Breathing life into respiratory disease research - Veterinary Practice
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Breathing life into respiratory disease research

With the 2014 London Vet Show almost upon us, Veterinary Practice reports on one of the many papers presented at last year’s event, this one reviewing work at the RVC which may lead to the development of improved canine vaccines.

KENNEL cough is a respiratory disease common in densely housed dogs. Affecting large populations of shelter dogs or guide dogs, there have always been limitations in vaccination. Now, thanks to astute virology and pathology work at the Royal Veterinary College, the way is open to develop better vaccines.

Discussing his group’s work at the London Vet Show was Joe Brownlie, emeritus professor of veterinary pathology at the RVC. Canine infectious respiratory disease (CIRD) as the condition was renamed, is a worldwide problem. “Kennel cough rather trivialises how important this condition is,” he remarked.

Effects can be acute or chronic, leading from inappetence to bronchopneumonia and in severe cases death. Vaccines do not prevent it and transmission is rapid. “Not all respond to vaccines, which gives us a clue that viruses are involved,” he said. “Our aim was to define it clinically and pathologically then look for new and novel agents.”

Using a kennel population of more than 1,000 dogs, his research group developed clinical scoring for severity – one showed no abnormal signs, five severe respiratory disease; took serum on the day of entry and at days seven and 21 to examine pathology.

Any dogs that were euthanased, in this case for rehoming reasons or behaviour problems, provided post-mortem respiratory samples, lymphoid tissues and a full necropsy. The group was also able to obtain samples from other dog populations and build up a vivid picture of clinical issues, pathology and microbiology.

Sifting through viral strains the group assayed coronaviruses, syncytial viruses and aviviruses as well as bacteria, including bordetella, streptococcus and mycoplasma. “What we discovered was a new coronavirus,” said Joe: “This was a eureka moment for the group.

“We used PCR and found it was 98.8% identical to bovine coronavirus and 98.4% to the human common cold virus. We put it forward in 2002 and published in 2003, the same year SARS was discovered, and it is in the same group.”

SARS precipitated panic throughout Asia as the method of its spread was unknown. “Frightened Chinese were slaughtering dogs because people thought they were a SARS vector,” Joe recalled. “You may have heard of the Middle Eastern respiratory syndrome coronavirus (MERS-CoV) that is fatal in humans. This is in the same group.”

High mortality rate

MERS-CoV drew attention for its high mortality rate. In 49 laboratory confirmed cases there were 27 deaths. The director general of the World Health Organisation, Margaret Chan, called the novel coronavirus a threat to the entire world.

Seroconversion of this canine respiratory coronavirus (CRCoV) is as rapid as the disease. At day one it is 20%, day seven 27%, but by day 21 it is above 90%.

“Of the dogs that came in to the shelter with an antibody to coronavirus, only 50% got respiratory disease,” said Prof. Brownlie. “Dogs without that antibody were more likely to get the disease.”

The virus is found in the airway’s endothelial linings and its action is to disable the innate immune response. This affects mucus clearance and allows secondary infection to go deeper into the airways. “What this virus does is precipitate, it allows superinfection,” he said.

CRCoV has been associated with two outbreaks of CIRD in a guide dog training centre and is now recognised by US commercial diagnostic companies as a respiratory pathogen in PCR testing.

“This is an international virus and it has been in the UK and the US for a long time, yet we did not know about it until 2003,” he said. “We are now undertaking a survey across Europe in seven centres and looking for variation.”

Efforts are now being concentrated on looking for other viruses associated with respiratory disease. Viruses present in the UK dog population include canine pneumovirus, hepacivirus and bocavirus – a member of the same family as parvovirus.

“There are other viral causes associated with CIRD and we need to be aware and familiar with them,” Prof. Brownlie said. “There are so many new viruses coming up that what we need in veterinary medicine are teams who can understand which are important.”

Bacteriology has also revealed new targets for vaccine developers. Bordetella is important and already present in vaccines, but mycoplasma and streptococci are not. Mycoplasma is responsible for between five and 30% of mild pneumona cases in children aged five to 15. It also exhibits rising antimicrobial resistance in places like China.

Mycoplasma cynos has been picked out from more than 800 isolates due to its nature as a mollicute. “They don’t have a cell wall and that causes a problem with antibiotic treatment,” he said.

“There was little known about their virulence, so we did some experimental work in animals and showed that they can be severe pathogens.”

Worldwide incidence

The streptococcal strain zooepidemicus is also now associated with CIRD. “We isolated that from 22% of the dogs in a large UK shelter. Recent reports say it has worldwide incidence and there are a lot more papers being published about it.”

CIRD is characterised as a complex multicomponent disease thanks to the RVC’s research. Viruses and bacteria associated with it have rapid aerosol spread but do not by themselves cause severe pathology. “What they do is compromise immunity and allow infection,” Prof. Brownlie said. “This is where we think the mycoplasmas come in and then we get a superinfection with the streptococcus.”

RVC research groups are now working with commercial partners to develop new vaccines. “We are finding new causes that are important and we need to know more about these agents to improve vaccines,” he concluded.

“There is a long, expensive road ahead before we can obtain a regulatory licence. It is daunting and we need your help, but we are on the way.”

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