Efficacy of a combined oral formulation of derquantel-abamectin against the adult and larval stages of nematodes in sheep, including anthelmintic-resistant strains

Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(?)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal and respiratory nematode parasites of sheep, as follows: ≥ 98.9% efficacy against Haemonchus contortus (adult and L4); Teladorsagia circumcincta (adult, L4 and hypobiotic L4); Teladorsagia trifurcata (L4); Trichostrongylus axei (adult and L4); Trichostrongylus colubriformis (adult and L4); Trichostrongylus falculatus (adult); Trichostrongylus rugatus (adult); Trichostrongylus vitrinus (adult and L4); Cooperia curticei (adult and L4); Cooperia oncophora (adult and L4); Nematodirus spathiger (adult); Nematodirus battus (adult); Nematodirus spp. (hypobiotic L4); Strongyloides papillosus (adult); Strongyloides spp. (L4); Chabertia ovina (adult); Oesophagostomum venulosum (adult); Dictyocaulus filaria (adult); and Protostrongylus rufescens (adult); ≥ 97.0% efficacy against Trichuris ovis (adult); and ≥ 95.9% efficacy against T. trifurcata (adult). Derquantel-abamectin is a highly effective combination anthelmintic, which will provide an important new tool for controlling helminths of sheep when used in conjunction with sustainable drenching practices.     

The anthelmintic efficacy of netobimin against naturally acquired gastrointestinal nematodes in sheep

The broad-spectrum anthelmintic efficacy of netobimin (SCH 32481, Schering Corporation) was evaluated using 30 cross-bred spring lambs with naturally acquired infections of gastrointestinal nematodes. Three groups of 10 animals each were allotted into either control (given a tap water drench as a placebo) or 7.5 and 20 mg kg-1 dosage groups (given the netobimin as an oral drench). Seven to fourteen days post-treatment, animals were necropsied and nematodes recovered by standard techniques. Examination of fecal samples taken on dates of necropsy showed median egg production was reduced in treated animals (61.98% with 7.5 mg kg-1 and 100% with 20 mg kg-1). The compound was highly effective in removal of adult nematodes representing a number of genera and species of trichostrongyloids at the 7.5 and 20 mg kg-1 dose levels (shown, respectively, below). These included Ostertagia spp., with O. circumcincta, O. trifurcata, O. ostertagi and Teladorsagia davtiani (96.20%; 100%), Trichostrongylus spp., with T. axei, T. vitrinus and T. colubriformis (100%; 98.72%), Nematodirus spp., with N. spathiger, N. filicollis and N. battus (100% both levels) and Haemonchus contortus (100% both levels). High efficacies against other species of nematodes (at both dose levels) were not statistically significant (Cooperia spp., Chabertia ovina and Oesophagostomum venulosum). At 20 mg kg-1, netobimin significantly reduced populations of early and late fourth stage larvae of Ostertagia spp. by 100%. The overall efficacy (all life stages included) was 90.16% at 7.5 mg kg-1 and 98.77% at 20 mg kg-1 dose levels. No adverse reactions or signs of toxicosis were observed.     

Prevalence of anthelmintic resistant nematodes in sheep in south-east England

The prevalence of anthelmintic resistant nematodes among 52 commercial flocks in south-east England was investigated by comparing the faecal egg counts of groups of lambs before, and seven days after, treatment with thiabendazole and levamisole. Evidence of thiabendazole resistance was found on seven farms. in each case Haemonchus contortus was the only species of nematode involved. In vitro egg hatch assays carried out for isolates from these farms gave ED50 estimates of 0.065 to 0.332 micrograms thiabendazole/ml compared with estimates of 0.027 to 0.031 micrograms thiabendazole/ml for a known susceptible strain of H contortus assayed at the same time. In a series of slaughter trials, there was a 17 to 85 per cent reduction, as compared with controls, in the mean worm burdens of groups of lambs infected with these isolates and killed seven days after treatment with thiabendazole, confirming their resistance to this anthelmintic.     

An ivermectin tablet for sheep: Efficacy against gastro-intestinal nematodes and a bioavailability comparison with a liquid ivermectin formulation

An ivermectin tablet for o ral administration to sheep was developed for use in countries where it is customary to treat sheep with anthelmintic tablets. Tablets require no special administration equipment, and offer convenience for storage and transport. The ivermectin tablet, which delivers 10 mg of ivermectin (200 μg kg⁻¹ in a 50 kg sheep), had similar bioavailability to a liquid formulation of ivermectin (IVOMEC^® Liquid for Sheep) as determined by peak plasma ivermectin concentrations and area under the concentration curve in plasma (P>0.10). In dose confirmation trials in which nematode infections were induced in helminth-naive sheep, animals treated with the ivermectin tablet had significantly fewer adult and fourth-stage larval nematodes than untreated control sheep P<0.01 with efficacies >99% against all nematode species tested. In six field trials evaluating the efficacy of the ivermectin tablet in 240 Merino sheep, the reductions in faecal nematode egg counts ranged between 98 and 100%, as determined by comparison of pre- and post-treatment counts for the ivermectin-treated group.     

Comparative anthelmintic tests in sheep and goats infected with gastro-intestinal nematodes and lungworms in Iran

Summary In three controlled experiments the efficiency of thiabendazole, tetramisole, diethylcarbamazine citrate, emetine hydrochloride and iodine was tested against gastro-intestinal nematodes and lungworms in naturally infected sheep and goats in Iran. An oral dose of either 10 or 15 mg/kg bodyweight of tetramisole, and 100 mg/kg (twice the normally recommended dose) of thiabendazole gave excellent results against all stages of nematodes of the alimentary tract, andDictyocaulus filaria and Protostrongylus spp. in the lungs. Thiabendazole was also shown to have some effect againstMuellerius spp. Diethylcarbamazine citrate, given in three daily doses of 20 mg/kg, gave good results againstDictyocaulus filaria andProtostrongylus spp., respectively. Emetine was toxic at 3 mg/kg but appeared safe and effective againstP. rufescens at one mg/kg. Efficiency againstMuellerius at this dose was 68 per cent. Iodine gave no noticeable effect againstMuellerius spp. andProtostrongylus spp. The use of these anthelmintics for the control of mixed infections of gastrointestinal nematodes and lungworms in sheep and goats is discussed.

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Sumario En tres experimentos controlados se probóla eficiencia del thiabendazole, tetramizole, citrato de dietil carbamazine, clorhidrato de emetina y iodo contra nemátodes gastro-intestinales y parásitos pulmonares en ovinos y caprinos de Irán, naturalmente infectados. Una dosis oral de 10 ó 15 mg/kg de peso corporal, de tetramizole y 100 mg/kg (El doble de la dosis normalmente recomendada) de thiabendazole dió resultados excelentes contra todos los estadíos de nemátodes del tracto digestivo, yDictyocaulus filaria yProtostrongylus spp. de los pulmones. El thiabendazole también tuvo un peque?o efecto contraMuellerius spp. El citrato de dietil carbamazine administrado en tres dosis diarias de 20 mg/kg, dió buenos resultados contraDictyocaulus filaria yProtostrongylus spp., respectivamente. La emetina fué tóxica dada en 3 mg/kg, pero pareció segura y efectiva contraP. rufescens cuando fué administrada a razón de 1 mg/kg. La eficiencia contra elMeullerius en esta concentración fué del 68 per cent. Ei iodo no dió ningun efecto notable, contraMuellerius spp. yProtostrongylus spp. Se discute el uso de estos anti-helm?nticos para el control de infecciones mixtas de nemátodes gastro-intestinales y pulmonares.

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Résumé Dans trois essais contr?lés, l'efficacité du thiabendazole, du tétramisole, du citrate de diéthylcarbamazine, du chlorhydrate d'émétine et de l'iodine fut éprouvée sur des nématodes gastro-intestinaux et pulmonaires chez des chèvres et des moutons naturellement infestés en Iran. Une dose orale de 10 ou 15 mg/kg vif de tétramisole et de 100 mg/kg (deux fois la dose recommandée) de thiabendazole donna d'excellents résultats sur tous les stades des nématodes du tractus digestif et surDictyocaulus filaria etProtostrongylus spp. dans les poumons. Le thibendazole aussi se révèle efficace dans une certaine mesure contreMuellerius spp. Le citrate de diéthylcarbamazine, donné trois jours de suite à 20 mg/kg donna de bons résultats contreD. filaria etProtostrongylus spp. L'émétine était toxique à 3 mg/kg, mais apparut inoffensive et efficace contreP. rufescens à la dose de 1 mg/kg. A cette dose, son efficacité contreMuellerius était de 68 p. 100. L'iodine ne fournit aucun résultat appréciable contreMuellerius spp. etProtostrongylus spp. L'emploi de ces anthelminthiques pour la prophylaxie de ces infestations mixtes des moutons et des chèvres est discuté.

     

The anthelmintic efficacy of fenbendazole against a mixed nematode infection in sheep.

Fenbendazole (methyl-5-(phenylthio)-2-benzimidazole carbamate) at dose rates of 5 mg/kg and above was 100 per cent effective in eliminating a naturally acquired Dictyocaulus filaria infection in sheep. The drug was 100 per cent effective in eliminating concurrent infections of adult Trichostrongylus axei, Haemonchus contortus, Haemonchus placei, Ostertagia circumcincta, Ostertagia ostertagii, Cooperia oncophora, Cooperia mcmasterii, Nematodirus spathiger, Neumatodirus filcollis, Oesophagostomum venulosum and Chabertia ovina. Fenbendazole was 93 per cent and 97 per cent effective at doses of 5 and 10 mg/kg respectively in removing infection with adult T colubriformis, and post-treatment worm-egg production was completely suppressed in surviving female worms. No adverse side-effects were observed in treated sheep at either of the two dose rates used.     

Efficacy of a topical formulation of ivermectin against naturally acquired gastro-intestinal nematodes in weaner cattle

The efficacy of a topical formulation of ivermectin against naturally acquired gastro-intestinal nematodes in weaner cattle was evaluated. At slaughter, 14-15 days after treatment, burdens of Ostertagia spp, Trichostrongylus axei and Oesophagostomum radiatum were significantly lower in the treated calves than in the untreated controls (p<0.01). Efficacies (based on geometric mean worm burdens of treated and control groups) were 99.6%, 95.1% and 100% respectively. The sizes of the Cooperia spp and Trichuris ovis burdens in the treated group did not differ significantly at the 5% level of confidence from those in the control group.     

Slowing the spread of anthelmintic resistant nematodes of sheep and goats in the United Kingdom.

Anthelmintic resistant nematodes pose an increasing threat to animal welfare and lamb production on lowland sheep farms in the United Kingdom. Based on published information on anthelmintic resistance in nematodes and insecticide resistance in arthropods, seven recommendations are made for reducing the development and spread of anthelmintic resistant nematodes. The two most important are probably to prevent the introduction of resistant worms through the purchase of stock and to reduce the reliance on frequent anthelmintic treatments by using epidemiological principles of nematode control.     

The efficacy of mixtures of albendazole sulphoxide and levamisole against sheep nematodes resistant to benzimidazole and levamisole

Faecal egg count reduction tests and an anthelmintic efficiency assay were used to assess the efficacy of combinations of albendazole sulphoxide and levamisole against populations of Ostertagia and Trichostrongylus sp. which contained different proportions of worms resistant to both benzimidazole and levamisole anthelmintics. Compared to the effects of either drug alone, significantly greater efficacy was obtained using combinations which included dose rates similar to those recommended for the separate components. At these dose rates, the mixtures reduced mean faecal egg counts by 95% or more, and caused a reduction of 68% in adult Ostertagia sp. and more than 95% for 4th stage Ostertagia and T colubriformis. The increased efficacy of the mixtures could be accounted for by actions of the drugs acting independently.     

The anthelmintic efficacy of netobimin against experimental infections of Fasciola hepatica in sheep

Netobimin (coded SCH 32481, Schering Corporation), a new broad-spectrum anthelmintic having both fasciolicidal and nematocidal properties was evaluated for efficacy against mature Fasciola hepatica infections in sheep. The trial was conducted with 30 cross-bred spring lambs, each experimentally infected with 250 F. hepatica metacercariae. A single treatment of netobimin was administered at 17 weeks post-infection (PI) by oral drench at 7.5 or 20 mg kg-1 body weight while 10 animals remained as untreated controls. At necropsy (either 1 or 2 weeks post-treatment), the mean number of adult flukes recovered from the control, 7.5 and 20 mg kg-1 groups were 94.7, 35.9 and 8.8, respectively. The resulting efficacies were 62% (P less than or equal to 0.05) and 90.7% (P less than or equal to 0.01), respectively. No clinical signs of fascioliasis were noted in any sheep during the trial. No signs of toxicosis nor any adverse reactions to the drug were observed.     

Efficacy of a moxidectin/triclabendazole oral formulation against mixed infections of Fasciola hepatica and gastrointestinal nematodes in sheep

We have evaluated the efficacy in sheep of a combination drench formulation at the recommended dose rate of 0.2 mg moxidectin/kg bodyweight and 10 mg triclabendazole/kg bodyweight against an experimental infection with Fasciola hepatica and a natural infection with gastrointestinal nematodes. We confirmed that the efficacy of reducing fecal egg output was 98.3% for trichostrongyle eggs and 100% for F. hepatica eggs. Based on adult worm and fluke recovery, the efficacy varied according to the target species. A reduction was found in the number of Teladorsagia circumcincta, Trichostrongylus spp., Nematodirus spp., and Trichuris spp. greater than 95%, but the efficacy for Oesophagostomum spp. varied, with values below 90%. The reduction in F. hepatica was higher than 95% for all stages. The effectiveness of the formulation was also confirmed by an increase in total proteins and albumin following treatment.     

Use of pathophysiological indicators for individual decision of anthelmintic treatment of ewes against gastro-intestinal nematodes in Morocco

The targeted selective treatments (TST) aim at reducing the number of anthelmintic treatments but also to maintain productivity of animals. The aim of this work was to assess the validity of pathophysiological indicators for detecting individually ewes in need for treatments in two regions of Morocco with different management and climatic environment (Chaouia plain-seven farms, and Middle-Atlas-three farms). Although resistance to benzimidazoles was already present the same drug was used for TST. The indicators tested were: FAMACHA(?) (associated with anaemia), DISCO (diarrhoea score), and BODCON (body condition score). Only FAMACHA(?) and DISCO indicators were well correlated to the EPGs. DISCO only did permit a substantial reduction (up to 85%) of the number of treatment and EPG (nematode eggs per gramme) remained low on average (less than 160).     

The anthelmintic efficacy of albendazole against Fasciola hepatica and benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of albendazole (methyl [5-(propylthio) - 1H - benzimidazole -2 -yl] carbamate) against immature and adult Fasciola hepatica and against standardised strains of benzimidazole resistant Haemonchus contortus and Trichostrongylus colubriformis was evaluated in experimentally infected sheep. A single intrarumenal treatment of dose rates of 3.8 and 7.6 mg/kg was ineffective against immature (six weeks old) F hepatica. Dose rates of 5.7 and 7.6 mg/kg reduced the number of mature (12 weeks old) F hepatica by 70 and 91 per cent respectively. Dose rates of 5.7 and 7.6 mg/kg removed 92 and 99 per cent of four-week-old, benzimidazole resistant H contortus and 89 and 99 per cent of four-week-old, benzimidazole resistant T colubriformis.     

The anthelmintic efficacy of thiabendazole and levamisole against inhibited Haemonchus contortus larvae in sheep

Fifty-five dogs, 6 to 18 months old, from 11 areas of New Zealand were examined for gastro-intestinal helminths. Thirty-eight (69.1%) were infected. Twenty-one (38.2%) had Toxocara canis, 20 (36.4%) Trichuris vulpis, 20 (36.4%) Uncinaria stenocephala, 3 (5.5%) Toxuscaris leonina, 3 (5.5%) Dipylidium caninum and 1 (1.8%) Taenia sp. Helminth infections were less frequent and populations were smaller in females than in males.