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Effects of miltefosine treatment in fibroblast cell cultures and in mice experimentally infected with Neospora caninum tachyzoites

Published online by Cambridge University Press:  06 February 2012

KARIM DEBACHE  and
ANDREW HEMPHILL
KARIM DEBACHE
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
ANDREW HEMPHILL*
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
*
*Corresponding author: [email protected]
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Summary

Miltefosine was investigated for its activity against Neospora caninum tachyzoites in vitro, and was shown to inhibit the proliferation of N. caninum tachyzoites cultured in human foreskin fibroblasts (HFF) with an IC50 of 5·2 μM. Treatment of infected cells with 25 μM miltefosine for a period of 10 h had only a parasitostatic effect, while after 20 h of treatment parasiticidal effects were observed. This was confirmed by transmission electron microscopy of N. caninum-infected and miltefosine-treated HFF. Administration of miltefosine to N. caninum-infected Balb/c female mice at 40 mg/kg/day for 14 days resulted in 6 out of 10 mice exhibiting weight loss, ruffled coat and apathy between days 7 and 13 post-infection. In the group that received placebo, only 2 out of 8 mice succumbed to infection, but the cerebral burden was significantly higher compared to the miltefosine treatment group. In a second experiment, the time-span of treatment was reduced to 5 days, and mice were maintained without further treatment for 4 weeks. Only 2 out of 9 mice in the miltefosine treatment group exhibited signs of disease, while 8 out of 10 mice succumbed to infection in the placebo group. These results showed that miltefosine hampered the dissemination of parasites into the CNS during experimental N. caninum infection in mice.

Keywords

miltefosineNeospora caninumtachyzoitescultured fibroblastsproliferation
Type
Research Article
Information
Parasitology , Volume 139 , Issue 7 , June 2012 , pp. 934 - 944
Copyright
Copyright © Cambridge University Press 2012

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Supplementary material: File

Debache Supplementary Table

Supplementary Table 1. Supplementary data showing the day of euthanasia (if clinical signs occurred prior to termination of the experiment) and the cerebral parasite burden for each individual mouse as determined by real time PCR

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