Equine Grass Sickness (EGS) is characterised by extensive nerve damage, which affects the gastrointestinal tract most severely. The disease remains a deadly enigma.
With no known cause, little by way of treatment available and an alarmingly high fatality rate (85%), the condition remains a major threat to the UK’s equine population.
In 2013, H&H first reported news of a nationwide EGS vaccine trial. One year on, how close are we to being able to protect our horses from this devastating disease?
Blaming bacteria
The idea of a vaccine came about following research carried out almost a century ago.
In the early 1900s, it was suggested there was a connection between EGS and Clostridium botulinum (C. botulinum) bacteria. These are commonly found in soil and are capable of producing a range of toxins, including those that damage the nervous system (neurotoxins).
The current theory is that type C of this bacterium causes EGS. It is thought the disease occurs when a combination of risk factors trigger bacteria already present within the horse’s intestinal tract to produce neurotoxins.
Horses with EGS have lower antibody levels to this type of bacteria, while those with higher levels have a reduced risk of the disease.
Additionally, horses that have been in contact with an EGS case appear less likely to develop the disease, suggesting they may have acquired some degree of immunity.
Pushing for a cure
Vaccines are used successfully to prevent other equine clostridial diseases, such as tetanus and botulism, and it is hoped vaccination may also help reduce the risk of EGS.
Vaccination field trials conducted in the 1920s found a significant reduction in the incidence of EGS in vaccinated animals, but unfortunately research was then directed away from the association between C. botulinum and EGS.
Ninety years later, the Animal Health Trust (AHT) has launched a groundbreaking trial for a potential vaccine, in collaboration with the EGS Fund and the universities of Edinburgh, Liverpool and Surrey.
The trial will determine whether vaccinating against C. botulinum type C can help to prevent EGS.
A field trial of this magnitude has never been undertaken in equine medicine. Consequently, several preliminary studies were completed to determine whether it would be feasible to conduct the study on a nationwide scale.
Pilot trial success
Initially, a small study was carried out to confirm the vaccine was safe for use in horses.
A feasibility study then surveyed horse owners and veterinary practices that had participated in the EGS surveillance scheme, identifying eligible premises and exploring opinions on participating in the trial. Three-quarters of owners responding to the survey said they would be willing to participate, while 99% of vets agreed to take part in the vaccine trial if one of their clients wished to enrol.
Finally, we undertook a successful pilot trial. This was designed to test the methods used in the vaccine trial, rather than to test the vaccine.
Ninety-five horses and ponies from EGS-affected premises were enrolled and assigned at random to receive a full course of either the C. botulinum type C vaccine or the inactive placebo injection. Both the vaccine and placebo were shown to be safe, with a low number of mild injection site reactions reported — none of which required veterinary attention or treatment.
Scientists in the AHT’s immunology group developed a blood test to measure equines’ antibody levels to C. botulinum type C, which was used to measure the immune response to the vaccination.
Animals in the vaccine treatment group were found to have substantial increases in their antibody levels, demonstrating that the majority receiving the vaccine had a significant immune response following their primary vaccination course.
The pilot trial provided a huge amount of valuable information and feedback, but the number of horses enrolled and the time for which they were followed was too small to determine whether the vaccine can prevent EGS. A nationwide trial was the vital next step.
Gathering evidence
The EGS vaccine trial began in March 2014. Recruitment is ongoing, the aim being to enrol 1,100 horses and ponies that will be followed for two years.
The trial design is based on protocols used for clinical trials in human medicine, ensuring the highest standards and attaining the best-quality evidence for the preventive effect of vaccination.
Once eligible horses and ponies are enrolled, they are randomly selected to join one of two groups of equal size — receiving either the C. botulinum type C vaccine or an inactive placebo injection. This “randomisation” ensures the only difference between the two groups is whether they receive the vaccine or the placebo.
To guarantee scientific validity, owners, vets and researchers will not be informed of the random group assignments until the end of the trial. This is commonly referred to as “blinding” or “masking”, and is vital to ensure the findings are not influenced in any way by the expectations of people taking part.
The number of EGS cases in the vaccinated and the placebo-treated groups will then be compared statistically to determine if vaccination against C. botulinum type C significantly reduces the risk of EGS.
It is rare for any vaccination to offer complete protection against a disease. Some animals’ immune systems respond less well to vaccination than others, meaning they may be less well protected.
It would therefore be expected that cases of EGS could occur in both groups throughout the trial. If the vaccine were effective in preventing the condition, however, the number of EGS cases in the vaccinated group would be significantly lower.
If shown to be effective, the vaccine would represent the first preventive healthcare measure to reduce the impact of this devastating disease.
This article was first published in Horse & Hound magazine (7 August 2014)
