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Route of administration influences the concentration of ivermectin reaching nematode parasites in the gastrointestinal tract of cattle.

ABSTRACT: An animal trial was conducted to measure the concentrations of ivermectin occurring in abomasal and small intestinal contents and mucosa, and in the target parasites (Ostertagia ostertagi and Cooperia oncophora) following administration by subcutaneous, oral and pour-on routes. Twenty-five steers were infected with ivermectin-resistant isolates of O. ostertagi and C. oncophora and following patency randomly allocated to 3 treatment groups of 7 and 1 untreated control group of four. On day 0, animals in the treatment groups were administered ivermectin via the oral, injectable or pour-on routes. On days 1, 2, 3, 4, 5, 6 and 8, blood samples were collected from all live animals, one animal from each treatment group was euthanised and the abomasum and small intestine recovered. Control animals were euthanised on each of days 4, 5, 6 and 8. Samples of gastrointestinal tract organs, their contents, mucosa and parasites were collected and assayed for ivermectin concentration using HPLC. The highest plasma concentrations occurred following subcutaneous administration. In the gastrointestinal contents the highest levels occurred following oral administration, although one high value occurred following pour-on administration, which was attributed to self-licking by the treated animal. The lowest GI content levels followed subcutaneous injection. Ivermectin concentrations in the gastrointestinal mucosa were highest following subcutaneous injection. Drug levels in the abomasal parasite O. ostertagi were most closely correlated with levels in the abomasal mucosa whereas levels in the intestinal C. oncophora were most closely correlated with those in the intestinal contents. Thus, the maximun levels of drug reached C. oncophora in the small intestine following oral administration. In contrast, the highest levels of ivermectin in O. ostertagi followed subcutaneous injection. Therefore, route of administration is likely to influence the exposure to ivermectin for different parasite species.

SUBMITTER: Leathwick DM

PROVIDER: S-EPMC7591328 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Route of administration influences the concentration of ivermectin reaching nematode parasites in the gastrointestinal tract of cattle.

Leathwick D M DM Miller C M CM Waghorn T S TS Schwendel H H Lifschitz A A

International journal for parasitology. Drugs and drug resistance 20201020

An animal trial was conducted to measure the concentrations of ivermectin occurring in abomasal and small intestinal contents and mucosa, and in the target parasites (Ostertagia ostertagi and Cooperia oncophora) following administration by subcutaneous, oral and pour-on routes. Twenty-five steers were infected with ivermectin-resistant isolates of O. ostertagi and C. oncophora and following patency randomly allocated to 3 treatment groups of 7 and 1 untreated control group of four. On day 0, ani ...[more]

PMID: 33120249

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Project description:BackgroundBreeding livestock for improved resistance to disease is an increasingly important selection goal. However, the risk of pathogens adapting to livestock bred for improved disease resistance is difficult to quantify. Here, we explore the possibility of gastrointestinal worms adapting to sheep bred for low faecal worm egg count using computer simulation. Our model assumes sheep and worm genotypes interact at a single locus, such that the effect of an A allele in sheep is dependent on worm genotype, and the B allele in worms is favourable for parasitizing the A allele sheep but may increase mortality on pasture. We describe the requirements for adaptation and test if worm adaptation (1) is slowed by non-genetic features of worm infections and (2) can occur with little observable change in faecal worm egg count.ResultsAdaptation in worms was found to be primarily influenced by overall worm fitness, viz. the balance between the advantage of the B allele during the parasitic stage in sheep and its disadvantage on pasture. Genetic variation at the interacting locus in worms could be from de novo or segregating mutations, but de novo mutations are rare and segregating mutations are likely constrained to have (near) neutral effects on worm fitness. Most other aspects of the worm infection we modelled did not affect the outcomes. However, the host-controlled mechanism to reduce faecal worm egg count by lowering worm fecundity reduced the selection pressure on worms to adapt compared to other mechanisms, such as increasing worm mortality. Temporal changes in worm egg count were unreliable for detecting adaptation, despite the steady environment assumed in the simulations.ConclusionsAdaptation of worms to sheep selected for low faecal worm egg count requires an allele segregating in worms that is favourable in animals with improved resistance but less favourable in other animals. Obtaining alleles with this specific property seems unlikely. With support from experimental data, we conclude that selection for low faecal worm egg count should be stable over a short time frame (e.g. 20 years). We are further exploring model outcomes with multiple loci and comparing outcomes to other control strategies.

Project description:A large-scale Fecal Egg Count Reduction Test (FECRT) was integrated with ITS-2 rDNA nemabiome metabarcoding to investigate anthelmintic resistance in gastrointestinal nematode (GIN) parasites in western Canadian beef cattle. The study was designed to detect anthelmintic resistance with the low fecal egg counts that typically occur in cattle in northern temperate regions. Two hundred and thirty-four auction market-derived, fall-weaned steer calves coming off pasture were randomized into three groups in feedlot pens: an untreated control group, an injectable ivermectin treatment group, and an injectable ivermectin/oral fenbendazole combination treatment group. Each group was divided into six replicate pens with 13 calves per pen. Individual fecal samples were taken pre-treatment, day 14 post-treatment, and at monthly intervals for six months for strongyle egg counting and metabarcoding. Ivermectin treatment resulted in an 82.4% mean strongyle-type fecal egg count reduction (95% CI 67.8-90.4) at 14 days post-treatment, while the combination treatment was 100% effective, confirming the existence of ivermectin-resistant GIN. Nemabiome metabarcoding of third-stage larvae from coprocultures revealed an increase in the relative abundance of Cooperia oncophora, Cooperia punctata, and Haemonchus placei at 14 days post-ivermectin treatment indicating ivermectin resistance in adult worms. In contrast, Ostertagia ostertagi third-stage larvae were almost completely absent from day 14 coprocultures, indicating that adult worms of this species were not ivermectin resistant. However, there was a recrudescence of O. ostertagi third stage larvae in coprocultures at three to six months post-ivermectin treatment, which indicated ivermectin resistance in hypobiotic larvae. The calves were recruited from the auction market and, therefore, derived from multiple sources in western Canada, suggesting that ivermectin-resistant parasites, including hypobiotic O. ostertagi larvae, are likely widespread in western Canadian beef herds. This work demonstrates the value of integrating ITS-2 rDNA metabarcoding with the FECRT to enhance anthelmintic resistance detection and provide GIN species- and stage-specific information.

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Route of administration influences the concentration of ivermectin reaching nematode parasites in the gastrointestinal tract of cattle.

Publications

Route of administration influences the concentration of ivermectin reaching nematode parasites in the gastrointestinal tract of cattle.

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