The in vitro interactions and in vivo efficacy of atovaquone and proguanil against Babesia gibsoni infection in dogs.

In vitro interactions between atovaquone (ATV) and proguanil (PG) against Babesia gibsoni and the clinical efficacy of this combination therapy using Malarone(®) which is the antimalarial drug containing ATV and PG were evaluated. This combination showed synergism against uncloned wild-type and ATV-resistant B. gibsoni in vitro examinations using a modified fixed ratio method. Administration of Malarone(®) to experimentally B. gibsoni infected two dogs in chronic stage and three dogs in acute stage resulted in decrease in parasitemia, and clinical improvements were observed. However, all dogs showed relapse of parasitic infection with a single-nucleotide polymorphism in the cytchrome b gene (M121I). Some side effects were confirmed: self-limiting vomiting in two dogs and hyperphosphatasia in another dog. Mild increases in the levels of alanine aminotransferase were confirmed in two dogs. This is the first study to evaluate the interactions in vitro and the clinical efficacy of ATV and PG against canine B. gibsoni infection in dogs.