SILENCE OF THE LAMBS
Virus causing birth defects in Ontario sheep bears some similarities to Zika,
By now, the plot is familiar: A mysterious virus appears. The disease, spread by mosquitoes, is linked to an alarming surge in birth defects. There is no vaccine or treatment.
The world has been watching this nightmare unfold in countries like Brazil, where the Zika virus is suspected of causing birth defects and other neurological disorders. Now, in Ontario, another viral outbreak is being linked to a surge in newborn deformities, albeit in a different population: sheep.
The little-known Cache Valley virus has long circulated in Canada, but veterinarians are alarmed by what they say is the largest outbreak in recent memory.
And there are reasons to worry about Cache Valley beyond its disturbing impact on lambs. While its risk to humans is currently low, there are signs that the virus could be causing more problems than we realize — and, if it ever explodes the way Zika has, the world will be just as unprepared.
“Cache Valley is not very well understood at all. It was kind of ignored for a long time,” said medical entomologist Philip Armstrong, who studies the virus and conducts mosquito surveillance for the Connecticut Agricultural Experiment Station.
“As a veterinary pathogen of sheep, it’s certainly important . . . as to human disease, I think the jury’s still out.”
For veterinarian Paula Menzies, the first sign of trouble in Ontario came around Christmas.
“It was like this huge explosion of cases,” said Menzies, a professor at Guelph University. “Veterinarians were sending (us) these deformed fetuses and I got an email from a couple of (sheep) producers saying, ‘This is happening on my farm. What the heck is this?’ ”
The answer, as a Texas laboratory later confirmed, was Cache Valley virus. First discovered in 1956, Cache Valley is spread by several mosquito species and is believed to circulate in deer. It mostly affects other ruminants, such as sheep and goats.
While outbreaks have been documented in sheep flocks since the early 1980s, the recent Ontario outbreak has caught everyone by surprise.
“It’s certainly the largest that anybody that I’ve worked with is aware of,” said Menzies, who is trying to determine the scope of the outbreak but knows of at least seven affected flocks. “The question is why?”
Among Cache Valley’s many mysteries is also the extent to which it affects humans — a question that remains unresolved 60 years after the virus was discovered.
Zika suffered from a similar problem of neglect and, as some can’t help but notice, that virus has striking parallels with Cache Valley.
To be clear, the two viruses are very different in many ways — for one, Cache Valley belongs to the Bunyaviridae family, while Zika is a flavivirus. But like Zika, Cache Valley is also spread by mosquitoes, causes mostly asymptomatic infections in the affected population and lacks any vaccine or treatment.
Cache Valley causes birth defects in sheep, attacking the fetus’s brain development when pregnant ewes are infected during their first trimester — another echo of what Zika now appears to be doing in humans.
What scientists do know is that Cache Valley can be transmitted to people by mosquito bites (humans don’t catch the virus directly from animals). To date, three human infections have been documented in the United States, all with dire consequences: meningitis, encephalitis and death.
But experts suspect Cache Valley is probably causing more human disease then we realize. A 2012 study in Mexico found Cache Valley antibodies (suggesting previous exposure) in 18 per cent of 823 patients treated for fever.
The Public Health Agency of Canada has also analyzed blood samples from suspected West Nile patients in Saskatchewan and Manitoba, finding that between 5 per cent and 16 per cent had antibodies against Cache Valley.
It’s very likely that mild illnesses are going undiagnosed, Armstrong said.
“Most physicians have never heard of this virus,” he said. “It’s not on their radar.”
Another unresolved question is whether Cache Valley could also cause human birth defects, a hypothesis that now needs closer scrutiny in light of Zika, said Armstrong.
At least one paper has provided preliminary evidence that Cache Valley could be linked to a congenital malformation — not microcephaly, the condition linked to Zika, but its polar opposite, macrocephaly, where babies’ heads are larger than normal.
The paper — far from conclusive — called for further investigations, but none have been undertaken. It was published two decades ago.
“What surprises me is that nobody has followed this up,” said lead author and arbovirologist Charles Calisher, who is now retired. “Cache Valley is a representative of a problem that we refuse to face.”
Calisher notes, however, that there are many disease threats to worry about — including others that can cause animal outbreaks and congenital problems — and not all can be prioritized.
For Michael Drebot with the Public Health Agency of Canada, the Zika epidemic is casting a spotlight on all mosquito-borne viruses, which must be better understood, especially since they are always mutating.
In fact, there is already evidence that Cache Valley is evolving. Last year, Armstrong published a study reporting on a new strain of Cache Valley virus, apparently originating in Mexico, which emerged in Connecticut in 2010 and has now become the dominant strain.
That strain has now slipped into Canada and was the culprit behind a sheep outbreak in 2011, and possibly the recent one, too.
(The virus from last year’s outbreak has yet to be isolated and the outbreak was confirmed through antibody testing).
There is early evidence that this strain can grow a little faster and replicate more efficiently, said Drebot, who is now pursuing further research.
“Is it responsible for increased cases of lamb deformities?” he asked. “Could there be a higher risk for humans? We don’t know the answers to those questions but I think it is important to further study these particular agents.” Struggling to protect their flocks The first dead lamb looked like something from a Picasso nightmare. Delivered on Christmas Eve, its spine was curved into an unnatural S shape and one leg jutted awkwardly in the wrong direction, giving it the appearance of having three front legs.
Sheep farmer Sean McKenzie chalked it up to a genetic deformity, especially when the lamb’s three siblings came out similarly disfigured.
But then, another one of his ewes gave birth to a deformed lamb — and another and another and another. After an exhausting 10 days, McKenzie was left with a “pile of death” — between 16 and 18 stillborn lambs, all grossly deformed.
“Their joints are fused and nothing is pointing in the right direction; legs are backwards . . . It’s just a mess,” McKenzie said. “It was demoralizing.”
McKenzie owns a mid-size sheep farm just outside of Oshawa and was one of several Ontario farmers hit by a major outbreak of Cache Valley virus last year.
The little-known virus causes no symptoms in adult sheep, making it a silent spreader. But if pregnant ewes are infected during their first trimester, it will attack the developing brain cells of the fetus.
While Cache Valley is endemic in Canada, this is the first time McKenzie has seen the virus in his six years as a sheep farmer.
“What we can’t figure out is why all of a sudden this last year it’s exploded like this,” McKenzie said. “Some farmers I’ve talked to have been in the business 26 years and they’ve never seen it before.”
In Canada, the first laboratory-confirmed outbreak of Cache Valley occurred in 2011-12, when several flocks were affected in Ontario and Quebec. Many other outbreaks have also been reported anecdotally.
But this latest outbreak appears to be the most dramatic one yet. Farmers and veterinarians have heard of cases from Windsor to the Ottawa area. Paula Menzies, the Guelph veterinarian, is now conducting a survey to determine how many farms are involved.
Investigators suspect pregnant ewes were likely infected by a silent outbreak that spread in the late summer or early fall. One theory is that an unseasonably warm winter prolonged the mosquitobiting season; another is that a new strain of Cache Valley has recently emerged.
But either way, farmers like McKenzie are powerless to protect their flocks. There is no vaccine for Cache Valley, so all they can do is try to prevent mosquito bites — a hard enough task for people, let alone sheep.
“I just can’t put them all in barns,” McKenzie said. “One paper (I read) said to avoid having sheep outdoors breeding during mosquito season. Well, in Canada, that means you can have them outside from October to February and that’s about it.”
McKenzie estimates Cache Valley killed about 10 per cent of his lambs born this winter, representing a loss of about $5,000. But because ewes infected early in their pregnancy often just lose the embryo, he suspects his actual losses are even greater.
Still, he is relatively lucky. Another farmer he knows lost roughly half his lambs. “That was a huge hit,” McKenzie said
The worry now is that last year’s outbreak could signal the start of a new normal. “What happens if in the next couple of years, that virus mutates to become more pathogenic such that they’re having outbreaks every year?” asked Maria Spinato, a pathologist with the University of Guelph’s Animal Health Laboratory, who autopsied lambs killed in the recent outbreak.
This has already happened in Europe with a related virus called Schmallenberg, Spinato noted.
The good news is that sheep already exposed to Cache Valley appear to develop lifelong immunity.
But in the face of a mysterious new threat, farmers are bracing themselves for what other surprises the future may bring.
“If it became a recurring theme, it would drastically change the landscape in terms of how we do business,” McKenzie said. “It’s going to be a challenge to avoid it, if it’s going to come back.”