Journal ArticleDOI
A new class of anthelmintics effective against drug-resistant nematodes
Ronald Kaminsky,Pierre Ducray,Martin Jung,Ralph Clover,Lucien Rufener,Lucien Rufener,Jacques Bouvier,Sandra Schorderet Weber,Andre Wenger,Susanne Christine Wieland-Berghausen,Thomas Goebel,Noëlle Gauvry,François Pautrat,Thomas Skripsky,Olivier Froelich,Clarisse Komoin-Oka,Bethany Westlund,Ann Sluder,Pascal Mäser +18 more
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TLDR
The discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes are described.Abstract:
Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.read more
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Journal ArticleDOI
Efficacy of Current Drugs Against Soil-Transmitted Helminth Infections: Systematic Review and Meta-analysis
Jennifer Keiser,Jürg Utzinger +1 more
TL;DR: In this paper, the authors evaluated the efficacy of single-dose oral albendazole, mebendaxole, levamisole, and pyrantel pamoate against A lumbricoides, hookworm, and Trichuris trichiura infections.
Journal ArticleDOI
Anthelmintic resistance in nematode parasites of cattle: a global issue?
TL;DR: The number of reports in the literature over the past five years suggests a rapidly escalating problem of nematodes resistant to the most commonly used anthelmintics, and how previous research in small ruminants can improve the management of anthel Mintic resistance in cattle is discussed.
Journal ArticleDOI
The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery
Roz Laing,Taisei Kikuchi,Taisei Kikuchi,Axel Martinelli,Isheng J. Tsai,Isheng J. Tsai,Robin N. Beech,Elizabeth Redman,Nancy Holroyd,David J. Bartley,Helen Beasley,Collette Britton,David M. Curran,Eileen Devaney,Aude Gilabert,Martin Hunt,Frank Jackson,Stephanie L Johnston,Ivan Kryukov,Keyu Li,Alison A. Morrison,Adam J. Reid,Neil Sargison,Gary Saunders,Gary Saunders,James D. Wasmuth,Adrian J. Wolstenholme,Matthew Berriman,John S. Gilleard,James Cotton +29 more
TL;DR: The H. contortus genome and transcriptome provide an essential platform for postgenomic research in this and other important strongylid parasites and provide the most comprehensive understanding yet of the action of several important anthelmintics.
Journal ArticleDOI
Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective.
TL;DR: The importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods is emphasized.
Book ChapterDOI
The Drugs We Have and the Drugs We Need Against Major Helminth Infections
TL;DR: This review focuses on soil-transmitted helminthiasis (ascariasis, hookworm disease, strongyloidiasis and trichuriasis) and food-borne trematodiasis and discusses the few drugs that are currently available for their treatment and control.
References
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Journal ArticleDOI
Improved Prediction of Signal Peptides: SignalP 3.0
TL;DR: Improvements of the currently most popular method for prediction of classically secreted proteins, SignalP, which consists of two different predictors based on neural network and hidden Markov model algorithms, where both components have been updated.
Journal ArticleDOI
Drug resistance in nematodes of veterinary importance: a status report
TL;DR: There is an urgent need to develop both novel non-chemical approaches for parasite control and molecular assays capable of detecting resistant worms.
Journal ArticleDOI
Drug resistance in veterinary helminths
Adrian J. Wolstenholme,Ian Fairweather,Roger K. Prichard,Georg von Samson-Himmelstjerna,Nicholas C. Sangster +4 more
TL;DR: Some of the recent findings on resistance mechanisms are summarized, some recommendations for limiting its impact are put forward and some priorities for research in this area are suggested.
Journal ArticleDOI
Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map
TL;DR: In this paper, the authors used bulked segregant analysis (BSA) to identify 6,222 single nucleotide polymorphisms (SNPs) modifying restriction enzyme recognition sites ('snip-SNPs'), which are easily detected as RFLPs.