Heartworms Today: The Search for Solutions

Clarke Atkins, DVM, Diplomate ACVIM (Internal Medicine & Cardiology),
North Carolina State University

The author discusses new information on some of the most important issues faced by practitioners today, including: Development of heartworm resistance to common preventives, complexities of feline heartworm, and the role of Wolbachia in the heartworm complex.

The 14th Triennial Heartworm Symposium, which took place September 8 through 10, 2013, in New Orleans, was one of the most important scientific meetings held in the 40-year history of the American Heartworm Society (AHS).

In recent years, significant work has been undertaken to better understand the most important issues faced by practitioners today, including:

• Development of heartworm resistance to common preventives
• Complexities of feline heartworm
• Role of Wolbachia in the heartworm complex.

New information on these topics, as well their connection to the challenges of compliance, owner education, and shelter medicine, sparked lively discussion in New Orleans.

LACK OF EFFICACY & HEARTWORM RESISTANCE

For the past 10 to 15 years, heartworm experts and practitioners have become concerned that Dirofilaria immitis (heartworm) may be developing resistance to our current macrolides and avermectins, also known as macrocyclic lactones (MLs) (Table 1). Concern for decreased efficacy exists for all MLs.

These concerns have resulted in lively debate regarding the role of resistance in apparent lack of efficacy (LOE) reports emanating from the Mississippi Delta region (Figure 1).

Documentation of Resistance

It is now accepted that heartworm resistance to preventives, a class effect, has been documented, apparently in small pockets, both in and outside the Mississippi Delta. However, the true incidence of resistance is unknown at this time. According to Ray Kaplan, DVM, PhD (University of Georgia), we know very little about the development of heartworm resistance. We do know that it is different from that which occurs in livestock gastrointestinal nematodes.

Resistance Development

The practice of “slow kill” (also called “soft kill” or “trickle kill”)—killing adult heartworms with long-term, monthly use of a preventive dosage of ivermectin—has been implicated in the development of heartworm resistance. However, this is an area of controversy.

• Some experts, such as Dwight Bowman, MS, PhD (Cornell University), feel strongly that the “explosion of LOEs” in the Mississippi Delta region has resulted from use of the above eradication method.
• Dr. Ray Kaplan, however, sees slow kill as a factor that increases the rate and spread of resistance once it is established in a given area, but notes lack of scientific evidence implicating slow kill as a major risk factor for resistance.
• Dr. Clarke Atkins has proposed a more general explanation, based on a multiplicity of factors.

Product Efficacy

Resistance has occurred with all 4 licensed ML molecules, though not all products are equal in this regard. Imidacloprid/moxidectin topical has been demonstrated to be more effective in preventing heartworm infection (HWI) by 2 resistant isolates, as compared to other ML chemicals and formulations, but the overall clinical importance of these findings remains to be determined.¹

Adherence Importance

While more research is needed to better understand resistance, it is clear that client adherence (compliance) remains the major factor involved in the Mississippi Delta dilemma. In a recent study, only 1% to 3% of reported putative LOEs in the region were truly supported by product failure.²

Therefore, based on our current knowledge, the best course of action is to continue recommending on-label use of heartworm preventives, 12 months per year. Preventives are effective in the vast majority of patients and represent the best protection currently available to pets.

In the meantime, work is underway to develop a genetic test that will help veterinarians determine the relative risk of heartworm resistance in their practice areas. In addition, the AHS released a revised statement on heartworm resistance, available at http://www.heartwormsociety.org/pdf/Resistance_statement_FINAL.pdf.

WOLBACHIA & DOXYCYCLINE

Wolbachia’s Role in Treatment

Wolbachia (Figure 2) is a critical component in the well-being, long-term survival, and reproduction of heartworms and, therefore, plays an important role in the treatment of HWI:

• Eliminating Wolbachia disrupts heartworms’ life cycle and quickly reduces the numbers of circulating microfilariae.
• Wolbachia treatment causes the adult heartworm to deteriorate, reducing worm biomass and likely the amount of antigen released with worm death.
• Treating Wolbachia in dogs prior to adulticide therapy results in less inflammation (for example, in the lungs) associated with adulticide treatment and worm death.

For these reasons, the AHS guidelines for treatment of adult heartworms (see Updated AHS Guidelines) call for treatment with the antibiotic doxycycline prior to administering melarsomine in order to reduce post-adulticide side effects.

Combination Adulticide Therapy

Laura Kramer, DVM, PhD, Diplomate EVPC (University of Parma, Italy) noted in her presentation that doxycycline can be combined with an ML to create an alternative adulticide. While she combined doxycycline and ivermectin, similar studies have used moxidectin instead.

This combination of doxycycline and ivermectin:

• Produces an adulticide effect, with approximately 80% efficacy after 6 to 10 months of therapy
• Reduces microfilariae to very low levels within several weeks of therapy
• Is considered more effective than traditional slow kill therapy (defined as administering MLs alone to treat infection) because it rapidly reduces microfilarial numbers (thereby, reducing one concern for development of resistance) and quickens death of adult heartworms.

FELINE HEARTWORM DISEASE

Veterinarians have known for some time that heartworm disease (HWD) presents differently in cats than dogs and that heartworms mature and reproduce less frequently in cats. In fact, feline HWD is under-recognized by veterinarians and more common than originally thought.

HARD Syndrome

Cats can develop a condition known as heartworm-associated respiratory disease (HARD), which results in significant lung damage, cough, wheezing, and dyspnea, when developing stage 5 filarids are eliminated and no mature adult heartworms are present.

HARD, as used here, is different than the HWD produced by adult D immitis (Table 2). In HARD, heartworms die before maturing (early in stage 5 or immature adult stage) and producing antigen, making diagnosis challenging. Cats affected with HARD are typically antigen-negative, but antibody-positive and, while radiographic lesions are typically present, absence of adult worms renders cardiac ultrasound nondiagnostic.

Ray Dillon, DVM, MS, MBA, Diplomate ACVIM (Auburn University) explains that diagnosis of (mature) feline HWD and HARD is further complicated because other feline parasites, including Toxocara cati and Aelurostrongylus abstrusus, can cause lung disease similar to that induced by heartworms. He also noted that, while broad-spectrum preventives for heartworm and intestinal parasites prevent roundworms in the gastrointestinal tract of cats, they do not appear to prevent roundworm migration to the lungs.

Role of Radiography

Matt Miller, DVM, MS, Diplomate ACVIM (Cardiology) (Texas A&M University), demonstrates that some radiographic changes due to feline HWD are detectable and relatively specific, leading to a diagnosis of feline HWD (Figure 3). Radiography can also help rule in/out other diseases, such as neoplasia, foreign body, thoracic trauma, and heart failure.

HEARTWORM DISEASE IN ANIMAL SHELTERS

Animal shelters deal with extremely large volumes of animals, and many shelters face significant challenges when it comes to prevention and treatment of HWD due to the high prevalence of HWD in animals under their care and availability of little to no medical history. In addition, funding often is minimal, and staffing resources are generally limited.

The Care Gap

Katherine Polak, DVM, MPH, MA (University of Florida), explains that many shelters are unable to follow the AHS guidelines. For example, the shelter team may:

• Not have the time and resources to follow the full protocol for heartworm treatment
• Lack sufficient funding to test—much less treat—animals in their care
• Compromise by choosing the slow-kill approach, with or without use of doxycycline.

In addition, dogs sometimes test negative for heartworms and are adopted, only to become antigen-positive on the next retest.

Connecting Shelters& Resources

There are no easy solutions for these challenges, but the AHS is working toward connecting shelter veterinarians with informational resources that will help them provide the best possible care for patients with HWI/HWD. This will be a topic of discussion for the AHS this year (2014).

IN SUMMARY

HWD is arguably the most significant disease in small animal medicine, with an estimated 1 million dogs and an unknown number of cats affected. The 2013 Triennial Heartworm Symposium gave attendees a unique, firsthand opportunity to learn the latest about this serious disease. Practitioners and other veterinary professionals are urged to visit heartwormsociety.org for more information about the symposium, heartworm client educational resources, and HWI. n

AHS = American Heartworm Society; HARD = heartworm-associated respiratory disease; HW = heartworm; HWD = heartworm disease; HWI = heartworm infection; LOE = lack of efficacy; ML = macrocyclic lactone

Suggested Reading

Blagburn BL, Arther RG, Dillon AR, et al. Comparative efficacy of four commercially available heartworm preventive products against the JYD-34 laboratory strain of Dirofilaria immitis. 14th Triennial Heartworm Symposium, 2013, p 39.

Dillon AR, Tillson DM, Hathcock J, et al. Lung histopathology, radiography, high-resolution computed tomography, and bronchio-alveolar lavage cytology are altered by Toxocara cati infection in cats and is independent of development of adult intestinal parasites. Vet Parasitol 2013; 193:413-426.

Clarke Atkins, DVM, Diplomate ACVIM (Internal Medicine & Cardiology), is the Jane Lewis Seaks Distinguished Professor of Companion Animal Medicine at North Carolina State University. He is also a member of the Today’s Veterinary Practice Editorial Peer Review Board and American Heartworm Society’s Executive Board. Dr. Atkins’ research involves canine and feline heartworm disease and pharmacologic therapies for cardiac disease; he received the 2004 Norden Award for excellence in teaching.