Mar Vista Animal Medical Center

3850 Grand View Blvd.
Los Angeles, CA 90066

(310)391-6741

marvistavet.com

TREATMENT OF INFECTION

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TREATMENT OF INFECTION

It has been said that the treatment of heartworm infection is something of an art. There are several strategies that can be used depending on the dog's medical condition including the option of not treating at all. The important concept to realize is that, while there are "off label" alternative heartworm-killing protocols, the FDA approved method of killing adult heartworms involves very harsh arsenic based drugs and killing large adult heartworms is neither simple nor safe. Let us review some of the dangers and options in clearing the body of this parasite.

 

PATIENT EVALUATION

Prior to therapy, the heartworm patient is assessed and rated for risk into one of four categories. Important factors include: how many worms are thought to be present based upon the tests performed, the size of the dog, the age of the dog, concurrent health factors, severity of the heart disease, and the degree to which exercise can be restricted in the recovery period. Some hospitals use computerized formulas to categorize heartworm infected patients. The categories into which patients are grouped are as follows:

Chest radiograph from a moderately affected dog

Chest radiograph from a moderately affected dog
(Photocredit: Veterinary Information Network)

  • Class I: Lowest Risk. These dogs are typically without symptoms and their infection is a surprise discovery during a routine annual health examination when a positive test comes up. Other blood tests are normal and radiographs show mild changes if any change at all.
  • Class II: Moderately Affected. Healthy dogs with minimal signs as above, occasional coughing, fatigue only with exercise but with radiographs that show definite evidence of heart disease. Lab testing shows mild anemia, urine dipsticks show some protein present but not severe urinary protein loss.

Chest radiograph from a severely affected dog

Chest radiograph from a severely affected dog
(Photocredit: Veterinary Information Network)

  • Class III: Severely Affected. Dog is suffering from weight loss, cough, difficulty breathing, blatant damage to the vasculature is apparent on radiographs, lab work reveals a more severe anemia and marked urinary protein loss. The damage to the lung blood vessels from the worms creates extra resistance for the heart to pump against and often episodes of collapse occur with exercise. If the damage is severe enough, the heart can actually fail trying to pump through all the clogged up blood vessels. Class III dogs are expected to die without treatment but are, unfortunately, sick enough that treatment itself is not without risk.
  • Class IV: Caval Syndrome. Dog is collapsing in shock with dark brown urine evident. Heartworms visible by ultrasound in the AV valve of the right side of the heart, very abnormal bloodwork. These dogs are dying and can only be saved by the physical removal of adult heartworms via an incision through the jugular vein. If such a dog can be saved from this crisis, further heartworm infection treatment cannot be contemplated until the dog is stable enough to fit into one of the other categories above.

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To view the physical removal of adult heartworms from the jugular vein of a dog with caval syndrome, click here:

www.youtube.com/watch?v=VOLzFsNOJ-4

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After knowing what Class the patient fits in, treatment can be determined. The dog has three groups of heartworms in his or her body: microfilariae (basically newborn worms whose parents are living inside the dog in question), newly arrived immature worms (relatively fresh from the mosquito bite and living in the skin tissues), and adult worms themselves.

Microfilariae

  • Microfilariae are the first stage larvae (basically the youngest stage). Basically, these are the children of the adult worms living in the heart and blood vessels. The mother worm gives live birth (no eggs involved) and the babies swim freely in the host's bloodstream. They must be killed so that they cannot be picked up by mosquitos and transmitted to new dogs.

  (Photo Credit: Joel Mills via Wikimedia Commons)

The newly arrived heartworm larvae

  • The newly arrived heartworm larvae, freshly delivered from mosquito bites in the last 3 months. These are third and fourth stage larvae living in the skin. For practical purposes, we will include the L5 larvae in this group. The L5's are old enough to leave the skin tissues and enter the circulation but they are not really mature enough to be called adults. This group of young worms (L3's and L4's in the skin and L5's in the circulation) represent the first 5-7 months of infection. We need to kill them before they reach maturity and begin to wreak havoc on the cardiovascular system of the host.

  (original graphic by marvistavet.com)

fifth stage larvae and adult worms living inside the heart and pulmonary arteries
  • The older L5 larvae and adult worms living inside the heart and pulmonary arteries. This group requires the arsenic compounds for destruction while the other two groups can be killed with less toxic products.

  (original graphic by marvistavet.com)

NOW THAT WE HAVE STAGED OUR HEARTWORM INFECTION, LET'S WORK ON GETTING RID OF IT

The goal is to get rid of all the worms with as little inflammatory reaction as possible. Since the adult worms are the largest, it is not surprising that their deaths generate the most inflammation. We hope to stage the worm-killing process so that when the time comes to kill the adult worms, there are as few adult worms as possible and the patient should be as healthy as possible going into the process. For the sake of terminology, be aware that "adulticides" are products that kill the adult worms and "larvicides" kill the immature worms.

STABILIZATION FIRST:  Expect strict exercise restriction to be needed after adulticide therapy but moderately affected dogs will need restriction from the first. If heart failure is present, this will need to be controlled as well. Some dogs will need anti-inflammatory doses of steroids to control the inflammation that stems from the presence of worms. This is often done concurrently with the second step as described below.

KILLING THE MICROFILARIAE AND MIGRATING WORMS

The next step in treatment is clearing the migrating immature worms. Heartworm treatment is a project that lasts at least a couple of months. We do not want immature worms to mature in that time frame. Since our goal is to have fewer adult worms when the time comes to kill the adult worms, it behooves us to kill the younger worms right off the bat.

Happily the microfilariae, L3, and L4 larvae can all be killed by monthly heartworm preventives. The American Heartworm Society recommends 1-3 months of a preventive prior to treating the adult worms. How long one chooses to wait depends on how urgent the dog’s need is to remove the adult worms. After all, it is the adult worms that cause heartworm disease, not the immature worms addressed by the preventives..

KILLING WOLBACHIA

Wolbachia is a genus of rickettsial organisms (sort of like bacteria but not exactly) that live inside heartworms of all developmental stages but their numbers begin to expand once the young worms reach their infectious stage. Wolbachia organisms seem to be protective or beneficial to the heartworms that harbor them, aiding in metabolism and general worm health. Without Wolbachia colonization, many female worms are not able to reproduce and 3rd stage larvae are not able to infect new hosts. Wolbachia organisms possess very inflammatory surface proteins which are released when adult worms die (or are killed in treatment) and these proteins greatly increase the chances of severe circulatory reactions in the canine host.

A group of Wolbachia organisms

A group of Wolbachia organisms
(Photocredit: Scott O'Neill via Wikimedia Commons)

It has been found that killing the Wolbachia with an antibiotic such as doxycycline is very helpful in the treatment of the heartworm infection as the Wolbachia can be removed from their heartworm hosts, thereby weakening the worm and minimizing release of inflammatory proteins when the worm finally dies. The American Heartworm Society recommends using doxycycline along with heartworm preventives for a good month as soon as the heartworm diagnosis is made and prior to use of the arsenic compounds needed to kill the adult worms so as to minimize reactions.

The use of antibiotics in this way, along with the use of a heartworm preventive, forms the basis for what is called the "slow kill" method of treatment, as described below. As mentioned, this method is discouraged unless there is absolutely no choice. It is more appropriate to use doxycycline to "pre-treat" the dog prior to adulticide therapy as a way to reduce the number of worms to kill and reduce reactions when the arsenic based product is ultimately used.

KILLING THE ADULT WORMS

The only product currently available for the treatment of adult heartworms is melarsomine dihydrochloride (Immiticide® made by Boehringer Ingelheim or Diroban® made by Zoetis). If one goes by the manufacturer's recommendations, treatment can be done in 2 doses or 3 doses depending on the Class of heartworm infection. Most universities, however, opt to treat all patients with the 3 dose protocol as it creates a more gradual kill of the adult worms (which is safer in terms of embolism and shock).

The patient receives an intramuscular injection deeply in the epaxial (lower back) muscles as shown at right. This is a painful injection with a painful substance and it is common for the patient to be very sore at home afterwards. Pain medication may be needed. Be very careful of the injection site as the pet may bite. The site may actually form an abscess which requires warm compresses. Approximately 30% of dogs experience some sort of injection site reaction which resolves in 1-4 weeks. Some dogs develop a permanent firm lump at the site of the injection.

Dog getting injection illustration
(original graphic by marvistravet.com)

In the 2 dose protocol, the dog comes back for a second injection the next day on the opposite side of the lower back. In the 3 dose protocol, the dog comes back one month later for 2 doses 24 hours apart (the first dose representing an introductory treatment to kill some of the more sensitive worms.) Keep in mind, too many worms dying at once creates circulatory shock. The benefit of the 3 dose protocol (sometimes called the "split dose" protocol) is that the first injection serves to kill off any older or weaker worms without killing off the stronger, younger ones. When the two consecutive doses occur one month later, there will be fewer worms dying at once.

After treatment, the patient must be strictly confined for one month following the final treatment. No walks, no running around. The dog must live the indoor life. The reason for this is that embolism to some degree is inevitable and it is important to minimize embolism-related problems. Exercise increases heart rate and oxygen demand and we need the heart to rest during this recovery period.

Watch for:

  • Coughing
  • Fever
  • Nose bleeds

If any of these occur, report them to the vet as soon as possible. The most critical time is 7-10 days following a melarsomine treatment but they can occur anytime in the following month.

 

IVERMECTIN ONLY (THE "SLOW KILL" METHOD)

Melarsomine treatment is expensive and often out of reach for rescue groups, shelters, and many individuals. If the dog is stable (Class I) one option is to simply leave the dog on an ivermectin based preventive. This option has led to a great deal of misconception about the ability of ivermectin to kill adult heartworms. Let us lay the rumors to rest now:

  • Ivermectin does not kill adult heartworms.
  • Ivermectin does shorten the lifespan of adult heartworms.
  • Ivermectin does sterilize adult heartworms.
  • Ivermectin does kill microfilaria (keeping the dog from being a source of contagion)
  • Ivermectin does kill L3 and L4 larvae (preventing new infections).

This means that if one opts to treat a heartworm positive dog with an ivermectin heartworm preventive only, one can expect the dog to remain heartworm positive for as long as 2 years and the heartworm disease will be progressing during that 2 years. This is not good for the dog but certainly beats getting no treatment of any kind.

There is another aspect to this treatment which is important to mention and that is the development of resistant heartworm strains. Using heartworm preventives long term in dogs with adult heartworms, leads to the production of heartworm preventive resistant microfiliaria. In other words, this "slow kill" method of treating heartworm infection leads to strains of heartworm that cannot be stopped by any of the heartworm preventives presently available on the market. Heartworm preventive resistance has now been documented in some of the heartworm strains of the Mississippi river delta area and inappropriate use of heartworm preventives is felt to be the cause. Previously, the "slow kill" method of heartworm treatment was deemed acceptable for dogs in the Class I (early) stage of heart disease but this has changed given confirmation of resistant strains. The Companion Animal Parasite Council now recommends that the "slow kill" protocol using heartworm preventives NEVER be used regardless of whether the patient is in Class I stage of infection or not. Heartworm infection should be dealt with definitively and promptly so as to preserve the effectiveness of the medications we have.

  

MOX-DOX (A DIFFERENT SLOW KILL METHOD)

Adding doxycycline to ivermectin has changed the way "slow kill" works. As the protocol evolved, topical moxidectin has been substituted for ivermectin and a month of twice daily doxycycline is used to kill the Wolbachia bacteria that are so protective the living heartworms. The result seems to be a much faster "slow kill" with microfilaria clearing 3 weeks or so (addressing the resistance in microfilaria issue of slow kill). The adult worms die over 3-4 months which is similar to the 3 dose protocol (1-3 months on preventive, one dose of melarsemine with two doses following a month after that). Exercise restriction is still needed and relatively high doses of moxidectin are also needed. (The topical product is essential; long acting injectables wane too quickly). Heartworm antigen testing is performed 9 months after starting the protocol and continued monthly until negative. If the dog is still heartworm antigen positive after 15 months, new decisions should be made (do mox-dox again, use melarsomine etc.) The American Heartworm Society views this protocol as a "salvage procedure" meaning that it could be considered for a dog where melarsomine treatment is not an option. Research and controversy continue with regard to this method.

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 Page last updated: 11/18/2023