Resistance to a triple combination of broad-spectrum anthelmintics in naturally-acquired Ostertagia circumcincta infections in sheep

AIM: To measure the efficacy of two macrocyclic lactone-levamisole-benzimidazole combination drenches against naturally-acquired abomasal nematode infections on a sheep farm in the North Island, New Zealand. METHODS: Eighteen lambs carrying naturally-acquired worm burdens were removed from pasture and randomly allocated to one of three equal-sized groups, consisting of an untreated control group and two treatment groups. One treatment group was given a single oral dose of a triple-combination anthelmintic administered at the manufacturer's recommended dose rate of 0.2 mg/kg ivermectin, 7.5 mg/kg levamisole and 5.0 mg/kg albendazole. The other treatment group received a similar dose of another triple-combination drench consisting of 0.2 mg/kg abamectin, 8.0 mg/kg levamisole and 4.5 mg/kg oxfendazole. Worm counts were carried out post mortem on the abomasa of all animals in all groups, 10 days after treatment. RESULTS: While the abamectin-levamisole-oxfendazole combination was highly effective against all three abomasal nematode species present, the ivermectin-levamisole-albendazole combination was not. In the latter instance, a reduction of only 78% was achieved against infections of Ostertagia (=Teladorsagia) circumcincta. CONCLUSIONS: These results provide evidence of resistance to an ivermectin-levamisole-albendazole combination drench by O. circumcincta. CLINICAL RELEVANCE: Besides representing the first confirmed report of resistance to a combination drench consisting of three broad-spectrum anthelmintics, the present results provide further evidence of the continuing escalation of multiple anthelmintic resistance in sheep nematodes in New Zealand.     

Efficacy of albendazole for prevention of fascioliasis in sheep

Daily doses of albendazole administered as a premix in the feed for 35 days were effective in preventing Fasciola hepatica infections in 17 sheep in three groups: 5 mg/kg/day (6 sheep) was 100% effective; 3 mg/kg/day (5 sheep) was 98% effective; and 1 mg/kg/day (6 sheep) was 42% effective. Infective cysts were given daily for 5 days during the first week of treatment, treatment was continued an additional 28 days, and sheep were necropsied 14 weeks after final cyst inoculation. There were no visible lesions in any livers of sheep given albendazole at the rate of 5 mg/kg/day or in three of five livers of sheep dosed at the rate of 3 mg/kg/day. Sheep treated with albendazole had a mean weight gain of 2.7 kg, 4.0 kg, and 4.0 kg greater than the controls for the dosages of 1, 3, and 5 mg/kg/day, respectively. Determination of bile duct damage by measurement of serum gamma-glutamyl transpeptidase activity at 9 weeks after final cyst inoculation revealed increases of 3.0X, 1.0X, and 1.1X for the dosages of 1, 3, and 5 mg/kg/day, respectively, and 2.3X for the control, as compared with 7 weeks after final cyst inoculation.     

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.     

Efficacy of an albendazole feed formulation against bovine gastrointestinal nematodes including arrested larvae of Ostertagia ostertagi

The efficacy of an albendazole feed premix formulation was compared with that of an albendazole drench suspension for control of gastrointestinal nematodes in 31 beef cattle. The premix (11 cattle) and drench suspension (9 cattle) were found to have similar efficacies at a dosage of 7.5 mg/kg of body weight. When compared with controls (11 cattle), both formulations caused significant (P less than 0.05) reductions in worm counts with an efficacy of 98% or greater against adult Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia punctata, and C pectinata. There was no significant effect against arrested 4th-stage larvae of O ostertagi. Adverse effects of albendazole treatment were not observed, and the premix formulation was readily consumed by cattle.     

EFFECTIVENESS OF ANTHELMINTIC TREATMENTS AGAINST LEVAMISOLE-RESISTANT OSTERTAGIA

Adult worms from a population of Ostertagia consisting of 88% O. circumcincta and 12% O. trifurcata were found to survive a double drench (14 mg/kg) of levamisole. An anthelmintic assay on this population found that against levamisole the LD50 was 11.95 mg/kg and the LD99 was 67.75 mg/kg. Three benzimidazoles were also tested against this population and the LD50 and LD99 were respectively thiabendazole 11.8 and 144.9 mg/kg, oxfendazole 0.17 and 6.10 mg/kg and albendazole 0.08 and 2.55 mg/kg. The percentage of worms killed by the recommended dose rate was levamisole 24%; thiabendazole 91%; oxfendazole 99% and albendazole 99%.     

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.     

Efficacy of moxidectin 1% injectable and 0.2% oral drench against natural infection by Dictyocaulus filaria in sheep

Two separate trials (I and II) with 34 and 32 Churra ewes, respectively, and distributed into two groups, have been carried out to evaluate the efficacy of two different formulations of moxidectin at a dose rate of 0.2mg/kg body weight (b.w.) against natural infection by Dictyocaulus filaria in sheep. Trial I was designed to evaluate a 1% moxidectin injectable formulation, whereas in trial II a 0.2% moxidectin oral drench formulation was used. The efficacy was measured on the basis of the reduction of the faecal larval counts and of adult worm recoveries at slaughter.In each trial, a group of animals was treated on day 0 with moxidectin 1% injectable or moxidectin 0.2% oral drench and the other group acted as untreated control.When the faecal larval counts was compared within the treated groups, the efficacy was over 95% until day +13, and 100% at the remainder of the sampling dates after the application of injectable moxidectin, whereas in trial II, the larvae per gram (lpg) of faeces increased until the first sampling time post treatment (p.t.), day +6, and zero counts were recorded for all animals by the following days. On the basis of adult worm recoveries at necropsy, the efficacy of the treatment was 100% in both trials, however, adult worms were detected at slaughter for all control sheep. These results indicate that moxidectin 1% injectable and moxidectin 0.2% oral drench, administered at 0.2mg/kg b.w., were 100% effective against D. filaria infection in sheep. No adverse reactions to the treatments were observed in the animals.     

Use of praziquantel for the control of Moniezia expansa in lambs

The efficacy of a drench containing praziquantel in combination with levamisole was evaluated in four trials performed in the 1990-91 and 1992-93 seasons in the Waikato Region of New Zealand. The trials involved 93 naturally infected lambs and compared the efficacy of a 3.75 mg/kg praziquantel 7.5mg/kg levamisole drench against Moniezia expansa, with albendazole, an albendazole-levamisole combination and oxyclozanide-levamisole combination in controlled trials. There was no significant reduction in the number of Moniezia expansa scoleces or proglottids in the control, albendazole and albendazole-levamisole groups. Oxyclozanide gave a high clearance of proglottids, but a 28% reduction of scoleces. The praziquantel-levamisole combination demonstrated complete removal of segments in all trials, and of scoleces in two trials. One scolex was found in each of the two other trials. The combination was also tested for efficacy against nematode parasites. Total worm counts indicated that levamisole in the praziquantel-levamisole combination drench retained its efficacy. The economic benefits of the use of the praziquantel-levamisole drench were investigated. This trial compared the liveweight gains of three groups of 100 lambs treated twice 4 weeks apart with either levamisole or with the praziquantel-levamisole combination or acting as untreated control group. The group treated with the praziquantel-levamisole combination gained significantly more weight in both 4-week periods and overall, when compared with either the control or levamisole treated animals.     

Efficacy of thiophanate and albendazole against natural infections of Dicrocoelium dentriticum, Fasciola hepatica, and gastrointestinal nematodes and cestodes in sheep

The anthelmintic efficacy of thiophanate and albendazole was compared in sheep with heavy infestations of Dicrocoelium dentriticum. The effectiveness of each drug was determined by counting the numbers of D. dentriticum in animals killed 21 days after treatment. In one group, the dose of thiophanate recommended for use against gastrointestinal (GI) nematodes (50 mg kg-1 live weight) was found to be 74.4% effective against D. dentriticum. Two tablets (each containing 76 mg of active ingredient) of albendazole per 30 kg live weight were given to a second group and the dose repeated after 1 week. Under this regime, albendazole was found to be 12.7% effective against D. dentriticum. The effect of each drug on other parasites was as follows; thiophanate had no effect against Fasciola hepatica or cestodes, while albendazole was 71.5% effective against F. hepatica and 100% effective against cestodes. Both drugs were highly effective against GI nematodes.     

Activity of closantel against experimentally induced Fascioloides magna infection in sheep

The efficacy of closantel against experimentally induced Fascioloides magna infection in sheep was studied. In each of 3 experiments, closantel was administered 8 weeks after the sheep were given (oral inoculation) 100 metacercariae of F magna. In the 1st experiment, closantel was given orally to 5 groups of 6 sheep each at dosages of 0 (nontreated control), 5, 7.5, 10, and 15 mg/kg of body weight. In the 2nd and 3rd experiments, groups of 10 or 12 sheep were treated to confirm the efficacy of the previously determined optimal dosage of 15 mg/kg. An additional group of sheep (n = 10) was used in the 3rd experiment to evaluate the efficacy of closantel given IM at a dosage of 7.5 mg/kg. Closantel given orally at a dosage level of 15 mg/kg was highly effective (94.6% to 97.7%) in reducing F magna burdens. Also, pathologic scores associated with the F magna infection were reduced by 81.3% to 92.6% in sheep given this dosage of closantel. Efficacy of the IM administered dosage of 7.5 mg of drug/kg was equivalent to that of the 15 mg/kg oral dosage. Other than mild, transient lameness of the limbs which were injected with the drug (group 10), side effects were not observed.     

Efficacy of levamisole and netobimin against Haemonchus contortus in lambs in Louisiana

Efficacy of levamisole was evaluated in a suspected levamisole-resistant population of Haemonchus contortus in the Louisiana State University sheep flock. The efficacy of netobimin also was evaluated against this population of Haemonchus. In trial 1, 5 lambs naturally infected with H contortus were given 8 mg of levamisole/kg of body weight as a drench, and 5 lambs were not treated (controls). Nematode recovery after slaughter indicated 0% efficacy against H contortus. In trial 2, 30 nematode-free lambs were each given 8,300 F1 generation infective larvae of H contortus, which were derived from parent H contortus that survived 2 levamisole treatments in lambs being maintained in a nematode-free environment. Ten lambs were treated with 8 mg of levamisole/kg as a drench, 10 were treated with 20 mg of netobimin/kg as a drench, and 10 were not treated (control). Nematode recovery after slaughter revealed 62.3% and 99.8% efficacy for levamisole and netobimin, respectively, against H contortus.     

Doramectin and albendazole resistance in sheep in The Netherlands

A faecal egg count reduction test was conducted on a sheep farm with suspected avermectin resistance. Five groups of 10 sheep were formed. Group 1 was the untreated control group. Groups 2-5 were treated according to weight with the recommended dose of, respectively, levamisole, doramectin, moxidectin or albendazole. Resistance was found in the sheep treated with doramectin (15% efficacy) and albendazole (87% efficacy). Levamisole and moxidectin were 100 and 99% effective, respectively. Larval identification of the faecal cultures of the doramectin-treated sheep revealed 100% Haemonchus contortus larvae. After albendazole treatment, 77% of the cultured larvae were H. contortus and 23% Teladorsagia/Trichostrongylus. Because there is a lot of trade in sheep on the farm, it is probable that the resistant worms were introduced with livestock from other farms than being selected on the farm.     

Efficacy of closantel plus albendazole liquid suspension against natural infection of gastrointestinal parasites in camels.

Oral administration of closantel in a dose of 10 mg/kg plus albendazole in a dose of 5 mg/kg liquid suspension was studied in 75 camels naturally infected with various types of gastrointestinal parasites. The camels involved were 15 pregnant she-camels, 20 non-pregnant she-camels and 40 male camels of various ages. Each camel received a single oral dose of closantel (10 mg/kg) plus albendazole (5 mg/kg) orally. Two weeks later, 20 camels of this group were re-dosed again with the same dose of the anthelmintic. Fecal samples were collected per rectum from all camels at the time of treatment and again 14 and 42 days post treatment. Fecal egg counts and generic determination of third stage larvae was performed. Results indicated that six different species of gastrointestinal tract parasites were identified in camels. Single treatment of closantel plus albendazole mixture reduced egg counts in camels by 100%, 100%, 98% and 77% for Haemonchus longistipes, Ascaris spp., Monezia expansa and Fasciola hepatica, respectively. However, administration of the drug twice on the base of 2 weeks apart significantly raised the efficacy of the drug for clearance of the parasites from 92.5% to 100% in camels infected with various parasites. Camels were not adversely affected by treatment.     

Enhanced Plasma Availability of the Metabolites of Albendazole in Fasted Adult Sheep

Lifschitz, A., Virkel G., Mastromarino, M. and Lanusse C., 1997. Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep. Veterinary Research Communications, 21 (3), 201-211The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.     

Naphthalophos combinations with benzimidazoles or levamisole as effective anthelmintics for sheep

Objective: To investigate the relative efficacy and safety of the anthelmintic naphthalophos in sheep, either given alone or in combination with benzimidazole (fenbendazole and albendazole) or levamisole anthelmintics.
Design: A parasitological study using faecal egg count reduction tests, a validating slaughter trial and field safety trials.
Procedure: Faecal egg count reduction tests were carried out on 13 farms. Naphthalophos and combinations of naphthalophos with levamisole and fenbendazole were included in the drench tests. On one property a controlled efficacy study was carried out to validate faecal egg count reduction test findings. In this trial, sheep were slaughtered 10 days after treatment and the remaining parasites recovered from the gastro-intestinal tract. Safety trials were carried out on eight farms where approximately 50 000 sheep were treated with naphthalophos and albendazole that were tank mixed in the backpack.
Results: The efficacy of naphthalophos alone in faecal egg count reduction tests ranged from 59 to 98% with one test showing 95% reduction. The efficacy of naphthalophos and levamisole ranged from 74 to 100%, with 5 farms showing 95% reduction. The efficacy of naphthalophos and fenbendazole ranged between 88 and 100% with 95% reduction achieved on 10 farms. The controlled efficacy study showed a good correlation between the faecal egg count reduction tests and numbers of parasites recovered, except for Nematodirus where the faecal egg count reduction tests overestimated efficacy. The mortality rate in the safety trials was 0.05%, with most fatalities occurring on one farm.
Conclusion: The combination of naphthalophos and fenbendazole was more effective than a combination of naphthalophos and levamisole, and will provide a sufficiently safe drench rotation option.     

Comparative efficacy of albendazole against Fasciola hepatica in sheep and calves: Relationship to serum drug metabolites levels

Calves were given albendazole (ABZ) daily in feed at levels of 0,3 or 5 mg kg^?1 day^?1. None of the ABZ treatment levels was significantly effective in reducing Fasciola hepatica burdens. A dose rate of 5 mg kg^?1 day^?1 did significantly reduce the fecal egg count. Measurements of serum druf levels from calves following a single dose of ABZ showed ABZ levels to be low, but sulfoxide and sulfone metabolites of ABZ were present in (significant) larger quantities. The total available sulfoxide present in calves, however, was much lower than in sheep receiving the same dose of ABZ. Measurements of serum metabolite levels from sheep and calves which were given daily low-level doses of ABZ also indicated that the seum sulfoxide levels of calves were much lower than those of sheep receiving tha same ABZ dose. The results indicated that ABZ is not an effective prophylactic treatment for bovine fascioliasis and the differences in efficacy between sheep and cattle correlated with the differences in serum metabolites levels.     

Anthelmintics for the control of nematode infections in the brushtail possum (Trichosurus vulpecula)

AIMS: To determine the efficacy of eprinomectin, doramectin and a combination of albendazole and levamisole in suppressing or eliminating nematode infections or faecal egg counts (FEC) in possums naturally or experimentally infected with Parastrongyloides trichosuri, Paraustrostrongylus trichosuri and Trichostrongylus colubriformis. METHODS: To establish an effective dose of eprinomectin, groups of naturally infected possums were treated with 0, 0.5, 2.5, 5.0 or 7.5 mg/kg liveweight (LW) eprinomectin pour-on (n=6 possums/group) and changes in FEC and nematode worm counts at necropsy determined, 18 days later. Efficacy of the 7.5 mg/kg dose was re-examined in a second group of naturally infected possums (n=12) by monitoring FEC weekly for 28 days post-treatment. Persistence of the anthelmintic effect of doramectin injection was tested using nematode-free possums treated with 0, 0.2, 0.4, 0.6 or 0.8 mg/kg LW (n=3 possums/ group), which were experimentally infected 14 days later with T. colubriformis, Paraustrostrongylus trichosuri and Parastrongyloides trichosuri infective larvae. Response to treatment was assessed by FEC and nematode worm counts at necropsy, 42 days posttreatment. Efficacy of a 1.0 mg/kg dose of doramectin was subsequently examined using naturally infected possums (n=11) by monitoring FEC weekly for 28 days post-treatment. To determine the efficacy of a levamisole-albendazole combination drench, possums with naturally acquired nematode infections (n=6) were treated orally with 37.5 mg/kg LW levamisole plus 23.75 mg/kg LW albendazole on 2 occasions, 7 days apart, and response to treatment was assessed by monitoring FEC for 57 days. RESULTS: Eprinomectin 7.5 mg/kg LW reduced Paraustrostrongylus trichosuri worm counts by 98 % (p<0.05). Doramectin 0.6 mg/kg LW reduced Parastrongyloides trichosuri and Trichostrongylus spp worm counts by 99% (p<0.05) and 0.8 mg/kg LW reduced Paraustrostrongylus trichosuri by 100% (p<0.05), in possums challenged with larvae 14 days after treatment. Treating possums with a levamisole-albendazole combination orally, twice, 7-days apart, reduced FEC by 99%. CONCLUSIONS: The doses of anthelmintics required to effectively control nematodes in possums were higher than those recommended for animals for which they are currently registered. Possums tolerate the high dose rates of anthelmintics used in this study without apparent adverse effects.     

联合应用阿苯达唑和伊维菌素在线虫感染鄂尔多斯细毛羊体内的药动学研究

为阐明联合应用阿苯达唑(ABZ)和伊维菌素(IVM)在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学互作关系,以感染胃肠道线虫的鄂尔多斯细毛羊为研究对象,比较研究了单独或联合应用阿苯达唑和伊维菌素后的药物动力学特征。通过粪便虫卵检查法,选取感染胃肠道线虫的鄂尔多斯细毛羊15只,随机分成3组,每组5只。第1组口服给予阿苯达唑(15mg/kg),第2组皮下注射伊维菌素(0.2mg/kg),第3组皮下注射伊维菌素(0.2mg/kg)的同时口服阿苯达唑(15mg/kg)。于给药后不同时间,由颈静脉采集血样,分离血浆,并用高效液相色谱法测定各时间点血浆阿苯达唑、阿苯达唑亚砜、阿苯达唑砜和伊维菌素浓度,并用PK Solution 2.0药物动力学软件计算出各药动学参数。结果表明,联合用药组绵羊血浆伊维菌素峰浓度(Cmax)、药时曲线下面积(AUC)和平均滞留时间(MRT)分别为44.80ng/mL±6.12ng/mL、5 007.46ng.h/mL±1 301.42ng.h/mL和85.47h±5.03h,均显著(P<0.05)小于单独用药组的对应参数值67.62ng/mL±9.06ng/mL、7 125.08ng.h/mL±908.52ng.h/mL和113.39h±9.00h。口服阿苯达唑组绵羊血浆中仅检测到了阿苯达唑砜和阿苯达唑亚砜,而未检测到阿苯达唑母药。联合用药后,除阿苯达唑砜的达峰时间(T max)显著推迟外,阿苯达唑砜和阿苯达唑亚砜的其他各参数之间均无显著性差异。因此,联合应用IVM和ABZ可影响它们在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学特征,且对伊维菌素药动学特征的影响尤为明显,在临床联合用药过程中应予以重视。     

Use of an albendazole bolus against gastrointestinal nematode infections in first year cattle

Thirty first year grazing calves were allocated to two groups of 15 calves each on the basis of bodyweight and were administered albendazole boli or placebo boli, respectively, 30 days after turnout. The albendazole bolus prevented the nematode egg output almost completely for about 4 months, whereas the controls had mean egg counts of up to 206. Pepsinogen concentrations were significantly higher in the control group and reached mean values of 3055 mU tyrosine compared to less than 1000 mU tyrosine in the albendazole treated group after bolus administration. Pasture contamination with trichostrongylid larvae was markedly lower on pastures of the albendazole group than on the controls. Mean weight gains were significantly higher in the albendazole group than in the controls with a difference of 10.7 kg per animal at the end of the season.     

Duration of Anthelmintic Effect of Three Formulations of Ivermectin (Oral,Injectable and Pour-on) Against Multiple Anthelmintic-Resistant <Emphasis Type="Italic">Haemonchus contortus</Emphasis> in Sheep

We report the results of investigations that were conducted in a sheep flock in Uttaranchal, India where repeated failure of anthelmintic medication was noted. The study revealed that Haemonchus contortus in sheep had developed resistance to benzimidazoles (fenbendazole, mebendazole and albendazole), imidazothiazole (levamisole) and salicylanide (rafoxanide), while it was fully susceptible to avermectins (ivermectin). Further, the suppression of nematode egg output in faeces of sheep naturally infected with multiple anthelmintic-resistant H. contortus following treatment with ivermectin tablet (0.4 mg/kg body weight (bw), orally), ivermectin injection (1% w/v, 0.2 mg/kg bw, subcutaneously) and ivermectin pour-on (0.5 w/v, 0.5 mg/kg bw) was also studied over a period of 10 weeks post treatment. It was noted that ivermectin tablet after initial clearance of infection (faecal egg count reduction 100%), could not prevent establishment of new patent natural infection for even a single day, while ivermectin pour-on and injection prevented the establishment of new infection for 7 and 14 days post treatment, respectively. Maximum protection period (duration for which mean faecal egg count of sheep reaches 500 eggs per gram of faeces or more) of 68 days was recorded in sheep treated with injectable ivermectin, followed by pour-on (60 days) and oral (53 days) preparations.