Authors

Discussion

The preclinical assessment of new macrofilaricides against filarial parasites, which cause lymphatic filariasis and onchocerciasis, necessitates in vivo experimentation because currently, adult parasites cannot be generated from infectious stage larvae in vitro and adult female reproductively active parasites have a very limited life-span in culture.

The current in vitro systems are maintained for only short periods (<1 week). Arguably, this period of time is not sufficient to accurately simulate effects of in vivo drug exposures and may not accurately inform in vivo preclinical testing parameters. We have developed an in vitro co-culture system with human lymphatic endothelial and myeloid cell lines which more accurately replicates the environment in which lymphatic parasites inhabit, making it possible to maintain parasite ‘fitness’ for a period of 2-3 weeks, comparable to those isolated from animal hosts. The longevity of this culture system should facilitate the more accurate in vitro assessment of treatment efficacy, thereby reducing dependence upon in vivo models. As the in vitro co-culture system is more representative of the parasitic niche, it may be used for a first stage drug screen in order to reduce the numbers of animals used. Additionally, our in vitro co-culture system allows for interrogations of host-pathogen relationships and parasite biology to be explored in further detail, again reducing the need for animal experiments.