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AN IN VITRO LARVAL MOTILITY ASSAY TO DETERMINE ANTHELMINTIC SENSITIVITY FOR HUMAN HOOKWORM AND STRONGYLOIDES SPECIES

With the implementation of programs to control lymphatic filariasis and soil-transmitted helminths using broad spectrum anthelmintics, including albendazole and ivermectin, there is a need to develop an in vitro assay for detection of drug resistance. This report describes an in vitro assay for measuring the effects of ivermectin and benzimidazoles on the motility of larvae of the hookworm species Ancylostoma ceylanicum, A. caninum, and Necator americanus, and Strongyloides species including Strongyloides stercoralis, and S. ratti. A dose-response relationship was demonstrated with each of the parasite species, with distinct differences observed between the various species. In pilot field testing of the assay with N. americanus larvae recovered from human fecal samples, a dose-response relationship was observed with ivermectin. While the assay has demonstrated the ability to determine drug responsiveness, its usefulness in resistance detection will require correlation with the clinical outcome among individuals infected with parasite strains showing different drug sensitivities.

Received February 3, 2004. Accepted for publication May 11, 2004.

Acknowledgments: We thank Absalom Mai, Melinda Susapu, and Dr. Moses Bockarie (Papua New Guinea Institute for Medical Research, Madang, Papua New Guinea) and Will Kastens and Dr. James Kazura (Case Western Reserve University Center of Global Health and Disease, Cleveland, OH) for their assistance in enabling access to the human clinical samples used to develop the pilot assay, and Dr. Glen Coleman (Veterinary School of the University of Queensland) for undertaking parasitologic analysis on the canine fecal samples.

Financial support: This work was supported in part by grants from GlaxoSmithKline and from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR).

Authors’ addresses: A. C. Kotze and J. O’Grady, Commonwealth Scientific and Industrial Research Organisation Livestock Industries, St. Lucia, Queensland 4067, Australia. S. Clifford and J. M. Behnke, School of Biological Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. J. S. McCarthy, Queensland Institute of Medical Research, Centre for International and Tropical Health and Nutrition, The University of Queensland, Herston Road, Brisbane, Queensland 4029, Australia, Telephone: 61-7-3845-3796, Fax: 61-7-3362-0104, E-mail: J.McCarthy{at}uq.edu.au.

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