Pharmacology of anthelmintic resistance

Parasitology ◽  
1996 ◽  
Vol 113 (S1) ◽  
pp. S201-S216 ◽  
Author(s):  
N. Sangster
Keyword(s):  
Acetylcholine Receptors ◽  
Anthelmintic Resistance ◽  
Cross Resistance ◽  
Parasitic Nematodes ◽  
Parasitic Helminths ◽  
Nematode Parasites ◽  
Neuromuscular Systems ◽  
Free Living Nematode ◽  
Molecular Aspects

SUMMARYAnthelmintic resistance has compromised the control of nematode parasites in several animal-based industries. Studies of resistance have not only improved our understanding of this phenomenon but also shed light on physiological systems of parasitic helminths. In addition, research on molecular aspects of anthelmintic resistance may provide selectable markers for use in future transfection studies with helminths. Several anthelmintics act on helminth neuromuscular systems. Drugs such as levamisole are cholinergic agonists and, based on pharmacological studies, levamisole-resistant nematodes appear to have altered acetylcholine receptors. It is likely that anticholinesterase anthelmintics share cross resistance with levamisole. Ivermectin appears to be a glutamate agonist.In vitrostudies of ivermectin-resistant nematodes suggest that IVM receptors are located on pharyngeal and somatic muscle. The free-living nematodeCaenorhabditis elegansmay provide a model for anthelmintic resistance. It has been useful in cloning drug receptors from parasites but differences between its life history and habitat compared with parasitic nematodes may limit its usefulness for studying resistance in these parasites.

scholarly journals Comparison of two in vitro methods for the detection of ivermectin resistance in Haemonchus contortus in sheep

2016 ◽  
Vol 53 (2) ◽  
pp. 120-125 ◽  
Author(s):  
M. Urda Dolinská ◽  
A. Königová ◽  
M. Babják ◽  
M. Várady
Keyword(s):  
Drug Resistance ◽  
Haemonchus Contortus ◽  
Anthelmintic Resistance ◽  
Economic Losses ◽  
Parasitic Nematodes ◽  
Migration Inhibition ◽  
In Vitro Methods ◽  
Parasitic Helminths

SummaryGastrointestinal parasitic nematodes in sheep cause severe economic losses. Anthelmintics are the most commonly used drugs for prophylaxis and therapy against parasitic helminths. The problem of drug resistance has developed for all commercially available anthelmintics in several genera and classes of helminths. In vitro and in vivo tests are used to detect anthelmintic resistance. Two in vitro methods (larval migration inhibition test and micromotility test) for the detection of ivermectin (IVM) resistance were compared using IVM-resistant and IVM-susceptible isolates of Haemonchus contortus. The degree of resistance for each test was expressed as a resistance factor (RF). The micromotility test was more sensitive for quantitatively measuring the degree of resistance between susceptible and resistant isolates. The RFs for this test for IVM and eprinomectin ranged from 1.00 to 108.05 and from 3.87 to 32.32, respectively.

RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects

Parasitology ◽  
2006 ◽  
Vol 134 (5) ◽  
pp. 609-619 ◽  
Author(s):  
P. GELDHOF ◽  
A. VISSER ◽  
D. CLARK ◽  
G. SAUNDERS ◽  
C. BRITTON ◽  
...  
Keyword(s):  
Rna Interference ◽  
Culture Conditions ◽  
Gene Knockdown ◽  
Future Application ◽  
Parasitic Nematodes ◽  
Parasitic Helminths ◽  
Rnai Treatment ◽  
Free Living Nematode ◽  
Invaluable Tool

SUMMARYRNA interference (RNAi) has become an invaluable tool for the functional analysis of genes in a wide variety of organisms including the free-living nematode Caenorhabditis elegans. Recently, attempts have been made to apply this technology to parasitic helminths of animals and plants with variable success. Gene knockdown has been reported for Schistosoma mansoni by soaking or electroporating different life-stages in dsRNA. Similar approaches have been tested on parasitic nematodes which clearly showed that, under certain conditions, it was possible to interfere with gene expression. However, despite these successes, the current utility of this technology in parasite research is questionable. First, problems have arisen with the specificity of RNAi. Treatment of the parasites with dsRNA resulted, in many cases, in non-specific effects. Second, the current RNAi methods have a limited efficiency and effects are sometimes difficult to reproduce. This was especially the case in strongylid parasites where only a small number of genes were susceptible to RNAi-mediated gene knockdown. The future application of RNAi in parasite functional genomics will greatly depend on how we can overcome these difficulties. Optimization of the dsRNA delivery methods and in vitro culture conditions will be the major challenges.

scholarly journals In Vitro Efficacy of Aqueous and Methanol Extract of Cassia siamea Against the Motility of Caenorhabditis elegans

2020 ◽  
Vol 31 (3) ◽  
pp. 145-159
Author(s):  
Haladu Ali Gagman ◽  
Nik Ahmad Irwan Izzauddin Nik Him ◽  
Hamdan Ahmad ◽  
Shaida Fariza Sulaiman ◽  
Rahmad Zakaria ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Methanol Extract ◽  
Anthelmintic Resistance ◽  
Gastrointestinal Nematode ◽  
Parasitic Nematodes ◽  
Cassia Siamea ◽  
Methanol Extracts ◽  
C Elegans ◽  
Significant Difference

Gastrointestinal nematode infections can cause great losses in revenue due to decrease livestock production and animal death. The use of anthelmintic to control gastrointestinal nematode put a selection pressure on nematode populations which led to emergence of anthelmintic resistance. Because of that, this study was carried out to investigate the efficacy of aqueous and methanol extract of Cassia siamea against the motility of C. elegans Bristol N2 and C. elegans DA1316. Caenorhabditis elegans Bristol N2 is a susceptible strain and C. elegans DA1316 is an ivermectin resistant strain. In vitro bioassay of various concentrations of (0.2, 0.6, 0.8, 1.0 and 2.0 mg mL–1) aqueous and methanol extracts of C. siamea was conducted against the motility of L4 larvae of C. elegans Bristol N2 and C. elegans DA1316. The L4 larvae were treated with 0.02 μg mL–1 of ivermectin served as positive control while those in M9 solution served as negative control. The activity of the extracts was observed after 24 h and 48 h. A significant difference was recorded in the extract performance compared to control at (P < 0.001) after 48 h against the motility of the larvae of both strains. The methanol extracts inhibited the motility of C. elegans Bristol N2 by 86.7% as well as DA1316 up to 84.9% at 2.0 mg mL–1 after 48 h. The methanol extract was more efficient than aqueous extract (P < 0.05) against the motility of both strains of C. elegans. Cassia siamea may be used as a natural source of lead compounds for the development of alternative anthelmintic against parasitic nematodes as well ivermectin resistant strains of nematodes.

scholarly journals In vitro Efficacy of Albendazole against Strongyle eggs recovered from Trade Goats slaughtered at the Nsukka Abattoir: A Preliminary Survey of Resistance to Albendazole

2021 ◽  
Vol 40 (4) ◽  
pp. 287-295
Author(s):  
I.K. Idika ◽  
V.J. Ebuk ◽  
E.I. Okoro ◽  
T.A. Nzeakor ◽  
N.M. Uzonnah ◽  
...  
Keyword(s):  
Faecal Sample ◽  
Anthelmintic Resistance ◽  
Egg Hatch ◽  
Lc50 Value ◽  
Nematode Parasites ◽  
Faecal Culture ◽  
World Association ◽  
Egg Hatch Assay ◽  
Set Up

The efficacy of Albendazole against trichostrongyle nematode parasites in goats presented for slaughter at the Nsukka municipal  abattoir was evaluated using the In vitro Egg hatch assay (EHA) model. The abattoir was visited once every week for 4 consecutive months during which a total of 240 goats were sampled. Fecal samples were collected per rectum from a minimum of 15 goats on each day of the visit. Egg Hatch Assay was performed on strongyle eggs recovered from pooled faecal sample on each day of sampling with a 2.5% W/V Albendazole. Faecal culture was also set up from the pooled faecal sample on each sampling day to recover and identify the nematode parasites present in the goats. Among the 240 goats sampled, the prevalence of trichostrongylosis as observed by the presence of strongyle eggs was 94.6% (227/240). Faecal culture and larval identification revealed 69.8% of the strongyles as  Haemonchus contortus, while 25.5 and 4.8% were Trichostrongylus colubriformis and Oesophagostomum species respectively. In the EHA, Albendazole had mean LC50 value of 0.16 µg/ml which is slightly in excess of the discriminating dose of 0.1µg/ml as prescribed by the World Association for the Advancement of Veterinary Parasitology (WAAVP) as an indication of anthelmintic resistance. There is therefore an urgent need to screen the nematode parasite population in the Nigeria for the presence Albendazole resistance genes. Key words: GI nematode; egg hatch assay; goat; Albendazole; Resistance; Nigeria

scholarly journals Worm-control practices and prevalence of anthelmintic resistance using in vivo FECRTs on smallholder sheep farms in Lithuania

2016 ◽  
Vol 53 (1) ◽  
pp. 24-30 ◽  
Author(s):  
T. Kupčinskas ◽  
I. Stadalienė ◽  
A. Šalomskas ◽  
P. Trusevičius ◽  
M. Varady ◽  
...  
Keyword(s):  
Anthelmintic Resistance ◽  
Gastrointestinal Nematodes ◽  
Parasitic Nematodes ◽  
Future Studies ◽  
Faecal Samples ◽  
Two Samples ◽  
Faecal Egg Count ◽  
Worm Control

SummaryThis study determined the prevalence of anthelmintic resistance (AR) in parasitic nematodes on smallholder sheep farms in Lithuania from April to November 2014. Faecal samples were collected from two groups of 10-15 sheep treated with fenbendazole (FBZ) or ivermectin (IVM) on 18 sheep farms. Two samples were collected from each group: on day zero (T1) and 10-14 days after treatment. Faecal egg counts (eggs per gramme, EPG) were determined using a modified McMaster technique. Animals with < 140 EPG on day zero were removed from the analysis. The prevalence of AR was estimated using the in vivo faecal egg count reduction test. AR to FBZ was detected on three of 15 farms where FBZ was used (20 %) and was suspected on one farm (6.7 %). AR to IVM was detected on two of 16 farms where IVM was used (12.5 %). The main species of resistant gastrointestinal nematodes (GINs) identified after treatment were Teladorsagia spp. and Trichostrongylus spp. A questionnaire surveying 71 sheep farmers estimated that 71.8 % of sheep farmers used anthelmintics against GINs. IVM was the most frequently (68.6 %) applied anthelmintic, and 62.7 % of the respondents reported treating their animals twice a year. This study confirmed the presence of AR to GIN infections on sheep farms in Lithuania. Future studies should assess the prevalence of AR to GIN infection using in vitro methods.

scholarly journals Characterization of a Rhodanese Homologue from Haemonchus Contortus and its Immune-Modulatory Effects on Goat Immune Cells in Vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Parasitic Nematodes ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Suppression and modulation of the immune response of the host by nematode parasites have been reported widely. Rhodaneses or thiosulfate: cyanide sulfurtransferases are present in a wide range of organisms, such as archea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homology could bind by goat peripheral blood mononuclear cells (PBMCs) in vivo.Results: In the present study, we cloned and produced recombinant rhodanese protein originated from Haemonchus contortus (rHCRD), which was one of the parasitic nematodes of small ruminants. The effect of this protein on modulating the immunity of goat PBMC and monocyte was studied in the current work. The predominant localization of the natural HCRD protein was verified as the bowel wall and body surface of worms, according to the immunohistochemical tests. It was proved in this study that the serum produced by artificially infecting goats with H. contortus successfully recognized rHCRD which conjugated goat PBMCs. The rHCRD was co-incubated with goat PBMCs to observe the immunomodulatory effect on proliferation, apoptosis and secretion of cytokines exerted by HCRD. The results showed that the interaction of rHCRD suppressed proliferation of goat PBMCs stimulated by ConA but did not induce the apoptosis of goat PBMCs. After rHCRD exposure, the production of TNF-α and IFN-γ were significantly decreased, however, it significantly increased the secretion of IL-10 and TGF-β1 in goat PBMCs. Phagocytotic assay by FITC-dextran internalization showed that rHCRD inhibited the phagocytosis of goat monocytes. Moreover, rHCRD could down-regulate the expression of MHC-II on goat monocytes in a dose-dependent manner. Conclusions: These discoveries proposed a possible target as immunomodulator, which was potentially beneficial to illuminate the interaction between parasites and hosts in the molecular level and hunt for innovative protein species as candidate targets of drug and vaccine.

Morphological observations and the effects of artificial digestive fluids on the survival of Diploscapter coronata from a Japanese patient

2006 ◽  
Vol 80 (4) ◽  
pp. 341-348 ◽  
Author(s):  
N. Morimoto ◽  
M. Korenaga ◽  
K. Yagyu ◽  
N. Kagei ◽  
M. Fujieda ◽  
...  
Keyword(s):  
Intestinal Tract ◽  
Gastric Fluid ◽  
Culture Technique ◽  
Parasitic Nematodes ◽  
Japanese Female ◽  
Old Japanese ◽  
Free Living Nematode ◽  
Gastro Intestinal Tract ◽  
Schonlein Purpura

AbstractUnusual non-human parasitic nematodes and eggs were detected in the faeces of an 8-year-old Japanese female suffering from Henoch-Schönlein purpura. The worms were adult female rhabditiform nematodes measuring 325.6–441.2 μm in length and 18.3–26.5 μm in width. One pair of the labia oris was notched with many spiny projections, while the other pair was strongly curved outwards. The worms were identified using light and scanning electron microscopy as the free-living nematode Diploscapter coronata (Cobb) based on their characteristic morphology. The patient's faeces containing worms and eggs were cultured using a filter-paper culture technique and after 7 days of culture, male as well as female worms were recovered. Worm survival time and hatchability of the eggs were examined in vitro after treatment with an artificial gastric or intestinal fluid. Although adult worms survived for less than one minute, eggs hatched after treatment with artificial gastric fluid. This suggests that eggs accidentally ingested or produced by adult D. coronata could develop in the human gastro-intestinal tract. Some morphological features of male D. coronata are also described.

Measuring the effect of avermectins and milbemycins on somatic muscle contraction of adult Haemonchus contortus and on motility of Ostertagia circumcincta in vitro

Parasitology ◽  
2014 ◽  
Vol 141 (7) ◽  
pp. 948-956 ◽  
Author(s):  
JANINA DEMELER ◽  
GEORG VON SAMSON-HIMMELSTJERNA ◽  
NICHOLAS C. SANGSTER
Keyword(s):  
Muscle Contraction ◽  
Haemonchus Contortus ◽  
Anthelmintic Resistance ◽  
Parasitic Nematodes ◽  
Response Curves ◽  
Drug Potency ◽  
The Right ◽  
Sites Of Action

SUMMARYThe mechanism of anthelmintic resistance against the widely used macrocyclic lactones (MLs) is still not fully understood. Pharyngeal, somatic body muscles and the ovijector have been proposed as putative sites of action as well as resistance. In the present study the effects of three avermectins and three milbemycins on adult parasitic nematodes were evaluated in vitro. The Muscle Transducer system was used to investigate the effects of MLs on muscle contraction in female Haemonchus contortus and effects on motility were measured in Ostertagia (Teladorsagia) circumcincta using the Micromotility Meter. Concentration-response curves for all substances in both systems shifted to the right in the resistant isolates. Resistance was present to ivermectin (IVM) and its components IVM B1a and IVM B1b, suggesting that both components are involved in the mode of action and resistance. No consistent patterns of potency and resistance of the substances were observed except that milbemycins generally showed lower resistance ratios (RRs) than IVM. IVM and IVM B1b were the most potent inhibitors of contraction and motility in both susceptible isolates and also showed the highest RR in both species. Low RRs for milbemycins recorded in vitro for highly resistant isolates in vivo suggest that other factors such as pharmacokinetics influence drug potency in vivo.

Benzimidazole-resistant gastrointestinal nematodes in indigenous Chiapas and Pelibuey sheep breeds from Chiapas, Mexico

2013 ◽  
Vol 89 (1) ◽  
pp. 80-85 ◽  
Author(s):  
E. Liébano-Hernández ◽  
M. González-Olvera ◽  
C. Vázquez-Peláez ◽  
P. Mendoza-de-Gives ◽  
G. Ramírez-Vargas ◽  
...  
Keyword(s):  
Anthelmintic Resistance ◽  
Lethal Dose ◽  
Morphological Characteristics ◽  
Gastrointestinal Nematodes ◽  
Genetic Mutation ◽  
Parasitic Nematodes ◽  
Tubulin Gene ◽  
Sheep Breeds ◽  
Pelibuey Sheep

AbstractBecause of the natural adaptation of Mexican sheep, the aim of the present study was to identify the presence or absence of gastrointestinal parasitic nematodes (GIN) resistant to benzimidazole (BZ) in both Chiapas and Pelibuey sheep breeds on local farms. Both male and female GIN-infected grazing sheep of the two breeds were selected. Sheep faecal samples were collected to obtain infective larvae (L3). This evolving stage of the parasite was used for taxonomic identification of the genus, based on its morphological characteristics. BZ anthelmintic resistance was evaluated using a nematode–compound in vitro interaction bioassay and the allele-specific polymerase chain reaction technique to detect mutations of residues 198 and 200 on isotype 1 of the β-tubulin gene. Three BZ-based compounds (febendazole (FBZ), tiabendazole (TBZ) and albendazole (ABZ)) at concentrations of 1, 0.5, 0.25, 0.125, 0.062 and 0.03 mg/ml were used to estimate the anthelmintic efficacy and lethal dose (LD50, LD90 and LD99) of the drugs. Two parasitic nematodes, Haemonchus and Teladorsagia, were identified in both isolates. Also, the proportions of anthelmintic resistance identified in GIN of the two sheep breeds were 68% in isolates from the Chiapas breed and 71.8% in the Pelibuey breed. The specific lethal activity obtained with FBZ was higher than 90%. However, TBZ and ABZ showed a lethal activity lower than 50%. High variability in the discriminating dose values was found among the BZ drugs. For example, FBZ LD ranged from 0.01 to 1.20 mg/ml; on the other hand, TBZ and ABZ required a dose ranging from 0.178 to 759 mg/ml. In addition, amino acid changes of Phe (TTC) to Tyr (TAC) at codon 200 of the β-tubulin gene, showing resistance to BZ, and no changes at codon 198 Glu (GAA) to Ala (GCA) were observed for both isolates. These results confirmed the presence of a genetic mutation associated with BZ in both Chiapas and Pelibuey nematode isolates.

Association and predatory capacity of fungi Pochonia chlamydosporia and Arthrobotrys cladodes in the biological control of parasitic helminths of bovines

Parasitology ◽  
2019 ◽  
Vol 146 (10) ◽  
pp. 1347-1351 ◽  
Author(s):  
Ítalo Stoupa Vieira ◽  
Isabela de Castro Oliveira ◽  
Artur Kanadani Campos ◽  
Jackson Victor de Araújo
Keyword(s):  
Biological Control ◽  
Nematophagous Fungus ◽  
Nematophagous Fungi ◽  
Parasitic Nematodes ◽  
Pochonia Chlamydosporia ◽  
Parasitic Helminths ◽  
Infective Larvae ◽  
Volatile Metabolites ◽  
Nematode Parasites ◽  
Predatory Capacity

AbstractNematophagous fungi are used in the biological control of the parasitic helminths of animals and plants. The association of ovicidal and predator nematophagous fungi may present a complementary and increased action on the biological control of helminths. Joint growth compatibility and predation tests were carried out on infective larvae of nematode parasites of bovines with the nematophagous fungus ovicide Pochonia chlamydosporia and the nematophagous fungus predator Arthrobotrys cladodes. The tests of antagonism in direct confrontation, antibiosis and the effect of volatile metabolites between the isolates of P. chlamydosporia and A. cladodes indicated the viability of joint growth of these fungi. The association of the fungi P. chlamydosporia and A. cladodes presented a higher predatory capacity of infective larvae of the parasitic nematodes of bovines when compared to the predation of the fungi used alone. Therefore, under laboratory conditions, the fungi studied presented growth compatibility and the association of these increased the nematicidal activity against parasitic helminths of cattle.

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