The dog as a sentinel and animal model for coccidioidomycosis.

Coccidioidomycosis is a potentially fatal fungal disease of humans and animals that follows inhalation of Coccidioides spp. arthroconidia in the environment. The disease in dogs resembles that in people, and because dogs may be at increased risk of exposure due to their proximity to the ground and digging behavior, they are valuable models for the disease in humans. Dogs have been sentinels for identification of new regions of endemicity in Washington and Texas. Canine serosurveillance has also been used to predict variables associated with environmental presence of Coccidioides spp. Expansion of the endemic region of coccidioidomycosis with climate change-along with predicted population increases and increased development in the southwest United States-may result in 45.4 million additional people at risk of infection by 2090. Here we provide an overview of the value of dogs as sentinels for the disease and encourage the routine reporting of coccidioidomycosis cases in dogs to public health agencies. We also highlight the value of dogs as naturally occurring models for studying novel treatment options and preventatives, such as a novel live avirulent coccidioidomycosis vaccine.

Coccidioides spp. exposure among military working dogs in endemic regions of the United States.

Coccidioidomycosis is a fungal disease in arid regions of the United States that is predicted to expand with climate change. Cases in military personnel and military working dogs (MWDs) impact personnel readiness and result in healthcare costs. To examine Coccidioides exposure among MWDs, 276 banked serum samples were retrieved from dogs housed in California, Texas, Arizona, New Mexico, Nevada, and Utah. Using gel immunodiffusion, six (2.1%) specimens were IgG-positive and three (1.1%) were equivocally IgM-positive. The IgG-positive samples were from Arizona (2 [prevalence 8.0%]) and California (4 [3.7%]). These data will guide future efforts to study MWDs as sentinels for human coccidioidomycosis.

This study aimed to determine the prevalence of exposure to coccidioidomycosis, the cause of Valley Fever in both humans and animals, among military working dogs (MWDs)located in endemic regions of the United States. The data will be used to guide efforts to study MWDs as sentinels for human disease.

Selected Clinical Features of Coccidioidomycosis in Dogs.

Canine coccidioidomycosis, a systemic fungal infection endemic to arid and semiarid regions of North, Central, and South America, is commonly diagnosed in dogs living in or traveling through lower Sonoran life zones in the states of California and Arizona. Canine and human cases have geographic overlap. Similarities between clinical coccidioidomycosis in dogs and humans include asymptomatic infection, primary respiratory disease and disseminated disease. Differences include a high rate of dissemination in dogs, differences in predilection of dissemination sites, and a granulomatous or diffuse meningoencephalopathic form in the canine central nervous system (CNS) without the obstructive component seen in humans. Dogs presenting with CNS coccidioidomycosis most commonly experience seizures. Prior disease history and serology are unreliable indicators of CNS coccidioidomycosis. Magnetic resonance imaging (MRI) is advantageous for diagnosis of CNS coccidioidomycosis in dogs. Long-term administration of antifungal medication is promoted for treatment of both primary and disseminated coccidioidomycosis in dogs. Supportive treatment addressing pain, fever, inappetance, coughing, and other clinical signs improves patient care. Glucocorticoids and or anticonvulsants are also recommended for canine disseminated CNS disease. Protracted treatment times, lack of owner compliance, failure of the disease to respond to the first antifungal drug selected, and high cost are challenges of successfully treating dogs.

Flucytosine resistance in Cryptococcus gattii is indirectly mediated by the FCY2-FCY1-FUR1 pathway.

Cryptococcosis is an opportunistic fungal infection caused by members of the two sibling species complexes: Cryptococcus neoformans and Cryptococcus gattii. Flucytosine (5FC) is one of the most widely used antifungals against Cryptococcus spp., yet very few studies have looked at the molecular mechanisms responsible for 5FC resistance in this pathogen. In this study, we examined 11 C. gattii clinical isolates of the major molecular type VGIII based on differential 5FC susceptibility and asked whether there were genomic changes in the key genes involved in flucytosine metabolism. Susceptibility assays and sequencing analysis revealed an association between a point mutation in the cytosine deaminase gene (FCY1) and 5FC resistance in two of the studied 5FC resistant C. gattii VGIII clinical isolates, B9322 and JS5. This mutation results in the replacement of arginine for histidine at position 29 and occurs within a variable stretch of amino acids. Heterologous expression of FCY1 and spot sensitivity assays, however, demonstrated that this point mutation did not have any effect on FCY1 activities and was not responsible for 5FC resistance. Comparative sequence analysis further showed that no changes in the amino acid sequence and no genomic alterations were observed within 1 kb of the upstream and downstream sequences of either cytosine permeases (FCY2-4) or uracil phosphoribosyltransferase (FUR1) genes in 5FC resistant and 5FC susceptible C. gattii VGIII isolates. The herein obtained results suggest that the observed 5FC resistance in the isolates B9322 and JS5 is due to changes in unknown protein(s) or pathway(s) that regulate flucytosine metabolism.

In vivo development of fluconazole resistance in serial Cryptococcus gattii isolates from a cat.

Elevated fluconazole minimum inhibitory concentrations (MICs) are more frequently observed in Cryptococcus gattii compared to C. neoformans isolates; however, the development of in vivo resistance and the molecular mechanisms responsible have not been reported for this species. We report a case of Cryptococcus gattii (molecular type VGIII) that developed reduced susceptibility to fluconazole during therapy and delineate the molecular mechanisms responsible. Multilocus sequence typing and quantitative DNA analysis of the pre- and post-treatment isolates was performed using well-characterized methods. Pre- and post-treatment clinical isolates were confirmed isogenic, and no differences in ERG11 or PDR11 sequences were found. qPCR found an overexpression of ERG11 and the efflux pump PDR11 in the resistant isolate compared to the isolate collected prior to initiation of antifungal therapy. Reversion to wild-type susceptibility was observed when maintained in antifungal-free media confirming the in vivo development of heteroresistance. The in vivo development of heteroresistance to fluconazole in our patient with C. gattii is secondary to overexpression of the efflux pump PDR11 and the drug target ERG11. Additional work in other clinical isolates with elevated fluconazole MICs is warranted to evaluate the frequency of heteroresistance versus point mutations as a cause of resistance.

Sarcocystis caninum and Sarcocystis svanai n. spp. (Apicomplexa: Sarcocystidae) Associated with Severe Myositis and Hepatitis in the Domestic Dog (Canis familiaris).

There are several reports of Sarcocystis sarcocysts in muscles of dogs, but these species have not been named. Additionally, there are two reports of Sarcocystis neurona in dogs. Here, we propose two new names, Sarcocystis caninum, and Sarcocystis svanai for sarcocysts associated with clinical muscular sarcocystosis in four domestic dogs (Canis familiaris), one each from Montana and Colorado in the USA, and two from British Columbia, Canada. Only the sarcocyst stage was identified. Most of the sarcocysts identified were S. caninum. Sarcocysts were studied using light microscopy, transmission electron microscopy (TEM), and polymerase chain reaction. Based on collective results two new species, S. caninum and S. svanai were designated. Sarcocystis caninum and S. svanai were structurally distinct. Sarcocystis caninum sarcocysts were up to 1.2 mm long and up to 75 µm wide. By light microscopy, the sarcocyst wall was relatively thin and smooth. By TEM, the sarcocyst wall was "type 9", 1-2 µm thick, and contained villar protrusions that lacked microtubules. Bradyzoites in sections were 7-9 µm long. Sarcocysts of S. svanai were few and were identified by TEM. Sarcocystis svanai sarcocysts were "type 1", thin walled (< 0.5 µm), and the wall lacked villar protrusions but had tiny blebs that did not invaginate. DNA was extracted either from infected frozen muscle biopsies or formalin-fixed paraffin-embedded sections. Dogs were either singly infected with S. caninum or multiply co-infected with S. caninum and S. svanai (the result of a mixed infection) based on multilocus DNA sequencing and morphology. BLASTn analysis established that the sarcocysts identified in these dogs were similar to, but not identical to Sarcocystis canis or Sarcocystis arctosi, parasites found to infect polar bears (Ursus maritimus) or brown bears (Ursus arctosi), respectively. However, the S. caninum sequence showed 100% identify over the 18S rRNA region sequenced to that of S. arctica, a parasite known to infect Arctic foxes (Vulpes lagopus).

Phenotypic differences of Cryptococcus molecular types and their implications for virulence in a Drosophila model of infection.

Compared to Cryptococcus neoformans, little is known about the virulence of the molecular types in Cryptococcus gattii. We compared in vitro virulence factor production and survival data using a Drosophila model of infection to further characterize the phenotypic features of different cryptococcal molecular types. Forty-nine different isolates were inoculated into wild-type flies and followed for survival. In vitro, isolates were assessed for growth at 30 and 37°C, melanin production, capsule size, resistance to H(2)O(2), and antifungal susceptibility. A mediator model was used to assess molecular type and virulence characteristics as predictors of survival in the fly model. VGIII was the most virulent molecular type in flies (P < 0.001). At 30°C, VGIII isolates grew most rapidly; at 37°C, VNI isolates grew best. C. gattii capsules were larger than those of C. neoformans (P < 0.001). Mediator model analysis found a strong correlation of Drosophila survival with molecular type and with growth at 30°C. We found molecular-type-specific differences in C. gattii in growth at different temperatures, melanin production, capsule size, ability to resist hydrogen peroxide, and antifungal susceptibility, while growth at 30°C and the VGIII molecular type were strongly associated with virulence in a Drosophila model of infection.

Antifungal drug susceptibility and phylogenetic diversity among Cryptococcus isolates from dogs and cats in North America.

Molecular types of the Cryptococcus neoformans/Cryptococcus gattii species complex that infect dogs and cats differ regionally and with host species. Antifungal drug susceptibility can vary with molecular type, but the susceptibility of Cryptococcus isolates from dogs and cats is largely unknown. Cryptococcus isolates from 15 dogs and 27 cats were typed using URA5 restriction fragment length polymorphism analysis (RFLP), PCR fingerprinting, and multilocus sequence typing (MLST). Susceptibility was determined using a microdilution assay (Sensititre YeastOne; Trek Diagnostic Systems). MICs were compared among groups. The 42 isolates studied comprised molecular types VGI (7%), VGIIa (7%), VGIIb (5%), VGIIc (5%), VGIII (38%), VGIV (2%), VNI (33%), and VNII (2%), as determined by URA5 RFLP. The VGIV isolate was more closely related to VGIII according to MLST. All VGIII isolates were from cats. All sequence types identified from veterinary isolates clustered with isolates from humans. VGIII isolates showed considerable genetic diversity compared with other Cryptococcus molecular types and could be divided into two major subgroups. Compared with C. neoformans MICs, C. gattii MICs were lower for flucytosine, and VGIII MICs were lower for flucytosine and itraconazole. For all drugs except itraconazole, C. gattii isolates exhibited a wider range of MICs than C. neoformans. MICs varied with Cryptococcus species and molecular type in dogs and cats, and MICs of VGIII isolates were most variable and may reflect phylogenetic diversity in this group. Because sequence types of dogs and cats reflect those infecting humans, these observations may also have implications for treatment of human cryptococcosis.

Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases).

BACKGROUND: Superficial bacterial folliculitis (SBF) is usually caused by Staphylococcus pseudintermedius and routinely treated with systemic antimicrobial agents. Infection is a consequence of reduced immunity associated with alterations of the skin barrier and underlying diseases that may be difficult to diagnose and resolve; thus, SBF is frequently recurrent and repeated treatment is necessary. The emergence of multiresistant bacteria, particularly meticillin-resistant S. pseudintermedius (MRSP), has focused attention on the need for optimal management of SBF. OBJECTIVES: Provision of an internationally available resource guiding practitioners in the diagnosis, treatment and prevention of SBF. DEVELOPMENT OF THE GUIDELINES: The guidelines were developed by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases, with consultation and advice from diplomates of the American and European Colleges of Veterinary Dermatology. They describe optimal methods for the diagnosis and management of SBF, including isolation of the causative organism, antimicrobial susceptibility testing, selection of antimicrobial drugs, therapeutic protocols and advice on infection control. Guidance is given for topical and systemic modalities, including approaches suitable for MRSP. Systemic drugs are classified in three tiers. Tier one drugs are used when diagnosis is clear cut and risk factors for antimicrobial drug resistance are not present. Otherwise, tier two drugs are used and antimicrobial susceptibility tests are mandatory. Tier three includes drugs reserved for highly resistant infections; their use is strongly discouraged and, when necessary, they should be used in consultation with specialists. CONCLUSIONS AND CLINICAL IMPORTANCE: Optimal management of SBF will improve antimicrobial use and reduce selection of MRSP and other multidrug-resistant bacteria affecting animal and human health.

Lessons learned: Shaping the evolution of veterinary specialty education.

In response to concerns regarding numerous complex issues facing the veterinary specialty profession, several organizations, including the American College of Veterinary Internal Medicine, have made a clarion call to the American Veterinary Medical Association to begin discussions surrounding the formation of an accrediting body for internships, residencies, and fellowships. A proposed name for such a body is the Accreditation Council on Graduate Veterinary Medical Education, in alignment with the Accreditation Council on Graduate Medical Education (ACGME); the term "graduate" refers to specialty education that occurs after the first 4 years of the MD or DVM degree. Although the structure and financing of graduate education differ between the human medical and veterinary professions, we can nevertheless learn much from the history of evolution of human medical specialization as we navigate the path ahead.

An imminent need for veterinary medical educators: are we facing a crisis?

A potential emerging shortage of veterinary medical educators requires the profession to acknowledge and understand the factors leading to this outcome. Expanding class sizes within existing schools and colleges of veterinary medicine and the expected expansion of new programs seeking AVMA-Council of Education accreditation have heightened the need to address an impending shortage of veterinary medical educators. A solution-oriented approach that accurately projects educator workforce needs and identifies factors contributing to the shortage requires effective collaboration across various partnering organizations to develop innovations in pedagogy and educational delivery methods. The veterinary profession must also identify and reduce disincentives that deter students and post-DVM trainees from pursuing careers in education. Finally, efforts at the state and federal level are critical to advocate for financial support and incentives for expansion of the veterinary medical educator workforce. Through these collective approaches and partnerships, the veterinary medical educator workforce can be strengthened to overcome obstacles for educating the next generation of veterinarians to meet societal needs.

Prevalence of and risk factors for isolation of meticillin-resistant Staphylococcus spp. from dogs with pyoderma in northern California, USA.

BACKGROUND: Canine pyodermas associated with meticillin-resistant Staphylococcus spp. (MRS) have increased in prevalence over the past decade. HYPOTHESIS/OBJECTIVES: To compare the prevalence of MRS isolation from dogs with superficial pyoderma at a primary care clinic (PCC) and those at a tertiary care facility (VMTH) in California, USA, and identify associated risk factors. ANIMALS: Client-owned dogs from the VMTH (80 dogs) and the PCC (30 dogs). METHODS: Aerobic bacterial culture and antibiotic susceptibility were performed on swab specimens collected from dogs, and meticillin resistance was determined using microdilution methods according to Clinical and Laboratory Standards Institute guidelines. A mecA gene PCR assay was used to confirm meticillin resistance when possible. RESULTS: Of 89 staphylococcal isolates from the VMTH, 34 (38.2%) were meticillin resistant. In 31 dogs, pyoderma persisted, and one or more follow-up isolates were obtained. The species isolated and drug susceptibility changed unpredictably during treatment. Of 33 PCC isolates, nine (27.3%) were meticillin resistant. Multiple drug resistance was identified in 41 of 53 (77.3%) MRS isolates from the VMTH and five of nine from the PCC. The sensitivity and specificity of PCR for the detection of meticillin resistance was 34 of 39 (87%) and 86 of 87 (99%), respectively. Risk factors for meticillin resistance for both sites were antibiotic treatment within the last year (P = 0.001), and for VMTH, hospitalization of dogs within the last year (P = 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE: The prevalence of meticillin resistance was not different between VMTH and PCC isolates (P = 0.29). Previous antimicrobial therapy was an important risk factor for the isolation of MRS at both sites.

Updated ACVIM consensus statement on leptospirosis in dogs.

Since publication of the last consensus statement on leptospirosis in dogs, there has been revision of leptospiral taxonomy and advancements in typing methods, widespread use of new diagnostic tests and vaccines, and improved understanding of the epidemiology and pathophysiology of the disease. Leptospirosis continues to be prevalent in dogs, including in small breed dogs from urban areas, puppies as young as 11 weeks of age, geriatric dogs, dogs in rural areas, and dogs that have been inadequately vaccinated for leptospirosis (including dogs vaccinated with 2-serovar Leptospira vaccines in some regions). In 2021, the American College of Veterinary Internal Medicine (ACVIM) Board of Regents voted to approve the topic for a revised Consensus Statement. After identification of core panelists, a multidisciplinary group of 6 experts from the fields of veterinary medicine, human medicine, and public health was assembled to vote on the recommendations using the Delphi method. A draft was presented at the 2023 ACVIM Forum, and a written draft posted on the ACVIM website for comment by the membership before submission to the editors of the Journal of Veterinary Internal Medicine. This revised document provides guidance for veterinary practitioners on disease in dogs as well as cats. The level of agreement among the 12 voting members (including core panelists) is provided in association with each recommendation. A denominator lower than 12 reflects abstention of ≥1 panelists either because they considered the recommendation to be outside their scope of expertise or because there was a perceived conflict of interest.

Evaluation of Leptospira infection and exposure in free-roaming cat populations in northern California and southern Texas.

OBJECTIVES: Leptospirosis is a re-emergent zoonotic bacterial disease associated with renal and hepatic injury. In free-roaming cats in some regions, a high prevalence of Leptospira antibodies has been identified, and pathogenic leptospires have been detected in renal tissue, indicating that they may play a role in Leptospira epidemiology. The objective of this study was to determine the prevalence of Leptospira seroreactivity and urinary shedding of Leptospira DNA in free-roaming cats from northern California and southern Texas. A secondary objective was to compare the results of a point-of-care (POC) assay, designed to detect Leptospira antibodies, with the results of the microscopic agglutination test (MAT) when applied to serum samples from feral cats. METHODS: Specimens were obtained from free-roaming cats from northern California (n = 52; 2020) and southern Texas (n = 75; 2017). Leptospira quantitative PCR was performed on blood and urine specimens from Californian cats. Serum samples from Californian and Texan cats were subjected to MAT to categorize them as Leptospira antibody-positive or antibody-negative. The performance of the POC assay was assessed using the MAT as the gold standard. RESULTS: Leptospira DNA was not detected in the blood or urine of any cats tested. The results of the MAT were positive in 17.3% (n = 9) of Californian cats and 10.7% (n = 8) of Texan cats (P = 0.3). The median MAT titer was 1:100 (range 1:100-1:200) in Californian cats and 1:200 (range 1:100-1:800) in Texan cats. The POC assay was negative in all specimens. CONCLUSIONS AND RELEVANCE: Free-roaming cats in California and Texas are exposed to Leptospira species and may have the potential to act as sentinel hosts. No cats had evidence of current infection, as determined using PCR on blood and urine specimens. The POC test did not reliably detect anti-Leptospira antibodies in these cats. The role of cats in the maintenance or shedding of pathogenic leptospires requires further investigation.

Characteristics of Extended-Spectrum ß-Lactamase Producing Enterobacterales Isolated from Dogs and Cats, 2011-2021.

The rising prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales is a significant threat to animal and human health. This study aims to describe the clinical features, antimicrobial susceptibility patterns, and genotypic features of infections associated with ESBL-producing Enterobacterales in dogs and cats seen at a tertiary referral veterinary teaching hospital. Enterobacterales isolated from dogs and cats that underwent ESBL testing during the study period were identified using a search of the hospital antimicrobial susceptibility test software database. Medical records of confirmed ESBL isolates were reviewed, and the source of infection, clinical findings, and antimicrobial susceptibility were recorded. Genomic DNA from bacterial isolates was evaluated for antimicrobial resistance genes with whole genome sequencing. Thirty ESBL-producing isolates were identified based on phenotypic testing (twenty-nine from dogs, one from a cat); twenty-six were Escherichia coli and the remainder were Klebsiella spp. Bacterial cystitis was the most commonly identified (8/30, 27%) clinical problem associated with infection. Resistance to three or more antimicrobial classes was identified in 90% (27/30) of isolates, and all isolates were susceptible to imipenem. Over 70% of isolates were susceptible to piperacillin-tazobactam, amikacin, and cefoxitin. BlaCTX-M-15 was the most common ESBL gene identified, present in 13/22 (59%) isolate genomes. A wide range of clinical infections were identified. Piperacillin-tazobactam and amikacin may be alternatives to carbapenem therapy. Further, larger-scale studies are needed.

Evaluation of a rapid immunoassay for bacteriuria in dogs.

BACKGROUND: The ability to detect bacteriuria in dogs with a point-of-care test might improve medical care and antimicrobial stewardship. HYPOTHESIS AND OBJECTIVE: A rapid immunoassay (RIA; RapidBac) will provide acceptable sensitivity and specificity for diagnosis of bacteriuria. ANIMALS: Forty-four client-owned dogs with a clinical indication for urinalysis and aerobic bacterial urine culture. METHODS: Prospective study. Urine, collected by cystocentesis, was submitted for urinalysis and culture at a diagnostic laboratory. Owners completed an enrollment questionnaire regarding their dogs' clinical signs. The RIA was performed according to the manufacturer's guidelines. Results were compared to culture. RESULTS: Forty-four urine specimens were evaluated from 44 dogs. The sensitivity and specificity of the RIA test to detect bacteriuria compared to urine culture were 81.8% (95% CI, 65.7%-97.9%) and 95.5% (95% CI, 86.8%-99.9%), respectively. For cultures yielding ≥103  CFU/mL, sensitivity increased to 90.0% (95% CI, 76.9%-100%) and specificity was similar at 95.2% (95% CI, 86.1%-99.9%). Malodorous urine, bacteriuria, and pyuria were more likely to be present in dogs with positive RIA or urine culture results compared to dogs with negative results. CONCLUSIONS AND CLINICAL IMPORTANCE: The RIA was easy to perform and had good sensitivity and excellent specificity in this group of dogs. The RIA might be a useful screening test for decision-making regarding antimicrobial therapy in dogs with a clinical indication for urine culture. Consideration could be given to amending the International Society for Companion Animal Infectious Disease definition of bacterial cystitis as the presence of signs of lower urinary tract disease together with positive culture or a positive RIA.

Prevalence of antibiotic use for dogs and cats in United States veterinary teaching hospitals, August 2020.

BACKGROUND: Awareness of prescribing practices helps identify opportunities to improve antibiotic use (AU). OBJECTIVES: To estimate AU prevalence in dogs and cats in U.S. veterinary teaching hospitals (VTHs) and identify antibiotic drugs commonly prescribed, indications for use, and evidence of bacterial infection. ANIMALS: Medical record data were collected from dogs and cats examined at 14 VTHs. METHODS: Data were collected from VTH medical records of dogs and cats examined by primary care, urgent care, emergency and critical care, internal medicine, and surgery services on a single day during August 13-September 3, 2020. Data included signalment; clinical service; inpatient or outpatient status; clinical conditions; diagnostic tests; evidence of bacterial infection; intended reason for AU; name and route of antibiotics prescribed. RESULTS: Of 883 dogs and cats, 322 (36.5%) were prescribed at least 1 antibiotic. Among 285 antibiotics administered systemically intended for treatment of infection, 10.9% were prescribed without evidence of infection. The most common class of antibiotics presribed for systemic administration was potentiated penicillin for dogs (115/346, 33.3%) and cats (27/80, 33.8%). For dogs and cats, first-generation cephalosporins (93/346, 26.9% and 11/80, 13.8%, respectively) and fluoroquinolones (51/346, 14.7% and 19/80, 23.8%, respectively) was second or third most-prescribed. Common AU indications included skin, respiratory, and urinary conditions, and perioperative use. CONCLUSIONS AND CLINICAL IMPORTANCE: Collaborative data collection provides a sustainable methodology to generate national AU prevalence estimates and bring attention to areas requiring additional research and detailed data collection. These efforts can also identify practice improvement opportunities in settings where future veterinarians are trained.

Preshipment testing success: resolution of a nasal sinus granuloma in a captive koala (Phascolarctos cinereus) caused by Cryptococcus gattii.

A 3-yr-old female koala (Phascolarctos cinereus) was diagnosed with a nasal sinus granuloma caused by Cryptococcus gattii after a pre-shipment examination revealed a latex cryptococcal agglutination titer of 1:512. Successful medical and surgical treatment of the granuloma was monitored using serial latex cryptococcal agglutination titers, serum levels of antifungal drugs, and advanced imaging.

Nasopharyngeal cryptococcosis in a cat: interlaboratory variation in cryptococcal antigen assay test results.

Case summary: An indoor-only 6-year-old spayed female domestic cat was evaluated for a history of stertorous respiration. Skull radiographs revealed increased soft tissue density within the caudal aspect of the left nasal cavity. CT and rhinoscopy revealed a mass lesion in the choana, plus a smaller lesion, nearly completely occluding flow through the nasal passages. Rhinoscopy was used to collect a biopsy specimen from a fleshy, tan-yellow mass visualized in the caudal nasopharynx. Histopathology was diagnostic for Cryptococcus species infection and systemic antifungal therapy with fluconazole was initiated. Following a series of discordant results, serum samples were submitted to a veterinary diagnostic laboratory that utilized a cryptococcal antigen latex agglutination system with pretreatment of serum with pronase. Twenty-three months after the initial diagnosis, the cat's serum cryptococcal antigen titer declined to 1:5 and the cat has responded well to continuing treatment. Relevance and novel information: This case illustrates challenges associated with discordant test results for cryptococcal antigen among laboratories. Discordancies may be due to differences in assay design, or the underlying disease state itself, or whether serum is pre-treated with pronase; with some tests relying on the training and experience of the operator if the cryptococcal antigen detection test requires a subjective interpretation. It also resolves some confusion in the literature related to the assay types available and terminology used to describe them, and emphasizes the importance of considering cryptococcosis as an important differential for cats with upper respiratory signs, without nasal discharge, even if the cat is kept exclusively indoors.