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==Treatment==
==Treatment==
Treatment in Dogs:
The extent of the preadulticide evaluation will vary depending on the clinical status of the patient and the likelihood of coexisting diseases that may affect the outcome of treatment. Clinical laboratory data should be collected selectively to complement information obtained from a thorough history, physical examination, antigen test, and usually thoracic radiography.
The most important variables influencing the probability of postadulticide thromboembolic complications and the outcome of treatment are the extent of concurrent pulmonary vascular disease and the severity of infection. Assessment of cardiopulmonary status is indispensable for evaluating a patient’s prognosis. Postadulticide pulmonary thromboembolic complications are most likely to occur in heavily infected dogs already exhibiting clinical and radiographic signs of severe pulmonary arterial vascular obstruction, especially if CHF is present.
The only available heartworm adulticide is melarsomine dihydrochloride, which is effective against mature (adult) and immature heartworms of both genders. For Class I and II patients, melarsomine is given at 2.5 mg/kg, deep IM in the epaxial (lumbar) musculature in the L3-L5 region using a 22 g needle (1 in. long for dogs <10 kg or 1.5 in. for dogs >10 kg). Pressure is applied during delivery and for 1 min after the needle is withdrawn to prevent SC leakage. The procedure is repeated on the opposite side 24 hr later. Approximately one-third of dogs will exhibit local pain, swelling, soreness with movement, or sterile abscessation at the injection site. Local fibrosis is uncommon.
Dogs with high worm burdens are at risk of severe pulmonary thromboembolism from several days to 6 wk postadulticide. Dogs with Class III infection receive the alternate (split-dose) regimen of 1 injection, followed in 1 mo by 2 injections 24 hr apart. Administration of a single initial dose results in a graded (~50%) worm kill and reduced pulmonary complications. By initially killing few worms and completing the treatment in 2 stages, the cumulative impact of worm emboli on severely diseased pulmonary arteries and lungs can be reduced. This 3-injection protocol is becoming the treatment of choice of many veterinarians regardless of stage of disease, due to its increased safety and efficacy.
Other treatment protocols recommend the administration of prophylactic doses of ivermectin for 1-6 mo prior to administration of melarsomine, if the clinical presentation does not demand immediate intervention. The rationale for this approach is to greatly reduce or eliminate circulating microfilariae and migrating D immitis larvae, stunt immature HW, and reduce female worm mass by destroying the reproductive system. This results in reduced antigenic mass, which in turns reduces the risk of pulmonary thromboembolism.
Following melarsomine injection, exercise must be severely restricted for 4-6 wk to minimize thromboembolic lung complications. A low cardiac output should be maintained in order to reduce thrombosis and endothelial damage and facilitate lung repair. Adverse effects of melarsomine are otherwise limited to local inflammation, brief low-grade fever, and salivation. Hepatic and renal toxicity are seldom seen.
Class III patients should be stabilized prior to melarsomine administration. Stabilizing treatment variably includes cage confinement, oxygen, corticosteroids, and heparin (75-100 U/kg, SC, tid) for 1 wk prior to the alternate melarsomine treatment protocol.
Patients with right-sided CHF should be treated with furosemide (1-2 mg/kg, bid), a low-dose angiotensin-converting enzyme (ACE) inhibitor such as enalapril (0.25 mg/kg, bid, possibly increased to 0.5 mg/kg, bid after 1 wk pending renal function test results), and a restricted sodium diet. Digoxin, digitoxin, and arteriolar dilators, such as hydralazine and amlodipine, should not be administered. Digoxin is not effective for cor pulmonale; arteriolar dilators, and occasionally even ACE inhibitors, are likely to cause systemic hypotension.
Postadulticide thromboembolic complications can occur 2-30 days following treatment, with signs most likely 14-21 days after treatment. Clinical signs are coughing, hemoptysis, dyspnea, tachypnea, lethargy, anorexia, and fever. Laboratory findings may include an inflammatory leukogram, thrombocytopenia, and prolonged activated clotting time or prothrombin time. A postinjection increase in serum CK may be noted. Local or disseminated intravascular coagulopathy may occur when platelet counts are <100,000/µL. Treatment for severe thromboembolism should include oxygen, cage confinement, a corticosteroid at an anti-inflammatory dosage (eg, prednisone at 1.0 mg/kg, PO, sid), and low-dose heparin (75-100 U/kg, SC, tid) for several days to 1 wk. Most dogs respond within 24 hr. Severe lung injury is likely if, after 24 hr of oxygen therapy, no improvement is noted and partial pressures of oxygen remain <70 mm Hg.
Both the standard melarsomine protocol and the alternate regimen kill all or most worms in ~75% of dogs. Antigen testing is performed 6 mo after the first 2 doses of the standard protocol or 4-6 mo after the third dose of the alternate protocol. A positive test result should be followed by retreatment (2 injections, 24 hr apart) if the antigen test is strongly positive, if the patient is still symptomatic, and if the patient is an athlete or a working dog. Mild infection, a weakly positive antigen test, absence of clinical signs, advanced age, and a sedentary dog are factors that may negate the need for a repeat melarsomine treatment. Maintaining dogs on ivermectin/pyrantel pamoate to slowly kill residual worms over the following 20 mo is an alternative in nonperforming dogs with a post-melarsomine weakly positive antigen test result.
Ivermectin/pyrantel pamoate administered monthly for ~2 yr beginning at 5-7 mo post-L3 inoculation eradicates most adult worms. Further, during this time period, some older worms are also killed. However, the use of ivermectin/pyrantel pamoate is seldom a substitute for melarsomine treatment because the slow kill may allow pulmonary pathology to progress in the interim.
In caval syndrome cases (class IV), surgical removal of worms from the right atrium and orifice of the tricuspid valve is necessary to save the life of the dog. This may be accomplished by using local anesthesia and either a rigid or flexible alligator forceps, or an intravascular retrieval snare, introduced preferentially via the right external jugular vein. With fluoroscopic guidance, if available, the instrument should continue to be passed until worms can no longer be retrieved. Immediately following a successful operation, the clinical signs should lessen or disappear. Fluid therapy may be necessary in critically ill, hypovolemic dogs to restore hemodynamic and renal function. Within a few weeks following recovery from surgery, adulticide chemotherapy is recommended to eliminate any remaining worms, particularly if many are still visible echocardiographically.
Microfilaricide Treatment:
At specific preventive dosages, the macrolide preventative drugs are effective microfilaricides, although not approved by the FDA for this purpose. Adverse reactions may occur in dogs with high microfilarial counts (>40,000/µL), depending on the type of macrolide given. However, the microfilarial count is usually lower, and mild adverse reactions occur in ~10% of dogs. Most adverse reactions are limited to brief salivation and defecation, occurring within hours and lasting up to several hours. Dogs, especially small dogs (<10 kg), with high microfilarial counts (>40,000/µL) may develop tachycardia, tachypnea, pale mucous membranes, lethargy, retching, diarrhea, and even shock. Treatment includes IV balanced electrolyte solution and a soluble corticosteroid. Recovery is usually rapid when treatment is administered quickly. Microfilarial counts are not routinely performed, and thus severe reactions are seldom expected. Treatment specifically targeting circulating microfilariae may be started as early as 3-4 wk following adulticide administration. More commonly, microfilariae are eventually eliminated, even from non-adulticide-treated dogs, after several months of treatment with prophylactic doses of the macrocyclic lactones. No drugs are currently approved as microfilaricides by the FDA. However, licensed veterinarians are permitted extra-label use of certain drugs if a valid veterinarian-client-patient relationship exists. The use of monthly administered HW chemoprophylactics as microfilaricides is governed by this regulation. The macrocyclic lactones are the safest and most effective microfilaricidal drugs available. Livestock preparations of these drugs should not be used to achieve higher doses for the purpose of obtaining more rapid results. The macrolide of choice for killing microfilariae quickly is milbemycin (0.5 mg/kg, PO, 1 dose). Performance of a microfilariae test is recommended at the time the antigen test is performed (6 mo after the adulticide treatment).
Developing Larvae:
Ivermectin/pyrantel pamoate, administered monthly for 1 yr to dogs with larvae that are no more than 4 mo post-L3 inoculation, prevents the development of infection. Continuous monthly administration of prophylactic doses of ivermectin, alone or in combination with pyrantel pamoate, is also highly effective against late precardiac larvae and young (<7 mo postinfection) quasi-adult HW. Comparable capability of the other macrocylic lactones has not been reported. This extended protection is important in dogs of unknown medical history that may have acquired HW infections because of lack of preventive drug administration or lack of compliance.
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Treatment in Cats:
There is currently no satisfactory treatment approach to heartworm infections in cats. Infection often is lethal, and a safe and effective melarsomine protocol has not yet been developed. Thus, all cats in canine HW-endemic regions should receive drug prophylaxis. The adult heartworm lifespan in cats is probably ≤2 yr, so spontaneous recovery is possible. Cats may remain asymptomatic, experience episodic vomiting and/or episodic dyspnea (resembling asthma), may die suddenly from pulmonary thromboembolism, or rarely, develop CHF. With each worm death, pulmonary complications occur. There does not appear to be an association between the presence, absence, or severity of clinical signs and the likelihood of acute complications.
Many cats are managed conservatively with restricted activity and corticosteroid therapy, such as prednisolone (1.0-2.0 mg/kg, PO, every 24-48 hr). Steroids reduce the severity of vomiting and respiratory signs. The hope is that episodes of pulmonary complications will not prove fatal as the worms die. Barring superinfection, 25-50% of cats may survive with this approach. Serial antibody testing (at 6-mo intervals) can be used to monitor status.
Surgical retrieval of worms from the right atrium, right ventricle, and vena cavae via jugular venotomy can be attempted in patients with high worm burdens detected by echocardiography. An endoscopic basket or horsehair brush can be advanced via the right jugular vein under fluoroscopy.
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1) '''Adulticidal'''
==Prevention==
Heartworm infection is completely preventable with macrolide prophylaxis. Preventive therapy in dogs is recommended beginning at 6-8 wk of age. No testing is necessary at this age. When started at ~1 yr of age, an antigen test is recommended. Before starting a prophylactic regime, all mature dogs that may have been infected >7 mo earlier should be antigen tested and, in appropriate instances, tested for presence of microfilariae. The determination of HW status before starting chemoprophylaxis will avoid unnecessary delay in detecting subclinical infections, and potential confusion concerning effectiveness of the preventive program, if a pre-existing infection becomes evident after beginning chemoprophylaxis. Year-round prevention is advised, but in northern climates, chemoprophylaxis is often initiated in the spring and continued through November. Year-round macrolide administration will arrest the development of larval stages (L3 and L4) that might have occurred prior to preventative initiation or when monthly doses were missed.
The macrolide preventives ivermectin, milbemycin oxime, moxidectin, and selamectin are safe and effective as prescribed for all breeds. Ivermectin/pyrantel pamoate (hookworms and roundworms) and milbemycin (hookworms, roundworms, and whipworms) also provide control of intestinal nematodes. Milbemycin, however, kills microfilariae (L1) quickly and shock can occur in the face of high microfilarial concentrations. Thus, milbemycin is not administered as a preventive in dogs with microfilariae. Selamectin is administered topically at a monthly dosage of ~6 mg/kg and also kills adult fleas and prevents flea eggs from hatching for 1 mo. It also is indicated for the treatment and control of Otodectes cynotis in dogs and cats, sarcoptic mange, Dermacentor variabilis infestations in dogs, Ancylostoma tubaeforme , and Toxocara cati in cats.
Annual antigen testing is recommended because overall owner compliance with macrolide prophylaxis is only ~50%. The injectable form of moxidectin is effective for at least 6 mo following 1 injection but use in microfilaremic dogs is not advised. At the time of publication, this formulation was not available in the USA because of concerns regarding toxicity in dogs. With macrolide administration for 6 mo and longer, microfilariae production by female worms ceases and antigen testing is required for detection of infection.
Heartworm prevention is recommended for all cats in endemic regions, regardless of housing status, because of the potential severe consequences. Ivermectin for cats is safe and effective at 25 µg/kg, PO, once monthly. At this dose, the formulation is also effective against Ancylostoma tubaeforme and A braziliense . Preventive treatment should be initiated in all adult cats, in kittens 6 wk of age, and continued lifelong. Annual antigen and antibody testing is of limited value in cats receiving prophylaxis.
==Prognosis==
==Prognosis==