Heartworm is a very complex parasite, and so is the disease it causes, explained Wallace Graham, DVM, president of the American Heartworm Society. "Many practitioners think of heartworm in the same terms as they did 10 years ago, and there is so much more about the organism and the disease that we know now that we didn’t know then,” said Graham, who is also an associate veterinarian at VCA Oso Creek Animal Hospital in Corpus Christi, Texas. "This information has implications on the decisions we make concerning testing and treatment.” Living worms damage the pulmonary arterial walls, lungs and heart if left untreated, but so do dying and dead worms. Dying and dead worms lodge in the arteries, block blood flow, cause platelets to cluster, and elicit an inflammatory cascade that severely damages the cardiovascular and respiratory systems, leading to problems like thromboembolism, Graham said. And the chances of severe cardiovascular or respiratory response to treatment are directly related to the worm burden. Multimodal Attack To mitigate this damage, AHS recommends a multimodal approach to treating heartworms. The goal of treatment is to eliminate all stages of the heartworm—microfilariae, larval, juveniles and adult—and mitigate the cardiorespiratory effects. The first step after diagnosis is to stabilize any dog with significant clinical signs, such as cough, dyspnea or syncope. This might require corticosteroids, fluids and/or cardiopulmonary medications, such as diuretics and vasodilators. Exercise restriction is required to minimize heart and lung pathology. The next step is to pre-treat the dogs with a monthly preventive and doxycycline before administering melarsomine. Graham said there are several reasons to pre-treat the dog: • Pre-treating with the monthly preventive begins to kill circulating microfilariae, and prevents new infection that would add to the worm burden. • Pre-treating with monthly preventive for two months prior to adulticide therapy allows the intermediate stages that are not susceptible to either preventives or melarsomine to mature to adults, so that the melarsomine, an adulticide, can kill the adult worms. • Pre-treating with doxycycline helps to kill Wolbachia, an endosymbiont that inhabits filarial nematodes, including Dirofilaria immitis, the cause of canine and feline heartworm. D. immitis and Wolbachia have a symbiotic relationship; each depends on the other for its survival, Graham explained. Wolbachia are found in all stages of D. immitis, and they contribute to the pathogenesis of heartworm disease. By killing Wolbachia, veterinarians decrease the worm biomass, as well as the inflammatory response to the death of those worms, he said. Understanding the host-parasite relationship is the first step. "We put the dog on doxycycline because the antibiotic helps to render any circulating microfilaria noninfective. It makes the adult heartworms easier to kill, and it reduces the post-treatment side effects from the dying worms in the pulmonary arteries,” he said. However, there has been a shortage of doxycycline, said Charles Thomas Nelson, DVM, owner of the Animal Medical Center in Anniston, Ala. Until manufacturers begin producing and distributing more doxycycline, veterinarians might be wondering what they can use. There are no data supporting the use of other antibiotics for the treatment of heartworm, but experts have combed the literature for a solution. They believe minocycline, which is in the same antibiotic class as doxycycline and has been used to treat canine rickettsial infections, may be the solution because Wolbachia is a rickettsial organism. "In addition, minocycline has been shown to be effective in reducing Wolbachia infection in human onchocerciasis, a human nematode infection that causes river blindness. So, it seems to be a good drug,” Dr. Nelson said. No Kill with Slow Kill What veterinarian does not want to do is switch to a "slow kill” method of treating heartworm, Nelson said. The slow-kill method, which the AHS does not endorse, relies solely on the monthly preventive to treat an existing heartworm infection. Some veterinarians suggest it because it is cheaper than treating the disease properly, but Nelson said they are doing the animal and the client a disservice. He cited three problems with the slow-kill method: • Nothing is done to mitigate the possible damage to the body when the worms die. • If this damage occurs, the dog is going to need emergency care that is very expensive and could be life-threatening. • It might add to selective pressure of the organisms. (Selective pressure is any factor that can alter the health of an organism within its environment. Selective pressure is the driving force in the evolution of resistance. If an organism develops the ability to survive a drug, it passes that ability onto its offspring. If selective pressure is great enough, resistance can develop.) "I don’t like the slow-kill method because the veterinarian is not controlling when the worms die,” explained Dwight Bowman, MS, Ph.D., professor of parasitology at Cornell University College of Veterinary Medicine in Ithaca, N.Y. "You have these foot-long worms dying in your pulmonary arteries, and being pushed further into your lungs. The advantage of being given an immiticide while under a doctor’s care is that he or she can take care of you when that happens. If a few worms die while you are alone at home on your coach, you will probably feel pretty bad when that happens.” In addition, Graham worries about whether owners are restricting the animal’s exercise. If the worms die over the course of nine or more months and the animal is exercising, there will be increased pathology of the disease. "Think about what the heart does and what the heartworms do. There is an increased load on the heart and all of that activity seems to accelerate the changes in the walls of the pulmonary arteries and in the heart itself,” Graham explained. "In my part of the world, quail hunting dogs with heartworm disease seem to get sick really quickly compared with sedentary dogs, and I think it’s due to the extreme activity levels of these high-performance dogs. "I doubt that veterinarians who use this method recommend exercise restriction during the nine to 30 months that it takes for these worms to die. And quite frankly, most owners would not comply with that recommendation anyway,” he said. The biggest reason not to use the slow-kill method is to preserve a precious resource—heartworm preventives, according to Nelson and Bowman. A dog on the slow-kill method is a dog that serves as a reservoir for infection and that reservoir is filled with worms that have been living on small amounts of macrocyclic lactones. That could be a recipe for the development of selective pressure. At the moment, there are no documented cases of heartworm preventive resistance, they said, but misuse could change that paradigm. "That is one reason we don’t recommend this slow-kill method, because you are putting selective pressure on these organisms. You are exposing them to low levels of drug and not killing them,” Nelson said. Bowman worries a lot about the possibility of resistance developing. "Resistance has not been proven,” he said, "but I think it is something that we need to worry about and be diligent in looking for it. I spend a lot of time thinking about resistance because if it occurs, we need to be ready. "People should use the approved preventives as indicated and use the approved treatments as indicated for treatment,” he said. "We have excellent preventives,” Nelson added. The AHS and the Companion Animal Parasite Council recommend year-round preventive for all dogs and cats. That makes sense, Graham said, because heartworm has spread to areas that traditionally haven’t seen it. (Check the incidence maps at the AHS website: www.heartwormsociety.org/veterinary-resources/incidence-maps.html.) Year-round preventives should not be a hard sell, they said, because that is the best course for the animal. "Pet owners need to understand how tremendously important it is to protect their dogs and to be compliant with the veterinarian’s instructions as to what to give and when to give it,” Graham said. The American Heartworm Society offers a continuing education program that veterinarians might find useful, Graham said. To find out more: www.heartwormsociety.org/hwu. The group’s triennial meeting will be held Sept. 8-10, 2013, in New Orleans. For more information: www.heartwormsociety.org/annual/2013symposium.html. Diagnosis Tougher in Cats As a general rule, the rate of feline heartworm infection in a heartworm endemic areas is about one-tenth that in dogs, said Wallace Graham, DVM, president of the American Heartworm Society. So, if feral dogs in an area have a 70 percent infection rate, feral cats would have a 7 percent rate. Therefore, seven out of 10 cats that are not on a preventive could have heartworm. Heartworm disease in cats is difficult to diagnose because cats have a lower worm burden, so it is harder to detect the protein secreted by the female worm, Graham said. An antibody test is a better choice for a cat with suspected heartworm infection than the antigen test, but remember that the antibody test just detects exposure and not necessarily active infection. Graham recommended running both an antibody and an antigen test. "The diagnosis in cats is more difficult and less precise than it is in dogs, and there is no treatment,” he said. Cats can have vague symptoms. Just about every veterinarian knows about the asthmatic symptoms, but cats can also present with chronic vomiting, Graham said. In an endemic area, veterinarians should think of heartworm in cats that present with chronic vomiting. Cats with heartworm can also present with sudden death, due to the tremendous inflammatory response in the lungs either when the heartworm first emerges on when it dies of natural causes. The AHS and CAPC recommend year-round preventives for cats.
