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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.

 

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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Fruit bat population covering central Africa is carrier of two deadly viruses

By sj387 from News feed generator. Published on Nov 19, 2013.

The study, conducted jointly by the University of Cambridge and the Zoological Society of London’s Institute of Zoology and published today in the journal Nature Communications, found that the “gregarious” bats span over 4,500 km of central Africa (around the distance from California to New York). The researchers also discovered that thirty-four per cent of the bats had been infected with Lagos bat virus, a disease similar to rabies, and 42 per cent had been infected with henipaviruses.

The African straw-coloured fruit bat (Eidolon helvum), which can live in roosts of over one million and often congregates near cities, was previously known to be a reservoir for these viruses, but it was not known to what extent.

For the study, the researchers tested over 2,000 bats in 12 different countries across Africa, measuring DNA from blood and tissue samples. They discovered that the bats were largely genetically similar, meaning that they travelled and mated across the continent without any evidence of population subgroups or specific migratory patterns – the largest example of this freely mixing population structure ever found in mammals. The species’ homogeneity and extensive movement means that the two viruses can be spread easily.

Professor James Wood, the study’s senior author from the University of Cambridge’s Department of Veterinary Medicine, said: “We now not only know how widespread viral infections are in this bat population, but we also know much more about its population structure. This new information indicates that the unique population of freely mixing bats across the entire continent facilitates the spread of the viruses. This has important implications for the monitoring of these viruses in order to prevent its spread to other animals, including humans.”

Fruit bats are often hunted for meat, a process which can result in a spill-over of these pathogens from animals to humans. Henipaviruses can also be spread through contact with urine and faeces. While no instances of either disease have been reported in humans in Africa, the viruses have previously been detected in pigs in Ghana. Henipaviruses have caused fatal disease in humans, pigs and horses in SE Asia and Australia.

Although potential human infection raises public health concerns, the study’s lead author, Dr Alison Peel, cautions restraint. She said: “Sometimes, a knee-jerk response can be to try and remove bats from urban areas via culling or dispersal. However, there is evidence to suggest that actions such as this can stress the bats and lead to a greater risk of spill-over. The most appropriate response is ongoing studies and public awareness to avoid handling bats, and to wash the wound thoroughly if you are bitten by a bat.”

A population of fruit bats which is found across much of continental Africa is widely infected with two deadly viruses that could spread to humans, new research reveals.

This new information indicates that the unique population of freely mixing bats across the entire continent facilitates the spread of the viruses
Professor James Wood
Bats

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Sustainable livestock production is possible

By gm349 from News feed generator. Published on Sep 25, 2013.

Consumers are increasingly demanding higher standards for how their meat is sourced, with animal welfare and the impact on the environment factoring in many purchases. Unfortunately, many widely-used livestock production methods are currently unsustainable. However, new research out today from the University of Cambridge has identified what may be the future of sustainable livestock production: silvopastoral systems which include shrubs and trees with edible leaves or fruits as well as herbage.

Professor Donald Broom, from the University of Cambridge, who led the research said: “Consumers are now demanding more sustainable and ethically sourced food, including production without negative impacts on animal welfare, the environment and the livelihood of poor producers. Silvopastoral systems address all of these concerns with the added benefit of increased production in the long term.”

Current cattle production mostly occurs on cleared pastures with only herbaceous plants, such as grasses, grown as food for the cows. The effects on the local environment include the removal of trees and shrubs as well as the increased use of herbicides, all of which result in a dramatic decrease in biodiversity. Additionally, there is also contamination of soil and waterways by agricultural chemicals as well as carbon costs because of vehicles and artificial fertiliser necessary to maintain the pasture.

The researchers advocate that using a diverse group of edible plants such as that in a silvopastoral landscape promotes healthy soil with better water retention (and less runoff), encourages predators of harmful animals, minimizes greenhouse gas emissions, improves job satisfaction for farm workers, reduces injury and stress in animals, improves welfare and encourages biodiversity using native shrubs and trees.

Additionally, shrubs and trees with edible leaves and shoots, along with pasture plants, produce more food for animals per unit area of land than pasture plants alone. Trees and shrubs have the added benefit of providing shade from hot sun and shelter from rain. It also reduces stress by enabling the animals to hide from perceived danger.

“The planting as forage plants of both shrubs and trees whose leaves and small branches can be consumed by farmed animals can transform the prospects of obtaining sustainable animal production,” said Professor Broom. “Such planting of ‘fodder trees’ has already been successful in several countries, including the plant Chamaecytisus palmensis which is now widely used for cattle feed in Australia.”

Another success has been in Colombia where a mixed planting of the shrub Leucaena with a common pasture grass resulted in a 27% increase in dry matter for food and 64% increase of protein production.

When ruminants, such as cows, goats and sheep, are consuming the plants from a silvopastoral system, researchers have seen an increase in growth and milk production. Milk production in the tropical silvopastoral system mentioned above was 4.13 kg per cow when compared with 3.5 kg per day on pasture-only systems. As the numbers of animals per hectare was much greater, production of good quality milk per hectare was four to five times greater on the silvopastoral system.

One of the additional benefits of using the silvopastoral system is that it increases biodiversity. Biodiversity is declining across the globe, and the main culprit is farming – 33% of the total land surface of the world is used for livestock production.  If farmers were to switch to sustainable livestock production methods, such as the silvopastoral system, the result would be much greater biodiversity with no increase in land use.

Professor Broom added: “It is clear that silvopastoral systems increase biodiversity, improve animal welfare and provide good working conditions while enabling a profitable farming business. The next step is to get farmers to adopt this proven, sustainable model.”

The paper ‘Sustainable, efficient livestock production with high biodiversity and good welfare for animals’ was published today, 25 September, in the journal Proceedings of the Royal Society B.

New research advocates use of pastures with shrubs and trees as it is more sustainable, improving animal welfare and increasing biodiversity.

It is clear that silvopastoral systems increase biodiversity, improve animal welfare and provide good working conditions while enabling a profitable farming business.
Professor Donald Broom

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New research reveals how cat dander triggers allergic responses

By amb94 from News feed generator. Published on Jul 24, 2013.

New research reveals how the most common cause of severe allergic reactions to cats, the Fel d 1 protein which is found in cat dander, triggers an allergic response.

Scientists have discovered that when the cat protein Fel d 1 is in the presence of very low doses of the ubiquitous environmental bacterial toxin, lipopolysaccharide (LPS), it activates the pathogen recognition receptor Toll-like receptor 4. Until now, it was not understood how Fel d 1 generated such a large inflammatory response in the immune system.

Allergic reactions are the result of the immune system overreacting to a perceived danger. Instead of identifying and responding to a harmful virus or bacteria, it misidentifies different allergens, including dander (microscopic pieces of animal skin often accompanied by dried saliva from grooming), as dangerous and mounts an immune response.

In order to find out how Fel d 1 triggers these allergic reactions, the researchers exposed human cells to cat and dog dander proteins in the presence or absence of low levels of LPS. The researchers found that when the bacterial toxin LPS is present, it increases the signalling to the body’s immune system, intensifying the body’s inflammatory response to the cat protein Fel d 1.

They also discovered that the part of the immune system that recognises the LPS contaminated Fel d 1  is the pathogen recognition receptor Toll-like receptor 4 (TLR4). (TLR4 also plays a role in a heightened immune response, and subsequent allergic reaction, to dust mite allergens and as well as the metal nickel.) The researchers then used a drug which inhibits the TLR4 response and found that it blocks the effects of the cat dander protein on human cells, thereby preventing an inflammatory response.

Dr Clare Bryant, lead author of the research from the University of Cambridge’s Department of Veterinary Medicine, said: “How cat dander causes such a severe allergic reaction in some people has long been a mystery. Not only did we find out that LPS exacerbates the immune response’s reaction to cat dander, we identified the part of immune system that recognises it, the receptor TLR4.”

Additional research revealed that the dog allergen Can f 6 (a protein found in dog dander) also enhances LPS-induced activation of TLR4. The researchers believe that dog-allergy sufferers could also benefit from new drugs which inhibit TLR4. 

Dr Bryant continued: “As drugs have already been developed to inhibit the receptor TLR4, we are hopeful that our research will lead to new and improved treatments for cat and possibly dog allergy sufferers.”

The research was funded by the Wellcome Trust and the Medical Research Council (MRC). It was published in the The Journal of Immunology.

For more information about this story, please contact: Genevieve Maul, Office of Communications, University of Cambridge. Email: Genevieve.Maul@admin.cam.ac.uk; Tel: 01223 765542.

Immune system’s extreme reaction to cat allergen previously poorly understood; study could lead to new treatments for those with cat and dog allergies

We are hopeful that our research will lead to new and improved treatments for cat and possibly dog allergy sufferers
Clare Bryant
Turkish Angora cat

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African Horse Sickness: mapping how a deadly disease might spread in the UK

By amb206 from News feed generator. Published on May 25, 2013.

As its name suggests, African Horse Sickness (AHS) is associated with the continent of Africa, where it is feared as a deadly disease. It has long been assumed by British veterinarians and horse-owners that the disease, which is carried by midges, could not spread to cooler northern climates.

But researchers now think that its arrival in northern Europe could be only a matter of time – and perhaps more importantly, that it could spread if it did arrive.

A study undertaken by scientists at the University of Cambridge Department of Veterinary Medicine, in collaboration with the Animal Health Trust and The Pirbright Institute, shows how dangerous it could be for the horse and pony population if AHS was introduced into the UK. The research also identified which regions would be worst hit at different times of the year. 

This information could be vital to strategies for coping with an outbreak if it arrived. The study also emphasises the importance of the continued exclusion of the disease.

The research was led by Dr Gianni Lo Iacono, a multidisciplinary scientist whose expertise lies in the mathematical modelling of a range of problems related to the interface between biology and physics. He worked with a team of colleagues from complementary fields including Professor James Wood, a renowned specialist in infectious diseases.

Most strikingly, East Anglia emerges from the study as the region that is most vulnerable to AHS spread which could occur if the disease was not identified early enough for action to be taken to contain it.

In Africa, the disease is spread by infected insects from species of midge known as Culicoides imicola, which carry the African Horse Sickness virus, an orbivirus of the family Reoviridae. Once a horse is infected by AHS, there is no treatment and no cure: the animal will have a high fever within 24 hours and most infected animals will be dead within 48 hours.

Other equidae, zebras and donkeys, are susceptible to AHS infection but do not have such severe disease. Infected zebras do not exhibit any apparent symptoms: as seemingly healthy animals they are potentially lethal carriers. Donkeys develop symptoms but can survive the disease.

First recorded references of AHS occurred in 1327 in Yemen, and in the mid-1600s following the introduction of horses to southern Africa. The disease was clearly identified by the British Army in South Africa 150 years ago when scores of cavalry horses perished in an epidemic.

Ever since, European horse owners have taken comfort from the fact that the disease could not strike in cooler countries. The British climate was considered too cold for the Culicoides imicola midges to survive. On top of this, the UK (and Europe more generally) has protective mechanisms in place that prohibit horses from Africa entering the country.

A growing number of veterinarians now believe that AHS can now arrive in the UK. Well-documented outbreaks were reported in Morocco (1965, 1989–1991), Spain (1987, 1988,1990) and Portugal (1989). The British climate is warming and global transportation of perishable fresh goods – such as flowers and vegetables – offers a possible route for infected midges to enter the country.

The prospect of AHS brings sharply into focus the need for greater research into ways of preventing an incursion of AHS – and ways to cope in the event of an outbreak. “Our work demonstrates that there is no place for complacency about the ability of the virus to spread here,” said Professor Wood. 

A greater understanding of AHS requires a multi-stranded approach covering the behaviour and life cycle of the midge and the geographical distribution and movement of horses, plus possible routes for infection to enter the country. Midge numbers and activity are highest during the warmer summer months, when the arrival of infection from overseas would be most serious.

In the UK, all horses have passports as a legal requirement but these documents record the owners’ address rather than the location where their animals are kept. If horses were mapped according to their owners address, London, for example, would emerge as the centre with the densest horse population. Clearly most horses owned by Londoners are kept outside the city, many of them within easy driving distance of their owners’ homes.

Correcting this issue posed problems. However, satellite data on land usage and a survey which recorded the distribution of distances between horses and their owners in different land-use settings (people live closer to their horses in rural areas than they do in urban areas) allowed the researchers to produce a more meaningful map of the risk of the disease. This showed that East Anglia is particularly vulnerable to an outbreak: not only is the region warm and dry, but it also has distinct clusters of horses, notably around Newmarket. 

The team has also investigated another important aspect of the disease: the possible 'dilution effect' that could be achieved through keeping animals not susceptible to the virus, such as cattle and sheep, close to horses.

Dr Lo Iacono explained: “In some communities in Africa people keep cattle or sheep near their houses in the belief that this will distract mosquitoes carrying malaria away from people. Some midges show apparent preference for cattle over sheep, so in South Africa deploying cattle to protect sheep from bluetongue (a similar disease to AHS in cattle and sheep) has been proposed as a way to control the disease. On the other hand, the presence of other species might well prove to be an added attraction for midges, exacerbating the threat to horses.”

The research re-emphasises the importance of veterinary education to allow early disease identification, which can reduce the critically important reaction times to allow optimal control.

The tools that Dr Lo Iacono has developed have potential applications in mapping and responding to the spread of other diseases, some of which are ecologically even more complex – such as Rift Valley Fever, a mosquito-borne disease that affects both humans and animals, causing a serious disease and in some cases death.

The research provides a good example of how theoretical models can identify biological knowledge gaps (identifying midge biting preferences). This is now being taken forward in other studies.

‘Where are the horses? With the sheep or cows? Uncertain host location, vector-feeding preferences and the risk of African horse sickness transmission in Great Britain’ by Giovanni Lo Iacono, Charlotte Robin, Richard Newton, Simon Gubbins, and James Wood is published by the Journal of the Royal Society, Interface  (2013) 20130194 doi:10 .1098/rsif.2013.0194  

For more information on this story contact Alex Buxton, Office of Communications, University of Cambridge amb206@admin.cam.ac.uk 01223 761673.

A disease lethal to horses, until now confined to hot countries, could arrive in the UK. New research creates a picture of its possible spread and pinpoints the area that would be worse hit. 

Our work demonstrates that there is no place for complacency about the ability of the virus to spread here.
Professor James Wood
Early morning, Newmarket

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New study shows how Salmonella colonises the gut

By ns480 from News feed generator. Published on Apr 19, 2013.

Salmonella is a major cause of human diarrhoeal infections and is frequently acquired from chickens, pigs and cattle, or their products. Around 94 million such infections occur in people worldwide each year, with approximately 50,000 cases in the UK per annum.

In a BBSRC-funded collaboration between the University of Cambridge’s Department of Veterinary Medicine, the University of Edinburgh’s Roslin Institute and the Wellcome Trust Sanger Institute, scientists have studied how Salmonella colonises the intestines of food-producing animals. This is relevant both to the welfare of the animal hosts and to contamination of the food chain and farm environment.

To unravel how Salmonella persists in farm animals, the scientists studied the role of thousands of its genes. Using a novel DNA-sequencing method the team screened 10,000 mutants of Salmonella for their ability to colonise the guts of chickens, pigs and cattle.  This was achieved by using a novel technique based on high-throughput DNA sequencing which enabled the screening of 475 mutants of the bacteria per single animal. In the process, they assigned roles in infection to over 2700 Salmonella genes in each of the farm animal hosts. This has yielded roles for over half the genetic instructions of the bacterium and is by far the most comprehensive survey for any pathogen in its natural hosts to date.

Professor Duncan Maskell at the University of Cambridge said, “We found that hundreds of genes are important for colonisation; this provides vital new data for the design of strategies to control Salmonella in animals and reduce transmission to humans. Our data indicate that Salmonella contains a core set of genes that is important when it infects all three hosts, but that there are smaller sets of genes that are required for infection of each individual host species.”

Professor Mark Stevens at The Roslin Institute added, “We are always trying to develop new ways of reducing the number of animals used in experiments. The methods we applied allowed us to survey the fate of hundreds of bacterial mutants simultaneously in one animal, rather than us having to test them one-by-one. This represents a significant advance in the study of microbial diseases, and can be applied to other pathogens and host animals.”

The team now plans to use the data it has collected to design vaccines or treatments to reduce the burden of salmonellosis in animals and humans.

Researchers plan to use data collected to develop vaccines to control Salmonella in animals and humans

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Congratulations

Mike Herrtage and Julie Sales completed their 250-mile cycle ride from London to Paris raising money for CAMVET. They have raised more than £6500 so far, which will gotowards equipping the new Clinical Skills Lab. The hardest part was the 17% ascent of Bexley Hill, the best part was cycling down the Champs Elysees despite Julie doing this with her fifth puncture!

Research into the control of CTVT

Dr Elizabeth Murchison and Andrea Strakova publishes their latest research into the control of CTVT.

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