Prevalence of anthelmintic resistance on sheep and goat farms in the mid-Atlantic region and comparison of in vivo and in vitro detection methods

Crook, E.K.; O’Brien, Dahlia; Howell, Sue; Storey, Bob E.; Whitley, Niki; Burke, J.M.; Kaplan, Ray M.

doi:10.1016/j.smallrumres.2016.09.006

Cited by 47 publications

(29 citation statements)

References 18 publications

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“…Furthermore, the results of Várady et al [ 22 ] also suggest that LDT provides a more accurate quantitative estimate of the level of benzimidazole resistance compared to EHT. In the some cases using the in vitro methods for the detection of AR could be more suitable and sensitive, especially in herds where the resistant alleles are present in the proportion of GIN population [ 24 – 26 ].…”

Section: Discussionmentioning

confidence: 99%

The first report of multidrug resistance in gastrointestinal nematodes in goat population in Poland

et al. 2020

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Background: Prophylactic anthelmintic treatment with one of three basic classes of anthelmintics (benzimidazoles, macrocyclic lactones and imidazothiazoles) is still the mainstay of control of gastrointestinal nematode infections in small ruminants worldwide. As a consequence, anthelmintic resistance is a serious threat to small ruminant health and production. While the resistance to one class of anthelmintics has already been reported in most of countries, the newly-emerging problem is the resistance to two or even all of classes referred to as multidrug resistance. This study aimed to evidence the presence of multidrug resistance of gastrointestinal nematodes in goats in Poland. Results: The combination of one in vivo method (fecal egg count reduction test) and two in vitro methods (egg hatch test and larval development test) performed in two goat herds in the southern Poland showed the presence of gastrointestinal nematodes resistant to fenbendazole and ivermectin in both herds. Moreover, in one herd it revealed the development of resistance to the last effective anthelmintic, levamisole, in response to one-year intensive use. Haemonchus contortus was the most prevalent gastrointestinal nematode in samples in which resistance to benzimidazoles and ivermectin was found, whereas Trichostrongylus colubriformis predominated when resistance to levamisole was observed. Conclusion: This study shows for the first time that multidrug resistance of gastrointestinal nematodes to three basic classes of anthelmintics is already present in goat population in Poland. Moreover, it may indicate that different species or genera of gastrointestinal nematodes are responsible for the resistance to specific anthelmintics.

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Section: Discussionmentioning

confidence: 99%

The first report of multidrug resistance in gastrointestinal nematodes in goat population in Poland

et al. 2020

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“…Recent results indicate that BZ resistance is heterogeneous (Crook et al, 2016;Howell et al, 2008). Population-wide sequencing of beta-tubulin alleles have found different alleles in the same population (Avramenko et al, 2019;Hinney et al, 2020;Mohammedsalih et al, 2020;Redman et al, 2015;von Samson-Himmelstjerna et al, 2009).…”

Section: Causal Relationships Between Genes and Phenotypes Require Emmentioning

confidence: 99%

Quantitative benzimidazole resistance and fitness effects of parasitic nematode beta-tubulin alleles

Dilks

Hahnel

Sheng

et al. 2020

Preprint

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AbstractInfections by parasitic nematodes inflict a huge burden on the health of humans and livestock throughout the world. Anthelmintic drugs are the first line of defense against these infections. Unfortunately, resistance to these drugs is rampant and continues to spread. To improve treatment strategies, we must understand the genetics and molecular mechanisms that underlie resistance. Studies of the fungus Aspergillus nidulans and the free-living nematode Caenorhabditis elegans discovered that a beta-tubulin gene is mutated in benzimidazole (BZ) resistant strains. In parasitic nematode populations, three canonical beta-tubulin alleles, F200Y, E198A, and F167Y, have long been correlated with resistance. Additionally, improvements in sequencing technologies have identified new alleles - E198V, E198L, E198K, E198I, and E198Stop - also correlated with BZ resistance. However, none of these alleles have been proven to cause resistance. To empirically demonstrate this point, we independently introduced the three canonical alleles as well as two of the newly identified alleles, E198V and E198L, into the BZ susceptible C. elegans N2 genetic background. These genome-edited strains were exposed to both albendazole and fenbendazole to quantitatively measure animal responses to BZs. We used a range of doses for each BZ compound to define response curves and found that all five of the alleles conferred resistance to BZ compounds equal to a loss of the entire beta-tubulin gene. These results prove that the parasite beta-tubulin alleles cause resistance. The E198V allele is found at low frequencies in natural parasite populations, suggesting that it could affect fitness. We performed competitive fitness assays and demonstrated that the E198V allele reduces animal health, supporting the hypothesis that this allele is less fit in field populations. Overall, we present a powerful platform to quantitatively assess anthelmintic resistance and effects of specific resistance alleles on organismal fitness in the presence or absence of the drug.HighlightsAll three canonical parasitic nematode beta-tubulin alleles (F167Y, E198A, F200Y) and two newly identified alleles (E198V, E198L) confer equal levels of benzimidazole resistance in a defined genetic background using single-generation, high-replication drug response assays.Beta-tubulin variants are strongly selected in albendazole conditions in multigenerational competitive fitness assays, but these alleles confer different levels of benzimidazole resistance over time.Only the E198V allele confers a fitness cost in control (non-benzimidazole) conditions as compared to all other tested beta-tubulin alleles, suggesting that this intermediate allele might only be found in field populations at low frequency because it causes reduced fitness.Graphical Abstract

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“…Recent results indicate that BZ resistance is heterogeneous ( Howell et al, 2008 ; Crook et al, 2016 ). Population-wide sequencing of beta-tubulin alleles have found different alleles in the same population ( von Samson-Himmelstjerna et al, 2009 ; Redman et al, 2015 ; Avramenko et al, 2019 ; Hinney et al, 2020 ; Mohammedsalih et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Quantitative benzimidazole resistance and fitness effects of parasitic nematode beta-tubulin alleles

Dilks

Hahnel

Sheng

et al. 2020

International Journal for Parasitology: Drugs and Drug Resistan

101

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Infections by parasitic nematodes inflict a huge burden on the health of humans and livestock throughout the world. Anthelmintic drugs are the first line of defense against these infections. Unfortunately, resistance to these drugs is rampant and continues to spread. To improve treatment strategies, we must understand the genetics and molecular mechanisms that underlie resistance. Studies of the fungus Aspergillus nidulans and the free-living nematode Caenorhabditis elegans discovered that a beta-tubulin gene is mutated in benzimidazole (BZ) resistant strains. In parasitic nematode populations, three beta-tubulin alleles, F167Y, E198A, and F200Y, have long been correlated with resistance. Additionally, improvements in sequencing technologies have identified new alleles - E198V, E198L, E198K, E198I, and E198Stop - also correlated with BZ resistance. However, none of these alleles have been proven to cause resistance. To empirically demonstrate this point, we independently introduced the F167Y, E198A, and F200Y alleles as well as two of the newly identified alleles, E198V and E198L, into the BZ susceptible C. elegans N2 genetic background using the CRISPR-Cas9 system. These genome-edited strains were exposed to both albendazole and fenbendazole to quantitatively measure animal responses to BZs. We used a range of concentrations for each BZ compound to define response curves and found that all five of the alleles conferred resistance to BZ compounds equal to a loss of the entire beta-tubulin gene. These results prove that the parasite beta-tubulin alleles cause resistance. The E198V allele is found at low frequencies along with the E198L allele in natural parasite populations, suggesting that it could affect fitness. We performed competitive fitness assays and demonstrated that the E198V allele reduces animal health, supporting the hypothesis that this allele might be less fit in field populations. Overall, we present a powerful platform to quantitatively assess anthelmintic resistance and effects of specific resistance alleles on organismal fitness in the presence or absence of the drug.

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Prevalence of anthelmintic resistance on sheep and goat farms in the mid-Atlantic region and comparison of in vivo and in vitro detection methods

Cited by 47 publications

References 18 publications

The first report of multidrug resistance in gastrointestinal nematodes in goat population in Poland

The first report of multidrug resistance in gastrointestinal nematodes in goat population in Poland

Quantitative benzimidazole resistance and fitness effects of parasitic nematode beta-tubulin alleles

Quantitative benzimidazole resistance and fitness effects of parasitic nematode beta-tubulin alleles

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