Heart to Heart: Is heartworm resistance an issue?

Debbie had scheduled Rex, her one-year old Vizsla, for his annual check-up in early spring. As she and Rex entered Dr. Jenson’s office, Debbie guided Rex to the floor scale so Tina, one of Dr. Jenson’s technicians, could check his weight. “Fiftyfour point eight.” Tina recorded Rex’s weight on his chart. “You’re getting to be a big boy now, “ Debbie cooed as she scratched Rex’s ears and then followed Tina into one of the exam rooms.

Dr. Jenkins came in, said “hi” to Debbie, and dropped to one knee to play with Rex. He clipped Rex’s nails, then checked him all over, gave him a distemper booster shot and bordetella vaccination, and drew blood for a heartworm check. As he gave Rex a biscuit, he asked Debbie if she had any concerns or questions. Since Debbie didn’t, Dr. Jenkins excused himself to see another patient. Debbie paid her bill and drove back home. The call she received later that week was the furthest thing from her mind.

“He what?!” exclaimed Debbie as Dr. Jenkins told her that Rex had heartworms. “How can that be? I give him his medication religiously every month.” Dr. Jenkins explained that Rex had been taking a dose specified for dogs up to 50 pounds and he now weighed more than that. “His dose was correct at the time of your last visit but, at his current weight, he might have been vulnerable. Also, some experts believe that certain strains of heartworms are developing resistance to medication.” Dr. Jenkins then assured Debbie that he would give Rex the best treatment available and scheduled an appointment for the next morning.

How did Rex become infected? There are many possibilities. Despite Debbie’s insistence that she always dosed on schedule, most owners are non-compliant in some manner. Even if Debbie never missed a dose, Rex’s increased weight meant that he should have been on a higher dose as soon as he exceeded 50 pounds. Maybe his immune system was compromised temporarily, or a previous test missed an infection that was now detectable, or maybe the heavy spring rains had boosted the population of infected mosquitoes. Or, just maybe, Rex’s heartworms were resistant to medication.

The first heartworm preventive for dogs, diethylcarbamazine, was introduced in 1977 as a daily oral tablet. In 1987, monthly oral preventives were launched. By 2000, topical and injectable products had received FDA approval.1

In 1998, the FDA received the first report of heartworms in a dog that had been receiving a preventive.1 Whether that case was due to owner noncompliance or other reasons was never confirmed. Since 1998, though, the number of complaints received by the FDA has been growing. However, the method of reporting these cases has been inconsistent across the industry. To further complicate the analysis, the dog population has been growing, owner utilization of veterinary services has been variable, weather patterns have been changing, and there are larger populations of mosquitoes and other members of the communication chain (e.g., coyotes and feral dogs).

For insight, I consulted thought leaders from academia, industry, and private practice. I encountered 2.5 schools of thought. The first group is adamant that most heartworm-positive treated dogs are the result of owner non-compliance. An opposing group believes that certain isolates are indeed resistant to macrocyclic lactone heartworm anthelmintics. In the middle are those who think that resistance is possible but very hard to prove. According to these experts, we must first disqualify all other factors such as genetic changes in the isolates, sensitivity and reporting of antigen testing, research inconsistencies, interactions with other drugs and nutraceuticals, immune system health, feral dog and coyote population, mosquito population, weather changes, economic factors that influence preventive use, animal weight changes, and owner compliance. For scientific rigor, most (if not all) of these factors would have to be evaluated in a controlled environment.

Though a scrupulously compliant dog owner myself, I know that many owners are not. As an industry proponent, I would like to believe that the second group is mistaken. However, after more than thirty years in the health care industry, on both the human and veterinary sides, in both delivery and research, I am most comfortable in the middle. What I know for sure is that, after 25 years of administering an oral monthly heartworm preventive during what is considered mosquito season in the North Eastern US, I am switching to year-round dosing for both of my dogs.

Acknowledgments. I am grateful to the following people who generously provided their thoughts on this topic: Byron Blagburn, PhD; Doug Carithers, DVM; Doug Hepler, PhD; Ray Kaplan, DVM, PhD; John McCall, PhD; Tom Nelson, DVM; Dan Synder, DVM, PhD; and Cristiano von Simson, DVM.

1Hampshire, V.A., 2005. Evaluation of efficacy of heartworm preventive products at the FDA. Veterinary Parasitology 133:192.