title: A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility.
abstract: BACKGROUND
  Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-throughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods.
  
  
  RESULTS
  Here we describe a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC(50) values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and -resistant isolates of H. contortus.
  
  
  CONCLUSIONS
  Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing.
authors.affiliation: James Cook University, Cairns, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Smout
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Kotze
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000032:analysis / Q000494:pharmacology*; D004283:Dog Diseases / Q000188:drug therapy / Q000469:parasitology; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004351:Drug Resistance; D006373:Helminthiasis / Q000188:drug therapy* / Q000469:parasitology; D006374:Helminthiasis, Animal / Q000188:drug therapy* / Q000469:parasitology; D006376:Helminths / Q000187:drug effects / Q000502:physiology; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D051379:Mice; D021261:Parasitic Sensitivity Tests; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology
chemical_list: D000871:Anthelmintics