Impact on beef cattle productivity of infection with anthelmintic-resistant nematodes

ABSTRACT

Aims: The main goal of the current study was to evaluate, on a commercial beef cattle farm, the impact of infection with gastrointestinal nematodes resistant to both ivermectin (IVM) and moxidectin (MXD) on the productivity of calves.

Methods: Male Aberdeen Angus calves, aged 9–11 months, with faecal nematode egg counts (FEC) ≥200 epg and body weight ≥190?kg, were allocated to two herds. Herd A (n?=?90) grazed a maize-winter forage crop rotation and Herd B (n?=?90) grazed a 2-year-old Agropyrum pasture. On Day 0 in each herd, calves were randomly allocated into five groups (n?=?18), which were treated with 0.2?mg/kg IVM; 0.2?mg/kg MXD; 3.75?mg/kg ricobendazole (RBZ), both IVM and RBZ, or remained untreated. Faecal samples collected on Days ?1 and 19 were used to determine the percentage reduction in FEC, and genera of the nematodes were determined by the identification of the third-stage larvae recovered from faecal cultures. Total weight gain was determined from body weights recorded on Days ?1 and 91.

Results: Overall mean reduction in FEC was 42% for IVM, 67% for MXD, 97% for RBZ and 99% for IVM?+?RBZ. The reduction in FEC for Cooperia spp. was ≤78% for IVM and MXD, and for Haemonchus spp. was 0 and 36% for IVM and MXD, respectively, confirming the presence of parasites resistant to both anthelmintics. Only IVM?+?RBZ treatment resulted in 100% efficacy against Haemonchus spp. The overall estimated mean total weight gain for calves treated with IVM was 15.7 (95% CI?=?11.9–19.7) kg and for calves treated with IVM?+?RBZ was 28.8 (95% CI?=?25–32.5) kg (p?<?0.001). Mean total weight gain for calves treated with MXD was 23.5 (95% CI?=?19.7–27.2) kg.

Conclusions and clinical relevance: In calves naturally infected with resistant nematodes, under the production system assessed here, weight gains were lower in calves treated with anthelmintics that were moderately or highly ineffective compared to those treated with highly effective anthelmintics. These results demonstrate to farmers and veterinarians the importance of a sustainable and effective nematode control under field conditions.     

Moxidectin and ivermectin metabolic stability in sheep ruminal and abomasal contents

The oral administration of macrocyclic lactones to sheep leads to poorer efficacy and shorter persistence of the antiparasitic activity compared to the subcutaneous treatment. Gastrointestinal biotransformation occurring after oral treatment to ruminant species has been considered as a possible cause of the differences observed between routes of administration. The current work was addressed to evaluate on a comparative basis the in vitro metabolism of moxidectin (MXD) and ivermectin (IVM) in sheep ruminal and abomasal contents. Both compounds were incubated under anaerobic conditions during 2, 6 and 24 h in ruminal and abomasal contents collected from untreated adult sheep. Drug concentrations were measured by high-performance liquid chromatography with fluorescence detection after sample clean up and solid phase extraction. Neither MXD nor IVM suffered metabolic conversion and/or chemical degradation after 24-h incubation in ruminal and abomasal contents collected from adult sheep. Unchanged MXD and IVM parent compounds represented between 95.5 and 100% of the total drug recovered in the ruminal and abomasal incubation mixtures compared with those measured in inactive control incubations. The partition of both molecules between the solid and fluid phases of both sheep digestive contents was assessed. MXD and IVM were extensively bound (>90%) to the solid material of both ruminal and abomasal contents collected from sheep fed on lucerne hay. The results reported here confirm the extensive degree of association to the solid digestive material and demonstrates a high chemical stability without evident metabolism and/or degradation for both MXD and IVM in ruminal and abomasal contents.     

Resistance of Cooperia to ivermectin treatments in grazing cattle of the Humid Pampa, Argentina

A field experiment and a controlled efficacy trial were conducted to demonstrate resistance of cattle trichostrongylid nematodes to endectocidal compounds in grazing cattle on the Humid Pampa, Argentina. Male Polled Hereford calves, aged 9-11 months old, with a history of frequent treatments with compounds of the avermectin/milbemycin class, were used for the trial. The field experiment involved six groups of 10 animals each, which were subcutaneously treated with either ivermectin (IVM), long-acting ivermectin (LA-IVM), moxidectin (MXD) or doramectin (DRM) at a dosage of 0.2mg/kg BW. A fifth group was treated orally with fenbendazole at a dosage of 5mg/kg BW; the sixth group of calves served as non-treated control. Faecal samples were collected from each animal on the day of treatment and at 14 days after treatment. Nematode egg counts were performed to estimate the faecal egg count reduction test (FECRT). The FECRT showed that reductions were 65% (IVM), -20% (LA-IVM) and 85% (DRM). Egg counts from calves treated with MXD or fenbendazole were reduced by 95 and 100%, respectively. For the controlled efficacy trial, six animals with the highest egg counts from the IVM, LA-IVM and non-treated control groups, were necropsied on day 18 after treatment to determine numbers and nematode species in the abomasum and small intestine. The results indicated that efficacy against Cooperia oncophora was 62.7 and 48% for IVM and LA-IVM, respectively. Neither of the IVM formulations showed efficacy against Trichostrongylus spp. in the small intestine. However, the absence of Trichostrongylus spp. in some animals of both treated and control groups precluded a valid assessment of efficacy or resistance. It was concluded that resistance of trichostrongylid nematodes to the avermectin/milbemycin class of compounds in grazing cattle of the Humid Pampa, Argentina, may be strongly established on farms where cattle are treated at frequent intervals throughout the year.     

Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats

A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.     

A comparison of the efficacy of subcutaneously administered ivermectin,doramectin, and moxidectin against naturally infected <Emphasis Type="Italic">Toxocara vitulorum</Emphasis> in calves

This study was conducted to investigate the efficacy of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD) against Toxocara vitulorum in calves. In the study, 20 calves naturally infected with T. vitulorum were divided into four groups: three different treatment groups (n?=?5) and one positive control (n?=?5). The animals in each group received either IVM (Baymec®, Bayer), DRM (Dectomax®, Pfizer), or MXD (Cydectin®, Fort Dodge) by subcutaneous injection at a single dose of 0.2 mg/kg. Fecal egg counts were performed on all animals on days 0, 2, 4, 8, 12, and 16 post-treatment. In conclusion, IVM, DRM, and MXD significantly reduced the fecal egg counts on day 8 post-treatment (99.90%, 98.77%, and 99.57%, respectively). After the 12th day, IVM, DRM, and MXD were found to be 100% effective. There was no significant difference in efficacy between the three treatment groups at any of the sampling dates (P?>?0.05). No side effects associated with nervous, respiratory, and gastrointestinal systems were observed. This is the first study to evaluate the comparative efficacy of subcutaneous administration of ivermectin, doramectin, and moxidectin against naturally infected T. vitulorum in calves.     

Characterisation of two triple resistant field isolates of Teladorsagia from Scottish lowland sheep farms

The anthelmintic resistance status of two field isolates derived from farms (farm A and B) located near Edinburgh were examined using both controlled efficacy tests (CET) and faecal egg count reduction tests (FECRT). Efficacies against fenbendazole (FBZ), levamisole (LEV) and ivermectin (IVM) and, for one isolate, against combinations of these anthelmintics and moxidectin were determined in na?ve lambs, artificially infected with the isolates and treated with the compounds at the manufacturers recommended dose rates. (FBZ, 5mg/kg bodyweight (BW); LEV, 7.5mg/kg BW; IVM, 0.2mg/kg BW; Moxidectin (MOX) 0.2mg/kg BW). In both field isolates, the predominant species found pre-treatment and the only species found post-treatment was Teladorsagia circumcincta. Resistance to FBZ, LEV and IVM was confirmed in CET and FECRT on farm A and to the latter two compounds on farm B, which had a history of benzimidazole resistance and where TBZ resistance was also demonstrated using an egg hatch assay (EHA). For the farm A isolate CET efficacies against FBZ; IVM; LEV; FBZ + IVM; FBZ + LEV; FBZ, LEV + IVM and MOX were 59, 60, 88, 94,93, 92 and 98%, respectively. The CET efficacies for the farm B isolate were 51% and 72% for LEV and IVM, respectively.     

Resistance to a triple-combination anthelmintic in Trichostrongylus spp. on a commercial sheep farm in New Zealand

Abstract

AIM: To evaluate resistance to anthelmintics containing abamectin, levamisole, and oxfendazole (AB-LEV-OX), derquantal and abamectin (DEQ-AB), moxidectin, and monepantel in naturally acquired gastrointestinal nematodes present on a sheep farm.

METHODS: Faecal nematode egg count reduction tests (FECRT) were carried out on lambs that were approximately 7 months-old and infected with naturally acquired nematodes. Lambs were randomly allocated to one of five groups (n=15 per group): treatment with 2?mg/kg derquantel and 0.2?mg/kg abamectin; 0.2?mg/kg abamectin, 8?mg/kg levamisole HCl and 4.5?mg/kg oxfendazole; 2.5?mg/kg monepantel; 0.2?mg/kg moxidectin, or no treatment. Post-treatment samples were collected 12 days later. Abomasa and small intestines were collected from two slaughtered lambs from each of the DEQ-AB, AB-LEV-OX, moxidectin and control groups 15 days after treatment, for nematode counting.

RESULTS: The FECRT demonstrated that efficacy was 90.3 (95% CI=84.2–94.1)% for AB-LEV-OX, 54.5 (95% CI=28.4–71.1)% for moxidectin, 99.2 (95% CI=97.4–99.8)% for DEQ-AB and 100% for monepantel, across all genera. For Trichostrongylus spp. efficacy was 85.5% for AB-LEV-OX and 46.7% for moxidectin. Haemonchus spp. were fully susceptible to all treatments. Post-treatment nematode counts indicated that the resistant Trichostrongylus spp. were from the small intestine.

CONCLUSIONS: Anthelmintic resistance to both AB-LEV-OX and moxidectin was present in the Trichostrongylus genus on a commercial sheep farm. Monepantel and DEQ-AB were both effective against Trichostrongylus spp. based on FECRT results.

CLINICAL RELEVANCE: This finding of resistance to an AB-LEV-OX triple-combination anthelmintic in the Trichostrongylus genus in sheep in New Zealand further limits anthelmintic treatment options available, and calls into question whether this combination is suitable for use as a quarantine treatment.     

Comparison of the pharmacokinetics of moxidectin (Equest®) and ivermectin (Eqvalan®) in horses

A study was undertaken in order to evaluate and compare plasma disposition kinetic parameters of moxidectin and ivermectin after oral administration of their commercially available preparations in horses. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups of five horses. Group I was treated with an oral gel formulation of moxidectin (MXD) at the manufacturers recommended therapeutic dose of 0.4 mg/kg bw. Group II was treated with an oral paste formulation of ivermectin (IVM) at the manufacturers recommended dose of 0.2 mg/kg b.w. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Computerized kinetic analysis was carried out. The parent molecules were detected in plasma between 30 min and either 30 (IVM) or 75 (MXD) days post-treatment. Both drugs showed similar patterns of absorption and no significant difference was found for the time corresponding to peak plasma concentrations or for absorption half-life. Peak plasma concentrations (Cmax) of 70.3+/-10.7 ng/mL (mean +/- SD) were obtained for MXD and 44.0+/-23.1 ng/mL for IVM. Moreover, the values for area under concentration-time curve (AUC) were 363.6+/-66.0 ng x d/mL for the MXD treated group, and 132.7+/-47.3 ng x d/mL for the IVM treated group. The mean plasma residence times (MRT) were 18.4+/-4.4 and 4.8+/-0.6 days for MXD and IVM treated groups, respectively. The results showed a more prolonged residence of MXD in horses as demonstrated by a four-fold longer MRT than for IVM. The longer residence and the higher concentrations found for MXD in comparison to IVM could possibly explain a more prolonged anthelmintic effect. It is concluded that in horses the commercial preparation of MXD presents a pharmacokinetic profile which differs significantly from that found for a commercial preparation of IVM. To some extent these results likely reflect differences in formulation and doses.     

Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle

The persistence of the broad-spectrum antiparasitic activity of endectocide compounds relies on their disposition kinetics and pattern of plasma/tissues exchange in the host. This study evaluates the comparative plasma disposition kinetics of ivermectin (IVM), moxidectin (MXD) and doramectin (DRM) in cattle treated with commercially available injectable formulations. Twelve (12) parasite-free male Hereford calves (180–210 kg) grazing on pasture were allocated into three groups of four animals each. Animals in each group received either IVM (Ivomec 1%, MSD AGVET, Rahway, NJ, USA), MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) or DRM (Dectomax 1%, Pfizer Inc., New York, NY, USA) by subcutaneous injection at a dose of 200 μg/kg. Jugular blood samples were collected from 1 h up to 80 days post-treatment, and plasma extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The parent molecules were detected in plasma between 1 h and either 70 (DRM) or 80 (IVM and MXD) days post-treatment. The absorption of MXD from the site of injection was significantly faster (absorption half-life (t_½ab) = 1.32 h) than those of IVM (t_½ab= 39.2 h) and DRM (t_½ab= 56.4 h). MXD peak plasma concentration (C_max) was reached significantly earlier (8.00 h) compared to those of IVM and DRM (4–6 days post-treatment). There were no differences on C_max values; the area under the concentration–time curve (AUC) was higher for IVM (459 ng.d/mL) and DRM (627 ng.d/mL) compared to that of MXD (217 ng.d/mL). The mean plasma residence time was longer for MXD (14.6 d) compared to IVM (7.35 d) and DRM (9.09 d). Unidentified metabolites were detected in plasma; they accounted for 5.75% (DRM), 8.50% (IVM) and 13.8% (MXD) of the total amount of their respective parent drugs recovered in plasma. The comparative plasma disposition kinetics of IVM, MXD and DRM in cattle, characterized over 80 days post-treatment under standardized experimental conditions, is reported for the first time.     

A comparative kinetic study of ivermectin and moxidectin in lactating camels (Camelus dromedarius).

The plasma and milk kinetics of ivermectin (IVM) and moxidectin (MXD) was evaluated in lactating camels treated subcutaneously (0.2 mg kg(-1)) with commercially available formulations for cattle. Blood and milk samples were taken concurrently at predetermined times from 12 h up to 60 days post-administration. No differences were observed between plasma and milk kinetics of IVM, while substantial differences were noted between plasma and milk profiles of MXD in that both the maximal concentration (Cmax) and the area under concentrations curves (AUC) were three to four-fold higher for milk than for plasma. The time (Tmax) to reach Cmax was significantly faster for MXD (1.0 day) than that for IVM (12.33 days). The Cmax and the AUC were significantly higher for MXD (Cmax = 8.33 ng ml(-1); AUC = 70.63 ng day ml(-1)) than for IVM (Cmax = 1.79 ng ml(-1); AUC = 30.12 ng day ml(-1)) respectively. Drug appearance in milk was also more rapid for MXD (Tmax = 3.66 days) compared to IVM (Tmax = 17.33 days). The extent of drug exchange from blood to milk, expressed by the AUCmilk/AUCplasma ratio, was more than three-fold greater for MXD (4.10) compared to that of IVM (1.26), which is consistent with the more lipophilic characteristic of MXD. However, the mean residence time (MRT) was similar in both plasma and milk for each drug.     

Efficacy of Ivermectin Pour-on Against Nematodes Infecting Foals on Pasture: Coprological and Biochemical Analysis

The efficacy of topical ivermectin (IVM) on foals naturally infected by parasitic nematodes was evaluated. Two dosages of IVM were applied pour-on (F-Nor0.5; 0.5 mg/kg body weight [BW] and F-Nor1; 1 mg/kg BW) and results compared with the oral administration (F-Eq0.2; 0.2 mg/kg BW of IVM). The efficacy was measured by estimating the reduction in the fecal egg counts (fecal egg count reduction) and in the numbers of horses shedding parasite eggs (positive horse reduction). Several biochemical and enzymatic serum parameters were measured in the groups F-Eq0.2 and F-Nor1. Before the deworming of the horses, eggs of Parascaris equorum, Cyathostomum, Gyalocephalus spp, and Oxyuris equi were identified. In all the treated groups, the excretion of ascarid eggs ended 4 days after the treatment. The orally administered IVM suppressed the egg output of strongyles and pinworms 4 days after the treatment, whereas for the F-Nor1 group this occurred 8 days after the treatment. Eggs of strongyles were detected in the F-Nor0.5 group throughout the study. The levels of blood urea nitrogen, creatinine, total proteins, albumin, globulins, and lactate dehydrogenase (LDH) reduced significantly after the administration of IVM, but values not within the normal range were only achieved for LDH. A significant positive correlation between the fecal egg output of cyathostomins and the LDH was investigated. Clinically, no adverse reactions in the horses receiving the topical IVM were observed. It was concluded that the pour-on administration of 1 mg/kg BW IVM provides similar results to the oral administration, and offers a very useful tool to control infestation by the intestinal nematodes affecting wild grazing horses.     

Effects of age and immune suppression of sheep on fecundity, hatching and larval feeding of different strains of Haemonchus contortus

The effects of host age and immune suppression on abomasal parasitic infection in sheep were investigated following single experimental oral infections with MHco3 (ISE), MHco4 (WRS) and MHco10 (CAVR) strains of Haemonchus contortus in naïve 5-month-old crossbred lambs (n = 1 per group) and 15-month-old Greyface sheep treated with methyl prednisolone acetate (n = 2 per group) or without corticosteroid treatment (n = 2 per group). Adult female H. contortus in 5-month-old lambs (n = 1 per group) shed on average 6.5, 3.1 and 8.0 times more eggs than in 15-month-old sheep (n = 4 per group) following infection with MHco3 (ISE), MHco4 (WRS) and MHco10 (CAVR) strains of H. contortus, respectively, over a period of 28 days following the commencement of patency. There was no obvious effect of age of sheep or corticosteroid treatment on the abomasal establishment of H. contortus or on in vitro assays for egg hatching or larval feeding at different concentrations of anthelmintics, although statistical analysis could not be performed due to the small group sizes.     

Pharmacokinetics of ivermectin in sheep following pretreatment with Escherichia coli endotoxin

The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 μg LPS/kg bw at ?24, ?16, and ?0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non‐compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half‐life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day^?1 ml^?1), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.     

Influence of Pluronic 85 and ketoconazole on disposition and efficacy of ivermectin in sheep infected with a multiple resistant Haemonchus contortus isolate

Non-specific mechanisms involving ATP-binding cassette drug efflux transporters may play an important role in xenobiotic clearance in ovine gastro-intestinal nematodes. By using transporter inhibitors, the aim of this trial was to assess the possibility of increasing drug bioavailability in the host in an attempt to improve treatment efficacy. Thirty-six lambs were infected with 5000 multiple-drug resistant Haemonchus contortus third stage larvae and separated into six groups (n=6): ivermectin alone (IVM; 0.2 mg/kg body-weight, BW), ketoconazole alone (KET; 10 mg/kg BW), Pluronic 85 alone (P85; 4 mg/kg BW), IVM+KET, IVM+P85 or untreated control. Ivermectin was administered once on day 28 post-infection for all appropriate groups, whereas KET and P85 were administered as five separate doses on day 26-30 post-infection inclusive. The resultant data showed that concomitant administration of KET or P85 with IVM induced increases in plasma and tissue concentrations of IVM in treated animals, resulting in a two-fold increase in the area under the time-concentration curve (p<0.05). Faecal egg counts and worm burdens of the IVM+KET and IVM+P85 groups were lower than in the untreated, KET and P85 alone control animals. Worm burdens were reduced by between 16% and 51% with IVM+KET and IVM+P85 respectively compared to untreated control animals. The co-administration of P85 with IVM increased the efficacy by 34%, compared with IVM alone, in terms of worm count reduction of the multi-resistant isolate of H. contortus.     

Moxidectin has a lower neurotoxic potential but comparable brain penetration in P‐glycoprotein‐deficient CF‐1 mice compared to ivermectin

The anti‐parasitic drugs ivermectin (IVM) and moxidectin (MOX) normally show limited brain penetration in vertebrates because of effective drug efflux at the blood–brain barrier by P‐glycoprotein, encoded by the multi‐drug resistance (MDR1) gene. However, dogs with homozygous nt230(del4) mutation in the MDR1 gene do not express a functionally active P‐glycoprotein and show increased brain penetration of these drugs, resulting in neurological toxicity to different degrees. Thus, whereas IVM provokes neurological toxicity at 0.1 mg/kg, MOX is tolerated at this dosage. To investigate whether this difference is attributable to lower brain penetration of MOX in the absence of P‐glycoprotein or to their neurotoxic potential, we applied IVM and MOX to P‐glycoprotein‐deficient CF‐1 mice and comparatively analysed the absolute drug concentrations in the brain. Furthermore, we quantified drug‐induced neurotoxicity by measuring the walking performance of the mice on a rotarod setup. We found that at a dosage of 0.2 mg/kg, representing 0.23 μmol/kg IVM and 0.31 μmol/kg MOX, the absolute drug concentrations in the brain were comparable with 100.8 pmol/g and 140.2 pmol/g, respectively. However, MOX induced the same degree of neurotoxicosis at the higher dosage of 1.09 μmol/kg (0.7 mg/kg) compared with IVM at 0.40 μmol/kg (0.35 mg/kg), demonstrating the 2.7‐fold lower neurotoxic potential of MOX compared to IVM. This could be explained by a lower binding affinity or lower intrinsic activity of MOX at the relevant central nervous system receptors compared with IVM.     

Comparison of two versions of larval development test to detect anthelmintic resistance in Haemonchus contortus

Larval development (LDT) and micro-agar larval development tests (MALDT) were used to compare the reliability and sensitivity of two methods for detecting anthelmintic resistance in Haemonchus contortus. The tests were conducted using three resistant and four susceptible isolates of H. contortus. Both versions of the tests provided comparable results with regard to the characterization of benzimidazole and levamisole susceptibility but neither test was sufficiently sensitive to discrimination between an ivermectin (IVM) susceptible and an IVM resistant isolate. Each test has its own merits with the LDT having the advantage of being less time-consuming.     

Assessing resistance against macrocyclic lactones in gastro-intestinal nematodes in cattle using the faecal egg count reduction test and the controlled efficacy test

The main objective of the present study was to evaluate the accuracy of the faecal egg count reduction test (FECRT) to assess the resistance status of ivermectin (IVM)-resistant isolates of the cattle nematodes Ostertagia ostertagi and Cooperia oncophora, using the controlled efficacy test (worm counts) as a reference. The second objective was to investigate whether both IVM-resistant isolates showed side-resistance against moxidectin (MOX) under controlled conditions. Thirty male Holstein calves were experimentally infected with 25,000 L3 of an IVM-resistant O. ostertagi isolate and 25,000 L3 of an IVM-resistant C. oncophora isolate. Twenty-eight days later the calves were randomly divided into 2 treatment groups and 1 untreated control group. Animals in groups 1 and 2 received MOX (Cydectin(?) 1%, Pfizer) and IVM (Ivomec(?) 1%, Merial) respectively, by subcutaneous injection at a dose rate of 0.2mg/kg bodyweight. Faecal samples were collected 7 and 14days after treatment and animals were necropsied 14/15days post-treatment. Both the FECRT and the controlled efficacy test demonstrated that the O. ostertagi and C. oncophora isolates were resistant against IVM, with efficacies below 90%. The IVM-resistant O. ostertagia isolate was still susceptible to MOX treatment, as shown by over 99% reduction in egg counts and worm burden. The FECRT suggested borderline resistance against MOX in the IVM-resistant C. oncophora isolate, with egg count reductions between 97% (95% CI: 76; 100) at day 7 and 86% (95% CI: 49; 96) at day 14. However, the controlled efficacy test clearly showed MOX-resistance, with a decrease of only 31% (95% CI: -12; 57) in C. oncophora worm numbers. After MOX treatment, a significantly lower number of eggs per female C. oncophora worms was counted compared to the control group (43% reduction). Due to this reduced fecundity, the FECRT may fail to detect MOX-resistance.     

Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.     

Response of Corriedale and Crioula Lanada Sheep to Artificial Primary Infection with Haemonchus Contortus

Clinical, parasitological and biochemical parameters were evaluated in Corriedale and Crioula Lanada sheep after a single experimental infection with Haemonchus contortus. Ten 4-month-old worm-free lambs, of each breed, were infected with 200 L₃ H. contortus per kg live weight and four uninfected animals of each breed were used as controls. Every week, the animals were weighed and blood and faecal samples were collected for measurement of packed cell volume (PCV), total serum protein (TSP) and albumin (ALB), and the number of eggs per gram of faeces (EPG), respectively. Twelve weeks after infection, the animals were slaughtered. The worm burden was determined and samples of the abomasal mucosa were processed for determination of the number of eosinophils, mast cells and globule leukocytes. No significant differences in PCV, TSP, ALB, parasite burden or the cell populations of the abomasal mucosa were observed between breeds, but Crioula lambs had a lower EPG count. The comparison of the infected groups with their respective controls revealed significant alterations in PCV, TSP and ALB in the Corriedale lambs and in PCV, TSP, ALB and the density of eosinophils and mast cells in the Crioula lambs.