Ivermectin-resistant Nematodes Research Articles

In vitro assessment of deworming potential of Guiera senegalensis in Nigerian ethnoveterinary industry using Caenorhabditis elegans

BackgroundAlthough Guiera senegalensis is used as a dewormer in ethnoveterinary health care in Nigeria, its anthelmintic potential has not been validated. Hence, this work investigated the in vitro anthelmintic potential of G. senegalensis extracts on two Caenorhabditis elegans strains: Bristol N2 (wild type/ivermectin susceptible) and DA1316 (ivermectin resistant).ResultsAqueous and methanol extracts of G. senegalensis were tested against the motility of the L4 larvae at two exposure periods of 24 and 48 h and found to be active against the C. elegans strains. Motility of C. elegans DA1316 was reduced to 18.6% and 8.3% by aqueous and methanol extracts, respectively, at 2.0 mg/ml after 48 h, whereas that of C. elegans DA1316 treated with ivermectin (0.02 µg/ml) remained above 95%. The motility of C. elegans Bristol N2 was reduced to 16.6% and 7.2% by aqueous and methanol extracts, respectively, at 2.0 mg/ml after 48 h and ≤ 2.7% by ivermectin (0.02 µg/ml). Activity of the plant extracts was concentration and time dependent.ConclusionsThis work confirms the anthelmintic activity of G. senegalensis and its effectiveness against ivermectin-resistant nematodes, thus validating its ethnoveterinary use as an animal dewormer in Nigeria and pharmacological potential as a source of anthelmintic compounds against ivermectin-resistant nematodes. There is, however, the need for in vivo studies to confirm the in vitro efficacy of the extracts.

Resistance of strongylid nematodes to anthelmintic drugs and driving factors at Czech goat farms

BackgroundStrongylid nematode infections may negatively affect both animal health and welfare, with deleterious consequences for livestock productivity. Many farmers in recent decades have relied on anthelmintics as the sole strategy of control, but the intensive use of these chemotherapeutics has led to the development of anthelmintic resistance (AR). Knowledge of both the efficacy of anthelmintics and factors promoting AR are essential to effectively control nematode infections, but no information on these topics for goats in the Czech Republic (CR) is available. This survey aimed to determine the occurrence of AR at Czech goat farms and to identify risk factors for the development of AR. A total of 24 herds of dairy goats across the CR were evaluated using in vitro tests for detecting AR, and a questionnaire survey was carried out to evaluate factors associated with AR.ResultsResistance against benzimidazoles was confirmed at 18 (75%) farms, and the level of resistance was high in four (22%) of the affected herds based on the egg hatch test. Ivermectin-resistant nematodes were detected in 13 (54%) herds using the larval development test; Teladorsagia/Trichostrongylus and Haemonchus were the predominant types of resistant larvae. Eight (62%) of the affected herds were evaluated as highly resistant to ivermectin. Eleven (46%) of the herds were resistant to both benzimidazoles and ivermectin. This report is the first on dual AR in the CR. A univariate logistic regression analysis indicated that a high stocking rate and farmer inexperience were significantly associated with ivermectin and benzimidazole resistance, respectively.ConclusionsThe results of our survey suggest that AR is widespread amongst herds of dairy goats in the CR, likely due to inappropriate practices of pasture and health management. AR may be an issue for expanding dairy-goat production in the CR in the near future unless both veterinary practitioners and farmers widely adopt strategies to prevent the development of AR.

Ivermectin treatment failure on four Irish dairy farms

We report on the use of the faecal egg count reduction test to evaluate the performance of ivermectin in treating gastrointestinal nematode infections in first grazing season (FGS) calves on four dairy farms in Co. Kilkenny, Ireland. On each farm, FGS calves were injected subcutaneously with ivermectin in accordance with their live weight (day 0). Calves were individually faecal sampled on both day 0 and day 14. Faecal egg counts were determined using the Mini-FLOTAC technique. Composite faecal cultures for each farm were performed on each sampling occasion. The faecal egg count reductions (mode) ranged from 17.3–80.2% with the lower 95% confidence limit ranging from 3.1–72.3% on the four farms, respectively. Ivermectin-resistant nematodes were detected on all farms, with evidence of Ostertagia resistance on one farm. This study highlights the urgent need for Irish producers to reappraise their parasite control practices.

Prevalence of cattle herds with ivermectin resistant nematodes in the hot sub-humid tropics of Mexico

The objective was to determine the prevalence of semi-intensive Bos indicus and Bos indicus×Bos taurus cattle herds with ivermectin (IVM) resistant nematodes in a sub-humid tropical zone of Mexico using the faecal egg count reduction test (FECRT). Thirty-three herds (28 beef and 5 dual purpose herds) were monitored in a period of 6 months (September 2008 to February, 2009). Only 14 of the 33 herds were included in the trial. The other herds had not enough animals with sufficient nematode eggs per gram of faeces (EPG) to be included in a FECRT. Some farms were visited twice trying to find more animals with egg counts higher than 150 EPG. In the 14 surveyed herds the calves were randomly distributed into two groups: (a) treatment group received 0.2mg of IVM/kg BW sc on day 0, and (b) control group without treatment. Faecal samples were obtained from each animal on days 0 and 14 post-treatment. Reduction percentages (% R) and 95% CI were calculated. The prevalence of cattle herds with IVM resistant nematodes was 78.6%. Those suspected of IVM resistance were 21.4%. All surveyed herds used IVM from two to three times a year (mainly beginning and end of the wet season) during 1–11 consecutive years. The farm with stronger resistance used IVM for 11 consecutive years (% R=0%; 95% CI=0–47%). Genera of nematodes resistant to IVM were: Ostertagia, Haemonchus, Cooperia and Trichostrongylus. A considerable effort is needed to perform FECRT in cattle herds under hot sub-humid tropical conditions.

Influência do parasitismo por nematódeos sobre o perfil hematológico de caprinos

The interaction between ivermectin-resistant and ivermectin-sensitive nematodes and the effect of this anthelmintic on the hematological status of naturally infected goats was assessed using 36 animals. Of these animals, 12 were infected by ivermectin-sensitive gastrointestinal nematodes of the superfamily Trichostrongyloidea (G1s e G1s) 12 were infected by ivermectin-resistant nematodes (G2r e G2r) and 12 uninfect goats (G3np). Six infected goats of each group (G1sm e G2rm) received oral ivermectin al the dose of 200µg/kg, while six were used as controls (G1sc e G2rc). Blood and fecal samples were collected on the day of medication (day zero), at seven, and at 14 days thereafter. The erythrocyte count and hematocrit levels in goats infected by sensitive strains of Haemonchus was greater than that of the group infected by a resistant strain. These values are lower in comparison to those observed in uninfected goats. The increase in the number of eggs per gram of feces, regardless of the strain, is inversely related to the hematocrit level. The use of ivermectin did not significantly change the hematological parameters of goats.

Cyclooctadepsipeptides—an anthelmintically active class of compounds exhibiting a novel mode of action

There are three major classes of anthelmintics for veterinary use: the benzimidazoles/prebenzimidazoles, the tetrahydropyrimidines/imidazothiazoles, and the macrocyclic lactones. In nematodes, there are five targets for the existing anthelmintics: the nicotinergic acetylcholine receptor which is the target of tetrahydropyrimidines/imidazothiazoles and indirectly that of the acetylcholineesterase inhibitors; the GABA receptor which is the target of piperazine, the glutamate-gated chloride channel as the target of the macrocyclic lactones, and ß-tubulin as the target of prebenzimidazoles/benzimidazoles. All these anthelmintics are now in serious danger because of the worldwide spread of resistant nematodes in sheep, cattle, horses and pigs. The class of cyclooctadepsipeptides has entered the scene of anthelmintic research in the early 1990s. PF1022A, the first anthelmintically active member, is a natural compound from the fungus Mycelia sterilia that belongs to the microflora of the leaves of the Camellia japonica. PF1022A contains 4 N-Methyl- l-leucines, 2 d-lactic acids and 2- d-phenyllactic acids arranged as a cyclic octadepsipeptide with an alternating l- d- l-configuration. Emodepside is a semisynthetic derivative of PF1022A with a morpholine ring at each of the two d-phenyllactic acids in para position. The anthelmintic activity is directed against gastrointestinal nematodes in chicken, mice, rats, meriones, dogs, cats, sheep, cattle and horses. Moreover, emodepside is active against Trichinella spiralis larvae in muscles, microfilariae and preadult filariae and Dictyocaulus viviparus. PF1022A and emodepside are fully effective against benzimidazole-, levamisole or ivermectin-resistant nematodes in sheep and cattle. In Ascaris suum both cyclooctadepsipeptides lead to paralysis indicating a neuropharmacological action of these compounds. Using a PF1022A-ligand immunoscreening of a cDNA library from Haemonchus contortus a cDNA clone of 3569 base pairs could be identified. This clone codes for a novel 110 kDa heptahelical transmembrane receptor, named HC110R. Database- and phylogenetic analysis reveals that this receptor is a homolog to B0457.1 from Caenorhabditis elegans and has significant similarity to latrophilins from human, cattle and rat. HC110R is located in the plasma membrane and in lysosomes and endosomes. α-Latrotoxin, the poison of the black widow spider, binds at a 54 kDa aminoterminal fragment of HC110R. After binding a Ca 2+-influx into HEK293 cells is induced which can be blocked by EGTA, Cd 2+ or nifedipin. PF1022A or emodepside also bind to this 54 kDa aminoterminal region of HC110R and interact with the functional responses of α-latrotoxin. In C. elegans antibodies against the C-or N-terminus of HC110R bind to the B0457.1 protein located in the pharynx. Electrophysiological studies reveal that emodepside inhibits pharyngeal pumping of the nematodes in a concentration dependent way with an IC 50 value of about 4 nM. Thus, it is tempting to speculate that emodepside exerts its action on nematodes via a latrophilin-like receptor which might have an important regulatory function on pharyngeal pumping.

L-glutamate binding sites of parasitic nematodes: an association with ivermectin resistance?

Nematode membrane preparations contain high amounts of low-affinity specific L-glutamate binding sites. The numbers of these sites were increased in 2 isolates, one field-derived and the other laboratory-derived, of ivermectin-resistant Haemonchus contortus and a field isolate of ivermectin-resistant Telodorsagia circumcincta, when compared to control, drug-sensitive isolates. Specific [3H]ivermectin binding to these membrane preparations showed no differences between ivermectin-sensitive and resistant isolates and the number of ivermectin binding sites was approximately 100-fold less than the number of L-glutamate binding sites. Kinetic analysis of L-glutamate binding suggested the presence of at least 2 classes of binding site. L-Glutamate binding was blocked by ibotenic acid, kynurenic acid and beta-hydroxyaspartate, but not by ivermectin, argiopine, kainate, quisqualate or NMDA. Competition assays with ibotenic acid suggested that there were 2 distinct populations of glutamate binding sites and that the site with the lower affinity for ibotenate was upregulated in the ivermectin-resistant nematodes. In the field isolate of resistant H. contortus we found no coding changes in the cDNAs encoding glutamate-gated chloride channel subunits HG2, HG3 and HG4, nor were any changes in channel expression detected using subunit-specific antibodies. The low-affinity binding site is unlikely to be associated with the ivermectin receptor in these nematodes.

Resistance of field isolates of Trichostrongylus colubriformis and Ostertagia circumcincta to ivermectin

Twelve Romney lambs and 10 Angora goats were infected with 7000 infective third-stage larvae (89% Trichostrongylus, 11% Ostertagia) collected from goats suspected of harbouring ivermectin-resistant nematodes. On 28 days p.i., the lambs and goats were divided into treatment and control groups of six and five animals, respectively. The animals in the treatment groups were treated with ivermectin (0.2 mg/kg) and necropsied 35 days p.i. Faecal egg counts were estimated on days 28 and 35 p.i. and larval development assays (LDAs) were conducted on 22, 24, 26, 28, 30, 32, 34 and 35 days p.i. The ivermectin treatment reduced Trichostronglus colubriformis burdens by 39% and 13% and Ostertagia circumcincta by 33% and 0% in lambs and goats, respectively. When compared with a susceptible strain, the LDAs indicated a resistance factor before treatment in lambs for T. colubriformis of 2.6 and 1.5 with ivermectin and avermectin B 2, respectively, which rose to 3.4 and 2.0 after treatment. The LD 50 values of the two control groups were relatively constant throughout the experiment. Prior to ivermectin treatment the LD 50 values of the treated groups were similar ( P>0.05) to the control groups but following ivermectin treatment their LD 50 values increased steadily until the animals were killed on 35 days p.i. The LD 50 values for ivermectin and avermectin B 2 of sheep were always slightly higher and significantly different ( P<0.01) than those of goats indicating a host effect on this parameter. The greater reduction in worm counts in goats suggests a difference in the efficacy of ivermectin between lambs and goats. This is the first confirmed report of ivermectin resistance in a field strain of T. colubriformis.

Prevalence of anthelmintic resistant nematodes in sheep and goats in Western France

Twenty-three sheep farms and 15 dairy goat farms, located in western France and randomly selected, were surveyed for gastrointestinal nematodes resistant to anthelmintics. On each of the 23 sheep farms, 60 lambs were randomly distributed into four groups of 15: untreated control group, fenbendazole (benzimidazole) group (5 mg/kg BW), ivermectin group (0.2 mg/kg BW) and levamisole hydrochloride group (6.8 mg/kg BW). On each of the 15 goat farms, 30 adult goats were allocated into two groups of 15: untreated control group and fenbendazole group (10 mg/kg BW). Faecal egg counts and larval cultures were done 10 to 14 days after anthelmintic treatment. Furthermore, egg hatch assays conducted with thiabendazole were performed on pooled faeces of fenbendazole treated goats, results being expressed as Logarithmic Concentration 50 (LC 50). Faecal egg count reductions (FECR) less than 95% are indicative of anthelmintic resistance and LC 50 values above 0.1 μg/ml suggest benzimidazole (BZ) resistance. On this basis, in the sheep survey, anthelmintic resistance occurred on 83% of farms for benzimidazole and on 50% of farms for levamisole. Post-treatment larval cultures indicated Teladorsagia/ Trichostrongylus and Cooperia were the predominant resistant genera. A negative relationship was found between FECR with fenbendazole and the average number of annual BZ treatments given to ewe-lambs ( P<0.01). In contrast, no case of ivermectin resistant nematodes was seen in the 23 sheep farms. In goat survey, virtually all the 15 surveyed farms showed the occurrence of benzimidazole resistant nematodes according to the results of both FECR test and egg hatch assay. In post-treatment coprocultures, Teladorsagia/ Trichostrongylus was the predominant larval type on seven farms, and Haemonchus on two farms, while on the remaining farms there was a well-balanced mixture of all the genera including Oesophagostomum/ Chabertia. Although no relationship could be established between drenching practices and results of in vivo and in vitro tests, the frequent and sometimes exclusive use of BZ compounds associated with a permanent underdosing of these drugs achieved by using sheep dose rates are probably the main causes of the very high frequency of BZ resistance in nematodes on goats. The consequences of anthelmintic resistance on sheep and goat parasitism management are discussed.

Pharmacology of anthelmintic resistance.

Anthelmintic 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 vitro studies of ivermectin-resistant nematodes suggest that IVM receptors are located on pharyngeal and somatic muscle. The free-living nematode Caenorhabditis elegans may 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.

Moxidectin against ivermectin‐resistant nematodes ‐ a global view

Australian Veterinary JournalVolume 71, Issue 5 p. 158-158 Moxidectin against ivermectin-resistant nematodes - a global view JT ROTHWELL, JT ROTHWELL Regional Veterinary Laboratory, Parasitology Section, NSW Agriculture, EMAI, PMB 8, Camden, New South Wales 2670Search for more papers by this authorP. ROLFE, P. ROLFE Regional Veterinary Laboratory, Parasitology Section, NSW Agriculture, EMAI, PMB 8, Camden, New South Wales 2670Search for more papers by this author JT ROTHWELL, JT ROTHWELL Regional Veterinary Laboratory, Parasitology Section, NSW Agriculture, EMAI, PMB 8, Camden, New South Wales 2670Search for more papers by this authorP. ROLFE, P. ROLFE Regional Veterinary Laboratory, Parasitology Section, NSW Agriculture, EMAI, PMB 8, Camden, New South Wales 2670Search for more papers by this author First published: May 1994 https://doi.org/10.1111/j.1751-0813.1994.tb03375.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume71, Issue5May 1994Pages 158-158 RelatedInformation