INFECTIOUS DISEASE

Flexible and Opportunistic

Dry Cough? Nasal Discharge? Keep S. zooepidemicus in the Differential for Respiratory Diseases

Marie Rosenthal, MS

The organism, Streptococcus equi subspecies zooepidemicus is the bacterium that is most often recovered from a horse’s oropharynx even when healthy, which might suggest that it is not a serious threat, but Andrew Waller 3rd, PhD, the chief scientific officer at Intervacc in Sweden, thinks it is cause for concern.

Several recent studies show that S. zooepidemicus is quite the opportunist and can cause a variety of diseases in many animals, including humans. Often by the time there are clinical signs, the organism has already spread around the barn, according to Dr. Waller.

“The disease is often subclinical, so it can be quite tricky to pick up—sort of a bit like COVID—it can spread around without many signs, and then every now and then, you get a flare up of severe disease,” he explained.

You might consider including it in the differential in an animal with obvious cough, he said, and be vigilant about biosecurity and wearing personal protective equipment (PPE). Not only does it spread swiftly among a group of horses, but it can sometimes affect the people caring for them.

“It is something to watch out for,” he said at the American Association of Equine Practitioners Annual Convention 2021. “If you ever treat animals that are obviously coughing, just be aware that it can jump into humans. It's flexible and opportunistic, and it's got a variety of mechanisms to allow it to cause disease in different animal hosts.”

Human cases of S. zooepidemicus can be extremely serious, he added, mentioning one case in a caregiver in Iceland during an outbreak who suffered septicemia and a miscarriage, and tested positive for the particular strain of S. zooepidemicus that was causing the outbreak.

“It’s just something to bear in mind, if you go and see an animal that has obvious respiratory signs of disease, it might be worth wearing some sort of PPE,” he said. “The risk of it transferring to humans is really small, but when it does, it can cause really nasty disease.” Streptococci occur in many different animals, and they cause a variety of different diseases. Most veterinarians are familiar with S. equi, the cause of strangles, a common infectious disease in horses, often characterized by fever and abscesses of the lymph nodes. They might be less familiar with S. zooepidemicus, although it has been associated with respiratory diseases, uterine infections and ulcerative keratitis in horses.

He talked about an outbreak in Iceland that was particularly interesting because of how quickly it spread in this closed community. Icelandic horses are an extremely robust breed that can tolerate the country’s extreme weather conditions, so the country has taken great efforts to keep the breed robust—imports are banned. “Because of this lack of import, they're free from the most serious diseases in horses, such as equine influenza virus, equine herpesvirus 1, and of course, strangles, but that means that they're extremely vulnerable to these and other new agents that might be introduced into Iceland,” Dr. Waller explained.

In April 2010, a respiratory disease was identified in several horses in an equine center at Holar University in the northern part of Iceland. Most of the animals had a dry cough with a serous nasal discharge that became mucopurulent over time; laryngitis and mucus in the tracea were also signs. Most horses did not have a fever. The incubation period was around 2 weeks and the signs lasted 4 to 6 weeks, but largely depended on the dose of the pathogen that the horses received, he explained. “So, if they were densely packed together in barns, then they seemed to have a shorter incubation time and a longer duration of signs than if they were outside in the fresh air.”

The outbreak quickly spread to other regions of the country, and by May, cases were found in the East and south as well. That quick spread suggested “the incursion of a new viral agent,” he explained.

To determine the cause, 3 healthy horses were introduced to an infected stable and monitored carefully every day for respiratory signs. After about 19 days, the horses had a cough and mucus discharge. They were euthanized on day 21 or 28.

There was excess mucus in the respiratory tract. Samples were taken and sent to various laboratories around Europe for extensive investigation, looking not only for equine pathogens, but also pathogens of humans and other animals as well, but no viral agent was identified that was consistent with disease in these horses. They also looked for S. equi even though there was no lymph node abscesses. All the samples were negative on both culture and polymerase chain reaction testing.

“So it wasn't, Streptococcus equi, however, almost all cases of animals that were ill with the respiratory signs had Streptococcus zooepidemicus recovered from them.”

They performed genome sequencing on 257 isolates from Iceland and found that 199 of these were clustered into 4 closely related groups that they called clade 1, 2, 3 and 4. They found clade 4 in 37 isolates from 8 horses clustered in one geographic area. They found clade 3 in 52 isolates from 14 horses and 1 dog at 8 farms. They found clade 2 in 28 isolates from 14 horses at 10 farms, and in 1 person.

They determined that none of them were the epidemic strain due to several factors, such as diversity and geography.

The researchers found their answer in clade 1, where they found 83 isolates from 45 horses at 21 farms, as well as 1cat and the woman discussed earlier. The isolates only differed by a maximum of 25 bases, so the researchers decided it had to be the epidemic strain.

“The amazing thing was that all these strains from all around Iceland—even though the geographical distribution was really high—only differed by 25 bases at the DNA level. They were incredibly closely related to one another. And so, this had to be the strain that was responsible for the disease that was being seen in Iceland at the time,” he explained.

They then did a trace-back and looked at the various affected premises and found 1 yard in the south of Iceland that used a submerged treadmill to train and rehabilitate horses.

“What we think happened is a horse that was underperforming had gone to this yard to be improved and trained, and it had shed S. zooepidemicus into the water. And then the subsequent horses that went through that treadmill during that day were being exposed to it,” he explained.

Since horses were typically only at the yard for a short period, the horses were returned to the original barn before they exhibited signs of respiratory disease.

“And then, of course, they were able to cough and spread it to all of the horses that were there, and we had the epidemic,” he said.

“Clearly this strain had just gone everywhere in Iceland, and there is no possibility of being able to eradicate it from the horse population.”

Three years later, they did a quick survey to see if the strain was still present, and they found S. zooepidemicus was a commensal agent. “And maybe that's because it's just present in the population, and we can't actually tease apart which strains are causing disease from the strains that are colonizing,” he said.

Their research suggests the strain was present in Iceland before the outbreak, but perhaps, that particular environment with the submerged treadmill enabled spread of a more virulent strain.

“Streptococcus zooepidemicus causes disease in a huge variety of animal hosts including humans, so it is something to watch out for,” he said,adding that it can spread without patient zero having any clinicalsigns.

EMERGING STRAINS

New strains are constantly emerging and spreading, according to Dr. Andrew Waller. Right now, they are tracking a variant (SD194) that was first identified in China and led to the death of hundreds of thousands of pigs in China.

It spread through Asia and was just recently identified and recovered from pigs that were dying of disease in North America, as well.

“And we've just recently had evidence that it can transfer to humans via consumption of raw pork products,” he said.

“One thing that we'd like to be able to do is to identify more disease-causing strains and use that information to understand how they're causing disease, so that we can minimize their effects and keep animals, whether it's horses or pigs or sheep or goats or so on, healthy in the future.

There was a report of a viral outbreak in more than 3,000 horses around New Market, U.K., but no virus was ever identified. “And unfortunately, no bacteria were recovered from these particular horses, either,” he said, “but the clinical signs—coughing and nasal discharge—were exactly what we saw in Iceland.

“So, it does make me wonder whether this could have been S. zooepidemicus.

“If you get cases like this, please get in touch because we've now got all of the tools that are required to be able to examine these in more depth and understand what might be causing the problem,” he said. Tools such as the Global

Platform for Genomic Surveillance can identify outbreak strains and track transmission. So far, they have 670 isolates of S. equi from 19 countries.

Platform for Genomic Surveillance can identify outbreak strains and track transmission. So far, they have 670 isolates of

“It's a really fantastic technique to understand what might be causing disease in particular groups of horses or other animals as well,” he said.