Distribution of anticoagulant resistance in the brown rat in Belgium

Kristof Baert; Jan Stuyck; Peter Breyne; Dirk Maes; Jim Casaer

doi:10.26496/bjz.2012.135

Authors

Kristof Baert Research Institute for Nature and Forest (INBO), Brussels, Belgium
Jan Stuyck Research Institute for Nature and Forest (INBO), Brussels, Belgium
Peter Breyne Research Institute for Nature and Forest (INBO), Brussels, Belgium
Dirk Maes Research Institute for Nature and Forest (INBO), Brussels, Belgium
Jim Casaer Research Institute for Nature and Forest (INBO), Brussels, Belgium

DOI:

https://doi.org/10.26496/bjz.2012.135

Keywords:

blood clotting response, rodent control, warfarin, bromadiolone, difenacoum, VKORC1

Abstract

Anticoagulant resistance is known as one of the major factors interfering with rodent control. Within this context we investigated the distribution of anticoagulant resistance in Flanders, northern Belgium. From 2003 to 2005, we tested 691 rats from different locations with blood clotting response tests for their susceptibility to the anticoagulant compounds warfarin, bromadiolone and difenacoum. Of these, 119 were also screened for a mutation in the VKORC1 gene that is suspected to be responsible for anticoagulant resistance. Warfarin resistant rats were found in the western and eastern parts of Flanders. The same distribution pattern was found for bromadiolone with the exception of the south-eastern area, where this form of resistance was largely absent. We detected difenacoum resistance in only six rats and did not observe any resistant rats in the central part of Flanders. Susceptible rats were found all over Flanders. Genetic analyses showed that anticoagulant resistance in Belgium was related to two different mutations in VKORC1, namely Y139F and L120Q. Our results indicate that rodent control should be regionally tailored to be most effective.

References

Atterby H, Kelly MJ & Macnicoll AD (2001). Difenacoum resistance in rats is not a consequence of increased metabolism and excretion. In: Pelz HJ, Cowan DP & Feare CJ (Eds.), Advances in Vertebrate Pest Management, Filander Verlag, Fürth: 193-201.

Breckenridge AM, Cholerton S, Hart JA, Park BK & Scott AK (1985). A study of the relationship between the pharmacokinetics and the pharmacodynamics of the 4-hydroxycoumarin anticoagulants warfarin, difenacoum and brodifacoum in the rabbit. British Journal of Pharmacology, 84: 81-91.

Boyle CM (1960). Case of apparent resistance of Rattus norvegicus Berkenhout to anticoagulant poisons. Nature, 188: 517.

Brakes CR & Smith RH (2005). Exposure of nontarget small mammals to rodenticides: short-term

effects, recovery and implications for secondary poisoning. Journal of Applied Ecology, 42: 118-

Buckle AP (1994a). Rodent control methods: chemical. In: Buckle AP & Smith RH (eds), Rodent Pests and Their Control, CAB International, Wallingford: 127-160.

Buckle AP (1994b). Resistance to the first and second generation anticoagulant rodenticides -

a new perspective. Proceedings Vertebrate Pest Conference, 16: 138–144.

Buckle AP (2006). The Current status of anticoagulant resistance in rodents, resistance monitoring and management strategies. Forum for Sustainable Management of Disease Vectors. Beijing 21-23 April 2006.

Chou LS, Gedge F & Lyon E (2005). Complete Gene Scanning by Temperature Gradient Capillary

Electrophoresis Using the Cystic Fibrosis Transmembrane Conductance Regulator Gene as a Model. Journal of Molecular Diagnostic, 7: 111–120.

Dohoo I, Martin W & Stryhn H (2003). Veterinary epidemiologic research. AVC Inc. Charlottetown.

EEA (2007). Halting the loss of biodiversity by 2010: proposal for a first set of indicators to monitor

progress in Europe. Technical Report 11/2007. European Environment Agency.

EPA (2007) Proposed risk mitigation decision for nine rodenticides. United States Environmental

protection agency. Washington, D.C.

EPPO (1995). Guideline for the Evaluation of Resistance to Plant Protection Products: Testing rodents for resistance to anticoagulant rodenticides. EPPO Bulletin, 25: 575-593.

Frantz SC & Padula CM (1998). Warfarin resistance revisited. In: Baker RO & Crabb AC (eds), Proceedings Eighteenth Vertebrate Pest Conference, Costa Mesa, California: 276-280.

Gill JE, Kerins GM & MacNicoll AD (1992). Inheritance of low grade brodifacoum resistance in

the Norway rat. Journal of Wildlife Management, 56: 809–816.

Gill JE, Kerins GM, Langton SD & MacNicoll AD (1993). The development of a blood clotting response test for discriminating between difenacoum-resistant and susceptible Norway rats (Rattus norvegicus, Berk.). Comparative Biochemistry and Physiology, 104C: 29-36.

Gill JE, Kerins GM, Langton SD & MacNicoll AD (1994). Blood-clotting response test for

bromadiolone resistance in Norway rats. Journal of Wildlife Management, 58: 454-461.

Grandemange A, Michael HK, Lasseur R, Longin-Sauvageon C, Berny P & Benoit E (2009). Consequences of the Y139F Vkorc1 mutation on resistance to AVKs: in-vivo investigation in a 7th generation of congenic Y139F strain of rats. Pharmacogenetics and Genomics, 19:742-750.

Grandemange A, Lasseur R, Longin-Sauvageon C, Benoit E & Berny P (2010). Distribution of

VKORC1 single nucleotide polymorphism in wild Rattus norvegicus in France. Pest Management

Science, 66: 270-276.

Greaves JH (1994). Resistance to anticoagulant rodenticides. In: Buckle AP & Smith RH (Eds.), Rodent Pests and Their Control, CAB International, Wallingford: 127-160.

Gratz N (2006). Vector- and Rodent-borne Diseases in Europe and North America. Cambridge

University Press, New York.

Heiberg AC (2009). Anticoagulant resistance: a relevant issue in sewer rat (Rattus norvegicus)

control? Pest Management Science, 65: 444-449.

Heyman P, Baert K, Plyusnina A, Cochez C, Lundkvist A, Esbroeck M, Goossens E, Vandenvelde C, Plyusnin A & Stuyck J (2009). Serological and genetic evidence for the presence of Seoul hantavirus in Rattus norvegicus in Flanders, Belgium. Scandinavian Journal of Infectious Diseases, 41: 51-56.

Hoare JM & Hare KM (2006). The impact of brodifacoum on non-target wildlife: gaps in knowledge. New Zealand Journal of Ecology, 30: 157-167.

Kerins GM, Dennis N, Atterby H, Gill JE & MacNicoll AD (2001). Distribution of resistance to anticoagulant rodenticides in the

Norway rat (Rattus norvegicus Berk.) in England 1995-98. In: Pelz HJ, Cowan DP & Feare CJ (Eds.), Advances in Vertebrate Pest Management, Filander Verlag, Fürth: 149-160.

Lodal J (2001). Distribution and levels of anticoagulant resistance in rats (Rattus norvegicus) in Denmark. In: Pelz HJ, Cowan DP & Feare CJ (Eds.), Advances in Vertebrate Pest Management,

Filander Verlag, Fürth: 139-148.

Lund M (1984). Resistance to the second-generation anticoagulant rodenticides. Proceedings Vertebrate Pest Conference, 11: 89–94.

MacNicoll AD & Gill JE (1987). The occurrence and significance of rodenticide resistance in

the UK. In: British Crop Protection Council Monograph No. 37, British Crop Protection Council, Thornton Heath: 85–95.

MacNicoll AD & Gill JE (1993). Revised methodology for a blood clotting response test for identification of warfarin-resistant Norway rats (Rattus norvegicus). EPPO Bulletin, 23: 701–707.

Markussen MD, Heiberg A-C, Fredholm M & Kristensen M (2008). Differential expression of

cytochrome P450 genes between bromadiolone resistant and anticoagulant-susceptible Norway

rats: a possible role for pharmacokinetics in bromadiolone resistance. Pest Management Science, 64: 239-248.

Martin AD, Steed LC, Redfern R, Gill JE & Huson LW (1979). Warfarin-resistance genotype determination in the Norway rat, Rattus norvegicus. Laboratory Animals, 13: 209-214.

Meehan AP (1984). Rats and mice. Their biology and control. Rentokil limited, East Grinstead.

Oldenburg J, Marinova M, Müller-Reible C & Watzka M (2008). The vitamin K cycle. Vitamins and Hormones, 78: 35-62.

Pelz HJ (2001). Extensive distribution and high frequency of resistance to anticoagulant rodenticides in rat populations from northwestern Germany. In: Pelz HJ, Cowan DP & Feare CJ (Eds.), Advances in Vertebrate Pest Management, Filander Verlag, Fürth: 161-170

Pelz HJ, Hänisch D & Lauenstein G (1995). Resistance to anticoagulant rodenticides in Germany and future strategies to control Rattus norvegicus. Pesticide Science, 43: 61-67.

Pelz HJ, Rost S, Hunerberg M, Fregin A, Heiberg AC, Baert K, MacNicoll AD, Prescott CV, Walker AS, Oldenburg J & Muller CR (2005). The genetic basis of resistance to anticoagulants in rodents. Genetics, 170: 1839-1847.

Prescott CV, Buckle AP, Hussain I & Endepols S (2007). A standardised BCR resistance test for all anticoagulant rodenticides. International Journal of Pest Management, 53: 265-272.

Prescott CV, Buckle AP, Gibbings JG, Allana NW & Stuart AM (2011) Anticoagulant resistance in Norway rats (Rattus norvegicus Berk.) in Kent - a VKORC1 single nucleotide polymorphism, tyrosine139phenylalanine, new to the UK. International Journal of Pest Management, 57: 61-65.

Rost S, Fregin A, Ivaskevicius V, ConzelmannE, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM & Oldenburg J (2004). Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 427: 537-541.

Rost S, Pelz HJ, Menzel S, MacNicoll A, Leon V, Song KJ, Jakel T, Oldenburg J & Muller C (2009). Novel mutations in the VKORC1 gene of wild rats and mice - a response to 50 years of selection pressure by warfarin? BMC Genetics, 10: 4.

Stuyck J (2003). Bruine rat. In: Verkem S, De Maeseneer J, Vandendriessche B, Verbeylen G & Yskout S (Eds.), Zoogdieren in Vlaanderen. Ecologie en verspreiding van 1987 tot 2002, Natuurpunt Studie & JNM-Zoogdierenwerkgroep, Mechelen & Gent: 211-215.

Thijssen HHW (1995). Warfarin-based rodenticides: mode of action and mechanism of resistance.

Pesticide Science, 43: 73-78.

Ye S, Dhillon S, Ke X, Collins AR & Day INM (2001). An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Research, 29: e88.