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.     

Anthelmintic resistance on goat farms in Georgia: efficacy of anthelmintics against gastrointestinal nematodes in two selected goat herds

Gastrointestinal nematode (GIN) parasitism is a major constraint to production of goats in the southeastern United States. The conventional method of control used by producers in this region is frequent use of anthelmintics during the warm season. Overuse of anthelmintics has led to an increase in the incidence of anthelmintic resistance in many parts of the world, but data on prevalence of anthelmintic resistance in GIN of goats in the southeastern United States are very limited. To address this issue, anthelmintic efficacy was determined in goat herds at the Fort Valley State University, Agricultural Research Station (FVSU-ARS) and the University of Georgia, College of Veterinary Medicine (UGA-CVM) using fecal egg count reduction (FECR) tests and DrenchRite((R)) larval development assays (LDA). At FVSU-ARS, 2-year-old Spanish goat does were randomly allocated to one of nine different treatment groups (n = 10): albendazole (ABZ; 20mg/kg body weight (BW)), fenbendazole (FBZ; 20mg/kg BW), ivermectin (IVM; 0.4 mg/kg BW), doramectin (DRM; 0.4 mg/kg BW), moxidectin (MOX; 0.4 mg/kg BW), levamisole (LEV; 12 mg/kg BW), morantel tartrate (MOR; 10mg/kg BW), a combination of IVM (0.4 mg/kg BW) and ABZ (20 mg/kg BW), and untreated controls. At UGA-CVM, goats were randomly allocated to one of five different treatment groups (n = 8): ABZ (20 mg/kg BW), IVM (0.4 mg/kg BW), MOX (0.4 mg/kg BW), LEV (12 mg/kg BW), and untreated controls. All drugs in both experiments were administered orally. Anthelmintic efficacy was calculated by comparing 14-day post-treatment FEC of treated and control animals, and percent reductions were interpreted using the World Association for the Advancement of Veterinary Parasitology guidelines for resistance. For the LDA, nematode eggs were isolated from pooled fecal samples of untreated control goats in each herd and used to perform DrenchRite((R)) assays. In the FVSU-ARS herd, MOX, LEV, the combination of IVM and ABZ, IVM, DRM, ABZ, MOR, and FBZ reduced FEC by 100, 91, 88, 78, 76, 62, 48, and 10%, respectively. In the UGA-CVM herd, MOX, LEV, ABZ and IVM, reduced FEC by 100, 94, 87, and 0%, respectively. In both herds moxidectin was the only drug tested that was fully effective. Results of the LDA were in agreement with results of the FECR tests for both herds. These data demonstrate the presence of GINs resistant to all three major anthelmintic classes in both goat herds.     

Efficacy of major anthelmintics against horse cyathostomins in France

This paper reports a survey conducted in France during 2011 to evaluate the efficacy of commonly used anthelmintics against horse cyathostomins. A total of 40 farms and 1089 horses were screened for the presence of cyathostomins. All farms but one were positive, with an overall animal infection rate of 53.7%, ranging from 9% to 83% on individual farms. On 445 horses from 30 of these farms, a faecal egg count reduction test (FECRT) was performed to evaluate the efficacy of oral formulations of fenbendazole (FBZ), pyrantel embonate (PYR), ivermectin (IVM) and moxidectin (MOX). Calculation of the mean FECR and 95% confidence intervals (95% CI) around the mean was performed using bootstrap analysis. Resistance to FBZ was found on 17 of 18 farms investigated, with a mean reduction of 57% (95% CI: 38.5-71.2%). Suspected resistance for PYR was found on 6 of 30 farms, and confirmed on another 3 of 30 farms, with a mean reduction for PYR of 94.7% (95% CI: 88.9-98.5%). Reduced efficacy simultaneously of FBZ and PYR was found in 7 farms. Reduced efficacy of IVM was found in one animal on one farm and of MOX in one animal on another farm, and was combined with resistance against FBZ and/or PYR. These results indicate that single and multiple drug resistance and reduced efficacy in equine cyathostomins is present in France. Macrocylic lactones proved to be highly effective compounds against cyathostomins, with reduced efficacy for IVM and MOX in two farms only. These results extend present knowledge on the occurrence of drug resistant cyathostomins in Europe, and illustrate the necessity to use anthelmintics in appropriate worm control programmes.     

Efficacy of some anthelmintics on an ivermectin-resistant strain of Haemonchus contortus in sheep

Following evidence of reduced efficacy of ivermectin in a field population of Haemonchus contortus in Brazil, this strain of the parasite was submitted to a controlled anthelmintic test. Eighty worm-free lambs were randomly split into two groups of 40. Each lamb in the first group was infected with 5000 third stage larvae (L3) of the ivermectin-resistant strain; the remaining 40 lambs were each infected with 5000 L3 of a H. contortus strain of known susceptibility to the major groups of anthelmintic compounds used in sheep. On Day 28 post-infection, each group was subdivided according to egg counts and at random into four sub-groups of ten lambs, each of which was treated with albendazole (ABZ) at 3.8 mg kg-1, levamisole (LEV) at 7.5 mg kg-1 or ivermectin (IVM) at 0.2 mg kg-1, or was left as untreated control. At slaughter, 7 days later, all the anthelmintics reduced worm burdens in animals infected with the susceptible strain (ABZ 98.9%, LEV and IVM 100%). By contrast, in the lambs infected with the ivermectin-resistant strain, LEV was 99.8% effective, but ABZ reduced worm counts by only 14.7% and IVM by only 10.4%. Interestingly at necropsy on Day 7 post-treatment, the egg counts in the resistant strain treated with ABZ had been reduced by 92.5%, although worm counts were reduced by only 14.7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

A comparison of two integrated approaches of controlling nematode parasites in small ruminants

Control of gastrointestinal nematodes (GIN) in small ruminants in regions of the world where anthelmintic resistance is prevalent must rely on more than just chemical deworming strategies. The objective of this experiment was to compare two integrated treatment protocols for control of GIN (primarily Haemonchus contortus in this region) using anthelmintics, copper oxide wire particles (COWP) and FAMACHA(?), compared to traditional anthelmintic use only. Three separate trials were conducted on mature ewes, weaned goats, and weaned lambs in which three deworming management strategies were applied: 1) all animals were dewormed with levamisole at four week intervals (LEV), 2) individual animals were dewormed with moxidectin when scored≥4 (ewes) or ≥3 (kids and lambs) using FAMACHA(?) (FAM/MOX), 3) all animals were dewormed with moxidectin initially and again with COWP (2g) when group mean FEC exceeded 500 (ewes), 3000 (kids), or 1000 (lambs) eggs/g (MOX/COWP). In this final group, during periods between group treatments, individual animals were dewormed with albendazole and levamisole according to FAMACHA(?) score. Fecal egg counts (FEC) and blood packed cell volume (PCV) were determined every 7 days and body weight every 28 days for 30, 20, or 16 weeks in ewes, goats, and lambs, respectively. Efficacy of levamisole was 83.4-86.4%, efficacy of moxidectin was 93.5-100%, and efficacy of COWP was 10.8-98.1% among the three trials. The mean number of deworming treatments per animal that occurred for the LEV, FAM/MOX, and MOX/COWP groups, respectively, was 7.9, 0.6, and 2.5±0.4 (P<0.001) for ewes, 5.2, 1.6, and 3.4±0.3 (P<0.001) for goats, and 4.0, 1.7, and 3.6±0.2 (P<0.001) for lambs. Production (body weight of lambs weaned from ewes or final body weight of kids and lambs) was similar among management strategy groups for ewes and kids, but FAM/MOX lambs were lighter by the end of the trial (P<0.003). While more time and labor was required to use the FAMACHA(?) system, a more conservative use of anthelmintics occurred in the FAM/MOX group.     

Evidence that moxidectin is a greater risk factor than ivermectin in the development of resistance to macrocyclic lactones by Ostertagia spp in sheep in south eastern Australia

AIM: To determine associations between resistance of Ostertagia (=Teladorsagia) spp to macrocyclic lactone (ML) anthelmintics and history of use of anthelmintics, by type, on commercial sheep farms in temperate regions of southern South Australia and Victoria, Australia. METHODS: Faecal egg count reduction tests (FECRTs) were conducted during a 2.5-year period (from August 2001 to January 2004) and records of the type of anthelmintic used in the 5 years preceding the FECRTs were collected from commercial sheep farms (n=103) in southern South Australia and Victoria, and data analysed retrospectively. ML resistance was defined as <95% reduction of Ostertagia spp 10-14 days after treatment with ivermectin (IVM), orally, at half the manufacturer's recommended dose rate. Use of anthelmintics in the preceding 5 and 10 years on each property was classified according to the nett number of years each of the following classes of drug had been used: IVM oral liquid (IVO), IVM controlled-release capsules (CRCs), abamectin (ABA), moxidectin (MOX) or a non-ML anthelmintic. The prevalence of ML resistance, by property, was analysed for associations with prior use of anthelmintics. RESULTS: Resistance by Ostertagia spp to ML anthelmintics was evident on 51/103 (49.5%) properties. The prevalence of resistance was lowest (23%) on properties on which MOX had not been used, and was significantly higher (64-77%) on properties on which MOX had been used for > or =2 of the preceding 5 years (p<0.001). In contrast, the prevalence of resistance was highest (70-74%) on the properties on which IVM, or IVM and/ or ABA, had not been used in the previous 5 years (on which the use of MOX was predominant), and was markedly lower (20- 42%) on properties that had used IVM or IVM and/or ABA for at least one of the preceding 5 years. Prevalence of resistance was higher for properties on which the only ML anthelmintic used was MOX (19/29=66%) than for those on which the only ML used was IVO (2/19=11%; p<0.001). Properties on which the only ML used was MOX were 2.72 times more likely to have resistance than properties on which the only ML used was IVO (95% confidence interval (CI) = 1.01-5.08). CONCLUSION: Use of MOX for > or =2 of the preceding 5 years was associated with a higher prevalence of resistance to ML by Ostertagia spp on sheep farms in south eastern Australia than the use of IVO.     

Evidence that moxidectin is a greater risk factor than ivermectin in the development of resistance to macrocyclic lactones by Ostertagia spp in sheep in south eastern Australia

AIM: To determine associations between resistance of Ostertagia (= Teladorsagia) spp to macrocyclic lactone (ML) anthelmintics and history of use of anthelmintics, by type, on commercial sheep farms in temperate regions of southern South Australia and Victoria, Australia.

METHODS: Faecal egg count reduction tests (FECRTs) were conducted during a 2.5-year period (from August 2001 to January 2004) and records of the type of anthelmintic used in the 5 years preceding the FECRTs were collected from commercial sheep farms (n=103) in southern South Australia and Victoria, and data analysed retrospectively. ML resistance was defined as <95% reduction of Ostertagia spp 10–14 days after treatment with ivermectin (IVM), orally, at half the manufacturer's recommended dose rate. Use of anthelmintics in the preceding 5 and 10 years on each property was classified according to the nett number of years each of the following classes of drug had been used: IVM oral liquid (IVO), IVM controlled-release capsules (CRCs), abamectin (ABA), moxidectin (MOX) or a non-ML an- thelmintic. The prevalence of ML resistance, by property, was analysed for associations with prior use of anthelmintics.

RESULTS: Resistance by Ostertagia spp to ML anthelmintics was evident on 51/103 (49.5%) properties. The prevalence of resistance was lowest (23%) on properties on which MOX had not been used, and was significantly higher (64–77%) on properties on which MOX had been used for ≥2 of the preceding 5 years (p<0.001). In contrast, the prevalence of resistance was highest (70–74%) on the properties on which IVM, or IVM and/ or ABA, had not been used in the previous 5 years (on which the use of MOX was predominant), and was markedly lower (20– 42%) on properties that had used IVM or IVM and/or ABA for at least one of the preceding 5 years. Prevalence of resistance was higher for properties on which the only ML anthelmintic used was MOX (19/29=66%) than for those on which the only ML used was IVO (2/19=11%; p<0.001). Properties on which the only ML used was MOX were 2.72 times more likely to have resistance than properties on which the only ML used was IVO (95% confidence interval (CI) = 1.01–5.08).

CONCLUSION: Use of MOX for ≥2 of the preceding 5 years was associated with a higher prevalence of resistance to ML by Ostertagia spp on sheep farms in south eastern Australia than the use of IVO.     

Efficacy of albendazole, levamisole and fenbendazole against gastrointestinal nematodes of cattle, with emphasis on inhibited early fourth stage Ostertagia ostertagi larvae.

An experiment was conducted to compare the anthelmintic efficacy of albendazole (ABZ), levamisole (LEV) and fenbendazole (FBZ) against inhibited early fourth stage larvae (EL4) of Ostertagia ostertagi during April in Louisiana. Forty cross-bred beef heifers (average weight 165 kg) were acquired during winter and grazed on pastures contaminated with O. ostertagi and other nematodes until early April. The cattle were weighed and randomly allotted into four groups of ten animals on 6 April and treatments were administered on 7 April. Experimental groupings were: Group 1, non-treated controls; Group 2, ABZ by oral drench at 10 mg kg-1; Group 3, LEV by topical, pour-on administration to back midline at 10 mg kg-1; Group 4, FBZ by oral drench at 10 mg kg-1. Equal numbers of cattle from each group were slaughtered daily between 10 and 13 days after treatment. Mean numbers of O. ostertagi developmental stages present in untreated controls were: adults, 13,714; developing L4 (DL4), 6487; inhibited EL4, 21,719. The mean percentage of inhibited EL4 was 51.8. Smaller numbers of Haemonchus placei, Trichostrongylus axei and Cooperia spp. were recovered uniformly in control cattle. Percentage reduction values for the three compounds against O. ostertagi adults, DL4 and EL4, respectively, were: ABZ, 99.0, 95.3, 84.9; LEV, 1.0, 21.8, 32.1; FBZ, 99.2, 97.2, 97.5. Differences between ABZ and LEV EL4 counts were not significant, but in all other cases worm counts in ABZ and FBZ-treated cattle were significantly lower (P less than or equal to 0.05) than in LEV-treated and control cattle. Both ABZ and FBZ were 98-100% effective against Haemonchus adults and L4, T. axei adults, and Cooperia spp. adults and L4. LEV was 100% effective against Haemonchus adults and L4, 85.6% against T. axei, and 94.6% and 89.59% effective against Cooperia spp. adults and L4, respectively.     

Anthelmintic evaluation of a thiabendazole-resistant strain of Ostertagia circumcincta recovered from sheep in England

A total of 35 worm-free lambs were infected with a strain of Ostertagia circumcincta isolated earlier from sheep in Cheshire, England, and found to be resistant to thiabendazole (TBZ). When patency was established the sheep were divided into groups of six, and dosed orally with either TBZ (44 mg kg-1, 88 mg kg-1), fenbendazole (FBZ; 5 mg kg-1) or levamisole (7.5 mg kg-1) or not treated. Three of the remaining five animals were dosed with FBZ at 10 mg kg-1. Egg hatch tests, post-dosing faecal egg counts and post-mortem worm counts confirmed resistance to TBZ, and a degree of side-resistance to FBZ was also revealed. Only levamisole gave the clearance expected of modern anthelmintics.     

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.     

Resistance to macrocyclic lactone anthelmintics and associated risk factors on sheep farms in the lower North Island of New Zealand

AIM: To estimate the prevalence of resistance to macrocyclic lactone (ML) anthelmintics over a 3-year period on sheep farms in the Taihape area, and to determine associations between the presence of ML resistance and farm management practices. METHODS: All farmers with >1,000 lambing ewes served by one veterinary practice in the Taihape area of the central North Island of New Zealand were invited to take part in the study (n=157); respondents were selected on their willingness to participate. Resistance to ML was measured during 2004-2006, using a standard faecal egg count reduction test (FECRT) and a half dose of oral ivermectin (IVM; 0.1 mg/kg; n=84). Additional FECRTs were conducted separately on some farms, using full doses of IVM (n=47), levamisole (LEV; n=49), a benzimidazole (BZ; n=76), and a BZ/LEV combination (n=42). Resistance was defined as <95% faecal nematode egg count reduction (FECR) 7-10 days post-treatment. Larval cultures were performed on pooled faecal samples from all pre- and post-treatment groups for which any positive faecal nematode egg counts (FEC) were recorded. To ascertain whether particular management or drenching strategies were associated with the presence of resistance, a questionnaire comprising 50 questions was developed, and each farmer interviewed individually. RESULTS: Of all farmers invited, 84/157 (54%) participated in this study. Based on undifferentiated FEC, ML resistance to the half-dose IVM was evident on 46/84 (55%) participating farms. The majority of these cases (71%) involved Ostertagia (Teladorsagia) circumcincta. Resistance was also evident to full doses of IVM on 22/47 (47%), BZ on 41/76 (54%), LEV on 18/49 (37%), and BZ/LEV on 2/42 (5%) farms. Positive associations (p<0.05) were evident between the presence of ML resistance and management practices, such as: weaning over half of the lambs onto paddocks not grazed by lambing ewes since June; not always returning lambs to the same paddock after drenching; and the use of visual signs to assess 'worminess'. Measuring drench efficacy in January to March rather than later in the year, and presence of resistance to BZ or LEV were associated with a higher apparent prevalence of ML resistance (p<0.05). CONCLUSIONS: Anthelmintic resistance, and particularly ML resistance, was widespread on sheep farms in the Taihape area, and mostly involved O. circumcincta. The prevalence of resistance was lower on farms on which management practices, particularly those involving lambs, maintained refugia of unselected nematodes. Further investigation is required to develop control strategies which minimise selection for resistant worms, and how these may vary with climate.     

Effects of diet and Aspergillus oryzae extract or Saccharomyces cervisiae on growth and carcass characteristics of lambs and steers fed to meet requirements of natural markets

Two studies were conducted to determine the effects of diet and feed additive on growth and carcass characteristics of lambs and cattle destined for all natural markets. In Exp. 1, 48 Dorset × Hampshire lambs (initial BW 29.4 ± 0.1 kg) were used in a randomized complete block experiment to determine the effects of Aspergillus oryzae extract, Amaferm (AMF) supplementation (1 g/d) in an 85% concentrate diet on growth and carcass characteristics. Lambs were allotted to 12 pens (4 lambs per pen), and blocked by sex and BW. Lambs were fed until the average BW of each pen reached a target BW (55.4 kg for wethers and 50.0 kg for ewes), at which time the entire pen of lambs was slaughtered. Amaferm resulted in a greater (P=0.07) G:F. In Exp. 2, 168 crossbred steers (initial BW 300 ± 0.7 kg) were used in a trial with a 3 × 2 factorial arrangement of treatments to examine the effects of 0.5 g/d of Saccaromyces cervisiae boulardii CNCM 1079-Levucell SB (LEV), or 3 g/d of AMF with 2 corn sources, dry whole-shelled corn or high moisture corn, on growth and carcass characteristics. Neither LEV nor AMF improved (P>0.10) carcass characteristics compared with control or non-feed-supplemented steers. Addition of LEV to high-concentrate, corn-based diets did not improve (P>0.10) growth performance of feedlot steers. However, addition of AMF to a diet composed of dry whole-shelled corn resulted in an improvement (P<0.05) in G:F (0.208 vs. 0.194). Results indicate that at the amounts fed, AMF may improve G:F for lambs and steers fed dry corn-based finishing diets.     

A field evaluation of anthelmintics for control of cyathostomes of horses in Brazil

The anthelmintic efficacy of ivermectin (IVM), piperazine citrate (PPZ) and fenbendazole (FBZ) alone, and combinations of FBZ with varying dosages of PPZ, was evaluated for the control of strongyles of Mangalarga equids. In all cases of positive strongly egg counts per gram of faeces (EPG) before and after treatment, pure populations of cyathostome larvae with eight gut cells were consistently observed in faecal cultures. The faecal egg count reductions (FECR) were evaluated between Day 7 and Day 56 post-treatment. Significant differences (P less than or equal to 0.05) were found between Day 7 and Day 49 when comparing the mean EPG values of IVM with those of the other anthelmintics. PPZ alone and the combination of FBZ (7.5 mg kg-1) and PPZ (55 mg base kg-1) did not show significant differences during the trial; both groups exhibiting an FECR of greater than 90% between Day 7 and Day 30. Horses treated with the combinations of FBZ (7.5 mg kg-1) and PPZ at either 40 or 25 mg base kg-1, and with FBZ alone at either 7.5 or 15 mg kg-1, showed an FECR of less than 90% 2 weeks after treatment. The emergence of a degree of resistance of strongyles to FBZ and PPZ in a segment of the cyathostomes in this population is suggested.     

The efficacy of a combined oral formulation of derquantel-abamectin against anthelmintic resistant gastro-intestinal nematodes of sheep in the UK

The objective of the present studies was to evaluate the efficacy of a combined formulation (Startect(?) Dual Active Oral Solution for Sheep, Pfizer Animal Health) of derquantel (DQL) and abamectin (ABA) for the treatment of: (1) sheep experimentally infected with a moxidectin (MOX)-resistant isolate of Teladorsagia circumcincta, and (2) multi-drug resistant gastrointestinal nematode parasites under UK field conditions. In the first study, a total of 40 animals were allocated into 4 treatment groups, and were either left untreated or treated with DQL+ABA, MOX or ABA. Faecal samples were collected on days 1-5 and on day 7 after treatment to examine the reduction in faecal egg excretion and to evaluate the egg viability. On day 14 post treatment all animals were euthanised for abomasal worm counts. There was a 100% reduction in geometric mean worm counts for the DQL+ABA treated animals compared to the untreated control animals (P<0.0001), whereas the percentage reduction in worm counts for the MOX- (P>0.05) and ABA-treated (P=0.0004) animals was 12.4% and 71.8%, respectively. The data from the egg hatch assay (EHA) indicated that in the MOX-treated and the ABA-treated animals, the majority of the eggs hatched after treatment. In the field study, performed on four farms, animals were allocated into 6 groups of 11-15 animals each in order to conduct a faecal egg count reduction test (FECRT), based on arithmetic mean egg counts. One group of animals remained untreated, whereas the other animals were treated with DQL+ABA, MOX, fenbendazole (FBZ), levamisole (LV) or ivermectin (IVM). On each of the farms the reduction in egg excretion after treatment with FBZ, LV or IVM was below 95.0%, indicating anthelmintic resistance. The efficacy of DQL+ABA ranged from 99.1 to 100%, yielding significantly lower egg counts compared to the untreated control group (P≤0.003). For MOX the egg counts were significantly (P≤0.003) lower compared to the untreated group at each farm, with reductions varying from 98.2 to 100%. The post-treatment copro-cultures for larva identification indicated that T. circumcincta was the most abundant worm species after treatment (52-99% of the larvae). The results of these studies confirm the high efficacy of the DQL+ABA combination formulation against anthelmintic resistant nematodes in the UK.     

Evaluation of the comparative efficacy of a moxidectin plus triclabendazole pour-on solution against adult and immature liver fluke, Fasciola hepatica, in cattle

The objective of this study was to evaluate the efficacy of a pour-on solution containing moxidectin plus triclabendazole (MOX plus TCBZ) against immature and adult stages of the liver fluke in cattle and compare the efficacy with other commercially available preparations. To this end, 104 male Holstein-Friesian calves aged between 3 and 4 months, were randomly allocated to 13 groups of eight animals each, and infected with approximately 500 Fasciola hepatica metacercariae. One group remained untreated, four groups were treated with MOX plus TCBZ at a dose rate of 0.1mL/kg, four other groups were treated with ivermectin (IVM) plus clorsulon injectable at a dose rate of 0.02mL/kg, and the remaining four groups were treated with IVM plus closantel pour-on at a dose rate of 0.1mL/kg. Each treatment was applied to one of the groups at 4 weeks, 6 weeks, 8 weeks and 12 weeks after the experimental infection. At necropsy (99-102 days after infection), all untreated animals were infected with a minimum of 30 flukes. The MOX plus TCBZ treated animals had significantly (P<0.0001) lower fluke counts compared to the untreated control animals at all time points after treatment. Efficacy against 8-week old and adult flukes was >99.5%. For 6-week old immature fluke, the efficacy was 98.0% and for 4-week old immature fluke the efficacy was 90.9%. The IVM plus closantel pour-on treated animals had significantly lower fluke counts compared to the untreated control animals for adult and 8-week old flukes (P<0.0001), and for 6-week old flukes (P=0.002). The efficacy was 26.8%, 68.2%, 90.6% and 99.3% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. The IVM plus clorsulon treated animals had significantly lower fluke counts compared to the untreated control animals for adult (P<0.0001) and 8-week old (P<0.05) flukes. The efficacy was 29.7%, 43.4%, 53.2% and 99.2% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. For treatments at 4, 6 and 8 weeks after infection, the fluke counts were significantly (P<0.0001) lower for the MOX plus TCBZ treatment than for IVM plus closantel or IVM plus clorsulon. The results confirm the high efficacy (>90%) of the MOX plus TCBZ pour-on combination against 4-week old to adult liver fluke in cattle. The IVM plus closantel pour-on combination was effective (>90%) against 8-week old and adult flukes, but had low efficacy against 4- and 6-week old fluke. The IVM plus clorsulon injectable combination was effective (>90%) against adult fluke only.     

Small strongyle infection: consequences of larvicidal treatment of horses with fenbendazole and moxidectin

The study was undertaken to evaluate adverse effects of larvicidal treatment in horses naturally infected with cyathostomins. Out of 24 ponies kept on pasture, four animals were housed in September and anthelmintically cured to serve as worm-free controls (group C-0). The others were housed in December. Eight animals each were treated 8 weeks later with 5 x 7.5mg/kg fenbendazole (FBZ) or 1 x 0.4 mg/kg moxidectin (MOX). Four animals remained untreated (group C-i). Two, 4, 6 and 14 days after the end of treatment two animals of each of the treated groups were necropsied together with group C-0 and C-i animals. Infected animals before treatment showed weight loss, eosinophilia, increased plasma protein and globulin contents. Treatment was followed by weight gain and temporal plasma protein and globulin increase. Proportions of CD4+ and CD8+ T lymphocytes in the peripheral blood did not differ between the groups before treatment but dropped significantly temporally after FBZ treatment. Group C-0 was worm-free at necropsy. Group C-i animals contained variable numbers of luminal and tissue cyathostomins. Histological sections showed larval stages in the lamina propria und submucosa surrounded by macrophages. Either treatment was effective against luminal parasites and reduced the number of larvae in the bowel wall beginning 4-6 days after FBZ and 6-14 days after MOX treatment. Histologically, as a first reaction after FBZ application T lymphocytes accumulated around morphologically intact L4 in the submucosa. Subsequently T lymphocytes associated with eosinophils infiltrated the submucosa. Parasites became enclosed by granulomas with eosinophils adhering to and invading the larvae which started to disintegrate on day 4. Later on, particularly on day 14 inflammation extended into the mucosa and was frequently associated with ulcerations. Third stage larvae in general and L4 in the lamina propria, however, seemed not to be affected until day 14 and even then, parasites did usually not generate extensive inflammation. After MOX treatment severe morphologically detectable alterations of tissue larvae could not be observed earlier than day 14. Different from FBZ treatment, larvae disintegrated and were obviously resorbed without causing severe inflammation in the gut wall. In conclusion treatment with either drug was efficacious against tissue larvae of cyathostomins but there may be different clinical consequences: in contrast to MOX effects, killing of larvae due to FBZ was associated with severe tissue damage, which clinically may correspond to reactions caused by synchronous mass emergence of fourth stage larvae, i.e., may mimic larval cyathostominosis.     

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.     

Pharmacokinetics of moxidectin and ivermectin following intravenous injection in pigs with different body compositions

Macrocyclic lactones (ML) are highly effective anthelmintics that provide a long protective period after administration because of their extensive distribution into fat. This study examined whether the body composition of the animal at the time of treatment had any influence on the pharmacokinetics of two MLs, moxidectin (MOX) and ivermectin (IVM). 'Fat' and 'lean' lines of pigs were established using two different diets, with weekly determination of liveweight and backfat thickness confirming the difference in body condition between the groups. Blood samples were taken at regular intervals following i.v. injection of IVM or MOX at a dose of 300 microg/kg and the plasma was analysed using fluorescence high performance liquid chromatography (HPLC) to determine the concentration of IVM or MOX in the samples. Regardless of body composition IVM and MOX kinetics were very different with MOX having a greater apparent volume of distribution, longer distribution and elimination half-lives and a slower clearance rate than IVM, which led to MOX being detectable in plasma for >40 days compared with only 8-10 days for IVM. Altering body composition had no detectable influence on the kinetic disposition of IVM in this study. In contrast, although there was no difference in AUC or the volume of distribution, MOX was distributed within and eliminated from the lean animals more rapidly than from the fat animals.     

Individual intake and antiparasitic efficacy of free choice mineral containing fenbendazole for grazing steers

A 95-day study (June 25-September 27, 2001) was conducted using 120 steers (311.9+/-2.4 kg) randomly allocated to two treatments: (1) mineral containing 0.55% fenbendazole (FBZ) and (2) control, no FBZ in the mineral. Animals in the FBZ group were individually identified by an electronic tag that was read each time an animal attended the mineral feeder. The feeder was equipped with load cells that enabled individual mineral intakes to be estimated. The FBZ group was provided with non-medicated mineral during a 14-day adaptation period (July 23-August 5) and an 8-day post-medication period (September 17-24). The intake of FBZ was monitored for 14 days during each of the two treatment periods; August 6-19 and September 3-16, separated by a 14-day non-medicated period, August 20-September 2. Control animals had access to non-medicated mineral for the entire 95-day study period. All steers were grazed on alfalfa-grass pasture for the duration of the study and had free access to flocculated, filtered and chlorinated water via an automatic waterer. Fecal samples were collected from steers three times during the experiment July 23, August 27 and September 27, and analyzed for nematode eggs and Giardia sp. cysts. Seventy-five and 83% of the steers in the FBZ group visited the mineral feeder during the first and second treatment periods, respectively. Individual daily mineral and FBZ intake for the first and second treatment periods was 52.9+/-6.6g per day and 10.1+/-1.2mg/kg BW; 72.3+/-8.4 g per day and 11.8+/-1.4 mg/kg BW, respectively. FBZ animals were separated into three groups during each treatment period based on the recommended dose (RD) of FBZ (5 mg/kg/BW), those that received > the RD, those that received < RD but > 50% RD and those that received < 50% of RD. Nematode egg counts and the number of animals infected with nematodes was reduced (p < 0.05) in all cattle that consumed FBZ as compared to control animals. In contrast to nematode eggs, numbers of Giardia cysts was not reduced (p > 0.05) by FBZ as compared to controls in either treatment period. These results may be a reflection of Giardia re-infection occurring following treatment and highlight the need for variation in treatment regimes specifically targeted at the parasite of interest.