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Clinical outcome and vertical transmission variability among canine Neospora caninum isolates in a pregnant mouse model of infection

Published online by Cambridge University Press:  22 October 2013

ANDREA DELLARUPE ,
JAVIER REGIDOR-CERRILLO ,
ELENA JIMÉNEZ-RUIZ ,
GEREON SCHARES ,
JUAN MANUEL UNZAGA ,
MARÍA CECILIA VENTURINI  and
LUIS M. ORTEGA-MORA
ANDREA DELLARUPE
Affiliation:
SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain Laboratorio de Inmunoparasitología, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 118, 1900 La Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
JAVIER REGIDOR-CERRILLO*
Affiliation:
SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
ELENA JIMÉNEZ-RUIZ
Affiliation:
SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
GEREON SCHARES
Affiliation:
Friedrich-Loeffler-Institut, Institute of Epidemiology, Greifswald –Insel Riems, Germany
JUAN MANUEL UNZAGA
Affiliation:
Laboratorio de Inmunoparasitología, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 118, 1900 La Plata, Argentina
MARÍA CECILIA VENTURINI
Affiliation:
Laboratorio de Inmunoparasitología, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 118, 1900 La Plata, Argentina
LUIS M. ORTEGA-MORA
Affiliation:
SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
*
* Corresponding author: SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040-Madrid, Spain. E-mail: [email protected]
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Summary

We compared the clinical outcome and vertical transmission of six canine Neospora caninum isolates using a pregnant BALB/c model. Four of the isolates were obtained from oocysts of naturally infected dogs (Nc-Ger2, Nc-Ger3, Nc-Ger6 and Nc-6Arg) and two were from diseased dogs with neurological signs (Nc-Bahia and Nc-Liv). The dams were inoculated with 2×106 tachyzoites of each isolate at day 7 of pregnancy. Morbidity, mortality and the antibody responses were evaluated in both the dams and the offspring, as was parasite transmission to the progeny. The mortality rates varied from 100% in Nc-Bahia and Nc-Liv-infected pups to 19% or less for those infected with the isolates from oocysts. The vertical transmission rates varied from 9 to 53% for N. caninum from oocysts, compared with 100% for the Nc-Liv and Nc-Bahia isolates. All dams showed specific IgG responses against tachyzoite and rNc-GRA7 antigens, confirming Neospora infection. The highest IgG levels were detected in mice inoculated with the Nc-Liv and Nc-Bahia isolates. These results demonstrate marked differences in virulence between the N. caninum isolates obtained from oocysts and neurologically affected dogs. This variability could help us to explain the differences in the outcome of the infection in definitive and intermediate hosts.

Keywords

Neospora caninumcanine isolatesvirulencevertical transmissionpregnant mouse model
Type
Research Article
Information
Parasitology , Volume 141 , Issue 3 , March 2014 , pp. 356 - 366
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Copyright
Copyright © Cambridge University Press 2013 

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References

REFERENCES

Aguado-Martinez, A., Ortega-Mora, L. M., Alvarez-Garcia, G., Rodriguez-Marco, S., Risco-Castillo, V., Marugan-Hernandez, V. and Fernandez-Garcia, A. (2009). Stage-specific expression of Nc SAG4 as a marker of chronic Neospora caninum infection in a mouse model. Parasitology 136, 757–764. doi: 10.1017/S0031182009006076.CrossRefGoogle ScholarPubMed
Atkinson, R., Harper, P. A., Ryce, C., Morrison, D. A. and Ellis, J. T. (1999). Comparison of the biological characteristics of two isolates of Neospora caninum . Parasitology 118, 363–370.Google ScholarPubMed
Barber, J. S. and Trees, A. J. (1998). Naturally occurring vertical transmission of Neospora caninum in dogs. International Journal for Parasitology 28, 57–64.Google Scholar
Barber, J. S., Holmdahl, O. J., Owen, M. R., Guy, F., Uggla, A. and Trees, A. J. (1995). Characterization of the first European isolate of Neospora caninum (Dubey, Carpenter, Speer, Topper and Uggla). Parasitology 111, 563–568.Google Scholar
Barber, J. S., Payne-Johnson, C. E. and Trees, A. J. (1996). Distribution of Neospora caninum within the central nervous system and other tissues of six dogs with clinical neosporosis. Journal of Small Animal Practice 37, 568–574.CrossRefGoogle ScholarPubMed
Bartley, P. M., Wright, S., Sales, J., Chianini, F., Buxton, D. and Innes, E. A. (2006). Long-term passage of tachyzoites in tissue culture can attenuate virulence of Neospora caninum in vivo . Parasitology 133, 421–432. doi: 10.1017/S0031182006000539.CrossRefGoogle ScholarPubMed
Basso, W., Venturini, L., Venturini, M. C., Hill, D. E., Kwok, O. C., Shen, S. K. and Dubey, J. P. (2001). First isolation of Neospora caninum from the feces of a naturally infected dog. Journal of Parasitology 87, 612–618. doi: 10.1645/0022-3395(2001)087[0612:FIONCF]2.0.CO;2.CrossRefGoogle ScholarPubMed
Basso, W., Herrmann, D. C., Conraths, F. J., Pantchev, N., Vrhovec, M. G. and Schares, G. (2009 a). First isolation of Neospora caninum from the faeces of a dog from Portugal. Veterinary Parasitology 159, 162–166. doi: 10.1016/j.vetpar.2008.10.025.CrossRefGoogle ScholarPubMed
Basso, W., Schares, S., Barwald, A., Herrmann, D. C., Conraths, F. J., Pantchev, N., Vrhovec, M. G. and Schares, G. (2009 b). Molecular comparison of Neospora caninum oocyst isolates from naturally infected dogs with cell culture-derived tachyzoites of the same isolates using nested polymerase chain reaction to amplify microsatellite markers. Veterinary Parasitology 160, 43–50. doi: 10.1016/j.vetpar.2008.10.085.CrossRefGoogle ScholarPubMed
Bland, J. M. and Altman, D. G. (1998). Survival probabilities (the Kaplan-Meier method). BMJ (Clinical Research ed.) 317, 1572.Google Scholar
Bland, J. M. and Altman, D. G. (2004). The logrank test. BMJ (Clinical Research ed.) 328, 1073. doi: 10.1136/bmj.328.7447.1073.CrossRefGoogle ScholarPubMed
Caspe, S. G., Moore, D. P., Leunda, M. R., Cano, D. B., Lischinsky, L., Regidor-Cerrillo, J., Alvarez-Garcia, 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 189, 171–181. doi: 10.1016/j.vetpar.2012.04.034; 10.1016/j.vetpar.2012.04.034.CrossRefGoogle ScholarPubMed
Cavalcante, G. T., Monteiro, R. M., Soares, R. M., Nishi, S. M., Alves Neto, A. F., Esmerini Pde, O., Sercundes, M. K., Martins, J. and Gennari, S. M. (2011). Shedding of Neospora caninum oocysts by dogs fed different tissues from naturally infected cattle. Veterinary Parasitology 179, 220–223. doi: 10.1016/j.vetpar.2011.02.026; 10.1016/j.vetpar.2011.02.026.CrossRefGoogle ScholarPubMed
Collantes-Fernandez, E., Lopez-Perez, I., Alvarez-Garcia, 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, 2491–2494. doi: 10.1128/IAI.74.4.2491-2494.2006.Google Scholar
Collantes-Fernandez, E., Arrighi, R. B., Alvarez-Garcia, G., Weidner, J. M., Regidor-Cerrillo, J., Boothroyd, J. C., Ortega-Mora, L. M. and Barragan, 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; 10.1371/journal.pone.0032123.CrossRefGoogle ScholarPubMed
Debache, K., Alaeddine, F., Guionaud, C., Monney, T., Muller, J., Strohbusch, M., Leib, S. L., Grandgirard, D. and Hemphill, A. (2009). Vaccination with recombinant NcROP2 combined with recombinant NcMIC1 and NcMIC3 reduces cerebral infection and vertical transmission in mice experimentally infected with Neospora caninum tachyzoites. International Journal for Parasitology 39, 1373–1384. doi: 10.1016/j.ijpara.2009.04.006.Google Scholar
Dijkstra, T., Eysker, M., Schares, G., Conraths, F. J., Wouda, W. and Barkema, H. W. (2001). Dogs shed Neospora caninum oocysts after ingestion of naturally infected bovine placenta but not after ingestion of colostrum spiked with Neospora caninum tachyzoites. International Journal for Parasitology 31, 747–752.Google Scholar
Dijkstra, T., Barkema, H. W., Bjorkman, C. and Wouda, W. (2002). A high rate of seroconversion for Neospora caninum in a dairy herd without an obvious increased incidence of abortions. Veterinary Parasitology 109, 203–211.Google Scholar
Dubey, J. P. (1999). Recent advances in Neospora and neosporosis. Veterinary Parasitology 84, 349–367.Google Scholar
Dubey, J. P. (2003). Review of Neospora caninum and neosporosis in animals. Korean Journal of Parasitology 41, 1–16.Google Scholar
Dubey, J. P. and Schares, G. (2011). Neosporosis in animals–the last five years. Veterinary Parasitology 180, 90–108. doi: 10.1016/j.vetpar.2011.05.031; 10.1016/j.vetpar.2011.05.031.Google Scholar
Dubey, J. P., Buxton, D. and Wouda, W. (2006). Pathogenesis of bovine neosporosis. Journal of Comparative Pathology 134, 267–289. doi: 10.1016/j.jcpa.2005.11.004.CrossRefGoogle ScholarPubMed
Dubey, J. P., Schares, G. and Ortega-Mora, L. M. (2007). Epidemiology and control of neosporosis and Neospora caninum . Clinical Microbiology Reviews 20, 323–367. doi: 10.1128/CMR.00031-06.Google Scholar
Dubey, J. P., Jenkins, M. C., Rajendran, C., Miska, K., Ferreira, L. R., Martins, J., Kwok, O. C. and Choudhary, S. (2011). Gray wolf (Canis lupus) is a natural definitive host for Neospora caninum . Veterinary Parasitology 181, 382–387. doi: 10.1016/j.vetpar.2011.05.018.Google Scholar
Eiras, C., Arnaiz, I., Alvarez-Garcia, G., Ortega-Mora, L. M., Sanjuanl, M. L., Yus, E. and Dieguez, F. J. (2011). Neospora caninum seroprevalence in dairy and beef cattle from the northwest region of Spain, Galicia. Preventive Veterinary Medicine 98, 128–132. doi: 10.1016/j.prevetmed.2010.10.014.Google Scholar
French, N. P., Clancy, D., Davison, H. C. and Trees, A. J. (1999). Mathematical models of Neospora caninum infection in dairy cattle: transmission and options for control. International Journal for Parasitology 29, 1691–1704.Google Scholar
Gondim, L. F., Pinheiro, A. M., Santos, P. O., Jesus, E. E., Ribeiro, M. B., Fernandes, H. S., Almeida, M. A., Freire, S. M., Meyer, R. and McAllister, M. M. (2001). Isolation of Neospora caninum from the brain of a naturally infected dog, and production of encysted bradyzoites in gerbils. Veterinary Parasitology 101, 1–7.Google Scholar
Gondim, L. F., Gao, L. and McAllister, M. M. (2002). Improved production of Neospora caninum oocysts, cyclical oral transmission between dogs and cattle, and in vitro isolation from oocysts. Journal of Parasitology 88, 1159–1163.Google Scholar
Gondim, L. F., McAllister, M. M. and Gao, L. (2005). Effects of host maturity and prior exposure history on the production of Neospora caninum oocysts by dogs. Veterinary Parasitology 134, 33–39. doi: 10.1016/j.vetpar.2005.06.011.Google Scholar
Hall, C. A., Reichel, M. P. and Ellis, J. T. (2005). Neospora abortions in dairy cattle: diagnosis, mode of transmission and control. Veterinary Parasitology 128, 231–241. doi: 10.1016/j.vetpar.2004.12.012.Google Scholar
Heckeroth, A. R. and Tenter, A. M. (2007). Immunoanalysis of three litters born to a Doberman bitch infected with Neospora caninum . Parasitology Research 100, 837–846. doi: 10.1007/s00436-006-0328-3.Google Scholar
Jimenez-Ruiz, E., Alvarez-Garcia, G., Aguado-Martinez, A., Salman, H., Irache, J. M., Marugan-Hernandez, V. and Ortega-Mora, L. M. (2012). Low efficacy of NcGRA7, NcSAG4, NcBSR4 and NcSRS9 formulated in poly-epsilon-caprolactone against Neospora caninum infection in mice. Vaccine 30, 4983–4992. doi: 10.1016/j.vaccine.2012.05.033; 10.1016/j.vaccine.2012.05.033.Google Scholar
Jimenez-Ruiz, E., Bech-Sabat, G., Alvarez-Garcia, G., Regidor-Cerrillo, J., Hinojal-Campana, L. and Ortega-Mora, L. M. (2013). Specific antibody responses against Neospora caninum recombinant rNcGRA7, rNcSAG4, rNcBSR4 and rNcSRS9 proteins are correlated with virulence in mice. Parasitology 140, 569–579. doi: 10.1017/S0031182012002041; 10.1017/S0031182012002041.Google Scholar
King, J. S., Brown, G. K., Jenkins, D. J., Ellis, J. T., Fleming, P. J., Windsor, P. A. and Slapeta, J. (2012). Oocysts and high seroprevalence of Neospora caninum in dogs living in remote Aboriginal communities and wild dogs in Australia. Veterinary Parasitology 187, 85–92. doi: 10.1016/j.vetpar.2011.12.027; 10.1016/j.vetpar.2011.12.027.Google Scholar
Lopez-Perez, I. C., Risco-Castillo, V., Collantes-Fernandez, E. and Ortega-Mora, L. M. (2006). Comparative effect of Neospora caninum infection in BALB/c mice at three different gestation periods. Journal of Parasitology 92, 1286–1291.Google Scholar
Lopez-Perez, I. C., Collantes-Fernandez, E., Aguado-Martinez, A., Rodriguez-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, 175–183. doi: 10.1016/j.vetpar.2008.05.018.Google Scholar
McAllister, M. M., Dubey, J. P., Lindsay, D. S., Jolley, W. R., Wills, R. A. and McGuire, A. M. (1998). Dogs are definitive hosts of Neospora caninum . International Journal for Parasitology 28, 1473–1478.Google Scholar
More, G., Bacigalupe, D., Basso, W., Rambeaud, M., Beltrame, F., Ramirez, B., Venturini, M. C. and Venturini, L. (2009). Frequency of horizontal and vertical transmission for Sarcocystis cruzi and Neospora caninum in dairy cattle. Veterinary Parasitology 160, 51–54. doi: 10.1016/j.vetpar.2008.10.081; 10.1016/j.vetpar.2008.10.081.Google Scholar
Pena, H. F., Soares, R. M., Ragozo, A. M., Monteiro, R. M., Yai, L. E., Nishi, S. M. and Gennari, S. M. (2007). Isolation and molecular detection of Neospora caninum from naturally infected sheep from Brazil. Veterinary Parasitology 147, 61–66. doi: 10.1016/j.vetpar.2007.03.002.Google Scholar
Pereira Garcia-Melo, D., Regidor-Cerrillo, J., Collantes-Fernandez, E., Aguado-Martinez, A., Del Pozo, I., Minguijon, E., Gomez-Bautista, M., Aduriz, G. and Ortega-Mora, L. M. (2010). Pathogenic characterization in mice of Neospora caninum isolates obtained from asymptomatic calves. Parasitology 137, 1057–1068. doi: 10.1017/S0031182009991855.Google Scholar
Quinn, H. E., Miller, C. M., Ryce, C., Windsor, P. A. and Ellis, J. T. (2002). Characterization of an outbred pregnant mouse model of Neospora caninum infection. Journal of Parasitology 88, 691–696.Google Scholar
Regidor-Cerrillo, J., Gomez-Bautista, M., Pereira-Bueno, J., Aduriz, G., Navarro-Lozano, V., Risco-Castillo, V., Fernandez-Garcia, A., Pedraza-Diaz, S. and Ortega-Mora, L. M. (2008). Isolation and genetic characterization of Neospora caninum from asymptomatic calves in Spain. Parasitology 135, 1651–1659. doi: 10.1017/S003118200800509X.CrossRefGoogle ScholarPubMed
Regidor-Cerrillo, J., Gomez-Bautista, M., Del Pozo, I., Jimenez-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, 52. doi: 10.1051/vetres/2010024.CrossRefGoogle Scholar
Regidor-Cerrillo, J., Gomez-Bautista, M., Sodupe, I., Aduriz, G., Alvarez-Garcia, 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, 41. doi: 10.1186/1297-9716-42-41.Google Scholar
Reichel, M. P., Ellis, J. T. and Dubey, J. P. (2007). Neosporosis and hammondiosis in dogs. Journal of Small Animal Practice 48, 308–312. doi: 10.1111/j.1748-5827.2006.00236.x.Google Scholar
Rodrigues, A. A. R., Gennari, S. M., Aguiar, D. M., Sreekumar, C., Hill, D. E., Miska, K. B., Vianna, M. C. B. and Dubey, J. P. (2004). Shedding of Neospora caninum oocysts by dogs fed tissues from naturally infected water buffaloes (Bubalus bubalis) from Brazil. Veterinary Parasitology 124, 139–150. doi: 10.1016/j.vetpar.2004.07.007.Google Scholar
Rojo-Montejo, S., Collantes-Fernandez, E., Blanco-Murcia, J., Rodriguez-Bertos, A., Risco-Castillo, V. and Ortega-Mora, L. M. (2009 a). Experimental infection with a low virulence isolate of Neospora caninum at 70 days gestation in cattle did not result in foetopathy. Veterinary Research 40, 49. doi: 10.1051/vetres/2009032.Google Scholar
Rojo-Montejo, S., Collantes-Fernandez, E., Regidor-Cerrillo, J., Alvarez-Garcia, G., Marugan-Hernandez, V., Pedraza-Diaz, S., Blanco-Murcia, J., Prenafeta, A. and Ortega-Mora, L. M. (2009 b). Isolation and characterization of a bovine isolate of Neospora caninum with low virulence. Veterinary Parasitology 159, 7–16. doi: 10.1016/j.vetpar.2008.10.009.Google Scholar
Schares, G., Heydorn, A. O., Cuppers, A., Conraths, F. J. and Mehlhorn, H. (2001 a). Cyclic transmission of Neospora caninum: serological findings in dogs shedding oocysts. Parasitology Research 87, 873–877.Google Scholar
Schares, G., Heydorn, A. O., Cuppers, A., Conraths, F. J. and Mehlhorn, H. (2001 b). Hammondia heydorni-like oocysts shed by a naturally infected dog and Neospora caninum NC-1 cannot be distinguished. Parasitology Research 87, 808–816.Google Scholar
Schares, G., Pantchev, N., Barutzki, D., Heydorn, A. O., Bauer, C. and Conraths, F. J. (2005). Oocysts of Neospora caninum, Hammondia heydorni, Toxoplasma gondii and Hammondia hammondi in faeces collected from dogs in Germany. International Journal for Parasitology 35, 1525–1537. doi: 10.1016/j.ijpara.2005.08.008.Google Scholar
Whitten, M. K. (1957). Effect of exteroceptive factors on the oestrous cycle of mice. Nature 180, 1436.Google Scholar