title: Resistance testing and the effectiveness of difenacoum against Norway rats (Rattus norvegicus) in a tyrosine139cysteine focus of anticoagulant resistance, Westphalia, Germany.
abstract: BACKGROUND
  Anticoagulant resistance in Norway rats at foci in Belgium, Denmark, France, Germany, the Netherlands and the United Kingdom is genetically characterised by the same single nucleotide polymorphism (SNP) and consequent amino acid exchange from tyrosine to cysteine at location 139 of the vkorc1 gene (i.e. tyrosine139cysteine or Y139C). The purpose of this study was to assess the degree of resistance among rats at two infested farm sites in the Y139C focus in Westphalia, Germany, using blood clotting response (BCR) tests, and to determine the practical efficacy of applications of a commercial 50 ppm difenacoum bait (Neokil™) against them.
  
  
  RESULTS
  BCR tests showed that the difenacoum resistance factor (RF) among the Y139C rats was about 2.5. DNA analysis for the Y139C mutation revealed that it was present among rats at the two sites with a prevalence of 75 and 93%. Applications of difenacoum bait at the two sites achieved 86.8 and 59.9% control. The different outcomes did not appear to be due to differences either in the degree and prevalence of resistance or in the quantities of poisoned bait consumed.
  
  
  CONCLUSIONS
  The study showed that, although the RF for difenacoum among rats carrying the Y139C SNP was apparently low, an acceptable level of control of resistant Norway rat infestations was not achieved using difenacoum. Continued use of anticoagulants against rats that are resistant to them will exacerbate resistance problems in terms of both increased severity and prevalence. These conclusions are likely to apply elsewhere in Europe where the Y139C SNP occurs.
authors.affiliation: Vertebrate Pests Unit, School of Biological Sciences, The University of Reading, Reading, UK. a.p.buckle@reading.ac.uk
authors.forename: Alan
authors.initials: A
authors.lastname: Buckle
authors.forename: Stefan
authors.initials: S
authors.lastname: Endepols
authors.forename: Nicole
authors.initials: N
authors.lastname: Klemann
authors.forename: Jens
authors.initials: J
authors.lastname: Jacob
mesh_terms: D015110:4-Hydroxycoumarins / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D004351:Drug Resistance; D005858:Germany; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D051381:Rats / Q000235:genetics* / Q000378:metabolism; D012375:Rodent Control / Q000379:methods*; D012378:Rodenticides / Q000494:pharmacology*; D064417:Vitamin K Epoxide Reductases
chemical_list: D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D012378:Rodenticides; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; C012903:difenacoum