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Trends in Parasitology Mar 2021Anthelmintic drugs are the major line of defense against parasitic nematode infections, but the arsenal is limited and resistance threatens sustained efficacy of the... (Review)
Review
Anthelmintic drugs are the major line of defense against parasitic nematode infections, but the arsenal is limited and resistance threatens sustained efficacy of the available drugs. Discoveries of the modes of action of these drugs and mechanisms of resistance have predominantly come from studies of a related nonparasitic nematode species, Caenorhabditis elegans, and the parasitic nematode Haemonchus contortus. Here, we discuss how our understanding of anthelmintic resistance and modes of action came from the interplay of results from each of these species. We argue that this 'cycle of discovery', where results from one species inform the design of experiments in the other, can use the complementary strengths of both to understand anthelmintic modes of action and mechanisms of resistance.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Drug Resistance; Haemonchus; Nematoda; Nematode Infections; Research
PubMed: 33317926
DOI: 10.1016/j.pt.2020.11.008 -
Veterinary Parasitology Jun 2023The faecal egg count reduction test (FECRT) remains the method of choice for establishing the efficacy of anthelmintic compounds in the field, including the diagnosis of... (Review)
Review
World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guideline for diagnosing anthelmintic resistance using the faecal egg count reduction test in ruminants, horses and swine.
The faecal egg count reduction test (FECRT) remains the method of choice for establishing the efficacy of anthelmintic compounds in the field, including the diagnosis of anthelmintic resistance. We present a guideline for improving the standardization and performance of the FECRT that has four sections. In the first section, we address the major issues relevant to experimental design, choice of faecal egg count (FEC) method, statistical analysis, and interpretation of the FECRT results. In the second section, we make a series of general recommendations that are applicable across all animals addressed in this guideline. In the third section, we provide separate guidance details for cattle, small ruminants (sheep and goats), horses and pigs to address the issues that are specific to the different animal types. Finally, we provide overviews of the specific details required to conduct an FECRT for each of the different host species. To address the issues of statistical power vs. practicality, we also provide two separate options for each animal species; (i) a version designed to detect small changes in efficacy that is intended for use in scientific studies, and (ii) a less resource-intensive version intended for routine use by veterinarians and livestock owners to detect larger changes in efficacy. Compared to the previous FECRT recommendations, four important differences are noted. First, it is now generally recommended to perform the FECRT based on pre- and post-treatment FEC of the same animals (paired study design), rather than on post-treatment FEC of both treated and untreated (control) animals (unpaired study design). Second, instead of requiring a minimum mean FEC (expressed in eggs per gram (EPG)) of the group to be tested, the new requirement is for a minimum total number of eggs to be counted under the microscope (cumulative number of eggs counted before the application of a conversion factor). Third, we provide flexibility in the required size of the treatment group by presenting three separate options that depend on the (expected) number of eggs counted. Finally, these guidelines address all major livestock species, and the thresholds for defining reduced efficacy are adapted and aligned to host species, anthelmintic drug and parasite species. In conclusion, these new guidelines provide improved methodology and standardization of the FECRT for all major livestock species.
Topics: Animals; Horses; Cattle; Sheep; Swine; Parasite Egg Count; Ovum; Anthelmintics; Feces; Goats; Drug Resistance
PubMed: 37121092
DOI: 10.1016/j.vetpar.2023.109936 -
Journal of Traditional Chinese Medicine... Aug 2022Helminths or Parasitic worms of humans may cause chronic and sometimes deadly diseases, considered as neglected tropical diseases (NTDs) that infect around two billion... (Review)
Review
Helminths or Parasitic worms of humans may cause chronic and sometimes deadly diseases, considered as neglected tropical diseases (NTDs) that infect around two billion people worldwide. Plants have been used as anthelmintics from ancient times. This review is a compilation of plants as source of anthelmintic drug. All information presented in this review article regarding the anthelmintic activities of plants from 2005 and has been acquired by approaching various electronic databases, including Scopus, Google scholar, Web of science and PubMed. Literature was surveyed for anthelmintic activity of plants which showed that secondary metabolites of plants like terpenes, glycosides, saponins, flavonoids, tannins and alkaloids were having anthelmintic activity. Since this review is a compilation of anthelmintic activity of plants from the year 2005, it will definitely be a fruitful study for researchers working in this field.
Topics: Anthelmintics; Flavonoids; Humans; Plant Extracts; Saponins
PubMed: 35848982
DOI: 10.19852/j.cnki.jtcm.2022.04.007 -
International Journal For Parasitology.... Aug 2019Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management... (Review)
Review
Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management strategies increasingly aim to preserve a proportion of the parasite population in 'refugia', unexposed to treatment. While persuasive in its logic, and widely advocated as best practice, evidence for the ability of refugia-based approaches to slow the development of drug resistance in parasitic helminths is currently limited. Moreover, the conditions needed for refugia to work, or how transferable those are between parasite-host systems, are not known. This review, born of an international workshop, seeks to deconstruct the concept of refugia and examine its assumptions and applicability in different situations. We conclude that factors potentially important to refugia, such as the fitness cost of drug resistance, the degree of mixing between parasite sub-populations selected through treatment or not, and the impact of parasite life-history, genetics and environment on the population dynamics of resistance, vary widely between systems. The success of attempts to generate refugia to limit anthelmintic drug resistance are therefore likely to be highly dependent on the system in hand. Additional research is needed on the concept of refugia and the underlying principles for its application across systems, as well as empirical studies within systems that prove and optimise its usefulness.
Topics: Animals; Anthelmintics; Drug Resistance; Helminthiasis; Helminths; Humans; Refugium
PubMed: 31125837
DOI: 10.1016/j.ijpddr.2019.05.001 -
Molecules (Basel, Switzerland) Nov 2022Helminths, with an estimated 1.5 billion annual global infections, are one of the major health challenges worldwide. The current strategy of the World Health... (Review)
Review
Helminths, with an estimated 1.5 billion annual global infections, are one of the major health challenges worldwide. The current strategy of the World Health Organization to prevent helminth infection includes increasing hygienic awareness, providing better sanitation and preventative anthelmintic drug therapy in vulnerable populations. Nowadays, anthelmintic drugs are used heavily in livestock, both in case of infection and as a preventative measure. However, this has led to the development of resistance against several of the most common drugs, such as levamisole, ivermectin and thiabendazole. As many as 70% of the livestock in developed countries now has helminths that are drug resistant, and multiple resistance is common. Because of this, novel anthelmintics are urgently needed to help combat large-scale production losses. Prior to this review, no comprehensive review of the anthelmintic effects of essential oils and their components existed. Multiple review articles have been published on the uses of a single plant and its extracts that only briefly touch upon their anthelmintic activity. This review aims to provide a detailed overview of essential oils and their components as anthelmintic treatment against a wider variety of helminths.
Topics: Animals; Humans; Oils, Volatile; Anthelmintics; Helminths; Helminthiasis; Levamisole; Drug Resistance
PubMed: 36500419
DOI: 10.3390/molecules27238327 -
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 -
Molecules (Basel, Switzerland) Jul 2022Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined...
Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives - obtained during reactions of -substituted amidrazones with itaconic anhydride. Two groups of compounds, - and - differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives - and the anti-inflammatory activity of and - were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds and - was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives and - on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds - was studied in the sp. nematodes model. Most compounds (-) proved to be non-toxic to human PBMC. Derivatives - showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds and - significantly reduced the production of TNF-α and derivatives - decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound . Compounds and demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.
Topics: Anthelmintics; Anti-Infective Agents; Anti-Inflammatory Agents; Humans; Imidazoles; Leukocytes, Mononuclear; Sulfonamides; Thiophenes; Triazoles; Tumor Necrosis Factor-alpha
PubMed: 35889357
DOI: 10.3390/molecules27144488 -
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 -
International Journal For Parasitology Jul 2023
Topics: Anthelmintics; Vaccines; Drug Resistance
PubMed: 37257805
DOI: 10.1016/j.ijpara.2023.05.004 -
WormBook : the Online Review of C.... Nov 2007C. elegans is sensitive to the majority of anthelmintic drugs that are used against parasitic worm infections of humans and livestock. This has provided the opportunity... (Review)
Review
C. elegans is sensitive to the majority of anthelmintic drugs that are used against parasitic worm infections of humans and livestock. This has provided the opportunity to use molecular genetic techniques in the worm for mode of action studies. These approaches continue to be of considerable value to the field of parasitology. In addition, there are numerous examples of anthelmintic drugs providing exceptionally useful pharmacological tools to delineate fundamental aspects of cell signalling in C. elegans. This has primarily been achieved through the use of anthelmintics in forward genetic screens followed by the mapping and characterization of genes that confer altered susceptibility to the drug. Less fruitful so far, but nonetheless useful, has been the direct use of C. elegans for anthelmintic discovery programmes. In this brief review we provide an introduction to the use of C. elegans as a 'model parasite', outline the actions of the main classes of anthelmintics, and highlight approaches that have been of particular value.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Forecasting; Models, Animal
PubMed: 17988075
DOI: 10.1895/wormbook.1.143.1