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    Efficacy of cyclooctadepsipeptides and aminophenylamidines against larval, immature and mature adult stages of a parasitologically characterized trichurosis model in mice (2014)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Kulke, Daniel
    Krücken, Jürgen (WE 13)
    Harder, Achim
    von Samson-Himmelstjerna, Georg (WE 13)
    Quelle
    PLoS Neglected Tropical Diseases; 8(2) — S. e2698
    ISSN: 1935-2727
    Sprache
    Englisch
    Verweise
    URL (Volltext): http://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000021597
    DOI: 10.1371/journal.pntd.0002698
    Pubmed: 24587460
    Kontakt
    Institut für Parasitologie und Tropenveterinärmedizin

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35, 22, 23
    14163 Berlin
    Tel.+49 30 838 62310 Fax.+49 30 838 62323
    email:parasitologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    The genus Trichuris includes parasites of major relevance in veterinary and human medicine. Despite serious economic losses and enormous impact on public health, treatment options against whipworms are very limited. Additionally, there is an obvious lack of appropriately characterized experimental infection models. Therefore, a detailed parasitological characterization of a Trichuris muris isolate was performed in C57BL/10 mice. Subsequently, the in vivo efficacies of the aminophenylamidines amidantel, deacylated amidantel (dAMD) and tribendimidine as well as the cyclooctadepsipeptides emodepside and in particular PF1022A were analyzed. This was performed using various administration routes and treatment schemes targeting histotropic and further developed larval as well as immature and mature adult stages.

    Duration of prepatent period, time-dependent localization of larvae during period of prepatency as well as the duration of patency of the infection were determined before drugs were tested in the characterized trichurosis model. Amidantel showed no effect against mature adult T. muris. Tribendimidine showed significantly higher potency than dAMD after oral treatments (ED50 values of 6.5 vs. 15.1 mg/kg). However, the opposite was found for intraperitoneal treatments (ED50 values of 15.3 vs. 8.3 mg/kg). When emodepside and PF1022A were compared, the latter was significantly less effective against mature adults following intraperitoneal (ED50 values of 6.1 vs. 55.7 mg/kg) or subcutaneous (ED50 values of 15.2 vs. 225.7 mg/kg) administration. Only minimal differences were observed following oral administration (ED50 values of 2.7 vs. 5.2 mg/kg). Triple and most single oral doses with moderate to high dosages of PF1022A showed complete efficacy against histotropic second stage larvae (3 × 100 mg/kg or 1 × 250 mg/kg), further developed larvae (3 × 10 mg/kg or 1 × 100 mg/kg) and immature adults (3 × 10 mg/kg or 1×100 mg/kg). Histotropic first stage larvae were only eliminated after three doses of PF1022A (3 × 100 mg/kg) but not after a single dose.

    These results indicate that the cyclooctadepsipeptides are a drug class with promising candidates for further evaluation for the treatment of trichurosis of humans and livestock animals in single dose regimens.