Imidocarb Dipropionate Clears PersistentBabesia caballiInfection 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.

Clinical, haematological and therapeutic studies on babesiosis in Arabian horses in the Qassim region, central of Saudi Arabia

“…Treatment results revealed that early intervention using imidocarb dipropionatein in conjunction with supportive treatments as phosphorous and vitamin B12 and two liters of 10% dextrose saline was highly efficient. Similar results were obtained previously by Bruning (1996), de Wall (1990, Friedhoff and Soule (1996) and Schwint et al (2009). Forty percent of the treated horses showed side effects in the form of salivation, colic and sometimes recumbence.…”

Serum Antibodies from a Subset of Horses Positive for Babesia caballi by Competitive Enzyme-Linked Immunosorbent Assay Demonstrate a Protein Recognition Pattern That Is Not Consistent with Infection

“…The observation that none of the recipient horses became infected with B. caballi suggests that the U.S. horses were not infected with a B. caballi-divergent isolate. Importantly, our previous study demonstrated that blood from carrier horses with B. caballi successfully infected naive seronegative recipient horses via blood transfusion (6).…”

“…The restriction of movement is based on the identification of infected animals by direct and indirect methods (5,6). However, several diagnostic assays have failed to detect all infected animals due to a lack of sensitivity in the diagnostic tests, pathogen mutation or recombination, or deficiencies in host immunity (6,23).…”

“…Several serological tests are used to identify horses infected with B. caballi and T. equi. However, they have various degrees of specificity and sensitivity (5,6,13). The complement fixation test (CFT) was the official regulatory test in the United States until it was determined to yield an unacceptable number of false-negative results due to the inability of equine IgG subclass 5 to fix complement (14,15).…”

“…Importation of animals and animal by-products from areas with a high prevalence of infectious agents is tightly regulated, and imported animals are screened and quarantined at all entry points for further testing and evaluation (4). Both direct and indirect diagnostic tests are performed to determine infection status, and the use of these tests to prohibit the entrance of infected animals into areas where pathogens are nonendemic has been critical in preventing disease outbreaks (5,6).…”