Study on the use of toltrazuril to eliminate Neospora caninum in congenitally infected lambs born from experimentally infected ewes

Syed-Hussain, Sharifah Salmah; Howe, Laryssa; Pomroy, W.E.; West, D.M.; Hardcastle, Michael; Williamson, N. B.

doi:10.1016/j.vetpar.2015.03.019

Cited by 11 publications

(7 citation statements)

References 20 publications

(22 reference statements)

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“…The latter two options have been identified as economically viable, provided suitable targets and efficacious drugs can be made available ( Häsler et al, 2006a , b ). Although experimental studies have revealed potent effects of several drugs in vitro and in laboratory animal models ( Müller and Hemphill, 2011 ; Hemphill et al, 2016 ), only triazinon derivatives, such as ponazuril ( Kritzner et al, 2002 ) and toltrazuril ( Haerdi et al, 2006 ; Syed-Hussain et al, 2015 ), and the polyether ionophore antibiotic monensin ( Vanleeuwen et al, 2011 ) have been tested in ruminants experimentally infected with N. caninum, but results remained ambiguous. To date, pregnant ruminant models of neosporosis have not been used for assessments of drug efficacy against N. caninum infection and vertical transmission.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites

Sánchez-Sánchez

Ferre

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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Neospora caninum is one of the main causes of abortion in cattle, and recent studies have highlighted its relevance as an abortifacient in small ruminants. Vaccines or drugs for the control of neosporosis are lacking. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. We here present the pharmacokinetics, safety and efficacy of BKI-1553 in pregnant ewes and foetuses using a pregnant sheep model of N. caninum infection. BKI-1553 showed exposure in pregnant ewes with trough concentrations of approximately 4 μM, and of 1  μM in foetuses. Subcutaneous BKI-1553 administration increased rectal temperatures shortly after treatment, and resulted in dermal nodules triggering a slight monocytosis after repeated doses at short intervals. BKI-1553 treatment decreased fever in infected pregnant ewes already after two applications, resulted in a 37–50% reduction in foetal mortality, and modulated immune responses; IFNγ levels were increased early after infection and IgG levels were reduced subsequently. N. caninum was abundantly found in placental tissues; however, parasite detection in foetal brain tissue decreased from 94% in the infected/untreated group to 69–71% in the treated groups. In summary, BKI-1553 confers partial protection against abortion in a ruminant experimental model of N. caninum infection during pregnancy. In addition, reduced parasite detection, parasite load and lesions in foetal brains were observed.

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Section: Introductionmentioning

confidence: 99%

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites

Sánchez-Sánchez

Ferre

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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“…Four to six months after birth, a stronger antibody reactivity was found in the treated animals than in the untreated calves. Conversely, in a study to evaluate whether the treatment of congenitally infected lambs with toltrazuril PO at 20 mg/kg on days 0, 7, 14 and 21 after birth eliminated N. caninum , toltrazuril did not show any effect on the reduction of N. caninum presence or on the severity of histopathological lesions, and the lambs were all seropositive, although they had significantly lower specific antibody levels than those in the untreated animals, suggesting higher antigenic stimulation in the non-treated lambs than in the treated lambs [141].…”

Section: Available Drug Treatments For Ruminant Toxoplasmosis and Neomentioning

confidence: 99%

Treatment of Toxoplasmosis and Neosporosis in Farm Ruminants: State of Knowledge and Future Trends

Sánchez-Sánchez

Vázquez

Ferre

et al. 2018

CTMC

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Toxoplasmosis and neosporosis are closely related protozoan diseases that lead to important economic impacts in farm ruminants. Toxoplasma gondii infection mainly causes reproductive failure in small ruminants and is a widespread zoonosis, whereas Neospora caninum infection is one of the most important causes of abortion in cattle worldwide. Vaccination has been considered the most economic measure for controlling these diseases. However, despite vaccine development efforts, only a live-attenuated T. gondii vaccine has been licensed for veterinary use, and no promising vaccines against ne-osporosis have been developed; therefore, vaccine development remains a key goal. Additionally, drug therapy could be a valuable strategy for disease control in farm ruminants, as several drugs that limit T. gondii and N. caninum proliferation and dissemination have been evaluated. This approach may also be relevant to performing an initial drug screening for potential human therapy for zoonotic parasites. Treat-ments can be applied against infections in adult ruminants to minimize the outcomes of a primo-infection or the reactivation of a chronic infection during gestation or in newborn ruminants to avoid infection chronification. In this review, the current status of drug development against toxoplasmosis and neosporo-sis in farm ruminants is presented, and in an effort to promote additional treatment options, prospective drugs that have shown efficacy in vitro and in laboratory animal models of toxoplasmosis and neosporosis are examined

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“…Neospora caninum é um protozoário intracelular obrigatório que pertence ao filo Apicomplexa e é o agente causador da neosporose. Canídeos têm sido descritos como seus hospedeiros definitivos -por exemplo, cães, coiotes, lobos e dingos australianos, enquanto bovinos, ovinos, caprinos, veados, cavalos, búfalos asiáticos e outras espécies de sangue quente agem como seus hospedeiros intermediários (KING et al, 2010;LOPEZ-GATIUS, 2013;DUBEY et al, 2011;REICHEL et al, 2013;DONAHOE et al, 2015;REICHEL et al, 2015;SYED-HUSSAIN et al, 2015).…”

Section: Neospora Caninum E Seus Hospedeirosunclassified

“…O controle da neosporose bovina é baseado principalmente na prevenção da contaminação ambiental com oocistos eliminados nas fezes dos cães, restringindo o acesso desses animais nas proximidades do rebanho e sacrificando animais infectados (WILLIAMS;TREES, 2006). Além disso, várias outras estratégias para o controle da infecção por N. caninum e abortos em bovinos têm sido testadas, como a implementação de uma abordagem de teste e abate de bovinos soropositivos, o tratamento com parasiticida, tais como medicamentos coccidiostáticos (por exemplo, toltrazuril) e vacinação (HEMPHILL et al, 2015;MANSILLA et al, 2015;ELLIS, 2009;SYED-HUSSAIN et al, 2015).…”

Section: Controle Da Neosporoseunclassified

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Papel do adaptador indutor de Interferon-β contendo domínio TIR (TRIF) na resistência de camundongos a infecção por Neospora caninum

Miranda¹

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Study on the use of toltrazuril to eliminate Neospora caninum in congenitally infected lambs born from experimentally infected ewes

Cited by 11 publications

References 20 publications

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites

Treatment of Toxoplasmosis and Neosporosis in Farm Ruminants: State of Knowledge and Future Trends

Papel do adaptador indutor de Interferon-β contendo domínio TIR (TRIF) na resistência de camundongos a infecção por Neospora caninum

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