title: Mice congenitally infected with low-to-moderate virulence Neospora caninum isolates exhibited clinical reactivation during the mating period without transmission to the next generation.
abstract: Endogenous transplacental transmission (EnTT) is the major transmission route of Neospora caninum in cattle. Thus, the development of a standardised experimental model of EnTT is needed for more appropriate testing of parasite biology and control strategies. A recent study reported up to 40-50% EnTT rates in chronically infected dams with either high or low-to-moderate virulence isolates, although low fertility rates were observed in dams inoculated with the high virulence isolate. Therefore, low-to-moderate virulence N. caninum isolates (Nc-Spain 3H; G1 and Nc-Spain 8; G2) that previously showed high TT rates versus low mortality and morbidity rates in a congenital mouse model were inoculated into BALB/c dams (first generation). The new approach followed in the present study aimed to start with a high number of congenitally infected mice (second generation), which allowed a more efficient EnTT from congenitally infected dams to their progeny (third generation). Interestingly, a reactivation of infection occurred in several congenitally infected non-pregnant females (second generation) from both infected groups. This fact was evidenced by neosporosis-associated clinical signs after mating accompanied by an increase of specific antibody levels (IgG1, IgG2a and specific antibodies against rNcGRA7) (P<0.0001; one-way ANOVA). Moreover, a higher number of PCR-positive mice compared to pregnant females were observed (P<0.05; Fisher's exact test). These results support the hypothesis that only mice without clinical signs and with a low parasite burden in the brain became pregnant, which may explain the posterior failure in inducing EnTT from the second to the third generation. These findings confirm that this mouse model is not a suitable experimental EnTT model for testing the efficacy of drugs and vaccine candidates against EnTT. The employment of other putative suitable species with a similar placenta structure, such as small ruminants, should be taken into consideration.
authors.affiliation: SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Jiménez-Ruiz
authors.forename: Gema
authors.initials: G
authors.lastname: Álvarez-García
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguado-Martínez
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ortega-Mora
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D003048:Coccidiosis / Q000151:congenital / Q000276:immunology / Q000469:parasitology / Q000635:transmission*; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D051379:Mice; D018688:Neospora / Q000276:immunology* / Q000472:pathogenicity; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology* / Q000469:parasitology; D014774:Virulence
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G