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The widespread use of anticoagulant rodenticide for controlling commensal rodent pests over the past 50 years has raised concerns about the development of genetic resistance that could diminish the efficacy of these toxicants. These rodenticides primarily target the VKORC1 protein synthesized by the Vkorc1 gene. Mutations in the 139 codon altering binding sites and conferring resistance. While studies in Europe and Asia have documented such Vkorc1 mutations and associated anticoagulant rodenticide resistance in commensal rodents, few investigations have explored this issue in the Americas according to the Rodenticide Resistance Action Committee (RRAC). This study is one of the first efforts to survey Vkorc1 resistance mutations in commensal rodents in eastern North America. The lack of genetic mutations in sampled Norway rats collected from Richmond, Virginia and Helsinki Finland provides a baseline for future monitoring as anticoagulant rodenticide selection pressure continues. However, as Norway rat populations continue to grow, regular screening will be critical for early detection of rodenticide resistant genotypes. Municipalities should incorporate Vkorc1 resistance testing into integrated pest management (IPM) programs for rodents. If resistance alleles emerge, control strategies may need to transition towards alternative toxicant modes of control and greater emphasis on IPM tactics that reduce food and harborage resources for these rodents.

Abstract Anticoagulant rodenticides (AR) remain the most effective chemical substances used to control rodents in order to limit their agricultural and public health damage in both rural and urban environments. The emergence of genetically based resistance to AR worldwide has threatened effective rodent control. This study gives a first overview of the distribution and frequency of single nucleotide polymorphism in the vitamin K epoxide reductase subcomponent 1 (Vkorc1) gene in rodents in Lebanon. In the Mus genus, we detected two missense mutations Leu128Ser and Tyr139Cys, that confer resistance to anticoagulant rodenticides in house mice and a new missense mutation Ala72Val in the Mus macedonicus species, not previously described. In the Rattus genus, we found one missense mutation Leu90Ile in the roof rat and one missense mutation Ser149Ile in the Norway rat. This is the first study to demonstrate potential resistance to AR in Lebanese rodents and therefore it provides data to pest control practitioners to choose the most suitable AR to control rodents in order to keep their efficacy.

Background: We conducted a vitamin K epoxide reductase subcomponent 1 (Vkorc1)-based nonsynonymous Single Nucleotide Polymorphism (nsSNP) screen with focus on the house mouse (Mus musculus domesticus), but that also considered the Norway rat (Rattus norvegicus) and roof rat (R. rattus) in the USA., Results: We detected six Vkorc1 nsSNPs underlying the amino-acid polymorphisms Ala21Thr, Trp59Leu, Ile104Val, Val118Leu, Leu128Ser and Tyr139Cys in house mice (average coverage/SNP; n = 182 individuals), two nsSNPs underlying Arg35Pro and Gly46Ser in the Norway rat (n = 93), with the notable absence of Tyr139Cys (n = 179), and one nsSNP underlying Tyr25Phe in the roof rat (n = 27). Inferred resistance frequency is 29.1% for mice (variability of states 0-98.8%), 6.5% (0-33.3%) for the Norway rat, and 39.3% (0-52.6%) for the roof rat based on Tyr25Phe frequencies., Conclusions: Resistance detected in the USA in the 1980s likely was the consequence of Vkorc1 mutations in mice (Leu128Ser and Tyr139Cys), Norway rats (Arg35Pro) and roof rats (Tyr25Phe). Patterns of variant sharing between the USA and Europe indicate the importance of convergent evolution and gene flow in spreading resistance. The spread of nsSNPs in mice between continents appears to have been more effective than in Norway rats. We hypothesize that Arg35Pro may have originated in Norway rats in the USA, whereas Tyr139Cys variants originated in Europe. Tyr25Phe is the likely cause for resistance in roof rats. Further genetic testing in the USA is required to close sampling gaps, and population genomic data are needed to study the origin and spread of this adaptive trait., (© 2020 Society of Chemical Industry.)

Since anticoagulant rodenticide resistance was first discovered in the United States in 1971, it has become apparent that the phenomenon is widespread. In cooperation with the Center for Disease Control, a nationwide surveillance program was initiated in 1977 to obtain statistically valid samples of rats from federally funded projects of the Urban Rat Control Program. A summary is given of the basic sampling, testing, and analysis components of this study. Problems encountered in all aspects of the first three years of the program are discussed along with results from the 40 completed samples. The 16 cities with significant Anticoagulant Resistance Problem Areas are distinguished from those in which resistance has merely been observed. Levels of resistance in various rat populations are discussed and recommendations are made in support of integrated pest management programs. Recent findings from retesting resistant rats, half of which die, are presented with regard to application of the surveillance program.

While the problem of anticoagulant resistance in commensal rodents has been well-documented from certain areas of northern Europe in recent years, this paper describes its first known occurrence in North America in 1971. Over a rural area of about 5 square miles in Johnson County, North Carolina, it was noted that attempts to control Norway rats using typical warfarin rodenticide bait were increasingly ineffective. Diphacinone was alternated with warfarin with no success. On one farm, 200 lbs of bait had been used in bait boxes in a single month. Laboratory trials on rats captured at this location demonstrated resistance. It was concluded that at this location, intensive use of anticoagulants (mostly warfarin) over a decade, in the absence of adequate sanitation and building maintenance, provided the selective agent to develop resistant populations. This likely will be repeated elsewhere in the U.S.

The brown rat (Rattus norvegicus) is a relatively recent (

Adaptive introgressive hybridization refers to the natural transfer of genes after interspecific mating between species, and subsequent expression of these genes in the recipient species as a new trait that confers selective advantages. Conceptually, the process harnesses immense potential to explain rapid evolution of traits. However, the process requires that reproductive isolation be overcome. Here we present a case of the adaptive introgression of anticoagulant rodenticide resistance from the Algerian mouse (Mus spretus Lataste, 1883) to the Western European house mouse (M. musculus domesticus Linnaeus, 1758). These once allopatric species have come into secondary geographic contact and hybridize occasionally. However, only for an approximately ~20.3 megabase-sized genomic fragment, carrying the vitamin K 2,3-epoxide reductase subunit 1 gene (vkorc1) of M. spretus (vkorc1spr), has hybridization resulted in introgression into the M. m. domesticus genome. This vkorc1spr allele carries amino-acid substitutions, conferring resistance to anticoagulants, has evolved under positive selection in M. spretus (Ka/Ks=1.54-1.93) and displays adaptive population genetic dynamics in M. m. domesticus populations. Since its natural inception

Abstract: Once rats have invaded farm buildings, efficient rat control usually requires the application of rodenti-cides. Efficacy of control measures may be lost by physiological resistance to anticoagulant rodenticides and by behavioural reactions of the target rat population. On a farm within the area of anticoagulant resistance in north-west Germany, two consecutive rodenticide treatments were carried out against rats, using different anticoagulant bait preparations. Bait consumption was monitored in combination with direct individual video-monitoring of bait uptake behaviour. Almost half of the rats survived the first three-week treatment using coumatetralyl bait. This result was ascribed to the high overall degree of anticoagulant resistance prevailing in the rat population. The second treatment of the same population using difenacoum bait totally failed to reduce population numbers. Dietary preferences, neophobia, social interactions and habitat structure are important behavioural parameters determining bait uptake. They are discussed in relation to the results of the treatment and a conceptual model for the factors determining rodent control efficacy is presented. The combined results of the two monitoring techniques applied demonstrate the significance of resistance and bait uptake behaviour for the efficacy of rat control measures and suggest the need for adapted rat-control strategies to reduce hygienic problems and the risk of non-target poisoning hazards for livestock and wildlife. This can be achieved if the choices of bait base and active ingredient as well as the methods of bait positioning are adapted to the behavioural peculiarities of the rats and the specific structural conditions on each farm. [Copyright &y& Elsevier]

BACKGROUND Rodenticide resistance to anticoagulants in Rattus norvegicus will lead to increased difficulties in combating these pest animals. Here, the authors present the results of a survey in the Netherlands where tissue samples and droppings were tested using a newly developed TaqMan PCR test for genotypic variation at codon 139 in the Vkorc1 gene associated with anticoagulant rodenticide resistance. Test results are linked to results of a questionnaire that was conducted among pest controllers. RESULTS Genetic mutations at codon 139 of the Vkorc1 gene in R. norvegicus can be encountered in many parts of the Netherlands. In 34/61 rat tails, a genotype was found that is linked to anticoagulant rodenticide resistance (56%). In droppings, 42/169 samples (25%) showed a resistance-mediating genotype. In addition, indications of a clear genetic substructure in the Netherlands were found. In some regions, only resistance-mediating genotypes were found, corroborating results from the questionnaire in which pest controllers indicated they suspected resistance to anticoagulant rodenticides. CONCLUSION This is the first study to demonstrate the presence of multiple genetic mutations at codon 139 of the Vkorc1 gene in R. norvegicus in the Netherlands. As rodenticides should keep their efficacy because they are a last resort in rodent management, more studies are urgently needed that link specific genetic mutations to the efficacy of active substances. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

BACKGROUND: Genetically based resistance to anticoagulants has led to increasing difficulties in the control of rodents over recent decades. The possible impact of rodenticide-resistant rats on the infection risk of humans and livestock by zoonotic pathogens is generally unknown. Hence, in a monitoring programme in the German federal states of Lower Saxony and Hamburg, more than 500 Norway rats were analysed for both Tyr139Cys polymorphisms within the VKORC1 gene and zoonotic agents. RESULTS: Evidence of resistance was almost completely restricted to the known resistance area in southern Lower Saxony. Homozygous mutations were only found in urban areas sampled owing to the occurrence of rat control problems and were missing in bycatches of rats by muskrat trappers in rural areas. In more than 25% of the rats, zoonotic bacteria (Leptospira, Salmonella, Yersinia and Coxiella) were detected. There was no obvious correlation between the occurrence of rats carrying zoonotic pathogens and anticoagulant resistance. CONCLUSION: Zoonotic agents and genetically based resistance conferred by the Tyr139Cys polymorphism are both unevenly distributed in Lower Saxony. The study provides the basis for further studies focusing on districts with high levels of pathogens and resistance to assess the potential health risk of their combined occurrence. © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Anti-blood coagulation rodenticides, such as warfarin, have been used all over the world. They inhibit vitamin K epoxide reductase (VKOR), which is necessary for producing several blood clotting factors. This inhibition by rodenticides results in lethal hemorrhage in rodents. However, heavy usage of these agents has led to the appearance of rodenticide-resistant rats. There are two major mechanisms underlying this resistance, i.e. , mutation of the target enzyme of warfarin, VKOR, and enhanced metabolism of warfarin. However, there have been few studies regarding the hepatic metabolism of warfarin, which should be related to resistance. To investigate warfarin metabolism in resistant rats, in situ liver perfusion of warfarin was performed with resistant black rats ( Rattus rattus ) from Tokyo, Japan. Liver perfusion is an in situ methodology that can reveal hepatic function specifically with natural composition of the liver. The results indicated enhanced hepatic warfarin hydroxylation activity compared with sensitive black rats. On the other hand, in an in vitro microsomal warfarin metabolism assay to investigate kinetic parameters of cytochrome P450, which plays a major role in warfarin hydroxylation, the V max of resistant rats was slightly but significantly higher compared to the results obtained in the in situ study. These results indicated that another factor like electron donators may also contribute to the enhanced metabolism in addition to high expression of cytochrome P450. [ABSTRACT FROM AUTHOR]

The most common rodent control method worldwide is anticoagulant rodenticides (ARs), which cause death by internal bleeding. ARs can transfer to non-target predators via secondary exposure, i.e. by consuming contaminated rodents. Here we quantify the prevalence of seven AR substances in the liver tissues of altogether 17 mammalian or avian predator or scavenger species in Finland. In addition, we identify the environmental and biological factors potentially linked to secondary AR poisoning. No previous AR screenings have been conducted in the country, despite the widespread use of ARs and their potential impacts on the high levels of the ecosystem food chain. ARs were detected (≥0.3 μg/kg) in 82% of the 131 samples. The most prevalent and the AR with highest concentrations was bromadiolone (65% of samples). In 77% of the positive samples more than one (2–5) different ARs were detected. Of the environmental variables, we only found a weakly positive relationship between the coumatetralyl concentration and the livestock farm density. Conversely, overall AR concentration and number, as well as the concentration of three separate ARs (coumatetralyl, difenacoum and bromadiolone) differed among the three species groups tested, with the group “other mammals” (largely represented by red fox and raccoon dog) having higher values than the groups presented by mustelids or by birds. ARs are authorized only as biocides in Finland and a national strategy on risk management (e.g. for minimising secondary poisoning of non-target species) of ARs was adopted in 2011. Based on these results it appears that the risk mitigation measures (RMMs) either have not been followed or have not been effective in preventing wide scale secondary exposure. Continued monitoring of AR residues in non-target species is needed in order to evaluate the effectiveness of current RMMs and a need for new ones to reduce the risk of secondary poisoning. [ABSTRACT FROM AUTHOR]

Anticoagulant rodenticides (ARs) are used worldwide to control populations of agricultural and urban rodents, but these pesticides may be accumulated in and poisoned non-target species of wildlife. Slugs may feed on rodenticide bait following field applications. Thus, it can be assumed that their predators are exposed to rodenticides through food chain transfer. However, AR exposure in the slugs has not been systematically studied. We investigated the accumulation of three ARs (chlorophacinone, bromadiolone or brodifacoum) in the slug Deroceras reticulatum exposed for a period of 5 days followed by depuration time of 4 days in the laboratory. Moreover, we studied the exposure of slugs to brodifacoum in the field. In the laboratory exposure, the slugs consumed rodenticide baits, but no mortality was observed. After 1 day, their concentrations were stable over the time and no differences were detected between the concentrations of the three ARs. After 5 days of exposure, mean concentrations in slugs were 1.71, 1.91 and 0.44 mg/kg wet weight for chlorophacinone, bromadiolone and brodifacoum respectively. A significant decrease of bromadiolone and brodifacoum in slugs was observed in the post exposure period. In the field study, brodifacoum was detected in > 90% of analyzed slugs after application of brodifacoum baits. Then, based on a toxicity-exposure ratio approach, we found that slug consumption may represent a risk of secondary poisoning for three of their predators under acute, repeated or subchronic exposure scenarios. These results suggest that the slugs are not only the potential subject to primary exposure, but also the source of secondary exposure for their predators following application of rodenticide baits. [ABSTRACT FROM AUTHOR]