The anthelmintic efficacy of ivermectin in experimentally infected cattle

The 22,23-dihydro derivative (ivermectin) of the major B₁ components of the avermectins was evaluated, by oral and parenteral routes, for anthelmintic activity in cattle experimentally infected with 7 gastro-intestinal nematode species and lungworm. Treatment at three dosage levels was administered when the parasites were in the L₄ developmental stage or when adult. The dosage expected to remove 95% of the nematodes (ED₉₅) by each route of administration against the various developmental stages of each species of parasite was calculated by methods of linear regression to choose dose levels to be used in subsequent developmental field trials. Parenterally, efficacy against L₄ stages of Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, T. colubriformis, Cooperia oncophora, C. punctata, Oesophagostomum radiatum and Dictyocaulus viviparus exceeded 99% with treatment at 0.2 mg ivermectin/kg. Parenteral treatment of the adult parasites resulted in at least 98% reduction of worm burdens, except $\text{? 90\%}$ for T. colubriformis, with 0.2 mg/kg. Oral treatment of L₄ stages of development with 0.2 mg/kg resulted in at least a 95% reduction in worm burdens of each of the 8 species of parasite. Oral treatment of the adult worms with 0.1 mg ivermectin/kg produced at least a 98% decrease in each parasite species, except for T. colubriformis (90% reduction) for which dose-response calculations suggest 95% efficacy with oral treatment at 0.2 mg/kg.     

The efficacy of used engine oil against ticks on cattle

The study was conducted in a peri-urban agricultural system at Botshabelo, a city in the south-eastern Free State. A questionnaire survey revealed that 88.5% of cattle farmers in the area experienced problems related to ticks and tick-borne diseases. Because of the cost of commercial acaricides the Botshabelo farmers use alternative, cheaper methods of tick control, including the application of used engine oil. The specific aim of the study was to determine whether used engine oil can effectively control ticks on cattle. From March to August 1996 the tick burdens of ten control animals and six animals treated by their owner with used engine oil were compared. The total tick burdens for the 6 month period differed significantly between the two experimental groups. The efficacy of the used engine oil on the treated group varied between 15.1% and 64.8% with a mean of 38.1%. Although commercial acaricides can be more cost-effective, the application of used engine oil can be useful to reduce tick numbers on cattle during periods of peak abundance. Another advantage in that the use of the oil will not influence existing endemic stability of Anaplasma marginale and Babesia bigemina infections because of the residual tick burdens after treatment.     

Comparison of the persistent activity of ivermectin, abamectin, doramectin and moxidectin in cattle in Zambia

The persistent efficacy of four commercially available macrocyclic lactones (ML) in maintaining reduced faecal egg counts in cattle grazing naturally infested pastures was evaluated in 44 zebu animals aged 1–2 years in Zambia. The study started in February (rainy season) when the strongyle egg output was increasing. Four days before the start of the trial, all animals were treated with a double dose of oxfendazole. They were then divided into five groups which were again treated on day 0. Groups A, D, I and M received 0.2 mg kg⁻¹ of abamectin, doramectin, ivermectin and moxidectin, respectively. Animals of group C received albendazole (7.5 mg kg⁻¹). Faecal samples were collected twice a week for egg counts and larval differentiation. Faecal egg counts in the C group increased from day 21 onwards and plateaued from day 42 between 180 and 380 eggs per gram. The main genera found in cultures were Cooperia (90%) and Haemonchus (7%). Faecal egg excretion in groups M, A, D and I started on day 35, 42, 42 and 45, respectively. subsequently and until day 84, average counts in these four groups were always significantly lower than in group C. Compared with albendazole, all four ML gave over 95% reduction in cumulative faecal egg counts for 42 days after treatment. The percentage efficacy was still over 84% by day 84 when an average cumulative egg count of 11 320 eggs per gram faeces was calculated in group C. In addition, there was no significant difference in efficacy between the four ML groups at any of the sampling dates. During the trial no significant difference in weight gain between any of the groups was observed.     

Perception of cattle farmers of the efficacy of east coast fever immunization in Southern Zambia

A study using a structured questionnaire was conducted to assess the perception of cattle farmers of the efficacy of East Coast fever (ECF) immunization in southern Zambia. One hundred and seventy-nine farmers from five districts in southern Zambia were interviewed. The majority of farmers (85%) perceived ECF immunization as being very effective and about half of them (51.4%) preferred immunization to other ECF control strategies. The study showed that the number of calves immunized was strongly associated with the farmer's perception of the benefits of immunization. There was no association between the number of calves immunized and the number of veterinary assistants in a given district or their transport situation. Overall mortality in ECF-immunized calves from various causes stood at 4.2%. Based on farmers' reports, the majority of these deaths seemed to have been caused by anaplasmosis, another tick-borne disease, and might have resulted from relaxation of tick control after ECF immunization. The reasons identified by farmers for not immunizing their animals included failure by immunizing teams to reach certain areas, not having calves of immunization age, and lack of money. These findings provide valuable information on how livestock farmers perceive and adopt new animal disease control strategies and the information could be useful in their planning and implementation.     

The efficacy of ivermectin against the eyeworm, Thelazia skrjabini, in experimentally infected cattle.

The anthelmintic efficacy of ivermectin (administered subcutaneously at 200 micrograms kg-1 body weight) was assessed for control of Thelazia skrjabini in experimentally infected calves. Twenty-four uninfected male Holstein calves, 1-2 weeks old, were artificially infected with Thelazia skrjabini by placing 15 third-stage larvae under the third eyelid of calves. The challenge larvae were recovered from naturally infected face flies, Musca autumnalis. The exposed calves were randomly assigned to either an ivermectin treatment group or a control group within pairs ranked by weight. Equal numbers of calves were housed in each of four indoor fly-free rooms. The calves were treated with ivermectin or saline 35 days post-infection, then slaughtered 14 days later to determine eyeworm numbers. All eyes and associated tissues (including the lacrimal glands and ducts) were removed and examined for total number, species and viability of eyeworms. Thelazia skrjabini was found in the control group of calves only. The efficacy of ivermectin against Thelazia skrjabini was thus shown to be 100%.     

Effects of ivermectin on control of gastrointestinal nematodes and weight gain in weaner-yearling beef cattle

Four groups of 16 crossbred beef calves were used in evaluating different anthelmintic treatment schedules: group 1 was given ivermectin (IVM) at weaning only (October 31) and grazed on initially safe pasture; group 2 was given IVM at weaning, on January 28, and on April 22, and grazed on contaminated pasture; and group 3 was given IVM at weaning and on April 22, and grazed on contaminated pasture; and group-4 was group treated with fenbendazole (FBZ) at weaning only, with provision for individual salvage treatment, and grazed on contaminated pasture. The investigation was from Oct 31, 1984, to Oct 9, 1985. Initially high fecal egg counts at weaning were more effectively reduced by IVM than by FBZ, and the effect of safe pasture was evident in minimal worm burdens in tracer calves grazed with group-1 cattle during November and least amount of weight loss in group-1 yearlings during winter. Fecal egg counts, pasture larval counts, and plasma pepsinogen concentrations remained low in group 2 after the January treatment. Fecal egg counts of the other groups increased substantially during late winter and spring, but pasture larval counts increased only on group-1 and group-4 pastures. During spring, highest worm burdens were found in group-1 and group-4 tracer calves (grazed in April) and in group-3 and group-4 yearlings (slaughtered in early April). Six cattle of group 4 were salvage treated with FBZ in February and April. Greatest gains were observed from March through June, with group-2 and group-1 cattle gaining the most.(ABSTRACT TRUNCATED AT 250 WORDS)     

Persistent anthelmintic activity of ivermectin in cattle

Two studies are described which demonstrate the persistent activity of ivermectin injected subcutaneously into cattle at 200 micrograms/kg in preventing the establishment of induced infections with the gastrointestinal parasites Ostertagia ostertagi and Cooperia oncophora and the lungworm Dictyocaulus viviparus. These results indicated a reduction in mean worm count compared with the control group for O ostertagi of more than 99, 45 and 94 per cent with a seven, 14 or 21 day interval between treatment with ivermectin and the administration of infective larvae, respectively, in trial 1 and more than 99, more than 99 and 99 per cent at seven, 10 or 14 days, respectively, in trial 2. Corresponding values against C oncophora were 99, 0 and 45 per cent at seven, 14 and 21 days in trial 1 and more than 99, 84 and 31 per cent at seven, 10 and 14 days in trial 2. Against D viviparus, reduction in counts were more than 99, 98 and more than 99 per cent at seven, 14 and 21 days, respectively, in trial 1 and 100, 100 and 100 per cent at seven, 10 and 14 days, respectively, in trial 2. The relevance of these results to the build-up of infective larvae on pasture and infection in cattle is discussed.     

Chemical control of Haematobia irritans with 0.5% topical ivermectin solution in cattle.

A field trial was conducted to evaluate the efficacy of a topical formulation of ivermectin administered at the dose of 500 micrograms/kg against horn flies (Haematobia irritans) in cattle. Eighty-eight cattle in four herds naturally exposed to horn flies were used in the trial. Replicates were formed of two herds. Within replicates, one herd was randomly allocated to the untreated control and the other to the ivermectin treatment group. Horn fly counts were taken on the treatment day (Day 0) and on Days 7, 14, 21, 28, and 35 post-treatment. There were no horn flies on any cattle in the treatment group, whereas all the control cattle were continuously infested by horn flies on each examination day.     

The efficacy of ivermectin against Thelazia rhodesii (Desmarest, 1828) in the eyes of cattle.

One hundred cattle with confirmed natural infections of Thelazia rhodesii were included in three studies to evaluate the efficacy of ivermectin for the treatment of eyeworm infection. Thelazia rhodesii were counted in situ in each eye of each animal on Day 0 (prior to treatment) and the cattle were paired by the number of worms, within categories of sex, age or number of infected eyes. Within each pair, one animal was randomly assigned to serve as an untreated control, while the other was treated subcutaneously with ivermectin at 200 micrograms kg-1 body weight. Eight days later, parasites were recovered from each eye separately, identified and counted. In each study, significantly (P less than 0.01) fewer T. rhodesii were collected on Day 8 from ivermectin-treated cattle than from controls. Overall, the reduction in numbers of T. rhodesii collected from treated cattle was greater than 99% (P less than 0.05) relative to controls, with reductions of 100% being recorded in two of the three studies.     

Evaluation of the persistent efficacy of doramectin and ivermectin injectable against Ostertagia ostertagi and Cooperia oncophora in cattle

The persistent efficacy of doramectin and ivermectin injectable against moderate and high infection levels of Ostertagia ostertagi and Cooperia oncophora were evaluated in cattle. Calves were allocated to six groups of six animals. On Day 0 animals of Groups I1/I2 and D1/D2 were treated with 0.2mg/kg ivermectin and doramectin injectable, respectively. Animals of the C1, I1 and D1 groups received a daily (moderate) infection of 1000 L3 of O. ostertagi and 1000 L3 of C. oncophora, and animals of the C2, I2 and D2 groups received a daily (high) infection of 10,000 L3 of each species. The animals were infected for 21 days with both species, the infections with C. oncophora and O. ostertagi started from Days 8 and 15 post treatment, respectively. Animals were necropsied on Day 40. The calculation of the persistent activity of ivermectin and doramectin was based on the efficacy against the different developmental and adult stages of both parasites. The present study confirmed that infection levels may influence the duration of persistent efficacy of an anthelmintic. Doramectin had at the moderate infection level a persistent efficacy of at least 35 days against O. ostertagi and at least 28 days against C. oncophora; at the high infection dose persistent efficacy was somewhat shorter i.e. up to 33 days and approximately 28 days, respectively. The duration of persistent efficacy of ivermectin against O. ostertagi at the moderate infection level was between 14 and 25 days, at the high dose level up to 25 days. Persistent efficacy of ivermectin against C. oncophora could, at both infection doses, not be measured, with the present experimental design.     

The pharmacodynamics of ivermectin in sheep and cattle

The concentrations of ivermectin in the gastrointestinal tract of sheep and cattle were determined after subcutaneous administration of ivermectin. Ivermectin was not detected (limit of detection 1 ng/ml) in abomasal and ruminal fluids either after a normal therapeutic dose of 200 micrograms/kg or even at an increased dose of 2000 micrograms/kg. It was also not detected in abomasal and ruminal fluids of a sheep infected with the abomasal parasite Ostertagia circumcincta. However, ivermectin was detectable at similar concentrations in abomasal mucus and in small intestinal mucus. Excretion of ivermectin was high in bile but the concentrations in small intestinal mucus, distal and proximal to the bile duct opening, were similar. It is hypothesized that the low efficacy of ivermectin against small intestinal nematodes compared with abomasal nematodes is not due to differences in ivermectin concentrations in the predilection sites but is probably due to tachyphylaxis in the nematodes allowing the small intestinal nematodes to re-establish before they have left their predilection site. Ivermectin was excreted in the milk of ewes at concentrations similar to those in plasma. Lambs suckling ivermectin-treated ewes received about 4% of a normal therapeutic dose (200 micrograms/kg) via the milk.     

Bioequivalence of ivermectin formulations in pigs and cattle

The vehicle in which endectocide compounds are formulated plays a relevant role in their absorption kinetics and resultant systemic availability. The pharmaceutical bioequivalence and comparative plasma disposition kinetics of ivermectin (IVM), following the subcutaneous administration of two injectable formulations to pigs and cattle were investigated using parallel experimental designs. Sixteen parasite-free male Duroc Jersey-Yorkshire crossbred pigs (90-110 kg) (Expt 1) and 16 parasite-free male Holstein calves (100-120 kg) (Expt 2) were divided into two groups and treated subcutaneously at either 300 (pigs) or 200 (calves) microg/kg with two different propylene glycol/glycerol formal (60: 40) based IVM formulations; in both experiments pigs or calves in Group A received the test (IVM-TEST) formulation and those in Group B were treated with the reference formulation (IVM-CONTROL). Heparinized blood samples were taken from 0 h up to either 20 (pigs) or 30 (calves) days post-treatment and plasma was extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. Early detection of IVM (12 h) with a peak plasma concentration (C(max)) between 33 and 39 ng/mL was observed in pigs. The drug was detected in plasma up to 20 days post-administration of either formulation, resulting in elimination half-lives between 3.47 and 3.80 days. There were no differences between the IVM-TEST and IVM-CONTROL formulations in the kinetic parameters (except t(max)) obtained in pigs. IVM was detected in plasma between 12 h and 30 days post-administration of both formulations under investigation in cattle. The plasma disposition kinetics of IVM in calves was similar following treatment with both formulations. C(max) values (between 40.5 and 46.4 ng/mL) were achieved at 2 days post-administration of both formulations. None of the estimated kinetic parameters were statistically different between drug formulations. The injectable IVM formulations investigated were bioequivalent after their subcutaneous administration to both pigs and calves at recommended dose rates.