e. claerebout – factors promoting anthelmintic resistance · pharmacology, parasitology • new...
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FACTORS PROMOTING ANTHELMINTIC RESISTANCE European Medicines Agency
June 13, 2016
Edwin ClaereboutLaboratory for Parasitology, Faculty of Veterinary Medicine,
Ghent University, Belgium
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• Contents– Important helminth parasites in livestock and horses– Prevalence of anthelmintic resistance– Factors promoting anthelmintic resistance– Sustainable use of anthelmintics
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Cooperia spp.Ostertagia ostertagiDictyocaulusviviparusFasciola hepatica
Nematodirus helvetianusTeladorsagia circumcinctaHaemonchus contortusFasciola hepatica
Ascaris suumTrichuris suis
Small strongylesParascaris equorumOxyuris equi
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• Imidothiazoles (levamisole) • Tetrahydropyrimidines (pyrantel)• Benzimidazoles• Macrocyclic lactones• Amino-‐acetonitril derivates (monepantel)• Spiroindoles (derquantel)• Phenol and salicylanilide derivates (closantel,
nitroxinil, oxyclosanide)
•Limited introduction of new anthelmintics•No real alternative control strategies
CRUCIAL TO MAINTAIN THE EFFECTIVENESS OF THESE DRUGS
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Anthelmintic resistance in animalsHost Species Benzimidazoles Levamisole Macrocyclic
lactonesOther
Cattle Cooperia spp.Haemonchus placeiOstertagia ostertagiTrichostrongylus axei
XXXX
XX
XXX
Sheep & Goats
Haemonchus contortusTeladorsagia spp.Trichostrongylus spp.Nematodirus spp.
XXXX
XXX
XXX
MonepantelMonepantelMonepantel
Horses CyathostominaeParascaris equorum
XX
Pyrantel
Pigs Oesophagostomum spp. x x x
Dogs Ancylostoma caninum Pyrantel
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ARGENTINA
URUGUAYBRAZIL
PARAGUAY
MEXICO
UNITED STATESVENEZUELA
INDIA
PAKISTAN
AUSTRALIA
NEW ZEALAND
BANGLADESH
SOUTH AFRICA
EUROPEAN UNIONTURKEY
ZIMBABWE
Cameroon
NIGERIA
KENYA
Adapted from ‘Anthelmintics and Resistance: A Review’ (Novartis)
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Photos courtesy of Dr Neil Sargison (Edinburgh Vet School)
‘Drug resistance in nematodes: a paper tiger or a real problem ?’(Waller, 1985)
2001 2003
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Case study of a cattle farm:
Effic. D212006 73,02007 40,02008 0,0
Surviving species: Cooperia oncophora
Ivermectin efficacy:
El-‐Abdellati et al., 2010. Veterinary Parasitology 171, 167-‐171
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-‐ Anthelmintic resistance-‐ Quality of the products-‐ Underdosing-‐ Drug formulation (injectable, oral, pour-‐on)-‐ Sensitivity of the detection technique-‐ …
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Development of anthelmintic resistance
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Refugia = proportion of helminth population that is not under selection pressure
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Factors promoting anthelmintic resistance• Few published studies
– Mostly observational studies– Few clinical studies– Systematic review and meta-‐analysis (sheep) :
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Factors promoting anthelmintic resistance• Introduction of anthelmintic resistance (no quarantine treatment)
– Suter et al., 2004, 2005• Frequent treatments*
– Treatment interval close to pre-‐patent period
Falzon et al., 2014. Prev Vet Med 117(2):388-‐402 (sheep)Suarez & Christel, 2014. Rev Bras Parasitol Vet 23(2):129-‐35 (cattle)
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Factors promoting anthelmintic resistance• Long term use of the same anthelmintic class vs. rotation?
– Leignel et al., 2010• Under-‐dosing
– No weighing prior to treatment– Treating goats with sheep dose– ‘Tailing off’ of long acting formulation (e.g. intraruminal bolus)NS-‐> Survival of worms with heterozygous resistance alleles.
Falzon et al., 2014. Prev. Vet. Med. 117(2):388-‐402
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Factors promoting anthelmintic resistance• Lack of efficacy testing• Treatment when environmental refugia is low
– Treating ewes at lambing (Haemonchus contortus)– Treating during draught period– Treat and move to clean pasture (‘Dose and move’, ‘Drench-‐and-‐shift’) NS
Falzon et al., 2014. Prev. Vet. Med. 117(2):388-‐402
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Factors promoting anthelmintic resistance• Mixed-‐species grazing? NS
– Protective or risk factor?
• Flock/herd size? NS
Falzon et al., 2014. Prev. Vet. Med. 117(2):388-‐402
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Sustainable use of anthelmintics• Avoid risk factors mentioned above
– SCOPS (www.scops.org.uk)• Reduced number of treatments (‘targeted treatments’)
– Monitoring infection levels (FEC, pepsinogen, antibodies)– Monitoring production (weight, milk)
• Treatment of individual animals (‘targeted strategic treatments’) – Monitoring infection levels (FEC, milk antibodies)– Monitoring production (weight, milk)
• Combination anthelmintics?• Development of alternative control methods
– Vaccines – Anthelmintic plant components (condensed tannins)
• Development of economic farm system models with integrated worm control (e.g. ParaCalc®)
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Integrated control of parasites in livestock
Epidemiology
• Monitoring parasite infections•Identify risk factors
Pharmacology, Parasitology
• New drugs•Sustainable use of existing antiparasitics
Farm management
• Financial impact of infection & treatment
Economics
Immunology & vaccinology
• Vaccines
Genetics
• Resistant cattle•Identification of susceptible animals
improved managementof parasitic infections
more effective treatment
vaccination
Solution = integrated parasite control