Efficacy of moxidectin 0.5% pour-on against swine nematodes

Forty pigs with induced infections of Ascaris suum, Trichuris suis, Metastrongylus spp., Oesophagostomum dentatum and O. quadrispinulatum were assigned to five-dose groups of moxidectin 0.5% pour-on with eight pigs per dose group. The doses were: moxidectin, 0 (vehicle control), 0.75, 1.00, 1.25, and 1.50 mg/kg(-1) body weight. Worm egg counts (EPG) were made from fecal samples collected on Day 2 pretreatment and on Day 14 or 15 post-treatment. Animals were ranked according to the descending order of A. suum egg counts made on Day 2 and blocked in groups of five. Pigs in blocked groups were assigned randomly to each of the five dose groups. Treatment doses were calculated on the basis of weights taken on Day 1 and were administered topically from the neck to the base of the tail. Pigs were housed by pairs in individual pens provided with self-feeders and automatic waterers. Necropsies were performed on equal numbers of pigs from each treatment group on days 14 and 15 post-treatment. Adult and larval worms were collected, identified and counted by standard parasitological techniques. All counts were transformed by Y=log10 (count+1) transformation prior to analysis. A two-way analysis of variance was conducted and treatment effect was tested for significance at the 5% level. Efficacies based on geometric means and optimal doses were as follows: Ascaris suum, 98.3% at 1.25; Metastrongylus spp., 100% at 0.75; Oesophagostomum quadrispinulatum, 100% at 1.50; and Trichuris suis, 93.5% at 0.75. Efficacy for O. dentatum was from 81.3% to 100%; however, the average number of O. dentatum (30) was too small for significance. Two species of lungworms were present, Metastrongylus apri and M. pudendotectus but they were not speciated at necropsy. As reported for several anthelmintics, the efficacy of moxidectin was variable for Trichuris. The highest efficacy was in the 0.75 dose group with six pigs harboring a few or no worms. The lowest efficacy was in the 1.25 group with only two pigs harboring a few or no worms.     

Dose confirmation of moxidectin pour-on against natural nematode infections in lactating dairy cows.

The nematocidal effectiveness of moxidectin, administered topically at the rate of 500 mcg/kg BW, was determined for lactating dairy cows. Naturally infected animals were given either topical vehicle or moxidectin (Cydectin Pour-On Fort Dodge Animal Health) at the rate of 1 ml/10 kg BW (10 animals per treatment group), and sacrificed 14-18 days post-treatment for nematode enumeration. 100% efficacies were recorded for Ostertagia lyrata males, Cooperia punctata males and Oesophagostomum radiatum L4, with treatment group differences in geometric means significant (P < 0.05) for all. Populations of Trichostrongylus L4 and adult O. radiatum were also reduced by 100%, but low prevalence rates in the control animals precluded meaningful statistical inference. Nematode populations for which efficacies ranged from 96.7 to 99.6% (based on geometric means) and for which treatment group differences were significant (P < 0.05) included Ostertagia spp. adult females, inhibited L4 and developing L4, O. ostertagi adult males, Trichostrongylus axei adults and Cooperia spp. adult females. For all nematodes combined, moxidectin was 98.9% efficacious. In addition to exhibiting excellent nematocidal effectiveness, topical moxidectin was demonstrated to be safe, with animal health and milk production unaffected during the study.     

Dose confirmation studies of moxidectin 1% non-aqueous injectable and moxidectin 0.5% pour-on formulations against experimentally induced infections of larval and adult stage Oesophagostomum radiatum and Trichuris discolor in cattle

Separate controlled trials were conducted to evaluate the efficacy of two formulations of moxidectin (1% non-aqueous injectable solution and 0.5% pour-on (Cydectin) against larval or adult stages of Oesophagostomum radiatum and Trichuris discolor infecting cattle. Fifty-three strongylate-free dairy breed steer calves were obtained from commercial sources. After a brief acclimation period, calves were randomly divided into two pools to evaluate the efficacy of the moxidectin formulations against targeted larval (n = 27 calves) or adult (n = 26 calves) parasites. Calves in the larvacidal trial were inoculated on Day -16 relative to treatment with approximately 1000 embryonated Trichuris spp. eggs and approximately 640 infective Oesophagostomum spp. larvae. Calves were allocated by lottery to one of three treatment groups (n = 8 per group), which included: Group 1--moxidectin 0.5% pour-on (0.5 mg/kg body weight (BW)) applied topically; Group 2--moxidectin 1% non-aqueous injectable (0.2 mg/kg BW) administered subcutaneously; Group 3--untreated controls. Treatments were administered on Day 0 and calves were housed by group with no contact among animals of different treatments. Three sentinel calves were necropsied on Day 0 of the larvacidal trial to assess viability of larval inocula. On Days 14, 15 and 16 after treatment, calves were euthanatized (two or three from each group per day) and samples of gut contents were collected for determination of total worm counts. On Day -63 relative to treatment, calves in the adulticidal efficacy trial were inoculated with approximately 1000 embryonated Trichuris eggs and then on Day -35 with approximately 2500 infective Oesophagostomum spp. larvae. Fecal samples were collected on Day -7 and the 24 calves with the highest egg counts were assigned by lottery to the following three treatment groups (n = 8 per group): Group 4--moxidectin 0.5% pour-on; Group 5--moxidectin 1% injectable; Group 6--untreated controls. Details of experimental treatments, calf housing and necropsy scheduling were similar to the larvacidal trial. In both the larvacidal and adulticidal trials, inocula contained a variety of parasites in addition to the targeted species. Based on geometric means, both moxidectin 0.5% pour-on and moxidectin 1% non-aqueous injectable significantly reduced (P < 0.05) numbers of Oesophagostomum spp. and Trichuris spp. with anthelmintic efficacies of >99% when used against adult or larval stages of infection. In addition, both formulations of moxidectin demonstrated >95% efficacy (P < 0.05) against larval stages of Strongyloides papillosus. The pour-on formulation had >97% adulticidal and larvacidal efficacy against Cooperia spp. females, while the injectable product was effective against female Cooperia spp. larvae and Cooperia oncophora adult males.     

Efficacy of moxidectin 0.5% pour-on against naturally acquired nematode infections in cattle in the Mexican tropics

The efficacy of 0.5% moxidectin pour-on in cows with naturally acquired nematode infections was evaluated. The study was carried out in a ranch in Veracruz, Mexico. Four groups of 15 cows were randomly allocated. Animals in the treated group received 0.5% moxidectin pour-on at a dose of 0.5 mg/kg body weight on a single occasion. The other two groups remained as untreated controls. Fecal samples from all cattle were taken on days 0 (pre-treatment), 7, 14, 28 and 60 (post-treatment, PT). Fecal egg-counts were determined using a modified McMaster technique and fecal cultures were performed to identify gastrointestinal nematodes infected larvae (L(3)). Treatment with moxidectin was associated with a significant reduction in fecal trichostrongyle egg-counts compared with the controls; efficacy was 100% at 28 days PT. Haemonchus spp. and Strongyloides spp. were the two genera identified from coprocultures.     

Inefficacy of moxidectin and doramectin against ivermectin-resistant Cooperia spp. of cattle in New Zealand

Two cases are described in which strains of Cooperia spp. of cattle were found to be resistant to either the oral or the injectable formulations of ivermectin. Injectable moxidectin was not effective against the latter strain and doramectin was not effective against either of the ivermectin-resistant Cooperia isolates. In both cases, the anthelmintic efficacy of oral levamisole was 100%.     

Inefficacy of moxidectin and doramectin against ivermectin-resistant Cooperia spp. of cattle in New Zealand

Two cases are described in which strains of Cooperia spp. of cattle were found to be resistant to either the oral or the injectable formulations of ivermectin. Injectable moxidectin was not effective against the latter strain and doramectin was not effective against either of the ivermectin-resistant Cooperia isolates. In both cases, the anthelmintic efficacy of oral levamisole was 100%.     

The difference in efficacy of ivermectin oral, moxidectin oral and moxidectin injectable formulations against an ivermectin-resistant strain of Trichostrongylus colubriformis in sheep

AIM: To evaluate the efficacy of ivermectin oral, moxidectin oral and moxidectin injectable formulations against an ivermectin-resistant strain of Trichostrongylus colubriformis in sheep. METHODS: Twenty-four mixed breed lambs were infected with 15,000 infective third-stage larvae of an ivermectin-resistant strain of T. colubriformis which had originally been isolated from a goat farm in Northland in 1997. Twenty-six days post infection, the lambs were divided into 3 treatment groups and a control group (n=6 lambs/group). Treatment consisted of either ivermectin oral formulation (0.2 mg/kg), moxidectin oral formulation (0.2 mg/kg), or moxidectin injectable formulation (0.2 mg/kg). Faecal egg counts (FECs) were determined at 0, 3, 5, 7 and 10 days after treatment. All animals were necropsied 12 days after treatment and worm counts were performed. Larval development assays were conducted 24 days post infection. A further 3 lambs were infected with 15,000 infective third-stage larvae of a fully susceptible strain of T. colubriformis for comparative purposes in the larval development assay. The efficacy of the moxidectin injectable formulation was also confirmed in these 3 lambs. RESULTS: The FEC reduction test at day 10 after treatment revealed 62%, 100% and 0% reductions in arithmetic-mean FECs for ivermectin oral, moxidectin oral and moxidectin injectable groups, respectively. The ivermectin oral, moxidectin oral and moxidectin injectable formulations achieved 62%, 98% and 4% reductions in arithmetic-mean worm burdens, respectively. Larval development assays showed resistance ratios for ivermectin of 4:1, avermectin B2 of 2.7:1, ivermectin aglycone of 37:1, moxidectin of 1.4:1, thiabendazole of 14.6:1 and levamisole of 1.8:1. CONCLUSIONS: The moxidectin oral formulation provided a high degree of control against ivermectin-resistant T. colubriformis whereas the moxidectin injectable formulation had very low efficacy. Ivermectin aglycone was the analogue of choice for diagnosis of ivermectin resistance in T. colubriformis in the larval development assay.     

Persistent efficacy of doramectin and moxidectin against Cooperia oncophora infections in cattle

Duplicate studies in France and Northern Ireland were carried out to determine the persistent efficacy of topical moxidectin and doramectin against natural infections of Cooperia oncophora. In each study, groups of 15 nematode-na?ve calves were treated either with topical doramectin or moxidectin, and put out to graze on pasture contaminated with C. oncophora infective larvae. The persistent efficacy for preventing establishment of infection was assessed by the time to faecal egg excretion of C. oncophora eggs. It was found that the moxidectin treatment prevented infection for less than 10 days and the effect of doramectin lasted for 24 days.     

Ineffikacy of ivermectin against Cooperia spp. infection in cattle

Ivermectin, either as an injectable or topical formulation, is used widely to control parasites in New Zealand cattle. These formulations have been well documented as having high efficacy against the major nematode species which infect tattle^(1)(2)(3)(4), although the efficacy against adult Cooperia oncophora is reported to be 95%⁽⁵⁾. This is considered to be one of the doselimiting species. There have been two reports of lower than expected efficacy of the topical formulation against Cooperia spp. in cattle. In a slaughter trial, Bisset et al. ⁽⁶⁾ found that ivermectin applied topically at the recommended dose rate of 500 𝛍g/kg failed to achieve a statistically significant reduction in the burden of Cooperia spp. worms compared with untreated calves. The geometric mean of adult Cooperia spp. worms present in the treated calves was 5788 compared with 7524 present in the untreated calves. This reduced efficacy was not attributed to acquired anthelmintic resistance because ivermectin had not been used on the farm previously. In Australia, Eagleson and Allertonc⁽⁷⁾ found in controlled field trials that ivermectin applied topically at 500 𝛍g/kg ranged in efficiency in reducing faecal egg counts from 80.7% to 100% ; four out of 13 trials achieving less than 90% and a further four were in the range of 90–95% reduction. Larvae obtained from the faeces of ivermectin-treated cattle on days 11–14 after treatment were predominantly Cooperia spp.     

Efficacy of milbemycin oxime against fourth-stage larvae and adults of Ancylostoma tubaeforme in experimentally infected cats

The efficacy of milbemycin oxime against fourth-stage (L4) larvae and adults of Ancylostoma tubaeforme was investigated in a trial involving 24 young domestic shorthair cats. The animals were inoculated with approximately 300 infective stage three (L3) larvae and divided into three groups. After 12 days, eight cats (group 1) were treated with medicated tablets containing 4 mg milbemycin and 10 mg praziquantel to test the efficacy against L4 larvae; eight cats in group 2 were treated with the same tablets after 33 days to test the efficacy against adult worms; and eight cats in group 3 were treated with a placebo tablet. Faecal egg counts were determined periodically in each cat and after 40 or 41 days the number of worms in each animal was determined postmortem. The egg count reduction was determined by comparing the geometric mean numbers of eggs per gram of faeces in the placebo and medicated groups, and the worm reduction by comparing the geometric mean numbers of worms. The egg count reduction was more than 99 per cent in both treated groups, while the number of worms in groups 1 and 2 were reduced by 94.7 per cent and 99.2 per cent, respectively.     

The use of flumethrin 1% pour-on for the control of Amblyomma spp. in various southern African countries

Efficacy trials with flumethrin 1% pour-on were conducted in 9 different areas in 3 southern and central African countries against Amblyomma hebraeum and A. variegatum on cattle. A dose volume of 10 ml/100 kg body mass applied at bi-weekly intervals provided excellent control of both tick species on their predilection sites, irrespective of locally and seasonally high tick pressure. The trial results demonstrate clearly that this new concept of tick control can be effectively applied in commercial and traditional cattle husbandry situations.     

The efficacy of benzimidazole anthelmintics against late fourth stage larvae of Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats

The efficacy of eight benzimidazole anthelmintics has been examined against Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats, when the parasites were entering into the fourth and final moult. The dose--response slopes obtained from the data for both host--parasite systems did not deviate significantly from a non-parallel model, and were used for relative potency determinations. The T. colubriformis assay ranked the benzimidazoles in order of potency as follows: albendazole, oxfendazole, fenbendazole, cambendazole, mebendazole, oxibendazole, parbendazole and thiabendazole. This compares favourably with the expected relative efficacies against trichostrongyles in sheep. N. brasiliensis was found to be far less useful in this respect. All compounds tested, with the exception of thiabendazole, were highly effective against both parasites. The T. colubriformis/gerbil assay could be a very useful tool for preliminary in vivo evaluation and possibly in the early selective optimisation of chemical series.     

Evaluation of ivermectin against experimental infections of Haemonchus contortus and Trichostrongylus colubriformis in goats.

Fourteen nematode parasite-na?ve kids were given a mixed larval inoculum (approximately 17,250 infective larvae) via stomach tube. Twenty-two days after infection, the kids were randomly assigned to control and treatment groups of seven animals each. Mean eggs per gram for control and treatment groups were 4304 and 5315, respectively. Kids in the treatment group were given ivermectin (0.2 mg kg-1) administered by subcutaneous injection. At necropsy, the mean numbers of Haemonchus contortus and Trichostrongylus colubriformis for control and treatment groups were 2259 and 0, and 3033 and 773, respectively. This reduction was significant (P less than 0.05) for both species, resulting in an efficacy of 100.0% and 74.5%, respectively. The lower efficacy against T. colubriformis may be a sign of resistance, a reduced effectiveness due to route of administration, or a higher dose may be required with subcutaneous administration, as has been observed previously.     

Efficacy of moxidectin against multiple resistant Ostertagia spp. in lambs

Moxidectin was demonstrated to have a high efficacy in lambs against Ostertagia spp. which were resistant to albendazole, levamisole and ivermectin in goats. Moxidectin reduced the number of eggs in faeces by 99.6% and the number of worms found at post-mortem dissection of the lambs by 99.9%. Of the adult worms found in abomasa, 91% were identified as Ostertagia circumcincta and 9% as Ostertagia trifurcata.     

Dose determination of the persistent activity of moxidectin long-acting injectable formulations against various nematode species in cattle

The effectiveness, safety and production-enhancing benefit (improved weight gains) of moxidectin long-acting injection given subcutaneously in the ear at the rates of 0.75, 1.0 and 1.5mg/kg bw were evaluated in three studies under common protocol. The only adverse reaction to treatment was a mild (<2 tablespoons in volume), and for the most part transient (<28 days for the treatment rate of 1.0mg/kg bw) injection site swelling as noted in a minority of the animals (12.2% of the animals treated at the rate of 1.0mg/kg bw). Regardless of study site, post-treatment interval or dose rate, average daily gains were improved over control cattle by approximately 33%. Reductions in strongyle EPG counts relative to controls were > or = 90% for all dose rates of moxidectin for a post-treatment period of 42 days (Wisconsin), 84 days (Arkansas) and 140 days (Louisiana). In Arkansas and Louisiana, the majority (>80%) of post-treatment strongyle eggs, as determined by coproculture, were Cooperia spp. As determined by sequential necropsies, periods of continuous, post-treatment protection (> or = 90% efficacy in at least two out of three studies) for moxidectin long-acting injection given at the rate of 1.0 mg/kg bw were 90 days (adult Haemonchus spp.), 120 days (Dictyocaulus viviparus and adult Ostertagia and Oesophagostomum) and 150 days (Ostertagia spp. EL4).     

Efficacy of oral,injectable and pour-on formulations of moxidectin against gastrointestinal nematodes in cattle in New Zealand

The efficacy of moxidectin administered by different routes, against naturally acquired infections of gastrointestinal nematode parasites of cattle, was compared using faecal egg count reduction tests on 14 commercial farms throughout New Zealand. On each farm, groups of 15 calves were sampled for faecal nematode egg count and then treated with ivermectin administered orally, or with moxidectin administered either by the oral, subcutaneous injection or topical (pour-on) route. Samples were again collected 14 days after treatment and efficacy was calculated as the percentage reduction in-group mean egg count between the pre- and post-treatment samples. In addition, efficacy was calculated for individual animals, in order to compare the variability of the different treatments. On four farms untreated control groups were run and five animals from each of the control and all of the moxidectin-treated groups were bled over time to estimate plasma–moxidectin concentrations.Averaged across all tests, the reduction in faecal egg count was significantly greater after treatment with moxidectin oral (91.1%) than following treatment with moxidectin injection (55.5%) or with moxidectin pour-on (51.3%). Low efficacies were invariably against Cooperia oncophora. The oral treatments were significantly less variable in efficacy than the injection and pour-on treatments. Moxidectin concentrations in plasma were highest following subcutaneous injection and lowest following pour-on administration. Plasma levels following oral administration were intermediate, being significantly lower than post-injection and significantly higher than post-pour-on. There was no evidence of transfer of moxidectin to untreated animals through licking. Based on these results, along with those of other studies, it is proposed that oral administration of macrocyclic lactone anthelmintics results in higher concentrations of active reaching the target worms in the gastrointestinal tract than following either administration by injection or by pour-on.     

Efficacy of moxidectin injectable and pour-on formulations in a pilot control program against bovine hypodermosis in Southern Italy

Bovine hypodermosis is a myiasis caused by Hypoderma bovis and Hypoderma lineatum (Diptera, Oestridae) larvae, which has a severe economic impact on the livestock industry. Though myiasis is widespread throughout Italy, no nationwide eradication program has ever been planned, unlike in other European Countries. With a view to setting up a national control program, a pilot study was carried out in Southern Italy on 9939 cattle bred in an area with a high prevalence of cattle hypodermosis, using moxidectin 0.5% pour-on (Cydectin, Fort Dodge) and 1% injectable (Cydectin, Fort Dodge) formulations. At the recommended dosage, moxidectin displayed efficacy levels of 99.9% in the pour-on and 100% in the injectable formulation, whereas the microdose (1 mg per head regardless of body weight) was less effective (65.7%). This trial contributed to a significant reduction in infestation rates in the study area and represented the first step through which a national program for eradicating warble fly infestation in Italy.