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Study on the activity of antiparasitic agents against Onchocerca lienalis third stage larvae in vitro
Abstract:
The in vitro drug response of third stage larvae of the cattle filarial worm Onchocerca lienalis has been studied. Larvae were maintained in Minimum Essential Eagles medium supplemented with 10% inactivated foetal calf serum and exposed to the following drugs: Mel W, caparsolate sodium, suramin, ivermectin, flubendazole, levamisole and amoscanate plus 3 novel melaminylthioarsenites. Antiparasitic activity of these compounds has been assessed on their killing effects and their ability to totally inhibit the moult from the third to the fourth stage. Unfortunately, moulting occurred at a low rate in the culture system used and was not suitable as a quantitative parameter for describing drug activity. However, the results indicated that if the rate of ecdysis could be increased by improving the culture conditions, moulting could be used in this manner since exsheathment has inhibited by certain compounds at concentrations where killing effects were less than 50%. Of the compounds evaluated ivermectin demonstrated good activity, totally preventing ecdysis at 0.001 microgram/ml. The drug assay system used in this study may offer a starting point for the eventual development of a meaningful and specific in vitro screen for new anti-Onchocerca agents.
Insights
Ivermectin effectively inhibited the molting of cattle filarial worm larvae in vitro. This study suggests a new method for screening anti-Onchocerca drugs, though larval molting rates need improvement for better results.
Area of Science:
- Veterinary Parasitology
- Drug Discovery
- Molecular Biology
Background:
- Filarial worms like Onchocerca lienalis cause significant disease in cattle.
- Effective in vitro models are crucial for developing new antiparasitic drugs.
- Current drug screening methods for Onchocerca species require optimization.
Purpose of the Study:
- To evaluate the in vitro efficacy of various drugs against third-stage larvae of Onchocerca lienalis.
- To assess the potential of larval molting inhibition as a quantitative measure for drug activity.
- To establish a foundation for developing a specific in vitro screen for novel anti-Onchocerca agents.
Main Methods:
- Culturing third-stage larvae of Onchocerca lienalis in supplemented Minimum Essential Eagles medium.
- Exposing larvae to a panel of antiparasitic drugs, including ivermectin, flubendazole, and novel melaminylthioarsenites.
- Assessing drug activity based on larval killing effects and inhibition of the third to fourth stage molt (ecdysis).
Main Results:
- Ivermectin demonstrated significant activity, completely inhibiting larval ecdysis at a concentration of 0.001 microgram/ml.
- Low molting rates in the current culture system limited its use as a quantitative drug activity parameter.
- Some compounds showed potential to inhibit exsheathment at concentrations with less than 50% killing effect.
Conclusions:
- The in vitro drug assay system shows promise for screening new anti-Onchocerca compounds.
- Optimizing culture conditions to increase larval molting rates is necessary for a robust quantitative assay.
- Ivermectin's potent inhibition of ecdysis highlights its potential in treating cattle filariasis.