title: Toltrazuril treatment to control diaplacental Neospora caninum transmission 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.
authors.affiliation: Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland. bruno.gottstein@ipa.unibe.ch
authors.forename: B
authors.initials: B
authors.lastname: Gottstein
authors.forename: G R
authors.initials: GR
authors.lastname: Razmi
authors.forename: P
authors.initials: P
authors.lastname: Ammann
authors.forename: H
authors.initials: H
authors.lastname: Sager
authors.forename: N
authors.initials: N
authors.lastname: Müller
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000469:parasitology; D001921:Brain / Q000469:parasitology; D003048:Coccidiosis / Q000188:drug therapy* / Q000635:transmission / Q000662:veterinary; D003049:Coccidiostats / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000378:metabolism; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control* / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D018688:Neospora / Q000187:drug effects* / Q000302:isolation & purification; D011247:Pregnancy; D015363:Quinolones / Q000627:therapeutic use; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D003049:Coccidiostats; D016054:DNA, Protozoan; D024841:Fluoroquinolones; D015363:Quinolones; D014227:Triazines; D000077422:Enrofloxacin; C036670:toltrazuril