Solutions to the Challenges of Heartworm Prevention

By Patricia Payne, DVM, PhD, DACVM
Contributing Author


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Introduction
Major challenges still exist for small-animal clinicians who strive to protect their patients from becoming infected and adversely affected by the deadly heartworm parasite Dirofilaria immitis, also called heartworm. Heartworm disease is a widespread and potentially very serious disease, affecting dogs nationwide. Successful treatment of heartworm disease can also be challenging for the veterinary practitioner.

The treatment process needs to be handled carefully, or the treatment itself can have serious consequences. Equally important is the ongoing support that patients and their owners will need in the months following treatment, requiring effective client communication.

Table of Contents


Background
The American Heartworm Society (AHS) Guidelines on prevention, diagnosis and management of D. immitis detail the standard of care and treatment of this deadly parasite. These guidelines are updated frequently in response to new information from peer-reviewed, scientific studies and ongoing research. In response to complaints that there was an overwhelming amount of information, summaries of the current canine and feline guidelines have been written and are posted on the AHS website as well. These summaries may be more user-friendly for busy practitioners.

Maintaining the focus on D. immitis
Not too many years ago, the AHS considered opening its triennial symposium to vector-borne diseases other than D. immitis. However, it became obvious that new information has arisen that increases the complexity of the veterinarian’s role in prevention, diagnosis and treatment of this heartworm. This information includes dramatic climatic changes, changes in vector epidemiology, parasitized animals moving from one area of the country to another and the increase in the number of animal shelter adoptions.

There is new information about prevention, diagnostics and treatment, as well as the possibility of resistant heartworm strains. Therefore, the AHS stayed focused on D. immitis and related filarids with a dynamic and extremely educational 2013 triennial symposium. Because there are still new challenges, new scientific research and fortunately new solutions for this dynamic and complex parasite, D. immitis, will continue to be the focus of the 2016 symposium.

Epidemiology and incidence of transmission: More mosquitoes in more places
Recent environmental changes, including the continued concentration of human populations and variations in farming practices, have created environments that support increased mosquito reproduction in different locations. There are heartworm-positive dogs found in all 50 states.1
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Approximately 70 species of mosquitoes are capable of transmitting D. immitis infective L3, according to the Companion Animal Parasite Council (CAPC), and the number may be much higher. Heartworm transmission can occur anytime infected mosquitoes are active and feeding.

One incidence study in Arkansas showed that one kenneled dog with circulating microfilaria infected seven out of 10 trapped mosquitoes in one night.2 New information concerning the mosquito vectors was presented at the American Association of Veterinary Parasitologists meeting in Boston, Massachusetts, July 2015. This current research covered the diversity of mosquito vectors, D. immitis larval development in Ades aegypti (yellow fever mosquito), and the possible inhibition of D. immitis transmission from infected mosquitoes with the use of topical products.3

The possibility of dogs being bitten by a mosquito infected with D. immitis in the United States has increased dramatically. Detailed weather maps can be found on the CAPC website, and incidence maps as reported by veterinary clinics on the AHS website. Heartworms have even been recently diagnosed in a dog native to Sheridan, Wyoming.4

Animal movement and shelter animals
The adoption of dogs with unknown histories has certainly complicated the prevention, diagnosis and treatment of D. immitis infections. After hurricane Katrina, many dogs were transported from highly endemic areas in the southern United States to previously non-endemic areas farther north, bringing heartworms with them. Many of these animals arrived with adult or maturing juvenile heartworms.

This movement and adoption of infected dogs has now become a common occurrence with people adopting these shelter pets. Heartworm diagnosis and treatment protocols are a major health issue in developing shelter adoption policies.5,6

Some animals are tested and treated with AHS-recommended protocols; some are not. The Association of Shelter Veterinarians has taken steps to help shelters and adoptive families understand this complicated medical issue and arrive at affordable solutions.7 

Prevention: Remember, nothing is 100 percent
Year-round administration of macrocyclic lactone preventives is still the backbone of all heartworm prevention programs with client compliance inconsistency the number one reason for infection. Rarely, animals become infected with solid evidence of purchase and administration of an appropriate product.8   

In highly endemic areas, environmental mosquito control has become an important part of a preventive program. Mosquito traps have become highly effective and are reasonably priced.

Common sense avoidance suggestions such as keeping dogs inside or enclosed in a screened-in porch during peak mosquito feeding times are extremely helpful to reduce, but not eliminate, the number of mosquito bites and subsequent infection. There is no highly effective mosquito repellant that is safe for dogs.

Diagnosis: The diagnostic dilemma
The first step in D. immitis diagnosis is to gather a complete history including where the dog is from, how long the dog has been in this household, travel history and the preventive purchase and administration schedule. Perplexing situations of unexpected positive antigen results are usually solved by a good history and referencing the heartworm life cycle timeline (Figure 1, below).
 
Figure 1: Heartworm Life Cycle
heartworm-life-cycle.jpg©Illustration by Laurie O’Keefe, medical and biological illustrator
 
Common questions concern adopted dogs that tested No Antigen Detected (NAD) last year, that were put on preventive and now are testing antigen-positive 12 months later. Some infections would have been discovered if pets with unknown histories had been retested six months after the first visit.
 
Factors that must be considered include geographic location, time of year, parasite pre-patent time and the history of preventive administration, including any product switching.

The diagnosis of D. immitis infection has been based on patient-side antigen tests for many years. These tests are highly sensitive, easy to perform and practical. There are several different antigen tests available. Formats of these tests include “well” enzyme-linked immunosorbent assay (ELISA) tests, solid substratum ELISA tests, immunochromatographic (immunomigratory) tests and colloidal gold agglutination tests. The gold standard antigen tests are the microwell tests, according to CAPC.

All currently available canine heartworm antigen tests indicate the presence of an antigen produced by the female heartworm. Therefore, the color change (blue dot, blue microwell) of a positive test indicates the presence of this protein and, therefore, a live, reproducing adult female worm is present or was recently. However, the absence of a color change does not always indicate that there are no adult female worms present, only that there was no antigen present. False-positive (blue dot) as well as false-NAD (no blue dot) antigen test results can occur; therefore, veterinarians and staff must understand what the presence or absence of a blue dot really means.

If no antigen is detected, and clinically the pet has a high incidence of suspicion of infection, further testing is recommended. False-negative results are rare but can happen with any given test. They occur most commonly when infections are light, female worms are still immature, only male worms are present and/or the test kit instructions have not been followed. Ongoing research using heat treatment of serum samples before testing (see Further Reading at the end of this article) has muddied the heartworm diagnostic waters considerably. Heating serum causes heartworm antigen/antibody complexes to disengage; as a result, the antigen can then be detected. Currently, there is no practical protocol available for in-clinic use, but Oklahoma State University Center for Veterinary Health Sciences and other reference laboratories are making this testing available. Practitioners are cautioned not to try this in their clinics at this time.1

Another potential false result is the false-positive antigen test that may occur for several reasons, including technical and test errors. If the clinician thinks that the pet is an unlikely candidate to harbor adult heartworms, further testing should be performed by using a different antigen test. No pet should undergo adulticide treatment on the basis of one positive antigen test.

Current recommendations for timing of antigen tests:
  • Yearly antigen testing
  • Testing when changing preventive products and then again six months after the switch
  • Immediately after adoption of an animal with unknown history and six months after adoption
Microfilaria testing: Long forgotten but extremely useful if positive
Looking for D. immitis microfilaria using a concentration technique or in a direct smear has long been forgotten by many veterinary practitioners and even parasitologists. The AHS and CAPC have recently modified their recommendations by bringing back microfilaria testing to validate antigen-positive or suspect patients testing NAD.

The Knott’s test is a concentration technique that is more accurate than a direct smear. A positive microfilaria test is a positive, however not finding microfilaria does not rule out an infection. In the exam room, a demonstration of putting a drop of blood under the microscope and letting clients see for themselves the microfilaria in the blood is extremely dramatic and an impactful way to show clients the actual “baby” heartworms.

Reminder: An animal may have a NAD test result and be harboring larval stages of the parasite and test positive in six or seven months. This is a more common occurrence in adopted animals and also animals undergoing slow kill therapy.

Other diagnostic aids such as radiography and echocardiography are well described on the AHS and CAPC websites.

Several scientific papers were presented at the 2013 AHS symposium looking into possible biomarkers for heartworm disease. Although none were identified as specifically useful, this is a promising new concept and studies are ongoing.

Pre-adulticide evaluations: There are no set protocols for pre-treatment workups. The clinical status of each patient is the determinant.

Staging of heartworm cases is no longer recommended because there is no test or combination of tests to accurately determine the actual number of worms present or the extent of the individual’s immune response to the dead and dying worms.1 
 
Treatment
Melarsomine dihydrochloride is the only adulticidal drug approved by the U.S. Food and Drug Administration for D. immitis treatment. The AHS recommends the three-dose protocol in all cases except those with caval syndrome.1 Unfortunately, this drug is manufactured overseas and is at times in short supply. Availability of the medication should be determined when a patient is first diagnosed.

Adjunct therapy with prednisone and doxycycline, and post-treatment exercise restriction, are recommended for a successful treatment outcome.9 The AHS has developed treatment guidelines for the pet owner explaining the timeline and importance of the individual treatment procedures in terms the general public can understand.

Exercise restriction can be very problematic in some households, but is essential for minimizing complications post-treatment. As adult heartworms die, inflammation becomes extensive in the heart, lungs and other organs including the liver and kidneys. Exercise exacerbates the clinical and pathological damage including thrombosis and heart failure.

Doxycycline treatment not only kills the Dirofilaria endosymbiont Wolbachia, thus reducing inflammation in the lung tissue, but also renders the female worm sterile preventing microfilaria from circulating and infecting other mosquitoes.9

There are no natural or herbal remedies that have been shown to be effective.

The alternative slow kill method (macrocyclic lactones and doxycycline) of treating heartworm infections is not recommended on a general basis but may be used in some cases, especially if recommended adulticide agents are too costly. Veterinarians who are convinced they are eliminating heartworm infections using the slow kill method may actually be living in a “fool’s paradise.” Dogs with severe chronic inflammation caused by dead and dying worms develop immune complexes that make D. immitis antigen undetectable when using currently available testing methods. Retesting, after heat treating the serum of many of these animals, has “burst the bubble” of this illusion.10,11
 
Resistance
There are a few instances of parasite resistance to macrocyclic lactones (ML) backed by solid scientific data.12 This is a concern, however it is not a widespread problem. In a recently published review paper, Wolstenholm et al. explain the current understanding of the dynamics. Because the vast majority of D. immitis populations are susceptible to macrocyclic lactones, in dogs receiving consistent year-round prevention, infections with ML-resistant adult worms are rare.
 
The adulticide treatment, melarsomine dihydrochloride, is not an ML and therefore should remain effective against adult D. immitis. Also, refugia for all D. immitis genotypes remain in unprotected domestic canines as well as wild canids.13 This ensures populations of parasites that are not exposed to MLs, therefore, will remain susceptible.
 
 
Conclusion
Heartworm infections in pet dogs are considered to be readily preventable. The diagnosis and treatment of heartworms in dogs is challenging. High quality patient care and effective client communications are the keys to success in all aspects of prevention, diagnosis and treatment of this deadly parasite.
 
References
  1. American Heartworm Society Guidelines. American Heartworm Society. 2014. www.heartwormsociety.org/veterinary-resources/american-heartworm-society-guidelines. Accessed Aug. 14, 2015.
  2. McKay T, Bianco T, Rhodes L, et al. Prevalence of Dirofilaria immitis (Nematoda: Filarioidea) in mosquitoes from Northeast Arkansas, the United States. J Med Entomol. 2013;50:871-878.
  3. Gruntmeir J, Drake J, Allen L, et al. False negative antigen tests in dogs infected with heartworm (Dirofilaria immitis) – an update and case series. Abstract from AAVP 60th Annual Meeting. Boston, Mass. July 2015.
  4. Brantz A. Rare Case of heartworm diagnosed in Sheridan County. The Sheridan Press. Sheridan, Wyo. June 1, 2015.
  5. Colby KN, Levey JK, Dunn KF, et al. Diagnostic, treatment, and prevention protocols for canine heartworm infection in animal sheltering agencies. Vet Parasitol. 2011; (176):333-341.
  6. Polak KC, Smith-Blackmore M. Animal shelters: Managing heartworms in resource-scarce environments. Vet Parasol. 2014;206:78-82.
  7. Smith-Blackmore M. Managing heartworm disease in shelter animals. Today’s Veterinary Practice. May/June. 2015;5(3):53-56.
  8. Atkins CE, Murray MJ, Olavessen LJ, et al. Heartworm ‘lack of effectiveness’ claims in the Mississippi delta: Computerized analysis of owner compliance—2004-2011. Vet Parasitol. 2014; (206):106-113.
  9. McCall JW, Kramer L, Genchi C, et al. Effects of doxycycline on heartworm embryogenesis, transmission, circulating microfilaria, and adult worms in microfilaremic dogs. Vet Prasitol. 2014;206(1-2):5-13.
  10. Drake J, Gruntmeir J, Merritt H, et al. False negative antigen tests in dogs infected with heartworm and placed on macrocyclic lactone preventives. Parasit Vectors. 2015;8:68.
  11. Velasques L, Blagburn BL, Duncan-Decoq R, et al. Increased prevalence of Dirofilaria immitis antigen in canine samples after heat treatment. Vet Parasitol. 2014;206(1-2):67-70.
  12. Pulaski CN, Malone JB, Bourquinat C, et al. Establishment of macrocyclic lactone resistant Dirofilaria immitis isolates in experimentally infected laboratory dogs. Parasit Vectors. 2014;7:494.
  13. Wolstenholme AJ, Evans CC, Jimenez PD, et al. The emergence of macrocyclic lactone resistance in the canine heartworm, Dirofilaria immitis. Parasitol. 2015;142(10):1249-1259.
Further Reading
  1. Little SE, Raymond MR, Thomas JE, et al. Heat treatment prior to testing allows detection of antigen of Dirofilaria immitus in feline serum. Parasit Vectors. January 2014;7:1.
  2. Atkins CA. Avoid infection and broken hearts. Companion Animal Parasite Council. www.capcvet.org/expert-articles/are-we-doing-enough-to-prevent-heartworm-infections. Accessed Aug. 14, 2015.
  3. Bowman D, Marrinson R. CAPC parasite forecast reveals heartworm disease is still an issue in 2015. www.capcvet.org/expert-articles/capc-parasite-forecast-reveals-heartworm-disease-is-still-an-issue.
  4. Connecting with Today's Clients (CTC): The importance of local, timely parasite information study. Companion Parasite Council and Bayer Healthcare Animal Health. www.bayer.us/en/article.php?id=122795. Accessed Aug. 14, 2015.
  Websites:  
About the author:

Patricia A. Payne, DVM, PhD, DACVM, graduated from Kansas State University College of Veterinary Medicine (KSUCVM) in 1971 with her DVM. She worked in clinical small animal practices in Virginia for 23 years before returning to KSUCVM as a graduate student in the Parasitology Laboratory. In 2000 she earned her PhD in Insecticide Resistance in Fleas. She is a long-term member of the American Association of Veterinary Parasitologists, American Veterinary Medical Association, Kansas Veterinary Medical Association and now serves on the Board of Directors of the American Heartworm Society (AHS). She is also a Charter Diplomat of the American College of Veterinary Microbiologists, Parasitology. Dr. Payne has recently retired from her tenured faculty position at KSUCVM (Emeritus Associate Professor) where she taught Veterinary Clinical Parasitology, Integration III, Veterinary Public Health and Wildcat Parasitology. Her research centered on internal and external parasites of both large and small animals and she has authored many scientific publications.