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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 -
Research in Veterinary Science Dec 2022The objective of this study was to conduct research of the literature available in electronic media on anthelmintic intoxication in sheep and goats. The search for... (Review)
Review
The objective of this study was to conduct research of the literature available in electronic media on anthelmintic intoxication in sheep and goats. The search for primary studies was carried out in five electronic databases: ScienceDirect, PubMed, Scopus, Web of Science, and SciELO. The search terms used were (antihelmintic OR antiparasitic OR vermifuge) AND (poisoning OR toxicity OR overdose OR intoxication) AND (goat OR sheep). A total of 2361 articles were identified from the five databases: Science Direct (n = 1869), PubMed (n = 434), Scopus (n = 37), Web of Science (n = 16), and SciELO (n = 5). As 111 articles were found in duplicates, 2250 were left for review of the title and abstracts, of which 115 were read in full, and 28 were included in the systematic review. Of the 28 articles, 16 involved sheep, 9 involved goats, and 3 involved both species. Twelve drugs were identified in intoxication reports: albendazole (2), closantel (14), disophenol (1), ivermectin (1), levamisole (2), moxidectin (1), netobimin (1), nitroxinil (1), oxfendazole (2), parbendazole (2), tetramizole (1), and thiabendazole (1). The most prevalent symptoms of anthelmintic intoxication reported were showed involvement of the nervous, locomotor, and renal systems, as well as teratogenic influences. Data from this review underscore the need of the care required in the control of parasitic infections through the safe use of antiparasitic drugs to avoid cases of intoxication.
Topics: Sheep; Animals; Goats; Parasite Egg Count; Sheep Diseases; Anthelmintics; Albendazole; Antiparasitic Agents; Drug Resistance; Goat Diseases; Feces
PubMed: 36219891
DOI: 10.1016/j.rvsc.2022.09.038 -
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 -
Parasite (Paris, France) 2023
Topics: Animals; Ruminants; Anthelmintics; Drug Resistance
PubMed: 36762940
DOI: 10.1051/parasite/2023006 -
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 -
Trends in Parasitology Feb 2023Helminth infections of cattle place significant burdens on livestock production and farm economic efficiency. Heavy infections are relatively easy to detect and treat... (Review)
Review
Helminth infections of cattle place significant burdens on livestock production and farm economic efficiency. Heavy infections are relatively easy to detect and treat with anthelmintics. However, subclinical infections have major but often hidden impacts on animals, necessitating more refined diagnostics to detect them and ideally inform farmers about the likely impact of anthelmintic treatment on animal and herd performance. Here, we review recent advances in diagnosing three major cattle helminth infections - gastrointestinal nematodes (GINs), liver flukes, and lungworms - and the search for subclinical infection thresholds to guide treatment decisions. Combining refined diagnostic thresholds with farm-specific information on grazing systems and animal history enables farmers to tailor helminth treatments to specific epidemiological circumstances, thereby limiting anthelmintic resistance (AR) and boosting agricultural efficiency and food security.
Topics: Animals; Cattle; Asymptomatic Infections; Helminths; Nematoda; Anthelmintics; Fascioliasis; Cattle Diseases; Nematode Infections
PubMed: 36526548
DOI: 10.1016/j.pt.2022.11.014 -
Parasitology Research Oct 2022The equine ascarids, Parascaris spp., are important nematode parasites of juvenile horses and were historically model organisms in the field of cell biology, leading to... (Review)
Review
The equine ascarids, Parascaris spp., are important nematode parasites of juvenile horses and were historically model organisms in the field of cell biology, leading to many important discoveries, and are used for the study of chromatin diminution. In veterinary parasitology, Parascaris spp. are important not only because they can cause clinical disease in young horses but also because they are the only ascarid parasites to have developed widespread anthelmintic resistance. Despite this, much of the general biology and mechanisms of anthelmintic resistance are poorly understood. This review condenses known basic biological information and knowledge on the mechanisms of anthelmintic resistance in Parascaris spp., highlighting the importance of foundational research programs. Although two variants of this parasite were recognized based on the number of chromosomes in the 1870s and suggested to be two species in 1890, one of these, P. univalens, appears to have been largely forgotten in the veterinary scientific literature over the past 100 years. We describe how this omission has had a century-long effect on nomenclature and data analysis in the field, highlighting the importance of proper specimen identification in public repositories. A summary of important basic biology, including life cycle, in vitro maintenance, and immunology, is given, and areas of future research for the improvement of knowledge and development of new systems are given. Finally, the limited knowledge regarding anthelmintic resistance in Parascaris spp. is summarized, along with caution regarding assumptions that resistance mechanisms can be applied across clades.
Topics: Animals; Anthelmintics; Ascaridida Infections; Ascaridoidea; Drug Resistance; Horse Diseases; Horses
PubMed: 35986167
DOI: 10.1007/s00436-022-07627-z -
Molecular Diversity Nov 2020A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing...
A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing O-acylation, Fries rearrangement and potassium carbonate-induced cyclization. The anthelmintic properties of the obtained compounds were investigated in vivo in a model nematode, Caenorhabditis elegans. Five compounds, namely 2-phenyl[1]benzopyrano[2,3-c]pyrazol-4(2H)-one 33 and its 7-fluoro, 7-chloro-, 7-bromo- and 8-fluoro-analogues, 36, 38, 40 and 43, respectively, altered the development of C. elegans. While the activities of 33 and 43 were rather modest, compounds 36, 38 and 40 inhibited the growth of the worms at concentrations of approximately 1-3 µM. At these concentrations, the compounds did not kill the worms, but they strongly inhibited their development, with the majority of larvae never progressing past the L1 stage. Moreover, testing in non-cancer human cell lines showed that, with exception of 7-bromo derivative 40, the active compounds have favourable toxicity profiles.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Cell Line; Cyclization; Humans; Larva; Pyrazoles; Structure-Activity Relationship
PubMed: 31713185
DOI: 10.1007/s11030-019-10010-3 -
Immunology and Allergy Clinics of North... Aug 2019Helminth infections may inhibit the development of allergic diseases, including asthma. On the other hand, some helminth species may induce or worsen symptoms of asthma.... (Review)
Review
Helminth infections may inhibit the development of allergic diseases, including asthma. On the other hand, some helminth species may induce or worsen symptoms of asthma. This article discusses the impact of helminth infections on asthma as well as the potencial of helminth-derived molecules with regulatory characteristics in the prevention or treatment of this disease. The ability to induce regulation has been observed in animal models of asthma or cells of asthmatic individuals in vitro. Potential future clinical applications of helminth antigens or infection for prevention of asthma merit further translational research.
Topics: Animals; Anthelmintics; Asthma; Disease Susceptibility; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Immunomodulation
PubMed: 31284930
DOI: 10.1016/j.iac.2019.03.009