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Antimicrobial Agents and Chemotherapy, October 2009, p. 4327-4332, Vol. 53, No. 10
0066-4804/09/$08.00+0 doi:10.1128/AAC.00404-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Imidocarb Dipropionate Clears Persistent Babesia caballi Infection with Elimination of Transmission Potential
O. Nicolas Schwint,1
Massaro W. Ueti,1
Guy H. Palmer,1
Lowell S. Kappmeyer,2
Melissa T. Hines,3
R. Timothy Cordes,4
Donald P. Knowles,1,2* and
Glen A. Scoles2
Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, School for Global Animal Heath, Washington State University, Pullman, Washington 99164-7040,1 Animal Disease Research Unit, U.S. Department of Agriculture, Agricultural Research Service, Pullman, Washington 99164-6630,2 Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington 99164-7010,3 National Equine Programs, U.S. Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services, Riverdale, Maryland 20737-12344
Received 26 March 2009/ Returned for modification 9 June 2009/ Accepted 14 July 2009
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.
* Corresponding author. Mailing address: Animal Disease Research Unit, ARS-USDA-PWA, 3005 ADBF, Washington State University, Pullman, WA 99164-6630. Phone: (509) 335-6022. Fax: (509) 335-8328. E-mail: dknowles{at}vetmed.wsu.edu
Published ahead of print on 20 July 2009.
Antimicrobial Agents and Chemotherapy, October 2009, p. 4327-4332, Vol. 53, No. 10
0066-4804/09/$08.00+0 doi:10.1128/AAC.00404-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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