Influence of the gestational stage on the clinical course, lesional development and parasite distribution in experimental ovine neosporosis

Abstract

Neospora caninum is considered one of the main causes of abortion in cattle, yet recent studies have also emphasised its relevance as an abortifacient in small ruminants. In order to gain deeper insight into the pathogenesis of ovine neosporosis, pregnant ewes were intravenously inoculated with 106 tachyzoites of the Nc-Spain7 isolate at days 40, 90 or 120 of gestation. Infection during the first term resulted in the death of all foetuses between days 19 and 21 post-infection, showing mainly necrotic lesions in foetal liver and the highest parasite DNA detection and burden in both placenta and foetal viscera. After infection at day 90, foetal death was also detected in all ewes, although later (34–48 days post-infection). In this group, lesions were mainly inflammatory. Foetal livers showed the lowest frequency of lesions, as well as the lowest parasite detection and burden. All ewes infected at day 120 delivered viable lambs, although 3 out of 9 showed weakness and recumbency. Neospora DNA was detected in all lambs but one, and parasite burden was similar to that observed in day 90 group. Lesions in this group showed more conspicuous infiltration of inflammatory cells and higher frequency in foetal brain and muscle when compared to both previous groups. These results highlight the crucial role that the stage of gestation plays on the course of ovine neosporosis, similar to that reported in bovine neosporosis, and open the doors to consider sheep as a valid model for exogenous transplacental transmission for ruminant neosporosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-014-0139-y) contains supplementary material, which is available to authorized users.

Dose-dependent effects of experimental infection with the virulent Neospora caninum Nc-Spain7 isolate in a pregnant mouse model

“…The Nc-Spain7 isolate was selected due to its biological traits, as it has been shown to be highly virulent in vitro (Regidor-Cerrillo et al, 2011) andin vivo (Regidor-Cerrillo et al, 2010;Caspe et al, 2012;Collantes-Fernández et al, 2012;Dellarupe et al, 2014;Regidor-Cerrillo et al, 2014;Arranz-Solís et al, 2015). Moreover, the timing of parasite culture passage has been acknowledged to play an important role, since attenuation due to prolonged in vitro maintenance of N. caninum isolates has been previously described (Long et al, 1998;Bartley et al, 2006).…”

“…However, there are clear indications that this infection dose is much too high: (i) mice were infected with a similar number of parasites (2 × 10 6 ) as normally employed in ruminant models such as 10 7 for cows and 10 6 for sheep, which are sufficient to cause foetal death when inoculated during the first term of gestation (Williams et al, 2007;Caspe et al, 2012;RegidorCerrillo et al, 2014;Arranz-Solís et al, 2015); (ii) in terms of body weight mice differ from cattle and sheep to a much higher degree; (iii) in many of these mouse studies dams developed clinical signs of disease, something which does not occur in ruminants. This could give rise to biased results in vaccine screenings, and might lead to a premature dismissal of potential active formulations, even more if a highly virulent isolate, such as Nc-Liv, is used.…”

“…Challenge was carried out using the Nc-Spain7 isolate, which had been earlier obtained from an asymptomatic calf (Regidor-Cerrillo et al, 2008). This isolate has a controlled low number of passages in cell culture and its high degree of virulence has been demonstrated in vitro (RegidorCerrillo et al, 2011) andin vivo (Regidor-Cerrillo et al, 2010;Caspe et al, 2012;Collantes-Fernández et al, 2012;Dellarupe et al, 2014;Regidor-Cerrillo et al, 2014;Arranz-Solís et al, 2015). Our findings could provide the basis for a standardized pregnant mouse model for the evaluation of drug and vaccine candidates under unified experimental criteria.…”

Vaccines for bovine neosporosis: current status and key aspects for development

“…In a recent work, Arranz‐Solís et al . characterized the clinical, parasitological and lesional parameters in experimental ovine neosporosis at early stage (40 dg), mid‐stage (90 dg) and late stage (120 dg) of pregnancy under the same infection parameters (iv inoculation of Churra sheep with 10 6 tachyzoites of Nc‐Spain7 isolate). Results in this study agreed with previous studies .…”

“…Different researchers have carried out experimental infection in pregnant ewes (83), but similarly to the mouse models, there have been, until recently, no attempts to establish a standardized model of experimental ovine neosporosis. In a recent work, Arranz-Sol ıs et al (129) characterized the clinical, parasitological and lesional parameters in experimental ovine neosporosis at early stage (40 dg), mid-stage (90 dg) and late stage (120 dg) of pregnancy under the same infection parameters (iv inoculation of Churra sheep with 10 6 tachyzoites of Nc-Spain7 isolate). Results in this study agreed with previous studies (83).…”