Injectable Ivermectin Research Articles

Subcutaneously injected ivermectin-loaded mixed micelles: formulation, pharmacokinetics and local irritation study

Clinical application of ivermectin (IVM) is limited by several unfavorable properties, induced by its insolubility in water. Slight differences in formulation may change the plasma pharmacokinetics and efficacy. In this study, an IVM-loaded Soy phosphatidylcholine-sodium deoxycholate mixed micelles (IVM-SPC-SDC-MMs) were developed to improve its aqueous solubility, aiming to make it more applicable for clinical use. First, IVM-SPC-SDC-MMs were prepared using the co-precipitation method. After formulation optimization, the particle size was 9.46 ± 0.16 nm according to dynamic light scattering. The water solubility of IVM in SPC-SDC-MMs (4.79 ± 0.02 mg/mL) was improved by 1200-fold, comparing with free IVM (0.004 mg/mL). After subcutaneous administration, the pharmacokinetic study showed that IVM-SPC-SDC-MMs and commercially available IVM injection were bioequivalent. Also, the local irritation study confirmed that IVM-SPC-SDC-MMs reduced side reactions of the commercially available IVM injection. These results indicated that IVM-SPC-SDC-MMs represented a promising new drug formulation suitable for subcutaneous delivery of IVM.

Effect of Ivermectin on semen parameters and levels of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) enzymes in seminal plasma of Iraqi Awassi rams

The objective of this study was to evaluate the effect of Ivermectin on semen quality and estimation of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in seminal plasma. Six mature Awassi rams aged 2-3 years and weighing 38-42 Kg were used in this study. Semen collection was done weekly for five weeks from the same ram. The first two collection considered as training for the animal and discarded, the second two collection were considers for the control group. After administration of the drug (Ivermectin), semen samples were collected from the Awassi ram 1, 7,14 days. The parameter studies were included semen volume, percentage motility of sperm, sperm concentration, live sperm, and morphology percentage. Samples of seminal plasma were analyzed for the estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST). Results of this study indicate that Ivermectin leads to significant (P<0.05) decreased in semen parameters after the first semen collection. Reaction time significantly higher (P<0.05) in the treated group after 1 day of injection. Alanine aminotransferase ALT, Aspartate aminotransferase AST show no significant differences in activities in seminal plasma during the study. In conclusion: it is preferable to use the animals for the purpose of reproduction only after at least 7 days after Ivermectin injection due to it harmful effect on semen quality.

Comparative clinical competence of two commercial injectable ivermectin against caprine haemonchosis (Haemonchus contortus)

The foremost purpose of the study reported here was to perform a pharmacological evaluation of two different injectable ivermectin formulations in goats infected with haemonchosis. Twenty one (n=21) goats were randomly divided into three groups A, B and C whereas each group consisted of seven (n=7) goats. Product A and Product B were injected subcutaneously to the goat in group A and group B, respectively. Goat in group C was kept as infected control group giving any treatment. With 7th, 14th, 21th and 28th days of treatment, a significantly (P<0.01) decreased of egg per gram (EPG) count was found in treated goat of group A and B, respectively. In experimental period, the EPG count of control group C were significantly (P<0.01) increased. In group A and B reduction of mean EPG on 7th, 14 th , 21 th and 28th day after treatment were 83.9%-80.8%, 81.7%-80.7, 78.1%-77.0% and 73.7%-61.2%, respectively, whereas in control group C the mean EPG were 6.7%, 9.2%, 21.4% and 30.9%, respectively. The body weight was increased significantly (P<0.01) after treatments in group A and B, respectively except untreated control group C. To sum up, two commercial products contain ivermectin have similar clinical competence against haemonchosis in goat.

Bovine hypodermosis in indigenous cattle herd and its successful therapeutic management.

Warble fly infestation in cattle is a serious problem throughout the world. In India, it is mainly reported from northern parts of the country and is caused by the larvae of Hypoderma lineatum. The disease causes huge economic losses to animal production like milk and leather industry. The present article reports the outbreak and subsequent successful treatment of Warble fly infestation from an indigenous cattle herd. The animals were clinally examined for the presence of warbles and the larvae were collected by pressing the swellings on the back. The larvae were brought to the laboratory and were morphologically examined and morphometry was done. The animals were administered specific therapy consisting of two doses of subcutaneous injection of Ivermectin at weekly intervals. The epidemiology of the disease, its patho physiological impact on the animal and various strategies for clinical management are being described in the article.

Therapeutic Management of Psoroptes Cuniculi Infestations in Rabbit with Ivermectin

A New Zealand white rabbit was presented with clinical signs of pruritus, alopecia, white crusty lesion on the upper lip, ear pinnae, around the eye and also on the nose. Skin scrapping examination revealed the infestations of Psoroptes cuniculi mites. Subcutaneous injection of ivermectin at weekly intervals for three weeks resulted in remission of clinical signs and improvement of health condition.

Successful Treatment of Brugia pahangi in Naturally Infected Cats with Ivermectin

Lymphatic filariasis is a common parasitic disease of cats in tropical regions including Thailand. The objective of this study was to determine the efficacy of ivermectin against microfilariae of Brugia pahangi in naturally infected cats. Eight cats naturally infected with B. pahangi were divided into control (untreated) and treated groups. Cats in the latter group were given ivermectin injection at 400 µg/kg weekly for 2 months. Microfilariae were counted every week until 48 weeks. Microfilaremia was significantly decreased in the treated group 4 weeks after starting the treatment and become zero at week 9 and afterwards. On the other hand, cats in the control group had high microfilaremia throughout the study. It was successful to treat and control B. pahangi infection in naturally infected cats using ivermectin.

PGP expression in Cooperia oncophora before and after ivermectin selection

The aim of this study was to investigate genetic selection and P-glycoprotein (PGP) expression in three different isolates of Cooperia oncophora before treatment and after ivermectin (IVM) injection. Adult parasites were recovered from nine calves experimentally infected with the isolates represented by one IVM susceptible laboratory isolate, and two field isolates showing signs of phenotypic macrocyclic lactone resilience according to the faecal egg count reduction test. Five males and five females per isolate were examined both pre- and post-IVM treatment giving a total of 60 worms. A sequence from C. oncophora (Con-pgp) was identified, showing 83 % similarity to Pgp-9 of Caenorhabditis elegans. Primers specific to putative Con-pgp-9 mRNA were designed, generating a 153-bp PCR product. Total RNA was prepared from all worms, and Con-pgp-9 expression was measured by quantitative real-time reverse transcription PCR. Our results showed that mean PGP concentrations were four to five times higher in female as compared to male worms. No significant differences in gene expression between experimental groups pre- and post-IVM selection were detected. However, PGP gene expression tended to be increased by IVM treatment in male worms (p = 0.091), with 70 % higher mean expression in treated than in untreated male worms. Amplified fragment length polymorphism analysis did not demonstrate any bottleneck effect within the different isolates post-treatment. The total mean gene diversity values were 0.158 and 0.153 before and after treatment, respectively. Inbreeding coefficient in subpopulations compared to total population F ST was 0.0112, suggesting no genetic differentiation between or within the investigated isolates in relation to treatment. In conclusion, comparison of Con-pgp-9 expression showed no significant difference before and after treatment, but some tendency towards increasing expression in male worms.

OTITIS EXTERNA AND OTITIS MEDIA IN CATS IN ASSIUT: A RETROSPECTIVE STUDY OF PRESENTING SIGNS, CAUSES, DIAGNOSIS AND TREATMENT

In this study, records of cases admitted to the Small Animal Clinic (SAC), Veterinary Teaching Hospital (VTH) at Assiut University, between years 2007-2011 for investigation of signs of otitis were reviewed and data analyzed. Points of analysis comprised presenting clinical signs, results of otoscopic examination, identification of cause of otitis and outcome of treatment of each cat. Treatments used for these cases were either ivermectin injection or topical treatment with antimicrobial/anti-inflammatory ear drops as well as a ceruminolytic agent for cleansing the ear to increase effectiveness of medications used. Total number of cases with signs of otitis was 76 cats. Otitis cases comprised 19.8% of the total cases presented at the SAC in the study period. The most common presenting signs were head shaking, itching and ear wax in 67.11% of cases. 21.05% of cases were presented with severe inflammation, pain and alopecia around the ear pinna. A small number of cats were presented with signs of alopecia around the ear pinna and concomitant ring worm (3.95%). The remaining 7.89% were presented with very mild ear scratching in one or two ears. Sex was not a confounding factor as both males and females were equally represented among cases (51% males: 49% females). Turkish Angora and Persian cat breeds were over-represented (39.5% and 35.5% respectively). 68 cats were treated with ivermectin injections (1-4 injections) and ten cats were treated with topical antibacterial and anti-inflammatory. 67.11% of treated cases completely recovered and 32.89% of treated cases were not brought back for follow-up visits and therefore information regarding full recovery was not available. When evaluating a patient with otitis externa, it is important to determine the primary cause as well as the predisposing and perpetuating factors of the otitis so as to manage the otitis properly. The first diagnostic procedure that should be performed on a patient with a complaint of otitis externa is an otoscopic examination.

Clinico-biochemical and therapeutic studies on notoedric mange in pet rabbits.

Two male and two female pet rabbits of about 1year of age, naturally infested with Notoedres cuniculi were studied in the present investigation. Clinical examination revealed presence of crustaceous lesions on the head, ear pinnae, both the limbs and external genitalia. Microscopic examination of skin scrapings confirmed presence of Notoedres mange infestation. Biochemical parameters revealed altered values of total serum protein, albumin, globulin, and activities of aspartate amino transferase, alanine amino transferase and alkaline phosphatase respectively. The affected rabbits were treated with two injections of Ivermectin (400μg/kg, subcutaneously, at interval of 15days) along with supportive therapy. This treatment showed appreciable improvement in clinical signs and restoration in biochemical parameters.

Three cases of Parafilaria bovicola infection in Belgium, and a few recent epidemiological observations on this emergent disease

Parafilariosis is a vectorborne parasitic disease caused by the development of the nematode Parafilaria bovicola in the subcutaneous and intermuscular connective tissues of cattle. On February 28, 2012, the so-called...

Three cases of Parafilaria bovicola infection in Belgium, and a few recent epidemiological observations on this emergent disease

Parafilariosis is a vectorborne parasitic disease caused by the development of the nematode Parafilaria bovicola in the subcutaneous and intermuscular connective tissues of cattle. On February 28, 2012, the so-called...

Canine ocular thelaziosis caused by Thelazia callipaeda in Portugal

Ocular thelaziosis caused by Thelazia callipaeda is a vector-borne disease affecting dogs and humans. We report a case of thelaziosis in a 10-year-old German Shepherd dog from Vila Real city (Portugal). Ophthalmological examination revealed bulbar and nictitating membrane conjunctival hyperemia with serous discharge noted at the left medial canthus and blepharitis. Schirmer tear test value and intraocular pressure were within the reference ranges in both eyes, and biomicroscopy showed a transparent cornea without lesions or edema and no inflammatory reaction in the anterior chamber. No funduscopic alterations were detected by direct and indirect ophthalmoscopic examination. When testing the nasolacrimal patency, two white worms were observed on the caruncle conjunctival surface with undulating movements that increased with light intensity. In total, eight worms were collected and morphologically identified as T. callipaeda (seven mature females and one male). PCR amplification of a 689 sequence of partial cytochrome c oxidase subunit 1 target gene confirmed the nematodes were T. callipaeda, haplotype 1. The dog was treated with a single subcutaneous injection of ivermectin combined with additional topical application of ophthalmic fusidic acid drops and oral milbemycin oxime. One week after treatment, no worms were detected and the ocular clinical signs resolved. The most recent reports of canine thelaziosis in the Iberian Peninsula should alert local health authorities to the zoonotic potential of infestation with T. callipaeda, which should be included in the differential diagnosis of conjunctivitis in dogs and humans.

Comparison of efficacy, safety, and convenience of selamectin versus ivermectin for treatment of Trixacarus caviae mange in pet guinea pigs (Cavia porcellus)

To determine the efficacy and safety of topical administration of selamectin and to compare selamectin treatment with a common ivermectin protocol for the treatment of natural infestation with Trixacarus caviae in pet guinea pigs. Clinical trial. 17 mixed-breed pet guinea pigs with active mite infestation. Guinea pigs were randomly allocated to receive a single dose of selamectin topically (15 mg/kg [6.8 mg/lb]) or ivermectin (400 μg/kg [181.8 μg/lb], SC) every 10 days for 4 injections. Microscopic examination of skin scrapings from all animals was performed at 10-day intervals for 60 days, and the presence of mites or mite eggs was recorded. The efficacies of the 2 treatment protocols were compared at every time point. Pruritus resolved by day 10 in all animals. Animals were microscopically mite-free on days 30 and 40 in the selamectin and ivermectin treatment groups, respectively, but groups did not differ significantly in regard to the number of mite-positive animals at any timepoint. Recurrence of infection was not noted in either treatment group. No adverse reactions were observed in any of the treated animals. Results suggested that a single topical application of selamectin at a dose of 15 mg/kg or repeated SC injection of ivermectin at a dose of 400 μg/kg can eliminate T caviae mites from guinea pigs within 30 and 40 days, respectively. Although effectiveness did not significantly differ between the 2 treatments, the convenience associated with the single topical dose of selamectin made it a preferable treatment modality for both patients and owners.

Sarcoptic mange and cheetah conservation in Masai Mara (Kenya): epidemiological study in a wildlife/livestock system

The sanitary control of threatened wild animals is of pivotal interest for their conservation. This task, however, is highly complex in wildlife/livestock systems. In this paper we report findings from a 2-year cross-sectional study of the epidemiology and attempted control of a Sarcoptes mite infestation in the threatened cheetah population in Masai Mara (Kenya), and discuss its interaction with sympatric wild (lion, wildebeest and Thomson's gazelle) and domestic (dog, cattle and sheep) animals. Sarcoptes scabiei was isolated from cheetahs, Thomson's gazelles, wildebeests, lions, cattle, goats and dogs; Psoroptes ovis, on the other hand, was only isolated from sheep. The prevalence study revealed 12·77% infection rates in cheetahs, 4·7% in dogs, 0·8% in Thomson's gazelles, 0·8% in sheep, 0·09% in cattle, and 0·09% in goats, while it opportunistically affected lions and wildebeest. Our study revealed that prevalence of Sarcoptes mite in cheetah population was not associated with the studied geographical blocks, animal sex or the presence of affected domestic animals. Cheetah infection with S. scabiei was associated with the climatic conditions (dry more than wet season) and the balancing between the total number of Thomson's gazelles and the prevalence of infected individuals. Apparently the high prevalence of mangy gazelles has a negative effect on cheetah; this negative effect was reduced when the number of healthy gazelles was increased. Treatment with injectable ivermectin of the clinically affected wild and domestic animals during the first year of this study was associated with much lower incidence of sarcoptic mange during the second year.

Evaluation of the Egg Hatch Assay and the Larval Migration Inhibition Assay to detect anthelmintic resistance in cattle parasitic nematodes on farms

Resistance to anthelmintic drugs, particularly to the widely used benzimidazoles (BZs) and macrocyclic lactones (MLs) is an increasing problem in cattle industries worldwide. Reliable methods for the assessment of anthelmintic efficacy in the field are required in order to react before resistance becomes an obvious problem on individual properties. The ability of the Egg Hatch Assay (EHA) and the Larval Migration Inhibition Assay (LMIA) to detect anthelmintic resistance under field conditions was evaluated on cattle farms in Northern Germany. As published previously Faecal Egg Count Reduction Test (FECRT) was performed using oral albendazole (Valbazen®) or injectable ivermectin (Ivomec®). Herein the FECRT results described earlier were compared with data from EHAs or LMIAs, respectively, performed with eggs from fresh faeces or larvae from faecal cultures of the tested animals before and after treatment. The obtained EC50 values allowed the assessment of efficacy of albendazole and ivermectin on farm level. The results of the FECRTs and the results of both in vitro assays were comparable. In comparison to the FECRT the in vitro assays are less time, labour and cost intensive and are able to assess the susceptibility status of a worm population without treatment. Therefore both are beneficial alternatives for the reliable detection of reduced efficacy of these two drug classes on farms.

Evaluation of generic injectable ivermectin for control of nematodiasis in feedlot heifers

Nematode parasitism of feedlot cattle has received very little research attention. It is assumed that anthelmintics administered at feedlot entry are effective and that feedlot conditions preclude post-treatment infection by helminths. Given the paucity of information about feedlot nematodiasis, the current research project was conducted. During October of 2010, 104 animals were selected at random from approximately 1600 beef heifers received at one feedlot in California and penned as a group. Of those, 96 were administered a generic, injectable formulation of ivermectin at label dose, while the remaining eight animals were left as untreated controls. Controls and eight randomly selected treated animals were necropsied for parasite quantifications at eight weeks post-treatment. At the end of the feeding period (approximately 135 days post-treatment), parasite quantifications were performed on nine animals selected at random from the remaining 88 animals. Fecal samples were periodically collected from cattle in the feedlot during the study. As evidenced by reductions in both fecal egg count and parasite quantifications at necropsy, a lack of drug efficacy was apparent for Cooperia and Ostertagia, and suspect for Haemonchus infections.

Dermatofitozisli Sığırlarda İvermektinin Klinik Etkinliği

Summary In the present study, clinical effectiveness of ivermectin on bovine dermatophytosis was evaluated. The material of the study consisted of 30 cattle, 20 experimental (Group I) and 10 control (Group II) animals aged between 3-14 months, diagnosed as dermatophytosis following clinical examination and microbiology. Clinical status of cases were scored on localization, size and number of lesions and condition of the cases were as follows mild (+), moderate (++) and severe (+++). During the study period, farm management practices of the animals were not changed. A single long acting injection of ivermectin at a dose of 0.2 mg/kg was subcutaneously administered to the animals in Group I. Animals in Group II served as a control and received no treatment. Following medical treatment and 45 days of observation period, recovery was recorded 18 animals from Group I (90%). No recovery was observed in the Group II. This study indicated that, ivermectin which is widely used as antiparasiter medicine, activate the immune system. For this reason, in the present study, first time, ivermectin was used in the treatment of dermatophytosis in ruminants with a 90% of recovery rate. These findings show that ivermectin can be used succesfully in the treatment of dermatophytosis infection in cattle.

Characterization of a multidrug resistant Teladorsagia circumcincta isolate from Spain

The aim of this work was to know the anthelmintic resistance (AR) status of a Spanish sheep flock infected by gastrointestinal nematodes (GIN) and the possible cross resistance among anthelmintics of the macrocyclic lactones (ML) family. The Faecal Egg Count Reduction Test (FECRT) was carried out to check the efficacy of albendazole (Zodalben®), levamisole (LEV) (Endex®) and an oral formulation of ivermectin (IVM) (Oramec®), at the recommended dose rates. Then, the study was extended to check the cross resistance between drugs of the ML family: injectable IVM (Ivomec®), oral moxidectin (Cydectin®), injectable moxidectin (Biodectin®) and doramectin (Dectomax®), at the recommended dose rates. The GIN species were identified after faecal cultures in all groups. The FECRT showed the resistance of a Teladorsagia circumcincta isolate against LEV (39-58%), IVM (88-92%) and doramectin (85%). This study is the first report to confirm the side resistance between these MLs, which belong to the avermectin chemical group, in a Spanish sheep flock. The in vitro efficacy of LEV and IVM was measured by the Larval Feeding Inhibition Assay (LFIA) using the IC(50) measurement (concentration needed to inhibit the ingestion of 50% L1). The values of the multidrug resistant isolate were 0.25 μg/ml for LEV and 3 ng/ml for IVM. Both results were higher than the values obtained with a susceptible isolate, which could be indicative of AR. However, further research examining the response of a greater range of susceptible and resistant nematodes isolates should be carried out to establish a discrimination threshold.

Cutaneous periocular Habronema infection in a dromedary camel (Camelus dromedarius)

A 6-year-old castrated dromedary camel (Camelus dromedarius) presented with a non-healing, severely pruritic, ulcerative fibrotic plaque located at the medial canthus. Histological examination of surgical biopsies identified degenerating nematode larvae within eosinophilic granulomas. Treatment involved repeated debridement of the lesion, injectable ivermectin and anti-inflammatory therapies, and injectable and topical antibiotics. A specially constructed mask with goggles to prevent the camel from continuing to self-traumatize the eye and lesion was also placed. Full recovery occurred approximately 1 month after diagnosis. Because of the location of the lesion, time of year, the gross and microscopic characteristics of the lesion, the presence of a likely nematode larva and the response to treatment, a diagnosis of cutaneous habronemiasis was made.

The influence of parasites on faecal glucocorticoid metabolite levels in raccoons: an experimental assessment in a natural setting

Parasites and glucocorticoid hormones interact and affect a variety of processes within vertebrates, such as immune system function and reproduction. The nature of the relationship between parasite infection and glucocorticoid levels has received relatively little attention among free-ranging animals and results of experimental research in natural settings are equivocal. We conducted a parasite-reduction experiment to determine if reductions in nematodes or ectoparasites affect levels of faecal glucocorticoid metabolites (FGM) in adult raccoons. Individual raccoons were randomly assigned to a parasite-reduction treatment (ivermectin injection and Frontline Plus® application) or control group (saline injection) and recaptured within 30 days to assess treatment-related differences in parasitism and FGM levels. Treated animals had reduced nematode and ectoparasite communities. The most common and energetically expensive ectoparasite of raccoons in the region, the American dog tick, was reduced five-fold from an average of 19.3 ± 2.5 (se) to 3.4 ± 8 ticks per animal, and was unable to feed to repletion on treated animals. The prevalence of four out of seven nematode species was significantly lower in treated versus control animals; prevalence of these four nematodes ranged from 0 to 19% among treated animals and from 21 to 55% among control animals. The parasite infracommunity was also significantly reduced; the average number of nematode species per individual was 2.5 ± 0.3 in treated animals and 1.1 ± 0.2 in control animals, and the average number of ectoparasite species per individual was 2.3 ± 0.1 on treated animals and 1.1 ± 0.12 on control animals. No differences in FGM values were observed within individuals or between treatment and control groups following parasite-reduction treatments, indicating that the observed reductions in nematodes and ectoparasites had no effect on FGM levels of raccoons across the time frame of this study.