Q and A: Veterinary client noncompliance and heartworm resistance

Here at dvm360.com we recently received a question from a reader based on a previously posted article. Since you might have the exact same question, we’ve provided it here, along with an expert’s response.

Question from a dvm360.com reader

I read with interest the recent article “CAPC changes heartworm guidelines due to evidence of resistance.” I agree with (and practice) the recently revised Companion Animal Parasite Council (CAPC) canine heartworm treatment protocols stating that dogs should not be given long-term macrocyclic lactones as part of a slow-kill treatment protocol due to the evidence pointing to the emergence of a macrocyclic lactone-resistant strain of heartworm in the Mississippi Valley region.

But I would like to know what CAPC suggests veterinarians do for the client whose dog is heartworm-antigen-positive yet who refuses to undergo melarsomine dihydrochloride treatment. Do we start the dog on monthly macrocyclic lactone therapy (with the appropriate precautions taken regarding potential anaphylactic reactions) to prevent further heartworm infection? That certainly seems logical, ethical and in the animal’s best interest.

Or do we withhold monthly macrocyclic lactones so as to lessen the likelihood of a resistant heartworm strain developing but leave that individual patient open to further heartworm infection and potentially worsening (and even life-threatening) clinical disease? That doesn’t seem logical or ethical for the individual patient, but I can certainly see the utilitarian argument there.

Since my clients, the veterinary profession and our society as a whole typically view dogs as beloved individual family members (albeit to varying standards of care) and not as part of some collective utilitarian subculture, unless given a better argument against it, I will continue to offer monthly heartworm prevention to a heartworm-positive canine patient—not because I’m stubborn or closed-minded, but because that’s what I would want for my dog.

Answer from Dwight Bowman, DVM, PhD

First of all, giving macrocyclic lactones as part of a slow-kill treatment protocol and giving these drugs as a true preventive do not produce the same effect. The life stages are different when the drug is used prophylactically versus when it’s used for slow kill. Third-stage larvae, the L3 and the developing L4, are remarkably sensitive to macrocyclic lactones (or were before resistant isolates were selected for). When dogs are treated prophylactically, there are comparatively very few worms being transmitted between dogs, so the chance of one slipping past—even if it is slightly resistant—is minimal.

Microfilariae, on the other hand, circulate in the bodies of dogs in the millions (at 50,000 per milliliter of blood, there are 1 million microfilariae in every 5 milliliters of an infected dog’s blood). And in Dr. Byron Blagburn’s work presented in Abstract 31 at the American Association of Veterinary Parasitologists meeting in Chicago,1 it has been demonstrated using molecular markers that if a dog with circulating resistant microfilariae strains is placed under selective pressure through the administration of escalating doses of ivermectin, the number of putative molecular markers will increase, suggesting that a population of microfilariae carrying a resistant assemblage is being selected for in the blood of the so-treated dog. This is the inherent danger in slow kill and has been ever since the practice began.

How you respond to a client who refuses melarsomine dihydrochloride treatment for his dog will most likely depend on how strongly you believe that slow kill is a bad idea. To me, the tone of your argument as it develops suggests that you think it’s not a “really” bad idea; rather, it’s one that we need to nuance for the purpose of promulgation. I disagree.

Because veterinarians have not understood the dangers of utilizing slow kill relative to the development of resistance, they have misused preventives as therapeutics and as a result have painted themselves into a corner. So now veterinarians need to help minimize the damage by only recommending preventives for their intended use and directing owners of infected dogs to the appropriate therapy. The fact is that slow kill is highly likely to speed the spread of heartworm resistance, because we can no longer clear dogs of their microfilariae by using these products in this fashion2 and because it selects for microfilariae that are even harder to kill.1

Misuse of preventives has placed us in the quandary of perhaps not being able to completely protect dogs from heartworm infections. As I have stated since realizing that dogs with heartworms will have circulating microfilariae in the face of macrocyclic lactone preventive treatment,3 slow kill is a bad idea. My concern that the misuse of prophylactic macrocyclic lactones for slow kill therapy would lead to resistance has, sadly, come true.

If you continue to use preventives as treatment, the dogs will continue to have heartworms for an extended period—two years or more—and the microfilariae that will persist in 20 percent of them will continue to put other dogs at risk. And now there is likely to be much greater risk, because isolates are out there with microfilariae that are much more likely to persist in the presence of the macrocyclic lactone. Twenty percent or more of dogs treated in this way will continue to have circulating microfilariae. So now that we have cracked the lid on Pandora’s box of plagues, I cannot tell you that it is OK to open it all the way.

In the face of all of this, veterinarians need to do several things:

> Work tirelessly with their clients to convince them of the dangers of not clearing their dogs of heartworms.

> Stress that it is best to kill the worms in the office with melarsomine so that any side effects of worm death can be mitigated immediately by the veterinarian’s skills.

> Prevent the potential threat of having other dogs in the neighborhood infected with this agent.

We would not be having this conversation about MRSA. While a client is not likely to have the same level of concern for drug resistance in the dog population, it is our job to emphasize the severity of the problem.

This is a situation that shelter veterinarians especially will need to wrestle with in the future. A shelter veterinarian told me at a national meeting that he treated thousands of dogs annually with slow kill. Treating a thousand dogs this way would leave 100 to 200 dogs with circulating microfilariae—potentially resistant microfilariae—in their blood more than a year after starting them on the process. This is worrisome. There is always talk about tossing doxycycline into the mix. But should we not preserve this product to treat the bacterial targets for which it is so wonderfully effective? It would be even worse if we created a second monster as we fought the first.

I am certain we agree that heartworms are agents of a horrible disease and are correctly called the “inexorable dreaded thread.” It might help for clients to imagine that these creatures were inside them—if 10- to 50-foot-long worms were crawling about in their pulmonary arteries, they would want their physician to get rid of them now. No one would countenance a plan to let them move around for the next two to three years while they slowly died. They would check into the hospital, take their medicine, and have them treated under a physician’s care. Most clients will want the same for their dog once they better understand the disease, the risks and the treatment considerations.

References

1. Blagburn B et al. Evidence of genetic selection following treatment of a heartworm-infected, microfilaremic dog with increasing dosages of ivermectin, in Proceedings. AAVP 2013; abstract 31.

2. Bourguinat C et al. 2011. Macrocyclic lactone resistance in Dirofilaria immitis. Vet Parasitol 2011;181:388-392.

3. Bowman DD et al., Effects of long-term administration of ivermectin or milbemycin oxime on circulating microfilariae and parasite antigenemia in dogs with patent heartworm infections, in Proceedings. Heartworm Symp 1992;151-157.