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| | ==Treatment== | | ==Treatment== |
| − | Treatment in Dogs:
| + | ADULTICIDAL TREATMENT |
| − | 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 decision as to whether or not to treat a dog with |
| − | 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.
| + | heartworm disease and the relative prognosis depend on |
| − | 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 Pressure is applied during delivery and for 1 min after the needle is withdrawn to prevent SC leakage.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.
| + | the severity of the infection. In an attempt to assess this, |
| − | 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.
| + | animals may be classified as: |
| − | 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.
| + | * CLASS 1. Patients with subclinical or no clinical signs; |
| − | 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 2. Patients with mild to moderate clinical signs |
| − | 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.
| + | and mild to moderate radiographic changes; |
| − | 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.
| + | * CLASS 3. Patients with severe clinical signs (eg, persistent |
| − | 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.
| + | cough, haemoptysis, dyspnoea, right-sided heart |
| − | 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.
| + | failure) and severe radiographic changes. |
| − | 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.
| + | The prognosis for dogs in class 1 following adulticidal |
| − | 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.
| + | treatment is generally very good. Dogs in class 2 |
| − | Microfilaricide Treatment:
| + | may have a positive outcome. Animals in class 3 have a |
| − | 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).
| + | guarded prognosis due to the high risk of pulmonary |
| − | Developing Larvae:
| + | thromboembolism; in these cases, the potential complications |
| − | 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.
| + | of adulticidal treatment should be thoroughly |
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| + | discussed with the owners. |
| − | Treatment in Cats:
| + | In cats, adulticidal treatment may be dangerous even |
| − | 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.
| + | in patients with low grade infection, and pulmonary |
| − | 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.
| + | thromboembolism due to premature death of parasites is a common complication. Considering that some cats |
| − | 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.
| + | may undergo spontaneous clinical remission if parasites |
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| + | die naturally, periodic monitoring of the patient is more |
| | + | appropriate than adulticidal treatment. Cats with respiratory |
| | + | signs can be treated symptomatically in the same way |
| | + | as patients with feline asthma. Cage rest, oxygen supplementation, |
| | + | fluid therapy, bronchodilators and injectable |
| | + | steroids (eg, dexamethasone) can be used to stabilise |
| | + | acutely ill cats. Adulticidal treatment should only be considered |
| | + | for cats in a stable condition that fail to respond to |
| | + | supportive treatments. |
| | + | Adulticidal treatment involves the administration of |
| | + | a new generation arsenical compound, melarsomine dihydrochloride |
| | + | (Immiticide, Merial; this product is not |
| | + | licensed for use in the UK). Melarsomine is less nephrotoxic |
| | + | and hepatotoxic than its predecessor thiacetarsamide, |
| | + | and has a higher efficacy. Melarsomine is injected |
| | + | intramuscularly into the lumbar muscles at a recommended |
| | + | dose of 2-5 mg/kg, repeated after 24 hours. However, |
| | + | only a single dose should be administered to class 3 dogs, |
| | + | to kill just a proportion of worms and hence minimise |
| | + | the risk of pulmonary thromboembolism. If the patient |
| | + | remains stable, the standard adulticidal protocol can be |
| | + | administered one month later. In the week following the |
| | + | administration of melarsomine, the likelihood of pulmonary |
| | + | thromboembolism can be minimised with cage |
| | + | rest and corticosteroids at anti-inflammatory doses. |
| | + | If adulticidal treatment is declined by the owner, |
| | + | monthly administration of prophylactic doses of ivermectin |
| | + | may represent a reasonable option because it will prevent |
| | + | further infection and may kill some adult nematodes. |
| | + | Patients with severe caval syndrome may benefit from |
| | + | physical removal of worms from the right side of the |
| | + | heart and the main pulmonary artery using flexible crocodile |
| | + | or basket-type retrieval forceps. This procedure is |
| | + | complex, requires general anaesthesia and fluoroscopic |
| | + | imaging, but may reduce the risk of thromboembolism |
| | + | following subsequent adulticidal treatment. |
| | + | MICROFILARICIDAL TREATMENT |
| | + | Circulating microfilariae should be eliminated four to six |
| | + | weeks after successful adulticidal treatment. There are |
| | + | no approved drugs for microfilaricidal treatment. However, |
| | + | a single administration of ivermectin (50 jig/kg) |
| | + | or milbemycin oxime (500 jig/kg) has been shown to be |
| | + | highly effective in eliminating microfilariae from the circulation |
| | + | within a few hours. Moxidectin and selamectin |
| | + | are also known to be potent microfilaricides but, at present, |
| | + | there is little experience of their use in the clinical |
| | + | setting. Oral prednisolone (1 to 2 mg/kg) administered |
| | + | with microfilaricidal drugs may control anaphylactic |
| | + | reactions which may occur secondarily to the sudden |
| | + | death of a large number of microfilariae. |
| | + | PREVENTION |
| | + | Prophylaxis of heartworm disease should be considered |
| | + | for all dogs and cats living in endemic areas during the |
| | + | transmission period. For example, in northern Italy, |
| | + | where a high prevalence of heartworm disease has been |
| | + | reported, mosquitoes are only present during the summer |
| | + | and, therefore, prophylaxis is recommended from May to |
| | + | October. |
| | + | The currently approved prophylactic drugs are listed |
| | + | in the table below. However, only milbemycin oxime |
| | + | (Program Plus; Novartis) and selamectin (Stronghold;Pfizer) are licensed in the UK for the prevention |
| | + | of heartworm disease. Preventive drugs kill migrating |
| | + | larvae of D immitis up to the sixth week of infection. |
| | + | Therefore, they all provide a high degree of protection |
| | + | when administered on a monthly basis. If a patient misses |
| | + | one or more doses in the prophylactic schedule, it |
| | + | should be tested for heartworm disease after six months. |
| | + | The risk of incomplete protection due to owner noncompliance |
| | + | can be eliminated with a recently introduced |
| | + | sustained-release injectable formulation of moxidectin |
| | + | (Proheart 6; Fort Dodge). |
| | + | High doses of ivermectin and milbemycin oxime are |
| | + | potentially toxic in approximately one-third of collies. |
| | + | However, side effects are not observed in these breeds |
| | + | when prophylactic drugs are administered at the recommended |
| | + | doses. |
| | | | |
| | ==Prevention== | | ==Prevention== |