Coccidioidomycosis in Dogs and Cats: A Review
The dimorphic fungi Coccidioides immitis and Coccidioides posadasii are the causative agents of coccidioidomycosis. Dogs and cats residing in and visiting endemic areas are at risk of exposure to infectious arthrospores. The primary infection is pulmonary and frequently results in chronic cough. Disseminated disease is common and causes cutaneous, osseous, cardiac, ocular, nervous system, or other organ disease. Radiographic changes include a variable degree of interstitial pulmonary infiltration, hilar lymphadenopathy, and osseous lesions. Serological titers support the diagnosis, but definitive diagnosis relies on identification of Coccidioides in cytological or tissue samples. Coccidioidomycosis should be considered in any dog or cat that has been potentially exposed during the previous 3 years and is presented with chronic illness, respiratory signs, lameness, lymphadenopathy, nonhealing cutaneous lesions, or neurological, ocular, or cardiac abnormalities.
Introduction
Coccidioides immitis and Coccidioides posadasii are dimorphic, soil-borne fungi that cause the systemic fungal disease called coccidioidomycosis (also known as San Joaquin Valley fever, valley fever, or desert fever) in humans and in a wide range of mammals, including dogs and cats.1–5
Characteristics of the Agent and Geographical Distribution
In soil and culture medium, Coccidioides grows as a mycelium composed of chains of thick-walled, multinucleated arthrospores alternating with smaller, nonviable brittle cells.2,6 Degeneration of the brittle cells releases infectious arthrospores into the environment. The mycelial phase of Coccidioides is adapted to live in the soil of specific locations and climate conditions found primarily in the semiarid desert regions of southern and central California, southern Arizona, southern New Mexico, western Texas, southern Nevada and Utah, northern Mexico, and parts of Central and South America [Figure 1].
During periods of increased temperature and minimal rainfall, Coccidioides lies dormant in the mycelial phase, below the soil surface.7 Periods of heavy rainfall cause mycelial proliferation, extension to the surface, and maturation to arthrospores. Infection occurs most often during dry weather following heavy rainfall, when arthrospores are easily dispersed.6–8
Pathogenesis
The primary route of infection is inhalation of infective arthrospores [Figure 2].1–19 Inhalation of very few spores (<10) can cause infection. Primary cutaneous infection can occur by direct inoculation of damaged skin, but this is uncommon.7 Dust-covered fomites harboring infectious arthrospores, such as automobile tires, have been suspected to be a rare cause of coccidioidomycosis in dogs having no history of being in endemic areas.11
Following inhalation, arthrospores disperse along the bronchial tree into the alveoli, where they are phagocytosed. In the presence of increased carbon dioxide and phagocytes, arthrospores are stimulated to undergo a structural change into spherules. Spherules enlarge and undergo endosporulation, ultimately rupturing and releasing hundreds of endospores into the surrounding tissue. Endospores mature into new spherules, and the cycle continues until host control is achieved.2,7,9
The time between inhalation of the arthrospores to formation of endospores is approximately 48 to 72 hours; however, clinical signs of respiratory illness usually do not manifest for 2 or more weeks.2,6,7 The disease is not spread from individual to individual.9,10
Infection usually remains localized in the lungs and hilar lymph nodes. Dissemination occurs when endospores spread via lymphatics and blood to distant sites in the body.6 Approximately 20% of recognized infections in dogs and 50% of recognized infections in cats are disseminated.12,20 The most common sites of dissemination in dogs are bones, joints, and lymph nodes. Less frequent sites include heart and pericardium, brain, eyes, testes, skin and subcutaneous tissues, spleen, liver, and kidney.6 In cats, the skin is the most common site of dissemination identified clinically;10,12 however, in a necropsy series of 15 cats, all had multiorgan involvement leading to death.a Subclinical infection is common in dogs and accounted for 70% of infections in one prospective study.13
Risk Factors
Young (especially <6 years of age), large-breed (>22 kg), outdoor, working and sporting dogs have an increased risk of developing coccidioidomycosis.15,17 In endemic areas, dogs that are outdoors during the day are almost five times more likely to become infected compared to dogs kept indoors.17 Breeds of dogs in which coccidioidomycosis appears to be overrepresented include boxers, Doberman pinschers, pointers, Australian shepherds, beagles, and Scottish terriers.20 In endemic areas, outdoor roaming time and space and walking in the desert have been identified as risk factors for infection in dogs.17
A proposed resistance to infection in cats has been disputed by a report of 48 cases of feline coccidioidomycosis.12 A survey of necropsy records at the Arizona Veterinary Diagnostic Laboratory from 1995 to 2005 found that one of four cases of fatal coccidioidomycosis occurred in cats.a This suggests that, although infection is less frequent in cats than in dogs, it may be more severe by the time it is recognized. Infection is most common in middle-aged cats. No breed predisposition is apparent. Interestingly, neither feline leukemia virus nor feline immunodeficiency virus appears to predispose to feline coccidioidomycosis.12
Host Response
A robust cell-mediated immune response is required for resolution of coccidioidomycosis and protection of the host against dissemination of the infection beyond the lungs.2,7,10,18 Antibodies, the humoral immune response, are made by the majority of hosts but have not been shown to play a significant role in clearance of infection.2,18 Antibody production is most useful diagnostically as a marker of infection.
People who have recovered from coccidioidomycosis are considered immune to reinfection for life.7 Relapse is common in dogs and cats, and it is not clear whether long-term immunity to Coccidioides occurs following infection in animals.10,12,15
Clinical Signs
The clinical signs associated with coccidioidomycosis are usually related to the organs infected; however, clinical signs are not pathognomonic, making differentiation from other diseases a diagnostic challenge to veterinarians, especially those practicing in nonendemic areas. In the dog, respiratory and skeletal diseases account for most of the presenting signs; but in the cat, manifestations are protean, making early identification of the disease difficult.
Dogs
The most common clinical sign in dogs is a chronic, dry or moist cough.6,10 Other clinical findings associated with primary pulmonary disease in dogs include pyrexia (>39.2°C [102.5°F]), weight loss, anorexia, listlessness, and depression.16 Despite the common name “valley fever,” approximately 50% of affected dogs have a normal temperature.16
Dissemination can manifest early in the course of disease or months after initial infection, and up to 22% of dogs with disseminated coccidioidomycosis will not have a history of respiratory illness.11 The most common presentation of disseminated disease is lameness due to osteomyelitis.3–6,11,16,19,21 Draining tracts in overlying skin, palpable bone pain and swelling, and regional lymphadenomegaly are additional signs of bone infection.19 Other clinical signs of disseminated disease are variable and are usually dependent on the organ infected; they include persistent or fluctuating fever, anorexia, weight loss, depression, lymphadenomegaly, draining skin lesions without underlying bone disease, orchitis, conjunctivitis, uveitis, and acute blindness.6,11,16,17,22 Generalized lymphadenomegaly is uncommon.16
Seizures, ataxia, behavioral changes, and coma are possible signs of coccidioidomycosis involving the central nervous system (CNS); seizures account for about 50% of such cases in dogs.4,6,10 The bulk of the remaining dogs presented for neurological signs (e.g., ataxia, paresis, paralysis, back or neck pain) have vertebral osteomyelitis.3 The typical age of presentation (<5 years) for dogs infected with coccidioidomycosis overlaps with the usual age of onset for idiopathic epilepsy, and these two diseases must be differentiated in dogs that are presented with seizures in endemic regions. Detection of a space-occupying lesion with computed tomography (CT) or magnetic resonance imaging (MRI) will rule out idiopathic epilepsy.
Coccidioidal infection of the heart or pericardium in dogs can lead to heart failure, arrhythmia, syncope, and sudden death.11,13–15,21,34 Right-sided heart failure as a result of pericardial effusion/constriction was present in 17 dogs with cardiac infection; 10 of these had no prior history of coccidioidomycosis.14 Pericardectomy combined with medical therapy resulted in a 2-year survival for about 65% of these dogs.14
Cats
Published information regarding coccidioidomycosis in cats is limited. Nonhealing cutaneous lesions (including abscesses, dermatitis, chronic draining tracts, and ulcerations) are the most common presenting complaints.12 Respiratory signs, which may be coughing or dyspnea, are observed in only 25% of cats with coccidioidomycosis.12 However, a necropsy study found lung infection in nearly all cases;a therefore, thoracic radiography may be helpful for severely ill cats in endemic areas and even for cats without obvious respiratory signs. Nonspecific clinical signs in cats are similar to those in dogs (i.e., fever, lethargy, anorexia, and weight loss).6 Profound weight loss may be the only finding. Other reported clinical signs in cats include lameness, chorioretinitis, anterior uveitis, retinal detachment, panophthalmitis, seizures, hyperesthesia, behavioral changes, and ataxia.12 Pericardial infection was found at necropsy in 26% of cats with coccidioidomycosis, although no clinical signs referable to heart disease were reported for any of the cases.a
Diagnosis
In endemic areas, veterinarians rely heavily on clinical suspicion of disease based on physical examination findings and coccidioidal serology. Travel history of animals will be important for veterinarians practicing in nonendemic areas. Radiography of the thorax and lame limbs is also valuable. More difficult cases may require aspiration, biopsy, or advanced imaging studies. Multiple diagnostic procedures may be necessary for diagnosis.4,24
Clinical Laboratory Findings
Complete blood count (CBC) and serum biochemical results help to rule out other conditions and to detect evidence of specific organ dysfunction in cases of disseminated disease. Common hematological findings in dogs are monocytosis with or without moderate neutrophilia, mild hypoalbuminemia, and hyperglobulinemia (most often a polyclonal gammopathy).4,6,13 In cats, hyperproteinemia occurs in only approximately 30% of cases; anemia, leukocytosis, and leukopenia are less common findings.12 Even very ill cats may have no clinical pathological changes.
Serology
Currently, most commercial laboratories run agar gel immunodiffusion (AGID) assays for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies; results of these assays are specific but relatively insensitive.6 Greene points out that the assays have not been fully characterized using animal serum.6 Due to the insensitivity, veterinarians encounter a “clinically relevant but undefined number” of canine cases that do have coccidioidomycosis but that are seronegative.3 More sensitive tests are the enzyme-linked immunosorbent assay (ELISA) to detect IgM and IgG and the latex particle agglutination (LA) test for IgM. These can be employed as rapid screening tests, but false-positive results occur with both.18,26 The more specific AGID test should be used to confirm positive test results.25
Immunoglobulin M test results are reported as positive or negative, whereas positive IgG tests are quantified by AGID to report a titer. Studies have failed to find a consistent correlation between the magnitude of the IgG titer and the severity or extent of coccidioidomycosis in dogs.13,16 Dogs with titers as low as 1:2 may be ill, and subclinically infected dogs were found to have titers as high as 1:16.13,17
In summary, serology is very helpful in establishing that a dog is infected with Coccidioides spp., but other diagnostic tests are often needed to confirm these organisms as a cause of illness or to identify the disease in seronegative dogs in which coccidioidomycosis is highly suspected. A general guideline for interpreting coccidioidal serology, based on the paradigm for human and veterinary clinical experience, is that a sick dog with an IgG titer =1:16 probably has clinically relevant coccidioidomycosis.18 A titer =1:32 is often associated with disseminated disease. Titers generally fall with treatment, unless they have started out low (i.e., 1:4 or 1:8), and serial monitoring can help to determine if the dog is recovering from infection. Following active infection, IgG titers can exist for months to years, usually at levels of =1:4, even after clinical signs are no longer apparent.6
Serological testing in cats has been said to be a poor diagnostic tool.6 But one study found IgM antibodies in 82% (29/35) and IgG antibodies in 100% (39/39) of infected cats in which serology was performed. The authors concluded that serology can be useful in diagnosing feline coccidioidomycosis, but that monitoring titers in cats does not detect progressive disease or help determine when treatment can be discontinued.12 Serological status of normal cats is currently unstudied, but another conclusion that may be cautiously drawn from the above study is that a sick cat with antibodies at any level is likely to have active coccidioidomycosis and should be treated.
Radiography
Radiographic findings are similar in dogs and cats12,16 and are not pathognomonic of coccidioidomycosis.12,16,24 A hallmark finding in dogs is hilar lymphadenomegaly, which is present in 50% to 75% of cases and sometimes with no or minimal observable changes in the lungs.16,24 A common radiographic finding in dogs is a diffuse, ill-defined, pulmonary interstitial pattern most severe in the hilar and central regions [Figures 3, 4].16,24 Other possible radiographic findings include nodules, consolidation of one or more lung lobes [Figure 4], pleural effusion, miliary pneumonia, and sternal lymphadenomegaly.16,24 Differential diagnoses include bacterial pneumonia, primary or metastatic neoplasia, asthma (in cats), chylothorax, pulmonary edema or hemorrhage, parasitic disease, and other fungal diseases. Given the possibility of cardiac involvement in dogs, silhouettes should be carefully evaluated for signs of pericardial effusion or cardiomegaly.11,14,23
Characteristic radiographic changes seen in bone are lytic and proliferative lesions, with periosteal new bone formation [Figure 5].16,24 Differential diagnoses include osteosarcoma, metastatic neoplasia, panosteitis, bone infarction, and osteomyelitis of bacterial or other fungal origin. The appendicular skeleton is more commonly affected than the axial skeleton, and endosteal and periosteal bone proliferation is more prominent than bone lysis.10,12,13,24 Multiple osseous lesions can occur.
Advanced imaging techniques are useful in diagnosing coccidioidomycosis.4 Ultrasonography can reveal abnormalities in internal organs and allow guided aspirates to obtain samples for cytology and culture. Magnetic resonance imaging and CT are the best ways to look for lesions in the brain or vertebral canal, and these may reveal subtle osteomyelitis lesions of the spine in dogs with neck or back pain and no obvious radiographic lesion.4
Cytological and Pathological Findings
Cytological identification of spherules provides a definitive diagnosis, but the relatively low number of spherules found in tissues often results in nondiagnostic samples.27 Often, inflammation can be characterized cytologically as pyogranulomatous but with no causative agents found. Samples for cytology can be taken from draining tracts, lymph nodes, transtracheal or bronchial washings, pleural fluid, or other infected tissues.6 Cytological samples of draining skin lesions and pleural fluid are most likely to contain organisms.10 Organisms are uncommon in tracheal wash and bronchoalveolar lavage fluids.6,27
Mature spherules are large (20 to 100 μm), round, double-walled organisms containing many endospores that are approximately 3 to 5 μm in diameter [Figure 6]. Immature spherules without endospores can be mistaken for other fungi or debris [Figure 7].19 Associated inflammation includes many neutrophils and macrophages and often giant cells [Figure 7]. Biopsies taken from infected tissue may yield more definitive diagnostic results than do cytological preparations [Figure 8].10 Multiple biopsy samples, especially of a bone lesion, will increase the probability of identifying Coccidioides spp.10
Gross findings at postmortem examination include foci of inflammation from a few millimeters to several centimeters in diameter. Inflammatory lesions vary from red to gray to white, from miliary to nodular, and from firm to caseous or liquefactive [Figure 9]. Pulmonary involvement is common, even if infection of another organ is the cause of death. Affected lymph nodes will be enlarged and firm [Figure 9].5,6 Coccidioidal effusions are often red-tinged and slightly cloudy. Affected pericardium is greatly thickened, inelastic, and fibrotic, and it may be adherent to the epicardium.23 Affected bones exhibit locally extensive expansion and periosteal/endosteal proliferation with replacement of marrow by inflammatory tissue.5,6
Fungal Isolation
Fungal cultures may be the only way to definitively diagnose some cases of coccidioidomycosis.4 Mature cultures of Coccidioides spp. develop infective arthrospores, and laboratory-acquired human infection is possible.2,5,6,9,19 Suspect samples should be sent to laboratories that are equipped to safely culture this organism.
Treatment
Currently, no single therapeutic approach is preferred in the treatment of coccidioidomycosis in animals. Oral preparations are prescribed most commonly because they are economical and convenient.3 Results of therapy are variable, and the lack of clinical trial data in animals makes comparison of the efficacy of various compounds difficult. None of them is approved for use in animals. A summary of currently available therapies is presented in the Table.
The current standard of care is to treat any dog or cat diagnosed with clinical coccidioidomycosis. How many dogs with primary respiratory disease would recover from disease without treatment is not known. Prior to the availability of oral medication, enough dogs progressed to dissemination and death that treatment for all became common practice. Any animal with disseminated disease should be treated.
Duration of therapy depends on the location and severity of infection. Most animals need to be treated for a minimum of 6 to 12 months.10 Animals with disseminated disease require extended treatment, often from 1 to several years. Relapses can occur even if treatment is given for the recommended length of time.
Antifungal Therapy
The two classes of antifungal drugs currently used to treat coccidioidomycosis are amphotericin B and azoles.28–35 Both classes diminish fungal cell membrane integrity by interfering with fungal sterol activity.28,31
Prior to development of ketoconazole in the 1980s, amphotericin B was the only drug available for the treatment of coccidioidomycosis. Intravenous amphotericin B is effective but has a high potential for nephrotoxicity.29,33 Ketoconazole and the newer triazole drugs, itraconazole and fluconazole, are currently the most commonly prescribed treatments.3,29 They can be administered orally and are less toxic than amphotericin B.
Amphotericin B
Amphotericin B is the most efficacious antifungal drug available, but serious side effects (especially renal tubular impairment, fever, vomiting, and anaphylactoid reactions) limit its use. Despite the high potential for nephrotoxicity, amphotericin B may still be indicated for treatment of animals that are unable to tolerate the azole antifungals and that have severe or rapidly progressing infection.15 Intravenous administration results in more rapid achievement of therapeutic levels.
Prior to initiating therapy with amphotericin B, renal function should be fully assessed. Ideally, the blood urea nitrogen (BUN), creatinine, packed cell volume, total protein, and body weight should be routinely rechecked prior to each dose.31 Therapy should be terminated if the BUN is >50 mg/dL, serum creatinine is >3 mg/dL, or if there are other clinical signs of systemic toxicity such as depression, anorexia, or vomiting. Administration of 5 mL/kg of 0.9% sodium chloride prior to and following amphotericin B treatment, or slow administration (1 to 5 hours) of amphotericin B diluted with 5% dextrose, may decrease the incidence of nephrotoxicity in dogs.29,31 A range of dosages can be employed [see Table]; the drug can be given intravenously every 48 hours until a cumulative dose of 4 to 12 mg/kg is reached or until azotemia develops.29,31 Cats are more sensitive to the nephrotoxic effects of this drug, and a reduced dose is indicated in cats [see Table].31
Lipid-based formulations of amphotericin B, such as amphotericin B lipid complex and liposomal amphotericin B, show promise for use in dogs and cats with systemic fungal infections.33 Studies in humans and dogs have demonstrated a significantly reduced risk of nephrotoxicity, apparently due to slower clearance by the kidneys.33,34 Treatment with amphotericin B lipid complex at 1 to 2 mg/kg three times weekly [see Table] appears to be safe and effective for severe canine coccidioidomycosis,b but a controlled study is needed.
Azoles
Due to the ease of oral administration, reasonable efficacy and cost, and moderate risk of side effects, azole drugs are most commonly used. Ketoconazole, an imidazole, was the first of this class to become available and is still commonly used in animals.6,10,29 The triazole antifungals, itraconazole and fluconazole, have less toxicity and greater bioavailability than ketoconazole.28 Fluconazole has become the most common treatment against coccidioidomycosis in dogs. All three of these drugs are considered fungistatic, with itraconazole showing the most potency in vitro against Coccidioides spp., followed by fluconazole and ketoconazole.28 Currently, all three drugs are available in a generic form in the United States.
The toxicity profile of the drugs is similar, as all induce the cytochrome P450 enzyme and may result in hepatotoxicity, either as an idiosyncratic reaction or in a dose-related manner. Eighty percent to 90% of fluconazole is excreted unchanged by the kidney and is not metabolized by the liver, so it is less likely to cause hepatotoxicity; however, a reduced dose is warranted in patients with impaired renal function.29,31 Side effects common to all azoles include anorexia, nausea, vomiting, and diarrhea; but they occur less frequently with fluconazole. Ketoconazole causes a reversible lightening of the hair coat, and fluconazole can cause thinning of the hair coat.3,31 Itraconazole can cause a vasculitis that results in sterile, suppurative to ulcerative skin lesions at mucocutaneous junctions.32 A dose reduction may result in resolution of the lesions;36 if not, a different medication should be used. Rarer side effects of ketoconazole include cataracts, thrombocytopenia, and stillbirths in pregnant bitches.5,29,30 All azoles are considered a risk for birth defects and are recommended for use in pregnant animals only when the benefits to the mother outweigh the risk to fetuses. Cats appear to be more sensitive to the hepatotoxic effects of ketoconazole than are dogs.29,31 Polyuria and polydipsia are uncommon anecdotal side effects of fluconazole, and they may respond to a dose reduction.3
Oral absorption of the azoles is variable by drug. Fluconazole is soluble in water and considered to be 100% bioavailable after oral administration; this contributes to its efficacy against systemic coccidioidomycosis in spite of a relatively poor in vitro potency.28 Fluconazole is not dependent upon gastric pH for solubility, and therefore it is easily administered to animals that are not eating—a condition common with coccidioidomycosis. Itraconazole and ketoconazole are less water soluble, require an acidic gastric pH, and are best administered with a meal for optimal absorption.31 Itraconazole suspension is believed to be better absorbed in cats and, unlike the capsules, should be administered on an empty stomach.35 Dosages of ketoconazole, itraconazole, and fluconazole published in a veterinary formulary for treatment of coccidioidomycosis range from 2.5 mg/kg q 12 hours to 20 mg/kg q 12 hours [see Table].31 The dosages that veterinarians in Arizona report using to treat dogs are in line with what is published, with the exception of a wider range of fluconazole dosages employed.3 Because the data with high dosages of fluconazole are anecdotal, it is difficult to make a best recommendation for treatment. Cases that do not respond to low dosages of fluconazole and cases with CNS infection often respond to high dosages of fluconazole (10 mg/kg q 12 hours).b Fluconazole crosses the blood-brain barrier and penetrates ocular fluids, making it the drug of choice for both CNS and ocular infections. Itraconazole becomes concentrated in the skin and may be indicated for animals with cutaneous involvement.31,32
Other Drug Therapies
Drugs of the glucan synthase inhibitor and chitin synthase classes, as well as more potent azoles (i.e., voriconazole, posaconazole), are being investigated as therapies for human coccidioidomycosis, and some may prove to be valuable in veterinary medicine. Both the glucan and chitin synthase inhibitors affect enzymes essential for fungal cell wall synthesis, and they have the advantage of no such pathways being present in mammals. Voriconazole, posaconazole, and several glucan synthase inhibitors are commercially available. The glucan synthase inhibitors can only be given intravenously, while voriconazole and posaconazole are available for oral administration. Voriconazole is about 10 times more potent than fluconazole and has similar tissue penetration and good absorption characteristics, but it is more hepatotoxic than fluconazole.28 No clinical information is available on the use of any of these drugs in animals.37
Lufenuron, a chitin synthesis inhibitor, has been suggested for use as therapy for canine coccidioidomycosis.38 Other studies suggest that it is not effective against Coccidioides spp.37
Drug Interactions
Some important drug interactions occur in animals receiving azole therapies.31 Other drugs metabolized via cytochrome P450 (e.g., digoxin, tricyclic antidepressants, phenobarbital, cyclosporine) will have increased blood levels in the face of azole therapy. Bromide is a useful alternative to phenobarbital for treatment of seizures in dogs that are on azole therapy for coccidioidomycosis. Any drug that raises gastric pH (e.g., H2 receptor blockers, antacids, omeprazole) will reduce the absorption of itraconazole and ketoconazole.
Monitoring
Animals under treatment should be examined, with appropriate diagnostic testing, on a monthly basis at first.10 Monitoring of azole therapy includes measuring parameters (i.e., CBC, serum biochemical levels, coccidioidal serology) that indicate the infection is improving and assessing possible metabolic effects (i.e., liver enzyme activities; liver function tests, if needed; and renal parameters with fluconazole) of the medication on the animal. Liver enzyme activities should be monitored within 3 to 4 weeks of initiating therapy, and then be repeated every 2 months until the practitioner is comfortable that the animal is tolerating the medication. Animals on long-term medication should have full CBCs and serum biochemical panels once or twice yearly. Monitoring of the disease process is done with repeated physical examinations, clinicopathological testing, radiography, and serology.
The effectiveness of therapy is determined by the resolution of clinical signs and radiographic lesions and reduction in serological titers.6 However, the decision to terminate therapy should not be based on serological titers alone, since titers may stabilize or decrease only slightly after recovery.6,10 Animals should be treated until the clinical signs have resolved and the clinician is satisfied no evidence of active disease is present. Discontinuing medication should include educating the client that the disease may relapse, and lifelong treatment of animals with CNS infection should be considered. For animals with disseminated disease that have had a relapse of infection, the decision may be made to continue long-term or lifetime treatment with an azole. The dosages of medication needed to keep an animal in remission may be lower than those needed to induce remission. A reasonable approach is to reduce medication levels by 25% to 50% every 6 months until reaching the desired maintenance dosage, which is usually 25% of the original therapeutic dosage.
Prognosis
The likelihood of complete recovery following treatment of an infected animal depends on the severity of disease and degree of dissemination. Animals with only pulmonary infection have the best prognosis for recovery, whereas complete recovery is uncommon in animals with multifocal osseous dissemination.6 Relapse following cessation of therapy is common.12
Prevention
Research possibly will provide an effective vaccine for coccidioidomycosis in the future.2 At this time, however, the only way to decrease the incidence of coccidioidomycosis is to limit exposure to infectious arthrospores. Infected carcasses should not be buried. Animals in endemic areas should be kept indoors whenever possible, especially during dust storms following rainy seasons. Digging should be discouraged. Animals should be kept away from desert soil and from construction sites and other locations where soil is disrupted.
Conclusion
The most common manifestation of coccidioidomycosis in dogs is respiratory infection, whereas cutaneous infection is common in cats. Diagnosis of coccidioidomycosis may require multiple diagnostic procedures. Thoracic radiography to evaluate for pulmonary, cardiac, or pericardial infection is often warranted. Several treatment regimes are available, but results are variable, and long-term therapy is often needed. The best prevention is to limit exposure to infected soil.
Dr. Sharon M. Dial, Veterinary Diagnostic Laboratory, University of Arizona, Tucson, AZ, 2007
Dr. Lisa F. Shubitz, Valley Fever Center for Excellence, University of Arizona, Tucson, AZ, 2007
Acknowledgments
The authors thank Ms. Jill Bartlett for artwork and Dr. Barry Cooper for photographic assistance.
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Citation: Journal of the American Animal Hospital Association 44, 5; 10.5326/0440226
Geographic distribution of coccidioidomycosis in North and South America.
Pathogenesis of coccidioidomycosis in dogs and cats.
Left lateral thoracic radiograph; canine coccidioidomycosis. A mixed interstitial and bronchovascular pattern is most severe in the hilar and central regions of the lung fields. Narrowing of the terminal trachea suggests hilar lymphadenomegaly.
Ventrodorsal thoracic radiograph; canine coccidioidomycosis. The left lung lobes are consolidated, and a central nodular interstitial infiltrate is on the right side. The heart shadow is obscured by the lung infiltrate.
Radiograph of the radius and ulna in a dog with coccidioidomycosis disseminated to bone. Radiographic changes include cortical expansion and lysis, periosteal elevation with sub-periosteal bone formation, columnar periosteal proliferation, and endosteal lysis and proliferation. Extensive soft-tissue swelling surrounds the radial and ulnar lesions.
Cytological appearance of a partially ruptured Coccidioides spp. spherule containing numerous endospores (arrow) (Giemsa-Wright stain, bar=10 μm).
Cytological appearance of an immature spherule of Coccidioides spp. in thoracic fluid. Endospores are not evident. Inflammation includes numerous foamy macrophages (arrowhead) and neutrophils (arrow) (Giemsa-Wright stain, bar=30 μm).
Histopathological appearance of Coccidioides spp. in tissue from a dog with coccidioidomycosis. Three spherules with varying maturation of internal endospores are present. An associated intense neutrophilic and histio-cytic (pyogranulomatous) inflammation is evident. Two intact spherules in the center are contained within the cytoplasm of a multinucleated giant cell (Hematoxylin and eosin stain, bar=50 μm).
Thoracic cavity of a cat with coccidioidomycosis. The lungs and heart have been removed. Severe suppurative pleuritis and mediastinal lymphadenomegaly are evident.
