title: Imidocarb dipropionate clears persistent Babesia caballi infection with elimination of transmission potential.
abstract: Antimicrobial treatment of persistent infection to eliminate transmission risk represents a specific challenge requiring compelling evidence of complete pathogen clearance. The limited repertoire of antimicrobial agents targeted at protozoal parasites magnifies this challenge. Using Babesia caballi as both a model and a specific apicomplexan pathogen for which evidence of the elimination of transmission risk is required for international animal movement, we tested whether a high-dose regimen of imidocarb dipropionate cleared infection from persistently infected asymptomatic horses and/or eliminated transmission risk. Clearance with elimination of transmission risk was supported by the following four specific lines of evidence: (i) inability to detect parasites by quantitative PCR and nested PCR amplification, (ii) conversion from seropositive to seronegative status, (iii) inability to transmit infection by direct inoculation of blood into susceptible recipient horses, and (iv) inability to transmit infection by ticks acquisition fed on the treated horses and subsequently transmission fed on susceptible horses. In contrast, untreated horses remained infected and capable of transmitting B. caballi using the same criteria. These findings establish that imidocarb dipropionate treatment clears B. caballi infection with confirmation of lack of transmission risk either by direct blood transfer or a high tick burden. Importantly, the treated horses revert to seronegative status according to the international standard for serologic testing and would be permitted to move between countries where the pathogen is endemic and countries that are free of the pathogen.
authors.affiliation: Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, School for Global Animal Heath, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: O Nicolas
authors.initials: ON
authors.lastname: Schwint
authors.forename: Massaro W
authors.initials: MW
authors.lastname: Ueti
authors.forename: Guy H
authors.initials: GH
authors.lastname: Palmer
authors.forename: Lowell S
authors.initials: LS
authors.lastname: Kappmeyer
authors.forename: Melissa T
authors.initials: MT
authors.lastname: Hines
authors.forename: R Timothy
authors.initials: RT
authors.lastname: Cordes
authors.forename: Donald P
authors.initials: DP
authors.lastname: Knowles
authors.forename: Glen A
authors.initials: GA
authors.lastname: Scoles
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001403:Babesia / Q000187:drug effects* / Q000472:pathogenicity*; D001404:Babesiosis / Q000188:drug therapy* / Q000382:microbiology / Q000635:transmission*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D006736:Horses; D007095:Imidocarb / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013987:Ticks / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D007095:Imidocarb; C031719:imidocarb dipropionate