Weak phenotypic reversion of ivermectin resistance in a field resistant isolate of Haemonchus contortus by verapamil

Abstract

Recent advances in anthelmintic resistant phenotype reversion by Pgp modulating drugs in ruminant nematodes indicate that this can be a useful tool to helminth control. The aim of the present study was to evaluate the efficacy of ivermectin (IVM) in combination with verapamil (VRP), in oil or water-based vehicle, against an IVM-resistant field isolate of Haemonchus contortus through a larval migration assay and experimental infection trial. In the in vitro assay was observed a phenotypic reversion of H. contortus resistance to ivermectin at a high concentration of VRP, increasing IVM efficacy from 53.1% to 94.3. In the in vivo trial, IVM + VRP demonstrated 36.02% efficacy compared to the 7.75% of IVM alone. The vehicle formulation showed no influence in efficacy. These are the first results demonstrating the effect of VRP as a partial IVM-resistance phenotype reverser in a field isolate of IVM-resistant H. contortus experimentally inoculated in sheep.

Chemical Characterization of Opuntia ficus-indica (L.) Mill. Hydroalcoholic Extract and Its Efficiency against Gastrointestinal Nematodes of Sheep

“…Our results showed that OFIEOH plus IVM increased L3 inhibition by 1.5 times. A synergistic effect was also observed by reference [ 22 ] when using IVM in combination with verapamil, a calcium channel blocker, with LMT and [ 45 ] in vivo, against H. contortus naturally infected sheep. The effect of the combination of phenolic compounds and/or flavonoids with commercial drugs to control gastrointestinal parasites of livestock still has to be extensively tested to secure maximum animal safety.…”

Experimental infection of calves with Haemonchus placei and Haemonchus contortus: Assessment of parasitological parameters

“…Abomasums were individually subjected to digestion with a pepsin hydrochloric acid solution (Wood et al 1995). The contents of each segment were fixed in 70.0% alcohol (Borges et al 2011). Remaining organs were also inspected for the presence of possible helminth species (Wood et al, 1995).…”

The induction and inhibition of UDP-glycosyltransferases in Haemonchus contortus and their role in the metabolism of albendazole

“…For example, in triclabendazole resistant Fasciola hepatica the roles of flavin monooxygenases and cytochromes P450 were proved using the inhibitors methimazole ( Devine et al, 2009 ) and piperonyl butoxide ( Devine et al, 2011 ), respectively. Verapamil, a well-known inhibitor of efflux transporters P-glycoproteins (Pgp), reversed the resistance to ivermectin in Fasciola hepatica ( Savage et al, 2013 ) and H. contortus ( Borges et al, 2011 ). The UGT inhibitors 5-NU, DNP and SP have often been used in various organisms to demonstrate the role of UGTs in resistance.…”