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PubMed1996

In vitro screening of Haemonchus contortus third stage larvae for ivermectin resistance.

The indiscriminate repeated use of ivermectin has resulted in the emergence of ivermectin resistant field strains of Haemonchus contortus in sheep in South Africa. There is a need for a rapid and cost effective in vitro test to detect such strains. Infective H contortus larvae known to be resistant to ivermectin, were incubated in vitro in a diluted concentration of the drug. Subsequently their ability to migrate was compared with that of larvae of isolates known to be susceptible to ivermectin. The criterion used to determine resistance was the ability of the larvae to migrate out of gelled agar after exposure to ivermectin using diluted propylene glycol as the control compound. The results obtained by this technique confirmed the results obtained with critical controlled tests; significant differences between the ivermectin sensitive and resistant isolates were demonstrated, thereby confirming that this in vitro technique may be used as a screening method to identify ivermectin resistant isolates of H. contortus.

Animals↗
PubMed1996

Comparison of moxidectin oral gel and ivermectin oral paste against a spectrum of internal parasites of ponies with special attention to encysted cyathostome larvae.

Two dosages of moxidectin oral gel were evaluated and compared to a therapeutic dose of ivermectin oral paste in the control of a spectrum of gastrointestinal parasites of ponies naturally infected in southern Louisiana or Mississippi. Thirty-two mixed-breed ponies ranging in age from one to 21 years were used in this controlled test. Eight weeks prior to the experiment, ponies grazing on contaminated pasture were moved to a paddock and fed a pelleted ration, thus reducing or eliminating the potential for additional infection and ensuring the existence of a population of encysted larvae. Ponies were then allocated to replicates of four animals based on values of fecal strongyle egg counts and percent strongyle larvae composition determined from Baermann sedimentations of fecal cultures. Members of replicates were allocated to one of four treatment groups: moxidectin oral gel administered at 300 micrograms kg-1 body weight, moxidectin oral gel at 400 micrograms kg-1, the oral gel vehicle as negative control, and ivermectin oral paste at 200 micrograms kg-1. Prior to treatment, ponies were confined in pairs to covered concrete runs by treatment group. Two weeks following treatment, necropsy examinations of all animals were performed. Parasites were recovered from the lumen of the stomach, the intestinal tract, the cranial mesenteric artery and its major branches, the peritoneal body wall and from pepsin digests of mucosal scrapings taken from the cecum and large colon. Encysted cyathostome larval burdens were also compared using mural transillumination of segments of the large colon for visualization of the encysted forms. Control ponies were not uniformly infected with the spectrum of parasites; however, moxidectin, at either dosage, compared favorably with ivermectin in the control of the adults of Strongylus vulgaris, Strongylus edentatus, Triodontophorus spp., Oesophagodontus robustus, Trichostrongylus axei, Oxyuris equi, Parascaris equorum, Habronema muscae, as well as both the adult and larval Cyathostominae recovered from the lumen. Moxidectin also appears as efficacious as ivermectin against migrating large strongyle larvae at the two weeks post-treatment evaluation. Moxidectin demonstrated a trend towards greater efficacy against encysted cyathostome larvae than a therapeutic dosage of ivermectin, but this difference was not statistically significant. Moxidectin was less effective than ivermectin against Gasterophilus intestinalis and was equally ineffective as ivermectin against Anoplocephala perfoliata.

Administration, Oral↗
PubMed2006

Ivermectin inhibits AMPA receptor-mediated excitotoxicity in cultured motor neurons and extends the life span of a transgenic mouse model of amyotrophic lateral sclerosis.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitotoxicity contributes to the selective motor neuron death in amyotrophic lateral sclerosis (ALS). In this study, we investigated the effect of P2 receptor-influencing substances on kainate-induced motor neuron death in an in vitro model for AMPA receptor-mediated excitotoxicity. Complete protection was found after preincubation of the motor neurons with ivermectin or Cibacron Blue 3G-A. Preincubation with both P2X4 modulators did not influence the number or Ca2+ permeability of the AMPA receptors and addition during kainate stimulation alone had no effect. Preincubation with a low concentration of ATP, the natural agonist of the P2X4 receptor, also protected the motor neurons against a subsequent excitotoxic stimulation, while high concentrations of ATP were toxic. Moreover, ivermectin increased the toxicity of low ATP concentrations, indicating that ivermectin can potentiate the effect of ATP on its receptor. Ivermectin and ATP also protected against hypoxia/hypoglycemia. To further investigate the relevance of these findings for ALS, we treated SOD1(G93A)-mice, a transgenic animal model for familial ALS, with ivermectin. This resulted in an extension of the life span of these mice with almost 10%. We conclude that ivermectin induces a mechanism in motor neurons, in vivo and in vitro, that protects against subsequent excitotoxic insults. Our in vitro data indicate that this protective mechanism is due to the potentiation by ivermectin of an effect of ATP mediated by the P2X4 receptor.

Adenosine Triphosphate↗
PubMed2004

Efficacy of abamectin against ivermectin-resistant strain of Trichostrongylus colubriformis in sheep.

The efficacy of two formulations of abamectin, i.e. oral and injectable was determined against ivermectin-resistant strain of T. colubriformis in sheep. Twenty-four lambs were infected with 10,000 third stage larvae of ivermectin-resistant strain of T. colubriformis. Twenty-four days post-infection, the lambs were divided randomly into four groups of six animals each according to egg counts. The first group was left untreated and kept as a control. The second group was treated with ivermectin (oral) at 0.2mg kg(-1) body weight. The third group was treated with oral formulation of abamectin at 0.2mg kg(-1) body weight. The fourth group was treated with injectable formulation of abamectin at 0.2mg kg(-1) body weight. Fecal egg count and controlled slaughter tests were employed to determine the efficacy of abamectin (oral and injection) against ivermectin-resistant strain of T. colubriformis in sheep. Reduction in arithmetic mean fecal egg counts achieved by ivermectin (oral), abamectin (oral) and abamectin (injection) was 66, 98 and 76%, respectively 10 days after treatment. Ivermectin (oral), abamectin (oral) and abamectin (injection) reduced arithmetic mean worm burden by 63, 97 and 74%, respectively. The findings demonstrated that abamectin oral formulation was more effective than abamectin injection against ivermectin-resistant strain of T. colubriformis in sheep.

Administration, Oral↗
PubMed2001

Licking behaviour and environmental contamination arising from pour-on ivermectin for cattle.

Pour-on formulations of endectocides are extensively used to treat and control systemic parasitic diseases in cattle, worldwide. The purpose of the present study was to investigate the influence of the natural licking behaviour of cattle on the plasma and faecal disposition of topically administered ivermectin. Twelve Holstein cattle were given one single intravenous (i.v.) (200 microg/kg) and topical (500 microg/kg) administration of ivermectin at a 5-month interval. For the pour-on administration, the animals were allocated into two groups (n=6): one control group (lickers) and one group where licking was prevented (non-lickers). Ivermectin plasma (total) clearance (270+/-57.4 ml/kg/day) was very homogeneous among the 12 cattle. In contrast, major differences between lickers and non-lickers were observed following pour-on administration. Prevention of licking resulted in an extended terminal plasma half-life (363+/-16.2 vs. 154+/-7.4 h in lickers) and in a lower and less variable systemic availability of ivermectin (19+/-4.9 vs. 33+/-18.5% in lickers). More importantly, nearly 70% of the pour-on dose was recovered as parent drug in the faeces of lickers vs. only 6.6% in non-lickers. Altogether, these results are consistent with an oral rather than percutaneous absorption of topical ivermectin in control animals, the non-systemically available fraction of ingested ivermectin providing a major contribution (80%) to the drug faecal output. The consequences of licking on the disposition of pour-on ivermectin are discussed in terms of environment, given the known ecotoxicity of this drug, and of cross-contamination. Animals licking themselves and each other could result in unexpected residues in edible tissues of untreated animals and in possible subtherapeutic drug concentrations, a factor in drug resistance. According to the Precautionary Principle, these considerations elicit concern over the use of topical drug formulations in cattle.

Administration, Topical↗
PubMedDate not supplied

The potential of ivermectin to control the malaria vector Anopheles farauti.

We investigated mortality in Anopheles farauti mosquitoes, a major coastal malaria vector in the south-west Pacific, fed on a volunteer who had taken a 250 micrograms/kg dose of ivermectin. High mortality was recorded in mosquitoes feeding during the first week after treatment of the volunteer, for instance 100-80% failed to survive 3 days. A long-term residual effect of ivermectin in the blood was indicated by a small but significantly higher mortality in mosquitoes fed 6 weeks after ivermectin was taken. These effects were included in malaria transmission models that incorporated host choice and host-induced mortality parameters. For the zoophilic An. farauti, ivermectin treatment of animals resulted in a greater reduction in malaria than ivermectin treatment of humans alone, whereas for an anthropophilic vector, treatment of humans was more important. This suggests that ivermectin treatment of animals could have an important role in malaria control where An. farauti is the vector. Improvement in the health of humans and domestic animals through control of parasitic worms and mites might encourage community participation in strategies involving ivermectin.

Animals↗
PubMedDate not supplied

A randomized double-blind placebo-controlled field trial of ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana.

The efficacy and safety of single-dose ivermectin (150-200 micrograms/kg) and albendazole (400 mg) treatment administered separately or in combination for Wuchereria bancrofti infections were assessed in 1996-98 in a randomized double-blind placebo-controlled field trial in Ghana: 1425 individuals from 4 lymphatic filariasis-endemic villages, 340 of whom were microfilaria (mf)-positive before treatment, were randomized into 4 groups to receive albendazole alone, ivermectin alone, combination of albendazole and ivermectin, or placebo, respectively. Individuals were followed for 5 days after treatment to record any adverse reactions, and the effect of treatment on microfilaraemia was monitored in night-blood samples after 3, 6 and 12 months. Treatment efficacy was analysed for 236 mf-positive individuals who had > or = 100 mf/mL of blood and who were also present for examination at 12 months after treatment. Compared to the placebo group, the ivermectin and combination groups both showed statistically significant reductions in geometric mean mf intensities at the follow-up examinations (to 6.7% and 0.9%, 9.9% and 6.9%, and 21.7% and 11.4% of pre-treatment levels, respectively, at 3, 6 and 12 months after treatment). Compared to the ivermectin group, however, the reduction in the combination group was significantly greater only at 3 months after treatment, but not after 6 or 12 months. The albendazole group showed a slow but non-significant reduction over the same period. Adverse reactions were few and mostly mild (no severe reactions were recorded), and no significant differences were observed between the treatment groups. Both ivermectin and combination treatment thus appeared effective and safe for treatment of lymphatic filariasis, but the difference in efficacy was minor and the study did not provide clear evidence for the combination drug therapy, as compared to ivermectin therapy alone, to be superior for control of lymphatic filariasis.

Adolescent↗
PubMed1996

The effects of multiple doses of ivermectin on ocular onchocerciasis. A six-year follow-up.

BACKGROUND: Ivermectin has been shown to be a safe treatment for onchocerciasis and is now being distributed through mass treatment programs. Previous studies of up to 3 years of treatment have demonstrated that ivermectin improves anterior segment lesions and reduces the incidence of optic atrophy. The benefit of multiple doses of ivermectin on visual acuity and chorioretinitis has yet to be shown. METHODS: A community-based, double-blind, randomized, controlled trial of ivermectin was started in Bo, Sierra Leone, in 1987. Two cohorts are reported in this study: (1) 214 subjects had received four 6-month doses of ivermectin followed by up to six additional 6-month treatments. The second cohort, with 185 subjects, had received four 6-month doses of placebo followed by up to four annual doses of ivermectin. All subjects received a full ophthalmic examination in 1989 and again in 1994. For both cohorts, there was an 18-month gap between the fifth and sixth rounds of treatment. RESULTS: There was no significant difference in the prevalences of any ocular lesion nor of visual acuity categories between the cohorts at the second examination. Comparisons of the prevalences of anterior segment lesions for both cohorts combined between the first and second examinations show highly significant improvement (P < 0.001) for all lesions. Posterior segment lesions show a more variable pattern, with chorioretinitis showing highly significant deterioration (P < 0.001) and the emergence of new lesions in both groups. CONCLUSION: The authors conclude that annual treatment with ivermectin is effective in controlling ocular onchocerciasis apart from chorioretinal lesions and that a 6-month treatment gives no additional benefit.

Adult↗
PubMed2001

High-affinity ivermectin binding to recombinant subunits of the Haemonchus contortus glutamate-gated chloride channel.

Glutamate-gated chloride channels (GluCls) are targets for the avermectin anthelmintics. A family of five GluCl subunit genes encoding seven subunits has been identified in Caenorhabditis elegans. We have previously shown that two orthologous genes in the parasite, Haemonchus contortus, encode three GluCl subunits (HcGluClbeta, Hcgbr-2A and Hcgbr-2B) with high amino-acid identity (>80%) to their C. elegans counterparts. We amplified and cloned a further subunit cDNA, HcGluClalpha, from H. contortus eggs. Sequence comparisons suggested that this subunit was closely related to, but not orthologous with, the C. elegans GluClalpha1, alpha2 or alpha3/GBR-2 subunits ( approximately 55% amino-acid identity). The HcGluClalpha cDNA from an ivermectin-resistant isolate contained no coding changes from the wild-type. All of the known H. contortus GluCl cDNA clones were subcloned into the expression vector pcDNA3.1 and transiently expressed in COS-7 cells. As predicted by functional data from the C. elegans orthologues, the Hcgbr-2A and HcGluClbeta subunits failed to bind [3H]ivermectin. The Hcgbr-2B and HcGluClalpha subunits bound [3H]ivermectin with high affinity; the K(d) values were 70+/-16 and 26+/-12 pM, respectively. This binding was inhibited by a variety of avermectins, though cold ivermectin was the most potent inhibitor of [3H] ivermectin binding. Picrotoxin, fipronil, glutamate and GABA all failed to compete for ivermectin binding to either subunit. The affinity of [3H]ivermectin binding to H. contortus L3 P2 larval membrane preparations was re-examined and found to be 70+/-7 pM. The properties of orthologous GluCl subunits are likely to be conserved across species, but the repertoire and relative importance of those subunits may vary.

Animals↗
PubMed2000

A comparative study of oral ivermectin and topical permethrin cream in the treatment of scabies.

BACKGROUND: The conventional antiscabietics have poor compliance. Ivermectin, an oral antiparasitic drug, has been shown to be an effective scabicide and could be a useful substitute. OBJECTIVE: This study compares the efficacy of oral ivermectin with topical permethrin cream in the treatment of scabies. METHODS: Eighty-five consecutive patients were randomized into 2 groups. Forty patients and their family contacts received 200 microg/kg body weight of ivermectin, and another 45 patients and their family contacts received a single overnight topical application of 5% permethrin cream. Patients were followed up at intervals of 1, 2, 4, and 8 weeks. RESULTS: A single dose of ivermectin provided a cure rate of 70%, which increased to 95% with 2 doses at a 2-week interval. A single application of permethrin was effective in 97.8% of patients. One (2.2%) patient responded to 2 applications at a 2-week interval. Permethrin-treated patients recovered earlier. CONCLUSION: A single application of permethrin is superior to a single dose of ivermectin. Two doses of ivermectin is as effective as a single application of permethrin. The temporal dissociation in clinical response suggests that ivermectin may not be effective against all the stages in the life cycle of the parasite.

Administration, Oral↗
PubMed2001

Efficacy of a long-acting formulation of ivermectin against Psoroptes ovis (Hering, 1838) on cattle.

A study was conducted in cattle experimentally infested with Psoroptes ovis to compare the prophylactic control against P. ovis provided by a long-acting injectable formulation of ivermectin to that of a commercially available injectable formulation of doramectin. Thirty Holstein steers were used. Animals were allocated by restricted randomization based on Day 0 body weight, forming six replicates of five animals each. Within each replicate, one animal was randomly allocated to one of the following treatment groups, with ivermectin and doramectin administered subcutaneously where indicated: (1) untreated controls; (2) ivermectin long-acting injectable (LAI) 630 mcg/kg, 56 days before challenge; (3) ivermectin LAI 630 mcg/kg, 42 days before challenge; (4) ivermectin LAI 630 mcg/kg, 35 days before challenge; or (5) doramectin 200 mcg/kg, 35 days before challenge. Animals were housed in individual pens 1 week prior to treatment. All animals were experimentally infested with P. ovis mites in the area between the shoulders, on the same day. Live mites were counted in scrapings from mange lesions at 2 sites on each animal 14, 21 and 28 days after challenge. Live mites were found in 33, 67 and 83% of the untreated controls on each respective evaluation. No P. ovis mites were found in steers treated with ivermectin LAI. Those animals showed lower (P < 0.05) mite counts than untreated controls on evaluations conducted 21 and 28 days after challenge. These results indicate that the ivermectin long-acting injectable formulation prevents induced infestations by P. ovis for at least 56 days after treatment. Doramectin injectable formulation, used at 200 mcg/kg, did not have a prophylactic effect 35 days after treatment.

Animals↗
PubMed1997

Comparative pharmacokinetics of doramectin and ivermectin in cattle.

Plasma pharmacokinetics were compared for 40 cattle dosed by subcutaneous injection with doramectin or ivermectin (200 micrograms kg-1), commercial formulations of doramectin or ivermectin, 20 cattle per product). Doramectin exhibited a similar peak plasma concentration to ivermectin (about 32 ng ml-1), but the time to Cmax was longer for doramectin (5.3 +/- 0.35 days) than for ivermectin (4.0 +/- 0.28 days). The area under the curve from time 0 to infinity post-injection was significantly higher (p < 0.001) for doramectin (511 +/- 16 ng day ml-1) than for ivermectin (361 +/- 17 ng day ml-1). This was explained by a lower clearance, a lower volume of distribution and, probably, a higher bioavailability of doramectin over ivermectin. It is concluded that the pharmacokinetic differences between doramectin and ivermectin may explain the longer duration of preventive efficacy of doramectin.

Animals↗
PubMed1997

Therapeutic and protective efficacy of doramectin injectable against gastrointestinal nematodes in cattle in New Zealand: a comparison with moxidectin and ivermectin pour-on formulations.

Two similar studies were conducted in New Zealand to compare the therapeutic and persistent activity of doramectin injectable, moxidectin pour-on, ivermectin pour-on and oxfendazole oral drench when administered to nematode-infected cattle which were then grazed on common pastures. On day 0 (treatment day), 40 cattle were weighed, faecal sampled and allocated on the basis of day--3 faecal egg counts (FEC) to four treatment groups. Cattle were then treated with either doramectin by subcutaneous (s.c.) injection, moxidectin and ivermectin by topical application, or oxfendazole orally using label-recommended dosages. Oxfendazole treatment served primarily as a control to monitor reinfection without persistent activity. Faecal samples for nematode egg counts and coprocultures for larval differentiation were collected six times between day 0 and day 56 and all cattle were reweighed on day 56. Doramectin reduced pretreatment FEC by 99.1% in the first study and by 100% in the second study when assessed at 14 days posttreatment. Corresponding reductions for moxidectin were 80.8% and 85.2%, for ivermectin 86.0% and 80% and oxfendazole 78.3% and 100%, respectively. Posttreatment rise in FEC indicated that reinfection of moxidectin-treated animals occurred at the same time as oxfendazole controls in both trials. Posttreatment rise in FEC with ivermectin pour-on was similar to moxidectin and oxfendazole in one study, but in the other study ivermectin pour-on delayed the rise by 14-21 days. The rise in FEC for doramectin was delayed for 14-21 days in one study and at least 21 days in the other. The better parasite control provided by doramectin resulted in greater weight gains for cattle over the 56-day period as compared to moxidectin pour-on, ivermectin pour-on and oxfendazole in both trials. Gains of doramectin treated cattle were significantly (p < 0.05) greater than those of ivermectin and moxidectin groups in one trial and the oxfendazole group only in the other.

Administration, Oral↗
PubMed1998

Comparative efficacy evaluation of moxidectin gel and ivermectin paste against internal parasites of equines in Brazil.

A total of 24 male and female equines of mixed breed, 10-20 months of age and naturally infected with internal parasites was utilized in a controlled test to evaluate the efficacy of a moxidectin 2% gel formulation at the dosage of 0.4 mg moxidectin per kg of live weight and an ivermectin 1.87% commercial paste formulation at the dosage 0.2 mg ivermectin per kg applied orally. Animals were allocated into three groups of eight horses each based on pre-treatment eggs per gram (EPG) counts and treatments were randomized among the groups. One group was kept as untreated controls. One animal in the moxidectin-treated group died before the end of the trial from a cause unrelated to treatment leaving a total of seven animals in this group. Fecal egg counts were performed three times post-treatment and the number of parasites remaining in each animal was determined. Statistical analyses using geometric means were performed at the 1% level of significance. Both moxidectin and ivermectin preparations reduced initial EPG from a mean of 1600 to 0 on Days 5, 7 and at the end of the trial on Day 14. Efficacy percentages of moxidectin and ivermectin against immature and adult nematodes were as follows: Trichostrongylus axei, Parascaris equorum, Strongylus edentatus, S. vulgaris, Triodontophorus spp. and Gyalocephalus capitatus, 100% for both products; Habronema muscae 99.5 and 99.6%, respectively, Strongyloides westeri, 100 and 99.2%, respectively; Oxyuris equi, 99.6 and 100%, respectively; small strongyles, 99.7% for both products. Of the latter, the most numerous were: Cylicocyclus insigne, Cylicostephanus longibursatus and Cyathostomum catinatum. No Gasterophilus nasalis were found in horses from either treated group, while two of eight control horses had infections with thisparasite. Moxidectin showed greater efficacy (84.9%) than ivermectin (67.8%) against Strongylus vulgaris larvae found in the mesenteric artery aneurisms, but the difference was not statistically significant. Total parasite counts for both treated groups were significantly lower (p<0.01) than in the non-treated group. No significant differences were noted between moxidectin and ivermectin. Efficacy against the 30 nematode species found in this study was very evident for both products. As expected, neither moxidectin nor ivermectin was effective in controlling the tapeworm Anoplocephala perfoliata. No adverse reactions were observed during the experimental period.

Animals↗
PubMed1999

Decreased ivermectin and moxidectin sensitivity in Haemonchus contortus selected with moxidectin over 14 generations.

Ivermectin resistance in the nematode Haemonchus contortus has been reported in many parts of the world and many ivermectin resistant isolates have been found to have reduced sensitivity to moxidectin. However, it is unclear whether parasites that are selected with moxidectin would demonstrate reduced sensitivity to ivermectin. In this study, the effects of moxidectin and ivermectin on an unselected strain and a strain of H. contortus derived from the unselected strain but selected over 14 generations with moxidectin, were compared in jirds. The recovery of adult worms and fourth stage (L4) larvae following treatment were compared between strains and anthelmintics. Moxidectin-selected H. contortus showed reduced sensitivity to ivermectin as well as to moxidectin. Doses of 0.1 mg/kg of moxidectin and 0.4 mg/kg of ivermectin were necessary to obtain an efficacy of 95% or above against the moxidectin-selected strain of H. contortus compared with 0.025 mg/kg for moxidectin and 0.1 mg/kg for ivermectin required for a similar efficacy in the unselected strain.

Animals↗
PubMed2000

Efficacy of an ivermectin controlled-release capsule against some rarer nematode parasites of sheep.

A controlled trial was conducted to evaluate the efficacy of the intraruminal ivermectin controlled-release capsule (CRC) (IVOMEC Maximizer CR Capsule for Sheep, Merial Ltd.) against induced incoming third-stage larvae and established adult infections with some rarer gastrointestinal nematode parasites of sheep. Twenty-one worm-free lambs were allocated by restricted randomisation based on body weight within sex to one of the following treatments: unmedicated control, ivermectin CRC given on Day 0 prior to induced infection, and ivermectin CRC given on Day 70 after establishment of induced infection. The ivermectin CRC delivers ivermectin at a minimum dose rate of 20 microg/kg/day for 100 days. Infections were induced by daily administration of third-stage larvae for five consecutive days. Nematodes were counted on Day 84, 14 days after treatment of established infection. The treatment with the ivermectin CRC prevented the establishment of Ostertagia leptospicularis, O. ostertagi, Bunostomum trigonocephalum, Cooperia oncophora, C. punctata, C. surnabada, Nematodirus helvetianus, N. roscidus and Strongyloides papillosus by >99% as compared with the untreated controls (p < 0.01). The administration of the ivermectin CRC reduced established adult infections of O. ostertagi, B. trigonocephalum, C. oncophora, C. punctata, C. surnabada, N. roscidus and S. papillosus by >99% (p < 0.01), and reduced established adult infections of O. leptospicularis and N. helvetianus by 96.5 and 98.4% (p < 0.01), respectively.

Abomasum↗
PubMed1996

Onchocerca retinol- and ivermectin-binding protein activity.

The presence of retinol-binding protein (RBP) activity in Onchocerca cervicalis adult worms and interaction with ivermectin has been studied using high pressure size exclusion chromatography (HPSEC). Four distinct peaks of [3H]-retinol incorporation were obtained corresponding to approximate molecular weights of 150, 67, 19.7 and 4.6 kDa, the 2 smaller M(r) peaks accounting for most of the binding activity. Competition for binding using non-labelled retinol at 200-fold molar excess indicated that specific binding of retinol occurred only to the 19.7 kDa fraction. Competition by ivermectin also inhibited binding of [3H]-retinol to the third peak. Following incubation with [3H]-ivermectin 4 peaks of similar molecular weights were also detected by HPSEC in soluble adult worm homogenate. However, in this case the 150 kDa fraction was most prominent. Both non-labelled ivermectin and non-labelled retinol at 200-fold molar excess reduced binding of [3H]-ivermectin to all 4 fractions. These data indicate that the putative Onchocerca RBP has an approximate molecular weight of 19.7 kDa, that retinol also binds to 3 additional fractions non-specifically, that the pattern of binding of ivermectin to adult worm material is quantitatively and qualitatively different from the binding exhibited by retinol, and that ivermectin interferes with the binding of retinol to the 19.7 kDa Onchocerca protein.

Animals↗
PubMed2005

Evidence for macrofilaricidal activity of ivermectin against female Onchocerca volvulus: further analysis of a clinical trial in the Republic of Cameroon indicating two distinct killing mechanisms.

During a 3-year trial of the effects of ivermectin (Mectizan) on adult worms and microfilariae of Onchocerca volvulus in the Republic of Cameroon, comparison was made between the percentages of calcified and uncalcified moribund (M) and dead (D) adult female worms dying following (a) the standard dose (150 microg/kg) given annually; (b) high doses (400, then 800 microg/kg) given annually; and (c and d) these same doses given at 3-monthly intervals. In the killing of adult female O. volvulus worms, the relative rôles of (a) natural causes; (b) a presumed, direct, anthelminthic, macrofilaricidal action of ivermectin; and (c) a potentially fatal pleomorphic ovarian neoplasm (PN), of which the incidence is increased by ivermectin treatment, are herein further investigated and discussed. It is concluded that ivermectin per se has a considerable direct macrofilaricidal action against female worms and that this lethal effect is supplemented by the drug's ability in some worms to increase the incidence, and the spread throughout the body of the worm, of the potentially fatal PN ovarian tumour. In moribund and dead ivermectin-treated female worms that were heavily invaded by PN, it is probable that the neoplasm was chiefly responsible for their death, but the additional direct anthelminthic action of the drug, which by itself has been responsible for the death of many other female worms, cannot be excluded as having played a supplementary lethal rôle. Similar problems as to the exact means by which adult female worms are killed may arise now that ivermectin is used in Africa for the mass treatment of lymphatic filariasis; or if and when the macrofilaricidal actions on O. volvulus of other drugs, which are closely related to ivermectin, come to be investigated.

Administration, Oral↗