A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia.

Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

Factors associated with clinical interpretation of tracheal wash fluid from dogs with respiratory disease: 281 cases (2012-2017).

BACKGROUND: Clinicians face several dilemmas regarding tracheal washes (TWs) for the diagnosis of respiratory disease, including method and prediction of bacterial growth from cytology results. OBJECTIVE: To compare cytology and culture of endotracheal and transtracheal washes and identify factors associated with discordancy and bacterial growth. ANIMALS: Two hundred forty-five dogs with respiratory disease. METHODS: Retrospective study. Tracheal wash submissions were included if cellularity was sufficient for cytologic interpretation and aerobic cultures were performed. Collection technique, cytology, bacterial growth, and antibiotic history were analyzed. RESULTS: Fewer transtracheal specimens (9/144, 6.3%) were excluded for hypocellularity than endotracheal (28/174, 16.1%); otherwise, results were similar and were combined. Of 281 specimens with cellularity sufficient for interpretation, 97 (34.5%) had bacteria on cytology and 191 (68.0%) had bacterial growth. Cytology positive/culture negative discordancy was uncommon (8/97, 8%). Cytology negative/culture positive discordancy was frequent (102/184, 55.4%), but occurred less often (28/184, 14.2%) when only 1+ growth or greater was considered positive. Oropharyngeal contamination was associated with bacterial growth, but not discordancy. No association was found between antibiotic administration and bacterial growth. CONCLUSIONS AND CLINICAL IMPORTANCE: Endotracheal wash fluid, in particular, should be screened for gross mucus or turbidity to maximize the likelihood of an adequate specimen. Otherwise, endotracheal and transtracheal specimens were similar. Presence of bacteria on cytology was a good predictor of any growth, while their absence was a good predictor of the absence of growth of 1+ or more. Recent antibiotic usage should not discourage TW culture if there is compelling reason to avoid delay.

Heterobilharzia americana infection in dogs: A retrospective study of 60 cases (2010-2019).

BACKGROUND: The trematode Heterobilharzia americana (HA) causes granulomatous gastrointestinal and hepatic disease in dogs. Before 2008, diagnosis relied on saline fecal sedimentation or histopathology, and earlier reports primarily described dogs with advanced disease or cases diagnosed incidentally at necropsy. The advent of a fecal PCR test has facilitated the diagnosis of HA and provided insights into manifestations and response to treatment. OBJECTIVES: Describe the clinical findings, response to treatment, and outcome for dogs infected with HA. ANIMALS: Sixty dogs diagnosed with HA between 2010 and 2019. METHODS: Retrospective study. Medical records were searched for dogs diagnosed with HA by fecal PCR testing, identification of ova in feces, or histopathology. RESULTS: Mean age was 7.5 (±4.1) years and weight was 23.2 (±10.18) kg. Clinical signs included diarrhea (55.8%), vomiting (46.2%), and weight loss with or without anorexia (15.4%). Laboratory abnormalities included hyperglobulinemia (42.6%) and increased liver enzyme activities (30%). More than 40% of dogs had an eosinophil count >500/µL. Hypercalcemia attributable to HA was identified in only 4 dogs. Pinpoint hyperechoic foci were noted in intestines, liver, or mesenteric lymph nodes during transabdominal ultrasonography in 64.4% of dogs. Survival data was available for 34 dogs, of which 73.5% (25) were alive 6 months after diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperglobulinemia, high eosinophil count, and ultrasonographic evidence of visceral mineralization were suggestive of infection. Hypercalcemia was uncommon. Combination treatment with praziquantel and fenbendazole was variably effective, and 17.6% of treated dogs with known outcome died as a result of HA infection.