What You Might Not Know About this Toxicity

For reasons that baffle their disgusted owners, many dogs are unable to resist the temptation to ingest sheep poop. 

Their attraction to the stuff isn’t entirely non-sensical; sheep droppings can contain undigested food particles that contain fats, proteins, and minerals, and if these are nutrients missing in a dog’s diet (underscoring the importance of a high-quality diet), a dog is going to be attracted to the smell and taste of “Ewe Berries.”

There are darn good reasons to discourage a dog from eating “sheep sheeze,” and two of them rhyme with ‘parasites’ and ‘disease transmission.’

But there is another BIG reason to discourage certain breeds from eating the droppings of several farm animals, and to illustrate, we share a story with which many of you are already familiar.

Back in 2015, “Bristol,” an Australian Shepherd, became seriously ill after a herding lesson. Her symptoms included seizures, vomiting, excessive drooling and diarrhea. The veterinarian who treated her,  Dr. Theresa E. O’Toole, a critical care specialist at Tufts University School of Veterinary Medicine, believed the Aussie had ingested the droppings of sheep from that herding lesson, “woolybacks” that had recently been treated with an ivermectin-based dewormer.  In short, Bristol suffered from ivermectin toxicity poisoning and it could have killed her. To everyone’s great relief, Bristol did recover, but the intensive treatment kept her in the hospital for over forty days.

Bristol’s harrowing saga was a needed reminder to dog owners that Ivermectin Toxicosis does not discriminate on the basis of age or gender (though very young dogs may have an increased risk), and toxicity is presented whether products are administered orally, topically, or parenterally.

There is irony here in that Ivermectin is generally safe for most dogs when used at the recommended low doses for heartworm prevention because they are able to metabolize and eliminate ivermectin effectively without issues. Some breeds, however, can be more sensitive and develop toxicosis due to a genetic mutation (MDR1 gene) that makes them less able to eliminate ivermectin from their bodies.This can lead to a buildup of high levels of ivermectin in the brain causing neurological side effects or toxicosis, and this is why young dogs are at increased risk because of immature blood–brain barriers. 

Ivermectin Toxicosis poses a risk to certain breeds:

  • Australian Shepherd
  • Border Collie
  • Collie
  • German Shepherd Dog
  • Miniature American Shepherd
  • Old English Sheepdog
  • Shetland Sheepdog
  • Skye Terrier
  • Mixed-breeds that may have herding-breed heritage

What is the mechanism that poses such a high risk to these breeds? What is it about the mutation that affects their ability to process the drug?

We go back to the mutation MDR1. This genetic gene alteration codes for a P-glycoprotein that is responsible for pumping many drugs and toxins out of the dog’s brain and other sensitive tissues. The protein acts as a protective barrier and prevents excessive accumulation of these substances in the body. In dogs with the MDR1 mutation, however, this P-glycoprotein doesn’t function properly and drugs like ivermectin (and also moxidectin, loperamide, milbemycin, and chemotherapeutic agents)  that are normally pumped out can accumulate to toxic levels in the dog’s brain and other tissues, and this is what leads to neurological toxicity.  Normal dogs can safely tolerate ivermectin doses up to 2.5 mg/kg before showing toxicity signs, but dogs with the MDR1 mutation can exhibit neurological toxicity at much lower doses, as little as 0.1-0.2 mg/kg. 

With certain breeds, the importance of genetic testing (and the need for caution around livestock dewormers) can’t be overstressed.
The MDR1 test works by detecting the presence of the specific mutation in a DNA sample from the dog. It’s analyzed using a technique called polymerase chain reaction (PCR) which amplifies and makes multiple copies of the specific region of the MDR1 gene that has the mutation.  The amplified DNA is examined to see is there is the presence of a 4 base pair deletion mutation in the MDR1 gene, a particular deletion causes a shift in the reading frame and results in a non-functional P-glycoprotein.  Based on the analysis, the dog’s MDR1 genotype is determined as either normal, norma/mutant (one copy of the mutated gene, and the potential for drug sensitivity), or mutant/mutant which means that two copies of the mutated gene indicate a high risk of drug toxicity.

The MDR1 test works by detecting the presence of the specific mutation in a DNA sample from the dog. It’s analyzed using a technique called polymerase chain reaction (PCR) which amplifies and makes multiple copies of the specific region of the MDR1 gene that has the mutation.  The amplified DNA is examined to see is there is the presence of a 4 base pair deletion mutation in the MDR1 gene, a particular deletion causes a shift in the reading frame and results in a non-functional P-glycoprotein.  Based on the analysis, the dog’s MDR1 genotype is determined as either normal, norma/mutant (one copy of the mutated gene, and the potential for drug sensitivity), or mutant/mutant which means that two copies of the mutated gene indicate a high risk of drug toxicity.

The MDR1 test offers important information not just to veterinarians, but to the owners of the impacted breeds if the dogs are working farm/ranch dogs, or if they may be participating in instinct testing or herding trials. It’s important for dog owners to ASK the owners of the stock when their sheep/horses were last treated with ivermectin.

Why?

In one study, it was found that the maximum concentration of ivermectin in horse manure is reached 2-4 days after oral dosing at the recommended rate, while another study showed that ivermectin remained detectable in horse manure for up to 40 days after oral administration.  In sheep, droops from animals drenched (orally dosed) with ivermectin caused significant mortality to fly larvae for up to a whole week after treatment, and this indicates the presence of ivermectin residue a full seven days later.

Bottom line: Ivermectin remains present in droppings/manure for an extended period after treatment, and detectable levels can last for weeks.

Though we have a herding breed which hasn’t indicated the presence of this mutation, we got curious.  We learned that Dr. Katrina Mealey discovered the MDR1 mutation and developed the first test at Washington State University. The Veterinary Genetics Laboratory at UC Davis offers the MDR1 test (as does Washington State University and its PrIMe™ MDR1 genetic test) and notes:

“This test identifies the well-known and relatively widespread 4-bp deletion associated with multi-drug sensitivity in several purebred and mixed-breed dogs.”

Did you catch that?  We repeat: “This test identifies the well-known and relatively widespread 4-bp deletion associated with multi-drug sensitivity in several purebred and mixed-breed dogs.” If a mixed breed dog include one of the sensitive breeds in its background, that dog should be tested, too.

We also wondered what the different is between an MDR1 test and a heartworm test. They are, in fact, two completely different tests that serve distinct purposes. The MDR1 Test detects the presence of that specific genetic mutation while a heartworm test screens for the presence of a heartworm parasite infection by detecting the heartworm antigen or microfilariae in the blood. A heartworm test cannot detect the MDR1 gene mutation. 

We conclude with two words if you own a certain breed: Test and ask!

To learn more about the MDR1 genetic mutation, you might find this page interesting.

Our image is by Kanashi on Unsplash

Leave a Reply

Your email address will not be published. Required fields are marked *

*
*
Website