countries surveyed.

The researchers found that the only cases of CTVT reported in countries in Northern Europe, where free-roaming dogs are absent, were found in dogs that had been imported from abroad. There were no reports of CTVT in New Zealand, a country with strict dog quarantine policies. On the other hand, the disease was more likely to be present in countries or areas with free-roaming dog populations.

Andrea Strakova from the Department of Veterinary Medicine says: “Although CTVT can usually be effectively treated, lack of awareness of the disease and poor access to veterinary care mean it can go untreated and impact the welfare of dogs. Research and monitoring of this disease may lead to improved methods for disease prevention, detection and treatment.”

Dr Elizabeth Murchison adds: “Our study has suggested that free-roaming dogs are a reservoir for CTVT. Our review of the historical literature indicated that CTVT was eradicated in the UK during the twentieth century, probably as an unintentional result of the introduction of dog control policies. Careful management of free-roaming dog populations, as well as inclusion of CTVT in dog import/export quarantine policies, may help to control CTVT spread.”

The research also highlighted the importance of dog sterilisation programs in controlling CTVT spread. However, dog spaying and neutering may not always be protective against CTVT, possibly because the disease can also be spread by biting, licking or sniffing.

The research highlights the remarkable global spread of a single canine cancer which has continued to survive beyond the animal that first spawned it.

Adapted from a press release from BioMed Central.

Reference
Andrea Strakova and Elizabeth Murchison. The changing global distribution and prevalence of canine transmissible venereal tumour. BMC Veterinary Research; 3 Sept 2014

While countries with dog control policies have curbed an infectious and gruesome canine cancer, the disease is continuing to lurk in the majority of dog populations around the world, particularly in areas with many free-roaming dogs. This is according to research published in the open access journal BMC Veterinary Research.

The disease was eradicated in the UK during the twentieth century, probably as an unintentional result of the introduction of dog control policies
Elizabeth Murchison
Nap Time

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First national model for bovine TB calls for greater focus on cattle

By cjb250 from News feed generator. Published on Jul 02, 2014.

Cows

The model, developed by researchers at the University of Warwick and University of Cambridge, suggests that improved testing, vaccination of cattle and culling of all cattle on infected farms would be the most effective strategies for controlling the disease. It found that whilst badgers – the subject of controversial culling plans to stem the spread of the disease – form part of the environmental reservoir, they only play a relatively minor role in the transmission of infection.

Based on a study of cattle and the causes of bovine TB in Great Britain, the model, published in the journal Nature, sought to ascertain how and why the epidemic has grown over the past 15 years. Using data from the Animal Health and Veterinary Laboratories Agency and the Department for the Environment, Food and Rural Affairs (Defra), the researchers developed a mathematical model that incorporated both within- and between-farm bovine TB transmission.

“Our model offers a dispassionate, unbiased view of the spread of bovine TB through the cattle industry of Great Britain,” says Professor Matthew Keeling, from the University of Warwick’s School of Life Sciences and Department of Mathematics. “The model is based on the recorded pattern of positive and negative tests and uses the known movement of cattle around the country. We aim for it to provide policy-makers with the best evidence possible from which to make decisions relating to bovine TB and to contribute to the ongoing discussions on this sensitive issue.”

The model allowed the researchers to tease apart how different routes involved in transmission interact and overlap.

Dr Ellen Brooks-Pollock from the Department of Veterinary Medicine at the University of Cambridge adds: “By using the most recent data, our model predicts that it is most likely that both cattle movements and the local environment are driving the front of the epidemic. Imperfect cattle skin tests contribute to the spread by delaying the time until infected herds are detected for the first time and incorrectly identifying herds as clear of infection.”

One of the key results from the model is the large variation in what happens to farms once they are infected.

“We found that the vast majority of infected farms don’t spread the infection to any other farms before they clear infection themselves. Only a small number of farms spread the infection, and they can cause the majority of new cases”, says Dr Brooks-Pollock.

The researchers argue that the findings are essential for improving the targeting of control measures. If infected farms can be identified and caught early then it might be possible to make substantial progress in tackling the epidemic.

“The model we are putting forward can be used to address several potential control methods – but there is no single panacea,” says Professor Keeling. “All controls have advantages and disadvantages. However, we find only three controls have the power to reverse the current increase in cases: more frequent or more accurate testing, vaccination of cattle and culling all cattle on infected farms.”

The control measures the researchers investigated were designed to be ‘idealised’ control options to understand what measures in theory could stop the increasing epidemic. The researchers did not consider the practicalities or economics of implementing control measures.

The research was funded by the Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the Engineering and Physical Sciences Research Council.

Adapted from a press release from the University of Warwick.

The majority of outbreaks of bovine TB within cattle herds are caused by multiple transmissions routes – including failed cattle infection tests, cattle movement and reinfection from environmental reservoirs such as infected pastures and wildlife – according to the first national model of bovine TB spread, published today.

It's most likely that both cattle movements and the local environment are driving the bovine TB epidemic
Ellen Brooks-Pollock
Cows (cropped image)

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Winners of the first Odile Bain Memorial Prize announced

By pbh25 from News feed generator. Published on Jun 12, 2014.

University Senior Lecturer Dr Cinzia Cantacessi is one of two winners of the inaugural Odile Bain Memorial Prize for early career scientists who have made an outstanding contribution to the fields of medical and veterinary parasitology.

The Odile Bain prize is sponsored by the open access journal Parasites & Vectors and the animal health company Merial. It is awarded in memory of Odile Bain’s outstanding contribution to medical and veterinary parasitology and her actions in encouraging productive collaborations among biologists, veterinarians, physicians, and fundamental and applied parasitologists worldwide.

Dr Cinzia Cantacessi is the winner of the Veterinary Parasitology category. She is a Senior Lecturer at  the University of Cambridge's Department of Veterinary Medicine and receives the prize in recognition of her significant advances to the application of bioinformatic methods in parasitology, across a wide span of organisms of great impact for veterinary and human health.

Domenico Otranto, chair of the prize evaluation committee and Parasites & Vectors Advisory Board member says: “Over almost half a Century, the research of Odile Bain had a major impact on the scientific community. Her charming personality, infectious enthusiasm for the research and her supportive attitude towards early career scientists inspired the establishment of this prestigious Award to perpetuate her name. Undoubtedly, Odile represents a role model for young generations of scientists.“

The prizes were formally awarded during the joint meeting of the Irish Society of Parasitology/British Association for Veterinary Parasitology/European Veterinary Parasitology College at University College Dublin this week.

Dr Cinzia Cantacessi says: “I feel extremely honoured and privileged to represent a generation of young parasitologists whose remarkable work keeps our discipline at the forefront of biomedical research. Truly dedicated mentors like Odile Bain have contributed to shape and inspire us all.”

The other scientist recognised was Dr Stefanie Knopp, winner of the Medical Parasitology category. She is a postdoctoral researcher at the Swiss Tropical and Public Health Institute in Basel, Switzerland and at the Natural History Museum in London.

 

University Senior Lecturer Dr Cinzia Cantacessi is one of two winners of the inaugural Odile Bain Memorial Prize for early career scientists who have made an outstanding contribution to the fields of medical and veterinary parasitology.

Hookworm x40mag (1)UK NEQAS

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11,000-year-old living dog cancer reveals its secrets

By fpjl2 from News feed generator. Published on Jan 23, 2014.

This cancer, which causes grotesque genital tumours in dogs around the world, first arose in a single dog that lived about 11,000 years ago. The cancer survived after the death of this dog by the transfer of its cancer cells to other dogs during mating.

The genome of this 11,000-year-old cancer carries about two million mutations – many more mutations than are found in most human cancers, the majority of which have between 1,000 and 5,000 mutations. The team used one type of mutation, known to accumulate steadily over time as a “molecular clock”, to estimate that the cancer first arose 11,000 years ago.

“The genome of this remarkable long-lived cancer has demonstrated that, given the right conditions, cancers can continue to survive for more than 10,000 years despite the accumulation of millions of mutations,” said Dr Elizabeth Murchison from Cambridge’s Department of Veterinary Medicine and the Wellcome Trust Sanger Institute, who is lead author on the study, published today in the journal Science.

The genome of the transmissible dog cancer still harbours the genetic variants of the individual dog that first gave rise to the cancer 11,000 years ago. Analysis of these genetic variants revealed that this dog may have resembled an Alaskan Malamute or Husky. It probably had a short, straight coat that was coloured either grey/brown or black. Its genetic sequence could not determine if this dog was a male or a female, but did indicate that it was a relatively inbred individual.

“We do not know why this particular individual gave rise to a transmissible cancer,” said Murchison, “But it is fascinating to look back in time and reconstruct the identity of this ancient dog whose genome is still alive today in the cells of the cancer that it spawned.”

Transmissible dog cancer is a common disease found in dogs around the world today. The genome sequence has helped scientists to further understand how this disease has spread.

“The patterns of genetic variants in tumours from different continents suggested that the cancer existed in one isolated population of dogs for most of its history,” says Dr Murchison. “It spread around the world within the last 500 years, possibly carried by dogs accompanying seafarers on their global explorations during the dawn of the age of exploration.”

Transmissible cancers are extremely rare in nature. Cancers, in humans and animals, arise when a single cell in the body acquires mutations that cause it to produce more copies of itself. Cancer cells often spread to different parts of the body in a process known as metastasis.

However, it is very rare for cancer cells to leave the bodies of their original hosts and to spread to other individuals. Apart from the dog transmissible cancer, the only other known naturally occurring transmissible cancer is an aggressive transmissible facial cancer in Tasmanian devils that is spread by biting.

“The genome of the transmissible dog cancer will help us to understand the processes that allow cancers to become transmissible,” said Professor Sir Mike Stratton, senior author and Director of the Sanger Institute.

“Although transmissible cancers are very rare, we should be prepared in case such a disease emerged in humans or other animals. Furthermore, studying the evolution of this ancient cancer can help us to understand factors driving cancer evolution more generally.”

Inset image: Elizabeth Murchison and Andrea Strakova, University of Cambridge and Genome Research Limited

Scientists have sequenced the genome of the world’s oldest continuously surviving cancer, a transmissible genital cancer that affects dogs.

It is fascinating to look back in time and reconstruct the identity of this ancient dog whose genome is still alive today in the cells of the cancer that it spawned
Elizabeth Murchison
Non svegliare il can che dorme
Cambridge Science Festival event - 8pm, Tuesday 18 March

Transmissible cancers in dogs and Tasmanian devils
Join Andrea Strakova for a talk which will reveal unexpected findings about two unique cancers which have adapted to transfer by the means of living cancer cells between their hosts – Tasmanian devils and domestic dogs. We will explore how a cancer can become transmissible, despite the fact that it is usually considered to be a malignant transformation of cells of your own body.

 

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