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 10(4.9) 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.
Publication Date: 2012-09-06 PubMed ID: 22970295PubMed Central: PMC3435266DOI: 10.1371/journal.pone.0044713Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research looks into the use of imidocarb dipropionate to eliminate the re-emerging apicomplexan Theileria equi in horses, in order to stop its transmission. The experiments indicate that the chemical was predominately successful in eradicating the pathogen with minimal side effects, hence reducing transmission risk.
Challenges of Asymptomatic Persistent Infections
- Arthropod-borne apicomplexan pathogens cause asymptomatic persistent infections, posing a significant challenge due to their life-long transmission potential.
- Despite the use of anti-microbials to minimize acute disease in animals, the efficacy of chemotherapy in pathogen elimination and removing transmission risk remains largely unconfirmed.
Re-emergence of Theileria equi
- Theileria equi, a type of apicomplexan, has recently re-emerged in horses in the United States, raising the need to verify the effectiveness of imidocarb dipropionate in eliminating this microorganism from naturally infected horses and alleviating transmission risk.
Effect of Imidocarb Dipropionate on T. equi
- The study shows that after imidocarb treatment, T. equi levels declined to undetectable levels by nested PCR in 24 out of 25 naturally infected horses.
- Blood transferred from treated horses that tested negative for T. equi failed to transmit the pathogen to healthy splenectomized horses, suggesting the elimination of the infection in the majority of instances.
- However, T. equi-specific antibodies continued to exist in most of the imidocarb-treated horses and the treatment was ineffective in one horse which remained infected. This horse could still infect a healthy recipient animal through intravenous blood transfer.
Second Round of Treatment and Implications
- Upon administering a second round of imidocarb treatments, successful elimination of T. equi infection was observed in the previously treatment-resistant horse.
- This supports the applicability of imidocarb chemotherapy not just in the control of, but also potentially in the eradication of this tick-borne pathogen. It provides a method to aid the global equine industry by eliminating transmission risk associated with infection.
- This successful treatment of persistently infected horses could facilitate the international movement of equids between endemic and non-endemic regions.
Cite This Article
APA
Ueti MW, Mealey RH, Kappmeyer LS, White SN, Kumpula-McWhirter N, Pelzel AM, Grause JF, Bunn TO, Schwartz A, Traub-Dargatz JL, Hendrickson A, Espy B, Guthrie AJ, Fowler WK, Knowles DP.
(2012).
Re-emergence of the apicomplexan Theileria equi in the United States: elimination of persistent infection and transmission risk.
PLoS One, 7(9), e44713.
https://doi.org/10.1371/journal.pone.0044713 Publication
Researcher Affiliations
- Animal Diseases Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, Washington, United States of America. massaro@vetmed.wsu.edu
MeSH Terms
- Animals
- Antiprotozoal Agents / therapeutic use
- Female
- Horse Diseases / drug therapy
- Horse Diseases / epidemiology
- Horse Diseases / parasitology
- Horse Diseases / transmission
- Horses
- Imidocarb / analogs & derivatives
- Imidocarb / therapeutic use
- Polymerase Chain Reaction
- Risk Factors
- Theileria / isolation & purification
- Theileriasis / epidemiology
- Theileriasis / parasitology
- Theileriasis / transmission
- United States / epidemiology
Conflict of Interest Statement
The authors have declared that no competing interests exist.
References
This article includes 35 references
- Palacpac NM, Leung BW, Arisue N, Tanabe K, Sattabongkot J, Tsuboi T, Torii M, Udomsangpetch R, Horii T. Plasmodium vivax serine repeat antigen (SERA) multigene family exhibits similar expression patterns in independent infections.. Mol Biochem Parasitol 2006 Dec;150(2):353-8.
- Futse JE, Brayton KA, Dark MJ, Knowles DP Jr, Palmer GH. Superinfection as a driver of genomic diversification in antigenically variant pathogens.. Proc Natl Acad Sci U S A 2008 Feb 12;105(6):2123-7.
- Gardner CL, Ryman KD. Yellow fever: a reemerging threat.. Clin Lab Med 2010 Mar;30(1):237-60.
- Sardelis MR, Turell MJ, Dohm DJ, O'Guinn ML. Vector competence of selected North American Culex and Coquillettidia mosquitoes for West Nile virus.. Emerg Infect Dis 2001 Nov-Dec;7(6):1018-22.
- Vasconcelos PF, Bryant JE, da Rosa TP, Tesh RB, Rodrigues SG, Barrett AD. Genetic divergence and dispersal of yellow fever virus, Brazil.. Emerg Infect Dis 2004 Sep;10(9):1578-84.
- Luz PM, Vanni T, Medlock J, Paltiel AD, Galvani AP. Dengue vector control strategies in an urban setting: an economic modelling assessment.. Lancet 2011 May 14;377(9778):1673-80.
- Ranson H, N'guessan R, Lines J, Moiroux N, Nkuni Z, Corbel V. Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?. Trends Parasitol 2011 Feb;27(2):91-8.
- Turell MJ, Dohm DJ, Sardelis MR, Oguinn ML, Andreadis TG, Blow JA. An update on the potential of north American mosquitoes (Diptera: Culicidae) to transmit West Nile Virus.. J Med Entomol 2005 Jan;42(1):57-62.
- Eriks IS, Palmer GH, McGuire TC, Allred DR, Barbet AF. Detection and quantitation of Anaplasma marginale in carrier cattle by using a nucleic acid probe.. J Clin Microbiol 1989 Feb;27(2):279-84.
- Bowman MC, Archin NM, Margolis DM. Pharmaceutical approaches to eradication of persistent HIV infection.. Expert Rev Mol Med 2009 Feb 11;11:e6.
- Howell JM, Ueti MW, Palmer GH, Scoles GA, Knowles DP. Persistently infected calves as reservoirs for acquisition and transovarial transmission of Babesia bovis by Rhipicephalus (Boophilus) microplus.. J Clin Microbiol 2007 Oct;45(10):3155-9.
- Cheevers WP, McGuire TC. Equine infectious anemia virus: immunopathogenesis and persistence.. Rev Infect Dis 1985 Jan-Feb;7(1):83-8.
- Holbrook AA, Frerichs WM. Equine piroplasmosis.. Proc Annu Meet U S Anim Health Assoc 1968;72:220-2.
- Ueti MW, Palmer GH, Scoles GA, Kappmeyer LS, Knowles DP. Persistently infected horses are reservoirs for intrastadial tick-borne transmission of the apicomplexan parasite Babesia equi.. Infect Immun 2008 Aug;76(8):3525-9.
- Gubbels MJ, Katzer F, Shiels BR, Jongejan F. Study of Theileria annulata population structure during bovine infection and following transmission to ticks.. Parasitology 2001 Dec;123(Pt 6):553-61.
- Mehlhorn H, Schein E. Redescription of Babesia equi Laveran, 1901 as Theileria equi Mehlhorn, Schein 1998.. Parasitol Res 1998 Jun;84(6):467-75.
- Ueti MW, Palmer GH, Kappmeyer LS, Statdfield M, Scoles GA, Knowles DP. Ability of the vector tick Boophilus microplus to acquire and transmit Babesia equi following feeding on chronically infected horses with low-level parasitemia.. J Clin Microbiol 2005 Aug;43(8):3755-9.
- Short MA, Clark CK, Harvey JW, Wenzlow N, Hawkins IK, Allred DR, Knowles DP, Corn JL, Grause JF, Hennager SG, Kitchen DL, Traub-Dargatz JL. Outbreak of equine piroplasmosis in Florida.. J Am Vet Med Assoc 2012 Mar 1;240(5):588-95.
- Stiller D, Goff WL, Johnson LW, Knowles DP. Dermacentor variabilis and boophilus microplus (Acari: Ixodidae): experimental vectors of Babesia equi to equids.. J Med Entomol 2002 Jul;39(4):667-70.
- Scoles GA, Hutcheson HJ, Schlater JL, Hennager SG, Pelzel AM, Knowles DP. Equine piroplasmosis associated with Amblyomma cajennense Ticks, Texas, USA.. Emerg Infect Dis 2011 Oct;17(10):1903-5.
- Frerichs WM, Allen PC, Holbrook AA. Equine piroplasmosis (Babesia equi): therapeutic trials of imidocarb dihydrochloride in horses and donkeys.. Vet Rec 1973 Jul 21;93(3):73-5.
- Kuttler KL, Zaugg JL, Gipson CA. Imidocarb and parvaquone in the treatment of piroplasmosis (Babesia equi) in equids.. Am J Vet Res 1987 Nov;48(11):1613-6.
- Zaugg JL, Lane VM. Efficacy of buparvaquone as a therapeutic and clearing agent of Babesia equi of European origin in horses.. Am J Vet Res 1992 Aug;53(8):1396-9.
- Butler CM, Nijhof AM, van der Kolk JH, de Haseth OB, Taoufik A, Jongejan F, Houwers DJ. Repeated high dose imidocarb dipropionate treatment did not eliminate Babesia caballi from naturally infected horses as determined by PCR-reverse line blot hybridization.. Vet Parasitol 2008 Feb 14;151(2-4):320-2.
- Brüning A. Equine piroplasmosis an update on diagnosis, treatment and prevention.. Br Vet J 1996 Mar;152(2):139-51.
- Schwint ON, Ueti MW, Palmer GH, Kappmeyer LS, Hines MT, Cordes RT, Knowles DP, Scoles GA. Imidocarb dipropionate clears persistent Babesia caballi infection with elimination of transmission potential.. Antimicrob Agents Chemother 2009 Oct;53(10):4327-32.
- Simpson CF, Neal FC. Ultrastructure of Babesia equi in ponies treated with imidocarb.. Am J Vet Res 1980 Feb;41(2):267-71.
- Ueti MW, Palmer GH, Kappmeyer LS, Scoles GA, Knowles DP. Expression of equi merozoite antigen 2 during development of Babesia equi in the midgut and salivary gland of the vector tick Boophilus microplus.. J Clin Microbiol 2003 Dec;41(12):5803-9.
- Adams LG. Clinicopathological aspects of imidocarb dipropionate toxicity in horses.. Res Vet Sci 1981 Jul;31(1):54-61.
- Nicolaiewsky TB, Richter MF, Lunge VR, Cunha CW, Delagostin O, Ikuta N, Fonseca AS, da Silva SS, Ozaki LS. Detection of Babesia equi (Laveran, 1901) by nested polymerase chain reaction.. Vet Parasitol 2001 Oct 31;101(1):9-21.
- Calder JA, Reddy GR, Chieves L, Courtney CH, Littell R, Livengood JR, Norval RA, Smith C, Dame JB. Monitoring Babesia bovis infections in cattle by using PCR-based tests.. J Clin Microbiol 1996 Nov;34(11):2748-55.
- Slifka MK, Ahmed R. Long-lived plasma cells: a mechanism for maintaining persistent antibody production.. Curr Opin Immunol 1998 Jun;10(3):252-8.
- Ndungu FM, Cadman ET, Coulcher J, Nduati E, Couper E, Macdonald DW, Ng D, Langhorne J. Functional memory B cells and long-lived plasma cells are generated after a single Plasmodium chabaudi infection in mice.. PLoS Pathog 2009 Dec;5(12):e1000690.
- Baird JK, Rieckmann KH. Can primaquine therapy for vivax malaria be improved?. Trends Parasitol 2003 Mar;19(3):115-20.
- Kumar S, Gupta AK, Pal Y, Dwivedi SK. In-vivo therapeutic efficacy trial with artemisinin derivative, buparvaquone and imidocarb dipropionate against Babesia equi infection in donkeys.. J Vet Med Sci 2003 Nov;65(11):1171-7.
Citations
This article has been cited 18 times.- Onzere CK, Hulbert M, Sears KP, Williams LBA, Fry LM. Tulathromycin and Diclazuril Lack Efficacy against Theileria haneyi, but Tulathromycin Is Not Associated with Adverse Clinical Effects in Six Treated Adult Horses.. Pathogens 2023 Mar 14;12(3).
- Chisu V, Serra E, Foxi C, Chessa G, Masala G. Molecular Investigation of Theileria and Babesia Species in Domestic Mammals from Sardinia, Italy.. Vet Sci 2023 Jan 14;10(1).
- Salinas-Estrella E, Ueti MW, Lobanov VA, Castillo-Payró E, Lizcano-Mata A, Badilla C, Martínez-Ibáñez F, Mosqueda J. Serological and molecular detection of Babesia caballi and Theileria equi in Mexico: A prospective study.. PLoS One 2022;17(3):e0264998.
- Sears KP, Knowles DP, Fry LM. Clinical Progression of Theileria haneyi in Splenectomized Horses Reveals Decreased Virulence Compared to Theileria equi.. Pathogens 2022 Feb 16;11(2).
- Nadal C, Marsot M, Le Metayer G, Boireau P, Guillot J, Bonnet SI. Spatial and Temporal Circulation of Babesia caballi and Theileria equi in France Based on Seven Years of Serological Data.. Pathogens 2022 Feb 9;11(2).
- Idoko IS, Edeh RE, Adamu AM, Machunga-Mambula S, Okubanjo OO, Balogun EO, Adamu S, Johnson W, Kappmeyer L, Mousel M, Ueti MW. Molecular and Serological Detection of Piroplasms in Horses from Nigeria.. Pathogens 2021 Apr 23;10(5).
- Dirks E, de Heus P, Joachim A, Cavalleri JV, Schwendenwein I, Melchert M, Fuehrer HP. First Case of Autochthonous Equine Theileriosis in Austria.. Pathogens 2021 Mar 4;10(3).
- Sears K, Knowles D, Dinkel K, Mshelia PW, Onzere C, Silva M, Fry L. Imidocarb Dipropionate Lacks Efficacy against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-Infected with T. haneyi.. Pathogens 2020 Dec 10;9(12).
- Hines SA, Brandvold J, Mealey RH, Call DR, Graça T. Exposure to ambient air causes degradation and decreased in vitro potency of buparvaquone and parvaquone.. Vet Parasitol X 2020 May;3:100023.
- Onyiche TE, Suganuma K, Igarashi I, Yokoyama N, Xuan X, Thekisoe O. A Review on Equine Piroplasmosis: Epidemiology, Vector Ecology, Risk Factors, Host Immunity, Diagnosis and Control.. Int J Environ Res Public Health 2019 May 16;16(10).
- Lobanov VA, Peckle M, Massard CL, Brad Scandrett W, Gajadhar AA. Development and validation of a duplex real-time PCR assay for the diagnosis of equine piroplasmosis.. Parasit Vectors 2018 Mar 2;11(1):125.
- Gimenez F, Hines SA, Evanoff R, Ojo KK, Van Voorhis WC, Maly DJ, Vidadala RSR, Mealey RH. In vitro growth inhibition of Theileria equi by bumped kinase inhibitors.. Vet Parasitol 2018 Feb 15;251:90-94.
- Van Voorhis WC, Doggett JS, Parsons M, Hulverson MA, Choi R, Arnold SLM, Riggs MW, Hemphill A, Howe DK, Mealey RH, Lau AOT, Merritt EA, Maly DJ, Fan E, Ojo KK. Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.. Exp Parasitol 2017 Sep;180:71-83.
- Mans BJ, Pienaar R, Latif AA. A review of Theileria diagnostics and epidemiology.. Int J Parasitol Parasites Wildl 2015 Apr;4(1):104-18.
- Hines SA, Ramsay JD, Kappmeyer LS, Lau AO, Ojo KK, Van Voorhis WC, Knowles DP, Mealey RH. Theileria equi isolates vary in susceptibility to imidocarb dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor.. Parasit Vectors 2015 Jan 20;8:33.
- Chen Z, Liu Q, Jiao FC, Xu BL, Zhou XN. Detection of piroplasms infection in sheep, dogs and hedgehogs in Central China.. Infect Dis Poverty 2014;3:18.
- Awinda PO, Mealey RH, Williams LB, Conrad PA, Packham AE, Reif KE, Grause JF, Pelzel-McCluskey AM, Chung C, Bastos RG, Kappmeyer LS, Howe DK, Ness SL, Knowles DP, Ueti MW. 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.. Clin Vaccine Immunol 2013 Nov;20(11):1752-7.
- Bastos RG, Suarez CE, Laughery JM, Johnson WC, Ueti MW, Knowles DP. Differential expression of three members of the multidomain adhesion CCp family in Babesia bigemina, Babesia bovis and Theileria equi.. PLoS One 2013;8(7):e67765.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists