High-content approaches to anthelmintic drug screening

Most anthelmintics were discovered through in vivo screens using animal models of infection. Developing in vitro assays for parasitic worms presents several challenges. The lack of in vitro life cycle culture protocols requires harvesting worms from vertebrate hosts or vectors, limiting assay throughput. Once worms are removed from the host environment, established anthelmintics often show no obvious phenotype - raising concerns about the predictive value of many in vitro assays. However, with recent progress in understanding how anthelmintics subvert host-parasite interactions, and breakthroughs in high-content imaging and machine learning, in vitro assays have the potential to discern subtle cryptic parasite phenotypes. These may prove better endpoints than conventional in vitro viability assays.

Automated summary

Most anthelmintics were discovered through in vivo screens using animal models, but developing in vitro assays for parasitic worms faces challenges. The lack of in vitro life cycle culture protocols results in limited assay throughput after harvesting worms from hosts, with established drugs often showing no obvious phenotype, raising doubts about the predictive value of many in vitro assays. However, recent progress in understanding how anthelmintics affect host-parasite interactions, along with advances in high-content imaging and machine learning, may enable in vitro assays to detect subtle cryptic parasite phenotypes better than conventional viability assays.