Heartworm: Where Are We Today?

Image courtesy of American Heartworm Society

Warnings and reports about pets infected with Dirofilaria immitis in the United States are not unusual. In fact, canine heartworms were first discovered on the southern US coast in 1856.¹ What should be making headlines is the fact that despite the preventive medications that have been widely available for decades, the incidence of heartworm disease continues to rise across the nation.

According to the triennial American Heartworm Society (AHS) incidence survey, the average number of dogs diagnosed with heartworm per clinic in 2016 was 21.7% higher than the number diagnosed in 2013.² The 5 states with the highest heartworm incidence: Mississippi, Louisiana, Arkansas, Texas, and Tennessee. But no state in the country is heartworm-free, and infection in dogs is considered at least regionally endemic in every state except Alaska.

RELATED:

• Does Heat Treatment Aid Heartworm Detection?
• ACVIM 2017: An Alternative Treatment for Heartworm Disease

Veterinary parasitologists continue to study heartworm infections extensively and periodically issue updated guidelines for the best methods of prevention, testing, diagnosis, and treatment. But what will it take to eradicate this potentially deadly disease?

Although longstanding preventive and treatment methods are highly effective, veterinarians should be aware of heartworm disease advances and updates, regardless of the prevalence of heartworm in their area.

Multimodal Approach to Prevention

In human medicine, the common approach to averting a parasite-derived disease starts with thwarting contact with the vector. Consider Zika virus, for which the first line of defense is preventing the bite of mosquitoes. Although the vector for Zika and heartworm is the same, veterinary medicine historically has taken an entirely different approach to prevention. To date, the mosquito—which the World Health Organization called one of the deadliest animals in the world—has been an aspect of the heartworm life cycle that generally has been ignored.³

“In the past, [veterinarians] were under the impression that heartworm preventives were 100% effective, and so whether a mosquito bit or not wasn’t really considered important,” explained Susan Little, DVM, PhD, DACVM (parasitology), a regents professor and Krull-Ewing chair in veterinary parasitology at Oklahoma State University. “We were allowing the natural infection cycle to take place and then relying on those ‘perfect’ preventives to keep the adult heartworms from developing.”

But with the understanding that preventives are not always 100% effective and pet owners are not always compliant in giving preventives to their pets, many veterinarians and parasitologists have begun calling for a stronger focus on the mosquito. “We should probably have been including mosquito prevention all along,” Dr. Little said. “For all other parasites we talk about the life cycle, but for heartworm, we hadn’t.”

This line of thinking has sparked a movement in veterinary medicine known as the Double Defense Heartworm Protocol, an initiative from Ceva Animal Health. The corresponding website is a resource veterinarians and pet owners can use to educate themselves on the advantages of a multimodal approach to prevention. As the practice gains in popularity, continued research has been published in support of double defense.

In a 2017 study, a group of investigators led by John McCall, PhD, professor emeritus in the Department of Infectious Diseases at the University of Georgia College of Veterinary Medicine and past president of AHS, assessed the effectiveness of a topical ectoparasiticide combined with a macrocyclic lactone on transmission of heartworm from mosquitoes to dogs and subsequent development of worms in treated dogs exposed to infected mosquitoes.⁴ In the study, 32 beagles were allocated evenly to 4 groups:

• Group 1: untreated controls
• Group 2: treated topically with an ectoparasiticide on day 0
• Group 3: treated orally with a macrocyclic lactone on day 51
• Group 4: treated with an ectoparasiticide on day 0 and a macrocyclic lactone on day 51

Dogs were sedated and exposed to D immitis—infected Aedes aegypti mosquitoes for 1 hour on days 21 and 28. Upon study completion, the investigators concluded that the Double Defense protocol of a topical ectoparasiticide combined with a macrocyclic lactone had better efficacy for protecting dogs against heartworm transmission and infection than a macrocyclic lactone alone.

Still, preventing mosquitoes from biting isn’t a one-size-fits-all approach. As many as 80 different species of mosquitoes can transmit heartworm. Instead, Tanja McKay, PhD, director of environmental sciences at Arkansas State University, said it opens up a variety of channels for studying how these tiny insects play a pivotal role in intensifying the spread of such a pervasive disease. “Each mosquito species is very different in its biology, ecology, and habitat,” she explained. “It is a very complex issue, but one that must be part of the heartworm conversation.”

In the multimodal approach, preventing mosquitoes from biting doesn’t negate the need for continued use of preventives. Repellents should be used an adjunct, not as a replacement.

Rising Temperatures, Shifting Distribution

Environmental temperature is another contributing factor to the increasing rates of heartworm infection, and investigators have paid particular attention to climate change in the wake of continuing debates about global warming and the trend of once rural areas turning into densely populated cities.

Temperature Increases

As Dr. McKay explained, even the slightest temperature changes have the potential to escalate the mosquito life cycle and, in turn, the spread of heartworm. “The higher the temperature, the faster a mosquito will develop from egg to adult,” she said. “The same is true for the temperature requirement for the nematode within the mosquito. A higher temperature will decrease the amount of time it takes for a nematode to develop into the necessary larval stage for infection.”

Elevated temperatures also present the potential for an increase in the number of mosquitoes that have the capability of carrying the parasitic roundworm. “If it’s warmer outside, maybe you have 1 or more days on the front end and on the back end of the time period of when heartworm might be more of an issue,” she said. “Does that have an effect on the number of canine heartworm cases?”

Temperature fluctuations not only affect how quickly mosquitoes and nematodes develop but may also have an impact on the migration patterns of mosquito species. “We know that in the past 30 to 40 years, we’ve had a dramatic expansion of mosquitoes and new mosquito species introduced,” Dr. Little added.

Urban Heat Island Effect

Temperatures in urban areas are typically a few degrees higher than in neighboring rural regions, an occurrence known as the urban heat island effect. In fact, the annual mean air temperature in a city with 1 million people or more can be 1.8°F to 5.4°F warmer than the surrounding areas. In the evening, the difference can be as high as 22°F.⁵

Not only does the urban heat island effect impact energy demand, but it has been linked to the increased prevalence of mosquitoes where the average temperature might not have historically supported breeding. This is particularly true when manmade bodies of water, such as ponds or fountains, are introduced. “Mosquitoes take advantage of that and survive well in urban, developed areas,” Dr. Little pointed out.

Preventive Resistance

Although instances are not widespread, Dr. Little noted that veterinarians should be aware that resistant biotypes of D immitis have been confirmed. “We don’t have a feel yet for what percent of heartworm cycling in nature is resistant to the preventives,” she said, “and I don’t think anybody has been able to determine that...but resistance does happen.”

A veterinarian might suspect resistance if a dog whose owner has been compliant with giving a monthly preventive becomes infected. However, Dr. Little warned that it’s important to keep in mind that in such instances the dog may have vomited or spit out the tablet, or a topical product may not have been absorbed entirely. Resistance isn’t always the chief reason.

The best indication of a resistant isolate is when a veterinarian treating a dog for heartworm is unable to clear microfilariae with high doses of macrocyclic lactones. In these cases, Dr. Little recommends seeking assistance from a veterinary parasitologist at a local teaching hospital or calling a national specialist. “There are other strategies to clear the microfilariae,” she said, “but we definitely want to document resistance too.”

Globally, preventives are still largely effective. “The most common reason a dog gets infected with heartworm despite the fact that a veterinarian prescribed a preventive is that the dog wasn’t given the preventive,” Dr. Little said.

The official AHS statement on resistance echoes Dr. Little’s explanation.⁶ “Every compound currently marketed in every form of administration (oral, topical, and parenteral) has been shown to be less than perfect in at least 1 study. However, while the evidence indicates that resistance affects all macrocyclic lactones, differences in active ingredients, doses, and product formulation among the available preventives can result in varying rates of failures.” Perhaps most important, AHS reiterates that research findings do not demonstrate any widespread ineffectiveness of available heartworm preventives. And macrocyclic lactones continue to be successful in the vast majority of cases.

If anything, Dr. Little said, the notion of possible resistance further emphasizes the importance of regular heartworm testing.

Testing By Pretreating the Sample

The standard strategies of testing for heartworm—both looking for microfilariae and antigen testing to detect the adult female worm—are considered highly sensitive and very effective in diagnosing infection. But these strategies are not without imperfections.

As Dr. Little explained, “We know that as many as 50% of dogs that are infected with heartworm won’t have that larval stage in their blood, that microfilariae.” Additionally, in antigen testing, sometimes the protein is present in the animal but is masked from detection. This block is believed to be attributed to immune complex formations that trap the antigen.⁷

To combat false-negative results, Dr. Little said she has returned to the lapsed method of pretreating the sample prior to testing, via heat or the addition of an acid or a pepsin. This works to disrupt the immune complexes and reveal the protein. “Pretreating the samples was used routinely in the 1980s until about 1990,” she explained. It was not used again until around 2014, “when we realized there were many dogs that were infected with heartworm but didn’t have the antigen—the protein—in their blood. So we started pretreating again on subsets of dogs to try to figure how common it was, and realized that in animal shelters in the South, as many as 5% to 10% of dogs will be false-negative on a heartworm antigen test; whereas if you pretreat, they’ll become positive.”

Dr. Little recalled a particular instance in which a local working dog had so many heartworms that a cardiologist was able to see them while performing an echocardiogram, but heartworm tests came back negative. Once a sample of the dog’s blood was pretreated prior to testing, however, it revealed a strong positive.

While effective at unmasking previously undetected antigens, Dr. Little said, pretreating samples is not necessary in all cases. For one, it is a very involved process that requires a larger blood sample. And because many clinics don’t have the equipment necessary to spin the sample at the required centrifugal force, samples usually need to be sent to a lab for proper testing.

Instead, Dr. Little said pretreating the sample is recommended when a veterinarian strongly suspects heartworm infection even though previous tests were negative. It may also be effective in animal shelters, where dogs should be tested for heartworm to the best degree possible prior to being adopted.

Drastically Reducing Incidence Rates

Even with improved research and additional testing, experts report that one of the major obstructions—if not the chief hurdle—standing in the way of eliminating heartworm infection is pet owners failing to abide by preventive guidelines. Simply put, “we have a compliance problem,” said Christopher J. Rehm, Sr, DVM, president of AHS. And one of the major thrusts of AHS is to increase the number of pets that are being protected with heartworm preventives on a year-round basis, he explained. “Right now, roughly two-thirds of pets are not on prevention,” he said.

Although veterinarians can’t physically oversee the administration of preventive treatments for every patient, they (and their teams) can help educate clients and engage in conversations about proper heartworm prevention.

“Sometimes I think we take for granted that our clients know more about it or have some more parasite common sense, if you will, than they actually do,” Dr. Rehm said. “And we don’t probe enough to find out where our clients are on the learning curve about parasite prevention.” To counteract this, he recommends that veterinarians ask open-ended questions, such as “When did you last give a parasite preventive?” rather than simply “Are you good on heartworm?” The latter question might elicit a knee-jerk, affirmative reaction.

“I think sometimes people have a false sense of security that they think their dog won’t get heartworm or, if it does, we’ll just treat it, and that’s just absolutely the wrong approach,” added Dr. Little. “It’s so much better to prevent the infection to start with, instead of trying to rescue the dog once it is infected.”

References:

• History of discovery. Stanford University website. web.stanford.edu/group/parasites/ParaSites2006/Dirofilariasis/History.htm. Accessed February 14, 2018.
• Survey of U.S. veterinarians uncovers per-practice increases in heartworm-positive cases. heartwormsociety.org/newsroom/in-the-news/347-ahs-announces-findings-of-new-heartworm-incidence-survey. American Heartworm Society website. Published April 20, 2017. Accessed January 25, 2018.
• Mosquito-borne diseases. World Health Organization website. who.int/neglected_diseases/vector_ecology/mosquito-borne-diseases/en/. Accessed February 14, 2018.
• McCall J, Varloud M, Hodgkins E, et al. Shifting the paradigm in Dirofilaria immitis prevention: blocking transmission from mosquitoes to dogs using repellents/insecticides and macrocyclic lactone prevention as part of a multimodal approach. Parasit Vectors. 2017;10(Suppl 2):525. parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-017-2438-4. Accessed March 15, 2018.
• Learn about heat islands. US Environmental Protection Agency website. epa.gov/heat-islands/learn-about-heat-islands. Accessed February 14, 2018.
• American Heartworm Society resistance statement. American Heartworm Society website. heartwormsociety.org/images/pdf/Resistance_statement_FINAL.pdf. Accessed February 14, 2018.
• Pre-treatment of samples to improve detection of heartworm antigen. Oklahoma State University website. cvhs.okstate.edu/sites/default/files/docs/pdf/Improved%20Heartworm%20Testing.pdf. Published June 21, 2016. Accessed January 30, 2018.