Efficacy of semi-annual therapy of an extended-release injectable moxidectin suspension and oral doxycycline in Dirofilaria immitis naturally infected dogs.

BACKGROUND: Dirofilaria immitis is a life-threatening nematode spreading globally. Arsenical treatment is currently recommended for removal of adult worms. However, arsenical treatment is not available in some countries, and there are dogs that cannot tolerate the rapid kill of adult worms; therefore, alternative adulticide slow-kill treatments are needed. Criticisms against the use of these alternative protocols include the potential for allowing disease to progress and for the development of ML-resistant worms. METHODS: The efficacy of a protocol that includes semi-annual doses (i.e. every 6 months) of commercially available extended-release injectable moxidectin suspension (ProHeart® SR-12) with 30-day oral administration of doxycycline was studied in 20 dogs with naturally occurring D. immitis infections. Each dog received treatment with ProHeart® SR-12 (0.5 mg moxidectin/kg) by subcutaneous injection and oral doxycycline (10 mg/kg/bid × 30 days) every 6 months until two consecutive negative antigen test results were obtained. Pulmonary and cardiac evaluations were performed by radiographic and echocardiographic parameters. Physical examinations, complete blood counts, clinical chemistry profiles, microfilariae and antigen tests were performed periodically. RESULTS: At enrollment, all dogs were positive for D. immitis antigen and 18 were microfilaremic. On day 30, microfilaremia counts decreased, and all dogs became amicrofilaremic by day 150. On day 180, 11 dogs were antigen-negative, and 7 more became negative by day 360. The two remaining antigen-positive dogs converted to negative by day 540 or 810. All antigen tests performed 180 days after the first negative test were negative. There was no decline in cardiac performance of the dogs throughout the study. Overall, pulmonary clinical conditions, presence of worms by echocardiography, and enlargement of caudal and main pulmonary arteries improved after treatment. Physical examinations, complete blood count results, and clinical chemistry profiles were within normal reference values. Respiratory conditions were improved, no damage to the heart was observed, and the treatment protocol was well tolerated by the animals. CONCLUSIONS: This alternative adulticide treatment was efficacious and well tolerated in naturally infected dogs. The injectable formulation provides the advantage of having veterinarians able to administer, monitor, and assess the efficacy and condition of the dog throughout the treatment and post-treatment periods.

Epidemiological study of Giardia duodenalis infection in companion dogs from the metropolitan area of São Paulo Brazil.

Giardia duodenalis is a zoonotic pathogen associated with gastrointestinal disease that has a direct life cycle, with cysts eliminated in the faeces of an infected host being ingested by a susceptible host. In Brazil, studies of chronically infected adult dogs estimated a prevalence of 10%-20%. Diagnosis of giardiasis, as a cause of diarrhoea is important for the global One-Health guidelines when controlling cyst dissemination in the environment. We investigated the prevalence of G. duodenalis in the pet dog population of the metropolitan area of Sao Paulo, compared the efficacy of direct tests available to the veterinary clinical practice and attempted to identify possible risk factors associated with the parasite. Ten veterinary practices distributed throughout the municipality randomly performed the rapid SNAP ELISA test on canine faecal samples, and dog owners provided information specific to the animal via a questionnaire. The samples were also analysed using sucrose and zinc sulphate flotation techniques. Sensitivity and specificity of the tests were used to calculate required number of samples and true prevalence. Significance, agreement among tests, and odds ratio (OR) were assessed with a confidence interval (CI) of 95%. The prevalence of G. duodenalis in dogs (n = 265) was 6.9% (CI 3.47-11.21). Positive tests were significantly more frequent in animals younger than 1 year, with an OR for G. duodenalis occurrence nearly 7-fold that of older dogs. Direct diagnosis tests showed high agreement (96.1%, κ = 0.729; p < .0001) showing that the combined techniques provide a highly accurate diagnosis. Results indicated that the control of the pathogen has been improving in the pet dog population in metropolitan Sao Paulo, but management tools including diagnosis, immunization, and treatment, especially in puppies, must be continued in order to advance towards continuous decrease of the disease.

A blinded, randomized, placebo-controlled trial of the safety of oclacitinib in cats.

BACKGROUND: Oclacitinib is a Janus kinase (JAK) 1 enzyme inhibitor and blocks JAK1-dependent cytokines and is used to control pruritus. Studies available in cats are very limited and as there is a potential role for oclacitinib in the control of pruritus in this specie, the aim of this study was to evaluate the safety and clinical effects of oral oclacitinib maleate in healthy cats. RESULTS: Thirty mixed-breed cats weighing from 2.1 to 5.3 kg each were randomly allocated to three treatment groups of 10 animals each. Cats in two groups received oclacitinib at 1 mg/kg or 2 mg/kg q 12 h orally for 28 days. Cats in the third group were given placebo tablets (cornstarch) q 12 h orally for 28 days. Oclacitinib maleate was well tolerated during the study and few adverse events were observed in treated cats. Clinical signs of toxicity were not observed in any animals treated at 1 mg/kg. Gastrointestinal clinical signs observed in the 2 mg/kg group included vomiting in two of the 10 cats and soft stools in two cats. One cat treated with placebo also exhibited soft stools. No significant differences were observed between the groups for hematologic analyses performed during the study. There was a slight increase in neutrophils and monocytes and a decrease in eosinophil mean counts in treated cats. Mean renal and liver enzymes remained normal throughout the entire study. A small, but significant increase in fructosamine levels was observed for both treated groups compared with placebo; however, values remained within the normal reference range. There were no significant difference between treated groups and the placebo group for urine specific gravity, pH, or urine protein to creatinine ratio mean values. CONCLUSIONS: Oclacitinib maleate was well tolerated by cats at 1 mg/kg and 2 mg/kg and appeared to be safe for this species when administered orally twice daily for 28 days. More studies would be needed to demonstrate if oclacitinib maleate may be a suitable alternative to treat pruritic cats.

Use of Slow-Release Injectable Moxidectin for Treatment of Dirofilaria immitis Infection During Pregnancy.

Canine heartworm disease is a life-threatening disease caused by Dirofilaria immitis and is prevalent in Brazil. The standard drug for its treatment, melarsomine dihydrochloride, is a fast-killing organic arsenical chemotherapeutic agent not approved in Brazil. Therefore, an alternative strategy, such as macrocyclic lactone in combination with a tetracycline antibiotic, has to be used. The alternative method is a long-term therapy that could lead to compliance issues during treatment. The aim of this case report is to present a preliminary assessment on the efficacy and safety of an off-label biannual administration of slow-release moxidectin (0.5 mg/kg every 6 months), which is formulated for annual administration (0.5 mg/kg annually). This overdose was chosen to test if moxidectin serum levels could be maintained high enough to harm the worms. It was administered to a 4-year-old female dog in combination with a 30-day doxycycline course. The second dose of moxidectin was administered approximately a week before she gave birth to three healthy puppies. Microfilariae were not detected on day 180 of treatment. Serological tests showed that the worms were eliminated, as two negative antigen tests were obtained 6 months apart (at day 180 and day 360 of treatment). Therefore, the off-label biannual use of moxidectin in combination with doxycycline was effective in eliminating D. immitis in 360 days and was harmless for the pregnant dog and her offspring, suggesting that this strategy is promising. Although these results are encouraging, further studies are needed to confirm safety and efficacy issues.

Selamectin for the prevention of canine Dirofilaria immitis infection: field efficacy in client-owned dogs in a high risk area.

BACKGROUND: Dog owners and veterinarians in small animal practices began to waive prevention of canine heartworm disease after heartworm infections seemed to have disappeared in Brazil. After 2013, infection rates rebounded, and an evaluation of the efficacy of chemoprophylactic drugs became necessary. Included in this re-evaluation was the efficacy of selamectin in client-owned dogs residing in a high infection-risk area. METHODS: The preventive efficacy of selamectin was evaluated by the topical application of selamectin to 24 client-owned dogs at the recommended rate (minimum of 6 mg/kg) by a veterinarian monthly for 36 months. Blood samples were collected before the first treatment and at the end of the study for testing to detect microfilariae by the modified Knott's test and Dirofilaria immitis antigens using a commercial antigen test. Exposure to risk of heartworm infection was confirmed by the presence of infection in dogs living in low-income communities within a 2 km radius from the homes of dogs in the study. The dogs were managed according to routine practice by the owners within each household throughout the study. RESULTS: All dogs tested negative by both tests after receiving topical treatment with selamectin monthly for 36 months. Testing of 204 dogs from the communities confirmed the presence of heartworm in the area by detection of microfilariae or D. immitis antigen in 44 dogs (21.6 %). CONCLUSIONS: Topical selamectin was 100 % effective for D. immitis prevention in 24 dogs that received monthly treatments by a veterinarian. Detection of heartworm infections in untreated dogs in the area suggests that clients need to be better informed regarding the prevalence of D. immitis and the importance of maintaining regular preventive treatments.

Updated canine infection rates for Dirofilaria immitis in areas of Brazil previously identified as having a high incidence of heartworm-infected dogs.

BACKGROUND: Canine heartworm infections were frequently diagnosed in Brazil before the new millennium. After the year 2000, the frequency of diagnosis showed a sharp decline; however, a few years later, new evidence indicated that the parasite was still present and that canine infection rates seemed to be increasing. Therefore, an updated survey of canine heartworm prevalence was conducted in several locations in south, southeast, and northeast Brazil. METHODS: Dogs from 15 locations having previously reported a high prevalence of heartworm infection were included in the survey according to defined criteria, including the absence of treatment with a macrocyclic lactone for at least 1 year. Blood samples from 1531 dogs were evaluated by an in-clinic immunochromatography test kit (Witness® Heartworm, Zoetis, USA) for detection of Dirofilaria immitis antigen. At each location, epidemiologic data, including physical characteristics and clinical signs reported by owners or observed by veterinarians, were recorded on prepared forms for tabulation of results by location, clinical signs, and physical characteristics. RESULTS: The overall prevalence of canine heartworm infection was 23.1%, with evidence of heartworm-infected dogs detected in all 15 locations studied. There was a tendency for higher prevalence rates in environmentally protected areas, despite some locations having less-than-ideal environmental temperatures for survival of vector mosquitoes. Among physical characteristics, it was noted that dogs with predominantly white hair coats and residing in areas with a high (≥20%) prevalence of heartworm were less likely to have heartworm infection detected by a commercial heartworm antigen test kit than were dogs with other coat colors. In general, dogs older than 2 years were more frequently positive for D. immitis antigen than were younger dogs. Clinical signs of heartworm infections were rare or owners were unable to detect them, and could not be used for reliable prediction of the presence of heartworm. CONCLUSIONS: These results indicate that the prevalence of D. immitis has increased in these areas of Brazil over the past few years. Small animal practitioners in these areas should include routine screening tests for heartworm infections in every dog's annual evaluation protocol and make sure to have uninfected dogs on prevention.

Ceruloplasmin concentration in dogs with multicentric lymphoma undergoing chemotherapy / Concentração de ceruplasmina em cães com linfoma multicêntrico submetidos à quimioterapia

Ceruloplasmin (Cp) is a positive acute phase protein, responsible for the transport of copper and protection of cells and tissue against oxidant compounds. The aim of this study was to evaluate Cp concentrations at diagnosis and during chemotherapy in dogs with multicentric lymphoma (ML). Cp was measured using orto dianisine technique, in two groups of dogs: ten healthy dogs (control) and 13 dogs with ML. All dogs were submitted to chemotherapy. Dogs with signs of concurrent disease or that have been previously treated with prednisone were excluded from the study. Cp measurement was done before treatment and once a week, during the first month of chemotherapy, and each 3-week intervals until the relapse for dogs with ML, and until the 16th week in control dogs. ANOVA test followed by multiple Tukey's tests were used to compare the groups. There was no difference between the mean of Cp concentration in dogs with ML at the diagnosis when compared to healthy dogs (p > .05). Levels of Cp decreased significantly at 4th week when compared to the first week, but Cp increase was not observed at the relapse. At all other times during the treatment, Cp concentrations for dogs with lymphoma were not significantly different from controls submitted to chemotherapy. As conclusion, Cp levels in ML at diagnosis were similar to healthy dogs, decreased when lymphoma remission was achieved and there was no change at the relapse.

Ceruloplasmina (Cp) é uma proteína positiva de fase aguda, responsável pelo transporte de cobre e proteção das células e tecidos contra compostos oxidantes. O objetivo deste estudo foi avaliar as concentrações de Cp no momento do diagnóstico e durante a quimioterapia em cães com linfoma multicêntrico (LM). Cp foi mensurada utilizando-se a técnica da orto dianisina em dois grupos de cães: dez cães sadios (controle) e 13 cães com LM. Todos os cães foram submetidos à quimioterapia. Cães com sintomas de doenças intercorrentes ou que haviam sido previamente tratados com prednisona foram excluídos do estudo. Cp foi mensurada antes do início do tratamento e uma vez por semana durante o primeiro mês de quimioterapia e depois a intervalos de três semanas até a recidiva.para cães com LM, e até 16 semanas nos cães do grupo controle. ANOVA seguida pelo teste de Tukey foi usada para comparar os grupos. Não houve diferença entre a media das concentrações de Cp em cães com LM ao diagnóstico quando comparados aos cães sadios (p > 0.05). Os níveis de Cp diminuíram significativamente na quarta semana de tratamento comparado ao momento do diagnóstico. Aumentos nas concentrações de Cp não foram observados na recidiva. Durante o tratamento, as concentrações de Cp em cães com linfoma não diferiram daquelas observadas nos animais do grupo controle submetidos à quimioterapia. Concluiu-se que os níveis de Cp nos cães com LM ao diagnóstico foram similares aos cães sadios, diminuiu quando se obteve a remissão e não se alterou na recidiva da doença.

Serum amyloid A is not a marker for relapse of multicentric lymphoma in dogs.

BACKGROUND: Serum amyloid A (SAA) is an acute phase protein whose concentration increases in inflammatory, infectious, and neoplastic conditions in animals and human beings. Multicentric lymphoma is a common cancer in dogs, and chemotherapy is indicated to attain long-term survival. However, frequent relapses lead to changes in chemotherapeutic protocols. OBJECTIVES: The aims of this study were to evaluate SAA as a marker for relapse of multicentric lymphoma in dogs and to determine whether chemotherapy induces changes in the concentration of SAA during treatment. METHODS: SAA was measured by an ELISA test in healthy control dogs (n=20), in healthy dogs receiving chemotherapy (n=8), and in dogs with lymphoma (n=20). All dogs receiving chemotherapy were randomly assigned to 2 treatment groups, one receiving cyclophosphamide, vincristine, and prednisone (CVP) and the other receiving vincristine, cyclophosphamide, methotrexate, and L-asparaginase (VCMA) protocols. SAA concentration was determined before chemotherapy at weeks 1-4 in healthy dogs receiving chemotherapy and in dogs with lymphoma, then every 3 weeks for 4 months in healthy dogs, and at relapse and in the sample prior to relapse in dogs with lymphoma. SAA was measured only once in the healthy control dogs. Results were analyzed using repeated measures ANOVA followed by Tukey multiple comparison tests to compare groups and weeks of treatment. RESULTS: Mean SAA concentration was significantly higher in dogs with lymphoma before chemotherapy compared with healthy and chemotherapy control dogs. No increase in SAA concentration was found at relapse. No differences were observed in SAA concentration based on type of chemotherapy protocol. CONCLUSIONS: SAA is not a marker of relapse in dogs with multicentric lymphoma, nor does chemotherapy regimen affect SAA concentration.

Serum C-reactive protein concentrations in dogs with multicentric lymphoma undergoing chemotherapy.

OBJECTIVE: To determine whether serum C-reactive protein (CRP) concentration is high in dogs with multicentric lymphoma, whether CRP concentration changes in response to chemotherapy, and whether CRP concentration can be used as a marker for relapse in dogs with multicentric lymphoma. DESIGN: Cohort study. ANIMALS: 20 dogs with multicentric lymphoma and 8 healthy control dogs undergoing chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) or with vincristine, cyclophosphamide, methotrexate, and L-asparaginase (VCMA) and 20 other healthy dogs. PROCEDURES: Serum CRP concentration was measured weekly during the first month of chemotherapy and then at 3-week intervals until relapse in dogs with multicentric lymphoma, weekly for 16 weeks in healthy dogs undergoing chemotherapy, and once in the healthy dogs not undergoing chemotherapy. RESULTS: For both groups of dogs with lymphoma, mean serum CRP concentration during week 1 (prior to treatment) was significantly higher than mean concentrations following induction of chemotherapy and at the time of relapse. Mean serum CRP concentration in the healthy dogs undergoing chemotherapy was not significantly different at any time from mean concentration for the healthy dogs not undergoing chemotherapy. No significant differences were observed between dogs treated with CVP and dogs treated with VCMA. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that serum CRP concentration is high in dogs with multicentric lymphoma but that serum CRP concentration is not a useful marker for relapse and that chemotherapy itself does not affect serum CRP concentration.