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PubMed1989

Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of collie dogs following administration of ivermectin.

Twelve adult Collie dogs were studied to determine the effects of ivermectin on neurotransmitter metabolites released from the brain into the cerebrospinal fluid (CSF) and on CSF pressure. Ten of the 12 Collies were given ivermectin orally at a concentration of 200 micrograms/kg body weight. Three of these 10 Collies showed clinical signs of ivermectin-induced toxicosis which progressed into a state of unresponsive recumbency in 2 dogs. Cerebrospinal fluid pressures and neurotransmitter metabolite concentrations in cisterna magna CSF were analysed 49 to 50 hours after administration of ivermectin in 6 of the 10 treated dogs, and in the 2 untreated control Collies. Cerebrospinal fluid pressures were within normal limits in all dogs. However, compared to the CSF concentrations in the 2 untreated and 3 non-reactive Collies, the 2 ivermectin-reactive Collies still in recumbency had elevated CSF concentrations of homovanillic acid (HVA), a metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin. These findings suggest an association between altered neurotransmission and severe ivermectin-induced neurological abnormalities. No evidence of elevated intracranial pressure was found.

Animals↗
PubMed1989

In-vivo effects of ivermectin on Rhipicephalus appendiculatus: the influence of tick feeding patterns and drug pharmacokinetics.

Sublethal effects seen amongst Rhipicephalus appendiculatus feeding on ivermectin-treated rabbits were diverse and dependent both on drug dose, pharmacokinetics and tick feeding patterns: changes in drug formulation, the time of infestation relative to treatment, and the tick instar used, profoundly influenced acaricidal activity. Death was a sequel to paralysis only if tick feeding was interrupted for sufficient time to produce irreversible dehydration. Concurrent pharmacokinetic investigations revealed that, for the larvae of R. appendiculatus, the mean critical lethal dose of ivermectin imbibed over a 5-day engorgement period was 3500 micrograms/kg. This quantity of ivermectin was achieved in the blood-meals of larvae feeding on rabbits treated subcutaneously with a single dose of Ivomec injection (MSD)* greater than or equal to 800 micrograms/kg, provided infestation took place within 24 h of treatment. At lower drug doses, or if larval infestations were delayed for greater than 24 h post-treatment, the quantity of circulating ivermectin (and thus imbibed by the tick larvae) fell below 3500 micrograms/kg and an increasing percentage of larvae successfully engorged and detached. More than 90% of such larvae moulted to the nymphal stage. Nymphae and larvae exhibited similar susceptibility to ivermectin on treated rabbits which could be explained by similar feeding patterns. However, adult female and male ticks were markedly less susceptible and interpretation of ivermectin-induced effects was more complex.

Animals↗
PubMed1992

The effect of protein binding on ivermectin uptake by bovine brain microvessel endothelial cells.

The effect of albumin binding on ivermectin uptake and transfer across the endothelial component of the blood-brain barrier (BBB) was determined with an in vitro model comprised of bovine brain microvessel endothelial cell (BMEC) monolayers. Cellular uptake of ivermectin was limited in the absence of albumin and 90% inhibited in the presence of 10% albumin. Cell membrane association of ivermectin, as followed by fluorescent probe labelling, was observed only at high (micromolar) concentrations of the drug. Membrane association was about 75% inhibited in the presence of albumin. Similarly, transfer across BMEC monolayers was restricted, equivalent to that of BBB impermeant markers. Unlike the uptake studies, however, albumin had little effect on the transfer of ivermectin across BMEC monolayers. These results support recent in vivo findings on the distribution of ivermectin into the brain and suggest that ivermectin has only a limited affinity for the endothelial component of the normal BBB.

Animals↗
PubMed1996

Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus.

OBJECTIVE: To determine the distribution of ivermectin in plasma and tissues of onchocerciasis patients following a single oral dose of 150 micrograms kg-1. SETTING: Medical Department at Soba University Hospital, Khartoum. PATIENTS: Twenty five patients and fourteen healthy volunteers. METHODS: Serial blood samples were obtained from both groups. Tissue samples were removed from various patients as full thickness skin punch biopsies or during nodulectomy. Ivermectin concentration was determined by radioimmunoassay. RESULTS: The plasma pharmacokinetic variables for patients were; maximum plasma concentration 52.0 ng ml-1; time to achieve maximum concentration, 5.2 h.; elimination half life, 35.0 h; and the area under the plasma concentration curve versus time, 2852 ng.h.ml-1. In healthy volunteers, the plasma ivermectin distribution was similar to that in patients, and both groups showed a tendency for a second rise in plasma concentration of the drug suggestive of enterohepatic recirculation. Ivermectin was detected in tissues obtained from patients. Fat showed the highest and most persistent levels, whilst values for skin, nodular tissues, and worms were comparable. Subcutaneous fascia contained the lowest concentrations. CONCLUSIONS: Infection with O. volvulus does not affect the pharmacokinetics of ivermectin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of depot formation in fat tissue.

Adipose Tissue↗
PubMed2002

Community response to repeated annual ivermectin treatment of onchocerciasis in Nigeria.

The evaluation of repeated annual treatment with ivermectin in onchocerciasis-endemic communities using output indicators such as acceptance rate (AR) and community compliance rate (CCR) are invaluable tools for assessing community response to onchocerciasis control measures. These indicators were employed in evaluating the responses to annual ivermectin treatment in ten communities in Lade District, Kwara State, Nigeria, where annual ivermectin treatment had reached the fourth round in 1995. The mean AR in all of the communities at the first round of treatment (Tx1) was 95.18% while the mean for Tx1-Tx4 varied between the communities and ranged from 62.82% to 98.49%. The CCR also differed between the communities and ranged from 38.56% to 96.97%. Adverse reactions to ivermectin treatment at Tx1 brought about non-compliance in Lile (CCR of 38.46%), one of the communities studied. AR in Lile also decreased from 94.87% at Tx1 to 61.54% at Tx2, 53.85% at Tx3 and 41.03% at Tx4. (The commencement of community mobilization in defaulting communities after Tx4 restored the acceptance at the next round of annual treatment. The drop in participation in Lile due to adverse reactions would have been averted if annual ivermectin treatment were properly monitored. This study advocates the need for the continuous monitoring and evaluation of onchocerciasis-endemic communities currently receiving treatment, especially in the implementation of the Community-Directed Treatment with Ivermectin (CDTI) programme, so that feedback from the communities can permit proper intervention if necessary.

Anthelmintics↗
PubMed2004

Efficacy of ivermectin in calves against a resistant Cooperia oncophora field isolate.

Since 1999, two Cooperia oncophora isolates, originally obtained from the United Kingdom, have been maintained by regular passage through calves at the Macdonald Campus, McGill University farm. One isolate, IVS, was originally susceptible to ivermectin, while the IVR isolate was originally resistant to ivermectin. These two isolates have been used to study the mechanisms of ivermectin resistance. To confirm the susceptible/resistant status after 4 years of passaging through calves, a controlled study was performed in which two worm-free calves were experimentally infected with IVS and another two worm-free calves with the IVR infective larvae. The calves were treated with ivermectin (0.2 mg/kg) subcutaneously (Ivomec Injection) 21 days after infection. Ivermectin at the recommended dose was 100% effective at eliminating the IVS isolate, since no eggs were found in feces, and no adult worms were found in the small intestine of the treated IVS-infected calf. In contrast, the IVR-infected calf continued to pass eggs in feces even after treatment with ivermectin, and adult worms (250) were found in the small intestine at necropsy. The untreated calves had 1,330 and 848 adult worms, respectively, for the IVS and IVR infected animals.

Animals↗
PubMedDate not supplied

A community trial of ivermectin for onchocerciasis in Sierra Leone: clinical and parasitological responses to the initial dose.

A double-blind placebo-controlled trial of ivermectin was started in 1987 in 6 villages in southern Sierra Leone. 1625 villagers, 93% of the total population, were surveyed before treatment and allocated at random to the trial. Onchocerciasis was hyperendemic and of moderate intensity in the area. Typical onchocerciasis skin lesions were seen in most cases; the blindness rate was 1.5% and a further 4.3% had visual impairment. Six months after treatment 988 subjects (80%) were reassessed and microfilarial loads in the ivermectin group were found to be 10% of control levels. Additionally, blood eosinophil concentrations were reduced by one-quarter. The severity, but not the prevalence, of skin lesions was significantly reduced in the ivermectin group, with a particularly marked effect on papular eruptions. There had been no reduction in the prevalence of itching, nor had markers of general health shown improvement after ivermectin. Ivermectin is an effective microfilaricidal agent and may improve Onchocerca-related skin lesions after a single dose. However, the lack of obvious benefit to a target population after the first dose of ivermectin may reduce compliance with subsequent doses. This has implications for planned mass treatment initiatives in onchocerciasis endemic regions.

Animals↗
PubMedDate not supplied

Ivermectin does not reduce the burden of itching in an onchocerciasis endemic community.

Degrees of itching were estimated before and for 6 months after a fourth dose of ivermectin or placebo was given to 97 subjects in Sierra Leone. There was no reduction in itching attributable to ivermectin at any stage, but there were non-significant increases in the prevalence, severity and localization of itching within the first 2 months after ivermectin compared to placebo. We also found that cell-mediated immune responses to Onchocerca volvulus were significantly increased 4 weeks after a single dose of ivermectin compared to before treatment. A temporary reversal of the state of immunosuppression in people with onchocerciasis may counterbalance the reduction in skin microfilarial loads following ivermectin, with no consequent reduction in itching. The lack of effect of ivermectin on itching, a major symptom of onchocerciasis, while disappointing, need not detract from the success of mass distribution programmes.

Adolescent↗
PubMedDate not supplied

Treatment of Strongyloides stercoralis infection with ivermectin compared with albendazole: results of an open study of 60 cases.

Ivermectin is highly effective against animal intestinal nematodes and is used in the treatment of onchocerciasis in humans. A study was undertaken to compare the efficacy of the drug with that of albendazole in the treatment of uncomplicated strongyloidiasis. Sixty patients with confirmed Strongyloides stercoralis infection were enrolled in an open randomized study and given either albendazole, 400 mg/d for 3 d or ivermectin, 150-200 micrograms/kg in a single dose. Efficacy and tolerance were evaluated on days 7, 30 and 90. Each visit included a parasitological examination of 3 stool specimens, using saline and Kato smears and formalin-ether and Baermann concentrations. Fifty-three patients were eligible for evaluation. Parasitological cure was obtained in 24 of the 29 patients treated with ivermectin (83%) and in 9 of the 24 patients who were given albendazole (38%); ivermectin was significantly more effective than albendazole (P < 0.01). Clinical and biological adverse reactions were negligible in both treatment groups. The 20 patients who failed therapy were given a second treatment course with 150-200 micrograms/kg of ivermectin in a single dose or on 2 consecutive days. Sixteen patients were cured and the other 4 had only incomplete follow-up. Ivermectin therefore constitutes an acceptable therapeutic alternative for uncomplicated strongyloidiasis.

Adolescent↗
PubMed1989

Effects of ivermectin on reproduction and neonatal toxicity in rats.

In this study we describe the effects of ivermectin (MK-0933) on the reproduction and neonatal toxicity of several generations of rats. Ivermectin was administered orally at dose levels of 0.05, 0.1, 0.2, 0.4, 1.2 or 3.6 mg/kg body weight/day. An increase in postnatal pup mortality up to approximately day 10 post-partum and a decrease in pup weights in the surviving offspring compared with those of the control groups indicated that ivermectin was toxic to neonatal rats at doses as low as 0.4 mg/kg body weight/day. Cross-fostering of the rats indicated that the neonatal toxicity was related not to in utero exposure but to postnatal exposure through maternal milk. Subsequent studies with tritiated ivermectin administered orally to rats showed that levels of radioactivity in maternal milk were 3-4-fold higher than those in the plasma, which resulted in significantly higher levels of ivermectin in the brain and plasma of nursing offspring. The period of enhanced neonatal sensitivity (up to approximately day 10 post-partum) correlates with increases in the plasma-brain ratios of total radioactivity in offspring from approximately 1 on day 4 post-partum to approximately 3 on day 10 post-partum. This is consistent with the postnatal formation of the blood-brain barrier in the species. In other mammalian species, including humans, sheep and rabbits, the blood-brain barrier is formed pre-natally. Therefore, the neonatal toxicity of ivermectin in rats is probably the result of a combination of excessive exposure through maternal milk and the increased permeability of the blood-brain barrier during the early postnatal period in this species.

Animals↗
PubMed1991

Performance of pigs with mixed nematode infections before and after ivermectin treatment.

Ninety crossbred parasitized pigs were used in two controlled experiments to compare performance before and after ivermectin treatment. Four groups of 15 pigs were sequentially infected with 2000 Ascaris suum, 10,000 Oesophagostomum spp. and 10,000 Strongyloides ransomi beginning at average pig weights of either 38 kg (Experiment I) or 14 kg (Experiment II). Two infected groups of pigs were treated with ivermectin on Day 34 (Experiment I) or 37 (Experiment II) of the experiments and all pigs were fed to slaughter weights of approximately 100 kg. Average daily gain (ADG) of heavier ivermectin-treated pigs was greater than that of infected non-treated pigs (P less than 0.03) and feed conversion was numerically greater by 5% (P greater than 0.10). ADG was not different between lighter treated or non-treated pigs, but feed conversion was numerically 4% greater in ivermectin-treated compared to non-treated pigs (P greater than 0.10). No differences existed in carcass dressing percentage among the three groups of heavier pigs, but among the lighter groups ivermectin-treated pigs had a higher dressing percentage (P less than 0.03) than infected non-treated or control pigs. Results of the calculation of production costs based on combined data from the two experiments for the post-treatment period, including feed, drug and maintenance costs, indicate that the production cost for ivermectin-treated pigs was $1.53 per pig less than that for infected non-treated pigs when the cost for each group to attain control pig weights is compared with the actual cost for control pigs.

Animals↗
PubMed1992

Efficacy of moxidectin against an ivermectin-resistant strain of Haemonchus contortus in sheep.

The efficacy of moxidectin was determined against ivermectin-susceptible and resistant strains of Haemonchus contortus. At the onset of the trial, 40 lambs were each infected with 5000 third stage larvae of one of two strains of Haemonchus contortus. The lambs were randomly sorted into eight treatment groups 28 days post-infection and were treated as follows: Group 1, susceptible strain with no treatment; Group 2, resistant strain with no treatment; Group 3, susceptible strain treated with 0.2 mg moxidectin kg-1 body weight; Group 4, resistant strain treated with 0.2 mg moxidectin kg-1; Group 5, resistant strain treated with 0.4 mg moxidectin kg-1; Group 6, susceptible strain treated with 0.2 mg ivermectin kg-1; Group 7, resistant strain treated with 0.4 mg ivermectin kg-1; Group 8, resistant strain treated with 0.8 mg ivermectin kg-1. The lambs were killed 1 week post-treatment. Comparisons were made among groups based on the number of eggs per gram of feces on the day of treatment and the numbers of worms recovered from each lamb. Both moxidectin and ivermectin were effective in removing susceptible Haemonchus with efficacies of 100% and 99.7%, respectively. The efficacy of moxidectin against the resistant strain was 99.9% and 100% at 0.2 mg kg-1 and 0.4 mg kg-1, respectively, whereas there were only 38.8% and 53.1% efficacies in the lambs treated with 0.4 mg ivermectin kg-1 and 0.8 mg kg-1 body weight, respectively.

Animals↗
PubMed1992

Isoenzyme analysis of Haemonchus contortus resistant or susceptible to ivermectin.

Three different strains of Haemonchus contortus (susceptible to ivermectin, S-IVM; selected for resistance to ivermectin, R-IVM; a multiple resistant strain, i.e. resistant to benzimidazole and ivermectin, R-IVM/SA) were examined for isoenzyme variation by starch gel electrophoresis. Using stains for seven enzymes separated in five different buffer systems, no differences in the electrophoretic mobility could be detected between any of the strains. Results demonstrate a low level of enzyme variation in H. contortus and no differences in enzyme electrophoretic profile between IVM-sensitive and IVM-resistant parasites. Differences between the ivermectin-sensitive and both ivermectin-resistant strains were observed with the propionyl esterases and although some of the differences are probably associated with benzimidazole resistance, others are associated with resistance to ivermectin. The three strains of H. contortus are generally identical; however, differences between all strains of H. contortus and a strain of Dictyocaulus viviparus were detected.

Animals↗
PubMed1995

Control of Sarcoptes scabiei var. suis with ivermectin: influence on scratching behaviour of fattening pigs and occurrence of dermatitis at slaughter.

The behaviour of fattening pigs, the occurrence of erythematous papular dermatitis in pigs at slaughter and the effects of treatment for mange with ivermectin at the start of the fattening period were evaluated at ten farms. At each farm, trial pigs were randomly allotted to a control or a treated group. At the start of the trial, the control group was injected intramuscularly with 5 mg kg-1 levamisole, and the treated group was injected subcutaneously with 300 micrograms kg-1 ivermectin. Skin scrapings, taken from each pig before medication at the start of the trial, and at slaughter, were examined for presence of sarcoptic mites. Pig behaviour was monitored at 2 week intervals from Week 5 to Week 13 of the trial. Carcasses of trial pigs were inspected for dermatitis at slaughter. Low to moderate Sarcoptes scabiei var. suis infestations were demonstrated at the start of the trial on five farms (S+ farms). At slaughter, the mean percentage of Sarcoptes-positive pigs per pen on S+ farms was 34.8% (range 11-60%) for the control group as compared with 0.5% (range 0-2.7%) for the ivermectin-treated group (P < 0.01). No S. scabiei was recovered from any pig at any time from the five other farms (mange-free (S-) farms). The low initial levels of mange in the controls at S+ farms resulted in a consistently high scratching index. Ivermectin treatment resulted in a significantly (P < 0.01) lower prevalence of scratching, comparable with the prevalence observed at S- farms. High prevalences of generalized dermatitis at slaughter were observed in control pigs from all S+ farms. Ivermectin treatment resulted in much lower prevalences, reflected in a significantly (P < 0.01) lower grand mean dermatitis index per pen for this group as compared with the controls. The majority of pigs from both treatment groups at all S- farms were free of papular lesions. These results indicate that low levels of sarcoptic mange at the start of fattening, left untreated, will result in a high prevalence of scratching during the fattening period and high prevalences of Sarcoptes and dermatitis at slaughter. Treatment with ivermectin at the start of fattening results in behaviour and dermatitis prevalences similar to those observed in mange-free herds.

Animal Husbandry↗
PubMed1994

Comparative efficacy of moxidectin and ivermectin against hypobiotic and encysted cyathostomes and other equine parasites.

Efficacies of moxidectin and ivermectin were compared in four groups of eight ponies with natural parasite infections: placebo (Control), oral moxidectin gel at 0.3 mg kg-1 of body weight (Mox 0.3), oral moxidectin gel at 0.4 mg kg-1 of body weight (Mox 0.4), and oral ivermectin paste at 0.2 mg kg-1 of body weight (Ivermectin). Fecal samples were taken 0 and 2 weeks after treatment. Animals were necropsied and worms were collected 2 weeks after treatment. Moxidectin and ivermectin showed similar efficacy (99%) against adult cyathostomes, Strongylus spp., Triodontophorus spp. and Habronema muscae. Both drugs were also more than 98% effective against luminal cyathostome and Oxyuris equi fourth stage larvae (L4). Neither drug was effective (0-10.1%) against hypobiotic early third stage cyathostome larvae (EL3). Moxidectin was moderately effective (62.6-79.1%) in removing encysted cyathostome late third stage larvae (LL3) and L4, whereas ivermectin was ineffective (0%) against these stages. By contrast, ivermectin was 95.4% effective against Gasterophilus spp. third instar stage, whereas moxidectin was only 0-20.4% effective.

Animals↗
PubMed2004

Endectocide exchanges between grazing cattle after pour-on administration of doramectin, ivermectin and moxidectin.

Self-licking behaviour in cattle has recently been identified as a determinant of the kinetic disposition of topically-administered ivermectin. In the present study, we document the occurrence and extent of transfer between cattle of three topically-administered endectocides, as a consequence of allo-licking. Four groups of two Holstein cows each received one pour-on formulation of doramectin, ivermectin, or moxidectin, or no treatment. The cows were then kept together in a paddock. Systemic exposure to each topically-administered endectocide was observed in at least five of six non-treated cattle. Plasma and faecal drug concentration profiles in non-treated animals were highly variable between animals and within an animal, and sometimes attained those observed in treated animals. Drug exchanges were quantified by measuring plasma and faecal clearances after simultaneous i.v. administration of the three drugs as a cocktail. Plasma clearances were 185+/-43, 347+/-77 and 636+/-130ml/kg/day, faecal clearances representing 75+/-26, 28+/-13, and 39+/-30% of the plasma clearance for doramectin, ivermectin and moxidectin, respectively. The amount of drug ingested by non-treated cattle attained 1.3-21.3% (doramectin), 1.3-16.1% (ivermectin), 2.4-10.6% (moxidectin) of a pour-on dose (500 microg/kg). The total amount of drug ingested by all non-treated cattle represented 29% (doramectin), 19% (ivermectin), and 8.6% (moxidectin) of the total amount of each drug poured on the backs of treated animals. The cumulative amounts of endectocide ingested by each non-treated cow ranged from 1.3 to 27.4% of a pour-on dose. Oral bioavailability after drug ingestion due to allo-licking was 13.5+/-9.4, 17.5+/-3.5 and 26.1+/-11.1% for doramectin, ivermectin and moxidectin, respectively. The extent of drug exchange demonstrated here raises concerns for drug efficacy and safety, emergence of drug resistance, presence of unexpectedly high residue levels in treated and/or untreated animals and high environmental burdens. Moreover, scientific and regulatory aspects of clinical and bioequivalence trials for topical drug administration in cattle should be explored.

Administration, Oral↗
PubMed2003

Efficacy of injectable and pour-on microdose ivermectin in the treatment of goat warble fly infestation by Przhevalskiana silenus (Diptera, Oestridae).

The prophylactic efficacy of microdoses of injectable and pour-on ivermectin formulations against larval stages of Przhevalskiana silenus was assessed in naturally infected goats in the region of Calabria (southern Italy).Sixty-eight goats from two goat farms were divided into five groups: one group remained untreated, while the other four groups were treated with microdoses of ivermectin (5 and 10 microg/kg injectable formulation and 10 and 20 microg/kg pour-on formulation). The microdoses of ivermectin were fully effective in the treatment of goat warble fly infestation (GWFI) as no larvae emerged from the warbles in the treated groups, while all the larvae emerged in the control groups. Irrespective of the type of formulation used, the difference between the treated groups and the control group was statistically significant (P< 0.001). By contrast, no statistical differences were found between the goats treated with the injectable formulation and those receiving the pour-on applications, and between the two doses of the injectable and pour-on formulations used. Given the plasma concentrations it attains at its lowest dose (0.052 - 0.042 ng/ml for the injectable formulation and 0.030 ng/ml for the pour-on) the injectable formulation seems to offer the most reliable route for the administration of ivermectin microdoses and it is acceptable for milk consumption. The introduction of ivermectin in the early eighties and the use of microdoses in some cases have made it possible to control cattle hypodermosis in large areas of Europe. As with cattle hypodermosis, the administration of ivermectin microdoses in goats is particularly interesting because of the low costs involved and the low levels of residues found in goat milk; it may thus constitute the basis for GWFI control campaigns in areas where the disease is prevalent.

Administration, Topical↗
PubMed2006

Larval immersion tests with ivermectin in populations of the cattle tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) from State of Sao Paulo, Brazil.

Larval immersion tests (LIT) with commercial formulation of ivermectin were carried out with larvae of two field populations of Rhipicephalus (Boophilus) microplus from commercial dairy farms of the State of Sao Paulo, Brazil and a susceptible strain (Porto Alegre) to differentiate resistant-suspected and susceptible strains. One of the populations tested (Barra Alegre) showed a LC(50) value significantly higher than the susceptible strain and a resistance ratio (CI95%) of 3.78 (3.47-4.12), leading to suspect that this population shows traces of resistance to ivermectin. Population Sao Francisco, with no records of ivermectin injections on cattle, showed no difference on the ivermectin response in relation to Porto Alegre strain characterizing it as susceptible. Although LIT is not yet recommended by FAO to diagnose resistance to acaricides, this technique was successful on the differentiation of resistance-suspected population and a susceptible strain and can be used to detect populations of R. (B.) microplus resistant to ivermectin. This is the first report of R. (B.) microplus resistant to ivermectin detected by an in vitro bioassay.

Animals↗