Resistance against macrocyclic lactones in Psoroptes ovis in cattle

Abstract

Background: Psoroptic mange is an important disease in Belgian Blue cattle. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is lacking. This study assessed the efficacy of macrocyclic lactone products on 16 beef farms in Belgium and the Netherlands in vivo and in vitro. Methods:On each farm a group of animals (n = 7-14) with psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone product with 7-10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts, clinical index (proportion of the body surface affected by lesions), the proportion of the animals with negative mite counts after the first treatment round and the number of treatment rounds needed to obtain zero mites counts in all animals. A mite population was categorized as sensitive when the mite count reduction after the first treatment round > 95% and the lower limit of the uncertainty interval > 90%. Resistance was detected when both parameters were below their threshold and suspected when one parameter was too low. In vitro knockdown and mortality were evaluated in a contact test. Results:The proportion of the animals with negative mite counts after the first treatment round varied from 0 to 80%. All farms needed two or more treatments rounds to obtain zero mite counts on all animals. Clinical index only started to reduce after the second treatment round. Mite populations from three farms were categorized as sensitive, one as suspected resistant and 12 as resistant. No correlation was found between in vitro lethal dose 50 and knockdown dose 50 values and in vivo efficacy parameters. Conclusions:Unambiguous treatment failure was detected on 12 out of 16 farms, confirming the presence of macrocyclic lactone resistance on Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo sensitivity. The mean reduction in mite counts and the lower limit of the confidence interval are proposed as parameters to identify acaricide resistance.

New insights into the use of a mite count reduction test for the detection of therapeutic acaricide efficacy in Psoroptes ovis in cattle

“…To mimic the field condition as much as possible, a simulation framework was constructed that accounts for both the variation in mite counts at different levels ( Level 1 : farm, Level 2 : animal and Level 3 : lesion), the difference in mite counts across lesions and non-lesions, the variation in size of lesions, and the removal of mites by taking skin scrapings. The parameterisation of these variables was based on re-analyses of field data ( van Mol et al, 2020 ) and collection of new field data.…”

“…To determine the mean (μ f ) and variance (σ 2 f ) of mite counts at farm level, the mite count data collected during a series of published acaricide drug efficacy trials were re-analysed. This dataset included mite counts of 154 animals from 16 farms (7–13 animals per farm) based on 3 scrapings of 9 cm 2 per animal taken from a varying number of lesions per animal (1–3) or predilection locations (withers, midback or tail-base) when lesions were considered too small ( van Mol et al, 2020 ). To cover a wide range of possible mean mite counts at farm level (μ f ) into the simulation, the 5th, 50th and the 95th percentile of the mean mite counts/9 cm 2 were determined at these 16 farms (per farm the mean mite counts at the individual level was averaged).…”

“…This can lead to treatment failure and consequently important animal welfare issues and more financial losses due to additional treatment costs and continuing production losses. At the time of writing, resistance in P. ovis in cattle has only been reported for the macrocyclic lactones ( Lonneux et al, 1998 ; Genchi et al, 2008 ; Lekimme et al, 2010 ; Sarre et al, 2015 ; Lifschitz et al, 2018 ; van Mol et al, 2020 ).…”

“…There is little compliance to these guidelines, as shown by the diversity in sampling strategies applied to assess drug efficacy under field conditions (number of animals included: 6 to 15; number of skin scrapings per animal: 1 to 6; surface of scraping: 4 cm 2 – 9 cm 2 ; Lonneux and Losson, 1992 ; Lonneux et al, 1997 ; Bridi et al, 2001 ; Rehbein et al, 2002 ; Committee for medicinal products for veterinary use(CVMP), 2005 ; Vercruysse et al, 2006 ; Genchi et al, 2008 ; Lekimme et al, 2010 ; Hamel et al, 2014 ; Sarre et al, 2015 ; Lifschitz et al, 2018 ; van Mol et al, 2020 ). This lack in standardisation jeopardises a direct comparison of results across studies and a reliable assessment of acaricide resistance.…”

“…This lack of P. ovis simulations is mainly because there are little insights on the biological distribution of mite counts at the level of farms, individual animals and skin surfaces (with and without lesions), yet these are of utmost importance to reliably mimic field conditions. For example, Sarre et al (2015) and van Mol et al (2020) reported details on the distribution of mite counts, reporting both mean and range of mite counts across farms, whereas others divided their mite counts in different arbitrary categories ( Lonneux and Losson, 1992 ; Genchi et al, 2008 ; Lekimme et al, 2010 ; Lifschitz et al, 2018 ). P. ovis mites are distributed throughout the entire lesion and not restricted to the periphery of the lesion, as is the case in sheep ( Losson et al, 1999 ), but a more detailed description of the distribution within lesions is still lacking.…”