Toltrazuril treatment to control diaplacentalNeospora caninumtransmission in experimentally infected pregnant mice

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.

Toltrazuril treatment of congenitally acquired Neospora caninum infection in newborn mice

“…Toltrazuril is one of those few compounds that have demonstrated antiparasitic activity against N. caninum infections not only in cell culture-based assays, but also in vivo as shown in experimentally infected mice and even cattle (Darius et al 2004a, b;Gottstein et al 2001;Gottstein et al 2005;Kritzner et al 2002;Härdi et al 2006). The present study was designed as a further step in assessing the efficacy of toltrazuril by addressing the effect of toltrazuril in congenitally N. caninum-infected newborn mice.…”

“…However, an efficient metaphylaxis required at least a T cell-mediated immunological support in mice (Ammann et al 2004). It was also reported that toltrazuril treatment of an acute N. caninum infection-induced during pregnancy in miceresulted in a significant reduction of fetal losses (Gottstein et al 2005). Furthermore, initially explorative approaches indicated a basic effectiveness of toltrazuril and its major metabolite, ponazuril, against experimental N. caninum infection in calves (Kritzner et al 2002;Härdi et al 2006).…”

Neospora caninum and neosporosis — recent achievements in host and parasite cell biology and treatment

“…We now recently showed that toltrazuril can contribute to the control of congenital neosporosis in mouse dams (Gottstein et al 2005). As a first finding, toltrazuril-treatment significantly reduced pre-and perinatal losses due to experimental N. caninum infection when compared to nontreated dams in their first gestation.…”

“…Although infected dams may remain carriers of the parasite, they seem not to act as sources of infection for the foetus in later pregnancies, conversely to the situation found in naturally infected cattle (Gottstein et al 2005).…”

“…Besides reducing abortion and infertility rates in pregnant mice, toltrazuril-treatment also affected directly the infection course in the foetuses, best demonstrated by the lack of postnatal death in offspring of toltrazuril-treated mothers versus postnatal death of some of the newborns of nontreated mothers (Gottstein et al 2005). Although infected dams may remain carriers of the parasite, they seem not to act as sources of infection for the foetus in later pregnancies, conversely to the situation found in naturally infected cattle (Gottstein et al 2005).…”