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The nucleoside analogue GS-441524 is a common treatment for cats with feline infectious peritonitis (FIP). In a previous study, 40 cats with FIP with effusion were treated with 15 mg/kg GS-441524 orally once daily for either 42 days or 84 days, and a 42-day treatment was as effective as the earlier recommended 84-day treatment. The aim of the present study was to describe unexpected clinical and laboratory observations occurring during and after treatment (within one year) in these cats and to compare them regarding the different treatment durations. Thirty-eight cats recovered rapidly during treatment, two cats had to be euthanized, and one cat was lost to follow-up. During treatment, 25 cats developed diarrhea. Lymphocytosis occurred in 26/40 cats during treatment, eosinophilia in 25/40 during treatment, increased alanine aminotransferase activity in 22/40, alkaline phosphatase activity in 7/40, and symmetric dimethylarginine levels in 25/40. These unexpected observations occurred equally in both treatment duration groups, but statistically significantly more cats developed lymphocytosis and eosinophilia when treated for 84 days. Although most of the unexpected observations during GS-441524 treatment improved or disappeared after treatment termination, these conditions have to be monitored, and treatment should not be given for longer than necessary.

Background B‐cell chronic lymphocytic leukemia (BCLL) in dogs generally is considered an indolent disease, but previous studies indicate a wide range in survival times. Objectives We hypothesized that BCLL has a heterogeneous clinical course, similar to chronic lymphocytic leukemia in humans. We aimed to assess presentation and outcome in dogs with BCLL and evaluate the prognostic relevance of clinical and flow cytometric factors. Animals One hundred and twenty‐one dogs with BCLL diagnosed by flow cytometry. Three breed groups were represented: small breed dogs (n = 55) because of increased risk of BCLL; Boxers (n = 33) because of preferential use of unmutated immunoglobulin genes; and other breeds (n = 33). Methods Retrospective study reviewing signalment, clinicopathologic data, physical examination findings, treatment, and survival of dogs with BCLL. Cellular proliferation, determined by the percentage of Ki67‐expressing CD21+ B‐cells by flow cytometry, was measured in 39 of 121 cases. Clinical and laboratory variables were evaluated for association with survival. Results The median survival time (MST) for all cases was 300 days (range, 1‐1644 days). Boxers had significantly shorter survival (MST, 178 days) than non‐Boxers (MST, 423 days; P < .0001), and no significant survival difference was found between small breeds and other non‐Boxer breeds. Cases with high Ki67 (>40% Ki67‐expressing B‐cells) had significantly shorter survival (MST, 173 days) than did cases with <40% Ki67 (MST undetermined; P = .03), regardless of breed. Cases with a high lymphocyte count (>60 000 lymphocytes/μL) or clinical signs at presentation had significantly shorter survival. Conclusions and Clinical Importance B‐cell chronic lymphocytic leukemia had a variable clinical course and Boxer dogs and cases with high Ki67 had more aggressive disease.

Background English bulldogs disproportionally develop an expansion of small B‐cells, which has been interpreted as B‐cell chronic lymphocytic leukemia (BCLL). However, clonality testing in these cases has often not been supportive of neoplasia. Hypothesis English bulldogs have a syndrome of nonneoplastic B‐cell expansion. Animals Eighty‐four English bulldogs with small‐sized CD21+ B‐cell lymphocytosis in the blood as determined by flow cytometry. Methods This is a retrospective study. We characterized this syndrome by assessing B‐cell clonality, clinical presentation, flow cytometric features, and immunoglobulin gammopathy patterns. We identified 84 cases with CD21+ lymphocytosis among 195 English bulldogs with blood samples submitted to the Colorado State University‐Clinical Immunology laboratory for immunophenotyping between 2010 and 2019. Flow cytometry features were compared to normal B‐cells and BCLL cases. PCR for antigen receptor rearrangements (PARR) by multiple immunoglobulin primers was performed to assess B‐cell clonality. A subset of cases with gammopathy were examined by protein electrophoresis, immunofixation, and immunoglobulin subclass ELISA quantification. Results Seventy percent (58/83) of cases had polyclonal or restricted polyclonal immunoglobulin gene rearrangements, suggesting nonmalignant B‐cell expansion. The median age of all dogs in the study was 6.8 years and 74% were male. The median (range) lymphocyte count was 22 400/μL (2000‐384 400/μL) and B‐cells had low expression of class II MHC and CD25. Splenomegaly or splenic masses were detected in 57% (26/46) of cases and lymphadenopathy in 11% (7/61). Seventy‐one percent (52/73) of cases had hyperglobulinemia and 77% (23/30) with globulin characterization had IgA ± IgM polyclonal or restricted polyclonal gammopathy patterns. Conclusions and Clinical Importance Polyclonal B‐cell lymphocytosis in English bulldogs is characterized by low B‐cell class II MHC and CD25 expression, splenomegaly and hyperglobulinemia consisting of increased IgA ± IgM. We hypothesize that this syndrome has a genetic basis.

Background Lymphocytosis is relatively common in cats, but few studies describe lymphocyte populations or the clinical course associated with different immunophenotypic expansions. Hypothesis/Objectives We hypothesized that cats frequently develop non‐neoplastic lymphocytosis and that different neoplastic immunophenotypes have variable prognoses. We aimed to characterize the lymphocyte expansions in a large population of cats with lymphocytosis and to assess clinical presentation and outcome in a subset. Animals Three cohorts of cats older than 1 year with lymphocytosis (>6000/μL) were examined to define immunophenotypic categories (n = 146), evaluate outcome (n = 94), and determine prevalence of immunophenotypes (n = 350). Methods Retrospective study of cats with blood submitted for flow cytometry. Medical records (n = 94) were reviewed for clinical data, treatment, and survival information. Results Five major immunophenotypic categories were identified: B cell, heterogeneous (≥2 lineages expanded), CD4+ T cell, CD4−CD8− (double negative [DN]) T cell, and CD5‐low‐expressing T cell. B‐cell and heterogeneous phenotypes were more consistent with a non‐neoplastic process, having polyclonal antigen receptor gene rearrangements, younger age at presentation, lower lymphocyte counts, and prolonged survival. The neoplastic phenotypes, CD4+ T cell, DN T cell, and CD5 low T cell, had different median survival times (752 days [n = 37], 271 days [n = 7], 27.5 days [n = 12], respectively). Among CD4+ T‐cell cases, cats with abdominal lymphadenopathy, intestinal involvement, or both and females had shorter survival. Among 350 cats with lymphocytosis, CD4+ T‐cell lymphocytosis was most common, followed by heterogeneous and B‐cell phenotypes. Conclusions and Clinical Importance Neoplastic CD4+ T‐cell lymphocytosis is common in cats and has a prolonged clinical course compared to aberrant T‐cell phenotypes. Cats with heterogeneous and B‐cell lymphocyte expansions commonly have non‐neoplastic disease.

Furthermore, BLV can be horizontally transmitted through the transfer of infected cells by bites of insects, such as stable flies (Stomoxys calcitrans) ( Buxton and others 1985 ). [...]in addition to the prevention of iatrogenic and contact transmissions, vector control is important for preventing the spread of BLV infection. In Farm A, where many blood-feeding stable flies were observed, vector control performed using a combination of insect repellents was very efficient as no new cases of BLV infection were observed after the treatment. Because there are many transmission risk factors, effective control measures depend on the identified risk factors. [...]recent studies in our laboratory have revealed that positive conversion in dairy and beef cattle herds remains high (data not shown). Because BLV prevalence was reported to be 35.2% in Japan ( Murakami and others 2013 ), risk factors must be determined and appropriate control measures must be taken to prevent the spread of BLV infection. [...]studies are now being conducted to evaluate risk factors for BLV transmission in different situations.

Bovine leukemia virus (BLV) is highly endemic in many countries, including Iraq, and it impacts the beef and dairy industries. The current study sought to determine the percentage of BLV infection and persistent lymphocytosis (PL) in cattle in central Iraq. Hematological, serological, and molecular observations in cross breeds and local breeds of Iraqi cattle naturally infected with BLV were conducted in the peripheral blood mononuclear cells of 400 cattle (340 cross breed and 60 local breed) using enzyme-linked immunosorbent assay and polymerase chain reaction (PCR). On the basis of the absolute number of lymphocytes, five of the 31 positive PCR cases had PL. Among these leukemic cattle, one case exhibited overt neutrophilia. Serum samples were used to detect BLV antibodies, which were observed in 28 (7%) samples. PCR detected BLV provirus in 31 samples (7.75%). All 28 of the seropositive samples and the 3 seronegative samples were positive using PCR. Associations were observed between bovine leukosis and cattle breed, age and sex. Age-specific analysis showed that the BLV percentage increased with age in both breeds. Female cattle (29 animals; 7.34%) exhibited significantly higher infectivity than male cattle (two animals; 4.34%). In conclusion, comprehensive screening for all affected animals is needed in Iraq; programs that segregate cattle can be an effective and important method to control and/or eliminate the BLV.

Major histocompatibility complex (MHC) is the best-characterized genetic region associated with resistance and susceptibility to a wide range of diseases. In cattle, the most important example of the relationship between the MHC and infectious diseases has been established by the resistance to Bovine leukemia virus (BLV) infection. The association of the bovine MHC class II BoLA-DRB3.2 alleles with BLV infection profiles was examined. BoLA-DRB3.2 allelic diversity was determined in 190 Iranian Holstein cattle using direct sequencing method. Association of the DRB3.2 alleles with BLV infection profiles was found as the odds ratio. Effects of the alleles on lymphocyte subsets were also evaluated by multivariate regression analysis and GLM procedures. The studied cattle were categorized into three groups: BLV seronegative, BLV seropositive with persistent lymphocytosis (PL), and BLV seropositive with lymphosarcoma (LS). The PL profile was significantly associated with the BoLA-DRB3.2*0101, *1101 and *4201 alleles, although the *3202 allele mediating resistance to PL was observed. Significant association was found between the BoLA-DRB3.2*1802, *3202, and *0901 alleles and susceptibility to LS, while the *0101 and *1101 alleles were associated with resistance to LS. BoLA-DRB3.2 alleles also showed a significant correlation with CD4, CD8, CD21 cells and CD4/CD8 ratio. Allelic differences influence the immune response to BLV infection and developing the disease profile. These differences also have important consequences for tumor resistance.

Leptospirosis is a zoonotic disease associated with a changing global epidemiology. Recently, an increased incidence of canine leptospirosis in the northeastern United States and Canada has been associated with increasing rates of infection among reservoir hosts, such as skunks, raccoons, and squirrels, that are common in suburban settings. We describe a case of leptospirosis that provides new insight into the epidemiology, diagnosis, and pathogenesis of this disease acquired in the suburban setting. Atypical lymphocytosis corresponded to an expansion of γ-δ T cells in peripheral blood.

A 7-year-old, mixed-breed dog was presented for evaluation of a possible lymphocytic leukemia. Results of laboratory testing included thrombocytopenia, large granular lymphocytosis, inverted CD4:CD8 ratio, hyperglobulinemia, and hypoalbuminemia. Results of a tick-borne disease panel indicated a positive immunoglobulin G serum titer (1:2,048) to Ehrlichia canis, supporting exposure to this organism. The dog responded to a combination treatment of doxycycline and prednisone. A review of the literature and novel diagnostic methods that aided in the diagnosis of this case are discussed.