Possible emergence of drug-resistant variants of Babesia gibsoni in clinical cases treated with atovaquone and azithromycin.

BACKGROUND

There is no well-established treatment strategy for Babesia gibsoni infection. A new therapeutic protocol using atovaquone (ATV) and azithromycin (AZM) has been proposed, but there is concern about the possible induction of relapse and the emergence of ATV-resistant variants after treatment.

OBJECTIVE

To evaluate the clinical use of combination therapy with ATV and AZM as a first-line treatment of clinical B. gibsoni infection in dogs, and to investigate the emergence of ATV-resistant variants.

ANIMALS

Eight B. gibsoni naturally infected dogs showing signs of acute onset of disease.

METHODS

Retrospective case study. Eight clinical cases received combination therapy with ATV and AZM at Kagoshima University Veterinary Teaching Hospital during 2007-2008, and their clinical courses and clinicopathological parameters were evaluated. In addition, alterations in the cytochrome b (CYTb) gene of B. gibsoni were analyzed by polymerase chain reaction and DNA sequencing techniques.

RESULTS

All of the dogs responded well to the treatment, with rapid improvement in their clinical condition and hematological parameters. However, 5 of the 8 dogs relapsed after treatment. Analysis of the CYTb gene strongly suggested the emergence of ATV-resistant variants after treatment.

CONCLUSIONS AND CLINICAL IMPORTANCE

The combination of ATV and AZM can be used as a first-line treatment for dogs with babesiosis, but relapses occur. Attention should be paid to the possible in vivo selection of drug-resistant variants.