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Journal of Korean Medical Science Feb 2020
Topics: Anthelmintics; Antineoplastic Agents; Fenbendazole; Hepatitis; Humans; Neoplasms; Social Media
PubMed: 32056406
DOI: 10.3346/jkms.2020.35.e75 -
International Journal For Parasitology.... Dec 2022Anthelmintic resistance is reported in equine nematodes with increasing frequency in recent years, and no new anthelmintic classes have been introduced during the past... (Review)
Review
Anthelmintic resistance is reported in equine nematodes with increasing frequency in recent years, and no new anthelmintic classes have been introduced during the past 40 years. This manuscript reviews published literature describing anthelmintic resistance in cyathostomins, Parascaris spp., and Oxyuris equi with special emphasis on larvicidal efficacy against encysted cyathostomin larvae and strongylid egg reappearance periods (ERP). Resistance to benzimidazoles and pyrimidines is highly prevalent in cyathostomin populations around the world, and macrocyclic lactone resistance has been documented in cyathostomins in recent years as well. Two recent studies have documented resistance to the larvicidal regimen of fenbendazole, whereas the larvicidal efficacy of moxidectin is variable, but with no evidence of a reduction from historic levels. In the 1990s, ERP estimates were 8-10 and 12-16 weeks for ivermectin and moxidectin, respectively, while several studies published after year 2000 found ERPs to be 5 weeks for both compounds. This is a clear change in anthelmintic performance, but it remains unclear if this is due to development of anthelmintic resistance or selection for other biological traits leading to a quicker resumption of strongylid egg shedding following anthelmintic treatment. Macrocyclic lactone resistance is common in Parascaris spp. around the world, but recent reports suggests that resistance to the two other classes should be monitored as well. Finally, O. equi has been reported resistant to ivermectin and moxidectin in countries representing four continents. In conclusion, multi-drug resistance is becoming the norm in managed cyathostomin populations around the world, and a similar pattern may be emerging in Parascaris spp. More work is required to understand the mechanisms behind the shortened ERPs, and researchers and veterinarians around the world are encouraged to routinely monitor anthelmintic efficacy against equine nematodes.
Topics: Horses; Animals; Horse Diseases; Anthelmintics; Fenbendazole; Macrolides; Ivermectin; Ascaridoidea; Drug Resistance; Parasite Egg Count; Feces
PubMed: 36342004
DOI: 10.1016/j.ijpddr.2022.10.005 -
Trends in Parasitology Sep 2021Most anthelmintics were discovered through in vivo screens using animal models of infection. Developing in vitro assays for parasitic worms presents several challenges.... (Review)
Review
Most anthelmintics were discovered through in vivo screens using animal models of infection. Developing in vitro assays for parasitic worms presents several challenges. The lack of in vitro life cycle culture protocols requires harvesting worms from vertebrate hosts or vectors, limiting assay throughput. Once worms are removed from the host environment, established anthelmintics often show no obvious phenotype - raising concerns about the predictive value of many in vitro assays. However, with recent progress in understanding how anthelmintics subvert host-parasite interactions, and breakthroughs in high-content imaging and machine learning, in vitro assays have the potential to discern subtle cryptic parasite phenotypes. These may prove better endpoints than conventional in vitro viability assays.
Topics: Animals; Anthelmintics; Drug Evaluation, Preclinical; Helminthiasis; Helminths; Host-Parasite Interactions
PubMed: 34092518
DOI: 10.1016/j.pt.2021.05.004 -
International Journal For Parasitology.... Dec 2020For more than four decades, the free-living nematode Caenorhabditis elegans has been extensively used in anthelmintic research. Classic genetic screens and heterologous... (Review)
Review
For more than four decades, the free-living nematode Caenorhabditis elegans has been extensively used in anthelmintic research. Classic genetic screens and heterologous expression in the C. elegans model enormously contributed to the identification and characterization of molecular targets of all major anthelmintic drug classes. Although these findings provided substantial insights into common anthelmintic mechanisms, a breakthrough in the treatment and control of parasitic nematodes is still not in sight. Instead, we are facing increasing evidence that the enormous diversity within the phylum Nematoda cannot be recapitulated by any single free-living or parasitic species and the development of novel broad-spectrum anthelmintics is not be a simple goal. In the present review, we summarize certain milestones and challenges of the C. elegans model with focus on drug target identification, anthelmintic drug discovery and identification of resistance mechanisms. Furthermore, we present new perspectives and strategies on how current progress in C. elegans research will support future anthelmintic research.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Drug Discovery; Nematoda
PubMed: 33249235
DOI: 10.1016/j.ijpddr.2020.09.005 -
Scientific Reports Dec 2023Parasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in...
Parasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in food production on a global scale. None of the currently available drugs ideally suit all treatment circumstances, and the development of drug-resistant nematode strains has become a challenge to control the infection. There is an urgent need to develop novel anthelmintic compounds. According to our previous report, N-methylbenzo[d]oxazol-2-amine (1) showed anthelmintic activity and lowest cytotoxicity. In this study, in vivo anthelmintic properties were evaluated using Trichinella spiralis infected mice. Toxicity was evaluated using the rats and mode of action using molecular docking and metabolomics approaches. The in vivo results demonstrate that a dose of 250 mg/kg reduced the T. spiralis abundance in the digestive tract by 49%. The 250 mg/kg Albendazole was served as control. The relatively low acute toxicity was categorized into chemical category 5, with an LD greater than 2000 mg/kg body. Molecular docking analysis showed the T. spiralis tubulin beta chain and glutamate-gated channels might not be the main targets of compound 1. Metabolomics analysis was used to explain the effects of compound 1 on the T. spiralis adult worm. The results demonstrated that compound 1 significantly up-regulated the metabolism of purine, pyrimidine and down-regulated sphingolipid metabolism. In conclusion, compound 1 could be a potential molecule for anthelmintic development. The bioavailability, pharmacokinetics, and absorption of this compound should be studied further to provide information for its future efficacy improvement.
Topics: Humans; Mice; Rats; Animals; Molecular Docking Simulation; Anthelmintics; Albendazole; Nematoda; Trichinella spiralis
PubMed: 38129499
DOI: 10.1038/s41598-023-50305-y -
Biology Letters May 2022Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the... (Review)
Review
Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the conditions under which wild ruminants can act as a source of helminths (including anthelmintic-resistant genotypes) for domestic ruminants, and vice versa, with the added possibility that wildlife could act as for drug-susceptible genotypes and hence buffer the spread and development of resistance. Helminth infections cause significant productivity losses in domestic ruminants and a growing resistance to all classes of anthelmintic drug escalates concerns around helminth infection in the livestock industry. Previous research demonstrates that drug-resistant strains of the pathogenic nematode can be transmitted between wild and domestic ruminants, and that gastro-intestinal nematode infections are more intense in wild ruminants within areas of high livestock density. In this article, the factors likely to influence the role of wild ruminants in helminth infections and anthelmintic resistance in livestock are considered, including host population movement across heterogeneous landscapes, and the effects of climate and environment on parasite dynamics. Methods of predicting and validating suspected drivers of helminth transmission in this context are considered based on advances in predictive modelling and molecular tools.
Topics: Animals; Anthelmintics; Drug Resistance; Haemonchus; Livestock; Ruminants
PubMed: 35506237
DOI: 10.1098/rsbl.2022.0057 -
Trends in Parasitology Jun 2021Helminth secretomes comprise many potential immunomodulators. The molecular and functional diversity of these entities and their importance at the host-parasite... (Review)
Review
Helminth secretomes comprise many potential immunomodulators. The molecular and functional diversity of these entities and their importance at the host-parasite interface have been increasingly recognized. It is now common to hypothesize that parasite-derived molecules (PDMs) are essential mediators used by parasites to establish and remain in their hosts. Suppression of PDM release has been reported for two anthelmintic drug classes, the benzimidazoles and macrocyclic lactones, the mechanisms of action of which remain incompletely resolved. We propose that bringing together recent insights from different streams of parasitology research, for example, immunoparasitology and pharmacology, will stimulate the development of new ways to alter the host-parasite interface in the search for novel anthelmintic strategies.
Topics: Animals; Anthelmintics; Helminthiasis; Helminths; Host-Parasite Interactions
PubMed: 33563557
DOI: 10.1016/j.pt.2021.01.007 -
Proceedings of the National Academy of... Apr 2021Estimating the impact of child health investments on adult living standards entails multiple methodological challenges, including the lack of experimental variation in...
Estimating the impact of child health investments on adult living standards entails multiple methodological challenges, including the lack of experimental variation in health status, an inability to track individuals over time, and accurately measuring living standards and productivity in low-income settings. This study exploits a randomized school health intervention that provided deworming treatment to Kenyan children, and uses longitudinal data to estimate impacts on economic outcomes up to 20 y later. The effective respondent tracking rate was 84%. Individuals who received two to three additional years of childhood deworming experienced a 14% gain in consumption expenditures and 13% increase in hourly earnings. There are also shifts in sectors of residence and employment: treatment group individuals are 9% more likely to live in urban areas, and experience a 9% increase in nonagricultural work hours. Most effects are concentrated among males and older individuals. The observed consumption and earnings benefits, together with deworming's low cost when distributed at scale, imply that a conservative estimate of its annualized social internal rate of return is 37%, a high return by any standard.
Topics: Adolescent; Adult; Anthelmintics; Child; Child Health; Cost of Illness; Drug Utilization; Employment; Helminthiasis; Humans; Income; Kenya
PubMed: 33790017
DOI: 10.1073/pnas.2023185118 -
WormBook : the Online Review of C.... Dec 2014Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for... (Review)
Review
Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for agriculture. As such, these nematodes place a major burden on human health, on livestock production, on the welfare of companion animals and on crop production. In the 21st century there are two major challenges posed by the wide-spread prevalence of parasitic nematodes. First, many anthelmintic drugs are losing their effectiveness because nematode strains with resistance are emerging. Second, serious concerns regarding the environmental impact of the nematicides used for crop protection have prompted legislation to remove them from use, leaving agriculture at increased risk from nematode pests. There is clearly a need for a concerted effort to address these challenges. Over the last few decades the free-living nematode Caenorhabditis elegans has provided the opportunity to use molecular genetic techniques for mode of action studies for anthelmintics and nematicides. These approaches continue to be of considerable value. Less fruitful so far, but nonetheless potentially very useful, has been the direct use of C. elegans for anthelmintic and nematicide discovery programmes. Here we provide an introduction to the use of C. elegans as a 'model' parasitic nematode, briefly review the study of nematode control using C. elegans and highlight approaches that have been of particular value with a view to facilitating wider-use of C. elegans as a platform for anthelmintic and nematicide discovery and development.
Topics: Animals; Anthelmintics; Antinematodal Agents; Caenorhabditis elegans; Drug Evaluation, Preclinical; Helminthiasis; Humans; Models, Biological
PubMed: 25517625
DOI: 10.1895/wormbook.1.143.2 -
Parasite (Paris, France) 2023
Topics: Animals; Ruminants; Anthelmintics; Drug Resistance
PubMed: 36762940
DOI: 10.1051/parasite/2023006