Measurement of ivermectin concentrations in target worms and host gastrointestinal tissues: influence of the route of administration on the activity against resistant Haemonchus contortus in lambs

The influence of the administration route on the relationship between efficacy and ivermectin concentration profiles achieved in the bloodstream, the gastrointestinal mucosal tissues/fluid contents and within a target abomasal parasite (Haemonchus contortus) was evaluated in lambs. Twenty-six (26) parasitized lambs were assigned into three experimental groups: untreated (control) and ivermectin treated by the subcutaneous and intraruminal route at 0.2mg/kg. Blood samples were collected between 0 and 15 days post-treatment (plasma disposition study). Four animals from each group were sacrificed at day 3 post-treatment. Mucosa and content samples from abomasum and small intestine and adult specimens of H. contortus were collected. Drug concentrations were measured by HPLC. Individual fecal egg counts were evaluated at -1, 3 and 15 days post treatment. Post-mortem examination was done at day 15 post-treatment. Adult nematodes recovered from the digestive tract were counted and identified by species. Ivermectin plasma availability was higher (P<0.05) after the subcutaneous administration (129 ng.d/ml) compared to the intraruminal treatment (58.4 ng.d/ml). However, ivermectin concentrations measured in the gastrointestinal contents were higher in lambs treated by the intraruminal route. The mean ivermectin concentrations achieved (3 days post-treatment) in the abomasal content were 143 ng/g (intraruminal) and 2.53 ng/g (subcutaneous). Ivermectin concentrations were 15-fold higher in H. contortus recovered from intraruminally treated lambs. Whereas the subcutaneous administration reduced the number of adult nematodes from 4376 to 1300, the number of adult nematodes after the treatment with ivermectin given by the intraruminal route was 206 (P<0.05). The higher ivermectin concentrations achieved in the digestive tract shortly after the intraruminal treatment may account for the observed enhanced efficacy compared to the parenteral administration against parasites of reduced susceptibility.     

Ivermectin against larval stages of Dirofilaria repens in dogs

The prophylactic efficacy of ivermectin against Dirofilaria repens infections in dogs was investigated. A first trial was carried out on 15 dogs exposed to four inoculations of L3 larvae at 15-day intervals and treated, in groups of five, with 0, 6 or 12 micrograms/kg body weight of ivermectin given per os 30 and 60 days after the first inoculation. Necropsy, performed about 9 months later, revealed that worm burdens were reduced by 86.6 and 92.8% for the 6 and 12 micrograms/kg dose levels, respectively. In a second trial with an otherwise identical protocol, a dose rate of 24 micrograms/kg of ivermectin was tested in 12 dogs. Only one of the six treated dogs was found worm free at necropsy. The worm burden was reduced by 87.9% in treated animals as opposed to controls. A lengthening of the prepatent periods, which might be considered dose related, was apparent in all treated groups. Ivermectin was not completely effective in preventing establishment of experimental infections with D. repens in dogs.     

Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3)

Ivermectin is a potent antiparasitic drug from macrocyclic lactone (ML) family, which interacts with the ABC multidrug transporter P-glycoprotein (Pgp). We studied the interactions of ivermectin with the multidrug resistance proteins (MRPs) by combining cellular and subcellular approaches. The inhibition by ivermectin of substrate transport was measured in A549 cells (calcein or 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, BCECF) and in HL60-MRP1 (calcein). Ivermectin induced calcein and BCECF retention in A549 cells (IC(50) at 1 and 2.5microM, respectively) and inhibited calcein efflux in HL60-MRP1 (IC(50)=3.8microM). The action of ivermectin on the transporters ATPase activity was followed on membranes from Sf9 cells overexpressing human Pgp, MRP1, 2 or 3. Ivermectin inhibited the Pgp, MRP1, 2 and 3 ATPase activities after stimulation by their respective activators. Ivermectin showed a rather good affinity for MRPs, mainly MRP1, in the micromolar range, although it was lower than that for Pgp. The transport of BODIPY-ivermectin was followed in cells overexpressing selectively Pgp or MRP1. In both cell lines, inhibition of the transporter activity induced intracellular retention of BODIPY-ivermectin. Our data revealed the specific interaction of ivermectin with MRP proteins, and its transport by MRP1. Although Pgp has been considered until now as the sole active transporter for this drug, the MRPs should be taken into account for the transport of ivermectin across cell membrane, modulating its disposition in addition to Pgp. This could be of importance for optimizing clinical efficacy of ML-based antiparasitic treatments. This offers fair perspectives for the use of ivermectin or non-toxic derivatives as multidrug resistance-reversing agents.     

Efficacy of ivermectin against Syphacia obvelata (Nematoda) in mice

Ivermectin was evaluated against natural and artificial pinworm (Syphacia) infections in mice. Ivermectin given in the diet for 6 days at 0.0005% was 99% effective against both immature and adult worms. A diet level of 0.0004% reduced immature and mature pinworm by 99 and 75%, respectively but 0.0001% was inactive. One oral dose of 2.0 mg/kg was 100 and 97% effective against gravid females and immature worms, respectively. A dose of 1.0 mg/kg was 96 and 66% effective against the same parasitic stages. A similar effect was observed against adult male worms where 94 and 86% were removed by one oral dose of ivermectin at 2.0 and 1.0 mg/kg, respectively.     

Ivermectin, an unconventional agonist of the glycine receptor chloride channel

The effects of the antihelmintic, ivermectin, were investigated in recombinantly expressed human alpha(1) homomeric and alpha(1)beta heteromeric glycine receptors (GlyRs). At low (0.03 microm) concentrations ivermectin potentiated the response to sub-saturating glycine concentrations, and at higher (> or =0.03 microm) concentrations it irreversibly activated both alpha(1) homomeric and alpha(1)beta heteromeric GlyRs. Relative to glycine-gated currents, ivermectin-gated currents exhibited a dramatically reduced sensitivity to inhibition by strychnine, picrotoxin, and zinc. The insensitivity to strychnine could not be explained by ivermectin preventing the access of strychnine to its binding site. Furthermore, the elimination of a known glycine- and strychnine-binding site by site-directed mutagenesis had little effect on ivermectin sensitivity, demonstrating that the ivermectin- and glycine-binding sites were not identical. Ivermectin strongly and irreversibly activated a fast-desensitizing mutant GlyR after it had been completely desensitized by a saturating concentration of glycine. Finally, a mutation known to impair dramatically the glycine signal transduction mechanism had little effect on the apparent affinity or efficacy of ivermectin. Together, these findings indicate that ivermectin activates the GlyR by a novel mechanism.     

Licking behaviour induces partial anthelmintic efficacy of ivermectin pour-on formulation in untreated cattle

Licking behaviour in cattle has been reported to account for the disposition of topically administered macrocyclic lactones. However, its impact on anthelmintic efficacy remains to be established. Therefore, we evaluated the impact of ivermectin exchange between cattle on the reduction in the faecal egg count (FEC) after pour-on administration in a group of 10 heifers experimentally infected with Ostertagia ostertagi and Cooperia oncophora. Four treated (500 μg/kg, pour-on) and six untreated animals were put together after treatment and plasma and faecal exposure to ivermectin as well as the FECs were evaluated before and over 40 days after treatment. Ivermectin was detected in plasma and faeces of the six untreated heifers, with maximal exposures two- to three-fold lower than the minimal exposures in treated animals. The interindividual variability of exposure was very high in untreated animals, with a ten-fold difference between the upper and lower limits compared with treated heifers, where there was only a two-fold difference. Anthelmintic efficacy, expressed as an average reduction of the FECs over the experimental period, was maximal in the treated group. In untreated heifers, anthelmintic efficacies ranged from zero to maximal efficacy, with intermediary values between 30% and 80%. The use of a classical pharmacodynamic model demonstrated a clear relationship between exposure and efficacy and enabled us to define the critical plasma or faecal ivermectin concentrations delimiting an exposure window associated with partial anthelmintic efficacy. This range of ivermectin plasma concentrations (0.1-1 ng/mL) could be considered as a potential selection window for anthelmintic resistance. Finally, our results show that macrocyclic lactone exchange between cattle after pour-on administration, resulting from natural grooming behaviour, can significantly impact on anthelmintic efficacy. This raises several issues such as the design of comparative clinical trials and the occurrence of partial efficacy which is considered a risk factor for the development of anthelmintic resistance.     

Field effects of faecal residues from ivermectin slow‐release boluses on the attractiveness of cattle dung to dung beetles

A 2‐year study was performed in two sites in southern France to assess the effect of ivermectin residues on the attractiveness of cattle dung to colonizing insects. Insect captures were compared between pitfall traps baited with dung from untreated cattle and dung from cattle that had been treated with a slow‐release (SR) bolus of ivermectin. Cattle dung was collected at different times after treatment (4, 14, 42, 70 and 98 days). Excretion showed a plateau, with levels ranging between 0.688 µg and 1.123 µg ivermectin per gram of wet dung. Faecal residues affected insect captures at both sites. Effects were independent of the time dung was collected after treatment, except for one result subsequent to a severe drought during the baiting period. Ivermectin‐contaminated dung showed a significant attractive effect, with increased captures regardless of the guild to which beetles belonged. This study demonstrates the attractiveness of ivermectin residues over a long period after the treatment of animals. It draws attention to the danger of widespread use of this endectocide‐based SR bolus, which is attributable to the preferential attraction of insects to treated dung, which potentially puts at risk the survival of their offspring.     

Brugia malayi and Brugia pahangi: transmission blocking activity of ivermectin and brugian filarial infections in Aedes aegypti

Brugia malayi- or Brugia pahangi-infected, microfilaremic jirds (Meriones unguiculatus) were treated with ivermectin at a single dose of 200 micrograms/kg body weight, administered subcutaneously. After different time intervals, Aedes aegypti mosquitoes were fed on treated or untreated jirds. Sausage stage, L2, and L3 larvae failed to develop in mosquitoes that fed on jirds from 15 to 30 days post-treatment. After 1 month, the numbers of L3 larvae recovered from mosquitoes fed on treated B. pahangi jirds were comparable to controls. However, the number of L3's recovered from mosquitoes fed on B. malayi jirds remained significantly lower than controls, 2 and 3 months after treatment. This reduction suggests that ivermectin may be more effective in blocking transmission of B. malayi than B. pahangi. Ivermectin treatment had no effect on the mean number of circulating microfilariae in treated jirds. Therefore, mosquitoes ingested comparable numbers of microfilariae when compared to those mosquitoes fed on untreated controls. Only in the case of jirds infected with B. malayi did the circulating microfilarial counts fall 30 days after treatment. The failure of microfilariae to develop to the L3 stage in mosquitoes fed on jirds within 30 days of treatment was not due to failure of mosquitoes to ingest microfilariae. Brugia malayi microfilariae also failed to develop to L3 in mosquitoes that were allowed to feed on microfilaremic jird blood treated with ivermectin (50 ng/ml) in vitro, indicating its efficacy at low concentrations. In addition to N-acetyl glucosamine, microfilariae obtained for a period of 15 days from ivermectin-treated but not control jirds showed D-mannose, N-acetyl galactosamine, and L-fucose moieties on the surface of the sheath.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channel

Ivermectin is an anthelmintic drug that works by activating glutamate-gated chloride channel receptors (GluClRs) in nematode parasites. GluClRs belong to the Cys-loop receptor family that also includes glycine receptor (GlyR) chloride channels. GluClRs and A288G mutant GlyRs are both activated by low nanomolar ivermectin concentrations. The crystal structure of the Caenorhabditis elegans α GluClR complexed with ivermectin has recently been published. Here, we probed ivermectin sensitivity determinants on the α1 GlyR using site-directed mutagenesis and electrophysiology. Based on a mutagenesis screen of transmembrane residues, we identified Ala288 and Pro230 as crucial sensitivity determinants. A comparison of the actions of selamectin and ivermectin suggested the benzofuran C05-OH was required for high efficacy. When taken together with docking simulations, these results supported a GlyR ivermectin binding orientation similar to that seen in the GluClR crystal structure. However, whereas the crystal structure shows that ivermectin interacts with the α GluClR via H-bonds with Leu218, Ser260, and Thr285 (α GluClR numbering), our data indicate that H-bonds with residues homologous to Ser260 and Thr285 are not important for high ivermectin sensitivity or direct agonist efficacy in A288G α1 GlyRs or three other GluClRs. Our data also suggest that van der Waals interactions between the ivermectin disaccharide and GlyR M2-M3 loop residues are unimportant for high ivermectin sensitivity. Thus, although our results corroborate the ivermectin binding orientation as revealed by the crystal structure, they demonstrate that some of the binding interactions revealed by this structure do not pertain to other highly ivermectin-sensitive Cys-loop receptors.     

Control of lone star ticks (Acari: Ixodidae) on Spanish goats and white-tailed deer with orally administered ivermectin

Ivermectin administered orally to Spanish goats, Capra hircus (L.), or to white-tailed deer, Odocoileus virginianus (Zimmerman), was highly effective against lone star ticks, Amblyomma americanum (L.). For Spanish goats, daily oral doses of 20 micrograms/kg resulted in greater than or equal to 2 ppb ivermectin in the blood. This level was sufficient to cause greater than 95% reduction of estimated larvae from feeding ticks. A bioassay with horn flies, Haematobia irritans (L.), was developed to estimate oral intake of ivermectin. Probit analysis of dose-mortality data indicated that a 50% reduction in adult horn fly emergence can be expected when the manure from goats treated orally with ivermectin at 10, 20, 35, and 50 micrograms/kg/d was mixed with untreated cow manure at a rate of 0.345, 0.110, 0.100, and 0.092%, respectively. In studies with white-tailed deer, daily oral doses of 35 and 50 micrograms/kg/d provided 100% control of adult and about 90% control of nymphs that were placed on treated fawns. A single oral dose of 50 micrograms/kg gave greater than 90% control of adult and nymphal ticks attached to treated fawns at the time of drug administration and 70% control of ticks placed on treated deer three days thereafter. When ticks were placed on fawns treated with a single dose of ivermectin (50 micrograms/kg) the engorgement period was longer, ticks were lighter in weight, and females laid fewer eggs than ticks detaching from control fawns. A single oral dose of ivermectin at 20 micrograms/kg prevented about 60% of the adult and nymphal ticks attached at the time of drug administration from engorging, but did not affect other ticks placed on the animals after treatment.     

A glycine residue essential for high ivermectin sensitivity in Cys-loop ion channel receptors

Ivermectin exerts its anthelmintic effect by activating nematode Cys-loop glutamate-gated receptors. Here we show that a glycine residue at a specific transmembrane domain location is essential for high ivermectin sensitivity in both glycine- and glutamate-gated Cys-loop receptors. We also show that ivermectin sensitivity can be conferred on an ivermectin-insensitive receptor by introducing a glycine at this position. Furthermore, comparison of amino acid sequences of ivermectin-sensitive and -resistant receptors reveals that the presence of a glycine reliably predicts ivermectin sensitivity. By providing a means of identifying ivermectin-sensitive receptors, this finding should help in characterising ivermectin-resistance mechanisms and identifying new anthelmintic targets.     

伊维菌素在环境中的降解及其对七种水生生物的急性毒性研究

伊维菌素作为一种高效的抗寄生虫兽药,在畜禽业有着广泛的应用。但药物随着畜禽动物的代谢产物的排放而进入自然生态系统也成为逐渐显现的环境问题。由于药物具有在自然环境中难以快速降解和对水生枝角类高毒性的特点,因此流入天然水体的伊维菌素存在着影响水生态平衡的风险。为了比较全面评估药物对水生动物潜在的毒害作用,研究模拟天然河道环境,对药物在底质中的降解速率进行了测定,并选取7种占据不同生态位的水生生物作为试验对象,通过关于急性毒性的国家标准试验方法来初步评价药物对水生态系统的风险。结果显示伊维菌素在自然水体中降解缓慢,在泥水混合25℃恒温条件下,70d的降解率仅为28.3%。急性毒性试验结果显示伊维菌素对发光细菌(Photobacterium)并不表现出毒性,对淡水小球藻(Chlorella vulgaris)的96h EC50=19.80 mg/L,属中毒;而对其他实验生物则表现出了较高的毒性,伊维菌素对斑马鱼(Brachydanio rerio)、食蚊鱼(Gambusia affinis)和鲫鱼鱼苗(Carassius carassius)的96h LC50分别为40.48、34.81和13.79μg/L,对罗氏沼虾(Macrobrachium rosenbergii)的96h LC50=7.87μg/L,对大型溞(Daphniamagna)的24h LC50=4.81 ng/L,均属极高毒。因此残留在天然水体的伊维菌素对水生态中的生物有较大影响,对含伊维菌素的废弃物排放进行监控和科学管理非常必要。     

Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children

Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10–15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy.     

Eradication of ear mites from naturally infested conventional research rabbits using ivermectin

Rabbits naturally infested with ear mites were treated with ivermectin injection for cattle, subcutaneously at the rate of 400 mcg/kg; which was repeated in 15 to 17 days. Rabbits treated as described and housed in a conventional vivarium environment were found to be free of mites during a subsequent 33 to 139 day observation period. Side effects were minimal and associated with occasional transient discomfort at the injection site. Ivermectin appears to be safe and effective for treating rabbits with ear mites. The prospects of eradicating mites from infested rabbit colonies using this method of treatment is promising.     

The efficacy of ivermectin against Strongyloides papillosus in cattle

The efficacy of ivermectin was evaluated against Strongyloides papillosus in four controlled trials in cattle. Thirty-four animals were inoculated subcutaneously with S. papillosus 3rd stage larvae 14-24 days before treatment. At 7-14 days after treatment, calves were slaughtered and the number of adult S. papillosus present in the small intestine counted. Faecal egg counts were carried out before and after treatment. Seventeen control animals received a single subcutaneous injection of vehicle solution at a dose volume of 1 ml/50 kg body weight, and 17 calves were treated once with ivermectin at 200 mcg/kg b.w. using a 1% injectable solution (IVOMEC Injection Merck & Co., Inc.), subcutaneously. The control animals had a mean burden of 5,913 worms, while ivermectin significantly (p less than 0.01) reduced the number of adults S. papillosus by more than 99%. There was a greater than 99% reduction in the faecal egg count of treated animals at the last faecal examination compared with that pre-treatment.     

Dynamics of Onchocerca volvulus Microfilarial Densities after Ivermectin Treatment in an Ivermectin-na?ve and a Multiply Treated Population from Cameroon

Background/Objective

Ivermectin has been the keystone of onchocerciasis control for the last 25 years. Sub-optimal responses to the drug have been reported in Ghanaian communities under long-term treatment. We assessed, in two Cameroonian foci, whether the microfilaricidal and/or embryostatic effects of ivermectin on Onchocerca volvulus have been altered after several years of drug pressure.

Methods

We compared the dynamics of O. volvulus skin microfilarial densities after ivermectin treatment in two cohorts with contrasting exposure to this drug: one received repeated treatment for 13 years whereas the other had no history of large-scale treatments (referred to as controls). Microfilarial densities were assessed 15, 80 and 180 days after ivermectin in 122 multiply treated and 127 ivermectin-naïve individuals. Comparisons were adjusted for individual factors related to microfilarial density: age and number of nodules.

Findings

Two weeks post ivermectin, microfilarial density dropped equally (98% reduction) in the ivermectin-naïve and multiply treated groups. Between 15 and 180 days post ivermectin, the proportion of individuals with skin microfilariae doubled (from 30.8% to 67.8%) in controls and quadrupled (from 19.8% to 76.9%) in multiply treated individuals but the mean densities remained low in both sites. In fact, between 15 and 80 days, the repopulation rate was significantly higher in the multiply treated individuals than in the controls but no such difference was demonstrated when extending the follow-up to 180 days. The repopulation rate by microfilariae was associated with host factors: negatively with age and positively with the number of nodules.

Conclusion

These observations may indicate that the worms from the multi-treated area recover mf productivity earlier but would be less productive than the worms from the ivermectin-naïve area between 80 and 180 days after ivermectin. Moreover, they do not support the operation of a strong cumulative effect of repeated treatments on the fecundity of female worms as previously described.     

Ivermectin and moxidectin against soil-transmitted helminth infections

Ivermectin and moxidectin, two macrocyclic lactones, are potent antiparasitic drugs currently registered and mainly used against filarial diseases; however, their potential value for improved soil-transmitted helminth (STH) control has been acknowledged. This review provides insights on recent studies evaluating the efficacy of ivermectin and moxidectin as single or coadministered therapy against human soil-transmitted helminthiases (including Strongyloides stercoralis infections) and on pharmacokinetic/pharmacodynamic parameters measured in treated populations. Furthermore, we discuss current gaps for research, highlight advantages – but also existing challenges – for uptake of ivermectin and/or moxidectin treatment schemes into routine STH control in endemic countries.     

Effect of chronic ivermectin treatment on GABA receptor function in ethanol withdrawal-seizure prone and resistant mice

Ivermectin, a potent, effective anthelmintic, is easy to administer, has a broad spectrum of action and a wide safety margin. However, no testing has been done in hosts genetically selected for seizure susceptibility which may be more sensitive to the effects of ivermectin than other animals. This was done in the present experiments with seizure prone and seizure resistant mice infested with Syphacia obvelata (pinworm). These subjects were treated daily with oral ivermectin in their drinking water every other week for six weeks, for a total of 21 days. The treatment cleared the mice of the pinworm infestation, but did not alter the seizure susceptibility or binding parameters of [3H]flunitrazepam in either of the selected lines.     

Adverse effects of ivermectin on the dung beetles, Caccobius jessoensis Harold, and rare species, Copris ochus Motschulsky and Copris acutidens Motschulsky (Coleoptera: Scarabaeidae), in Japan

Effects of the antiparasitic drug, ivermectin, on the dung beetles, Caccobius jessoensis Harold, 1867 and the rare species, Copris ochus Motschulsky, 1860 and Copris acutidens Motschulsky, 1860 were studied in laboratory and field experiments in Hokkaido, Japan. Ivermectin was detected in dung from 1 to 21 or 28 days following treatment, with a peak on the first day after treatment in two pour-on administrations (500 microg kg(-1)), although there were considerable differences between the two peaks. In C. jessoensis, brood balls constructed by the female were not reduced in the dung of treated cattle except for seven days after treatment in experiment 2. Also, there was no significant difference in the mean weight of brood balls between dung from treated and control cattle. However, the emergence rates were significantly reduced in dung 1-3 days after treatment. In the field study, brood balls constructed by C. jessoensis were more abundant in dung from treated cattle in experiment 1, but adult emergence was significantly reduced at one and seven days after treatments. Adult mortality of C. ochus Motschulsky at 90 days after the beginning of rearing was 11.1% in dung from control cattle with 22 brood balls constructed, whereas it was 84% in dung from treated cattle with no brood balls and/or ovipositioning. Also, in C. acutidens Motschulsky, adult mortality at 90 days after the beginning of rearing was 3.6% in dung from control cattle with 13 brood balls constructed, whereas it was 94.1% in dung from treated cattle with no brood balls or ovipositioning. The environmental risk in the use of ivermectin during breeding period of dung beetles in pasture is discussed.     

Effect of treatment with ivermectin on reproductive performance of yearling beef heifers

To determine the effect of treatment with ivermectin on reproductive parameters, 78 fall-born, yearling heifers were allotted to either an ivermectin treatment group or to the control, non-treatment group. The heifers were treated in June and October when they were approximately 7 and 11 mo old, respectively. Ivermectin effectively lowered fecal egg counts in the treated heifers compared with that of the controls. In heifers that were maintained on a marginal plane of nutrition, treatment with ivermectin not only improved weight gains during each recording period but also hastened the onset of puberty and improved the pregnancy rate during a 60-d breeding season. The positive effect of ivermectin on these reproductive characteristics could not be explained by increased weight gain alone, because the correlation between weight gain and puberty was not significant. Treatment with ivermectin positively affected pelvic area but not uterine score when compared with those of the controls.