Re-Emergence of the Apicomplexan Theileria equi in the United States: Elimination of Persistent Infection and Transmission Risk

Abstract

Arthropod-borne apicomplexan pathogens that cause asymptomatic persistent infections present a significant challenge due to their life-long transmission potential. Although anti-microbials have been used to ameliorate acute disease in animals and humans, chemotherapeutic efficacy for apicomplexan pathogen elimination from a persistently infected host and removal of transmission risk is largely unconfirmed. The recent re-emergence of the apicomplexan Theileria equi in U.S. horses prompted testing whether imidocarb dipropionate was able to eliminate T. equi from naturally infected horses and remove transmission risk. Following imidocarb treatment, levels of T. equi declined from a mean of 104.9 organisms/ml of blood to undetectable by nested PCR in 24 of 25 naturally infected horses. Further, blood transfer from treated horses that became nested PCR negative failed to transmit to naïve splenectomized horses. Although these results were consistent with elimination of infection in 24 of 25 horses, T. equi-specific antibodies persisted in the majority of imidocarb treated horses. Imidocarb treatment was unsuccessful in one horse which remained infected as measured by nested PCR and retained the ability to infect a naïve recipient via intravenous blood transfer. However, a second round of treatment eliminated T. equi infection. These results support the utility of imidocarb chemotherapy for assistance in the control and eradication of this tick-borne pathogen. Successful imidocarb dipropionate treatment of persistently infected horses provides a tool to aid the global equine industry by removing transmission risk associated with infection and facilitating international movement of equids between endemic and non-endemic regions.

Extended-spectrum antiprotozoal bumped kinase inhibitors: A review

“…Although the continental USA was declared free of EP in 1988 (United States. Animal and Plant Health Inspection Service., 2008), several well-described outbreaks of T. equi have occurred recently in U.S. horses (Scoles, et al, 2011, Short, et al, 2012, Ueti, et al, 2012, United States. Animal and Plant Health Inspection Service., 2008).…”

“…Treatment of infected animals with the goal to clear infection and eliminate the risk of transmission represents a feasible strategy for disease control in some regions. Imidocarb dipropionate, a dicationic diamidine of the carbanilide series of antiprotozoal compounds, has been effective against some of the T. equi strains causing infections in U.S. horses (Ueti, et al, 2012), making it the current drug of choice. However, variable responses to imidocarb treatment occur in both natural and experimental T. equi infection (Butler, et al, 2008, Frerichs, et al, 1973, Grause, et al, 2013, Knowles, 1996, Kumar, et al, 2003, Kumar, et al, 2009, Kuttler, et al, 1987, Ueti, et al, 2012), and we have recently documented treatment failure associated with in vitro imidocarb resistance (Hines, et al, 2015).…”

“…These include spasmodic colic and diarrhea (Meyer, et al, 2005). Therefore, pretreatment with anticholinergic drugs such as atropine sulfate (Meyer, et al, 2005), glycopyrrolate (Donnellan, et al, 2013), or N-butylscopolammonium bromide (Ueti, et al, 2012) is required. Imidocarb injections are painful and local injection site reactions are common (Meyer, et al, 2005).…”

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

“…Tick-borne pathogens that result in persistent infections represent significant disease control challenges (7,8). Among these are the apicomplexan hemoprotozoan parasites Babesia caballi and Theileria equi that both cause equine piroplasmosis (EP) (9).…”

“…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). The failure of the CFT to detect all persistently infected horses with T. equi may have resulted in the reintroduction of this pathogen, leading to the recent outbreaks in the United States (2,8,12). In 2005, the CFT was replaced with the competitive enzyme-linked immunosorbent assay (cELISA) as the official regulatory test for EP.…”