title: 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: BACKGROUND
  Piroplasmosis 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.
  
  
  METHODS
  Fifty-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.
  
  
  RESULTS
  Before 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.
  
  
  CONCLUSIONS
  IMI 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.
authors.affiliation: Department of Animal Health, Veterinary Faculty, Universidad Complutense de Madrid, Avenida Puerta de Hierro s/n, 28040, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Checa
authors.affiliation: Department of Animal Health, Veterinary Faculty, Universidad Complutense de Madrid, Avenida Puerta de Hierro s/n, 28040, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Montoya
authors.affiliation: Department of Animal Health, Veterinary Faculty, Universidad Complutense de Madrid, Avenida Puerta de Hierro s/n, 28040, Madrid, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Ortega
authors.affiliation: Xarope Veterinary Centre, C/Santa Lucía 42, 15145, Laracha, Coruña, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: González-Fraga
authors.affiliation: Gran Vía Veterinary Centre, C/Gran Vía 194, 15102, Carballo, Coruña, Spain.
authors.forename: Adrián
authors.initials: A
authors.lastname: Bartolomé
authors.affiliation: Department of Animal Health, Veterinary Faculty, Universidad Complutense de Madrid, Avenida Puerta de Hierro s/n, 28040, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Gálvez
authors.affiliation: Department of Animal Health, Veterinary Faculty, Universidad Complutense de Madrid, Avenida Puerta de Hierro s/n, 28040, Madrid, Spain.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marino
authors.affiliation: Department of Animal Health, Veterinary Faculty, Universidad Complutense de Madrid, Avenida Puerta de Hierro s/n, 28040, Madrid, Spain. gmiro@ucm.es.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Miró
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053626:Atovaquone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D041001:Babesia microti / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D001404:Babesiosis / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D004283:Dog Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D004285:Dogs; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005260:Female; D007095:Imidocarb / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009285:Naphthoquinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018512:Parasitemia / Q000188:drug therapy / Q000453:epidemiology / Q000662:veterinary; D016133:Polymerase Chain Reaction
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; C046326:buparvaquone; D017963:Azithromycin; D007095:Imidocarb; D053626:Atovaquone; C031719:imidocarb dipropionate
keywords: Atovaquone; Azithromycin; Babesia microti-like piroplasm; Buparvaquone; Canine piroplasmosis; Imidocarb dipropionate; Therapeutic efficacy