Veterinary Medicine


Angiostrongylus vasorum is a metastrongyloid parasite of dogs and foxes which primarily parasitizes the pulmonary artery and its branches; it may also inhabit the right ventricle. Natural A. vasorum infection has been reported in a number of European countries including Ireland. Denmark, southwest France. Spain. Italy and pans of the UK. In the UK the majority of reported cases have been confined to southwest England and south Wales. The parasite was first encountered In the UK in racing greyhounds imported from Ireland.

Life cycle of Angistrongylus vasorum

Adult worms lay eggs in the terminal pulmonary arteries after a pre-patent period of 38-60 days. The first stage larvae hatch into the alveoli, pass up the bronchial tree and are swallowed and shed in the faeces. Several species of slugs and snails act as intermediate hosts. Transmission of the infective L3 larvae is thought to occur if the snails are ingested or if the dog’s food becomes contaminated with faeces or slime. When ingested the third stage larvae migrate via the mesenteric lymph nodes and portal system to the liver before passing to the right ventricle and pulmonary arteries.

Clinical signs

Clinical signs include tachypnoea, coughing, haemoptysis, anaemia and haematoma formation. Some dogs with natural or experimental infections either have no clinical signs referable to the disease or show only mild exercise intolerance, others may develop signs of acute right-sided heart failure and die within a few days of the onset of clinical signs.

Radiographic findings

A diffuse interstitial / bronchial pattern with patchy coalescing alveolar densities especially in the caudal lung lobes may be visible. The latter are thought to represent focal areas of pneumonitis and haemorrhage. The right atrium and right ventricle may become enlarged and the pulmonary arteries may appear truncated. Occasionally there is evidence of pulmonary emphysema or pneumothorax.

Clinicopathologicat findings

Identification of A. vasorum larvae in faecal samples is the best method of diagnosing patent infections. Occult infections occur and the absence of faecal larvae does not preclude A. vasorum infection, since adult worms shed eggs intermittently. Haematological findings are inconsistent; an eosinophilia associated with larval migration may be present and some cases may be anaemic. Serum protein electrophoresis may reveal beta 2 and / or gamma globulin peaks.

The increased bleeding tendency has been attributed to a consumptive coagulopathy resembling chronic compensated disseminated intravascular coagulation which results in low platelet numbers and prolongation of the activated partial thromboplastin time. Decreased factor V concentrations have been reported in experimental infections.

Angiostrongylosis: Treatment

A. vasorum infections have been treated effectively with fenbendazole (20 mg kg-1 once daily for 10 days), levamisole (10 mg kg-1 daily for three days) and ivermectin (200 μg kg1 given subcutaneously as a single dose). The ability of these drugs to completely eliminate adult worms and / or larvae has yet to be determined.

Veterinary Medicine


Canine heart worm disease caused by Dirofilaria immitis is endemic in most temperate and tropical coastal zones of the world (United States. Japan and Australia especially). Heartworm disease is occasionally diagnosed in imported dogs in the United Kingdom. Affected animals are often between 4 and 7 years of age although the condition has been diagnosed in animals less than one year of age.

Life cycle of Dirofilaria immitis

When a mosquito bites an infected dog circulating microfilaria (first stage larvae) are ingested and develop into third stage (L3) larvae which migrate to the mouth parts of the mosquito. The third larval stage of the heartworm (Dirofilaria immitis) stage enters the subcutaneous tissues of the host via a bite from an infected mosquito. Young adult worms (L5 stage) reach the right side of the heart by 90-100 days postinfection. There is a prepatent time of approximately 6 months before microfilaria appear in the circulation. Occult infections occur where there is an absence of circulating microfilaria.

Pathophysiology of heartworm disease

Adult worms live most commonly in the right ventricle, main pulmonary artery and parenchymal pulmonary arteries. As the number of heart-worms increases they enter the right atrium and eventually migrate into the caudal vena cava. Large numbers of worms may obstruct the caudal vena cava and flow of blood to the right atrium (vena caval syndrome).

Adult worms initiate a parasite-host reaction which damages the pulmonary artery endothelium. Histologically this reaction is characterized by the proliferation of smooth muscle cells on the endothelial surface of the vessels. Circulating antibodies trap the microfilaria within the pulmonary arteries which results in pulmonary infarction and areas of consolidation around the affected vessels. Alveolar hypoxia increases pulmonary vascular resistance and leads to pulmonary hypertension. Pulmonary hypertension results in increased right ventricular afterload, right ventricular hypertrophy and eventually signs of right-sided heart failure (cor pulmonale).

Clinical signs

The clinical signs of heartworm disease, once apparent, are usually severe and progress rapidly. Damage to the pulmonary arteries results in coughing, haemoptysis, dyspnoea and decreased exercise tolerance. There is a rapid loss of body condition and pulmonary hypertension leads to right-sided heart failure. Tricuspid valve murmurs may be heard due to mechanical interference with valvular function by the adult worms.

Some infected dogs show few if any clinical signs. Those with occult heartworm disease develop an allergic pneumonitis characterized by severe coughing and dyspnoea. Two conditions which may have an immune-mediated pathogenesis, eosinophilic granulomatosis and pulmonary infiltrates with eosinophilia (eosinophilic pneumonia), may also occur in association with heart-worm disease. Severe pulmonary artery disease may result in thromboembolic complications and thrombocytopenia especially after adulticide therapy.

Haemolysis and haemoglobinuria may occur when a large number of worms obstruct the caudal vena cava and result in fragmentation of red cells. Dogs with the caval syndrome become severely dyspnoeic and show signs of acute hypotension (tachycardia, pale mucous membranes and prolonged capillary refill time).

Electro cartography

Electrocardiographs signs of right ventricular enlargement may be evident especially in dogs showing signs of right-sided heart failure.

Radiographic findings

Radiographic changes develop early during the course of heartworm infection. Typical abnormalities include right ventricular enlargement and a bulging pulmonary artery segement with enlarged lobar pulmonary arteries. As the disease progresses the peripheral pulmonary arteries become truncated and tortuous especially in the caudal lung lobes. Patchy alveolar densities may be apparent especially after adulticide therapy.

Clinicopathological findings

Eosinophilia often accompanied by basophilia are the most consistent haematological abnormalities, occurring once die young adult worms enter the circulation. A mild regenerative anaemia may be present and neutrophilia may occur following aduhicide treatment. Platelet numbers are often reduced as a result of increased consumption in response to endothelial damage. Liver enzymes may be increased especially if signs of right-sided cardiac failure are present; total plasma proteins may also be increased due to an increase in the globulin fraction. Proteinuria occurs in 20-30% of cases; some animals develop a glomerulonephropathy and nephrotic syndrome, and become hypoalbuminaemic.

Diagnosis of Dirofilariasis

The presence of microfilaria on a peripheral blood film implies the presence of adult worms. Dirofilaria immitis microfilaria should be differentiated from those of Dipetalonema reconditum and other Dipetalonema species which cause asymptomatic infections in dogs. This can be done by examining the acid phosphatase staining pattern of filter-treated micro-filariae. The blood of young dogs from endemic areas should be screened annually for the presence of microfilaria using a Knott’s test. With occult infections, no circulating microfilaria are present and diagnosis is dependent on the detection of appropriate radiographic abnormalities and the results of other serodiagnostic tests.

An indirect fluorescent antibodv test detecting antibodies to microfilarial antigens is useful in the diagnosis of occult heartworm disease. An ELISA test for detecting antibodies against adult worms has proved to be less satisfactory because of the high incidence of false positive results, although a negative ELISA result can be regarded as reliable evidence that occult heart-worm disease is not present. More recently, ELISA tests using monoclonal antibodies against circulating adult antigens have been developed which appear to be more sensitive and specific than tests which detect adult antibodies.

Dirofilariasis: Treatment

Adulticide therapy

Thiacetarsamide (22 mg kg-1 body weight intravenously twice daily for two days) eliminates a high percentage of the adult heart worms (young female heart worms are often resistant). The second dose should be given not more than 10 hours after the first. Treatment with thiacetarsamide should be delayed in dogs with radiographic signs of severe pulmonary artery disease since such animals are at risk from developing thromboembolic complications and thrombocytopenia post-treatment. Toxic reactions to thiacetarsamide occasionally occur; these include anorexia, vomiting, depression, fever, diarrhoea and the presence of tubular casts in the urine. Adulticide treatment is usually followed 4-6 weeks later by the administration of a microfilaricide. The benefits of giving a microfilaricide three weeks before treatment with thiacetarsamide are questionable.

Levamisole has been used as an alternative adulticide drug but is less effective than thiacetarsamide. It is more effective as a microfilaricidal drug but toxic side effects (vomiting and CNS signs) are common.

The prophylactic use of aspirin to combat the potential thromboembolic complications has been questioned. Recent studies have shown that even doses of aspirin greater than 50 mg kg-1 in some dogs will not prevent thromboembolism or imimal hyperplasia associated with heart worm emboli.

Corticosteroids are indicated if there is evidence of an eosinophilic pulmonary infiltrate. Heparin has been recommended for dogs showing signs of chronic or low-grade disseminated intravascular coagulation (DIC).

Microfilaricide treatment

Levamisole, milbemycin and ivermectin are available for use as microfilaricides (the last two can also be used prophylactically). The American Heartworm Society currently recommends that cither ivermectin (50 μg kg-1) or milbemycin (500 μg kg-1) be given 3-4 weeks after treatment with adulticide. Treatment of dogs with large numbers of microfilaria may lead to circulatory collapse due to rapid death of the microfilaria. Dogs should therefore be observed for 6-8 h after treatment. The use of ivermectin and milbemycin in collies and collie cross breeds has been associated with anaphylactic reactions and, in some cases, death; although both the microfilaricidal and the preventative doses of these drugs are reportedly safe in susceptible collies other drugs, for example levamisole (10 mg kg-1 day-1 for 7 days) have been recommended for this breed.

Prevention of heartworm disease

Chemoprophylaxis should be initiated 2-3 weeks after administration of a microfilaricide providing no microfilariae are detected in the blood; if microfilariae are still present microfilaricidal treatment should be repeated). In endemic areas, either ivermectin (6-12 μg kg-1) or milbemycin (500-999 μg kg-1) can be administered once a month. Young pups can be treated prophylactically from 6-8 weeks of age onwards. Although both drugs can be safely given to dogs which may already have circulating microfilariae, they only kill D. immitis larvae during the first six weeks of their development. Both drugs are also known to induce sterility in adult worms there-fore dogs greater than 6 months of age on monthly preventative treatment should be tested for antigen to detect occult infections which may develop within 6 months of starting monthly macrolide administration.


Diseases Of The Ear: Crusting And Scaling Dermatoses

Scabies and Mange

Erythematous, papular dermatitis of the distal pinnae associated with significant pruritus is an early manifestation of Sarcoptes scabiei in dogs. Crust and scale will usually first affect the tip of the pinna or ear margin. The pinnal-pedal reflex (i.e. rubbing the pinna resulting in a pelvic limb scratch reflex) is often associated with sarcoptic mange but is not pathognomonic for the condition. Concurrent lesions often involve the lateral hocks and elbows and may spread to the rest of the body. The diagnosis is usually made with skin scrapings; however, multiple scrapings may be necessary to achieve the diagnosis. The presence of a single mite, egg, or fecal droppings is diagnostic for the disease. All animals in the household should be treated, and the condition is zoonotic, so owners and handlers should be made aware of the condition. Initial treatment consists of removal of crusts and debris, followed by an acaracidal dip such as lime sulfur, permethrin, organophosphate, or amitraz, which may shorten time to resolution of clinical signs and diminish zoonotic potential. Ivermectin administered subcutaneously, twice at 14-day intervals, or orally three times at 7-day intervals, results in cure. A similar dose schedule exists for milbemcyin. Topical application of selamectin or fipronil may also be curative.

Feline mange, caused by Notoedres cati, results in alopecia, pruritus, excoriations, and thick crusts of the rostral pinnae and is usually restricted to the ears and head. The extremities and perineum may also be affected due to the sleeping and grooming habits of cats. The parasite may also inhabit dogs, foxes, and rabbits; transient lesions have been reported in humans. The diagnosis is made with skin scrapings, and lime sulfur or amitraz dips are effective treatments. Ivermectin given two or three times subcutaneously is also effective.

Fly Strike Dermatitis

Insect bite dermatitis, primarily caused by the stable fly, Stomoxys cakitrans, results in serosanguineous, crusting dermatitis on the ear tips in dogs with erect ears or on the folded edge of the pinna in dogs with pendulous ears. Chronic fly strike dermatitis can become granulomatous in nature. Horse flies (Tabanus species) and deer flies (Chrysops species) may also plague dogs that are housed outdoors, but their bites are usually less reactive than stable flies. The diagnosis is based on an environmental history and response to limiting outdoor exposure. Fly repellents containing permethrin, citronella, or diethyltoluamide (DEET) in petroleum jelly may be used to diminish repeated fly bites. Topical corticosteroid with an antibiotic may hasten the resolution of clinical signs. Black flies (Simulium species) may also cause papular dermatitis and alopecia in dogs.

Cats can develop a seasonal hypersensitivity to mosquito bites. Papules, erythema, alopecia, and hypopigmentation occur on the pinnae and face. Pyrexia, lymphadenopathy, and footpad lesions may also occur.

Actinic Dermatitis and Squamous Cell Carcinoma

Damage to the skin by long-term sun exposure occurs most often in white cats, although the condition is also reported in dogs and in cats with pigmented skin. The pinna is most often affected due to its sparse hair covering; the nose, lips, and eyelids may be similarly affected. Waxing and waning ear tip erythema may progress to the development of fine scale and alopecia early in the disease. Erosive, crusted, hemorrhagic lesions and folding of the pinna occur as a precancerous condition, which may ultimately lead to carcinomatous change., Squamous cell carcinoma is most often diagnosed in older cats (mean age, 12.8 years) with either skin scrapings or biopsy.

Treatment of actinic dermatitis ideally consists of limiting sun exposure between the hours of 10 AM and 4 pm by housing indoors and eliminating sunbathing behavior. Application of sunscreen of SPF 15 or greater may also decrease the effects of solar radiation. β-carotene and canthaxanthin administered orally and the use of retinoic acids (i.e. isotretinoin, etretinate) have also been reported. An initial response to therapy may be seen, but long-term effectiveness has not been thoroughly investigated. Strontium plesiotherapy has been used in the treatment of actinic dermatitis. Failure to respond to medical management is an indication for pinnectomy.

Squamous cell carcinoma is usually locally invasive and slow to metastasize to either local lymph nodes or the lung. Pinnectomy is an effective mode of therapy for severe actinic dermatitis and squamous cell carcinoma. Cryosurgery, radiotherapy, brachytherapy, hyperthermic, and photodynamic therapy have also been used on focal lesions; systemic chemotherapy is not considered effective.


Animals affected by frostbite are usually systemically ill or have recendy moved to a cold environment. The ear tips are pale, cyanotic, hypoesthetic, and cool to the touch after exposure. With warming, the tissues become hyperemic and develop scale, crust, and alopecia. The ear tips may curl, necrose, and eventually slough. Initial treatment consists of rewarming with warm water and subsequent symptomatic therapy for scaling and crusting dermatitis. Amputation of necrotic tissue results in improved cosmesis with haired skin and decreases the risk of recurrent freezing, which is more likely in previously frostbitten tissue.


The underlying cause of vasculitis is often unknown, but the condition occurs subsequent to Type I and Type III hypersensitivity reactions and the deposition of antigen and antibody complex within the vascular wall. The lesions are characterized by erythema, edema, and eventual necrosis and sloughing, leading to a “punched out” or ulcerated appearance to the pinnae. Other affected areas include the lips, tail, pads, and nails. A neutrophilic, eosinophilic, or lymphocytic vasculitis may be evident on histopathology. Proliferative thrombovascular necrosis of the pinnae is a form of vasculitis reported in dogs. Inflammatory vasculitis is not evident in this syndrome and cause is unknown. Conditions such as rickettsial disease, drug eruption, immune-mediated disease, and other underlying systemic conditions should be ruled out. Therapy should be directed at treating the underlying cause. Idiopathic vasculitis cases may respond to immunosuppressive doses of corticosteroids. Other reported treatments include pentoxy-phylline, sulfasalazine, or dapsone. Surgical excision of the affected portion of the pinna with wide surgical margins may be indicated if medical management is unsuccessful.


Crusting and scaling of the pinnae may be caused by idiopathic defects in keratinization, primary disease conditions causing seborrhea, and secondary changes in keratinization due to parasitism. Ear margin dermatosis is common in dachshunds and other breeds with pendulous ears. Seborrheic changes begin at the ear margin and progress to confluence of scale and significant alopecia. Pruritus is variable but may be present in severe cases. The condition is not curable but controllable with keratolytic keratoplastic shampoos (e.g. sulfur-asalicylic acid, benzoyl peroxide or benzoyl peroxide-sulfur, selenium sulfide). Severe cases may require topical or systemic corticosteroid treatment due to inflammation associated with removal of crusts or ear fissure formation.

Sebaceous adenitis is associated with an inflammatory process of the sebaceous glands. Follicular disruption, alopecia, and surface scale initially affect the pinna and may involve the ear canal and trunk. No direct therapy exists for lost sebaceous glands, and supportive care with fatty acids, humectants, and anti-inflammatory corticosteroids can be useful. Retinoids have been used in cases with a granulomatous response to the process.

Other less common disorders can cause hyperkeratosis of the pinna. Idiopathic benign lichenoid keratosis has been diagnosed in four dogs with multiple wartlike papules and hyperkeratotic plaques on the pinnae. Lichenoid psoriaform dermatosis is a rare condition in which erythematous papules and lichenoid plaques appear on the concave surface of the pinna, external ear canal, and ventral head and trunk. Treatment consists of antimicrobial shampoo, systemic antibiotics, and corticosteroids. Lupoid dermatosis is a heritable condition of German short-haired pointers in which progressive, nonpruritic scale occurs on the pinnae, face, and trunk. No therapy is available for the condition.

Nutritional Dermatoses

Zinc deficiency caused by dietary insufficiency or inability to absorb dietary zinc results in crusting lesions of the pinna, and perioral, periorbital, perianal, and perivulvar sites of dogs. Food allergy can result in steroid-resistant alopecia, crust, scale, hyperpigmentation, and lichenification of the pinnae. Dietary restriction followed by feeding trials is diagnostic of the condition, which may be associated with lesions and pruritus on other parts of the body.


Diseases of the Ear: Pathophysiology

Otitis extema describes any inflammatory condition of the external ear canal. The estimated incidence of otitis in dogs and cats ranges from 4% to 20% and 2% to 6.6%, respectively. Clinical signs associated with the condition vary, depending on the cause of the otitis General signs consist of head shaking, scratching, otic pain, and a variable accumulation of cerumen or exudate. The external canal responds to chronic inflammation of the dermis and epidermis with epithelial hyperplasia and hyperkeratosis, sebaceous gland hyperplasia, and ceruminous gland hyperplasia and dilation. These changes are associated with increased cerumen production; however, increased humidity, increased pH, and decreased lipid content of the cerumen predispose the animal to secondary infection. Apocrine gland rupture, sebaceous gland degeneration, ear canal stenosis, and fibrosis or ossification of the canal (or both) usually occur with the end stages of otitis. Because permanent changes of the ear canal can occur with any cause of otitis extema, primary, predisposing, and perpetuating factors should be investigated in all cases of otitis.

Primary Factors

Primary factors are capable of causing otitis in normal ears. Primary factors may not be cured but often are controlled with appropriate therapy.


Atopy and food hypersensitivity Otitis externa is a clinical sign in 50% to 80% of atopic or food-sensitive dogs and may be the sole clinical sign associated with atopy. Erythematous ceruminous otitis is most commonly associated with allergic skin disease. Early clinical signs of bilateral pruritus, concave pinnal erythema, and mild erythematous and ceruminous otitis of the proximal ear canal may progress to significant otitis externa and pinnal hyperpigmentation. The pet can develop end-stage otitis if the primary cause is not identified and treated. Aural pruritus is common to atopy and food hypersensitivity; however, steroid responsiveness is usually only seen with atopy. Atopic dogs also tend to have a slower progression of disease than food-sensitive dogs. Secondary infection with either Mcdassezia packydermatis or bacterial cocci is common. A definitive diagnosis is based on biopsy, intradermal skin testing, serologic testing, or dietary restriction and subsequent diet trials.

Contact hypersensitivity and irritant reaction Topical otic preparations may cause a delayed hypersensitivity or irritant reaction to the ear canal. A response to initial therapy is followed by progression of disease or change in the character of the otitis with continued therapy. Worsening of clinical signs can occur if the medication is discontinued then readminis-tered. Neomycin, propylene glycol, and dimethyl sulfoxide have been associated with irritant otitis. Reactions are occasionally noted with alcohol, glycerin, povidone-iodine, and concentrations of acetic acid greater than 2%. Contact hypersensitivity or an irritant reaction should be suspected any time otitis externa is exacerbated by therapy or upon changes in the gross or cytologic appearance of the otitis. Both contact hypersensitivity and irritant reaction act as perpetuating factors of otitis externa despite control of the primary factor.


Otodectes cynotis is the cause of otitis externa (otocariasis) in up to 50% of cats and 10% of dogs with otitis externa. The infestation in cats may be classified as one of the following: (1) otitis externa, (2) ectopic infestation, or (3) asymptomatic carrier. Signs of otitis include significant pruritus, pinnal erythema and crusting, and accumulation of cerumen in the external ear canal. Gross character of the cerumen is not correlated to the microscopic findings, but is usually dark brown to black in color. Mites may be observed on otoscopic examination; however, mineral oil cytology is recommended, because few mites are required to cause clinical signs. Mites may concurrently inhabit the skin of the head and neck in animals with otitis. True ectoparasite infestation usually results in miliary dermatitis and patchy alopecia in cats. Treatment can include any of the following: carbamates, pyrethrins, rotenone, ivermectin, thiabendazole, or fipronyl. Selamectin has recently been proven safe and effective for treating otocariasis in both dogs and cats. The 3-week cycle of the parasite should be considered in treatment planning.

Demodex canis has been associated with mild otitis and excessive cerumen production in dogs with the generalized form of demodicosis. The diagnosis is made with mineral oil cytology; other diagnostics (e.g. biopsy) are less often required. Other parasites such as harvest mites (Neotrombicula autumnahs and Euotrombicula alfredugesi) and ticks (Otobius megnini) may cause otitis externa. Reinfestation is a common problem due to environmental exposure to these parasites.

Foreign Bodies

Younger dogs, especially hunting or working breeds, are predisposed to otic foreign bodies. The most common foreign body associated with otitis is the grass awn; however, other foreign bodies include dirt, sand, cerumen, exudate mixed with hair, and conglomerates of dried ear medication. All can incite inflammation. Dogs are usually acutely painful, bilateral foreign bodies are possible, and approximately 20% of otic foreign bodies penetrate the tympanic membrane, leading to otitis media.

Keratinization Defects

Hypothyroidism, male feminizing syndrome, Sertoli cell tumor, hyperestrogenism, and idiopathic seborrhea may be associated with mild otitis externa. Idiopathic seborrhea in cocker spaniels and hereditary defects in cats leading to seborrhea may cause erythematous ceruminous otitis. Changes in the microenviron-ment of the ear canal lead to secondary purulent otitis.

Idiopathic Inflammatory or Hyperplastic Otitis

Cocker spaniels may be affected by severe, proliferative otitis externa at a young age. Concurrent dermatologic conditions are not necessarily present but should be ruled out for proper management. The cause of the condition is unknown but may be due to a primary glandular disorder.

Other Primary Factors

Immune-mediated disorders such as pemphigus complex may be associated with both pinnal lesions and otitis extema. Pemphigus foliaceus may involve only the ears in some cases, but lesions on other parts of the body are usually present. Drug eruption from systemically administered drugs may also cause both pinnal lesions and otitis extema. Older animals with chronic or recurrent otitis should be evaluated for benign or malignant neoplasia of the skin or adenexal structures of the ear.

Predisposing Factors Predisposing factors make otitis more likely by altering the environment of the external ear canal, thereby making the ear more susceptible to inflammation and secondary infection.

Anatomic Changes

Increased soft tissue within the ear canal, increased compound hair follicles in the canal, and stenotic canals (e.g. Shar Pei, bulldog, chow chow) or chronic changes associated with previous bouts of otitis may be predisposing factors for otitis externa. Dogs with pendulous ears are predisposed to otitis, and otitis is common in breeds of dogs exhibiting increased ceruminous compared with sebaceous gland area (e.g. cocker spaniel, Labrador retriever, springer spaniel). Hair is normally present in the ear canal, and increased numbers of hairs or presence of compound hair follicles have not been correlated to the incidence of otitis in dogs. Routine hair plucking is therefore not recommended and may incite an inflammatory response within the epithelium, perpetuating otitis extema.

External Environment

Increases in temperature and humidity in the environment may be reflected in the ear canal. The incidence of otitis extema is seasonally related to temperature, humidity, and rainfall. A lag period of 1 to 2 months is associated with cases of canine otitis and may vary with geographic location. Positive cultures of the ear canal are more likely during times of increased environmental temperature and humidity.

Perpetuating Factors Perpetuating factors exacerbate the inflammatory process and can maintain the disease after the primary factor has been eliminated. They can induce permanent pathologic changes to the ear canal and are the main reason for treatment failure in otitis externa.

Secondary Bacterial Colonization and Infection

Normal bacterial flora exist in the ear canal of dogs and cats. Staphylococcus species and Streptococcus species are often cultured, Pseudomonas is rarely cultured, and Proteus was not cultured from the normal canine ear canal. Malassezia has also been identified on cytologic examination in normal dogs and cats, and its numbers are significandy increased in erythema-tous ceruminous otitis. Bacteria and yeast are opportunistic pathogens but can cause significant secondary changes of the ear canal with chronic infection. Increased numbers of bacteria without an inflammatory response may represent colonization, which often responds to topical therapy. The presence of inflammatory cells suggests true infection, and culture and susceptibility is recommended due to resistance patterns of many bacteria. In colonization and infection, cleaning the external ear canal removes exudate, debris, toxins, free fatty acids, and bacteria that perpetuate inflammation and secondary changes of the ear canal.

Staphylococcus species are common in dogs with otitis as are Pseudomonas aeruginosa, Proteus species, Escherichia coli, Corynebacterium species, and Streptococcus species. Acute purulent otitis externa is less common than chronic, but with chronicity and repeated treatment, gram-negative bacteria, such as Pseudomonas and Proteus, predominate. The associated otitis may have surface erosions or ulcers and copious exudate. Cats may be secondarily infected with PasteureWa multocida and less often Pseudomonas aeruginosa, Proteus species, or E. coli.

Malassezia Pachydermatis Budding yeast has been identified on ear cytology of normal dogs (up to 50%) and cats (up to 17.6%). Malassezia are considered part of the normal flora and an opportunist in cases of otitis externa, particularly in cases of erythematous ceruminous otitis. Malassezia are lipid-dependent yeast that overgrow in conditions of increased moisture, increased surface lipids, and compromised barrier function of the stratum corneum. Enzymes produced by the yeast may allow depolymerization of the interstitial matrix (e.g. hyaluronidase, chondroitin-sulphatase) and cell membranes (e.g. proteinase, phospholipase), increasing tissue invasion and penetration. Cytologic examination is more valuable than culture, because some species of Malassezia require specific media supplemented with long-chain fatty acids.

Chronic Anatomic Changes

Increased soft tissue volume within the ear canal associated with chronic otic inflammation leads to ear canal stenosis and alters the otic microenvironment. Chronic changes of the epidermis, adenexa, dermis, and cartilage are described in the previous pathophysiology section. The microenviron-mental alterations associated with chronic ear canal stenosis and inflammation favor bacterial and yeast proliferation and the retention of exudate. The changes also hinder proper cleaning and medication of the deeper portions of the external ear canal.

Otitis Media

Untreated infection of the middle ear serves as a source for perpetuating otitis externa. Failure to identify the bacteria, yeast, or byproducts of inflammation in the middle ear may result in recurrent otitis externa and chronic pathologic changes of the middle and external ear.

Treatment Errors, Undertreatment, and Over-treatment

Incorrect treatment of otitis allows bacterial or yeast overgrowth or infection and denies treatment of the primary factor causing otitis. Overapplication of medication or use of occlusive medications increases the humidity of the ear canal, leading to epithelial maceration and inflammation, perpetuating otitis; accumulation of dried medication acts as a foreign body within the ear canal. Undertreatment allows progression of the disease and the development of resistance in the bacteria causing secondary infection.


Diseases of the Ear: General Principles Of Management

The therapeutic plan for otitis externa requires identification of the primary disease process and perpetuating factors. Ideally management is aimed at thoroughly cleaning and drying the ear canal, removing or managing the primary factors, controlling perpetuating factors, administering appropriate topical or systemic therapy (or both), and evaluating response to therapy.

Ear Cleaning

Ear cleaning serves several functions: (1) it removes material that supports or perpetuates infection; (2) it removes bacterial toxins, white blood cells (WBCs), and free fatty acids that stimulate inflammation; (3) it allows complete evaluation of the external ear canal and tympanum; (4) it allows topical therapy to contact all portions of the ear canal; and (5) it removes material that may inactivate topical medications. Significandy painful ears may benefit from initial anti-inflammatory therapy to decrease pain and swelling of the ear canal prior to cleaning. Severe cases of otitis externa often require general anesthesia to facilitate complete cleaning and evaluation of the external and middle ear.

Many different solutions are available for removing cerumen, exudate, and debris from the ear canal (Table Otic Cleaning Solutions). If the tympanic membrane cannot be visualized, only physiologic saline solution or water should be used, because many topical cleaning agents are ototoxic or incite inflammation of the middle ear. An operating otoscope, ear loops, and alligator forceps facilitate manual removal of large amounts of cerumen or debris. Debris is carefully removed under direct visualization, and care is taken deeper in the ear canal (close to the tympanic membrane). Aggressive hair removal is not advised, because inflammation and damage to the epithelium can result in secondary bacterial colonization and infection. Flushing may be performed after large accumulations of cerumen and debris are mechanically removed from the ear canal.

Otic Cleaning Solutions

Trade Name Acetic Acid Boric Acid Salicylic Acid Isopropyl Alcohol Propylene Clycol Dss Other
Ace-Otic Cleanser 2%   0.1%       Lactic acid 2.7%
Adams Pan-Otic         X X Parachlorometaxylenol, tris EDTA, methylparaben, diazolidinyl urea, popylparaben, octoxynol
Alocetic Ear Rinse X     X     Nonoxynol-12, methylparaben, alovera gel
Cerulytic Ear Ceruminolytic         X   Benzyl alcohol, butylated hydroxytoluene
Cerumene             25% Isopropyl myristate
DermaPet Ear/Skin Cleanser for Pets X X          
Docusate Solution         X X  
Earmed Boracetic Flush X X         Aloe
Earmed Cleansing Solution & Wash         X   50A 40B alcohol, cocamidopropyl phosphatidyl and PE dimonium chloride
Earoxide Ear Cleanser             Carbamide peroxide 6.5%
Epi-Otic Ear Cleanser     X   X X Lactic acid, chitosanide
Fresh-Ear X X X X X   Lidocaine hydrochloride, glycerin, sodium docusate, lanolin oil
OtiCalm     X       Benzoic acid, malic acid, oil of eucalyptus
Otic Clear X X X X X   Glycerin, lidocaine hydrochloride
Oticlean-A Ear Cleaning Lotion X X X 35% X   Lanolin oil, glycerin
Oti-Clens     X   X   Malic acid, benzoic acid
Otipan Cleansing Solution         X   Hydroxypropyl cellulose, octoxynol
Otocetic Solution 2% 2%          
Wax-O-Sol 25%             Hexamethyltetracosane

Flushing and evacuation of solution is done under direct visualization through an operating otoscope. A bulb syringe and red rubber catheter system may be used to both flush and evacuate solutions and accumulations from the ear canal. The operator, avoiding drastic pressure changes within the external ear canal that could damage the tympanum, should carefully control suction and manual evacuation of the contents of the bulb syringe from the ear canal. Other alternatives include tomcat catheters (3.5 F) or flexible, intravenous catheters (14 gauge, Teflon); stiff, narrow catheters should be used cautiously and under direct visualization deep in the external ear canal. Other reservoir systems for delivery or evacuation of solutions include a 12 mL syringe or suction tubing attached to in-house vacuum systems. In-house vacuum systems should be used cautiously and under direct visualization. Care should be taken to avoid trauma to the tympanic membrane until its integrity can be assessed. Initial flushes should be done with physiologic saline solution or water until the integrity of the tympanic membrane is established.

Other solutions may aid in the removal of wax in the ear canal. Ceruminolytics are emulsifiers and surfactants that break down ceruminocellular aggregates by causing lysis of squamous cells. A ceruminolytic agent in an alkaline pH may more effectively lyse squamous cells via cell surface protein disruption. Oil-based products soften and loosen debris to aid in their removal but do not cause cell lysis. Water-based ceruminolytics are easier to remove and dry more quickly than oil-based solutions, which are occlusive if they remain in the ear canal. Water-based products include dioctyl sodium sulfosuccinate, calcium sulfosuccinate, and carbamate peroxide, which has a foaming action with the release of urea and oxygen. Oil-based products include squalene, triethanolamine polypeptide, hexamethyltetracosane, oleate condensate, propylene glycol, glycerin, and mineral oil. In a recent study only the combination of squalene and isopropyl myristate in a liquid petrolatum base had no adverse effects on hearing, the vestibular system, and histopathologic examination. Other agents tested contained glycerin, dioctyl sodium sulfosuccinate (2% or 6.5%), parachlorometaxylenol, carbamide peroxide (6%), propylene glycol, triethanolamine polypeptide oleate condensate (10%), and chlorobutanol (0.5%).

Alcohol-based drying agents added to ceruminolytics include boric acid, benzoic acid, and salicylic acid, which decrease the pH of the ear canal, cause keratolysis, and have a mild antimicrobial effect. Drying the ear canal is important to combat increased humidity, which potentiates infection.

If the tympanum is intact, the ear canal is filled with a ceruminolytic agent for at least 2 minutes and the pinna is cleaned at the same time. The solution is flushed twice with warm water, and the canal inspected. The procedure is repeated until cleaning is complete. Other solutions commonly advocated for ear flushing include dilute chlorhexidine solution (0.05%), dilute povidone-iodine, and acetic acid (2.5%). The first two agents are potentially ototoxic or induce inflammation and should not be used if the tympanum is ruptured. A combination of propylene glycol malic, benzoic, or salicylic acid; 2% acetic acid; or dilute povidone-iodine have been suggested for use in dogs with a ruptured tympanum.

Owners may clean the ears at home with mild preparations of ceruminolytics and drying agents if mild otitis is present without severe accumulation of cerumen or exudate. Aqueous solutions are usually recommended because they are less occlusive and easier to clean from the ear, dog, and home environment.

The ear should be filled with the solution, then massaged for 40 to 60 seconds. The pet should be allowed to shake its head to remove the majority of the solution, and the excess should be wiped from the ear canal and pinna with a tissue. Daily flushing is usually recommended, followed by every other day, weekly, then as needed, depending on the solution. Ear swabs are not recommended for home use, because cerumen and debris may be forced into the horizontal ear canal and impact against the tympanic membrane

Topical Therapy

Erythematous ceruminous otitis externa is diagnosed 2.7 times more often than acute suppurative otitis according to one report. Yeast ± cocci were identified in those cases, with cocci or rods identified in suppurative otitis. Topical therapy should be based on the cytologic examination to diminish the incidence of inappropriate treatment (Table Topical Medications Used in the Treatment of Ear Disease). Many preparations combine anti-inflammatories and antimicrobials in an attempt to decrease the inflammation and combat bacterial or yeast overgrowth. All topical medications should be considered supportive, and specific treatment should be aimed at controlling the primary disease process.

Topical Medications Used in the Treatment of Ear Disease

Generic Name Trade Name Dose Frequency Description
Fluocinolone 0.01% DMSO 60% Synotic 4-6 drops; total dose<17mL q12h initially. q48-72h maintenance Potent corticosteroid anti-inflammatory
Hydrocortisone 1.0% HB101,

Burrows H,

2-12 drops, depending on ear size q12h initially. q24-48h maintenance Mild corticosteroid anti-inflammatory
Hydrocortisone 1.0%, lactic acid Epiotic HC 5-10 drops q12h for 5 days Mild corticosteroid anti-inflammatory, drying agent
Hydrocortisone 0.5%, sulfur 2%. acetic acid 2.5% Clear X Ear Treatment 2-12 drops, depending on ear size q12-24h initially. q24-48h maintenance Mild corticosteroid anti-inflammatory, astringent, germicidal
DSS 6.5%. urea (carbamide peroxide 6%) Clear X Ear Cleansing Solution 1-2 mL per ear Once per week to as necessary Ceruminolytic, lubricating agent
Chlorhexidine 2% Nolvasan Dilute 1:40 in water As necessary Antibacterial & antifungal activity
Chlorhexidine 1.5% Nolvasan Dilute 2% in

propylene glycol

q12h Antibacterial & antifungal activity
Povidone-iodine 10% Betadine solution Dilute 1:10-1:50 in water As necessary Antibacterial activity
Polyhydroxidine iodine 0.5% Xenodyne Dilute 1:1-1:5 in water As necessary, q12h, once weekly Antibacterial activity
Acetic acid 5% White vinegar Dilute 1:1-1:3 in water As necessary; q12-24h for Pseudomonas Antibacterial activity, lowers ear canal pH
Neomycin 0.25%, triamcinolone 0.1%, thiabendazole 4% Tresaderm 2-12 drops depending on ear size q12h up to 7 days Antibacterial & antifungal activity, parasiticide (mites), moderate corticosteroid anti-inflammatory
Neomycin 0.25%, triamcinolone 0.1%, nystatin 100,000 U/mL Panalog 2-12 drops depending on ear size q12h to once weekly Antibacterial & antifungal activity, moderate corticosteroid anti-inflammatory
Chloramphenicol 0.42%. prednisone 0.17%, tetracaine 2%, squalene Liquachlor, Chlora-Otic 2-12 drops depending on ear size q12h up to 7 days Antibacterial activity, mild corticosteroid anti-inflammatory
Neomycin 1.75 & polymyxin B 5000 lU/mL, penicillin C procaine 10,000 lU/mL Forte Topical 2-12 drops depending on ear size q12h Antibacterial activity
Centamicin 0.3%, betamethasone valerate 0.1% Centocin Otic Solution, Betagen Otic Solution 2-12 drops depending on ear size q12h for 7 to 14 days Antibacterial activity, potent corticosteroid anti-inflammatory
Centamicin 0.3%, betamethasone 0.1%, clotrimazole 0.1% Otomax, Obibiotic Ointment 2-12 drops depending on ear size q12h for 7 days Antibacterial & antifungal activity, potent corticosteroid anti-inflammatory
Centamicin 0.3%, betamethasone valerate 0.1%, acetic acid 2.5% Centaved Otic Solution 2-12 drops, depending on ear size q12h for 7 to 14 days Antibacterial activity, potent corticosteroid anti-inflammatory
Polymixin B 10,000 lU/mL, hydrocortisone 0.5% Otobiotic 2-12 drops, depending on ear size q12h Antibacterial activity, mild corticosteroid anti-inflammatory
Enrofloxacin 0.5%, silver sulfadiazine 1% Baytril Otic 2-12 drops, depending on ear size q12h for up to 14 days Antibacterial activity
Carbaryl 0.5%, neomycin 0.5%, tetracaine Mitox Liquid 2-12 drops, depending on ear size   Antibacterial activity, parasiticide (mites)
Pyrethrins 0.06%, piperonyl butoxide 0.6% Ear Mite and Tick Control 5 drops q12h Parasiticide (mites)
Pyrethrins 0.05%, squalene 25% Cerumite 2-12 drops, depending on ear size q24h for 7 to 10 days Parasiticide (mites), ceruminolytic
Isopropyl alcohol 90%, boric acid 2% Panodry Fill ear canal As necessary Drying agent
Acetic acid 2%, aluminum acetate Otic Domeboro Fill ear canal q12-48h Drying agent, antibacterial activity, lowers ear canal pH
Silver sulfadiazine Silvadene Dilute 1:1 with water, 1 g powder in 100 mL water q12h for 14 days Antibacterial & antifungal activity
Tris EDTA±

gentamicin 0.03%

  2-12 drops, depending on ear size q12h for 14 days 1 L distilled water, 1.2g Tris EDTA, 1 mL glacial acetic acid; antibacterial activity
Silver nitrate   Use sparingly As necessary Cauterization of

ulcerative otitis externa

Miconazole 1%; ± topical glucocorticoid (7.5 mL of dexamethasone phosphate (4 mg/mL] to10mLof1% miconazole) Conofite 2-12 drops, depending on ear size q12-24h Antifungal activity
Ivermectin 0.01% Acarexx 0.5 mL per ear Once Parasiticide (mites)
Pyrethrins 0.15%, piperonyl butoxide 1.5% Many 2-12 drops, depending on ear size Twice at 7-day interval Parasiticide (mites)
Pyrethrins 0.05%, piperonyl butoxide 0.5%, squalene 25% Cerumite 2-12 drops, depending on ear size q24h for 7 days Parasiticide (mites), ceruminolytic
Pyrethrins 0.04%, piperonyl butoxide 0.49%, DSS 1.952%, benzocaine 1.952% Aurimite 10 drops q12h  
Rotenone 0.12%, cube resins 0.16% Many 2-12 drops, depending on ear size Every other day Parasiticide (mites)

Topical glucocorticoids benefit most cases of otitis externa by decreasing pruritus, exudation, swelling, and proliferative changes of the ear canal. The most potent glucocorticoids available in topical preparations are betamethasone valerate and fluocinolone acetonide. Less potent corticosteroids include triamcinolone acetonide and dexamethasone; the least potent is hydrocortisone. Most dogs benefit from short-term therapy with topical corticosteroids at the initiation of therapy, with concurrent therapy aimed at the primary and other perpetuating factors. Long-term therapy with topical corticosteroids can be deleterious because of systemic absorption of drug. Increased serum liver enzymes and depressed adrenal responsiveness may occur; with prolonged use iatrogenic hyperadreno-corticism is possible. Glucocorticoids alone may be of benefit for short-term therapy in cases of allergic or erythematous ceruminous otitis.

Antimicrobials are important for controlling secondary bacterial or yeast overgrowth or infection. Antimicrobials are indicated in any case with cytologic evidence of bacterial overgrowth or infection, with attention paid to the morphology and gram-staining characteristics of the bacteria. Otic preparations commonly contain aminoglycoside antibiotics. Neomycin is effective against typical otitis bacteria such as Staphylococcus intermedium. Gentamicin and polymyxin B are also appropriate initial topical treatments for gram-negative bacterial otitis externa.The significant risk of bone marrow toxicity in people limits the use of chloramphenicol for treating otitis in dogs and cats despite its antibacterial spectrum and availability.

Due to the frequency of resistant gram-negative bacteria such as Pseudomonas, other topical preparations have been developed. Enrofloxacin, ophthalmic tobramycin, and topical application of injectable ticarcillin have been used to treat otitis in dogs.< Their use should be limited to cases of resistant bacteria, and culture and susceptibility testing should be performed prior to application. Other topical agents may be used to supplement treatment of resistant Pseudomonas, such as silver sulfadiazine solution and tris EDTA. Tris EDTA can render Pseudomonas susceptible to enrofloxacin or cephalosporins by enhancing membrane permeability and altering ribosome stability. Frequent ear cleaning may also assist in the treatment of resistant bacterial otitis; ceruminolytics have antimicrobial properties, and their use in clinical cases has been evaluated. Acetic acid in combination with boric acid is effective against both Pseudomonas and Staphylococcus, depending on concentration and duration of exposure. Ear cleaning removes proinflammatory products, cells, and substances that diminish the effectiveness of topical antibiotics.

Many topical preparations control yeast organisms, which may complicate erythematous ceruminous otitis and suppurative otitis. Common active ingredients include miconazole, clotrimazole, nystatin, and thiabendazole. Preparations containing climbazole, econazole, and ketoconazole have also been evaluated. Eighty percent of yeast were susceptible to miconazole and econazole, intermediately resistant to ketoconazole, and 90% were resistant to nystatin and amphotericin B in one in vitro study. Topical ear cleaning agents have some efficacy against Malassezia organisms. Other preparations (e.g. chlorhexidine, povidone-iodine, acetic acid) are also effective in the treatment of secondary yeast overgrowth.

Response to topical therapy should be gauged by re-evaluation of physical, cytologic, and otoscopic examinations every 10 to 14 days after the initiation of therapy. Any changes in the results of these examinations should be recorded. Most cases of otitis can be managed topically; failure to respond to therapy should prompt re-evaluation of the diagnosis and treatment.

Systemic Therapy

Systemic glucocorticoid administration may be beneficial in cases of severe, acute inflammation of the ear canal, chronic proliferative changes of the ear canal, and allergic otitis. Anti-inflammatory doses should be limited to 7 to 10 days. Cases of significant thickening or proliferative changes in the external ear canal benefit from systemic antimicrobial therapy. Systemic therapy should be considered if concurrent dermatologic changes of the surrounding skin, pinna, or other regions of the body are present. Long-term administration of appropriate antimicrobials based on culture and susceptibility is required in all cases of otitis media. Systemic therapy for yeast is rarely recommended in animals with otitis alone. One study evaluated oral itraconazole therapy, and in ear samples evaluated on cytology and culture, no change in cytology score was found.



Therapy For Specific Diseases Of The External Ear Canal


Thorough cleaning of the external ear canal, treatment of all household pets, and whole-body therapy should be considered in the treatment regimen for ear mites. Pets with no clinical signs may be asymptomatic carriers and a reservoir for reinfestation. Otic parasiticides such as pyrethrins, rotenone, amitraz, and carbaryl must be administered every 24 hours throughout the 20-day mite life cycle because they do not kill mite eggs. Thiabendazole eliminates all mite stages, but it must be applied every 12 hours for 14 days. Ivermectin (0.3 to 0.5 mg/kg) may be applied topically once weekly for 5 weeks. Otic administration of medication does not affect mites on adjacent or distant skin locations, and systemic or other total-body parasiticide may be indicated. Alternatively, ivermectin administered subcutaneously (0.2 to 0.3 mg/kg) 2 to 3 times at 10- to 14-day intervals or orally (0.3 mg/kg) every week for four treatments eliminates otic mites and those found elsewhere on the body. Other topicals proven safe and effective for ear mite treatment include selamectin (6 mg/kg) applied to the skin between the shoulder blades and fipronil spray. Selamectin administered once in cats and two times, 30 days apart in dogs gave results similar to topical pyrethrin therapy.

Idiopathic Inflammatory or Hyperplastic Otitis in Cocker Spaniels

Treatment is aimed at decreasing the secondary ear canal changes associated with this condition. Anti-inflammatory doses of corticosteroids administered orally may be useful. Topical corticosteroid preparations in combination with antimicrobials decrease the soft tissue mass affecting the ear canal but may not be as effective as oral administration. Maintenance therapy may be required both topically and orally; however, low doses of corticosteroids should be used. Re-evaluation should include attention to the potential side effects of corticosteroid therapy. Intermittent treatment of secondary bacterial or yeast overgrowth and infection may be required. Surgery is often indicated due to the severe secondary changes within the ear canal.

Excessive Moisture (Swimmer’s Ear)

Other primary disease conditions such as allergic otitis should be ruled out in any dog with erythematous ceruminous otitis. Dogs with frequent exposure to water, however, may require ear cleaning and drying agents to diminish the humidity of the ear canal. Many cleaning and drying agents also posses antimicrobial effects. Products that combine a drying agent and corticosteroid decrease the ear canal humidity and inflammation associated with allergic otitis complicated by swimming. Care should be taken to control primary disease (i.e. allergic otitis), however, and intermittendy manage the predisposing factor (i.e. excessive moisture) as necessary. The dog’s ears should be cleaned and dried the day of water exposure and for 2 to 5 days after. For continued frequent exposure, maintenance cleaning may be required every other day to twice weekly.

Chronic Bacterial Otitis

Resistant bacteria play an important role in the development of chronic otitis externa. Any dog not responding to initial therapy should be re-evaluated for primary and perpetuating conditions such as allergic disease, foreign body, neoplasia, otitis media, and secondary anatomic changes of the ear canal. Primary disease processes identified in one study included hypothyroidism, atopy, food allergy, and immune-mediated disease. Infection with Pseudomonas species frequently occurs with repeated treatment of otitis extema, and acquired resistance is common. Culture and susceptibility testing is imperative to guide therapy. Oral antimicrobials combined with topical therapy are used in severe cases with secondary changes of the ear canal. Identification of otitis media is vital to remove the middle ear as a source of otitis extema. Otitis media requires long-term treatment.

Ear cleaning prior to the application of topical medication may increase the efficacy of the agent by decreasing exudate in the ear canal that inactivates antimicrobial drugs such as polymyxin. In cases that fail to respond to first-line drug treatments such as polymyxin or gentamicin, other topical antimicrobial agents should be tried. Ophthalmic tobramycin and injectable amikacin have been described for use as topical antimicrobials in ear disease. The integrity of the tympanic membrane should be known prior to use; the clinician should avoid these medications if the tympanic membrane cannot be proven intact. Enrofloxacin or ticarcillin injectable preparations diluted in saline or water may be applied topically for resistant Pseudomonas. Parenteral ticarcillin was used in cases with a ruptured tympanic membrane until healing was observed, at which time topical therapy was instituted; clinical response occurred in 11 of 12 cases. Enrofloxacin and silver sulfadiazine combination is also available in an otic preparation (Baytril Otic, Bayer Shawne Mission, KS).

Other topical therapy may assist in eliminating resistant Pseudomonas from the ear canal.

Decreasing the pH of the ear canal with 2% acetic acid is lethal to Pseudomonas; diluted vinegar in water (1:1 to 1:3) may be used to flush the ear canal. Acetic acid combined with boric acid is lethal to Pseudomonas and Staphylococcus, depending on the concentration of each agent. Increasing the concentration of acetic acid may broaden its spectrum of activity but causes irritation of the external and middle ear. Silver sulfadiazine in a 1% solution exceeds the minimum inhibitory concentration of Pseudomonas and may be instilled into the ear canal. One gram of silver sulfadiazine powder mixed in 100 mL of water may be used for topical therapy and is also effective against Proteus species, enterococci, and Staphylococcus intermedium. Dilute acetic acid (2%) and silver sulfadiazine (1%) have not caused adverse effects in cases with a ruptured tympanic membrane.I Tris EDTA may be applied after thorough ear cleaning to increase the susceptibility of Pseudomonas to antimicrobial agents. It must be mixed, pH adjusted, and autoclaved prior to use or is available in an otic preparation (TrizEDTA, DermaPet ®, Potomac, MD), which is used to clean the ears prior to instillation of topical antibiotic. Topical antiseptics such as chlorhexidine and povidone-iodine solutions may be helpful, but ototoxicity is an issue, particularly in cases in which the tympanum is ruptured or cannot be evaluated.

Re-evaluation of the pet is important for monitoring response to therapy. Evaluation of the ear canal for progressive secondary changes and cytologic examination will allow alterations in therapy as needed. Significant narrowing of the ear canal is an indication for surgical intervention. Yeast overgrowth may occur with aggressive medical management of bacterial otitis and should be identified to maintain proper medical management.

Refractory or Recurrent Yeast Infection

Malassezia infection is a common perpetuating factor with erythematous ceruminous otitis and alterations in the otic microenvironment. Primary causes of the otitis should be identified and treated. Cytologic examination, not culture, should be relied upon for the diagnosis of yeast infection. If a case becomes refractory to therapy, reassessment of the primary condition and perpetuating factors should be done. Miconazole, clotrimazole, cuprimyxin, nystatin, and amphotericin B have all been described for treating Malassezia otitis. Climbazole had better in vitro activity against isolates of Malassezia pachydermatis in one study. Yeast were more susceptible to azole antifungals than polyene antifungals; however, oral ketoconazole, itraconazole, or fluconazole have been recommended for refractory cases. Long-term therapy may require topical antibacterial and antifungal combinations.

Ear cleaning may aid in the elimination of yeast organisms by removing cerumen, debris, or exudate and altering the microenvironment of the ear canal. Cleaning with antimicrobial agents such as chlorhexidine, povidone-iodine, and acetic acid may be beneficial; but as always the integrity of the tympanum should be established prior to use. Ear cleaning solutions may also have some efficacy against yeast organisms both in vitro and in clinical cases of otitis.


Chronic otitis externa may be the result of otic neoplasia, or otitis may be a predisposing factor in the development of neoplasia. Cocker spaniels are over-represented for benign and malignant neoplasia and otitis extema. Tumors of the skin and adenexal structures of the ear predominate. Benign tumors in dogs include sebaceous gland adenoma, basal cell tumor, polyp, ceruminous gland adenoma, and papilloma. Cats are more frequendy diagnosed with malignant neoplasms, but benign conditions include inflammatory polyps, ceruminous gland adenomas, ceruminous gland cysts, and basal cell tumors. Malignant neoplasms in both species include ceruminous gland adenocarcinoma, undifferentiated carcinoma, and squamous cell carcinoma. Ceruminous gland adenocarcinomas are the most frequendy diagnosed tumors of the ear canal in dogs and cats; however, one report stated that squamous cell carcinoma occurs with equal incidence in the cat.

The biologic behavior of otic tumors cannot be judged by their gross appearance; however, benign masses are usually nodular and pedunculated. Ulceration can be secondary to otitis associated with mass lesions, but malignant masses ulcerate more frequendy than benign masses. The tympanic bulla is involved in up to 25% of aural neoplasms, and neurologic signs occur in 10% of dogs and 25% of cats with otic neoplasia. The biologic behavior of malignant neoplasms tends to be local invasion with a low metastatic rate (e.g. 10% in dogs) to draining lymph nodes or lung.

Surgery is the mainstay treatment of otic neoplasia. Conservative excision may be possible for benign lesions, depending on the location of the tumor. Malignancies should be removed by total ear canal ablation and lateral bulla osteotomy. Incomplete excision results in recurrence of the mass and secondary otitis externa. Malignant neoplasia is associated with a median survival time (MST) of more than 58 months in dogs and 11.7 months in cats. Extensive tumor involvement and lack of aggressive management are associated with a poor prognosis in dogs. In cats a poor prognosis is associated with neurologic signs, squamous cell carcinoma or undifferentiated carcinoma, vascular or lymphatic invasion, and lack of aggressive therapy. Ceruminous gland adenocarcinoma has a median disease free interval of more than 36 months and 42 months in dogs and cats, respectively. The MST associated with squamous cell carcinoma and undifferentiated carcinoma in cats is 4 to 6 months.


Treatment And Prevention of Feline Heartworm Disease

The question arises as to whether heartworm prophylaxis is warranted for cats because they are not the natural host and because the incidence is low. Necropsy studies of feline heartworm infection in the Southeast have yielded a prevalence of 2.5% to 14%, with a median of 7%. When considering the question of institution of prophylaxis, it is worth considering that this prevalence approximates or even exceeds that of feline leukemia virus (FeLV) and feline immunodeficiency virus (FTV) infections. A 1998 nationwide antibody survey of over 2000 largely asymptomatic cats revealed an exposure prevalence of nearly 12%. It is also noteworthy that, based on owners’ information, nearly one third of cats diagnosed with heartworm disease at NCSU were housed solely indoors. Lastly, the consequences of feline heartworm disease are potentially dire, with no clear therapeutic solutions. Therefore the author advocates preventative therapy in cats in endemic areas. Three drugs with FDA approval are marketed for use in cats (Table Comparison of Spectra ofMacrolides Currently in Use in Cats). Ivermectin is provided in a chewable formulation, milbemycin as a flavored tablet, and selamectin (a broad-spectrum parasiticide) comes in a topical formulation. The spectrum and the formulation of these products varies; hence the clients’ individual needs are easily met in most cases (Table Comparison of Spectra ofMacrolides Currently in Use in Cats).

Comparison of Spectra ofMacrolides Currently in Use in Cats

Drug Heartwotm prevention Hookworms Whipworms Roundworms Tapeworms Fleas & Eccs Ticks Sarcoptes Ear Mites
Ivermectin (chewable) + +              
Milbemycin (flavored tablet) + +   +          
Selamectin (topical) + +   +   +/+ + + +

Because the vast majority of cats are amicrofilaremic, microfilaricidal therapy is unnecessary in this species. The use of arsenical adulticides is problematic. Thiacetarsemide (sodium caparsolate), if available, poses risks even in normal cats. Turner, Lees, and Brown reported death due to pulmonary edema and respiratory failure in 3 of 14 normal cats given thiacetarsemide (2.2 mg/kg twice over 24 hours). Dillon and colleagues could not confirm this acute pulmonary reaction in 12 normal cats receiving thiacetarsemide, but one cat did die after the final injection. More importantly, a significant, though unquantified, percentage of cats with HW1 develop pulmonary thromboembolism (PTE) after adulticidal therapy. This occurs several days to 1 week after therapy and is often fatal. In 50 cats with HWI, seen at NCSU, 11 received thiac-etarsemide. There was no significant difference in survival between those receiving thiacetarsemide and those receiving symptomatic therapy.

Data on melarsomine in experimental (transplanted) heartworm infection in cats are limited and contradictory. Although an abstract report exists in which one injection (2.5 mg/kg; one half the recommended canine dose) of melarsomine was used in experimentally infected cats without treatment-related mortality, the worm burdens after treatment were not significantly different from those found in untreated control cats. Diarrhea and heart murmurs were frequently noted in treated cats. A second abstract report, using either the standard canine protocol (2.5 mg/kg twice over 24 hours) or the split dose (one injection, followed by two injections, 24 hours apart, in 1 month) described in posts, gave more favorable results. The standard treatment and split-dose regimens resulted in 79% and 86% reduction in worm burdens, respectively, and there were no adverse reactions. Although promising, these unpublished data need to be interpreted with caution because the transplanted worms were young (<8 months old and more susceptible), and the control cats experienced a 53% worm mortality (average worm burden was reduced by 53% by the act of transplantation). Additionally, the clinical experience in naturally infected cats has been generally unfavorable, with an unacceptable mortality. Because of the inherent risk, lack of clear benefit, and the short life expectancy of heartworms in this species, this author does not advocate adulticidal therapy in cats. Surgical removal of heartworms has been successful and is attractive because it minimizes the risk of thromboemboli. The mortality seen in the only published case series was, unfortunately, unacceptable (two of five cats). This procedure may hold promise for the future, however.

Cats with heartworm infection should be placed on a monthly preventa-tive and short-term corticosteroid therapy (prednisone at 1 to 2 mg/kg every 48 hours, three times a day) used to manage respiratory signs. If signs recur, alternate-day steroid therapy (at the lowest dose that controls signs) can be continued indefinitely. For embolic emergencies, oxygen, corticosteroids (dexamethasone at 1 mg/kg intravenously or intramuscularly, or prednisolone sodium succinate at 50 to 100 mg intravenously/cat), and bronchodilators (aminophylline at 6.6 mg/kg intramuscularly every 12 hours, theophylline sustained release at 25 mg/kg orally, or terbutaline at 0.01 mg/kg subcutaneously) may be used. Bronchodilators have logic, based on the ability of agents, such as the xanthines (aminophylline and theophylline), to improve function of fatigued respiratory muscles. In addition, the finding of hyperinflation of lung fields may indicate bronchoconstriction, a condition for which bronchodilation would be indicated. Nevertheless, this author does not routinely use bronchodilators in feline HWD.

The use of aspirin has been questioned because vascular changes associated with HW1 consume platelets, increasing their turnover rate and effectually diminishing the antithrom-botic effects of the drug. Conventional doses of aspirin did not prevent angiographically detected vascular lesions. Doses of aspirin necessary to produce even limited histologic benefit approached the toxic range. Despite this, because therapeutic options are limited, at conventional doses (80 mg orally, every 72 hours), aspirin is generally harmless, inexpensive, and convenient. Because the quoted studies were based on relatively insensitive estimates of platelet function and pulmonary arterial disease (thereby possibly missing subtle benefits), the author continues to advocate aspirin for cats with HWI. Aspirin is not prescribed with concurrent corticosteroid therapy. Management of other signs of heartworm disease in cats is largely symptomatic.


Canine Heartworm Disease

Heartworm infection (HWI) (dirofilariasis), caused by Dirofilaria immitis, primarily affects members of the family Canidae. Dirofilariasis is widely distributed, being recognized in northern and southern temperate zones, in the tropics, and in the subtropics. Infections are recognized in most of the United States, although the distribution favors the Southeast and Mississippi River Valley. In some endemic areas in the United States, infection rates approach 45%, and in some hyperendemic tropical regions, virtually all dogs are infected. Dirofilariasis is generally infrequent in Canada. A recent survey of veterinarians indicated that in 2001 there were approximately 240,000 cases diagnosed in the United States.

Species known to have been infected with Dirofilaria immitis include the domestic dog, wolves, foxes, coyotes, domestic cats, ferrets, muskrats, sea lions, nondomestic cats, coatimundi, and humans. The species of greatest interest to die practicing veterinarian include the dog and domestic cat. Because the consequences, treatment, and prognoses differ between the two species, clinical aspects of canine and feline heartworm disease (HWD) will be discussed separately.

When heartworm infection is severe or prolonged, it may result in the pathologic process, called HWD. heartworm disease may vary from asymptomatic (radiographic lesions only) to severe, life-threatening, chronic pulmonary artery, lung, and cardiac disease. In chronic HWI, glomerulonephritis, anemia, and thrombocytopenia may also be recognized. Severe dirofilariasis may, in addition, produce acute and fulminant multisystemic presentations, such as caval syndrome (CS) and disseminated intravascular coagulation (DIC).

Life Cycle

Dirofilaria immitis is transmitted by over sixty species of mosquitoes, although important mosquito vectors probably number less than 12. Understanding the complex life cycle of Dirofilaria immitis is imperative for veterinary practitioners in heartworm endemic areas. Adult heartworms (L5) reside in the pulmonary arteries and, to a lesser extent in heavy infections, the right ventricle. After mating, microfilariae (LI) are produced by mature adult female heartworms (L5) and are released into the circulation. These LI are ingested by feeding female mosquitoes and undergo two moults (LI to L2 to L3) over an 8- to 17-day period. It is important to note that this process is temperature dependent; in times of the year when insufficient numbers of days occur in which the ambient temperature is adequate, moulting in the mosquito does not occur during the lifetime of the female mosquito and transmission cannot occur.The resultant L3 is infective and is transmitted by the feeding mosquito to the original or another host, most often a male dog. Another moult occurs in the subcutaneous, adipose, and skeletal muscular tissues shortly after infection (1 to 12 days), with a final moult to L5 3 months (50 to 68 days) after infection. This immature adult (1 to 2 cm in length) soon enters the vascular system, migrating to the heart and lungs, where final maturation (mature male adults range from 15 to 18 cm and females from 25 to 30 cm) and mating occur. Under optimum conditions, completion of the life cycle takes 184 to 210 days. The canine host typically becomes microfilaremic 6 to 7 months after infection. Microfilariae (LI), which are variably present in infected dogs, show both seasonal and diurnal periodicity, with greatest numbers appearing in the peripheral blood during the evening hours and during the summer. Adult heartworms in dogs are known to live up to 5 years and microfilariae up to 30 months. Dillon has recently emphasized that the disease process in heartworm disease begins with the moult to L5 (as soon as 2 to 3 months postinfection), at which time immature adults (L5) enter the vascular system, initiating vascular and possibly lung disease, with eosinophilia and eosinophilic infiltrates and signs of respiratory disease. It is important to note that this antedates the profession’s current ability to diagnose HWI.

Canine Heartworm Disease: Pathophysiology

Heartworm is a misnomer because the adult actually resides in the pulmonary arterial system for the most part, and the primary insult to the health of the host is a manifestation of damage to the pulmonary arteries and lung. The severity of the lesions and hence clinical ramifications are related to the relative number of worms (ranging from one to over 250), the duration of infection, and the host and parasite interaction. Immature and mature adult heartworms reside primarily in the caudal pulmonary vascular tree, occasionally migrating into the main pulmonary arteries, the right heart, and even the great veins in heavy infections.

Obstruction of pulmonary vessels by living worms is of little clinical significance, unless worm burdens are extremely high. The major effect on the pulmonary arteries is produced by worm-induced (toxic substances, immune mechanisms, and trauma) villous myointimal proliferation, inflammation, pulmonary hypertension (PHT), disruption of vascular integrity, and fibrosis.This may be complicated by arterial obstruction and vasoconstriction caused by dead worm thromboemboli and their products. Pulmonary vascular lesions begin to develop within days of worm arrival (as early as 3 months postinfection), With endothelial damage and sloughing, villous proliferation, and activation and attraction of leucocytes and platelets. The immigration of such cells and the release of trophic factors induce smooth muscle cell proliferation and migration with collagen accumulation and eventual fibrosis. Proliferative lesions eventually encroach upon and even occlude vascular lumina. Endothelial swelling with altered intracellular junctions increases the permeability of the pulmonary vasculature. Worms, which have died naturally or have been killed, elicit an even more severe reaction, inciting thrombosis, granulomatous inflammation, and rugous villous inflammation. Grossly, the pulmonary arteries are enlarged, thick-walled, and tortuous, with roughened endothelial surfaces. These changes are only partially reversible.

Although the role of exercise in exacerbation of the signs of thromboembolic heartworm disease is accepted, its role in the development of pulmonary vascular disease and pulmonary hypertension is less clear. Although Rawlings was unable to show an effect of 2.5 months controlled treadmill exercise on pulmonary hypertension in heavily infected dogs, Dillon showed more severe pulmonary hypertension in lightly infected, mildly exercised dogs than in more heavily infected but unexercised dogs receiving no exercise at 6 months postinfection.

Diseased pulmonary arteries are thrombosed, thickened, dilated, tortuous, noncompliant, and functionally incompetent, thereby resisting recruitment during increased demand; hence exercise capacity is diminished. Vessels to the caudal lung lobes are most severely affected. Pulmonary vasoconstriction results secondary to vasoactive substances released from heartworms. Furthermore, hypoxia (induced by ventilation-perfusion mismatching secondary to eosinophilic pneumonitis, pulmonary consolidation, or both), further contributes to vasoconstriction. The result is pulmonary hypertension and compromised cardiac output. Pulmonary hypertension is exacerbated with exercise or other states of increased cardiac output. The right heart, which is an efficient volume pump but does not withstand pressure overload, first compensates by eccentric hypertrophy (dilatation and wall thickening) and, in severe infections, ultimately decompensation (right heart failure). In addition, hemodynamic stresses, geometric changes, and cardiac remodeling may contribute to secondary tricuspid insufficiency, thereby complicating or precipitating cardiac decompensation. Pulmonary infarction is uncommon because of the extensive collateral circulation provided the lung and because of the gradual nature of vascular occlusion. Because of increased pulmonary vascular permeability, perivascular edema may develop. Although, along with an inflammatory infiltrate, this may be evident radio-graphically as increased interstitial and even alveolar density, in and of itself, it is seemingly of minimal clinical significance and does not indicate left heart failure (in other words, furosemide is not indicated).

Spontaneous or postadulticidal thromboembolization (PTE) with dead worms may precipitate or worsen clinical signs, producing or aggravating PHT, right heart failure or, in rare instances, pulmonary infarction. Dying and disintegrating worms worsen vascular damage and enhance coagulation. Pulmonary blood flow is further compromised and consolidation of affected lung lobes may occur. With acute and massive worm death, this insult may be profound, particularly if associated with exercise. Exacerbation by exercise likely reflects increased pulmonary artery flow with escape of inflammatory mediators into the lung parenchyma through badly damaged and permeable pulmonary arteries. Dillon has suggested that the lung injury is similar to that seen in adult respiratory distress syndrome (ARDS).

Pulmonary parenchymal lesions also result by mechanisms other than post-thromboembolic consolidation. Eosinophilic pneumonitis is most often reported in true occult HWD, when immune-mediated destruction of microfilariae in the pulmonary microcirculation produces amicrofilaremia. This syndrome results when antibody-coated microfilariae, entrapped in the pulmonary circulation, incite an inflammatory reaction (eosinophilic pneumonitis). A more sinister but uncommon form of parenchymal lung disease, termed pulmonary eosinophilic granulomatosis, has been associated with HWD. The exact cause and pathogenesis are unknown, but it is felt to be similar to HWD-related allergic pneumonitis. It is postulated that microfilariae trapped in the lungs are surrounded by neutrophils and eosinophils, eventually forming granulomas and associated bronchial lymphadenopathy.

Antigen-antibody complexes, formed in response to heart-worm antigens, commonly produce glomerulonephritis in heartworm-infected dogs. The result is proteinuria (albu-minuria) but uncommonly renal failure. Heartworms may also produce disease by aberrant migration. This uncommon phenomenon has been associated with neuromuscular and ocular manifestations, because worms have been described in tissues such as muscle, brain, spinal cord, and anterior chamber of the eye. In addition, arterial thrombosis with L5 has been observed when worms migrate aberrandy to the aortic bifurcation or more distally in the digital arteries. Adult heartworms may also migrate in a retrograde manner from the pulmonary arteries to the right heart and venae cavae, producing CS, a devastating process, described following.

Clinical Signs of Canine Heartworm Disease

The clinical signs of chronic heartworm disease depend on the severity and duration of infection and, in most chronic cases, reflect the effects of the parasite on the pulmonary arteries and lungs, and secondarily, the heart. It is important to point out that the vast majority of dogs with heartworm infection are asymptomatic. Historical findings in affected dogs variably include weight loss, diminished exercise tolerance, lethargy, poor condition, cough, dyspnea, syncope, and abdominal distension (ascites). Physical examination may reveal evidence of weight loss, split second heart sound (13%), right-sided heart murmur of tricuspid insufficiency (13%), and cardiac gallop. If right heart failure is present, jugular venous distension and pulsation typically accompanies hepatosplenomegaly and ascites. Cardiac arrhythmias and conduction disturbances are uncommon in chronic heartworm disease (<10%). With pulmonary parenchymal manifestations of HWD, cough and pulmonary crackles may be noted and, with granulomatosis (a rare occurrence), muffled lung sounds, dyspnea, and cyanosis are also reported. When massive pulmonary thromboembolization occurs, the additional signs of fever and hemoptysis may be noted.

Diagnosis of Canine Heartworm Disease

The Medical Management Of Heartworm Infection

Therapy of Canine Heartworm Disease

Canine Heartworm Disease: Ancillary Therapy

Canine Heartworm Disease: Complications And Specific Syndromes


The prognosis for asymptomatic heartworm infection is generally good and, although the prognosis for severe heartworm disease has to be guarded, a large percentage of such cases can be successfully managed. Once the initial crisis is past and adulticidal therapy has been successful, resolution of underlying manifestations of chronic heartworm disease begins. The prognosis is poorest with severe DIC, CS, massive embolization, eosinophilic granulomatosis, severe pulmonary artery disease, and heart failure After adulticidal therapy, intimal lesions regress rapidly. Improvement is noted as early as 4 weeks post-treatment in the main pulmonary artery, with all pulmonary arteries having undergone marked resolution within 1 year. Radiographic and arteriographic lesions of heartworm disease begin to resolve within 3 to 4 weeks, and pulmonary hypertension is reduced within months and may be normal within 6 months of adulticide therapy. Pulmonary parenchymal changes are worsened during the 6 months after adulticidal therapy and then begin to lessen in severity, with marked resolution within the next 2 to 3 months. Persistence of such lesions is suggestive of persistent infection. Corticosteroid therapy hastens the resolution of these lesions. Likewise irreversible renal disease is uncommon, with glomerular lesions resolving within months of successful adulticidal therapy. Signs of heart failure are also reversible with symptomatic therapy, cage rest, and successful clearing of infection.

Controversies In Canine Heartworm Disease

Yearlong Prevention

Macrolides As Adulticides

It is now proven that ivermectin (and possibly selamectin) has adulticidal efficacy that can approach 100% with prolonged, continuous administration. Ivermectin was demonstrated to be successful as an adulticide in experimental, young infections with 31 months’ continuous administration. The exact role of macrolides in the management of HWI, other than as preventatives, is unclear and likely to be a major controversy in upcoming years.

The appeal of macrolides for this use is that it takes the veterinarian out of the complication loop. Complications might indeed still occur but would not likely be temporally linked to the macrolide administration (as they are to arsenic use). In addition, reduced cost, patient discomfort, and inconvenience are appealing. Arguments against the use of ivermectin in this way include the following:

• Represents an off-label use of ivermectin

• Requires continuous more than 30 months’ compliance from a client that often has allowed heartworm infection to occur — often by poor compliance

• Lack of knowledge about the timing and degree of exercise restriction necessary; safe use might require 31 months of continuous exercise restriction

• Absence of a controlled kill as seen with melarsomine, reducing the ability to effectively monitor for adverse effects

• Lack of knowledge as to the effect of chronic antigen release from slowly dying adult heartworms on the kidneys and lungs

• Knowledge that macrolide “slow adulticidal therapy” does not alleviate the lung disease associated with HWI

• Fact that proven efficacy is only in young (<8 months old) experimental HWIs

• Concern that heartworm resistance to ivermectin might develop in dogs treated in this manner

At the 2001 American Heartworm Symposium, the audience and a panel of experts were polled as to their belief as to the role of ivermectin as an adulticide in their own practices. Five percent of the audience and none of the expert panelists used only ivermectin for adulticidal therapy. Approximately one third of both groups did not or would not use ivermectin as an adulticide under any circumstances. Finally, approximately 70% of the expert panel and 50% of the audience stated that they would use ivermectin for this purpose only under mitigating circumstances of financial or medical constraint.

The author recommends that melarsomine be the primary adulticidal tool and recommends or accepts the use of ivermectin in instances where a preventative is necessary in a heartworm-positive dog and the owner cannot afford arsenic therapy or in which medical conditions preclude its use; in the event of residual infection after appropriate treatment with melarsomine (assumes low worm burden); and, obviously, in unrecognized infections.


The Medical Management Of Heartworm Infection

The medical management of heartworm infection is complex because of the complicated parasite life cycle, the marked variability in clinical manifestations and severity of HWD, prophylactic considerations, adulticidal and microfilaricidal considerations, and the relative toxicity and complications associated with adulticidal therapy. For these reasons, the diagnosis, prevention, and treatment of heartworm infection remains a challenge


Prevention of heartworm infection is an obvious and attainable goal for the veterinary profession. Prevention failure results from ignorance on the part of owners as to the presence or potential severity of HWI, lack of owner compliance, or from inadequate instruction on preventative measures by the attending veterinarian. Studies of owner compliance have revealed that approximately 55% of dog owners that use veterinary care purchase heartworm preventative, and enough medication is dispensed only to meet the needs of approximately 56% of those dogs. Hence the proportion of “cared for” dogs in the population that receive adequate heartworm prophylaxis is less than one third. If one takes into consideration doses purchased but not administered and dogs that are never taken to a veterinarian, the percentage of protected dogs falls drastically. This was emphasized in North Carolina in 1999, when Hurricane Floyd caused extensive flooding and disruption in the poorest part of the state. Of dogs rescued from the floodwaters, 67% were infected with heartworms (personal communication, Dr. Kelli Ferris, North Carolina State University, 2003). In addition, evidence suggests that the veterinary profession is failing in its education of clients. New and colleagues, upon questioning veterinary clients purchasing macrolide preventatives, found that 38% did not realize that their prescribed drug’s spectrum was broader than solely preventing HWI.


Diethylcarbamazine (DEC), which long enjoyed popularity as the preventative of choice, has now been largely replaced by the safer and more convenient macrolide preventatives. This product is safe (only in amicrofilaremic dogs) and effective; however, it must be given daily, making owner compliance problematic. Diethylcarbamazine is thought to kill L3 and early L4 tissue migrating larvae but only has a small temporal window of therapeutic efficacy, thus explaining the need for frequent administration. Preventative should be administered daily from the onset of mosquito season, continuously until 1 to 2 months after a killing frost. In some geographic regions, the persistence of mosquitoes dictates yearlong prophylaxis, although this is controversial for much of the United States (see discussion of controversies, following).

Diethylcarbamazine must only be administered to dogs free of microfilariae, thus dictating a yearly heartworm test prior to reinstitution of preventative therapy. Inadvertent administration of diethylcarbamazine to microfilaremic dogs produces an adverse, possibly immune-mediated reaction in approximately 30%. Signs associated with this adverse drug reaction usually occur within 1 hour of medication and include depression, ptyalism, vomiting, diarrhea, weak pulse, pale mucous membranes with poor capillary refill time, and bradycardia. Subsequently some dogs may become recumbent, dyspneic, and tachycardic, and 18% of reactors succumb. Restated, 6% of microfilaremic dogs to which diethylcarbamazine is administered will die due an adverse reaction.

Not infrequently, owners inadvertently miss one or more doses of Diethylcarbamazine preventative. If 1 day of therapy is omitted, no problem exists and drug administration should continue. In the event of a more prolonged lapse in diethylcarbamazine treatment, reinstitution of medication should be advised, with the realization that infection may have occurred during the prophylactic hiatus.

These dogs should be reevaluated in 6 to 7 months to determine if infection has resulted. If a dog is found to be microfilaremic when receiving diethylcarbamazine, prophylaxis should be continued; however, if inadvertently stopped, reinstitution may result in the aforementioned adverse reaction.

Macrolide Antibiotics

The introduction of the macrolide agents (macrocyclic lactones) ivermectin (Heartgard ®), milbemycin oxime (Interceptor ®), moxidectin (ProHeart ® and ProHeart ® 6), and selamectin (Revolution ™) has provided the veterinary profession with effective heartworm preventatives in a variety of formulations. These agents, because they interrupt larval development during the first 2 months after infection, have a large window of efficacy and are administered monthly or less frequently. Macrolide agents are superior to Diethylcarbamazine in convenience. They produce less severe reactions when inadvertently given to microfilaremic dogs, allow a grace period for inadvertent lapses in administration, are more effective with treatment lapses of up to 2 to 3 months when used continuously for the next 12 months, and have a dual role as microfilaricides. Recently it has been shown that some macrolides have adulticidal activity, if used continuously for prolonged periods. (NOTE: ProHeart ® 6 is no longer oh the market.)


Ivermectin, a chemical derivative of avermectin B1 that is obtained from Streptomyces spp., is effective against a range of endo- and ectoparasites and is marketed as a once-monthly heartworm preventative. It is also marketed in a form with pyrantel pamoate to improve efficacy against intestinal parasites (). Macrolides provide a wide window of efficacy and provide some protection when lapses in therapy occur. Ivermectin is effective as a prophylactic with lapses of up to 2 months. Protection is extended, with continuous 12-month administration postexposure, with lapses of 3 months (98% efficacy) and of 4 months (95% efficacy). As stated previously, ivermectin is microfilaricidal at preventative doses (6 to 12 µg/kg/month), resulting in a gradual decline in microfilarial numbers. Despite this gradual microfilarial destruction, generally mild, adverse reactions (transient diarrhea) can occur if administered to microfilaremic dogs. Some breeds (collies and Shedand sheep dogs) are susceptible to ivermectin (and other macrolide) toxicosis at high doses, suffering neurologic signs. This has typically resulted with the use of concentrated livestock preparations, with clinical signs recognized with doses greater than 16 times the recommended dose. For this reason, only preparations designed for pet use should be administered to dogs. When used appropriately, ivermectin is virtually 100% effective in preventing HWI. Additionally, recent studies have shown ivermectin to have partial adulticidal properties when used continuously for 16 months and virtually 100% effective with continuous administration for 30 months. (See discussion of controversies, following.)


Milbemycin oxime is a member of a family of milbemycin macrolide antibiotics derived from a species of Streptomyces. At 500 to 999 Hg/kg, it has efficacy against developing filarial larvae, arresting development in the first 6 weeks. It can therefore be given at monthly intervals with a reachback effect of 2 months when doses are inadvertently delayed. With 12 months’ continuous treatment postexposure, this “safety net” can be extended to 3 months (97% efficacy), falling to 41% with lapses of 4 months. At the preventative dose, milbemycin is a broad-spectrum parasiticide, being also effective against certain hookworms, roundworms, and whipworms (). In microfilaremic dogs, milbemycin has greater potential for adverse reactions than do other macrolides, because it is a potent microfilaricide at preventative doses. Adverse reactions, similar to those observed with ivermectin at microfilaricidal doses, may be observed in microfilaremic dogs receiving milbemycin at preventative doses. As with microfilaricidal doses (50 ug/kg) of ivermectin, Benadryl (2 mg/kg intramuscularly) and dexamethasone (0.25 mg/kg intravenously) may be administered prior to milbemycin to prevent adverse reactions, particularly in dogs with high micro-filarial counts. Milbemycin is also safe for use in collies at the preventative dose. With appropriate use, milbemycin is virtually 100% efficacious as a heartworm prophylactic.


The macrolide preventative, moxidectin, has been more recently marketed as a narrow-spectrum heartworm preventative () and shown to be safe and virtually 100% effective at 3 ug/kg orally, given monthly or bimonthly up to 2 months postinfection. Moxidectin, at this dose, is gradually microfilaricidal and did not produce adverse reactions in a small number of microfilaremic dogs treated with the prophylactic dose. At 15 ug/kg, 98% reduction in micro-filarial numbers was documented 2 months post-treatment. Lastly, moxidectin appears to be safe in collies. A new liposomal formulation of moxidectin, which provides the potential to improve owner compliance, gives 6 months’ protection with one subcutaneous injection. With 12 months’ (two injections) continuous treatment, injectable moxidectin is 97% effective at preventing infection after a 4-month lapse in preventative therapy. (This product was removed from the market in late 2004 pending further study.)


Selamectin is a semisynthetic macrolide. It is unique in its broad spectrum and in the fact that it is applied topically once monthly (). Its efficacy is similar to that of other macrolides (virtually 100%, when used as directed). At 6 to 12 mg/kg topically, this preventative is effective at preventing heartworms infection and kills fleas and flea eggs, sarcoptic mange mites, ticks, and ear mites. Bathing and swimming, as soon as 2 hours after application, does not alter efficacy. Safety has been shown at tenfold topical doses, with oral consumption of single doses and, in ivermectin-sensitive collies, at recommended doses and fivefold overdoses for 3 months. Like other macrolides, selamectin has at least a 2-month reach-back effect and with 12 months’ continuous administration is 99% protective after 3-month lapses in prophylaxis. Selamectin has microfilaricidal activity similar to other macrolides. Chronic, continuous selamectin administration has adulticidal efficacy, although no published data indicate it is as effective in this role as ivermectin.

In summary, the macrolides offer a convenient, effective, and safe method of heartworm prophylaxis with varying spectra and methods of administration (). They each have microfilaricidal efficacy and render female heartworms sterile. Hence microfilarial tests for heartworm infection cannot be reliably used in dogs receiving these products. Prophylaxis should be commenced at 6 to 8 weeks of age in endemic areas or as soon thereafter as climatic conditions dictate. Although safer than Diethylcarbamazine in microfilaremic dogs, before first-time administration any dog over 6 months of age and at risk of infection should be tested (antigen test, followed by a microfilaria test, if antigen positive). Additionally, even though protective for at least 8 weeks postexposure, macrolides should be administered precisely as indicated by the manufacturer. If accidental lapses of more than 10 weeks occur, the preventative should be reinstituted at recommended doses and maintained for 12 consecutive months. Macrolides can also be used to “rescue” dogs that have lapsed in their Diethylcarbamazine daily therapy for up to 60 to 90 days. In the event of a lapse in preventative administration during a time of known exposure risk, an antigen heartworm test should be performed 7 months after the last possible exposure to determine if infection has occurred.

The necessary duration of protection is controversial. The American Heartworm Society indicates that in colder climates, yearlong prevention is not necessary, advocating beginning macrolides within 1 month of the anticipation of transmission season and continuing 1 month beyond the transmission season. On the other hand, some experts believe that yearlong prevention should be embraced, regardless of geographic location. This author advocates yearlong prevention, at least below the Mason-Dixon line in North America.


Therapy of Canine Heartworm Disease


In most cases of HWD, it is imperative to rid the patient of the offending parasite. Thiacetarsemide, for decades the only drug approved for this purpose, is no longer available. It has been replaced by melarsomine (Immiticide), an organoarsenic superior in safety and efficacy to thiacetarsemide. With two doses (2.5 mg/kg intramuscularly every 24 hours), the efficacy is over 96%. Melarsomine has a mean retention time five times longer than thiacetarsemide, and its metabolites are free in the plasma (on which heartworms feed). In a study of 382 dogs with heartworm infection receiving melarsomine, none required cessation of therapy due to hepatorenal toxicity (as compared with 15% to 30% with thiacetarsemide), and no case of severe postadulticidal thromboembolization was observed.

Despite the enhanced safety of this product, adverse reactions are still noted. In fact, successful pharmacologic adulticidal therapy, by definition, dictates thromboembolic events. The clinician can diminish the severity of this complication by restricting exercise after melarsomine administration. Perhaps the drug’s biggest asset is the possibility of flexible dosing (“split-dose” — three injections over 1 month or longer), allowing the potential for a safer 50% initial worm kill, followed by subsequent injections to approach 100% efficacy. Studies have shown that patients treated with the split-dose regimen have a higher seroconversion to a negative antigen status than patients treated with either caparsolate or the standard melarsomine dosing regimen.

Manufacturer’s Recommendations for the Use ofMelarsomine Dihydrochloride, Based on Patient Status


Heartworm Infection (Asymptomatic, Nitric Oxide Radiocraphic Lesions)

Class 2

Symptomatic Heartworm Disease (Mild To Moderate Signs)

Class 3

Symptomatic Heartworm Disease (Severe Signs)

Class 4

Caval Syndrome

Two doses melorsomine 24 hours apart (2.5 mg/kg IM) Two doses melarsomine 24 hours apart (2.5 mg/kg IM) One dose melarsomine (2.5 mg/kg IM), followed in approximately 1 month with 2 injections 24 hours apart Melarsomine not indicated for acute care

A split-dose protocol can be used in severely afflicted individuals or in those in which pulmonary thromboembolism is anticipated (Table Manufacturer’s Recommendations for the Use ofMelarsomine Dihydrochloride, Based on Patient Status). This method allows for destruction of only one half the worms initially (one intramuscular injection of 2.5 mg/kg), thereby lessening the chance for embolic complications. This single dose is followed by a two-dose regimen in 1 to 3 months, if clinical conditions permit. Although the manufacturer recommends this protocol for severely affected dogs, the author uses it for all cases unless financial constraint or underlying concern for arsenic toxicity exists (e.g., pre-existent severe renal or hepatic disease). Disadvantages to the split-dose method include additional expense, increased total arsenic dose, and the need for 2 months’ exercise restriction.

In 55 dogs with severe heartworm disease that were treated in this manner, 96% had a good or very good outcome with more than 98% negative for antigenemia 90 days post-therapy. Of the 55 severely affected dogs, 31% had “mild or moderate PTE,” but no fatalities resulted. The most common sign was fever, cough, and anorexia 5 to 7 days post-treatment. This was associated with mild perivascular caudal lobar pulmonary radiographic densities and subsided spontaneously or after corticosteroid therapy.

Microfilaricidal and Preventative Therapy in Heartworm-Positive Dogs

At the time of diagnosis (usually by a positive heartworm antigen test) a minimum data base is completed. This includes a microfilaria test, chemistry panel, complete blood count (CBC), urinalysis, and thoracic radiographic evaluation. If liver disease is suspected from clinical and laboratory findings, serum bile acid evaluation may be useful in evaluating liver function. At this time, monthly macrolide preventative is prescribed. This approach, which differs from the recommendations of the American Heartworm Society, is used to prevent further infection, to eliminate micro-filariae (chronic therapy renders the dog of no further risk to infect itself or other dogs and cats), and to destroy developing L4 (not yet susceptible to adulticidal therapy). In microfi-laremic dogs, the first macrolide dose is administered in the hospital or at home, with observation, so an adverse reaction might be recognized and treated promptly.

Corticosteroids with or without antihistamines (dexamethasone at 0.25 mg/kg intravenously and Benadryl at 2 mg/kg intramuscularly or 1 mg/kg of prednisolone orally 1 hour before +/- 6 hours after administration of the first dose of preventative) may be administered to reduce the potential for adverse reaction in highly microfilaremic patients. It is important to emphasize that adverse reactions are unusual with macrolides at preventative doses.

Depending on the time of year, up to 2 to 3 months might be allowed to lapse before adulticidal therapy is administered. Although monthly macrolide administration prevents further infection, this delay allows larval maturation to adulthood, ensuring that the only stage of the life cycle present is the adult, which is vulnerable to melarsomine therapy. This is more important if the diagnosis is made during or at the end of a mosquito exposure season. If the diagnosis is made in the spring or late winter, when infective larvae have matured, adulticidal therapy may be immediately administered.


The first injection of Melarsomine is administered by deep intramuscular injection (2.5 mg/kg) in the lumbar musculature (as described in the package insert) and the injection site recorded. Before injection, the needle is changed and care is taken to inject deep into the muscle and nowhere else. Patients are typically, but not necessarily, hospitalized for the day. The need for exercise restriction for 1 month is emphasized, and sedation is provided if necessary. Owners are also advised as to adverse reactions (fever, local inflammation, lassitude, inappetence, cough, dyspnea, collapse), to call if they have concerns, and to return for a second series of two injections in approximately 1 month.

If serious systemic reaction results, the second stage of the adulticidal treatment is delayed or, occasionally, even canceled. Typically, however, even with severe reactions, the entire treatment protocol is completed within 2 to 3 months. After a minimum of 1 month, the melarsomine injection procedure is repeated, again with a record of the injection site. If significant local reaction was noted after the first injection, subsequent injections are accompanied by dexamethasone or oral nonsteroidal anti-inflammatory drugs (NSAIDs) to minimize pain at the injection site. The next day (approximately 24 hours after the first injection) the process is repeated with melarsomine injection into the opposite lumbar area. Client instructions are similar to those previously given, with reemphasis of the need for 1 months’ strict restriction of exercise. Antigen testing is repeated 6 months after the second series of injections, with a positive test result indicating incomplete adulticidal efficacy. It is emphasized that despite the proven efficacy of melarsomine, not all worms are killed in every patient. The worm burden is typically markedly reduced, but if as few as one to three adult female worms remain, positive antigen tests are likely. Whether to repeat adulticidal therapy, under these circumstances is decided on a case-by-case basis with input from the owners.


It is now known that certain macrolides have adulticidal properties. Ivermectin, when administered monthly for 31 consecutive months, has nearly 100% adulticidal efficacy in young HWIs. Selamectin, when administered continuously for 18 months, killed approximately 40% of transplanted worms. Milbemycin and sustained release moxidectin appear to have minimal adulticidal efficacy. Although there may be a role for this therapeutic strategy in cases in which financial constraints or concurrent medical problems prohibit melarsomine therapy, the current recommendations are that macrolides not be adapted as the primary adulticidal approach (see discussion of controversies, following).

Exercise Restriction

Cage rest is an important aspect of the management of heartworm disease after adulticidal therapy, after PTE, or during therapy of heart failure. This can often be best, or only, accomplished in the veterinary clinic. If financial constraints preclude this, crating or housing in the bathroom or garage at home, tranquilization, or both, with only gende leash walks are useful alternatives. Nevertheless, some owners do not or cannot restrict exercise, resulting in or worsening thromboembolic complications.

Surgical Therapy

Sasaki, Kitagawa, and Ishihara have described a method of mechanical worm removal using a flexible alligator forceps. This method was 90% effective in 36 dogs with mild and severe HWD. Only two of the severely affected dogs (n = 9) died of heart and renal failure over 90 days postoperatively. These data suggest that, in skilled hands, the technique is safe. Subsequent studies by Morini and colleagues demonstrated superior results as compared with melarsomine, producing less postadulticidal thromboembolization and CS. It is important to note that the majority of dogs treated surgically required subsequent melarsomine administration for adequate worm destruction. Advantages to this technique include its diminished potential arsenic toxicity (subsequent adulticidal therapy would be administered to an asymptomatic dog) and relative freedom from thromboembolic complication. Disadvantages include the need for general anesthesia, a degree of operator skill, fluoroscopy, and subsequent arsenic administration. Nevertheless, it remains a potential alternative for the management of high-risk patients.