Parasitic gastrointestinal nematodes pose significant health risks to humans, livestock, and companion animals, and their control relies heavily on the use of anthelmintic drugs. Overuse of these drugs has led to the emergence of resistant nematode populations. Herein, a naturally occurring isolate (referred to as BCR) of the dog hookworm, Ancylostoma caninum, that is resistant to 3 major classes of anthelmintics is characterized. Various drug assays were used to determine the resistance of BCR to thiabendazole, ivermectin, moxidectin and pyrantel pamoate. When compared to a drug-susceptible isolate of A. caninum, BCR was shown to be significantly resistant to all 4 of the drugs tested. Multiple single nucleotide polymorphisms have been shown to impart benzimidazole resistance, including the F167Y mutation in the β-tubulin isotype 1 gene, which was confirmed to be present in BCR through molecular analysis. The frequency of the resistant allele in BCR was 76.3% following its first passage in the lab, which represented an increase from approximately 50% in the founding hookworm population. A second, recently described mutation in codon 134 (Q134H) was also detected at lower frequency in the BCR population. Additionally, BCR exhibits an altered larval activation phenotype compared to the susceptible isolate, suggesting differences in the signalling pathways involved in the activation process which may be associated with resistance. Further characterization of this isolate will provide insights into the mechanisms of resistance to macrocyclic lactones and tetrahydropyrimidine anthelmintics.

Soil-transmitted helminths, such as Ascaris lumbricoides, are the most prevalent parasites globally. Optimal anthelmintic treatment for A. lumbricoides in endemically infected communities is challenged by several host-related and environmental factors influencing infection acquisition. We assessed the risk of A. lumbricoides (re)infection after treatment in a Venezuelan rural community. Individual merthiolate-iodine-formaldehyde-fixed faecal samples were collected from 224 persons before a single-dose pyrantel treatment and at 1, 3, 6, 9 and 15 months after treatment. Effects of age, sex and socioeconomic status (SES) on A. lumbricoides prevalence, eggs/gram faeces (EPG) and infection (re)acquisition were assessed using both generalised linear mixed-effects models and survival analysis. Pre-treatment A. lumbricoides prevalence was 39.7%. Higher prevalence was associated with younger age and lower SES. Higher EPG values were observed among young children. Median time to A. lumbricoides infection was six months after treatment: at 1, 3, 6, 9 and 15 months post-treatment, cumulative incidence was 6.7%, 18.9%, 34.6%, 42.2%, and 52.6%, respectively. Younger age, lower SES, and pre-treatment A. lumbricoides infection status showed significantly elevated hazard ratios. Mass drug administration protocols would benefit from considering these factors in selective treatment strategies and possibly more than just annual or biannual treatments in the target population.

In the Anisakidae family, there are nematodes, most of which are parasitic for important commercial fish species. Both public health risks and socio-economic problems are attributed to these parasites. Despite these concerns, knowledge of the metabolism of these parasites remains unknown. Therefore, the main objective of this study was to investigate the receptors of drugs and oxidative metabolic status of two Anisakidae species, Pseudoterranova decipiens (s. s.) and Contracaecum osculatum (s. s.), under the influence of anthelminthic drugs, ivermectin (IVM) and pyrantel (PYR), at different concentrations: 1.56, 3.125 and 6.25 μg mL−1 of culture medium for 3, 6, 9, 12 and 72 h. The mRNA expressions of the γ-aminobutyric acid receptor, acetylcholine receptor subunits, adenosine triphosphate-binding cassette transporters and antioxidative enzymes were determined. The total antioxidant capacity and glutathione S-transferase activity were also examined. To the best of the authors' knowledge, this is the first time that IVM and PYR have been tested against these parasitic nematodes.

Three groups of anthelmintic drugs act directly and selectively on muscle membrane receptors of parasitic nematodes. These groups of anthelmintics are: (1) The Nicotinic Agonists(levamisole, pyrantel, morantel and oxantel) that act on acetylcholine receptors of nematode somatic muscle; (2) The GAB A Agonist, piperazine, that acts on nematode muscle GABA receptors; and (3) The Avermectins that open glutamate gated Cl- channels on nematode pharyngeal muscle. The electrophysiology and pharmacology of muscle and neuromuscular transmission the nematode parasite, Ascaris suum, is outlined and effects of anthelmintics that interfere with transmission described. Resistance to anthelmintics has appeared in some parasitic nematodes but the mechanisms of this resistance remain to be determined

Here we review molecular information related to resistance to the cholinergic anthelmintics in nematodes. The amount of molecular information available varies between the nematode species, with the best understood so far being C. elegans. More information is becoming available for some other parasitic species. The cholinergic anthelmintics act on nematode nicotinic acetylcholine receptors located on somatic muscle cells. Recent findings demonstrate the presence of multiple types of the nicotinic receptors in several nematodes and the numerous genes required to form these multimeric proteins. Not only are the receptors the product of several genes but they are subject to modulation by several other proteins. Mutations altering these modulatory proteins could alter sensitivity to the cholinergic anthelmitics and thus lead to resistance. We also discuss the possibility that resistance to the cholinergic anthelmintics is not necessarily the result of a single mutation but may well be polygenic in nature. Additionally, the mutations resulting in resistance may vary between different species or between resistant isolates of the same species. A list of candidate genes to examine for SNPs is presented.

This paper reviews sites of action of anthelmintic drugs including: (1) levamisole and pyrantel, which act as agonists at nicotinic acetylcholine receptors of nematodes; (2) the avermectins, which potentiate or gate the opening of glutamate-gated chloride channels found only in invertebrates; (3) piperazine, which acts as an agonist at GABA gated chloride channels on nematode muscle; (4) praziquantel, which increases the permeability of trematode tegument to calcium and results in contraction of the parasite muscle; (5) the benzimidazoles, like thiabendazole, which bind selectively to parasite β-tubulin and prevents microtubule formation; (6) the proton ionophores, like closantel, which uncouple oxidative phosphorylation; (7) diamphenethide and clorsulon, which selectively inhibit glucose metabolism of Fasciola and; (8) diethylcarbamazine, which appears to interfere with arachidonic acid metabolism of filarial parasites and host. The review concludes with brief comments on the development of anthelmintics in the future.