Monday, April 20, 2020


Canine Heartworm
By Caitlin McKinney
What is Canine heartworm disease?
We’ve all heard of the term “heartworm” at our veterinary clinics when taking our beloved pet in for their routine annual check-up or puppy vaccinations. But what really is it and how are our veterinarians informing us about it? Canine heartworm is a fatal disease that is prevalent in pets in the United States. Although the name implies that only animals in the dog family are susceptible to the disease, heartworm can infect cats, ferrets, sea lions, and even humans (1). The disease is caused when worms, or filarial nematodes called Dirofiliara immitis, enter the circulatory system of our pets through the bite of an infected mosquito (3). Many consequences can arise when these worms are passed from the mosquito to our furry friend, such as a localization of worms on the pulmonary arteries and other surface blood vessels that can cause eventual life-threatening cardiovascular collapse. With consequences as dire as heart failure, it’s no wonder our veterinarians persistently recommend a preventative deworming medication almost every clinical visit we attend.
Prevalence and transmission of heartworm
Heartworm is vectored by a mosquito, specifically known as the Aedes mosquito. This mosquito is also a known vector of diseases such as dengue, yellow fever, and other viral pathogens, as well as nematode (worm) parasites. Because of this, mosquitos are known as the most dangerous animal in the world. They are found in many climates and can take their blood meal from a variety of vertebrate hosts, such as mammals, birds, reptiles, amphibians, and even fish (3). It is also known as the most common blood-feeding arthropod (invertebrate animal with chitinous exoskeleton). The Aedes mosquito can be active throughout the year in tropical, humid climates, but inseminated females in temperate climates can hibernate through the winter. Thus, their eggs can survive at low temperatures.
 
Figure 1: Incidence of canine heartworm in average number of consumer cases per reported clinic across the United States in 2013.
In the U.S., heartworm has been diagnosed in all 50 states and can still be prevalent in areas that do not have high mosquito populations (4). This is due to infected pets traveling with their owners to areas where heartworm is more common. Additionally, strayed and neglected dogs and wildlife, like wolves, foxes and coyotes, can transmit D. immitis through bite of a mosquito.
Although mosquitos are found throughout the U.S., many actions can be taken to control the population. These include larvicides, removal of standing water, aerial pesticides, bacterial symbionts that interfere with mosquito reproduction, and more simple measures, such as bed nets, window screens, and insect repellent. 
Clinical History
The first documented finding of heartworm was by a man named Chez Iean Wolfe, who found a what he called a “monster” in the heart of a dead horse in 1586 (5). As any curious person does in the 1500’s he made a sketch of the so-called “monster,” which today is known as D. immitis. The first canine case of D. immitis was documented by a nobleman by the name of Francesco Bargo in the 17th century (5). Bargo identified adult worms in the hearts of his hunting dogs, but thought they were the larvae of a different type of parasitic worm. In 1856 in the southeastern coast of the U.S., canine heartworm was formally described by Joseph Mellick Leidy (5). Unfortunately, even our feline friends could not escape the historical patterns of heartworm, as the first case of feline heartworm was discovered in the 1920s. Finally, like all memorable diseases throughout world history, heartworm disease would not be note-worthy without a human case of infection in 1952 (6).
 
Figure 2: Sketch of D. immitis  in the heart of a horse done by Chez Iean Wolfe.
Heartworm symptoms
Symptoms in dogs may be subtle in early infections and light infections are usually asymptomatic. Lethargy, loss of appetite, weight loss, a mild, persistent cough during moderate exercise are telling symptoms if your pet has a heavy heartworm infection (larger number of D. immitis) (1). As the infection develops, D. immitis can cause blockages of blood flow in the pulmonary arteries and blood vessels which can lead to a life-threatening form of cardiovascular collapse, called caval syndrome (1). Signs of caval syndrome include a sudden onset of labored breathing, pale gums, and dark, bloody urine or coffee-colored urine. Caval syndrome requires the immediate surgical removal of the heartworm blockage. The appearance of a swollen belly is also common due to excess fluid in the abdomen.

Heartworm testing
Heartworm tests that are done by veterinarians require a small blood sample from your pet. By detecting the presence of certain proteins within the worms, the results of the test are very quickly received whether the test is given in a clinic or sent to a diagnostic laboratory. Usually these tests are given in the form of snap tests (Hartgard snap tests), that require just one drop of a blood in a blood sample that’s taken when you take your pet to get spayed or neutered.  To prevent initial infection or further development of infection, pets should be tested annually for D. immitis.
 
Figure 3: Heartgard snap test for heartworm showing positive results.
Treatment
Currently, there is no vaccine for canine heartworm which is why prevention is the of utmost importance. Prevention includes a monthly use of an oral dewormer, called prophylactic oral ivermectin or an injectable form administered every 6 months. This is a cream-like substance that is 99% effective in killing the D. immitis larval worms before maturing into adults, which are the cause of heavy infections in dogs. However, ivermectin has little, if any, effect on adult worms. Eradication of adult worms with this treatment could take as much as two years or more with a proper medication regimen. The other option for eradicating adult worms, an arsenic-based compound called melarsomine dihydrochloride, has been highly controversial due to its toxic properties and complex regimen. In this regimen, it’s important to restrict canine exercise for at least a month because worms can become dislodged from the pulmonary arteries and end up in the lungs, causing respiratory failure.
Could bacteria save the day?
New studies have found that D. immitis are the host to bacteria in the genus Wolbachia, a gram-negative intracellular organism. It’s been found that Wolbachia is essential to the survival and reproduction of female worms, and antibiotic treatment that kills the bacteria stunts larval development within the females. Thus, new combinations of treatments for heartworm have been administered that include a dose of antibiotics along with conventional therapies, like ivermectin (2). This combined treatment is being tested as an alternative to melarsomine dihydrochloride and plays a key role in the advancement of the treatment of canine heartworm in veterinary medicine.

 
Figure 4: Fluorescence microscopy of Wolbachia bacteria.
References
1.     Heartworm disease. (n.d.). Retrieved March 8, 2020, from https://www.avma.org/resources/pet-owners/petcare/heartworm-disease
2.     Kristina Kryda, Robert H. Six, Kelly F. Walsh, Susan J. Holzmer, Sara Chapin, Sean P. Mahabir, Melanie Myers, Tammy Inskeep, Jady Rugg, Blair Cundiff, Aleah Pullins, Michael Ulrich, John W. McCall, Tom L. McTier, & Steven J. Maeder. (2019). Laboratory and field studies to investigate the efficacy of a novel, orally administered combination product containing moxidectin, sarolaner and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs. Parasites & Vectors, 1, 1.
3.     Loker, E. S., & Hofkin, B. V. (2015). Parasitology: A conceptual approach.
4.     Meredith R. Spence Beaulieu, Jennifer L. Federico, & Michael H. Reiskind, (2020). Mosquito diversity and dog heartworm prevalence in suburban areas. Parasites & Vectors, 1, 1.
5.     (n.d.). Retrieved April 3, 2020, from https://web.stanford.edu/group/parasites/ParaSites2006/Dirofilariasis/History.htm
6.     Dog Heartworms. (n.d.). Retrieved April 3, 2020, from https://encyclopediaofarkansas.net/entries/dog-heartworms-14172/

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