Feature: New Technology Transfer award to tackle equine strangles
7 July 2009. By Chrissie Giles
"We had an outbreak in late 2008. One mare lost her foal and died herself four days later. We also lost our best mare for breeding and horse shows - she basically drowned in front of us. It was the worst thing I've ever seen, I'll never forget it."
Karoline Thorpe, a breeder of miniature Shetland ponies in Oxfordshire, is describing the effects of equine strangles, a highly infectious bacterial disease that causes breathing problems, and sometimes death, in horses and donkeys (see 'Strangles at a glance' below).
"The main problem with strangles is the time taken to diagnose it," says Dr Andrew Waller, Head of Bacteriology at the Animal Health Trust. "At the moment, if an outbreak is suspected it might take a couple of days after a vet has visited to get test results." He explains that owners often won't isolate horses until they have received a positive test result, so in the time spent waiting for results there could be horses shedding infectious material, potentially spreading strangles to healthy horses.
The impact of the disease can be devastating to horse owners and those whose livelihood depends on having fit animals. "The implications of saying you have strangles on site are massive," says Dr Waller. "Owners will remove horses from a livery yard or stop taking their animals to a stud farm. It can mean people lose a lot of business and the disease has the opportunity to spread even further."
Now, Dr Waller and colleagues have received a Translation Award of just over £580 000 from the Trust - the first veterinary award made through our Technology Transfer division - to develop an improved diagnostic test for the strangles bug in collaboration with Atlas Genetics Ltd. The new test should help vets identify infected horses more quickly than is currently possible, allowing owners to isolate horses sooner and minimise the risk of the infection spreading.
See the signs
Vets have several tests at hand to diagnose strangles. One is the culture test, where a sample is applied to specially coated petri dishes to see if the strangles bacterium, Streptococcus equi, grows. Results can take up to four days. Faster and more sensitive is the PCR (polymerase chain reaction) test, in which any S. equi DNA present in the sample is copied millions of times and detected. The advantages of this kind of test include that it can specifically identify S. equi in the face of other bacterial contamination, which could otherwise lead to a false-negative culture test.
Research by Dr Waller and colleagues at the Animal Health Trust has shown that the S. equi gene conventionally used as the 'target' in PCR tests can be lost in some bacterial strains that cause persistent infections. They have since designed a new test, still based on PCR, which targets a gene that remains present in all strains of the strangles bug tested to date.
The new Trust award will be used to support the integration of an Animal Health Trust PCR test and a rapid diagnostic technology developed by Atlas Genetics. The test would not only give results faster but could be run by vets wherever the horse is. "The end goal is to produce a point-of-care test that will give a result within 30 minutes," says Dr Waller. "The vet will take a swab, add a sample to a card and then slot this card into the machine." The PCR will take place entirely within the device, which he says will be the size of a desktop phone.
"This platform is going to be fantastic and will have huge ramifications for other diseases, both for veterinary and clinical diagnostics. The Animal Health Trust is also working on quantitative PCR tests for equine influenza and herpes viruses, and for infectious diseases in other animals. There are many potential applications of this technology."
Prevention
Early diagnosis is only one aspect of the fight against strangles. As with all infections, prevention is better than cure, and Dr Waller stresses the importance of vaccination and good management of animals in trying to stop cases of strangles occurring. However, a live vaccine introduced into the UK in 2004 has been withdrawn, and there is currently no vaccine against S. equi licensed for use in Europe. The Animal Health Trust is working on a live vaccine, as well as collaborating with the pharmaceutical industry on developing subunit vaccines, which are based on parts of the bacterium.
Good management is potentially easier to implement, although Dr Waller highlights a lack of awareness among some horse owners and handlers. Strangles is highly contagious and it can be spread by nose-to-nose contact between horses, and through shared equipment and water troughs.
So, even if these improvements are possible, will strangles ever be wiped out for good? Dr Waller is optimistic: "Strains of S. equi are so closely related over time and around the world that I think with good diagnosis and management and an effective vaccine you could eradicate it."
"Improving the time to diagnosis is critical in preventing disease spread. Lab tests have been great and have made a big difference, but point-of-care tests are what people want, and what I think is required to prevent this terrible disease spreading."
See our related feature on the study of the genome of S. equi.
Top image: A horse with strangles. Severe swelling under the jaw or neck is characteristic of strangles infection. Credit: Professor Derek C Knottenbelt, University of Liverpool.
References
Holden MTG et al. Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens. PLoS Pathog 2009;5(3):e1000346.
Waller AS, Jolley KA. Getting a grip on strangles: recent progress towards improved diagnostics and vaccines. Vet J 2007;173:492-501.
Heather Z et al. A novel streptococcal integrative conjugative element involved in iron acquisition. Mol Microbiol 2008;70:1274-92.
An equine plague?
Strangles is often compared to human plague, but what is the scientific basis, if any, of this comparison?
Streptococcus equi is thought to have evolved from Streptococcus zooepidemicus, yet there are key differences between the genomes of the bacteria, which researchers think are linked to the different diseases caused by the two species.
S. zooepidemicus affects a range of animals, including horses, cows, seals and dogs. It can also affect humans, usually causing a respiratory tract infection. S. equi is, by comparison, very specialised - it infects horses and donkeys only and targets the lymph nodes in the head and neck, where it replicates. Yersinia pestis, the organism that causes human plague, operates in a similar way, making buboes (swellings) at the lymph nodes, where it survives in the host.
Researchers think that certain genetic similarities between S. equi and Y. pestis could have evolved independently in each of the bacteria, an example of convergent evolution. In other words, the bacterial species have evolved similar strategies to target the same type of tissue (lymph nodes) rather than evolving the same genes.
Strangles at a glance
- Equine strangles is caused by infection with the bacterium Streptococcus equi.
- The disease causes fever, loss of appetite, depression, cough and nasal discharge in horses and donkeys.
- Strangles can produce abscesses in the lymph nodes, causing swelling under the jaw or neck which can restrict the airway, hence the 'strangles' name.
- Among the complications is 'bastard strangles', where abscesses form in lymph nodes distant from the head and neck, often affecting other organs.
- The lethality depends on many factors, including the age of the animal, infectious dose received, etc. but unpublished data from Dr Waller's lab suggests a mortality of around 2 per cent.
- Infected horses can act as carriers, spreading the disease to other animals, despite showing no symptoms of infection themselves.