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Bruno Gottstein - One of the best experts on this subject based on the ideXlab platform.
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An explorative study to assess the efficacy of Toltrazuril-sulfone (Ponazuril) in calves experimentally infected with Neospora caninum
Annals of Clinical Microbiology and Antimicrobials, 2002Co-Authors: Sandra Kritzner, Gisela Greif, Heinz Sager, Jürg Blum, Ralph Krebber, Bruno GottsteinAbstract:Background Neospora caninum is an important cause of infectious abortion and stillbirth in cattle world-wide. Infection is common and may frequently be passed from mother to calf (vertical transmission) with no signs of disease. Based on our previous observation that N. caninum -infection can be efficiently controlled with Toltrazuril-sulfone (Ponazuril) in experimentally infected mice, we addressed the question if efficacy could also be obtained in experimentally infected calves. Material and Methods The study included 19 calves and represents an initial explorative approach to document a basic effectiveness at first. Fifteen animals received each 2 x 10^8 N. caninum trophozoites, half of the dose being injected intravenously and the other half subcutaneously. Efficacy of treatment was assessed using molecular detection of parasite DNA with PCR and pathological alterations by immunohistochemistry in different organs of the animals. Assessment included also clinical, serological and pathophysiological parameters. Results In those calves medicated with Ponazuril (one, or six consecutive days, respectively, starting one day after infection), a complete abrogation of the parasite detectability was obtained in the brain and other organs, while 50% of non-treated calves became PCR-positive in brain and muscles. Clinically, Ponazuril chemotherapy of infected calves – in comparison to non-treated infected animals – reduced symptoms (fever), but no differences were observed between treated and non-treated animals with regard to serum enzymes and metabolites. Efficacy of a six-day treament was also reflected by significantly lower anti- Neospora antibody concentrations developed after infection, when compared to non-treated animals. Conclusion Based on our findings in this initially explorative approach that indicate a basic effectiveness of Ponazuril against experimental N. caninum infection in calves, we plan to follow our chemotherapeutical intervention strategy to control bovine neosporosis with a subsequent more extensive field study with naturally infected calves.
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an explorative study to assess the efficacy of toltrazuril sulfone Ponazuril in calves experimentally infected with neospora caninum
Annals of Clinical Microbiology and Antimicrobials, 2002Co-Authors: Sandra Kritzner, Gisela Greif, Heinz Sager, Jürg Blum, Ralph Krebber, Bruno GottsteinAbstract:Background Neospora caninum is an important cause of infectious abortion and stillbirth in cattle world-wide. Infection is common and may frequently be passed from mother to calf (vertical transmission) with no signs of disease. Based on our previous observation that N. caninum-infection can be efficiently controlled with Toltrazuril-sulfone (Ponazuril) in experimentally infected mice, we addressed the question if efficacy could also be obtained in experimentally infected calves.
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Annals 12002,
2002Co-Authors: Of Clinical Microbiology, Gisela Greif, Ra Kritzner, Heinz Sager, Jürg Blum, Ralph Krebber, Bruno GottsteinAbstract:An explorative study to assess the efficacy of Toltrazuril-sulfone (Ponazuril) in calves experimentally infected with Neospora caninu
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Efficacy of toltrazuril and Ponazuril against experimental Neospora caninum infection in mice
Parasitology Research, 2001Co-Authors: Bruno Gottstein, Andrew Hemphill, Simone Eperon, Wen Juan Dai, Angela Cannas, Gisela GreifAbstract:Neosporosis is a disease affecting predominantly fetal development in cattle and dog hosts; and it may cause neuromuscular disfunction in infected new-born calves and pups. Predispositions – including, e.g. transient immunosuppression during pregnancy – may result in an increased dissemination of the parasite within the host or its offspring. Chemotherapeutic treatment of neosporosis may be an issue, provided that an appropriate drug is made available. In this respect, we describe the use of a mouse model for the evaluation of toltrazuril and Ponazuril medication as a means of preventing parasite dissemination and subsequent formation of cerebral lesions. Toltrazuril- and Ponazuril-treated mice were experimentally infected intraperitoneally (i.p.) with 2 × 106Neospora caninum tachyzoites. The infection was monitored at three levels: clinically, by assessing symptoms, histologically, by assessing the occurrence of cerebral lesions and parasites by immunohistochemistry, and on the molecular level, by detection of parasite DNA using PCR. Chemotherapy using either toltrazuril or Ponazuril, both applied in a drinking-water formulation (20 mg toltrazuril or Ponazuril kg−1 body weight day−1) completely prevented the formation of cerebral lesions in all treated animals, as assessed by immunohistochemistry. PCR analyses of these treated animals showed that DNA-detectability was reduced by 91% and 90% upon toltrazuril and Ponazuril medication, respectively.
Gisela Greif - One of the best experts on this subject based on the ideXlab platform.
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An explorative study to assess the efficacy of Toltrazuril-sulfone (Ponazuril) in calves experimentally infected with Neospora caninum
Annals of Clinical Microbiology and Antimicrobials, 2002Co-Authors: Sandra Kritzner, Gisela Greif, Heinz Sager, Jürg Blum, Ralph Krebber, Bruno GottsteinAbstract:Background Neospora caninum is an important cause of infectious abortion and stillbirth in cattle world-wide. Infection is common and may frequently be passed from mother to calf (vertical transmission) with no signs of disease. Based on our previous observation that N. caninum -infection can be efficiently controlled with Toltrazuril-sulfone (Ponazuril) in experimentally infected mice, we addressed the question if efficacy could also be obtained in experimentally infected calves. Material and Methods The study included 19 calves and represents an initial explorative approach to document a basic effectiveness at first. Fifteen animals received each 2 x 10^8 N. caninum trophozoites, half of the dose being injected intravenously and the other half subcutaneously. Efficacy of treatment was assessed using molecular detection of parasite DNA with PCR and pathological alterations by immunohistochemistry in different organs of the animals. Assessment included also clinical, serological and pathophysiological parameters. Results In those calves medicated with Ponazuril (one, or six consecutive days, respectively, starting one day after infection), a complete abrogation of the parasite detectability was obtained in the brain and other organs, while 50% of non-treated calves became PCR-positive in brain and muscles. Clinically, Ponazuril chemotherapy of infected calves – in comparison to non-treated infected animals – reduced symptoms (fever), but no differences were observed between treated and non-treated animals with regard to serum enzymes and metabolites. Efficacy of a six-day treament was also reflected by significantly lower anti- Neospora antibody concentrations developed after infection, when compared to non-treated animals. Conclusion Based on our findings in this initially explorative approach that indicate a basic effectiveness of Ponazuril against experimental N. caninum infection in calves, we plan to follow our chemotherapeutical intervention strategy to control bovine neosporosis with a subsequent more extensive field study with naturally infected calves.
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an explorative study to assess the efficacy of toltrazuril sulfone Ponazuril in calves experimentally infected with neospora caninum
Annals of Clinical Microbiology and Antimicrobials, 2002Co-Authors: Sandra Kritzner, Gisela Greif, Heinz Sager, Jürg Blum, Ralph Krebber, Bruno GottsteinAbstract:Background Neospora caninum is an important cause of infectious abortion and stillbirth in cattle world-wide. Infection is common and may frequently be passed from mother to calf (vertical transmission) with no signs of disease. Based on our previous observation that N. caninum-infection can be efficiently controlled with Toltrazuril-sulfone (Ponazuril) in experimentally infected mice, we addressed the question if efficacy could also be obtained in experimentally infected calves.
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Annals 12002,
2002Co-Authors: Of Clinical Microbiology, Gisela Greif, Ra Kritzner, Heinz Sager, Jürg Blum, Ralph Krebber, Bruno GottsteinAbstract:An explorative study to assess the efficacy of Toltrazuril-sulfone (Ponazuril) in calves experimentally infected with Neospora caninu
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Efficacy of toltrazuril and Ponazuril against experimental Neospora caninum infection in mice
Parasitology Research, 2001Co-Authors: Bruno Gottstein, Andrew Hemphill, Simone Eperon, Wen Juan Dai, Angela Cannas, Gisela GreifAbstract:Neosporosis is a disease affecting predominantly fetal development in cattle and dog hosts; and it may cause neuromuscular disfunction in infected new-born calves and pups. Predispositions – including, e.g. transient immunosuppression during pregnancy – may result in an increased dissemination of the parasite within the host or its offspring. Chemotherapeutic treatment of neosporosis may be an issue, provided that an appropriate drug is made available. In this respect, we describe the use of a mouse model for the evaluation of toltrazuril and Ponazuril medication as a means of preventing parasite dissemination and subsequent formation of cerebral lesions. Toltrazuril- and Ponazuril-treated mice were experimentally infected intraperitoneally (i.p.) with 2 × 106Neospora caninum tachyzoites. The infection was monitored at three levels: clinically, by assessing symptoms, histologically, by assessing the occurrence of cerebral lesions and parasites by immunohistochemistry, and on the molecular level, by detection of parasite DNA using PCR. Chemotherapy using either toltrazuril or Ponazuril, both applied in a drinking-water formulation (20 mg toltrazuril or Ponazuril kg−1 body weight day−1) completely prevented the formation of cerebral lesions in all treated animals, as assessed by immunohistochemistry. PCR analyses of these treated animals showed that DNA-detectability was reduced by 91% and 90% upon toltrazuril and Ponazuril medication, respectively.
Heinz Mehlhorn - One of the best experts on this subject based on the ideXlab platform.
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Effects of toltrazuril and Ponazuril on the fine structure and multiplication of tachyzoites of the NC-1 strain of Neospora caninum (a synonym of Hammondia heydorni) in cell cultures
Parasitology Research, 2004Co-Authors: Anne Kathrin Darius, Heinz MehlhornAbstract:Rhesus monkey kidney cell cultures were used to propagate tachyzoites of the NC-1 strain of Neospora caninum (syn . Hammondia heydorni ). The infected cell cultures were incubated for 4–12 h in media containing 0, 1, 10 or 100 µg/ml of either toltrazuril or Ponazuril. The effects were studied by light and electron microscopy. Drug dosages of at least 30 µg/ml were needed to eliminate the parasites. Ponazuril was found (with respect to the reduction of the number of parasites) to be less effective at dosages of 30 µg/ml compared to toltrazuril. However, the damage to the tachyzoites being incubated in 30 µg toltrazuril or Ponazuril seen by electron microscopy was so significant that it was surely lethal. The initial damage occurred within the apicoplast and the tubular mitochondrion in all cases,thus destroying two of the most important cell organelles.
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effects of toltrazuril and Ponazuril on hammondia heydorni syn neospora caninum infections in mice
Parasitology Research, 2004Co-Authors: Anne Kathrin Darius, Heinz MehlhornAbstract:Mice infected with tachyzoites of Neospora caninum (syn.: Hammondia heydorni) must be pretreated with cortisone in order to show disease symptoms. This indicates the status of an opportunistic agent of disease. Toltrazuril was an effective curative agent.
Thomas J Kennedy - One of the best experts on this subject based on the ideXlab platform.
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effect of intermittent oral administration of Ponazuril on experimental sarcocystis neurona infection of horses
American Journal of Veterinary Research, 2008Co-Authors: Robert J. Mackay, Susan T Tanhauser, Karen Gillis, I G Mayhew, Thomas J KennedyAbstract:Objective—To evaluate the effect of intermittent oral administration of Ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts. Animals—20 healthy horses that were seronegative for S neurona–specific IgG. Procedures—5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered Ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day – 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia. Results—Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 ...
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effect of a single dose of Ponazuril on neural infection and clinical disease in sarcocystis neurona challenged interferon gamma knockout mice
Veterinary Parasitology, 2003Co-Authors: Robert P Franklin, Robert J. Mackay, Susan T Tanhauser, Karen Gillis, Pamela E Ginn, Thomas J KennedyAbstract:Abstract Interferon γ-knockout mice were challenged with 5000 Sarcocystis neurona sporocysts acquired from a naturally infected opossum. Ponazuril was administered once, by gavage, at day 1, 3, 7, 10, or 14 post-infection (pi). Ponazuril was given at either 20 or 200 mg/kg. Mice that survived to day 30 pi were euthanized. Severity of CNS infection was quantified as schizont density in the cerebellum. Unchallenged mice in treatment and non-treatment groups remained free of disease and gained weight throughout the experiment. All challenged mice, regardless of treatment, developed histologic evidence of CNS infection even though clinical signs were prevented in some groups. The greatest treatment benefits were seen in mice given 200 mg/kg Ponazuril between days 4 and 14 pi. Weight gain over the course of the experiment occurred only in mice that were given 200 mg/kg Ponazuril on day 7 or 10 pi. With the exception of groups given 200 mg/kg Ponazuril on day 7 or 14 pi, mice in groups that got sporocysts developed abnormal neurologic signs. No deaths before day 30 pi occurred in mice given Ponazuril at 20 mg/kg on day 7 pi or 200 mg/kg on day 1, 7, 10, or 14 pi. This effect was not significant. Mice given 200 mg/kg on day 7 pi had significantly fewer cerebellar schizonts than did those of the control group that was not given Ponazuril. These results indicate that single-dose administration of Ponazuril for prevention of CNS infection is partially protective when given between days 4 and 14 pi.
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determination of the activity of Ponazuril against sarcocystis neurona in cell cultures
Veterinary Parasitology, 2000Co-Authors: Thomas J KennedyAbstract:The present study examined the efficacy of Ponazuril in inhibiting merozoite production of Sarcocystis neurona in cell cultures. Ponazuril inhibited merozoite production by more that 90% in cultures of S. neurona treated with 1.0 μg/ml Ponazuril and greater than 95% inhibition of merozoite production was observed when infected cultures were treated with 5.0 μg/ml Ponazuril. Ponazuril may have promise as a therapeutic agent in the treatment of S. neurona induced equine protozoal myeloencephalitis (EPM) in horses.
Anne Kathrin Darius - One of the best experts on this subject based on the ideXlab platform.
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Effects of toltrazuril and Ponazuril on the fine structure and multiplication of tachyzoites of the NC-1 strain of Neospora caninum (a synonym of Hammondia heydorni) in cell cultures
Parasitology Research, 2004Co-Authors: Anne Kathrin Darius, Heinz MehlhornAbstract:Rhesus monkey kidney cell cultures were used to propagate tachyzoites of the NC-1 strain of Neospora caninum (syn . Hammondia heydorni ). The infected cell cultures were incubated for 4–12 h in media containing 0, 1, 10 or 100 µg/ml of either toltrazuril or Ponazuril. The effects were studied by light and electron microscopy. Drug dosages of at least 30 µg/ml were needed to eliminate the parasites. Ponazuril was found (with respect to the reduction of the number of parasites) to be less effective at dosages of 30 µg/ml compared to toltrazuril. However, the damage to the tachyzoites being incubated in 30 µg toltrazuril or Ponazuril seen by electron microscopy was so significant that it was surely lethal. The initial damage occurred within the apicoplast and the tubular mitochondrion in all cases,thus destroying two of the most important cell organelles.
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effects of toltrazuril and Ponazuril on hammondia heydorni syn neospora caninum infections in mice
Parasitology Research, 2004Co-Authors: Anne Kathrin Darius, Heinz MehlhornAbstract:Mice infected with tachyzoites of Neospora caninum (syn.: Hammondia heydorni) must be pretreated with cortisone in order to show disease symptoms. This indicates the status of an opportunistic agent of disease. Toltrazuril was an effective curative agent.