Using a health-rating system to evaluate the usefulness of Caenorhabditis elegans as a model for anthelmintic study

PLoS One. 2017 Jun 20;12(6):e0179376. doi: 10.1371/journal.pone.0179376. eCollection 2017.

Abstract

Soil-transmitted helminths (STHs) are intestinal parasitic nematodes that infect humans, and are transmitted through contaminated soil. These nematodes include the large roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancylostoma ceylanicum, Ancylostoma duodenale, and Necator americanus). Nearly 1.5 billion people (~24% of the population) worldwide are infected with at least one species of these parasites, burdening the poor, in particular, children and pregnant women. To combat these diseases, the WHO only recognizes four anthelmintic drugs, including the preferred drug, albendazole, for mass drug administration (MDA). These four drugs have a total of two different mechanisms of action, and, as expected, resistance has been observed. This problem calls for new drugs with different mechanisms of action. Although there is precedence for the use of Caenorhabditis elegans (C. elegans), a free-living nematode, as a model for drug screening and anthelmintic testing, their usefulness for such anthelmintic study is not clear as past research has shown that C. elegans did not show a strong response to albendazole, the MDA drug of choice, in comparison with various STHs under similar treatment. To further examine if C. elegans has the potential to be a good model organism for anthelmintic drug study, we employed a health rating scale in order to tease out potential effects of albendazole, and other anthelmintics, that may have been missed using a binary, dead/alive scale. Using the health-rating scale we found that although the worms may have not been dying, they were sick, showing dose responses to anthelmintic drugs, including albendazole, reinforcing C. elegans as a useful model for anthelmintic study.

MeSH terms

  • Albendazole / pharmacology
  • Albendazole / therapeutic use
  • Animals
  • Anthelmintics / pharmacology*
  • Anthelmintics / therapeutic use
  • Caenorhabditis elegans / drug effects*
  • Helminthiasis / drug therapy
  • Humans
  • Inhibitory Concentration 50
  • Ivermectin / pharmacology
  • Ivermectin / therapeutic use
  • Lethal Dose 50
  • Nitro Compounds
  • Parasitic Sensitivity Tests
  • Pyrantel / pharmacology
  • Pyrantel / therapeutic use
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use

Substances

  • Anthelmintics
  • Nitro Compounds
  • Thiazoles
  • Pyrantel
  • Ivermectin
  • Albendazole
  • nitazoxanide

Grants and funding

The authors received no specific funding for this work.