Heartworm disease (dirofilariasis) is a mosquito-borne infection caused by the parasitic nematode Dirofilaria immitis. The worms primarily affect the pulmonary arteries causing inflammation, vascular dysfunction, and pulmonary hypertension.
Canines are the definitive hosts of D. imitis. The parasite also affects felines, and the disease is usually more severe. A few developing immature or adult filariae can cause severe disease, or even death in cats. D. immitis has zoonotic potential and thus could be considered a public health issue. Humans can be accidentally infected with D. immitis. In many cases, these infections will progress, developing through the tissue stages, and reaching the pulmonary vasculature.
Related: Heartworm Disease in Dogs, 2nd Edition
The impact of heartworm disease in dogs is significant. Affected pets have a poor quality of life, and, in severe cases, may result in mortality. The disease is also a substantial economic burden for pet owners.
Veterinarians are at the forefront of client education regarding heartworm prevention, conducting accurate diagnostics, implementing effective treatment protocols, and monitoring patient outcomes. The evolving nature of dirofilariasis coupled with advancements in diagnostic and therapeutic modalities, underscores the significance of veterinarians staying abreast of the latest research and clinical guidelines.
Epidemiology and geographic distribution
Image courtesy of the American Heartworm Society
The 2022 Heartworm Incidence Map from the American Heartworm Society (AHS) shows an upward trend in heartworm cases in both heartworm “hot spots” and in locales where heartworm cases were once rare.
Based on the heartworm incidence survey conducted by the AHS every three years, states with the highest density of diagnosed heartworm cases are:
- Mississippi, Louisiana, Texas, Alabama, and Arkansas
States showing an increase in high-density areas:
- Arkansas, Mississippi, Texas, Georgia, Florida, Tennessee, North and South Carolina
Urban areas with significant increases in cases:
- Seattle, Boise, Bismarck, Tucson
The spread of heartworm disease
AHS considers several factors responsible for the increase in heartworm cases. These include a greater influx of heartworm-positive animals across state boundaries, higher testing rates, and higher infection rates.
There are two significant factors that currently influence the prevalence and spread of heartworm disease. In some parts of the world, increasing rates of infection can be attributed to climate and land cover, primarily given their impact on vector distributions and abundance. These factors can have a positive influence on the spread of certain species of mosquitoes. However, some regions are seeing a decrease in prevalence as a result of better awareness and intensified disease control measures. It could also be a result of an overall reduction of the mosquito population.
Mosquito vector presence has been identified as the primary determinant of canine heartworm prevalence within the United States, underscoring the critical role of vector control in disease prevention. At least 25 mosquito species, distributed across five genera (Aedes, Anopheles, Culex, Culiseta, and Psorophora), are considered potential vectors based on natural infections with L3 filarial larvae. Moreover, numerous additional species have exhibited vector competence in controlled laboratory settings.
Pathophysiology of heartworm disease
The severity of pathological manifestations is typically correlated with the parasite burden, specifically the quantity of adult worms. While the microfilariae released from adult females is essential for mosquito-borne transmission, these early-stage larvae appear to contribute minimally to the overall disease pathology. Infective 3rd stage larvae transmitted by mosquito vectors eventually develop in the tissues of the host into adult nematodes in the pulmonary arteries.
Infected dogs and cats eventually develop a cascade of pathological changes including right-side cardiac pressure overload and progressive pulmonary insufficiency. Other potential problems that can occur include heart failure, caval syndrome, aberrant heartworm migration and disseminated intravascular coagulopathies (DIC). Over time, infected pets may exhibit coughing, dyspnea, lethargy, and unexplained weight loss.
Feline infections may be asymptomatic, but when clinical manifestations arise, they typically occur approximately three months post-infection. These signs are commonly attributed to the inflammatory response within the pulmonary vasculature and parenchyma induced by immature adult parasites. Consequently, intermittent coughing, dyspnea, and wheezing may be observed.6
Diagnosis
The Companion Animal Parasite Council (CAPC) and the AHS advocate for annual testing of all dogs over 7 months of age, regardless of ongoing heartworm preventive medication, utilizing both antigen and microfilariae diagnostic assays.
Various parasitological, serological, and molecular diagnostic assays are available for the detection of various life cycle stages of the heartworm parasite. However, not all life stages may be present in an infected dog at any given time point. It is important to note that diagnostic test results are not fully predictive of posttreatment complications or success.
Diagnostic tests
A variety of diagnostic modalities are employed to detect different life cycle stages of Dirofilaria immitis. Microscopic examination of blood enables direct visualization of microfilariae. Antigen from immature and adult heartworms may be detected on commercial assays. Serological tests, on the other hand, can detect the host immune response to larval stages of the parasite.
All positive antigen test results should be confirmed through supplementary diagnostic procedures prior to initiating any therapeutic intervention. Confirmation is achieved by the identification of circulating microfilariae or by obtaining a subsequent positive result using a different antigen test.
Current diagnostic tests for dirofilaria immitis
Modified Knott’s Test
- Performed utilizing direct blood smears or from concentrated blood.
- The test enables differential diagnosis to other filariae, particularly Acanthocheilonema spp and D. repens.
- The technique may not be suitable for mixed filarial infections, and is, compared to other diagnostic tests, rather insensitive, and a test should not be defined as negative unless at least 1ml of blood has been investigated.9
- The number of circulating microfilariae does not correlate with the number of adult heartworms and therefore does not indicate disease severity.10
Serological Tests (Enzyme-linked immunosorbent assay (ELISA), Immunochromatographic (ICT) test, Hemagglutination)
- Detection of D. immitis adult antigens for in-clinic use.
- Easy to use, quick, cost effective, and don’t require any skill in parasite identification.
- Detect only mature infections about 7 months post infection. Antigens may not be detected in some dogs, unless the samples are heat pretreated to release antigens from immune complexes.
- Antigen tests detect free, unbound antigen from gravid females; thus, low worm numbers and single-sex infections can result in false-negative antigen test results.
- Antibody tests for cats primarily detect the humoral immune response to migrating third and fourth stage larvae in the pulmonary tissue.
- May not test positive in up to 7% of dogs due to the occurrence of “antigen-antibody complexes” that are formed in the dog’s blood.
Radiography and echocardiography
- Used for confirming the diagnosis and to assess the severity of heartworm disease, particularly in cats.
Molecular diagnosis for heartworm
This test is particularly appropriate for dogs suspected of being infected, but with microfilaria-negative results. The PCR approach may be quantitative or qualitative. The advantage of quantitative PCR is that DNA may stem from female as well as male worms. The Dirofilaria antigen ELISA test can detect only female worms, since only females produce the antigen.
Heartworm antigen testing represents the most dependable method for confirming the elimination of all adult heartworms. The AHS recommends that heartworm antigen test results be recorded as “positive” or as “no antigen detected” rather than negative.
Treatment options
The primary objectives of any heartworm treatment regimen are to:
- Improve the patient’s clinical condition.
- Eradicate all life stages of the heartworm parasite, including microfilariae, larval, juvenile, and adult stages.
- Minimize the occurrence of complications following treatment.
Canine patients with pronounced clinical manifestations of heartworm disease should be stabilized before administering an adulticide. Currently, the recommended adulticidal protocol consists of the administration of three doses of melarsomine dihydrochloride, preceded by the administration of macrocyclic lactones over two to three months. Melarsomine is the only adulticidal drug approved by the FDA.
Another protocol involves a month-long course of doxycycline to remove the symbiotic bacteria Wolbachia before killing the adults with melarsomine. This appears to reduce the pathology associated with the generation of large dead worms in the host.
To reduce new infections and eliminate existing susceptible larvae, administer a macrocyclic lactone preventive for 2 months prior to administering melarsomine. The effectiveness of the macrocyclic lactone can also be potentiated with concurrent use of doxycycline for 4 weeks. This will eliminate all developing larvae during the first 60 days of treatment.
Prior to treatment, it is important to thoroughly assess the owner’s capacity and commitment to effectively confine treated dogs. Exercise restriction is vital during the entire treatment and recovery process to minimize cardiovascular problems.
Dogs that are undergoing treatment or have been treated should be closely monitored for any adverse reactions caused by dying or dead worms, as well as significant inflammatory reactions.
References
- Atkins, C. E. (2023, May 15). Heartworm Disease in Dogs, Cats, and Ferrets. MSD Veterinary Manual. https://www.msdvetmanual.com/circulatory-system/heartworm-disease/heartworm-disease-in-dogs-cats-and-ferrets#Life-Cycle_v3259853
- Noack, S., Harrington, J., Carithers, D. S., Kaminsky, R., & Selzer, P. M. (2021). Heartworm disease – Overview, intervention, and industry perspective. International Journal for Parasitology: Drugs and Drug Resistance, 16, 65-89. https://doi.org/10.1016/j.ijpddr.2021.03.004
- New American Heartworm Society Heartworm Incidence Map Reveals Upward Trend in Heartworm Cases. (2023, April 11). American Heartworm Society. https://www.heartwormsociety.org/in-the-news/825-new-american-heartworm-society-heartworm-incidence-map-reveals-upward-trend-in-heartworm-cases
- Couper, L. I., & Mordecai, E. A. (2022). Ecological drivers of dog heartworm transmission in California. Parasites & vectors, 15(1), 388. https://doi.org/10.1186/s13071-022-05526-x
- Geary, T.G. New paradigms in research on Dirofilaria immitis. Parasites Vectors 16, 247 (2023). https://doi.org/10.1186/s13071-023-05762-9
- Smith-Blackmore, M. Heartworm Disease. 419-442. https://doi.org/10.1002/9781119294382.ch18
- American Heartworm Society. American Heartworm Society; 2020. Current canine guidelines for the prevention, diagnosis, and management of heartworm (Dirofilaria immitis) infection in dogs.https://d3ft8sckhnqim2.cloudfront.net/images/pdf/2020_AHS_Canine_Guidelines_Summary_11_12.pdf?1605556516
- Panarese, R., Iatta, R., Alfonso, J., Szlosek, D., Braff, J., Liu, J., Beugnet, F., Beall, M. J., & Otranto, D. (2020). Comparison of Diagnostic Tools for the Detection of Dirofilaria immitis Infection in Dogs. Pathogens, 9(6), 499. https://doi.org/10.3390/pathogens9060499
- OH, I. Y., KIM, K. T., & SUNG, H. J. (2017). Molecular Detection of Dirofilaria immitis Specific Gene from Infected Dog Blood Sample Using Polymerase Chain Reaction. Iranian Journal of Parasitology, 12(3), 433-440. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623924/
- Dryden, M. W. (2017). Canine Heartworm Antigen Tests. Kansas State University. Retrieved from https://ksvdl.org/resources/news/diagnostic_insights/january2017/canine.html
- Auburn University College of Veterinary Medicine. (n.d.). Heartworm. Retrieved from https://www.vetmed.auburn.edu/academic-departments/dept-of-pathobiology/diagnostic-services/molecular-diagnostics/heartworm/
- Carretón, E., Falcón-Cordón, Y., Falcón-Cordón, S., Morchón, R., Matos, J. I., & Montoya-Alonso, J. A. (2019). Variation of the adulticide protocol for the treatment of canine heartworm infection: Can it be shorter?. Veterinary parasitology, 271, 54–56. https://doi.org/10.1016/j.vetpar.2019.06.006
- Ketzis, J., & Epe, C. Antifilarial Chemotherapy: Current Options in Veterinary Medicine. 191-214. https://doi.org/10.1002/9783527823413.ch8