title: A novel isothermal microcalorimetry tool to assess drug effects on Ancylostoma ceylanicum and Necator americanus.
abstract: Soil-transmitted helminths, which affect the poorest communities, worldwide cause a range of symptoms and morbidity, yet few treatment options are available and drug resistance is a concern. To improve and accelerate anthelminthic drug discovery, novel drug screening tools such as isothermal microcalorimetry (IMC) have been tested with great potential. In this study, we used a novel microcalorimeter, the calScreener™, to study the viability on the hookworms Necator americanus and Ancylostoma ceylanicum as well as the whipworm Trichuris muris. Significant heat flow signals could be obtained with already one adult worm per channel for all three species. High-amplitude oscillations were observed for the hookworms; however, adult T. muris showed a twofold heat flow decrease during the first 24 h. Antinematodal effects of ivermectin and levamisole at 1, 10, and 100 μg/ml were evaluated on adult N. americanus and A. ceylanicum. Levamisole-treated hookworms showed a decline in heat flow and oscillation amplitude in a dose-response manner. Heat flow for ivermectin-treated hookworms increased proportionally with increased concentrations of ivermectin, though the wavelet analysis showed an opposite trend as observed by flatter wavelets. In conclusion, the calScreener™ is an excellent tool to study drug effects on intestinal hookworms at the adult worm stage as it offers a lower detection limit than other IMC devices and the possibility to monitor worm viability online.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002, Basel, Switzerland.|University of Basel, CH-4003, Basel, Switzerland.
authors.forename: Dayana
authors.initials: D
authors.lastname: Flores
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002, Basel, Switzerland.|University of Basel, CH-4003, Basel, Switzerland.
authors.forename: Gordana
authors.initials: G
authors.lastname: Panic
authors.affiliation: Center of Biomechanics & Biocalorimetry, University of Basel c/o Department Biomedical Engineering (DBE), CH-4123, Allschwil, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Braissant
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002, Basel, Switzerland. jennifer.keiser@unibas.ch.|University of Basel, CH-4003, Basel, Switzerland. jennifer.keiser@unibas.ch.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
mesh_terms: D000722:Ancylostoma / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D000977:Antiparasitic Agents / Q000494:pharmacology; D002151:Calorimetry / Q000295:instrumentation*; D006224:Cricetinae; D055808:Drug Discovery / Q000295:instrumentation*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006358:Hot Temperature; D007422:Intestines / Q000469:parasitology; D007559:Ivermectin / Q000494:pharmacology; D007978:Levamisole / Q000494:pharmacology; D051379:Mice; D017221:Necator americanus / Q000187:drug effects* / Q000502:physiology; D014258:Trichuris / Q000187:drug effects / Q000502:physiology
chemical_list: D000969:Antinematodal Agents; D000977:Antiparasitic Agents; D007978:Levamisole; D007559:Ivermectin
keywords: Drug discovery; Drug screening; Hookworm; Isothermal microcalorimetry; Whipworm