Failure of ivermectin efficacy against Psoroptes ovis infestation in cattle: Integrated pharmacokinetic-pharmacodynamic evaluation of two commercial formulations.

Psoroptic mange is an important parasitic disease that mainly affects beef cattle producing marked economic losses. Ivermectin (IVM) is considered one of the most effective treatments against psoroptic mange and is used worldwide to control both endo and ectoparasites in different species. The current work assessed the relationship between pharmacokinetic behavior of IVM and its efficacy against Psoroptes ovis after the subcutaneous administration of two commercial formulations in a cattle feedlot. Aberdeen Angus and Hereford steers were selected based on the presence of active mite infestations. Animals were allocated into 4 experimental groups and treated with a single (day 0) or repeated subcutaneous injection (days 0 and 7) of one of two commercial formulations of IVM (1%) at 0.2 mg/kg. Blood and skin samples were taken from 8 randomly selected animals of each experimental group to measure IVM concentrations by HPLC. Skin scrapings were also collected from six different sites in each animal, mites were counted and ranked based on a density score. Equivalent plasma concentrations of IVM were measured after the administration of IVM formulations under study. The repeated administration of both IVM formulations at day 0 and 7 accounted for a greater plasma drug availability compared with the single administration (P < 0.05). IVM was well distributed from the plasma to the skin without significant differences between both IVM formulations. There was a positive correlation between IVM concentrations in skin and plasma (r: 0.73 P < 0.0001). The mean ratios between IVM availabililty (measured as AUC) in the skin and in plasma were between 1.2 and 2.1. The repeated administration of IVM increased significantly the IVM concentrations in the skin of areas affected by mange. IVM failed to obtain a parasitological cure in the different groups affected by mange. The failure was observed with both formulations administeredat single or repeated doses. Based on the number of animals cured, the range of efficacy was between 0% on day 7 and 60% on day 28 post-treatment. No significant differences in the P. ovis density scores were observed after the IVM treatment at single or repeated doses. Additional studies are needed to confirm the presence of resistant strains of P.ovis and to establish the appropriate measures to control these parasitic infestations in feedlot cattle.

An attempt to replace an ivermectin-resistant Cooperia spp. population by a susceptible one on grazing pastures based on epidemiological principles and refugia management.

The maintenance of anthelmintic-susceptible parasite refugia to delay the onset of anthelmintic resistance is an almost impossible effort in many grazing livestock production countries given that current refugia consist of already resistant parasites. Rather, efforts could be focused on replacing the resistant parasite refugia by susceptible parasite ones and implementing sustainable parasite control measures from then on. To this purpose, a trial was conducted to attempt to establish a new population of ivermectin-susceptible Cooperia sp. on a beef cattle farm with proven problems of ivermectin-resistant Cooperia. During two consecutive years, 82 (Year 1) and 100 (Year 2) recently weaned and parasite-free heifers were inoculated with 40,000 or 30,000 susceptible Cooperia L3, respectively, at a time when levels of resistant parasite refugia were normally low. The animals were subsequently allowed to graze on the problem pastures during autumn until the end of spring. Levels of parasitism in the animals and on pasture were monitored monthly and animals were treated with levamisole when needed. The combination of parasitological monitoring and local epidemiological knowledge was essential to determine when treatments were to be administered. No clinical signs of gastrointestinal parasitosis in the herd were observed throughout the study and unnecessary treatments were avoided. Faecal egg counts reduction tests (FECRT) and controlled efficacy tests (CET) employing worm counts were carried out at different times throughout the study to determine the clinical efficacy (FECRT) and the absolute efficacy (CET) of ivermectin, respectively. The clinical efficacy of ivermectin increased from an initial 73% to 99.4%, while the absolute efficacy increased from 54.1% to 87.5% after just two animal production cycles. The switch from a resistant parasite population to a susceptible one requires knowledge of parasitological epidemiology, especially in relation to seasonal variations of parasite populations in both the host and in refugia.