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Coccidioidomycosis (Valley Fever) represents a serious threat to inhabitants of endemic areas of North America. Despite successful clinical isolations of the fungal etiological agent, Coccidioides spp., the screening of environmental samples has had low effectiveness, mainly because of the poor characterization of Coccidioides ecological niche. We explored Valle de las Palmas, Baja California, Mexico, a highly endemic area near the U.S.-Mexico border, where we previously detected Coccidioides via culture-independent molecular methods. By testing the serum from 40-trapped rodents with ELISA, we detected antibodies against Coccidioides in two species: Peromyscus maniculatus and Neotoma lepida. This study comprises the first report of wild rodent serum tested for coccidioidal antibodies, and sets the basis to analyze this pathogen in its natural environment and explore its potential ecological niche., (Copyright © 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

An 11 yr-old female Pacific walrus (Odobenus rosmarus divergens) demonstrated decreased appetite and weight loss approximately 4 wk after truck transport from a northern California facility to a southern California facility. An initial blood analysis revealed a leukocytosis of 22,800 white blood cells (WBC)/microl, with a left shift, low iron (58 microg/dl), and mild hyperglobulinemia (4.3 g/dl). Empiric antibiotic therapy was started with amoxicillin and clavulanic acid (14 mg/kg p.o. b.i.d.). Clinical improvement was observed initially; however, follow-up blood analysis demonstrated a persistent leukocytosis (24,000 WBC/microl), with left shift and progressive hyperglobulinemia (6.7 mg/dl). As a result of the relapse of clinical signs on antibiotic therapy, aggressive antifungal therapy was initiated with voriconazole (1.8 mg/kg p.o. s.i.d.). Concurrent fungal immunodiffusion antibody assays and complement fixation were repetitively positive for coccidioidomycosis. The walrus improved clinically over the next 3 mo and is currently stable on antifungal therapy at its originating facility in northern California.

Coccidioidomycosis (CM) is a mycotic disease that affects mammals, including humans. Official data relative to CM in Mexico has not been collected since 1995, thus its prevalence remains unknown. The objectives of this study were to identify the predominant Coccidioides species in Mexico, infer their current geographical distribution and explore the correlation between species and clinical presentation. We collected 154 strains, which were cultured, inactivated, and processed for DNA extraction. Nine microsatellite loci, the Ag2/PRA gene and Umeyama Region were amplified from each isolate. To infer the current geographical distribution of Coccidioides spp. and to establish a correlation between genotype and clinical presentation, we evaluated genetic population structure under the following grouping criteria: putative origin and clinical presentation records. Microsatellite analysis showed that 82% of the isolates corresponded to C. posadasii and 18% were C. immitis. The species identification results obtained using Umeyama region, Ag2/PRA, and microsatellites of five of the isolates were inconsistent with the data collected for the remaining isolates. C. posadasii strains were found primarily in the northeastern region and C. immitis in the northwestern region. However, there was no relationship between clinical presentation and Coccidioides species. The molecular markers used in this study proved to have a high power of resolution to identify the Coccidioides species recovered in culture. While we found C. posadasii to be the most abundant species in Mexico, more detailed clinical records are needed in order to obtain more accurate information about the infections in specific geographical locations.

An adult female, wild-caught red coachwhip snake (Masticophis flagellum piceus) was euthanized at the Phoenix Zoo due to severe neurologic signs. Necropsy and histopathology revealed an invasive liposarcoma of the vertebral column, which likely caused the neurologic signs. Histology of the small intestine revealed a granuloma with intralesional yeasts morphologically compatible with the genus Coccidioides. The diagnosis of coccidioidomycosis was confirmed with immunohistochemistry staining. Coccidioides posadasii is endemic to Arizona and is an important cause of disseminated fungal infections in mammals in this region. This is the first known report of intestinal coccidioidomycosis in a veterinary species and the second report of coccidioidomycosis in a reptile.

Nikkomycin Z (NikZ) is a chitin synthase inhibitor with antifungal efficacy against Coccidioides spp. and other endemic fungi. Dogs suffer a rate and range of natural coccidioidomycosis similar to humans and were considered an excellent model for initially testing NikZ against naturally acquired disease. Twelve dogs with coccidioidal pneumonia that had been present for an average of three months were treated with 250 mg (5-15 kg) or 500 mg (> 15-30 kg) twice daily for 60 days. Nine dogs completed the course of treatment and seven dogs had improvement in disease based on radiographs, clinicopathological parameters, physical examination findings, and subjective assessment by owners; three dogs had resolution or near resolution of disease. Based on this small study, NikZ shows efficacy to treat naturally acquired coccidioidomycosis and merits further development for trials in humans.

An 8-yr-old male buff-cheeked gibbon (Nomascus gabriellae) acutely developed abnormal behavior, decreased appetite, and dull mentation. Mild generalized muscle wasting and weight loss were the only other abnormalities noted on examination. Routine immunodiffusion serology for Coccidioides spp. were IgG and IgM positive. Magnetic resonance imaging of the brain was suggestive of an infectious meningoencephalitis with secondary obstructive hydrocephalus. A ventriculoperitoneal shunt was placed in standard fashion to reduce the imminent risk of mortality from increased intracranial pressure. Postoperative treatment included oral fluconazole, a tapered course of prednisolone, and physical therapy. Clinical signs improved steadily and the gibbon was fit to return to exhibit 8 wk post-shunt placement. This case of coccidioidomycosis demonstrates the complications that can occur with dissemination to the central nervous system and its management. It is the first published report describing the use of ventriculoperitoneal shunt placement in this species.

Overview: Rare fungal infections, including those hitherto not reported in Europe, may occur sporadically in non-endemic areas, or imported cases may be seen., Infections: Blastomycosis is mainly seen in North America; no cases have been reported in Europe. Histoplasmosis, which is endemic in the eastern US, Central and South America, has been diagnosed in Japan and Europe. Coccidioidomycosis is endemic in the southwestern US, Central and South America; only one imported case has been reported in Europe. The primary mode of transmission is inhalation of conidia or spores from the environment., Disease Signs: Most feline cases present with a combination of clinical signs (mainly respiratory, along with skin, eye, central nervous system and bone). Lymphadenopathy and systemic signs may be present., Diagnosis: Diagnosis is based on fungal detection by cytology and/or histology. Commercial laboratories do not routinely perform fungal culture. Diagnosis of coccidioidomycosis, which is more difficult, may be supported by antibody detection., Treatment: Treatment consists of prolonged systemic antifungal therapy, with itraconazole as the first-choice agent for histoplasmosis and blastomycosis. The prognosis is good if owner compliance is adequate and adverse drug effects do not occur., Prevention: Cat owners travelling to endemic areas should be warned about these diseases. There is no zoonotic risk.

Coccidioidomycosis or Valley Fever (VF) is an emerging soil-borne fungal zoonosis affecting humans and animals. Most non-human cases of VF are found in dogs, which we hypothesize may serve as sentinels for estimating the human exposure risk. The objective of this study is to use the spatial and temporal distribution and clusters of dogs seropositive for VF to define the geographic area in Texas where VF is endemic, and thus presents a higher risk of exposure to humans. The included specimens were seropositive dogs tested at a major diagnostic laboratory between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical Bayesian estimation to develop an isopleth map of VF seropositive rates using kriging. Clusters of seropositive dogs were identified using the spatial scan test. Both the isopleth map and the scan test identified an area with a high rate of VF-seropositive dogs in the western and southwestern parts of Texas (relative risk = 31). This location overlapped an area that was previously identified as a potential endemic region based on human surveys. Together, these data suggest that dogs may serve as sentinels for estimating the risk of human exposure to VF., (© 2012 Blackwell Verlag GmbH.)

To analyze the eco-epidemiologic aspects of Histoplasma capsulatum in Brazil, we tested 83 bats for this fungus. Although H. capsulatum was not isolated, Coccidioides posadasii was recovered from Carollia perspicillata bat lungs. Immunologic studies detected coccidioidal antibodies and antigens in Glossophaga soricina and Desmodus rotundus bats.

Antigen detection has been reported to be a promising method for rapid diagnosis of coccidioidomycosis in humans. Coccidioides antigen detection has not been previously reported in dogs with coccidioidomycosis and was evaluated in 60 cases diagnosed based on detection of anti-Coccidioides antibodies at titers of 1:16 or more in serum. Controls included dogs with presumed histoplasmosis or blastomycosis, other fungal infections, or nonfungal diseases and healthy dogs. Urine and serum specimens were tested using an enzyme immunoassay for Coccidioides galactomannan antigen. Antibody testing was performed at commercial veterinary reference laboratories. Antigen was detected in urine or serum of 12 of 60 (20.0%), urine only in 2 of 57 (3.5%), and serum only in 11 of 58 (19.0%) dogs with coccidioidomycosis. Antigen was detected in the urine of 3 of 43 (7.0%) and serum of 1 of 37 (2.7%) dogs with histoplasmosis or blastomycosis but not in 13 dogs with other fungal infections (serum, 9; urine, 13), 41 dogs with nonfungal diseases (urine, 41; serum, 18), or healthy dogs (serum, 21; urine, 21). Detection of antigen was an insensitive method for diagnosis of coccidioidomycosis in dogs in which the diagnosis was based primarily upon detection of antibodies at titers of 1:16 or higher, and the highest sensitivity was in serum.

A16-yr-old male koala (Phascolarctos cinereus) presented for nonspecific signs of illness and weight loss. Despite 2 mo of diagnostics and supportive care, the koala's health declined and euthanasia was elected. On histopathologic examination, lesions containing fungal organisms morphologically consistent with coccidioidomycosis were found in the lung, liver, spleen, kidney, lymph node, heart, eye, and bone marrow. Although disseminated infection was present, the koala was IgM and IgG seronegative for Coccidioides spp. 1 mo prior to euthanasia.

Coccidioidomycosis is a systemic fungal infection endemic to the southwestern United States. Although cell-mediated immunity is considered critical in control of the infection, little is known of the cellular population in naturally occurring lesions. To characterize the lymphocytic infiltration, archived formalin-fixed, paraffin-embedded tissues (subcutis, pericardium/heart, lung, bone, and synovium) from 18 dogs with coccidioidomycosis were studied with immunohistochemistry for CD3 and CD79a. In nearly all lesions, T lymphocytes were more numerous than B lymphocytes and were distributed throughout the lesion with concentration in the periphery of granulomas, whereas B lymphocytes were mostly confined to the periphery of granulomas. The predominance of T lymphocytes in lesions of canine coccidioidomycosis was independent of the tissue evaluated, the number of intralesional organisms, and the nature or severity of the inflammatory response.

Two atypical cases of canine coccidioidomycosis presenting as heart base masses are described. An echocardiogram performed in one of the two dogs revealed a large mass at the base of the heart and a computed tomography scan showed that the mass compressed the bronchi, left atrium, aorta and pulmonary arteries. A firm, white or pale yellow mass was found at the base of the heart at necropsy examination in both cases. Microscopical examination of the masses revealed severe, chronic, locally extensive granulomatous or pyogranulomatous inflammation with intralesional spherules consistent with Coccidioides spp. The diagnosis was further confirmed by immunohistochemistry and in-situ hybridization. Coccidioides spp. have been reported to cause pericarditis in dogs, but this is the first description of coccidioidomycosis mimicking a heart-based tumour in dogs., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To describe clinical and diagnostic features of ocular coccidioidomycosis in cats and the response to fluconazole and anti-inflammatory therapy., Animals Studied: Three cats with naturally acquired coccidioidomycosis., Procedure: Cats were treated with topical or systemic corticosteroids and systemic fluconazole, an antifungal of unproven efficacy against feline ocular coccidioidomycosis., Results: Two cats presented for periocular swellings, either subpalpebral or periorbital, with systemic signs including weight loss, unkempt hair coat, and lethargy. One cat presented for apparent blindness with no systemic signs. Clinical ophthalmologic abnormalities were bilateral in each cat and included hyperemic, conjunctival masses, fluid-filled periorbital swellings, granulomatous chorioretinitis, nonrhegmatogenous retinal detachments, and anterior uveitis. Cats were diagnosed with coccidioidomycosis using a combination of clinical findings, serology and, in two cases, visualization of Coccidioides spherules by either aspiration cytology or biopsy. Active anterior uveitis and periocular swelling were resolved in all cats during treatment. Chorioretinal granulomas, although persistent, significantly decreased in size., Conclusions: Coccidioidomycosis should be considered as a differential diagnosis for cats with a travel history to the southwestern United States that demonstrate periocular swelling, anterior uveitis, or granulomatous chorioretinitis, with or without evidence of systemic disease. Aspiration cytology or biopsy of suspicious conjunctival or skin lesions, if present, may aid in diagnosis. A combination of corticosteroids and fluconazole may be effective in treating ocular coccidioidomycosis, although chorioretinal granulomas may persist and long-term fluconazole therapy may be necessary.

Background: Three fungal species causing human disease, namely Paracoccidioides brasiliensis, Histoplasma capsulatum and Coccidioides sp., are endemic in different areas of Argentina. Rates of infection in domestic dogs have been used in other Latin American countries as indicators of the presence of these pathogens in a given area. We used such an approach to investigate the epidemiological relevance of paracoccidiodomycosis, histoplasmosis and coccidioidomycosis in our country., Aim: To investigate the presence of P. brasiliensis, H. capsulatum and Coccidioides sp. in a rural area of Argentina called Interfluvio Teuco-Bermejito, located in Chaco province., Methods: We applied Western Blotting to determine the presence of specific antibodies in sera from 89 domestic dogs inhabiting the area. Antibodies against the following extra-cellular fungal antigens were investigated: gP43 of P. brasiliensis, H/M of H. capsulatum and 120, 82 and 48kDa antigen bands of Coccidioides sp., Results: Specific antibodies against H. capsulatum were found in 9/89 (10%) sera: 8 reacted against both H and M antigens and 1 only reacted against antigen M. Of these 9 sera, one showed additional anti-gp43 activity and another reacted against all the fungal antigens tested., Conclusions: This is the first study using dog infection to assess the presence of endemic fungal pathogens in Argentina. Our results suggest that H. capsulatum is the main dimorphic fungal pathogen in the Interfluvio Teuco-Bermejito area. Therefore, the diagnosis of histoplasmosis should be taken into account in patients living in this geographic region who show pulmonary or mucocutaneous symptoms compatible with the disease., (2009 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

A 7-year-old male llama was examined for a 3-month history of weight loss, and unilateral keratouveitis. Clinical examination revealed nonulcerative corneal stromal abscessation, corneal vascularization, corneal edema, miosis, posterior synechia, cataract, and fibrin in the anterior chamber of the right eye. The left eye was normal. Histopathology of the right eye following enucleation revealed pyogranulomatous keratouveitis with intralesional fungal spherules consistent with Coccidioides spp. PCR amplification with DNA sequencing confirmed Coccidioides posadasii infection. To the authors' knowledge, this is the first reported case of ocular coccidioidomycosis in a llama.

A 5-yr-old female black rhinoceros (Diceros bicornis) was euthanized 11 mo after arrival at the Milwaukee County Zoo (Milwaukee, Wisconsin, USA) from Glen Rose, Texas (USA) for a severe progressive rear leg lameness of 6-mo duration. Gross necropsy revealed complete rupture of the capital ligament of the left femur with synovitis and osteomyelitis. Multifocal lymphadenopathy with chronic suppurative lymphadenitis of the tracheobronchial, left supramammary, and iliac lymph nodes was present. Granulomatous pneumonia with a focal abscess was also noted. Histologically, fungal elements were seen in the lung, lymph nodes, and synovium, and Coccidioides immitis was isolated on fungal culture. Coccidioides immitis is not endemic to Wisconsin; therefore, the animal had to have been infected, although asymptomatic, at the time of arrival at the Milwaukee County Zoo. Whether the disease was active at the time of arrival or whether it was quiescent and then became active with the stress of shipment or injury is unknown.

We report an unusual case of coccidioidomycosis in the arm of a veterinary assistant without pulmonary symptoms. The patient had been bitten on the hand by a cat which was later diagnosed with disseminated disease. The patient responded to fluconazole therapy and remained asymptomatic at 2 months after cessation of therapy.

Hilar lymphadenopathy is a common radiographic finding in coccidioides infections. Serologic studies are used most often for the diagnosis of coccidioidomycosis in endemic areas, with IgG titers > 1:8 considered positive for infection and lower IgG titers of < 1:8 considered indicative of exposure and not necessarily related to organism presence. The objective of this study was to determine the relationship of hilar lymphadenopathy to coccidioidomycosis titers for dogs in an endemic area. A positive association between these parameters would allow treatment to be initiated before obtaining titer results. Thoracic radiographs of 131 dogs from an endemic area were reviewed for evidence of hilar lymphadenopathy. These results were compared with serology results. There was a significant association between hilar lymphadenopathy and a positive serology result (P < 0.001). With hilar lymphadenopathy as a predictor of a positive titer result, sensitivity was 28.0%, specificity was 91.5%, the positive predictive value was 43.8%; and the negative predictive value was 84.4%. There was no association between the titer result and gender, age, or weight. The radiographic finding of hilar lymphadenopathy appears to be a useful indicator of coccidioidomycosis infection in an endemic population of dogs supporting the treatment of patients for coccidioidomycosis when hilar lymphadenopathy is present and before obtaining serology results.

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.

Coccidioides spp. appear capable of infecting all mammals and at least some reptiles. Development of disease as a result of infection is species-dependent. Dogs seem to have a susceptibility similar to that of humans, with subclinical infections, mild-to-severe primary pulmonary disease, and disseminated disease. Whereas central nervous system disease in humans is typically meningitis, brain disease in dogs and cats takes the form of granulomatous parenchymal masses. Osteomyelitis is the most common form of disseminated disease in the dog, while skin lesions predominate in the cat. Orally administered azole antifungal agents are the backbone of therapy in animals as they are in humans.

We report here the first documented case of ocular coccidioidomycosis in a chimpanzee (Pan troglodytes). In 1996, a 12-year-old female chimpanzee was undergoing treatment with an experimental triazole, BayR3783, for coccidioidomycosis when she was diagnosed with severe conjunctivitis in the right eye. Subsequent development of a coccidioidal granuloma of the ventral conjunctiva and anterior uvea was noted over the next several months, distorting the lens, iris, pupil, and sclera and progressing to uveitis. Treatment with BayR3783 and subconjunctival injections of triamcinolone were successful in reducing the ocular mass, but extensive damage was done to the lens and cornea. This case study provides an interesting comparison to ocular coccidioidomycosis cases observed in both humans and canines.

This research aimed to evaluate the effects of adding a combination of exogenous enzymes to starter diets varying in protein content and fed to broilers vaccinated at day of hatch with live oocysts and then challenged with mixed Eimeria spp. Five hundred four 1-d-old male Cobb-500 chickens were distributed in 72 cages. The design consisted of 12 treatments. Three anticoccidial control programs [ionophore (IO), coccidian vaccine (COV), and coccidia-vaccine + enzymes (COV + EC)] were evaluated under 3 CP levels (19, 21, and 23%), and 3 unmedicated-uninfected (UU) negative controls were included for each one of the protein levels. All chickens except those in unmedicated-uninfected negative controls were infected at 17 d of age with a mixed oral inoculum of Eimeria acervulina, Eimeria maxima, and Eimeria tenella. Live performance, lesion scores, oocyst counts, and samples for gut microflora profiles were evaluated 7 d postinfection. Ileal digestibility of amino acids (IDAA) was determined 8 d postinfection. Microbial communities (MC) were analyzed by G + C%, microbial numbers were counted by flow cytometry, and IgA concentrations were measured by ELISA. The lowest CP diets had poorer (P < or = 0.001) BW gain and feed conversion ratio in the preinfection period. Coccidia-vaccinated broilers had lower performance than the ones fed ionophore diets during pre- and postchallenge periods. Intestinal lesion scores were affected (P < or = 0.05) by anticoccidial control programs, but responses changed according to gut section. Feed additives or vaccination had no effect (P > or = 0.05) on IDAA, and diets with 23% CP had the lowest (P < or = 0.001) IDAA. Coccidial infection had no effect on MC numbers in the ileum but reduced MC numbers in ceca and suppressed ileal IgA production. The COV + EC treatment modulated MC during mixed coccidiosis infection but did not significantly improve chicken performance. Results indicated that feed enzymes may be used to modulate the gut microflora of cocci-vaccinated broiler chickens.

A retrospective study was performed to determine if there is an association between serological Coccidioides immitis antibody titres (IgG) and form/severity of coccidioidal disease in horses, and to identify trends in survival and treatment success based on the form of the disease. Data were obtained on horses with positive serological titres tested at the Coccidioidomycosis Serology Laboratory, School of Medicine, University of California, Davis from 1981 to 2004. Thirty-nine cases in which a diagnosis of coccidioidomycosis had been made were selected for inclusion. Six distinct categories were identified including abortion (n=6), miliary/interstitial pneumonia (n=6), pneumonia with thoracic effusion (pleural or pericardial) (n=11), disseminated (n=10), osteomyelitis (n=3) and external abscessation (n=3) both without pulmonary disease. Statistical differences in titre distribution were found between the abortion category and the pulmonary category (P=0.003), the abortion category and pneumonia with thoracic effusion (P=0.001), the abortion category and disseminated disease (P=0.001), and the pulmonary form and pneumonia with effusion (P=0.001). The other categories had overlapping titre results. Higher serological antibody titres seemed to be associated with a poorer prognosis for survival. Categories with the highest titres, disseminated (geometric mean titre=104) and pneumonia with thoracic effusion (geometric mean titre=226), were overwhelmingly fatal (19/21 known deaths) due to severe clinical disease. The categories with lower titres, abortion (geometric mean titre=4), bone involvement only (geometric mean titre=13) and cutaneous (geometric mean titre=5), had a better survival rate (10/12 known survivors) and less severe clinical disease. Measurement of serological titre may be a useful diagnostic aid in establishing form and severity of disease and thus inform prognosis.

A 19-yr-old, 78.2-kg captive female Indochinese tiger (Panthera tigris corbetti) from the El Paso Zoo (El Paso, Texas, USA) with chronic renal disease was euthanized after a 10-day course of anorexia, depression, progressive rear limb weakness, muscle fasciculations, and head tremors. Postmortem findings included pericardial effusion, generalized lymphadenopathy, glomerulosclerosis, glomerular atrophy with membranous glomerulonephropathy, and pancreatic adenocarcinoma. Pyogranulomatous pneumonia, pericarditis, and lymphadenitis were associated with fungal spherules histomorphologically consistent with Coccidioides immitis. Rising antibodies to C. immitis were detected on samples obtained perimortem and 2 mo before euthanasia. Retrospective serology was negative for two additional Indochinese tigers, two Iranian leopards (Panthera pardus saxicolor), two jaguars (Panthera onca), two bobcats (Lynx rufus texensis), two ocelots (Leopardus pardalis), and three Amur leopards (Panthera pardus orientalis) housed at the zoo over an 8-yr period. Despite being located within the endemic region for C. immitis, this is only the second case of coccidioidomycosis reported from this institution.

Pulmonary coccidioidomycosis in horses can often lead to severe systemic disease and its treatment has previously been expensive and has carried a poor prognosis. This paper describes the successful treatment of two horses with pulmonary coccidioidomycosis with a fluconazole product produced by a compounding pharmacy.

Early Holocene bison mandibles (Bison antiquus) from Nebraska, ca. 8500 y ago, were examined with a variety of modern histotechnological procedures and staining techniques. A pathological, anatomical diagnosis of moderately severe, locally extensive, mandibular osteomyelitis with intralesional spherules morphologically consistent with fungal pathogens in the genus Coccidioides was made. The modern distribution of the organisms in North America is restricted to the arid Southwest. This implies either the fossil home range of the fungi was larger than it is today or fossil bison migrated between endemic and nonendemic foci during the early Holocene.

Coccidioidomycosis is a systemic fungal infection acquired endemically in the southwestern United States. Clinical disease is quite common in the dog; though less frequently recognized in the cat, disease is often severe at the time of diagnosis. Diagnosis can be a challenge because serology, while specific, is not very sensitive and quantitative titration of antibodies does not correlate entirely with clinical disease in dogs. Radiographs, serum biochemistry tests and complete blood counts are beneficial additions to the database when establishing a diagnosis; cytology, histopathology, and culture are definitive when available. Advanced imaging can detect central nervous system and subtle skeletal lesions. Disease can occur in most organs of the body and may prove a diagnostic challenge requiring several modalities. Coccidioidomycosis may need to be considered both in animals in the endemic region and in those with a travel history through it.

Fungal infections of the central nervous system (CNS) in dogs and cats are uncommon. The purpose of this paper is to review the clinical signs, diagnostic tests, and therapeutic options of fungal infections of the CNS in the dog and cat. Clinical signs are dependent on lesion location and are often multifocal. Extraneural involvement is common. Antemortem diagnosis can be difficult and is definitively made via cytology, biopsy, or culture of an affected organ or cerebrospinal fluid (CSF). Magnetic resonance imaging can support a diagnosis and may assist in therapeutic decisions. Fungal serology can support a diagnosis when direct visualization of the organism is not possible. Long-term azole maintenance therapy is suggested to enhance survival and prevent relapse. Serial cerebrospinal fluid evaluation and magnetic resonance imaging may identify early relapse.

Objective: To determine the history, clinicopathologic findings, and results of surgery for effusive-constrictive pericarditis associated with Coccidioides immitis infection in dogs., Design: Retrospective study., Animals: 17 client-owned dogs that underwent a subtotal pericardectomy and epicardial excision., Procedure: Hospital records from May 1999 to June 2003 were reviewed. Data collected included history, clinicopathologic findings, treatments, and outcome. Follow-up information was obtained via recheck examination and by use of standardized telephone interviews with referring veterinarians and owners., Results: All dogs were of large breeds, and most were male (mean age, 4.66 years). Ten dogs had no prior history of C. immitis infection, and 7 dogs had chronic infection with C. immitis. Having a chronic C. immitis infection reduced the odds of survival, compared with no previous infection. All dogs had clinical signs of right-sided heart failure. All dogs had serum titers (range, 1:8 to 1:256) for antibodies against C. immitis prior to surgery, and titers were not significantly associated with outcome. Predominant echocardiographic findings were thickened pericardium, reduced right ventricular filling, and pleural or pericardial effusion. All dogs underwent a subtotal pericardectomy and epicardial excision and had fibrosing pyogranulomatous pericarditis in biopsy specimens obtained during surgery. The perioperative mortality rate was 23.5%, and the 2-year postdischarge survival rate was 82%., Conclusions and Clinical Relevance: Surgical treatment via subtotal pericardectomy and epicardial excision is successful at relieving right-sided heart failure in dogs with effusive-constrictive pericarditis secondary to C. immitis infection, but long-term treatment with antifungal agents may still be required.

Cokeromyces recurvatus, a zygomycete, was isolated by fungal culture from the peritoneal fluid of a cat with jejunal perforation secondary to intestinal lymphosarcoma. This organism has not been recovered previously from a veterinary patient. The tissue form of C. recurvatus is morphologically similar to those of Coccidioides immitis and Paracoccidioides brasiliensis and may be misdiagnosed as 1 of these organisms on the basis of cytologic or histopathologic specimens, particularly in geographic regions where these organisms are not endemic.

Objective: To determine the incidence of Coccidioides infection among dogs residing in a region in which the organism is endemic (Pima and Maricopa counties, Arizona) and estimate the rate of clinical illness., Design: Community-based longitudinal and cross-sectional studies., Animals: 124 healthy 4- to 6-month-old seronegative puppies (longitudinal study) and 381 4- to 18-month-old dogs with unknown serostatus (cross-sectional study)., Procedure: Dogs in the longitudinal study were tested at 6-month intervals for at least 1 year for anticoccidioidal antibodies. Dogs that became ill were evaluated for coccidioidomycosis. Dogs in the cross-sectional study were tested for anticoccidioidal antibodies once, and clinical abnormalities were recorded., Results: 28 of the 104 (27%) dogs that completed the longitudinal study developed anticoccidioidal antibodies. Thirty-two of the 381 (8%) dogs in the cross-sectional study had anticoccidioidal antibodies. Five seropositive dogs in the longitudinal study and 13 seropositive dogs in the cross-sectional study had clinical signs of disease. The remaining seropositive dogs were otherwise healthy and were classified as subclinically infected. Survival analysis indicated that the cumulative probability of infection by 2 years of age was 28%, and the cumulative probability of clinical infection by 2 years of age was 6%. Titers for clinically and subclinically infected dogs overlapped., Conclusions and Clinical Relevance: Results suggested that young dogs living in the study area had a high likelihood of becoming infected with Coccidioides spp, but few developed clinical illness. Serologic testing alone was insufficient for a diagnosis of clinical disease because of the overlap in titers between clinically and subclinically infected dogs.

Objective: To determine the seroprevalence of antibodies against Coccidioides immitis in healthy horses residing in an area in which the organism is endemic., Design: Prospective study., Animals: 197 healthy horses (in which coccidioidomycosis had not been previously diagnosed) that resided in an area of Arizona in which coccidioidomycosis is endemic., Procedure: Of the horses evaluated at the Arizona Equine Medical and Surgical Center during a 6-month period, 197 with no clinical signs of coccidioidomycosis were randomly selected for inclusion in the study; sera were evaluated for IgM and IgG antibodies against C immitis via an immunodiffusion assay (IgG-positive samples were assessed quantitatively). Within 6 months, recheck titer evaluations were attempted for all seropositive horses., Results: Serum antibodies against C immitis were detected in 8 of 197 horses (seroprevalence, 4.06%). Results of serologic assays were positive for IgG antibodies and negative for IgM antibodies in 7 horses and positive for both IgG and IgM antibodies in 1 horse; reciprocal serum IgG antibody titers were low (none > 8). Follow-up serologic data were obtained from 5 horses; compared with initial findings, horses had become seronegative or titers were unchanged or decreased. Duration of residence in the area was significantly shorter for seropositive horses than for seronegative horses., Conclusions and Clinical Relevance: Serum antibodies against C immitis may rarely be detected in healthy horses residing in an area in which the disease is endemic; any horse with a detectable serum antibody titer should be reevaluated after an interval of at least 3 weeks.

Objective: To evaluate potential risk factors for Coccidioides infection among dogs living in a region in which the organism is endemic (Pima and Maricopa counties, Arizona)., Design: Community-based longitudinal and cross-sectional studies., Animals: 104 healthy 4- to 6-month-old puppies (longitudinal study) and 381 4- to 18-month-old dogs with unknown serostatus (cross-sectional study)., Procedure: Dogs in the longitudinal study were tested 3 times at 6-month intervals for anticoccidioidal antibodies; dogs in the cross-sectional study were tested only once. Owners of all dogs completed a questionnaire on potential environmental exposures., Results: In the longitudinal study, the relative risk of infection for dogs that were outdoors during the day was 4.9 times the risk for dogs that were kept indoors. Seropositive dogs in the cross-sectional study were 6.2 times as likely to have access to > 1 acre to roam as were seronegative dogs. Logistic regression analysis indicated that the odds of infection increased with age (odds ratio [OR], 1.1), amount of roaming space (OR, 2.4), and walking in the desert (OR, 2.2). Walking on sidewalks had a protective effect (OR, 0.4)., Conclusions and Clinical Relevance: Results suggest that in regions in which the organism is endemic, dogs that spend more time outdoors or have more land in which to roam are at greater risk of infection with Coccidioides spp.

A 16-month-old intact female Poodle in Arizona had a history of intermittent coughing of a few weeks duration. Coccidiomycosis antibody screening test results were negative for immunoglobulin (Ig) M, but were positive (1:64) for IgG. Fine needle aspiration specimens of a draining lesion on the right palmar front foot contained large numbers of neutrophils, many of which contained bacteria, and lower numbers of macrophages. A few small structures also were observed, 2-5 microm in diameter with thin, nonstaining capsules and small, round to oval densely aggregated, eccentric nuclei. Cytologic findings were consistent with septic pyogranulomatous inflammation with Coccidiodes immitis endospores. Fungal culture of a sample from the draining lesion yielded white growth with barrel-shaped arthroconidia. Identification of the organism as C immitis was confirmed by a commercial DNA probe test. Although coccidioidomycosis often is diagnosed by microscopic identification of C immitis spherules in cytologic specimens, in this case only endospores, which are released from mature spherules, were observed. In cases of suspected coccidiodomycosis, the unique morphology of endospores may be useful in making a cytologic diagnosis.

Coccidioidomycosis is a rare, often subclinical infection in domestic animals caused by the fungus Coccidioides immitis. Because of an apparent high incidence of coccidioidomycosis in Przewalski's horses (Equus przewalskii) housed at a single facility, necropsy records and biomaterials from animals that died between 1984 and 2000 were reviewed (n = 30, 15 males, 15 females). Coccidioidomycosis was the leading cause of death (33%) in this population with lesions in the lungs and tracheobronchial lymph nodes of all animals and variable involvement of the skeletal muscle, heart, kidney, liver, skin, brain, spinal cord, spleen, as well as other regional lymph nodes. At the time of death, affected horses tended to be younger than unaffected animals, were from multiple lineages, and males were over represented. During the same time period, no other exotic equids (n = 76) housed at the same facility were diagnosed with coccidioidomycosis, suggesting that environmental factors are not the sole cause of the high incidence in E. przewalskii. Numbers of the lymphocyte subsets (CD3, CD4, CD5, CD8, CD21+ cells) quantified by flow cytometry were similar between Przewalski's horses and domestic horses (Equus caballus). Although responses of lymphocyte blastogenesis assays were similar between Przewalski's (n = 5) and domestic horses (n = 5) in response to the T cell mitogen concanavalin A, lymphocytes from two of the Przewalski's horses failed to proliferate in response to Coccidioides. One of these horses had systemic disease and the second developed coccidioidomycosis 2 yr later. These results suggest that the immune system of some Przewalski's horses fails to respond appropriately to Coccidioides.

Systemic fungal diseases cause significant morbidity and mortality in dogs and cats. Blastomycosis, histoplasmosis, coccidiomycosis, and cryptococcosis represent the four most common systemic fungal diseases. Young adult, large breed dogs generally are predisposed; cats usually do not have predictable predispositions. Intact cell-mediated immunity is essential to initial resistance to infection and response to treatment in animals. Several body systems can be affected. Diagnosis can be confirmed on the basis of clinical signs and demonstration of the causative organism. Serology is helpful with coccidiomycosis and cryptococcosis. Treatment is complicated by limited availability of fungicidal antimicrobials and the necessity of long-term treatment with expensive drugs.

Objective: To determine clinical, clinicopathologic, and radiographic abnormalities in dogs with coccidioidomycosis., Design: Retrospective case series., Animals: 24 dogs., Procedure: Clinical information and results of clinicopathologic testing were obtained from medical records. Thoracic radiographs were reviewed to characterize abnormalities., Results: Dogs ranged from 1 to 10 years old at the time of diagnosis, with 12 dogs being between 1 and 3 years old. Historical complaints included cough, lameness, signs of head or neck pain, and difficulty breathing. Mild anemia, neutrophilia, and monocytosis were common. All dogs had hypoalbuminemia, and 8 of 15 had hyperglobulinemia. Thoracic radiographs of 19 dogs were reviewed. Pulmonary infiltrates were seen in 13 dogs, with an interstitial pattern of infiltration being most common. Hilar lymphadenopathy was seen radiographically in 10 dogs. Serum from 20 dogs was tested for antibodies against Coccidioides immitis. One dog was positive for IgM antibodies, 5 were positive for IgM and IgG antibodies, and 14 were positive for IgG antibodies. Quantitative IgG titers measured in 14 dogs ranged from 1:2 to 1:128 (median and mode, 1:32). In 6 dogs, histologic examination of biopsy samples revealed fungal spherules ranging from 8 to 70 microm in diameter., Conclusions and Clinical Relevance: Results suggest that in dogs, coccidioidomycosis may be associated with a wide spectrum of nonspecific respiratory and musculoskeletal abnormalities. The chronic nature of the disease makes diagnosis difficult, even in regions in which the organism is endemic.

An 11-year-old, spayed female Alaskan malamute with a history of coccidioidal osteomyelitis was evaluated for inappetance and lethargy. Findings included generalized lymphadenopathy, pale mucous membranes, tachycardia, and labored breathing. Laboratory findings and radiographic imaging were consistent with generalized lymphoma and disseminated coccidioidomycosis. Treatment consisted of antibiotics, chemotherapeutic agents, and antifungals.

A 13-day-old foal with profound tachypnoea and respiratory distress was examined. Thoracic radiographs revealed a severe, diffuse miliary pattern, and the foal was markedly hypoxaemic. It failed to improve with empirical treatment, and was euthanased. Lesions associated with Coccidioides immitis infection were identified at postmortem examination, and were limited to the lower respiratory tract.

A 4-year-old castrated male mixed-breed dog with a history of coccidioidomycosis was referred for evaluation of abdominal and pleural effusion. Results of radiography, ultrasonography, cytologic evaluation of thoracic fluid, and serologic testing supported a diagnosis of constrictive pericarditis secondary to infection with Coccidioides immitis. Aggressive treatment for presumptive coccidioidomycosis was begun, but the dog's condition continued to deteriorate, and the dog was euthanatized. At necropsy, the pericardium was thicker than normal and fibrotic and adhered to the epicardium. Microscopically, the pericardium and 1 section of epicardium contained lymphoplasmacytic infiltrates with a few macrophages and neutrophils. Coccidioides immitis was cultured from pericardial fluid. A search of records from the Arizona Veterinary Diagnostic Laboratory for 1988 through 1998 revealed that of 46 dogs in which a diagnosis of coccidioidomycosis was confirmed at necropsy, 13 had involvement of the heart or pericardium.

Natural infection of armadillos with Coccidioides immitis was studied in the state of Piauí, northeast of Brazil, endemic for coccidioidomycosis. In 1998, 26 nine-banded armadillos (Dasypus novemcinctus) were captured in 4 different counties. The animals were sacrificed under deep anesthesia with ether. At necropsy fragments of spleen, liver, lungs and heart were homogenized and seeded onto Sabouraud dextrose agar with and without cycloheximide (BBL, USA). Part of each organ was also processed for histological examination. Suspected colonies of filamentous fungi observed after the second week of incubation at room temperature, exhibiting barrel-shaped arthroconidia alternating with empty spaces, were inoculated intraperitoneally into mice. Three armadillos proved to be infected with C. immitis. Mice inoculated with suspected colonies obtained from homogenized spleen of three and liver of two armadillos developed disseminated coccidioidomycosis and immature and mature spherules of C. immitis were disclosed in several organs. For the first time armadillos (D. novemcinctus) were found naturally infected with C. immitis, adding new data on the ecology and on a possible role of these ancestral mammals in the evolutionary life cycle of this fungus.

The principal route of infection for the disseminated fungal diseases discussed in this article is inhalation. In some cases, direct wound contamination and ingestion may also have an important role in the pathogenesis of the disease, especially in histoplasmosis. Another common theme of these diseases is the response of the immune system. If the inoculum is small and the animal is not immunocompromised, the infection may be limited to the respiratory tract and may resolve with few or no clinical signs. Dogs are usually presented to the veterinarian when the fungus has disseminated throughout the body via the circulatory or lymphatic systems, thus causing clinical signs secondary to specific organ infection. Draining skin tracts and lymphadenopathy occur in several of the diseases. The ocular location that is frequently affected is the choroid, where the organisms cause cell-mediated chorioretinitis. Early detection of these changes is important for saving vision and for diagnosing the systemic nature of the disease. Treatment is often effective, especially early in the disease, although it is expensive and long-term, with many animals needing over a year of treatment. Sometimes the treatment must continue lifelong. Ocular disease may not respond to treatment even when respiratory and other organ system clinical signs are rapidly improving. This isolation of the eye is similar to that of the CNS and requires regular monitoring of ocular disease, especially in the fundus, to ensure that systemic drugs are penetrating into the eye. Once the disease progresses to the anterior segment, the ocular prognosis worsens. Better penetration of the blood-retinal and blood-aqueous barriers may be achieved with fluconazole when compared with the other antifungal drugs. Secondary inflammatory ocular disease must also be monitored and treated appropriately to prevent scarring, which may cause vision loss or glaucoma.

Systemic fungal diseases are important diagnostic considerations in all sick cats, particularly in cats with ocular symptoms. The most common ocular manifestation of these diseases is posterior uveitis (choroiditis); however, anterior uveitis is sometimes present and is usually secondary to the inflammation in the posterior segment. Occasionally, adnexal diseases such as blepharitis, inflammation of the nictitating membrane, and ocular discharge may be present in cats with systemic mycoses. The prognosis for cats with systemic fungal diseases has changed with the advent of the triazole antifungal drugs. In the past, the prognosis was guarded to poor for survival of the cat. Today, with prolonged antifungal therapy, many cats recover completely from their disease. The prognosis for return of vision for eyes affected with systemic fungal disease is still guarded. Often, even if the infection is controlled systemically, the retina is severely damaged and may remain nonfunctional.

An adult mountain lion (Felis concolor) from the vicinity of Weldon, California (USA) was necropsied following euthanasia due to emaciation and proximity to semi-rural housing. There were spherules consistent with Coccidioides immitis within peritoneal surfaces with granulomatous inflammation and fungi consistent with C. immitis were cultured from abdominal fluid. This is the first reported case of coccidioidomycosis in a wild mountain lion.

Inflammatory diseases of the central nervous system (CNS) are important causes of seizures in dogs. Specific diseases include canine distemper, rabies, cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog encephalitis. Inflammatory disorders should be considered when a dog with seizures has persistent neurological deficits, suffers an onset of seizures at less than 1 or greater than 5 years of age, or exhibits signs of systemic illness. A thorough history, examination, and analysis of cerebrospinal fluid are important in the diagnosis of inflammatory diseases. However, even with extensive diagnostic testing, a specific etiology is identified in less than two thirds of dogs with inflammatory diseases of the CNS.