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Robert H Mealey - One of the best experts on this subject based on the ideXlab platform.
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Theileria equi isolates vary in susceptibility to Imidocarb Dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor
Parasites & Vectors, 2015Co-Authors: Siddra A Hines, Joshua D Ramsay, Lowell S Kappmeyer, Audrey Ot Lau, Kayode K Ojo, Wesley C Van Voorhis, Donald P Knowles, Robert H MealeyAbstract:Background The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb Dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed. Methods We quantified the in vitro susceptibility of two T. equi isolates and a lab generated variant to both Imidocarb Dipropionate and a bumped kinase inhibitor compound 1294. We also evaluated the capacity of in vitro Imidocarb Dipropionate exposure to decrease susceptibility to that drug. The efficacy of Imidocarb Dipropionate for clearing infection in four T. equi infected ponies was also assessed. Results We observed an almost four-fold difference in Imidocarb Dipropionate susceptibility between two distinct isolates of T. equi . Four ponies infected with the less susceptible USDA Florida strain failed to clear the parasite despite two rounds of treatment. Importantly, a further 15-fold decrease in susceptibility was produced in this strain by continuous in vitro Imidocarb Dipropionate exposure. Despite a demonstrated difference in Imidocarb Dipropionate susceptibility, there was no difference in the susceptibility of two T. equi isolates to bumped kinase inhibitor 1294. Conclusions The observed variation in Imidocarb Dipropionate susceptibility, further reduction in susceptibility caused by drug exposure in vitro , and failure to clear T. equi infection in vivo , raises concern for the emergence of drug resistance in clinical cases undergoing treatment. Bumped kinase inhibitors may be effective as alternative drugs for the treatment of resistant T. equi parasites.
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Theileria equi isolates vary in susceptibility to Imidocarb Dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor.
Parasites & Vectors, 2015Co-Authors: Siddra A Hines, Joshua D Ramsay, Lowell S Kappmeyer, Audrey Ot Lau, Kayode K Ojo, Wesley C Van Voorhis, Donald P Knowles, Robert H MealeyAbstract:Background The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb Dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed.
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re emergence of the apicomplexan theileria equi in the united states elimination of persistent infection and transmission risk
PLOS ONE, 2012Co-Authors: Lowell S Kappmeyer, Robert H Mealey, Massaro W. Ueti, Juanita F. Grause, Stephen N White, Nancy Kumpulamcwhirter, Angela M Pelzel, Thomas O. BunnAbstract: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 naive 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 naive 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.
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Re-emergence of the apicomplexan Theileria equi in the United States: elimination of persistent infection and transmission risk
2012Co-Authors: Massaro W. Ueti, Robert H Mealey, Juanita F. Grause, Thomas O. Bunn, Stephen N White, Angela M Pelzel, Nancy Kumpula, Andy Schwartz, Josie L. Traub, Amy HendricksonAbstract: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 o
Lowell S Kappmeyer - One of the best experts on this subject based on the ideXlab platform.
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Theileria equi isolates vary in susceptibility to Imidocarb Dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor
Parasites & Vectors, 2015Co-Authors: Siddra A Hines, Joshua D Ramsay, Lowell S Kappmeyer, Audrey Ot Lau, Kayode K Ojo, Wesley C Van Voorhis, Donald P Knowles, Robert H MealeyAbstract:Background The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb Dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed. Methods We quantified the in vitro susceptibility of two T. equi isolates and a lab generated variant to both Imidocarb Dipropionate and a bumped kinase inhibitor compound 1294. We also evaluated the capacity of in vitro Imidocarb Dipropionate exposure to decrease susceptibility to that drug. The efficacy of Imidocarb Dipropionate for clearing infection in four T. equi infected ponies was also assessed. Results We observed an almost four-fold difference in Imidocarb Dipropionate susceptibility between two distinct isolates of T. equi . Four ponies infected with the less susceptible USDA Florida strain failed to clear the parasite despite two rounds of treatment. Importantly, a further 15-fold decrease in susceptibility was produced in this strain by continuous in vitro Imidocarb Dipropionate exposure. Despite a demonstrated difference in Imidocarb Dipropionate susceptibility, there was no difference in the susceptibility of two T. equi isolates to bumped kinase inhibitor 1294. Conclusions The observed variation in Imidocarb Dipropionate susceptibility, further reduction in susceptibility caused by drug exposure in vitro , and failure to clear T. equi infection in vivo , raises concern for the emergence of drug resistance in clinical cases undergoing treatment. Bumped kinase inhibitors may be effective as alternative drugs for the treatment of resistant T. equi parasites.
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Theileria equi isolates vary in susceptibility to Imidocarb Dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor.
Parasites & Vectors, 2015Co-Authors: Siddra A Hines, Joshua D Ramsay, Lowell S Kappmeyer, Audrey Ot Lau, Kayode K Ojo, Wesley C Van Voorhis, Donald P Knowles, Robert H MealeyAbstract:Background The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb Dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed.
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Efficacy of Imidocarb Dipropionate in eliminating Theileria equi from experimentally infected horses.
Veterinary journal (London England : 1997), 2012Co-Authors: Juanita F. Grause, Lowell S Kappmeyer, Donald P Knowles, Massaro W. Ueti, Jeffrey T. Nelson, Thomas O. BunnAbstract:Abstract Theileria equi, one of the causative agents of equine piroplasmosis, is endemic in many regions of the world but is considered a ‘foreign’ animal disease in the USA. In an effort to prevent the importation of T. equi, stringent serological screening of horses is practiced prior to entry to the USA. Current regulatory options available where horses are found to be infected include permanent quarantine with or without chemotherapy, repatriation, or euthanasia. Chemotherapeutics that eliminate infection and subsequently transmission risk are critical in the management of infected horses. In this study, the efficacy of the drug Imidocarb Dipropionate against experimental T. equi infection was assessed. Of nine horses experimentally inoculated with T. equi isolated from an animal previously imported from Peru, six were treated with Imidocarb Dipropionate after the resolution of the acute phase of the disease. Elimination of the parasite was demonstrated in 5/6 by nested PCR, blood transfusions to naive horses, and reversion to seronegative status. The findings support the use of this drug as a potential treatment option in controlling outbreaks of T. equi, and also suggest that ‘combination testing’ using both serological and PCR detection methods are necessary to demonstrate clearance of infection.
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re emergence of the apicomplexan theileria equi in the united states elimination of persistent infection and transmission risk
PLOS ONE, 2012Co-Authors: Lowell S Kappmeyer, Robert H Mealey, Massaro W. Ueti, Juanita F. Grause, Stephen N White, Nancy Kumpulamcwhirter, Angela M Pelzel, Thomas O. BunnAbstract: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 naive 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 naive 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.
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Imidocarb Dipropionate Clears Persistent Babesia caballi Infection with Elimination of Transmission Potential
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: O. Nicolas Schwint, Lowell S Kappmeyer, Donald P Knowles, Massaro W. Ueti, Guy H. Palmer, Melissa T. Hines, R. Timothy Cordes, Glen A. ScolesAbstract: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.
Saroj Kumar - One of the best experts on this subject based on the ideXlab platform.
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in vitro growth inhibitory efficacy of some target specific novel drug molecules against theileria equi
Veterinary Parasitology, 2016Co-Authors: A Gopalakrishnan, C Maji, Rajesh K Dahiya, Amitabh B Suthar, Rajender Kumar, A K Gupta, Umesh Dimri, Saroj KumarAbstract:The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide (HDTAB), hesparidin methyl chalcone (HMC), andrographolide and Imidocarb Dipropionate against T. equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and Imidocarb Dipropionate for T. equi growth were 17.42 μM, 14.00 μM, 246.34 μM and 0.279 μM (equivalent to 0.139 μg/ml), respectively (P<0.05). The andrographolide was not effective in inhibiting in vitro growth of T. equi in the present study. Furthermore, the in vitro cytotoxicity of these five drugs was evaluated on horse PBMC. At 2000 μM concentration of HHD, HDTAB, HMC, andrographolide and Imidocarb Dipropionate were 8.34, 46.44, 58.53, 31.06, 15.14% cytotoxic on PBMC, respectively. Out of our four tested drug molecules, HHD was having low IC50 value along with least cytotoxicity, as compared to reference drug Imidocarb Dipropionate. The difference in IC50 value of HDTAB and HHD was significant, but HDTAB was moderately more cytotoxic on PBMC cell lines. HHD and HDTAB are selective inhibitor for heat shock protein 90 (Hsp90) and choline kinase pathway. It can be concluded that HHD and HDTAB are potential drug molecules against T. equi parasite by acting on Hsp90 and choline kinase pathway.
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In vitro growth inhibitory efficacy of some target specific novel drug molecules against Theileria equi.
Veterinary parasitology, 2015Co-Authors: A Gopalakrishnan, C Maji, Rajesh K Dahiya, Amitabh B Suthar, Rajender Kumar, A K Gupta, Umesh Dimri, Saroj KumarAbstract:The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide (HDTAB), hesparidin methyl chalcone (HMC), andrographolide and Imidocarb Dipropionate against T. equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and Imidocarb Dipropionate for T. equi growth were 17.42 μM, 14.00 μM, 246.34 μM and 0.279 μM (equivalent to 0.139 μg/ml), respectively (P
A Gopalakrishnan - One of the best experts on this subject based on the ideXlab platform.
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lumefantrine and o choline parasite metabolism specific drug molecules inhibited in vitro growth of theileria equi and babesia caballi in masp culture system
Ticks and Tick-borne Diseases, 2019Co-Authors: C Maji, A Gopalakrishnan, Amitabh B Suthar, Rajender Kumar, Praveen Goel, Kruti D Mandal, B N Tripathi, Sanjay KumarAbstract:Abstract Theileria equi and Babesia caballi are tick-borne apicomplexan haemoprotozoan parasites of equines and are responsible for considerable economic losses to stakeholders. Chemotherapeutic drugs that are available not only require multiple dosages but also prompt multiple organ toxicity in treated host though incapable of clearing parasitaemia completely. In this study, we have screened the in vitro inhibitory efficacy of four different drug molecules (o-choline, DABCO®, lumefantrine and eugenol) against T. equi and B. caballi, targeting different parasite metabolism pathways. Imidocarb Dipropionate and diminazene aceturate were used as reference control drugs. The 50% in vitro growth inhibitory concentration (IC50) of lumefantrine, o-choline, DABCO® and eugenol for T. equi were: 30.90 μM; 84.38 μM; 443 μM; 120 μM and for B. caballi growth inhibition were: 5.58 μM; 135.29 μM; 150 μM; 197.05 μM, respectively. Imidocarb Dipropionate inhibited the in vitro growth of T. equi at IC50 of 257.5 nM, while diminazene aceturate inhibited the in vitro growth of B. caballi at IC50 of 22 nM. DABCO® and eugenol were not so effective in inhibiting the in vitro growth of T. equi and B. caballi, while lumefantrine and o-choline significantly (p ≤ 0.05) inhibited the in vitro growth of these piroplasms targeting haem digestion and parasite membrane phospholipid synthesis.
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in vitro growth inhibitory efficacy of some target specific novel drug molecules against theileria equi
Veterinary Parasitology, 2016Co-Authors: A Gopalakrishnan, C Maji, Rajesh K Dahiya, Amitabh B Suthar, Rajender Kumar, A K Gupta, Umesh Dimri, Saroj KumarAbstract:The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide (HDTAB), hesparidin methyl chalcone (HMC), andrographolide and Imidocarb Dipropionate against T. equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and Imidocarb Dipropionate for T. equi growth were 17.42 μM, 14.00 μM, 246.34 μM and 0.279 μM (equivalent to 0.139 μg/ml), respectively (P<0.05). The andrographolide was not effective in inhibiting in vitro growth of T. equi in the present study. Furthermore, the in vitro cytotoxicity of these five drugs was evaluated on horse PBMC. At 2000 μM concentration of HHD, HDTAB, HMC, andrographolide and Imidocarb Dipropionate were 8.34, 46.44, 58.53, 31.06, 15.14% cytotoxic on PBMC, respectively. Out of our four tested drug molecules, HHD was having low IC50 value along with least cytotoxicity, as compared to reference drug Imidocarb Dipropionate. The difference in IC50 value of HDTAB and HHD was significant, but HDTAB was moderately more cytotoxic on PBMC cell lines. HHD and HDTAB are selective inhibitor for heat shock protein 90 (Hsp90) and choline kinase pathway. It can be concluded that HHD and HDTAB are potential drug molecules against T. equi parasite by acting on Hsp90 and choline kinase pathway.
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In vitro growth inhibitory efficacy of some target specific novel drug molecules against Theileria equi.
Veterinary parasitology, 2015Co-Authors: A Gopalakrishnan, C Maji, Rajesh K Dahiya, Amitabh B Suthar, Rajender Kumar, A K Gupta, Umesh Dimri, Saroj KumarAbstract:The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide (HDTAB), hesparidin methyl chalcone (HMC), andrographolide and Imidocarb Dipropionate against T. equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and Imidocarb Dipropionate for T. equi growth were 17.42 μM, 14.00 μM, 246.34 μM and 0.279 μM (equivalent to 0.139 μg/ml), respectively (P
Donald P Knowles - One of the best experts on this subject based on the ideXlab platform.
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Imidocarb Dipropionate lacks efficacy against theileria haneyi and fails to consistently clear theileria equi in horses co infected with t haneyi
Pathogenetics, 2020Co-Authors: Kelly P Sears, Donald P Knowles, Kelcey D Dinkel, Philip W Mshelia, Cynthia Onzere, Marta G Silva, Lindsay M FryAbstract:Control of Theileria equi, the primary cause of equine theileriosis, is largely reliant on acaracide use and chemosterilization with Imidocarb Dipropionate (ID). However, it is currently unknown if ID is effective against Theileria haneyi, the recently identified second causative agent of equine theileriosis, or if the drug maintains effectiveness against T. equi in the presence of T. haneyi co-infection. The purpose of this study was to address these questions using ID treatment of the following three groups of horses: (1) five T. haneyi infected horses; (2) three T. haneyi-T. equi infected horses; and (3) three T. equi-T. haneyi infected horses. Clearance was first evaluated using nPCR for each Theileria sp. on peripheral blood samples. ID failed to clear T. haneyi in all three groups of horses, and failed to clear T. equi in two of three horses in group two. For definitive confirmation of infection status, horses in groups two and three underwent splenectomy post-treatment. The T. equi-nPCR-positive horses in group two developed severe clinical signs and were euthanized. Remaining horses exhibited moderate signs consistent with T. haneyi. Our results demonstrate that ID therapy lacks efficacy against T. haneyi, and T. haneyi-T. equi co-infection may interfere with ID clearance of T. equi.
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Theileria equi isolates vary in susceptibility to Imidocarb Dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor
Parasites & Vectors, 2015Co-Authors: Siddra A Hines, Joshua D Ramsay, Lowell S Kappmeyer, Audrey Ot Lau, Kayode K Ojo, Wesley C Van Voorhis, Donald P Knowles, Robert H MealeyAbstract:Background The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb Dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed. Methods We quantified the in vitro susceptibility of two T. equi isolates and a lab generated variant to both Imidocarb Dipropionate and a bumped kinase inhibitor compound 1294. We also evaluated the capacity of in vitro Imidocarb Dipropionate exposure to decrease susceptibility to that drug. The efficacy of Imidocarb Dipropionate for clearing infection in four T. equi infected ponies was also assessed. Results We observed an almost four-fold difference in Imidocarb Dipropionate susceptibility between two distinct isolates of T. equi . Four ponies infected with the less susceptible USDA Florida strain failed to clear the parasite despite two rounds of treatment. Importantly, a further 15-fold decrease in susceptibility was produced in this strain by continuous in vitro Imidocarb Dipropionate exposure. Despite a demonstrated difference in Imidocarb Dipropionate susceptibility, there was no difference in the susceptibility of two T. equi isolates to bumped kinase inhibitor 1294. Conclusions The observed variation in Imidocarb Dipropionate susceptibility, further reduction in susceptibility caused by drug exposure in vitro , and failure to clear T. equi infection in vivo , raises concern for the emergence of drug resistance in clinical cases undergoing treatment. Bumped kinase inhibitors may be effective as alternative drugs for the treatment of resistant T. equi parasites.
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Theileria equi isolates vary in susceptibility to Imidocarb Dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor.
Parasites & Vectors, 2015Co-Authors: Siddra A Hines, Joshua D Ramsay, Lowell S Kappmeyer, Audrey Ot Lau, Kayode K Ojo, Wesley C Van Voorhis, Donald P Knowles, Robert H MealeyAbstract:Background The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb Dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed.
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Efficacy of Imidocarb Dipropionate in eliminating Theileria equi from experimentally infected horses.
Veterinary journal (London England : 1997), 2012Co-Authors: Juanita F. Grause, Lowell S Kappmeyer, Donald P Knowles, Massaro W. Ueti, Jeffrey T. Nelson, Thomas O. BunnAbstract:Abstract Theileria equi, one of the causative agents of equine piroplasmosis, is endemic in many regions of the world but is considered a ‘foreign’ animal disease in the USA. In an effort to prevent the importation of T. equi, stringent serological screening of horses is practiced prior to entry to the USA. Current regulatory options available where horses are found to be infected include permanent quarantine with or without chemotherapy, repatriation, or euthanasia. Chemotherapeutics that eliminate infection and subsequently transmission risk are critical in the management of infected horses. In this study, the efficacy of the drug Imidocarb Dipropionate against experimental T. equi infection was assessed. Of nine horses experimentally inoculated with T. equi isolated from an animal previously imported from Peru, six were treated with Imidocarb Dipropionate after the resolution of the acute phase of the disease. Elimination of the parasite was demonstrated in 5/6 by nested PCR, blood transfusions to naive horses, and reversion to seronegative status. The findings support the use of this drug as a potential treatment option in controlling outbreaks of T. equi, and also suggest that ‘combination testing’ using both serological and PCR detection methods are necessary to demonstrate clearance of infection.
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Imidocarb Dipropionate Clears Persistent Babesia caballi Infection with Elimination of Transmission Potential
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: O. Nicolas Schwint, Lowell S Kappmeyer, Donald P Knowles, Massaro W. Ueti, Guy H. Palmer, Melissa T. Hines, R. Timothy Cordes, Glen A. ScolesAbstract: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.
