Ivermectin Sustained-release Bolus Research Articles

Preparation and in vitro release kinetics of ivermectin sustained-release bolus optimized by response surface methodology.

Sustained-release formulations of ivermectin (IVM) are useful for controlling parasitic diseases in animals. In this work, an IVM bolus made from microcrystalline cellulose (MCC), starch and low-substituted hydroxypropyl cellulose (LS-HPC) was optimized by response surface methodology. The bolus was dissolved in a cup containing 900 mL of dissolution medium at 39.5 °C, under with stirring at 100 rpm. A quadratic model was formulated using analysis of variance according to the dissolution time. The optimized formulation of the bolus contained 8% MCC, 0.5% starch, and 0.25% LS-HPC. The length, width, and height of the prepared IVM bolus were 28.12 ± 0.14, 16.1 ± 0.13, and 13.03 ± 0.05 mm, respectively. The bolus weighed 11.4842 ± 0.1675 g (with a density of 1.95 g/cm3) and contained 458.26 ± 6.68 mg of IVM. It exhibited in vitro sustained-release for over 60 days, with a cumulative amount and percentage of released IVM of 423.72 ± 5.48 mg and 92.52 ± 1.20%, respectively. The Korsmeyer–Peppas model provided the best fit to the dissolution release kinetics, exhibiting an R2 value close to 1 and the lowest Akaike Information Criterion among different models. The parameter n (0.5180) of the Korsmeyer–Peppas model was between 0.45 and 0.89. It was demonstrated that the release mechanism of the IVM bolus followed a diffusive erosion style.

Soil Nematode Populations Beneath Faecal Pats from Grazing Cattle Treated with the Ivermectin Sustained-release Bolus or Fed the Nematophagous Fungus Duddingtonia flagrans to Control Nematode Parasites

The size and composition of the nematode assemblage in soil under faecal pats derived from young cattle treated or untreated with either ivermectin sustained-release boluses, or the nematophagous fungus Duddingtonia flagrans, were studied in each of three years. Soil samples taken 4, 6, 8 and 10 weeks after four deposition dates in 1998 showed significant temporal effects in many taxa and treatment effects in a few genera. In 2000, soil samples taken 10 weeks after deposition in July, August and September showed treatment effects in the plant-associated Tylenchus and Cephalenchus, and the bacterial-feeding Cephalobus 1 and Cephalobus 2 taxa. However, overall it was found that the nematode assemblages were similar below all three types of pat, and the assemblages varied with the season of deposition. D. flagrans, the novel biological control agent being tested against the free-living stages of nematode parasites of cattle, had no detectable impact on the size or the structure of the soil nematode communities under the faecal pats.

Disintegration of Dung Pats from Cattle Treated with the Ivermectin Anthelmintic Bolus, or the Biocontrol Agent Duddingtonia flagrans

An experiment was performed during the grazing seasons of 1998, 1999 and 2000 to study the influence of the antiparasitic drug ivermectin and the nematophagous fungus Duddingtonia flagrans on cattle dung disintegration. The faeces originated from groups of animals that were part of a separate grazing experiment where different control strategies for nematode parasite infections were investigated. Each group consisted of 10 first-season grazing cattle that were either untreated, treated with the ivermectin sustained-release bolus, or fed chlamydospores of D. flagrans. Faeces were collected monthly on 4 occasions and out of pooled faeces from each group, 4 artificial 1 kg dung pats were prepared and deposited on nylon mesh on an enclosed pasture and protected from birds. The position of the new set of pats was repeated throughout the 3 years of the study. Each year, the dung pats were weighed 4, 6, 8 and 10 weeks after deposition and immediately afterwards replaced to their initial positions.Results showed that there was no difference in faecal pat disintegration between groups. However, the time-lag between deposition and complete disintegration of the faeces varied significantly between deposition occasions. Dung pats disappeared within 2 weeks (visual observation) when subjected to heavy rainfall early after deposition, whereas an extended dry period coincided with faeces still remaining 12 months after deposition.

Environmental Impact on Soil Nematodes Following the Use of the Ivermectin Sustained-release Bolus or the Nematophagous Fungus Duddingtonia flagrans to Control Nematode Parasites of Cattle in Sweden

Management of nematode parasites of grazing livestock is essential, but there is concern about the potential environmental risk from agents used in their control. In this experiment, parasites in young cattle were controlled, using ivermectin boluses or the predacious fungus Duddingtonia flagrans , over 3 years. Treatment differences were sought among the soil nematodes recovered from soil samples collected from the paddocks on which treated animals grazed, and compared with similar samples taken from an untreated control paddock. Analysis of the soil nematode fauna on 21 occasions failed to demonstrate any impact of parasite management on soil nematodes. In 0-22 mm soil total nematode abundance averaged 524 000 m -2 , with 18 nominal taxa and H' diversity 2.41. There were both underlying paddock and year-to-year, climate-related, differences. The results of this trial not only confirm the lack of any adverse environmental impact of D. flagrans , a promising biological control agent, on soil nematodes, but also fail to show any impact arising from the use of ivermectin boluses.

Sub-clinical parasitism in spring-born, beef suckler calves: epidemiology and impact on growth performance during the first grazing season

Sub-clinical parasitism in spring-born single suckled beef calves was investigated from the middle of their first grazing season until weaning or housing later the same year. The study was conducted on four beef suckler herds in southern England over a 3-year period and involved a total of 334 spring-born beef suckler calves and their dams. The animals were grazed extensively on pastures naturally infected with nematode larvae. At the start of each period of observation, faecal samples were taken from calves and cows and subjected to routine worm egg counts; calves were re-sampled at the end of the grazing season. In July in each year and at each location the calves were ranked by initial weight within sex, paired according to rank and randomly allocated to either an untreated control group or a group in which the calves were each treated with an ivermectin sustained-release (SR) bolus. The calves in both trial groups, and their dams, were grazed together until weaning or housing. The calves were weighed at the initial allocation and at the end of the study. The adult cows were not treated with any anthelmintic during the study. The faecal nematode egg counts (FECs) conducted in July showed that the suckler cows were excreting worm eggs at low concentrations: range 0–100 eggs per gram (epg), with one individual count of 500 epg, 88% of the cows sampled had counts of <50 epg. Similarly, the counts from the calf samples were fairly low in July: range 0–250 epg, 73% of the calves sampled had counts of <50 epg. By the end of the grazing season, the faecal samples from the untreated control calves showed higher values: range 0–650 epg, with only 58% having an epg of <50. The average rate of daily liveweight gain in the untreated heifer calves was 0.79 kg per day, the corresponding figure for the heifer calves treated with the ivermectin SR bolus in mid-summer was 0.88 kg per day; the difference of 90 g per day was significantly different ( P=0.0118). The average rate of daily liveweight gain in the untreated bull calves was 0.91 kg per day, the corresponding figure for the bull calves treated with the ivermectin SR bolus in mid-summer was 1.01 kg per day; the difference was significantly different ( P=0.0169).

The negative effects of the residues of ivermectin in cattle dung using a sustained-release bolus on Aphodius constans (Duft.) (Coleoptera: Aphodiidae).

This paper reports the findings of two trials into the effects of the treatment of cattle with ivermectin slow-release (SR) bolus on the larval development of the dung beetle Aphodius constans Duft. Rectal faecal samples were collected prior to treatment and every 3 and 2 weeks in a first and second trial, respectively, and up to 156 days post-administration of the SR bolus. Faecal ivermectin concentration reached a peak at 63 days post-treatment (1427 ng g(-1)) and ivermectin was detected up to 147 days post-treatment in the first trial (7.2 ng g(-1)). First stage larvae of A. constans were reared with control or contaminated dung and adult beetles were counted after emergence. In the first trial, the comparison of pairwise samples showed that ivermectin prevented the development of larval A. constans until day 105, while at day 135 the rate of emergence was still significantly lower than the corresponding series of control (p < 0.05). In the second trial, the difference between control and treated series remained significant until 143 days post-treatment, with no emergence until 128 days post-administration of SR bolus to cattle. These results show the negative effect of ivermectin on the development of larval A. constans, even at a low concentration (38.4 ng g(-1)). The administration of ivermectin sustained-release bolus to cattle was highly effective in killing dung beetle larvae for approximately 143 days after treatment. The results were similar when dung was obtained from a single animal kept alone, or from a blending of faecal pats obtained from a group of animals kept in field conditions during the whole trial period.

A single pasture limited treatment approach to estimate production loss from gastrointestinal nematodes in grazing stocker cattle

The objective of this study was to evaluate the use of a single pasture, limited treatment methodology to assess the impact of gastrointestinal nematodes on weight gain in grazing cattle. From a group of 450 British crossbred, yearling spayed heifers, 60 animals were randomly selected (prospective randomization) prior to placement on summer pasture. Each of these 60 animals was weighed, a fecal sample obtained for nematode egg count and a uniquely numbered ear tag applied. A randomly assigned group of 30 received treatment with one ivermectin sustained release bolus, while the remaining 30 served as non-treated controls. The treatment and control groups rejoined the remaining non-treated 390 animals, and were grazed as a single group for 165 days. At grazing conclusion, treatment and control cattle were individually weighed, and fecal samples obtained for nematode egg counts. Treatment was associated with a 0.064 kg per grazing day gain increase, or a 10 kg increase over the grazing season ( P=0.02). Nematode egg counts at grazing initiation were not different between treatment and control ( P=0.30), though egg counts in treated cattle at study end were lower than control ( P<0.0001). Results of this study support the use of a single pasture limited treatment approach for measuring the effect that internal nematodes have on weight gain in grazing cattle under commercial range conditions.

The effect of first season chemoprophylaxis in calves on second season pasture contamination and acquired resistance and resilience to gastrointestinal nematodes

Two groups of second grazing season cattle, which had been treated with an ivermectin-sustained-release bolus (ISRB) in their first grazing season, were monitored during consecutive years (1995 and 1996) on the same second grazing season pasture. In the preceding year (1994), this pasture had been grazed by yearlings that had not received chemoprophylaxis in their first grazing season. The objectives of the study were, firstly, to investigate whether the chemoprophylactic-treated yearlings were less resistant to gastrointestinal nematodes upon subsequent exposure, and hence excreted more strongyle eggs compared to the control yearlings; secondly, whether an increased susceptibility of the previously treated animals resulted in a yearly increase of the pasture infestation on the second grazing season pasture; and finally, whether this affected the second year weight gain of the animals. In 1996, the yearlings that had been chemoprophylactic-treated in 1995 excreted higher numbers of nematode eggs, compared to the previously `untreated' yearlings. In addition, the proportion of Cooperia larvae was markedly higher in the faecal cultures from the chemoprophylactic treated-animals, suggesting a negative effect of preventive treatment with an ISRB on the acquired resistance of the animals. However, there was no evidence that the slightly higher egg output in the previously treated yearlings had an effect on the larval contamination of the second grazing season pasture. A significant yearly decrease in the second season average daily weight gains was observed, but it could not be inferred from the results of the parasitological parameters that the differences in second year growth were caused by different levels of resilience between chemoprophylactic-treated and -untreated animals. As the study covered three consecutive second grazing seasons, an effect of differences between years (e.g. in weather conditions or grass growth) on the results cannot be excluded.

Effects of preventive anthelmintic treatment on acquired resistance to gastrointestinal nematodes in naturally infected cattle

The objective of this study was to investigate the influence of different types of chemoprophylaxis in first season grazing calves on their resistance against a natural reinfection with Ostertagia ostertagi and Cooperia oncophora in the second grazing season. Thirty helminth-naive crossbred calves were randomly divided in three groups of 10 animals. The animals of group B received an ivermectin sustained release bolus on day 0. The calves of group D were treated on days 0 and 56 with a subcutaneous injection of doramectin (0.2 mg kg −1 BW). Group C was the untreated control group (`immune' controls). Although exposure to gastrointestinal nematodes in the first grazing season was only limited, the chemoprophylactic treatments in groups B and D resulted in three distinctly different infection levels (group C>group D>group B). At the start of the second grazing season, six helminth-naive steers (group N, `susceptible' controls) were turned out together with the second season animals. After 3 weeks of grazing, the `susceptible' controls were slaughtered, together with four animals from each other group. Parasitological and immunological parameters indicated that resistance to reinfection with Ostertagia was reduced in the chemoprophylactic treated animals, and was negatively related to the degree of suppression of host-parasite contact in the first grazing season (group C>group D>group B>group N). None of the groups had developed a complete resistance against Cooperia yet. A negative relationship was observed between reduction of first grazing season exposure, and weight gains early in the second grazing season. The remaining animals stayed on pasture until the beginning of November. At the end of the second grazing season, levels of acquired resistance against Ostertagia infection were similar in all groups, and all animals had become immune against Cooperia. No effect of first year chemoprophylaxis on total weight gains could be demonstrated. Because of discrepancy between pasture larval counts and tracer worm counts, it was not possible to draw firm conclusions on the effect of chemoprophylaxis on pasture infestation levels in the second year.

The effect of different infection levels on acquired resistance to gastrointestinal nematodes in artificially infected cattle

The objective of this study was to evaluate the effect of different infection levels of Ostertagia ostertagi and Cooperia oncophora in a simulated `first grazing season' on the resistance of calves to an artificial challenge infection. The infection levels were determined by the infection schedules and the chemoprophylaxis used. Thirty six 7–11-month old Holstein–Friesian bull calves were randomly divided into four groups. The animals of group B received an ivermectin sustained release bolus (ISRB) on day 0. The calves of group D were treated on days 0 and 56 with a subcutaneous injection of doramectin (0.2 mg kg −1 BW). Group C was the untreated control group. The calves of group N were used as helminth-naive controls, while the animals of groups B, C and D were trickle infected for 24 weeks. The infection schedules were designed to simulate the expected infection pattern for each treatment group under set-stocked conditions in temperate climate areas. After the last infection, all animals were treated with oxfendazole. One week later, all animals received a challenge infection of 50,000 O. ostertagi L3 and 100,000 C. oncophora L3, spread over 10 consecutive days. During the primary infection period the faecal egg output and the serum pepsinogen and antibody levels reflected the different levels of host–parasite contact between the groups (group C>group D>group B>group N). After the challenge infection, faecal egg counts, total Ostertagia burden, size of the adult worms and abomasal globule leucocyte counts all indicated a positive relationship between the level of Ostertagia infection during the primary infection period and the level of acquired resistance. A reduction of host–parasite contact during the primary infection period, as a consequence of the infection schedule and the chemoprophylaxis used, resulted in a diminished level of resistance to the artificial challenge infection with O. ostertagi. Faecal cultures and small intestine worm counts indicated that all previously infected groups had acquired a high degree of resistance to the Cooperia challenge infection.

Effect of chemoprophylaxis with an ivermectin sustained-release bolus on acquired resistance to gastrointestinal parasites in cattle

The influence of chemoprophylaxis with an ivermectin sustained-release bolus in the first grazing season on the resistance of cattle to gastrointestinal nematodes during the following grazing season was investigated. In...

Assessment of parasite control and weight gain after use of an ivermectin sustained-release bolus in calves

Objective To assess parasite control and weight gain after administration of an ivermectin sustained-release bolus over 135 days to calves grazing in the midwestern United States. Design Replicated pasture study. Animals 56 Bos taurus calves. Procedure Calves were matched for body weight and randomly allocated to remain untreated or to receive an ivermectin sustained-release bolus before turnout on day 0. Calves were grazed by treatment group on 8 pastures (4 replicates). Body weights and fecal egg counts were recorded on days −1 and 28, and then at 28-day intervals until day 168. Results Parasitism was not clinically evident prior to or during the study. In treated calves, mean fecal egg counts were at or near 0 at all posttreatment evaluations. Although the mean egg count exceeded 20 ova/g only once in control calves, the cumulative egg output was &gt; 42 million/calf. For the treated group, it was &lt; 0.1% of this number. Mean total weight gain was 33.9 kg (74.6 lb) greater for ivermectin-treated calves than for untreated control calves (P &lt; 0.02); a 34% increase. Clinical Implications Fecal trichostrongyle eggs from calves can accumulate over a grazing season to provide enormous potential for augmenting pasture infectivity. An ivermectin sustained-release bolus (administered to calves being placed on pasture) controls parasitism, limits pasture infectivity, and can substantially influence growth by limiting the impact of subclinical parasitism. (J Am Vet Med Assoc 1997;211:754–756)

Development of immunity to lungworm in vaccinated calves treated with an ivermectin sustained release bolus or an oxfendazole pulse release bolus at turnout

The ivermectin sustained release bolus (IVSRB), when used at turnout as recommended, will provide season-long control of parasitic bronchitis, thus obviating the need for use of a lungworm vaccine. However, some concerns have been expressed that calves treated with an IVSRB will receive so little exposure to Dictyocaulus viviparus that it will compromise their immunity in subsequent grazing seasons, which would be of particular importance in dairy herds. Although there is evidence that IVSRB-treated calves can develop immunity to D. viviparus when exposed to pasture infection, it was considered worthwhile to evaluate the compatibility of the IVSRB and lungworm vaccination to allow veterinary surgeons the option of using these products concurrently when they have particular concerns about the long term immune status of replacement dairy heifers. Thirty-two dairy replacement heifers were vaccinated with two doses of lungworm vaccine and, at turnout, half the calves received an IVSRB and the remainder an oxfendazole pulse release bolus (OPRB). At the end of the grazing season four replicate bolus treated pairs and four parasite-naive calves were challenged with 1000 D. viviparus infective larvae. At slaughter there was a 95% and 93% reduction in D. viviparus burdens in the IVSRB and OPRB treated calves respectively, compared with the unvaccinated, untreated controls. These results indicate that where it is considered necessary to use lungworm vaccination in addition to an IVSRB or an OPRB, the compatibility of these products with lungworm vaccine will allow development of a protective level of immunity to D. viviparus.

Effect of treatment with an ivermectin sustained-release bolus on productivity of stocker beef calves

Three groups of 30 crossbred beef steers, 8–10 months of age and ranging in weight from 158 to 320 kg, were used to compare effects of treatment with an ivermectin sustained-release bolus or two ivermectin injectable treatments on parasite control and productivity in relation to untreated controls during a 168 day winter-spring grazing period. Each group of 30 consisted of five cattle on each of six separate 1.6 ha pastures. Treatments on Day 0 (12 December) were: Group 1: untreated controls; Group 2: ivermectin injectable at 200 μg kg −1 bodyweight, s.c., on Day 0 and Day 56; Group 3: ivermectin sustained-release bolus to deliver ivermectin at 12 mg day −1 over approximately 135 days. All cattle were weighed at 28 day intervals and fecal samples were collected for egg per gram counts (EPG). Geometric mean EPG for Group 3 remained consistently less than 1.0 after Day 0 and were highest (2.4) on Day 168. All group EPG were significantly different ( P<0.01) by Day 56, and EPG of Group 2 had increased to 10.5 following initial treatment and to 42.8 on Day 112. With the exception of a low mean EPG of 6.8 for Group 1 on Day 112, EPG of the group were consistently highest (range 24.9–36.0) to the end of the experiment. Ostertagia ostertagi was predominant, along with smaller proportions of Haemonchus placei and Cooperia spp. Throughout the experiment Group 3 had highest liveweights and gains that were most often different from those of Group 1 at P<0.01 or greater. Group 2 had a similar advantage over Group 1, but at P<0.05. On Day 168, Group 3 had liveweight and cumulative gain advantages over Group 2 of 9.3 kg and 10.8 kg, respectively, but these were not significant. Advantages over Group 1 were 31.1 kg and 30.1 kg, respectively.

An ivermectin sustained release bolus in cattle: its effects on the tick Ixodes ricinus

Five calves were given an intraruminal bolus orally, designed to release ivermectin for 120 days at the rate of 8 mg/day. This is equivalent to a dose of 40 micrograms/kg/day for a calf expected to weigh 200 kg at the end of the delivery period. Five control calves were given a placebo bolus. On days 7 and 36 after treatment ten nymphs and ten adult female Ixodes ricinus (Linnaeus 1758) were placed in ear bags on the calves. The engorgement rates were monitored for 10 days and subsequent egg production and hatching percentages determined. There were no significant differences between treatment groups for female mortality. However, ivermectin treatment significantly reduced the numbers and weights of engorged females, females laying eggs, and the number of larvae produced on the treated calves was reduced to 3% of that of the control group. The effects on nymphs, although similar, were less consistent than on adults.

Phophylaxis of nematode infections in cattle with an indwelling rumino-reticular ivermectin sustained release bolus

Ivermectin delivered continuously from a rumino-reticular sustained release device was prophylactically effective in preventing establishment of nine nematode parasite species in multiply-exposed cattle. Ivermectin dosages which permitted ⩽1% of infected control calf worm populations to establish ranged from <2.5 μg kg −1 day −1, which totally prevented infection with Dictyocaulus viviparus and Oesophagostomum radiatum, to ≅30 μg kg −1 day −1 required to suppress Nematodirus helvetianus to the same extent. Between these extremes, in decreasing order of sensitivity to enterical sustained release ivermectin, were Ostertagia ostertagi, Trichostrongylus axei, Haemonchus placei, Copoperia punctata, C. oncophora and T. colubriformis which were maximally affected at ⩽10 μg kg −1 day −1 of ivermectin.