Verification of post-chemotherapeutic clearance of Theileria equi through concordance of nested PCR and immunoblot

Wise, L.N.; Kappmeyer, Lowell S.; Silva, MG; White, S.N.; Grause, JF; Dp, Knowles

doi:10.1016/j.ttbdis.2017.08.007

Cited by 20 publications

(18 citation statements)

References 22 publications

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“…The T. equi cELISA, and nPCR for T. equi and T. haneyi were utilized prior to splenectomy to assess infection status since horses in all experimental groups remained largely asymptomatic. In general, horses that have been successfully treated for Texas-isolates of T. equi exhibit a decline in cELISA values over time [19,23]. However, even when infection is eliminated, it can take years for the cELISA values to fall below the 40% positive cut-off [23].…”

Section: Imidocarb Dipropionate Fails To Clear T Equi In a Subset Ofmentioning

confidence: 99%

“…These side effects are often ameliorated using co-administration of anticholinergic and anti-spasmodic medications [18,21,22]. In equine piroplasmosis, chemosterilization, or clearance, is defined by inability to detect organisms using nested PCR (nPCR) assays and/or failure to transmit the organism to a naïve, splenectomized horse via whole blood transfer [7,23]. However, neither of the aforementioned criteria are utilized by the United States or by the OIE as definitive tests for importation [3,23].…”

Section: Introductionmentioning

confidence: 99%

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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<b></b>

Sears

Knowles

Dinkel

et al. 2020

Preprint

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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 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 2/3 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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Section: Imidocarb Dipropionate Fails To Clear T Equi In a Subset Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Imidocarb Dipropionate Lacks Efficacy Against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-infected with T. haneyi<b></b>

Sears

Knowles

Dinkel

et al. 2020

Preprint

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“…Tick-borne diseases caused by apicomplexan hemoparasites, such as Babesia and Theileria, impose serious economic impact on the cattle and horse industries worldwide [1,2]. Babesiosis and theileriosis share similar acute disease signs, including loss of weight, anorexia and fever.…”

Section: Introductionmentioning

confidence: 99%

Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi

Suárez

Silva

Bastos

et al. 2020

Preprint

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Background: The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. Endochin-like quinolones (ELQ)-300 and ELQ-316 proved safe and efficacious against related apicomplexans, such as Plasmodium spp., and ELQ-316 was also effective against B. microti, without showing toxicity in mammals.Methods: Inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. Percentage of parasitized erythrocytes was measured by flow cytometry. Effect of the ELQ drugs on the viability of actively replicating horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by ELISA. Results: We calculated IC50 ranging from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 at 72 hr among all cultured parasites tested. None of the parasites tested were able to replicate in cultures in the presence of the ELQs-300 and ELQ-316 at IC100, which range from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 hours. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing. Conclusions: ELQ-300 and ELQ-316 have a significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.

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Section: Introductionmentioning

confidence: 99%

Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi

Silva

Bastos

Doggett

et al. 2020

Preprint

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Background: The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. Endochin-like quinolones (ELQ)-300 and ELQ-316 proved safe and efficacious against related apicomplexans, such as Plasmodium spp., and ELQ-316 was also effective against B. microti, without showing toxicity in mammals.Methods: Inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. Percentage of parasitized erythrocytes was measured by flow cytometry. Effect of the ELQ drugs on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay.Results: We calculated IC50 ranging from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 at 72 h among all cultured parasites tested. None of the parasites tested were able to replicate in cultures in the presence of the ELQ-300 and ELQ-316 at IC100, which range from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing. Conclusions: ELQ-300 and ELQ-316 showed significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.

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Verification of post-chemotherapeutic clearance of Theileria equi through concordance of nested PCR and immunoblot

Cited by 20 publications

References 22 publications

Imidocarb Dipropionate Lacks Efficacy Against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-infected with T. haneyi<b></b>

Imidocarb Dipropionate Lacks Efficacy Against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-infected with T. haneyi<b></b>

Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi

Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi

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