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Low rates of Neospora caninum infection reactivation during gestation are observed in both chronically and congenitally infected mice



Endogenous transplacental transmission (EnTT) of Neospora caninum is the most common route of infection in cattle and occurs as a consequence of a reactivation of N. caninum infection that may lead to abortion or to the birth of congenitally infected calves. The reactivation of N. caninum infection was studied during the gestation of chronically infected dams and, for the first time, in their congenitally infected pups. BALB/c mice were infected with Nc-Spain 7 (Group 1) or Nc-Spain 3H (Group 2), high virulence isolates and low-to-moderate virulence isolates, respectively. The mice were mated after 90 days post-infection, and the morbidity, mortality, vertical transmission and humoral immune responses were recorded for 2 consecutive generations. In the first generation, higher morbidity and mortality rates were observed in G1 before mating than in G2 (P < 0·0001). In the second generation, low vertical transmission rates were observed in both inoculated groups (7·7% and 17·1% in G1 and G2, respectively) and were significantly diminished in the third generation (8·7% in G2 versus 0% in G1). Low rates of reactivation of N. caninum infection were induced in chronically infected mice and decreased in subsequent generations regardless of the isolate employed in the inoculations. Thus, further studies are needed to improve this reactivation mouse model.


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*Corresponding author: SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n. 28040-Madrid, Spain. Tel: +34 913944095. Fax: +34 913944098. E-mail:


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Aguado-Martínez, A., Álvarez-García, G., Fernández-García, A., Risco-Castillo, V., Marugán-Hernández, V. and Ortega-Mora, L. M. (2009 a). Failure of a vaccine using immunogenic recombinant proteins rNcSAG4 and rNcGRA7 against neosporosis in mice. Vaccine 27, 73317338. doi: 10.1016/j.vaccine.2009.09.050.
Aguado-Martínez, A., Ortega-Mora, L. M., Álvarez-García, G., Rodríguez-Marco, S., Risco-Castillo, V., Marugán-Hernández, V. and Fernández-García, A. (2009 b). Stage-specific expression of Nc SAG4 as a marker of chronic Neospora caninum infection in a mouse model. Parasitology 136, 757764. doi: 10.1017/S0031182009006076.
Aguado-Martínez, A., Álvarez-García, G., Fernández-García, A., Risco-Castillo, V., Arnaiz-Seco, I., Rebordosa-Trigueros, X., Navarro-Lozano, V. and Ortega-Mora, L. M. (2008). Usefulness of rNcGRA7- and rNcSAG4-based ELISA tests for distinguishing primo-infection, recrudescence, and chronic bovine neosporosis. Veterinary Parasitology 157, 182195. doi: 10.1016/j.vetpar.2008.08.002.
Álvarez-García, G., Pereira-Bueno, J., Gómez-Bautista, M. and Ortega-Mora, L. M. (2002). Pattern of recognition of Neospora caninum tachyzoite antigens by naturally infected pregnant cattle and aborted foetuses. Veterinary Parasitology 107, 1527.
Álvarez-García, G., Pitarch, A., Zaballos, A., Fernández-García, A., Gil, C., Gómez-Bautista, M., Aguado-Martínez, A. and Ortega-Mora, L. M. (2006). The NcGRA7 gene encodes the immunodominant 17 kDa antigen of Neospora caninum. Parasitology 134, 4150. doi: 10.1017/S0031182006001284.
Appleby, P. and Catty, D. (1983). Transmission of immunoglobulin to foetal and neonatal mice. Journal of Reproductive Immunology 5, 203213.
Bland, J. M. and Altman, D. G. (2004). The logrank test. BMJ (Clinical Research Edition) 328, 1073. doi: 10.1136/bmj.328.7447.1073.
Buxton, D. (1998). Protozoan infections (Toxoplasma gondii, Neospora caninum and Sarcocystis spp.) in sheep and goats: recent advances. Veterinary Research 29, 289310.
Caspe, S. G., Moore, D. P., Leunda, M. R., Cano, D. B., Lischinsky, L., Regidor-Cerrillo, J., Álvarez-García, G., Echaide, I. G., Bacigalupe, D., Ortega Mora, L. M., Odeon, A. C. and Campero, C. M. (2012). The Neospora caninum-Spain 7 isolate induces placental damage, fetal death and abortion in cattle when inoculated in early gestation. Veterinary Parasitology (in the Press). doi: 10.1016/j.vetpar.2012.04.034.
Cole, R. A., Lindsay, D. S., Blagburn, B. L. and Dubey, J. P. (1995). Vertical transmission of Neospora caninum in mice. The Journal of Parasitology 81, 730732.
Collantes-Fernández, E., Arrighi, R. B., Álvarez-García, G., Weidner, J. M., Regidor-Cerrillo, J., Boothroyd, J. C., Ortega-Mora, L. M. and Barragán, A. (2012). Infected dendritic cells facilitate systemic dissemination and transplacental passage of the obligate intracellular parasite Neospora caninum in mice. PloS One 7, e32123. doi: 10.1371/journal.pone.0032123.
Collantes-Fernández, E., López-Pérez, I., Álvarez-García, G. and Ortega-Mora, L. M. (2006). Temporal distribution and parasite load kinetics in blood and tissues during Neospora caninum infection in mice. Infection and Immunity 74, 24912494. doi: 10.1128/iai.74.4.2491-2494.2006.
Dubey, J. P. and Schares, G. (2011). Neosporosis in animals-The last five years. Veterinary Parasitology 180, 90108. doi: 10.1016/j.vetpar.2011.05.031.
Dubey, J. P., Schares, G. and Ortega-Mora, L. M. (2007). Epidemiology and control of neosporosis and Neospora caninum. Clinical Microbiology Reviews 20, 323367. doi: 10.1128/cmr.00031-06.
Entrican, G. (2002). Immune regulation during pregnancy and host-pathogen interactions in infectious abortion. Journal of Comparative Pathology 126, 7994. doi: 10.1053/jcpa.2001.0539.
Fernández-García, A., Risco-Castillo, V., Zaballos, A., Álvarez-García, G. and Ortega-Mora, L. M. (2006). Identification and molecular cloning of the Neospora caninum SAG4 gene specifically expressed at bradyzoite stage. Molecular and Biochemical Parasitology 146, 8997. doi: 10.1016/j.molbiopara.2005.08.019.
Innes, E. A., Wright, S., Bartley, P., Maley, S., Macaldowie, C., Esteban-Redondo, I. and Buxton, D. (2005). The host-parasite relationship in bovine neosporosis. Veterinary Immunology and Immunopathology 108, 2936. doi: 10.1016/j.vetimm.2005.07.004.
Jiménez-Ruiz, E., Álvarez-García, G., Aguado-Martínez, A., Salman, H., Irache, J. M., Marugán-Hernández, V. and Ortega-Mora, L. M. (2012). Low efficacy of NcGRA7, NcSAG4, NcBSR4 and NcSRS9 formulated in poly-e-caprolactone against Neospora caninum infection in mice. Vaccine 30, 49834992. doi: 10.1016/j.vaccine.2012.05.033.
Kano, R., Masukata, Y., Omata, Y., Kobayashi, Y., Maeda, R. and Saito, A. (2005). Relationship between type 1/type 2 immune responses and occurrence of vertical transmission in BALB/c mice infected with Neospora caninum. Veterinary Parasitology 129, 159164. doi:10.1016/j.vetpar.2005.01.004.
López-Pérez, I. C., Collantes-Fernández, E., Aguado-Martínez, A., Rodríguez-Bertos, A. and Ortega-Mora, L. M. (2008). Influence of Neospora caninum infection in BALB/c mice during pregnancy in post-natal development. Veterinary Parasitology 155, 175183. doi: 10.1016/j.vetpar.2008.05.018.
López-Perez, I. C., Collantes-Fernández, E., Rojo-Montejo, S., Navarro-Lozano, V., Risco-Castillo, V., Pérez-Pérez, V., Pereira-Bueno, J. and Ortega-Mora, L. M. (2010). Effects of Neospora caninum infection at mid-gestation on placenta in a pregnant mouse model. The Journal of Parasitology 96, 10171020. doi: 10.1645/GE-2347.1.
López-Pérez, I. C., Risco-Castillo, V., Collantes-Fernández, E. and Ortega-Mora, L. M. (2006). Comparative effect of Neospora caninum infection in BALB/c mice at three different gestation periods. The Journal of Parasitology 92, 12861291. doi: 10.1645/GE-883R.1.
Macaldowie, C., Maley, S. W., Wright, S., Bartley, P., Esteban-Redondo, I., Buxton, D. and Innes, E. A. (2004). Placental pathology associated with fetal death in cattle inoculated with Neospora caninum by two different routes in early pregnancy. Journal of Comparative Pathology 131, 142156. doi: 10.1016/j.jcpa.2004.02.005.
McCann, C. M., McAllister, M. M., Gondim, L. F., Smith, R. F., Cripps, P. J., Kipar, A., Williams, D. J. and Trees, A. J. (2007). Neospora caninum in cattle: Experimental infection with oocysts can result in exogenous transplacental infection, but not endogenous transplacental infection in the subsequent pregnancy. International Journal for Parasitology 37, 16311639. doi: 10.1016/j.ijpara.2007.05.012.
Morrison, D. A. (2002). How to improve statistical analysis in parasitology research publications. International Journal for Parasitology 32, 10651070.
Omata, Y., Nidaira, M., Kano, R., Kobayashi, Y., Koyama, T., Furuoka, H., Maeda, R., Matsui, T. and Saito, A. (2004). Vertical transmission of Neospora caninum in BALB/c mice in both acute and chronic infection. Veterinary Parasitology 121, 323328. doi: 10.1016/j.vetpar.2004.03.003.
Pereira García-Melo, D., Regidor-Cerrillo, J., Collantes-Fernández, E., Aguado-Martínez, A., Del Pozo, I., Minguijon, E., Gómez-Bautista, M., Aduriz, G. and Ortega-Mora, L. M. (2010). Pathogenic characterization in mice of Neospora caninum isolates obtained from asymptomatic calves. Parasitology 137, 10571068. doi: 10.1017/S0031182009991855.
Pérez-Zaballos, F. J., Ortega-Mora, L. M., Álvarez-García, G., Collantes-Fernández, E., Navarro-Lozano, V., García-Villada, L. and Costas, E. (2005). Adaptation of Neospora caninum isolates to cell-culture changes: an argument in favor of its clonal population structure. The Journal of Parasitology 91, 507510. doi: 10.1645/GE-381R1.
Regidor-Cerrillo, J., Gómez-Bautista, M., Del Pozo, I., Jiménez-Ruiz, E., Aduriz, G. and Ortega-Mora, L. M. (2010). Influence of Neospora caninum intra-specific variability in the outcome of infection in a pregnant BALB/c mouse model. Veterinary Research 41, 113. doi: 10.1051/vetres/2010024.
Regidor-Cerrillo, J., Gómez-Bautista, M., Sodupe, I., Aduriz, G., Álvarez-García, G., Del Pozo, I. and Ortega-Mora, L. M. (2011). In vitro invasion efficiency and intracellular proliferation rate comprise virulence-related phenotypic traits of Neospora caninum. Veterinary Research 42, 111. doi: 10.1186/1297-9716-42-41.
Reichel, M. P. and Ellis, J. T. (2009). Neospora caninum–how close are we to development of an efficacious vaccine that prevents abortion in cattle? International Journal for Parasitology 39, 11731187. doi: 10.1016/j.ijpara.2009.05.007.
Rettigner, C., De Meerschman, F., Focant, C., Vanderplasschen, A. and 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, 149160.
Rojo-Montejo, S., Collantes-Fernández, E., Rodríguez-Marcos, S., Perez-Zaballos, F., López-Pérez, I., Prenafeta, A. and Ortega-Mora, L. M. (2011). Comparative efficacy of immunization with inactivated whole tachyzoites versus a tachyzoite-bradyzoite mixture against neosporosis in mice. Parasitology 138, 13721383. doi: 10.1017/S0031182011001156.
Stanisic, D. I., Martin, L. B. and Good, M. F. (2003). The role of the 19-kDa region of merozoite surface protein 1 and whole-parasite-specific maternal antibodies in directing neonatal pups' responses to rodent malaria infection. Journal of Immunology 171, 54615469.
Trees, A. J. and Williams, D. J. L. (2005). Endogenous and exogenous transplacental infection in Neospora caninum and Toxoplasma gondii. Trends in Parasitology 21, 558561. doi: 10.1016/
Whitten, M. K. (1957). Effect of exteroceptive factors on the oestrous cycle of mice. Nature, London 180, 14361437.



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