Efficacy, safety and tolerance of imidocarb dipropionate versus atovaquone or buparvaquone plus azithromycin used to treat sick dogs naturally infected with the Babesia microti-like piroplasm

Abstract

BackgroundPiroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml.MethodsFifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity.ResultsBefore treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result.ConclusionsIMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended. The treatments ATO and BUP showed better efficacy, though they were still incapable to completely eliminate PCR-proven infection at the recommended dose. All three treatments showed good tolerance and safety with scarce adverse events observed.

Prevalence of Babesia spp. and clinical characteristics of Babesia vulpes infections in North American dogs

“…Treatment with atovaquone (13.5 mg/kg PO q8h) and azithromycin (10 mg/kg PO q24h) for 10 days was recommended for all dogs as soon as the B. vulpes infection was diagnosed. Follow‐up data were available for 9 dogs, all of which were clinically improved after treatment.…”

“…Although limited information was available, we observed that dogs infected with B. vulpes , with or without concurrent B. gibsoni infection, exhibited a range of laboratory abnormalities similar to those previously reported with other Babesia spp. infections, including regenerative anemia, thrombocytopenia, hyperglobulinemia, hypoalbuminemia, and proteinuria. Azotemia, although previously reported as a common complication for dogs infected with B. vulpes in Europe, was not common in the dogs in our study.…”

Targeting Channels and Transporters in Protozoan Parasite Infections

“…in vitro and in vivo in hamsters (Hughes and Oz, 1995 ; Wittner et al, 1996 ; Matsuu et al, 2008 ). In dog and human studies, combination with the antibiotic azithromycin turned out to be positive (Krause et al, 2000 ; Birkenheuer et al, 2004 ; Di Cicco et al, 2012 ; Checa et al, 2017 ). Treatment of L. donovani infections in a mouse model were less successful resulting only in a 30% lower parasite burden (Croft et al, 1992 ).…”

Overview of Canine Babesiosis

“…It is approved for treatment of different forms of Babesia spp. [39,57,63]. The adverse effects of this medication include pain during injection and cholinergic effects such as salivation, drooling, nasal drip or vomiting which can be mitigated by premedicating with atropine at 0.05 mg/kg.…”

“…Buparvaquone (Butalex ® ) is used in the treatment of bovine theileriosis [69]. It is also used to treat B. vulpes infection in dogs at an off-label dose of 5 mg/kg IM twice 48 h apart, in combination with azithromycin at 10 mg/kgPO once daily for 10 days [63]. Buparvaquone's mode of action on piroplasms is probably comparable to atovaquone's.…”