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Toltrazuril treatment to control diaplacental Neospora caninum transmission in experimentally infected pregnant mice

Published online by Cambridge University Press:  13 December 2004

B. GOTTSTEIN ,
G. R. RAZMI ,
P. AMMANN ,
H. SAGER  and
N. MÜLLER
B. GOTTSTEIN
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
G. R. RAZMI
Affiliation:
Department of Pathobiology, School of Veterinary Medicine, Ferdowsi University of Mashhad, Iran
P. AMMANN
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
H. SAGER
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
N. MÜLLER
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
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Abstract

We addressed the question whether diaplacental transmission of Neospora caninum can be controlled by metaphylactic chemotherapy using toltrazuril or enrofloxacin. Female C57/BL6 mice, infected on day 10 of pregnancy, were medicated for 6 consecutive days p.i. with 52·5 mg toltrazuril or – as an out-group control medication – 16·7 mg enrofloxacin per kg body weight per day. Other control groups received either infection but no medication or vice versa. Toltrazuril treatment significantly reduced pre- and perinatal losses (10 deliveries of healthy newborns, versus 1 abortion and 4 failures) when compared to control-enrofloxacin (2 deliveries, versus 1 abortion, 7 failures and 2 pre-parturient deaths of dams) and non-treated animals (3 deliveries, versus 6 abortions, 8 failures and 4 pre-parturient deaths). Simultaneously, PCR-based parasite detection in the brain of mothers, histopathological findings as well as clinical fatality were significantly less frequent in toltrazuril-treated dams. The overall toltrazuril treatment efficacy was determined as 87%, that of enrofloxacin-treatment as 17%. The progenies of toltrazuril-treated dams also exhibited a very low rate of PCR-positivity in their brain (3 out of 39), whereas untreated dams delivered litters with mostly PCR-positive brains (12 out of 14) and a relatively high death rate post-partum (5 out of 19 newborns died). Mice subjected to a second mating delivered newborns all negative by N. caninum-PCR, indicating that diaplacental tachyzoite passage does not occur in a later, repeated pregnancy. Overall, our experiments showed that toltrazuril-treatment of an acute N. caninum-infection – induced during pregnancy – results in a clear reduction of fetal losses and a marked reduction of diaplacental passage of the parasite to the fetal brain, whereas enrofloxacin, as an out-group control substance, failed to show the same effect.

Keywords

neosporosistoltrazurilenrofloxacinmousepregnancy
Type
Research Article
Information
Parasitology , Volume 130 , Issue 1 , January 2005 , pp. 41 - 48
Copyright
© 2004 Cambridge University Press

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References

REFERENCES

AMMANN, P., WALDVOGEL, A., BREYER, I., ESPOSITO, M., MÜLLER, N. & GOTTSTEIN, B. ( 2004). The role of B- and T-cell-immunity in toltrazuril-treated C57BL/6 WT, μMT and nude mice experimentally infected with Neospora caninum. Parasitology Research 93, 178–187.Google Scholar
ANDERSON, M. L., REYNOLDS, J. P., ROWE, J. D., SVERLOW, K. W., PACKHAM, A. E., BARR, B. C. & CONRAD, P. A. ( 1997). Evidence of vertical transmission of Neospora sp. infection in dairy cattle. Journal of the American Veterinary Medical Association 210, 1169–1172.Google Scholar
ANDRIANARIVO, A. G., ROWE, J. D., BARR, B. C., ANDERSON, M. L., PACKHAM, A. E., SVERLOW, K. W., CHOROMANSKI, L., LOUI, C., GRACE, A. & CONRAD, P. A. ( 2000). A POLYGEN™-adjuvanted killed Neospora caninum tachyzoite preparation failed to prevent foetal infection in pregnant cattle following i.v./i.m. experimental tachyzoite challenge. International Journal for Parasitology 30, 985–990.Google Scholar
ATHANASSAKIS, I. & ICONOMIDOU, B. ( 1996). Cytokine production in the serum and spleen of mice from day 6 to 14 of gestation: cytokines/placenta/spleen/serum. Developmental Immunology 4, 247–255.Google Scholar
BASZLER, T. V., LONG, M. T., McELWAIN, T. F. & MATHISON, B. A. ( 1999). Interferon-gamma and interleukin-12 mediate protection to acute Neospora caninum infection in BALB/c mice. International Journal for Parasitology 29, 1635–1646.CrossRefGoogle Scholar
COLE, H. A., LINDSAY, D. S., BLAGBURN, B. L. & DUBEY, J. P. ( 1995). Vertical transmission of Neospora caninum in mice. Journal of Parasitology 81, 730–732.CrossRefGoogle Scholar
DAVISON, H. C., OTTER, A. & TREES, A. J. ( 1999). Estimation of vertical and horizontal transmission parameters of Neospora caninum infections in dairy cattle. International Journal for Parasitology 29, 1683–1689.CrossRefGoogle Scholar
DUBEY, J. P., HATTEL, A. L., LINDSAY, D. S. & TOPPER, M. J. ( 1988). Neonatal Neospora caninum infection in dogs: isolation of the causative agent and experimental transmission. Journal of the American Veterinary Medical Association 193, 1259–1263.Google Scholar
DUBEY, J. P. ( 2003). Review of Neospora caninum and neosporosis in animals. The Korean Journal of Parasitology 41, 1–16.CrossRefGoogle Scholar
EPERON, S., BRÖNNIMANN, K., HEMPHILL, A. & GOTTSTEIN, B. ( 1999). Susceptibility of B-cell deficient C57BL/6 (μMT) mice to Neospora caninum infection. Parasite Immunology 21, 225–236.CrossRefGoogle Scholar
GOTTSTEIN, B., EPERON, S., DAI, W. J., CANNAS, A., HEMPHILL, A. & GREIF, G. ( 2001). Efficacy of toltrazuril and ponazuril against experimental Neospora caninum infection in mice. Parasitology Research 87, 43–48.CrossRefGoogle Scholar
GREIF, G. ( 2000). Immunity to coccidiosis after treatment with toltrazuril. Parasitology Research 86, 787–790.CrossRefGoogle Scholar
GREIF, G., HARDER, A. & HABERKORN, A. ( 2001). Chemotherapeutic approaches to protozoa: Coccidiae – current level of knowledge and outlook. Parasitology Research 87, 973–975.Google Scholar
HARDER, H. & HABERKORN, A. ( 1989). Possible mode of action of toltrazuril: studies on two Eimeria species and Ascaris suum enzymes. Parasitology Research 76, 8–12.CrossRefGoogle Scholar
HEMPHILL, A., GOTTSTEIN, B. & KAUFMANN, H. ( 1996). Adhesion and invasion of bovine endothelial cells by Neospora caninum. Parasitology 112, 183–197.CrossRefGoogle Scholar
INNES, E. A., ANDRIANARIVO, A. G., BJORKMAN, C., WILLIAMS, D. J. & CONRAD, P. A. ( 2002). Immune responses to Neospora caninum and prospects for vaccination. Trends in Parasitology 18, 497–504.CrossRefGoogle Scholar
INNES, E. A., BUXTON, D., EPERON, S. & GOTTSTEIN, B. ( 2000). Immunology of Neospora caninum infection in cattle and mice. International Journal for Parasitology 30, 896–900.Google Scholar
KIM, J. T., PARK, J. Y., SEO, H. S., OH, H. G., NOH, J. W., KIM, J. H., KIM, D. Y. & YOUN, H. J. ( 2002). In vitro antiprotozoal effects of artemisinin on Neospora caninum. Veterinary Parasitology 103, 53–63.CrossRefGoogle Scholar
KRITZNER, S., SAGER, H., BLUM, J., KREBBER, R., GREIF, G. & GOTTSTEIN, B. ( 2002). An explorative study to assess the efficacy of Toltrazuril-sulfone (Ponazuril) in calves experimentally infected with Neospora caninum. Annals of Clinical Microbiology and Antimicrobials 1, 4.CrossRefGoogle Scholar
KWON, H. J., KIM, J. H., KIM, M., LEE, J. K., HWANG, W. S. & KIM, D. Y. ( 2003). Anti-parasitic activity of depudecin on Neospora caninum via the inhibition of histone deacetylase. Veterinary Parasitology 112, 269–276.CrossRefGoogle Scholar
LIDDELL, S., JENKINS, M. C., COLLICA, C. M. & DUBEY, J. P. ( 1999). Prevention of vertical transfer of Neospora caninum in BALB/c mice by vaccination. Journal of Parasitology 85, 1072–1075.CrossRefGoogle Scholar
LINDSAY, D. S. & DUBEY, J. P. ( 1990). Effects of sulfadiazine and amprolium on Neospora caninum (Protozoa: Apicomplexa) infections in mice. Journal of Parasitology 7, 177–179.CrossRefGoogle Scholar
LINDSAY, D. S., RIPPEY, N. S., COLE, R. A., PARSONS, L. C., DUBEY, J. P., TIDWELL, R. R. & BLAGBURN, B. L. ( 1994). Examination of the activities of 43 chemotherapeutic agents against Neospora caninum tachyzoites in cultured cells. American Journal of Veterinary Research 55, 976–981.Google Scholar
LINDSAY, D. S., LENZ, S. D., COLE, R. A., DUBEY, J. P. & BLAGBURN, B. L. ( 1995). Mouse model for central nervous system Neospora caninum infections. Journal of Parasitology 81, 313–315.CrossRefGoogle Scholar
LONG, M. T. & BASZLER, T. V. ( 2000). Neutralization of maternal IL-4 modulates congenital protozoal transmission: comparison of innate versus acquired immune responses. Journal of Immunology 164, 4768–4774.CrossRefGoogle Scholar
MÜLLER, N., ZIMMERMANN, V., HENTRICH, B. & GOTTSTEIN, B. ( 1996). Diagnosis of Neospora caninum and Toxoplasma gondii infection by PCR and DNA hybridization immunoassay. Journal of Clinical Microbiology 34, 2850–2852.Google Scholar
NISHIKAWA, Y., INOUE, N., XUAN, X., NAGASAWA, H., IGARASHI, I., FUJISAKI, K., OTSUKA, H. & MIKAMI, T. ( 2001). Protective efficacy of vaccination by recombinant vaccinia virus against Neospora caninum infection. Vaccine 19, 1381–1390.CrossRefGoogle Scholar
RETTIGNER, C., DE MEERSCHMAN, F., FOCANT, C., VANDERPLASSCHEN, A. & LOSSON, B. ( 2004). The vertical transmission following the reactivation of a Neospora caninum chronic infection does not seem to be due to an alteration of the systemic immune response in pregnant CBA/Ca mice. Parasitology 128, 149–160.CrossRefGoogle Scholar
RITTER, D. M., KERLIN, R., SIBERT, G. & BRAKE, D. ( 2002). Immune factors influencing the course of infection with Neospora caninum in the murine host. Journal of Parasitology 88, 271–280.CrossRefGoogle Scholar
ROMATOWSKI, J. ( 2000). Pentatrichomonas hominis infection in four kittens. Journal of the American Veterinary Medical Association 216, 1270–1272.CrossRefGoogle Scholar
SCHARES, G., PETERS, M., WURM, R., BÄRWALD, A. & CONRATHS, F. J. ( 1998). The efficiency of vertical transmission of Neospora caninum in dairy cattle analysed by serological techniques. Veterinary Parasitology 80, 87–98.CrossRefGoogle Scholar
SHIBAHARA, T., KOKUHO, T., ETO, M., HARITANI, M., HAMAOKA, T., SHIMURA, K., NAKAMURA, K., YOKOMIZO, Y. & YAMANE, I. ( 1999). Pathological and immunological findings of athymic nude and congenic wild type BALB/c mice experimentally infected with Neospora caninum. Veterinary Pathology 36, 321–327.CrossRefGoogle Scholar
SRETER, T., SZELL, Z. & VARGA, I. ( 2002). Anticryptosporidial prophylactic efficacy of enrofloxacin and paromomycin in chickens. Journal of Parasitology 88, 209–211.CrossRefGoogle Scholar
YAMAGE, M., FLECHTNER, O. & GOTTSTEIN, B. ( 1996). Neospora caninum: specific oligonucleotide primers for the detection of brain “cyst” DNA of experimentally infected nude mice by the polymerase chain reaction (PCR). Journal of Parasitology 82, 272–279.CrossRefGoogle Scholar