Helminth infections still represent a huge public health problem throughout the developing world and in the absence of vaccines control is based on periodic mass drug administration. Poor efficacy of some anthelmintics and concerns about emergence of drug resistance has highlighted the need for new drug discovery. Most current anthelmintics were discovered through in vivo screening of selected compounds in animal models but recent approaches have shifted towards screening for activity against adult or larval stages in vitro. Larvae are normally available in greater numbers than adults, can often be produced in vitro and are small enough for microplate assays. However, the manual visualization of drug effects in vitro is subjective, laborious and slow. This can be overcome by application of automated readouts including high-content imaging. Incorporated into robotically controlled HTS platforms such methods allow the very large compound collections being made available by the pharmaceutical industry or academic organizations to be screened against helminths for the first time, invigorating the drug discovery pipeline. Here, we review the status of whole-organism screens based on in vitro activity against living worms and highlight the recent progress towards automated image-based readouts.
