Effect of repeated benzimidazole treatments with increasing dosages on the phenotype of resistance and the beta-tubulin codon 200 genotype distribution in a benzimidazole-resistant cyathostomin population.
Abstract: This study was designed to investigate the effect of repeated treatments with increasingly high fenbendazole (FBZ) dosages on the phenotype and genotype of a benzimidazole (BZ)-resistant cyathostomin population. An experimentally infected horse was treated repeatedly with FBZ dose rates between 7.5 and 30.0 mg/kg body weight (bw) over approximately 2 years. Faecal egg counts (FECs) and larval cultures were performed weekly. A total of 45 faecal egg count reduction tests (FECRTs) were analysed, revealing a high variability during the course of experiment with a mean value in faecal egg count reduction (FECR) of -17% (S.D. +/- 78). The FECR was always 0.36 microg/ml TBZ, confirming the phenotype of resistance. The LD(99) varied between 0.40 and 0.63 microg/ml TBZ. Despite consecutive treatments, no noticeable increase of the LD(50), LD(96) and LD(99) values was detected for the duration of the experiment. The molecular analysis of the codon 200 of 106 third stage larvae (L3) was carried out following repeated treatments with 30 mg FBZ/kg bw. Out of these larvae 32% were homozygous TTC/TTC, 60% showed the heterozygous TTC/TAC genotype, and 8% were homozygous TAC/TAC. The resulting allele frequencies were 62% for TTC and 38% for TAC. These findings suggest that repeated BZ treatments with increasing dosages do not alter significantly the FECRT and EHT characteristics of a BZ-resistant cyathostomin population. Furthermore, it may also be concluded that, in contrast to sheep trichostrongyles, such a selection regime does not result in beta-tubulin codon 200 TAC allele autocracy.
Publication Date: 2004-08-25 PubMed ID: 15325046DOI: 10.1016/j.vetpar.2004.06.019Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research paper discusses a study that examined how repeated treatments with increased doses of the drug fenbendazole impacted the phenotype and genotype of a cyathostomin population that showed resistance to benzimidazole, an anti-parasitic drug. The results suggest that the increasing drug dosages did not significantly alter the fecal egg count reduction and egg hatch test characteristics of the resistant cyathostomin population.
Study Structure and Methodology
- The experiment involved an infected horse that was repeatedly treated with increasing dose rates of fenbendazole over the span of about two years. The doses ranged from 7.5 up to 30.0 mg/kg body weight.
- Throughout the experiment, faecal egg counts (FECs) and larval cultures were examined on a weekly basis.
- The researchers conducted 45 faecal egg count reduction tests (FECRTs), and nine egg hatch tests. The egg hatch tests revealed lethal dose (LD) values, which confirmed resistance within the population.
- The research team performed a molecular analysis of third stage larvae’s codon 200 following repeated treatments with 30 mg fenbendazole/kg body weight.
Study Findings and Conclusions
- Throughout the experiment, a high variability was found in the fecal egg count reduction (FECR), with a mean reduction of -17%. The FECR was always less than 90%, indicating benzimidazole resistance.
- The lethal dose values from egg hatch tests remained consistent throughout the experiment, confirming the phenotype of resistance and showing no significant increase from the repeated treatments.
- The molecular analysis of the codon 200 (an area of interest in drug resistance studies) showed different genotypic results. Among the larvae, 32% were homozygous TTC/TTC, 60% were heterozygous TTC/TAC, while 8% were homozygous TAC/TAC.
- These findings imply that increased repeated dosages of benzimidazole did not notably influence the drug resistance characteristics of the cyathostomin population.
- Unlike in sheep parasites, the research shows that such a selection regime does not result in beta-tubulin codon 200 TAC allele domination in horse parasites.
Cite This Article
APA
Drogemuller M, Failing K, Schnieder T, von Samson-Himmelstjerna G.
(2004).
Effect of repeated benzimidazole treatments with increasing dosages on the phenotype of resistance and the beta-tubulin codon 200 genotype distribution in a benzimidazole-resistant cyathostomin population.
Vet Parasitol, 123(3-4), 201-213.
https://doi.org/10.1016/j.vetpar.2004.06.019 Publication
Researcher Affiliations
- Hannover School of Veterinary Medicine, Institute of Parasitology, Buenteweg 17, D-30559 Hannover, Germany.
MeSH Terms
- Alleles
- Animals
- Anthelmintics / therapeutic use
- Codon / genetics
- DNA, Helminth / chemistry
- DNA, Helminth / genetics
- Dose-Response Relationship, Drug
- Drug Resistance / genetics
- Feces / parasitology
- Fenbendazole / therapeutic use
- Horse Diseases / drug therapy
- Horse Diseases / parasitology
- Horses
- Lethal Dose 50
- Linear Models
- Parasite Egg Count / veterinary
- Polymerase Chain Reaction / veterinary
- Polymorphism, Single Nucleotide / drug effects
- Polymorphism, Single Nucleotide / genetics
- Strongylida Infections / drug therapy
- Strongylida Infections / parasitology
- Strongylida Infections / veterinary
- Strongyloidea / drug effects
- Strongyloidea / genetics
- Strongyloidea / growth & development
- Tubulin / chemistry
- Tubulin / genetics
Citations
This article has been cited 5 times.- George S, Suwondo P, Akorli J, Otchere J, Harrison LM, Bilguvar K, Knight JR, Humphries D, Wilson MD, Caccone A, Cappello M. Application of multiplex amplicon deep-sequencing (MAD-seq) to screen for putative drug resistance markers in the Necator americanus isotype-1 β-tubulin gene.. Sci Rep 2022 Jul 6;12(1):11459.
- Orr AR, Quagraine JE, Suwondo P, George S, Harrison LM, Dornas FP, Evans B, Caccone A, Humphries D, Wilson MD, Cappello M. Genetic Markers of Benzimidazole Resistance among Human Hookworms (Necator americanus) in Kintampo North Municipality, Ghana.. Am J Trop Med Hyg 2019 Feb;100(2):351-356.
- Morrison AA, Mitchell S, Mearns R, Richards I, Matthews JB, Bartley DJ. Phenotypic and genotypic analysis of benzimidazole resistance in the ovine parasite Nematodirus battus.. Vet Res 2014 Dec 9;45:116.
- Lake SL, Matthews JB, Kaplan RM, Hodgkinson JE. Determination of genomic DNA sequences for beta-tubulin isotype 1 from multiple species of cyathostomin and detection of resistance alleles in third-stage larvae from horses with naturally acquired infections.. Parasit Vectors 2009 Sep 25;2 Suppl 2(Suppl 2):S6.
- von Samson-Himmelstjerna G, Coles GC, Jackson F, Bauer C, Borgsteede F, Cirak VY, Demeler J, Donnan A, Dorny P, Epe C, Harder A, Höglund J, Kaminsky R, Kerboeuf D, Küttler U, Papadopoulos E, Posedi J, Small J, Várady M, Vercruysse J, Wirtherle N. Standardization of the egg hatch test for the detection of benzimidazole resistance in parasitic nematodes.. Parasitol Res 2009 Sep;105(3):825-34.
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