Veterinarians knew resistance would occur eventually. Some say it’s here now, while others remain confident in their products.
Fifty five percent of owned dogs and 95 percent of owned cats are not on a preventive heartworm treatment, according to Tom Nelson, DVM, of Animal Medical Center in Anniston, Ala., a past president of the American Heartworm Society.
Even when taking heartworm preventive purchases into consideration, there’s no evidence supporting compliance for these “treated” pets, which leads to the question: How many pets are receiving adequate protection?
Heartworm disease has been diagnosed in all 50 states and is increasing. With heartworm disease testing occurring in less than half of owned animals, experts are concerned that exposure, the slow-kill method and possibly resistance are leaving pets vulnerable to a potentially deadly threat.
“Out of 70 million U.S. dogs, 22 million are tested for heartworm disease and out of 90 million cats, 50,000-60,000 are tested,” Dr. Nelson says. “Prevention compliance is lower now than it has been in years past. Owners are more concerned about a flea or tick infestation because they can see it on their pets, but when it comes to heartworms, concern is low. Even when people are aware of risks, they still choose not to take precautions. Look at all of the cigarette smokers still out there—none of them are saying they don’t know it causes cancer.”
Manufacturers and veterinarians are continually trying to devise ways to relay the importance of prevention to pet owners. Despite such educational efforts as word of mouth, commercials and websites, warnings sometimes fall on deaf ears. Often, discussing treatment costs makes owners more receptive to preventive care.
“Depending on the size of a dog, treatment can cost $500 to $1, 000,” Nelson says. “Considering the regimen of injections, cage rest and the discomfort an infected animal experiences during heartworm treatment, common sense says prevention is the way to go, but not everyone uses that logic.
“Treatment success rate is at about 95 percent, but cost is always a heavy factor on lack of compliance, despite the alternative.”
All veterinary-recommended heartworm preventives come with stickers for the physical wall calendar, but as more people go digital, technology steps in to remind owners to administer their pets’ medication.
“Recently, we’ve added the service RemindMyPet.com, which provides pet owners reminders of when to give their pets medications,” says Jason Drake, DVM, director of professional services at Novartis Animal Health, with U.S. headquarters in Greensboro, N.C. “This is a nice innovation in that at its center is a pet owner portal with useful information, and the service allows for reminder messages to be sent through different digital media. RemindMyPet.com has gotten very positive feedback from both veterinarians and consumers.”
Intervet/Schering-Plough Animal Health of Summit, N.J., offers a reminder service for its Tri-Heart, but says owners can set up their own reminders on home computers as well.
“What’s important to remember with prevention is that timing is important,” says Andy Skibitsky, product director at Intervet/Schering-Plough. “Be sure to update your treatment to ensure appropriate protection [as the pet’s weight changes].”
Bayer Animal Health of Shawnee Mission, Kan., released study results in January that indicated its Advantage Multi for dogs (imidacloprid + moxidectin) topical solution was the only heartworm preventive of four leading brands tested that demonstrated 100 percent efficacy against the MP3 heartworm strain (Dirofilaria Immitis).
While thinking of heartworm disease in strains is a newer concept, Bayer says the MP3 strain—named for Miss Piggy, the Georgia dog microfilaria were extracted from during the study—is exceptionally difficult to eradicate.
Byron Blagburn, PhD, of Auburn University, led the study and says that efficacy of Bayer’s preventive has not been tested on all heartworm strains. But he says he followed protocols previously used by companies seeking FDA heartworm efficacy approval.
“At the time competitor preventives we tested in this study achieved FDA approval, it was required that 100 percent efficacy after a single treatment could be demonstrated for product approval,” says Cristiano von Simson, DVM, MBA, director of veterinary technical services for companion animal products at Bayer Animal Health.
“This indicates to us that if the products were effective when they received FDA approval, but cannot show the same efficacy now, resistance has occurred.”
But the meaning of the term “resistance” isn’t that clear cut, Nelson says.
“Strains of heartworm aren’t the same as a virus,” Nelson says. “Genetics in worms change each time a mating occurs, because of sexual reproduction, not a cloning. These worms share some of the same genetic material and might be less susceptible to certain products, but that doesn’t mean that it is caused by resistance.
“Life is a bell-shaped curve. Most of us are in the middle, and some are on the left and susceptible to aspirin, for example, while those on the right can take the whole bottle and be OK. It’s the same principle here with the microfilaria.”
Nelson suggests a plausible way resistance could occur is through the slow-kill method of treating dogs diagnosed with heartworm disease. For whatever reason veterinarians chose slow-kill—perhaps in treating an older dog or to achieve owner’s compliance for treatment—they were setting up a prime environment for resistance.
Slow-kill entails treating heartworm disease with heartworm preventive instead of immiticide, the faster, more potent treatment to rid a dog of adult worms. Worms build a tolerance to the low-dose meant for use as a preventive measure. They reproduce in the dog and their offspring are a bit stronger than those with no exposure to treatment.
A mosquito getting a blood meal from the canine host picks up the microfilaria and passes them to another animal.
“Veterinarians weren’t thinking about building resistance when they treated patients with a slow-kill method,” Nelson says. “They were more likely thinking, ‘This is how I can help this patient and the client doesn’t have funds to finance a more straightforward approach.’ Over time, they grew comfortable using this treatment as a solution.”
Given client forgetfulness and improper administration of preventives, a heartworm injection could be seen as the solution. An injection given at the veterinary office by a veterinarian or technician would limit human error issues and one visit could protect the animal for a year.
But the annual inoculation idea has had its obstacles.
“There have been concerted efforts to produce a vaccine to prevent heartworms, but the immunity produced is too short lived to be of any practical use,” Nelson says.
“Pfizer’s ProHeart6 (moxidectin) had reports of adverse reactions, which might have been caused in part because the injections were given with multiple vaccines in the same visit. It was off the market for a while, and then it returned in 2008. Many veterinarians remain cautious about administering it for fear of an allergic reaction.”
Some in the industry say the Bayer study is diverting focus from what should be the main concern in discussing heartworm disease—the lack of owned animals tested for the infection and on any form of prevention.
“There is much interest surrounding recent statements [specifically the Blagburn study sponsored by Bayer Animal Health] regarding the effectiveness of heartworm preventives in isolated geographies of the United States,” says Natasha J. Mahanes, a spokeswoman for Merial Ltd. of Duluth, Ga.
“Importantly, no scientific data have demonstrated reasons to doubt product efficacy, and the discussion itself has the potential to distract veterinarians from the real problem of heartworm prevention: Most dogs that visit veterinary clinics receive no heartworm prevention at all.
“Also, with those dogs that do receive a heartworm preventive product, there are many gaps in prevention when the pet is at risk of having a D. immitis larval infection develop past the tissue stage and reach the pulmonary vasculature.
“This happens when puppies are not started on heartworm preventive until they are older than 2 months and when pet owners fail to re-purchase heartworm preventive on time.”
“Educating pet owners and veterinary teams on the importance of monthly year-round prevention represents the greatest opportunity to reduce the number of heartworm cases,” Mahanes says.
Furthering veterinary education about the parasite will also be key in future advances in preventing and treating heartworms, experts say.
“We are a founding sponsor of the National Center for Veterinary Parasitology at Oklahoma State University, which we are very excited about,” says Novartis’ Dr. Drake.
“We have great partnerships all over the world with parasitologists engaged in research to better understand the key issues in parasite infection and infestation and how we might better address them.”