Chemical Compatibility and Safety of Imidacloprid/Flumethrin Collar (Seresto®) Concomitantly Used with Imidacloprid/Moxidectin (Advocate®, Advantage® Multi) and Emodepside/Praziquantel (Profender®) Spot-on Formulations.

Safety of concomitant use of veterinary products is of clinical interest. A series of studies was performed to evaluate the chemical compatibility and short term dermal and systemic safety of an imidacloprid/flumethrin collar (Seresto(®)/ Foresto(®), Bayer) used concomitantly with spot-on or tablet formulations.Chemical compatibility was evaluated in-vitro (study reference A) on collar pieces, followed by two small, non-controlled clinical studies (study reference B) in both, cats and dogs. The studies showed, that certain solvents affected the collar in-vitro, but not in their marketed formulations.Dermal and systemic safety of different spot-on or tablet formulations was first evaluated in a small, non-controlled clinical study (study reference C) in cats and dogs, via clinical observations only, followed by controlled clinical safety studies of concomitant use with imidacloprid/ moxidectin (Advocate(®)/ Advantage(®) Multi, Bayer) in dogs and cats (study reference D) and emodepside/ praziquantel (Profender(®), Bayer) in cats (study reference E), assessing safety aspects by clinical observations and statistical analyses of hematology and clinical chemistry parameters compared to baseline values and between treated and control groups.Dermal safety findings over all clinical studies (study references B to E) matched those already described for the respective products and included transient cosmetic changes (oily hair and crystal formation) at the site of spot-on application and broken hair, transient alopecia and skin alterations at the site of collar application. There were no indications of these findings aggravating under the conditions of concurrent use. There were no systemic safety findings of clinical significance in any of the clinical safety studies (study reference C to E). Assessment of blood parameters revealed some deviations from baseline levels and from the reference range in dogs as well as in cats, but no clinical relevance could be deduced. Hematology and clinical chemistry results confirmed the safety of the concomitant treatment. It is concluded that Seresto(®) is chemically compatible with solvents used in major spot-on formulations on the market and is dermally and systemically safe for adult dogs and cats when used concomitantly with Advocate(®) and Profender(®) spot-on formulations.

Evaluation of blood and bone marrow in selected canine vector-borne diseases.

BACKGROUND: Bone marrow (BM) is a major hematopoietic organ that can harbour a variety of vector-borne pathogens; however, knowledge of BM pathological changes in dogs infected with vector-borne pathogens is limited. Thus, the aim of the present study was to assess the pathological changes in canine BM associated with natural infections by four vector-borne pathogens, as well as to determine the relationships between such changes and abnormalities of the peripheral blood. METHODS: Cytological disorders and pathological changes of the BM of 83 dogs naturally-infected with one or more of four vector-borne pathogens (i.e., Anaplasma platys, Leishmania infantum, Babesia vogeli and Hepatozoon canis) were evaluated and compared with the corresponding hematological findings. RESULTS: Dysgranulopoiesis and dysmegakaryocytopoiesis were the most frequently observed BM abnormalities in infected dogs. Erythroid suppression, and lymphocytic, monocytic and macrophage hyperplasia were also observed. Interestingly, associations between suppression and hyperplasia of specific cell lines in the marrow and corresponding changes in numbers of circulating peripheral blood cells were not observed. CONCLUSIONS: Infections with one or more of the vector-borne pathogens examined in this study should be considered as differential diagnoses for secondary dysmyelopoiesis.

Anaplasma platys in bone marrow megakaryocytes of young dogs.

Anaplasma platys is an obligate intracellular rickettsial pathogen that infects platelets of dogs, forming basophilic intracellular morulae. In the present report, cellular inclusions were documented in bone marrow thrombocyte precursors of two young naturally infected dogs, indicating that A. platys can infect megakaryocytes and promegakaryocytes.

A flea and tick collar containing 10% imidacloprid and 4.5% flumethrin prevents flea transmission of Bartonella henselae in cats.

BACKGROUND: Bartonella henselae is transmitted amongst cats by Ctenocephalides felis and is associated with multiple clinical syndromes in cats and people. In a previous study, monthly spot-on administration of 10% imidacloprid/1% moxidectin was shown to block transmission of B. henselae amongst cats experimentally exposed to infected C. felis. The purpose of this study was to determine whether application of a flea and tick collar containing 10% imidacloprid and 4.5% flumethrin would lessen C. felis transmission of B. henselae amongst cats for 8 months. METHODS: Specific pathogen free cats (n = 19) were housed in three adjoining enclosures that were separated by mesh to allow C. felis to pass among groups but prevent cats in different enclosures from contacting one another. One group of 4 cats was inoculated intravenously with B. henselae and after infection was confirmed in all cats based on positive PCR assay results, the cats were housed in the middle enclosure. The B. henselae infected cat group was flanked by a group of 8 cats that had the collar placed and maintained for the duration of the study and a group of 7 cats that were not treated. Ctenocephalides felis (50 males and 50 females) raised in an insectary were placed on each of the 4 cats in the B. henselae infected group monthly for 7 applications and then every 2 weeks for 4 applications starting the day the collar was applied. Blood was collected from all cats weekly for Bartonella spp. PCR, serology and culture. RESULTS: While side-effects associated with the collars were not noted, persistent fever necessitating enrofloxacin therapy occurred in two of the untreated cats. While B. henselae infection was ultimately confirmed in 4 of 7 of the untreated cats, none of the cats with collars became infected (P = 0.026). CONCLUSIONS: In this study design, use of a collar containing 10% imidacloprid and 4.5% flumethrin was well tolerated and prevented C. felis transmission of B. henselae amongst cats for 8 months.

Diagnosis of Hepatozoon canis in young dogs by cytology and PCR.

BACKGROUND: Hepatozoon canis is a widespread tick-borne protozoan affecting dogs. The diagnosis of H. canis infection is usually performed by cytology of blood or buffy coat smears, but this method may not be sensitive. Our study aimed to evaluate the best method to achieve a parasitological diagnosis of H. canis infection in a population of receptive young dogs, previously negative by cytology and exposed to tick infestation for one summer season. RESULTS: A total of 73 mongrel dogs and ten beagles younger than 18 months of age, living in an animal shelter in southern Italy where dogs are highly infested by Rhipicephalus sanguineus, were included in this study. In March-April 2009 and in October 2009, blood and bone marrow were sampled from each dog. Blood, buffy coat and bone marrow were examined by cytology only (at the first sampling) and also by PCR for H. canis (second sampling). In March-April 2009, only one dog was positive for H. canis by cytological examination, whereas in October 2009 (after the summer season), the overall incidence of H. canis infection by cytological examinations was 43.9%. Molecular tests carried out on samples taken in October 2009 showed a considerably higher number of dogs positive by PCR (from 27.7% up to 51.2% on skin and buffy coat tissues, respectively), with an overall positivity of 57.8%. All animals, but one, which were positive by cytology were also PCR-positive. PCR on blood or buffy coat detected the highest number of H. canis-positive dogs displaying a sensitivity of 85.7% for both tissues that increased up to 98% when used in parallel. Twenty-six (74.8%) out of the 28 H. canis-positive dogs presented hematological abnormalities, eosinophilia being the commonest alteration observed. CONCLUSIONS: The results suggest that PCR on buffy coat and blood is the best diagnostic assay for detecting H. canis infection in dogs, although when PCR is not available, cytology on buffy coat should be preferred to blood smear evaluation. This study has also demonstrated that H. canis infection can spread among young dogs infested by R. sanguineus and be present in the majority of the exposed population within 6 months.