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PubMed1993

How long do the effects of ivermectin on adult Onchocerca volvulus persist?

The persistence of the effects of ivermectin on the viability, morphology and reproductivity of adult Onchocerca volvulus was examined eighteen months after treatment with a single or five six-monthly doses of ivermectin and compared with untreated controls. Treated nodules were removed from patients participating in a randomised controlled trial of ivermectin in Sierra Leone. Adult filariae, 545 females and 348 males, were isolated by collagenase digestion. The nodules were significantly smaller, contained fewer young worms and supported lower microfilarial production in those treated with five doses of ivermectin. The productivity index, a measure of the reproductive potential of a worm population, was still reduced by 83% eighteen months after five doses and by 63% after a single dose compared to controls. These results show that worms recover their fertility even after multiple doses of ivermectin, but do so slowly compared to standard dosage intervals. In addition ivermectin may have a partial chemoprophylactic effect which contributes to the maintenance of low microfilarial production in conditions of on-going transmission.

Adult↗
PubMed1995

Ivermectin treatment of hyperreactive onchodermatitis (sowda) in Liberia.

Seventeen male and 39 female Liberian patients, one third of them children, were diagnosed as having hyperreactive onchodermatitis (sowda). They presented with itching (98%), asymmetric (98%), chronic onchodermatitis (median 5 years), and swelling of femoral lymph nodes (89%). The geometric means of the microfilaria (mf) densities were 1.0 mf/mg in children and 0.7 mf/mg in adults. These patients not only suffered from their skin lesions, and severe itching resulting in disturbance of sleep but also from social stigmata. They urgently needed treatment. Ivermectin was administered as a single oral dose of 150 micrograms/kg body weight. The following adverse effects were observed in 30 patients within the first 72 hours after ivermectin treatment: increase of pruritus (93%), aggravation of dermatitis (73%), fever (25%), headache (20%), myalgia (20%), painful swelling of lymph nodes (13%) and severe swelling of arm or leg (10%). Symptomatic therapy was sufficient. No dangerous or life-threatening side effects were observed. At follow-up examinations 1-2 months after ivermectin treatment, the prevalence of mf carriers had decreased from 100% to 19%. Seventeen out of 18 patients felt their dermatitis had improved. Evaluation of the dermatitis by a physician using a score from 0 (no dermatitis) to 9 (severe dermatitis) revealed a reduction of the score from 4.3 before treatment to 0.7 (84%) after ivermectin. In contrary, at the follow-up examination of 16 patients 6-12 months after ivermectin some recrudescences were observed. In this group the prevalence of mf carriers was 47%, 13 out of the 16 patients felt their skin lesions had improved and the score had decreased from 2.2 to 0.5 (77%). Consequently, it is recommended to administer ivermectin to patients with hyperreactive onchodermatitis every 3-4 months.

Adult↗
PubMed1998

Efficacy and tolerance of oral ivermectin in scabies.

OBJECTIVE: The aim of this open-label study was to investigate the therapeutic effect and adverse reactions of oral ivermectin in scabies patients. BACKGROUND: There is much confusion over reports of efficacy, adverse reactions and relapses after oral treatment of scabies with ivermectin. METHODS: Nineteen patients, ten otherwise healthy outpatients with scabies, and nine inpatients with scabies and another skin disease (dermatomyositis, 3; pemphigus, 2; bullous pemphigoid, 1; pyoderma, 1; HIV, 1; Behçet's disease, 1) were treated with an oral dose of 0.2 mg/kg ivermectin (1% water solution) on days 1 and 8. The presence of live mites and ova in the patient's skin was investigated before, during and after the treatment. RESULTS: None of the 19 patients with scabies had evidence of scabies after the second dose of ivermectin. In seven patients we noted the enhancement of pruritus 24-72 h after the first administration of ivermectin. In three patients the skin manifestation, vesicle-pustular rash increased between the second and the fourth day. CONCLUSION: The advantages of oral ivermectin treatment in scabies patients are: high therapeutic efficacy against Sarcoptes scabiei, good tolerance and influence of the drug on the whole skin surface and on clinical symptoms. The administration of the drug is easy and quick.

Administration, Oral↗
PubMed1995

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.

Journal Article↗
PubMed1997

Efficacy of closantel, albendazole and levamisole on an ivermectin resistant strain of Haemonchus contortus in sheep.

Following evidence of reduced efficacy of oral ivermectin in a field population of Haemonchus contortus on a sheep farm in Kenya, this strain of the parasite was submitted to a controlled anthelmintic test. One hundred and twenty worm-free lambs were randomly split into two groups of 60. Each lamb in the first group was infected with 5000 third stage larvae (L3) of the suspected resistant strain the remaining 60 lambs were each infected with 5000 (L3) of a H. contortus strain of known susceptibility to the major groups of anthelmintic compounds used in sheep. On day 28 post-infection, each group was subdivided according to egg counts and at random into six sub-groups of ten lambs, each of which was treated with closantel at 5.0 mg kg-1, albendazole at 5.0 mg kg-1, levamisole at 7.5 mg kg-1, oral ivermectin at 0.2 mg kg-1 or injectable (Inj.) ivermectin at 0.2 mg kg-1, or was left as an untreated control. At slaughter, 10 days later, all the anthelmintics had resulted in reduced worm burdens in animals infected with the susceptible strain (albendazole 99.0%, levamisole 99.5%, closantel, Inj. and oral ivermectin 100%). By contrast, in the lambs infected with the suspected resistant strain, closantel was 100% effective, but inj. ivermectin, oral ivermectin, albendazole and levamisole reduced worm counts by 47.6%, 24.2%, 38.5% and 41.4%, respectively. Anthelmintic resistance to the other chemical groups had been confirmed previously on this farm and although benzimidazoles and levamisole had not been used for the last 4 years, this strain was still highly resistant to albendazole and levamisole; closantel remained as the only drug evaluated which was still effective against this population of H. contortus.

Administration, Oral↗
PubMed1985

Efficacy and pharmacokinetics of febantel and ivermectin in red deer (Cervus elaphus).

A trial was conducted to determine the efficacy and pharmacokinetics of fehantel and ivermectin in six month-old red deer calves (C. eluphus). Five calves received febantel by mouth at 7.5 mg/kg, five received a subcutaneous injection of ivermectin at 200 microg/kg and five were controls. All calves were killed seven days later and total lung and gastrointestinal worm counts carried out. Febantel was 85 and 99.8% efficient in removing immature and mature Dictyocaulus viviparus, respectively, and ivermectin was 100% efficient in both cases. There was no gastro-intestinal nematodes in any of the treated calves, compared to an average of 619 in the control calves. The metabolism of febantel resulted in plasma levels of fenbendazole, oxfendazole and sulphone for which the common curves fitted by compartmental model peaked at values (standard errors)-of 0.46 (0.03), 0.41 (0.02) and 1.73 (0.07) mg/l after approximately five, nine, and thirteen hours and were undetectable at 30,72 and 120 hours respectively. There was considerable variation among animals in response to ivermectin. The fitted common curve had a peak plasma level of 15.8 (0.08) microg/l at 20 hours after injection, which had dropped to 7.9 (1.1) microg/l seven days after injection. It was estimated that after 15 days plasma levels of ivermectin would not be detectable. It is concluded that the injectable form of ivermectin tested is a highly efficient anthelmintic in deer, and that plasma levels persist for over a week after subcutaneous injection. Fehantel is very efficient against mature D. viviparus in deer, but its reduced efficiency against immature D. viviparus may relate to the deer;s ability to metabolise and excrete benzimidazoles more quickly than sheep and cattle.

Journal Article↗
PubMed1990

A pilot study of the efficacy of topical ivermectin against lungworm in young red deer (Cervus elaphus).

Three groups of ten 4-month-old red deer (Cervus elaphus) calves naturally infected with lungworm (Dictyocaulus viviparus) were treated with either oral ivermectin (200 microg/kg), topical (pour-on) ivermectin (500 microg/kg) or oral oxfendazole (5 mg/kg). Faecal larval counts for lungworm were undetectable or very low for 14 days after treatment with oxfendazole, 28 days after treatment with oral ivermectin and for 49 days after treatment with topical ivermectin. This pilot study suggests that the topical formulation of ivermectin was very effective against lungworm and had a more persistent action than the oral ivermectin formulation in young red deer.

Journal Article↗
PubMed1997

Demonstration of the sustained anthelmintic activity of a controlled-release capsule formulation of ivermectin in ewes under field conditions in New Zealand.

Ten field trials were conducted in the North and South Islands of New Zealand to evaluate the anthelmintic efficacy of an intraruminal controlled-release capsule formulation of ivermectin. A total of 810 Coopworth, Perendale, Romney or Coopworth ' Romney ewes, weighing on average 42-70 kg, were used. Ewes were either untreated or treated shortly before lambing in late winter-early spring (eight trials) or in late spring (two trials) with an ivermectin controlled-release capsule which delivers ivermectin at 1.6 mg per day for 100 days (minimum dose rate 20microg/kg/day). Bodyweights, faecal nematode egg counts and dag scores were determined before treatment and at about 2 and/or 4, 6 or 8, 10 or 12, 14 and 16 weeks after treatment. Ewes treated with the ivermectin controlled-release capsule gained on average 1.1kg more than untreated sheep over the 16 weeks of the trials, but this difference was not significant (p > 0.10). Before treatment, faecal strongylid egg counts were equivalent (p > 0.10), but at each time point thereafter, egg counts in ivermectin controlled-release capsule treated sheep were significantly lower (p < 0.01; p < 0.05 at Week 2). Dag scores were not different at the start of the trial (p > 0.10), but at the end of the trial ivermectin controlled-release capsule treated ewes had significantly lower scores (p < 0.01) than untreated ewes. These findings indicated that treated animals shed significantly fewer nematode eggs and therefore pasture contamination with nematode eggs should be significantly reduced for at least 112 days. The control of dags should result in reduced direct losses due to the decreased value of dag wool, and indirect losses due to the cost of dagging sheep and the cost associated with the treatment and control of flystrike initiated by dags in the breech area.

Journal Article↗
PubMed2003

Programmatic and Communication Issues in Relation to Serious Adverse Events Following Ivermectin Treatment in areas Co-endemic for Onchocerciasis and Loiasis.

In areas co-endemic for loiasis and onchocerciasis, the classic Community-Directed Treatment using ivermectin (Mectizan(R)) must be adapted as additional program activities, better communication and tighter control of ivermectin stocks are required to minimize risk and manage serious adverse events following ivermectin treatment in patients co-infected with Loa loa. The importance of these serious adverse events on community participation in onchocerciasis control efforts has not been adequately studied. Program implementers do not as of yet fully understand the psychological impact of serious adverse events on communities and therefore have not designed communication strategies that adequately address the real concerns of community members. It is clear, however, that along with an effective case detection and management strategy, a reinforced communication strategy will be required to motivate at least 65% of the total population in onchocerciasis and loiasis co-endemic areas to participate in the treatment program and to take ivermectin over an extended period. This strategy must be based on research undertaken at the community level in order to address the concerns, fears and issues associated with adverse events due to ivermectin - to ensure that communities believe that the benefits of taking ivermectin outweigh the risks. In addition to an overall increase in the time required to sustain onchocerciasis control programs in co-endemic areas, each aspect of the reinforced program and communication strategy - rapid epidemiological assessments, materials development, training, advocacy, community sensitization and mobilization, case management and counselling, supervision, monitoring and evaluation will require additional resources and support from all stakeholders concerned.

Journal Article↗
PubMed1986

Treatment of onchocerciasis. The ocular effects of ivermectin and diethylcarbamazine.

The ocular changes that occur with diethylcarbamazine treatment of onchocerciasis seriously restrict its usefulness. Ivermectin, a newly developed antifilarial drug, was compared with diethylcarbamazine for treatment of onchocerciasis in a double-masked, placebo-controlled trial. Thirty men with moderate to severe infection and ocular involvement were randomly assigned to receive ivermectin as a single oral dose (200 micrograms/kg), diethylcarbamazine (administered for eight days), or placebo. Detailed ocular examinations were performed serially over a 12-month period. Diethylcarbamazine treatment caused a marked increase in living and dead microfilariae in the cornea, punctate opacities, and limbitis during the first week of therapy. Ivermectin had no such effect. However, ivermectin therapy resulted in a long-term reduction in intraocular microfilariae comparable to that seen with diethylcarbamazine. Ivermectin appears to have few ocular complications and be a better-tolerated and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.

Adult↗
PubMed1989

Control of induced infestations of three African multihost tick species with sustained-release ivermectin.

The efficacy of ivermectin, released intraruminally from a 28-day-delivery device was evaluated in two titration studies against induced infestations of adult Rhipicephalus appendiculatus, R. evertsi and Hyalomma truncatum on cattle. Cattle were given a sufficient number of devices to release ivermectin at approximately 20, 40, 60 or 80 micrograms kg-1 day-1 at a steady-state rate 7-28 days after administration. Tick mortality was recorded, engorged female ticks were weighed and individually incubated, and reproductive data were recorded to determine a reproductive index for the species at various dose levels. Mortality of male and female ticks compared to that of controls was directly related to the daily dose of ivermectin, as was the number of ticks not engorging. Ticks fed on ivermectin-treated cattle had a smaller mass when engorged and laid smaller egg-masses, both absolutely and as a proportion of engorged mass. The index of reproduction of R. appendiculatus was reduced by more than 99.9% at 20 micrograms kg-1 day-1, and the reproductive indices of R. evertsi and H. truncatum were reduced by more than 99.9% at dose rates of 40 micrograms kg-1 day-1 and above. Practical implications of the application of sustained-release ivermectin for the control of multihost ticks and tick-borne diseases are discussed.

Animals↗
PubMed1992

Bioavailability of ivermectin administered orally to dogs.

The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (Cmax) of ivermectin administered in the standard tablet formulation at 6 and 100 micrograms/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics. Cmax and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 micrograms/kg. Furthermore, Cmax was similar following administration of radiolabelled ivermectin at 6 micrograms/kg in either a beef-based chewable formulation or in the standard tablet formulation.

Administration, Oral↗
PubMed2006

Construction of ivermectin producer by domain swaps of avermectin polyketide synthase in Streptomyces avermitilis.

Ivermectin, 22, 23-dihydroavermectin B1, is commercially important in human, veterinary medicine, and pesticides. It is currently synthesized by chemical reduction of the double bond between C22 and C23 of avermectins B1, which are a mixture of B1a (>80%) and B1b (<20%) produced by fermentation of Streptomyces avermitilis. The cost of ivermectin is much higher than that of avermectins B1 owing to the necessity of region-specific hydrogenation at C22-C23 of avermectins B1 with rhodium chloride as the catalyst for producing ivermectin. Here we report that ivermectin can be produced directly by fermentation of recombinant strains constructed through targeted genetic engineering of the avermectin polyketide synthase (PKS) in S. avermitilis Olm73-12, which produces only avermectins B and not avermectins A and oligomycin. The DNA region encoding the dehydratase (DH) and ketoreductase (KR) domains of module 2 from the avermectin PKS in S. avermitilis Olm73-12 was replaced by the DNA fragment encoding the DH, enoylreductase, and KR domains from module 4 of the pikromycin PKS of Streptomyces venezuelae ATCC 15439 using a gene replacement vector pXL211. Twenty-seven of mutants were found to produce a small amount of 22, 23-dihydroavermectin B1a and avermectin B1a and B2a by high performance liquid chromatography and liquid chromatography mass spectrometry analysis. This study might provide a route to the low-cost production of ivermectin by fermentation.

Genetic Engineering↗
PubMed1999

Interaction of ivermectin with gamma-aminobutyric acid receptors in Trichinella spiralis muscle larvae.

The value of the gamma-aminobutyric acid (GABA) receptor of nematodes as a target for ivermectin's mode of action remains unclear. Using binding assays, we examined extracts from Trichinella spiralis muscle larvae for the presence of [3H]-ivermectin and [3H]-GABA binding sites. Tissue preparations displayed affinity binding sites for [3H]-ivermectin with a dissociation constant (Kd) of 83 nM and a receptor density (Bmax) of 145 fmol/mg protein. We also identified a specific [3H]-GABA binding activity with a Kd of 1.2 microM and a Bmax of 4.78 pmol/mg protein. In competition studies, ivermectin was found to be a competitive inhibitor of specific [3H]-GABA binding activity with an inhibition constant (K(i)) of 3.39 nM, suggesting that GABA receptors could be implicated in the mechanism of action of ivermectin in nematodes.

Animals↗
PubMed1999

Enhanced absorption of pour-on ivermectin formulation in rats by co-administration of the multidrug-resistant-reversing agent verapamil.

The effect of verapamil, a multidrug-resistance (Mdr)-reversing agent on the absorption of a pour-on formulation of ivermectin was evaluated in rats. Absorption of ivermectin was effectively enhanced (40%) by the presence of verapamil, suggesting that absorption of ivermectin involves Mdr-P-glycoprotein and that verapamil should act as a competitive inhibitor for the transport and extrusion of ivermectin by P-glycoprotein. This hypothesis is consistent with other studies describing verapamil as a blocking agent of P-glycoprotein involved in the efflux of ivermectin in a resistant strain of Haemonchus contortus.

Absorption↗
PubMed2004

Comparison of anthelmintic effects of two doses of ivermectin on intestinal strongyloidiasis in patients negative or positive for anti-HTLV-1 antibody.

Coinfection with HTLV-1 (T lymphotropic virus type I) has been observed in approximately 38% of cases of Strongyloides stercoralis infection in Japan. In the present study, we investigated whether the dose of ivermectin corresponding to approximately twice the conventional therapeutic dose could improve the anthelmintic rate without adverse effects in patients with intestinal strongyloidiasis, particularly in those positive for anti-HTLV-1 antibody. A single dose of 6 mg ivermectin (mean, 110 microg/kg) was administered and the same single dose was repeated 2 weeks later in 312 patients with intestinal strongyloidiasis during the period from 1990 to 1999. The long-term anthelmintic rate during the period of 12 months from 4 months after treatment was 77% (117/152) in all patients, and 92.7% (89/96) and 50% (28/56) in those negative and positive for anti-HTLV-1 antibody, respectively. Between 2000 and 2003, ivermectin was administered at 200 microg/kg in 97 patients, and repeated 2 weeks later. The long-term anthelmintic rate was 96.8% (60/62) in all patients, and 100% (42/42) and 90% (18/20) in those negative and positive for anti-HTLV-1 antibody, respectively. These results showed that the long-term anthelmintic rates in all patients in the 200 microg/kg dose group, and especially in those positive for anti-HTLV-1 antibody, were significantly higher than the respective rates of the 110 microg/kg dose group. Based on these results and the observed safety of the double dose of ivermectin, the recommended dose of ivermectin for treatment of intestinal strongyloidiasis should be 200 microg/kg in patients positive for anti-HTLV-1 antibody.

Administration, Oral↗
PubMed2005

Therapeutic and persistent efficacy of a single injection treatment of ivermectin and moxidectin against Boophilus microplus (Acari: Ixodidae) on infested cattle.

The effectiveness of a single treatment with either ivermectin or moxidectin was determined by administering a single subcutaneous injection of each endectocide at 200 microg per kg body weight to cattle infested with all parasitic developmental stages (adults, nymphs, and larvae) of Boophilus microplus (Canestrini). The percentage reduction in the number of females that reached repletion following treatment (outright kill) was 94.8 and 91.1% for ivermectin and moxidectin, respectively. In addition, the reproductive capacity of the females that did survive to repletion was reduced by > 99%, regardless of the endectocide. Based on these two factors, the therapeutic level of control obtained against ticks on the cattle at the time of treatment was 99.0 and 99.1% for ivermectin and moxidectin, respectively. Engorged females recovered from either group of treated cattle weighed approximately 3-times less than untreated females, and the egg masses produced by treated females weighed approximately 5-8-times less than egg masses produced by untreated females. Partitioning of data into three separate 7-d post-treatment intervals allowed for an estimation of the efficacy of each endectocide against each individual parasitic development stage (adult, nymph, and larva). Results indicated that both endectocides were > or =99.7% effective against ticks that were in either the adult or nymphal stage at the time of treatment. However, the level of control against ticks in the larval stage of development at treatment was significantly lower at 97.9 and 98.4% for ivermectin and moxidectin, respectively. Analysis of the persistent (residual) activity of the two endectocides indicated that neither material provided total protection against larval re-infestation for even 1-wk following treatment. Against larvae infested 1-4 wk following treatment, the level of control with moxidectin ranged from 92.4% (1 wk) to 19.5% (4 wk). These control levels were higher at each weekly interval than for ivermectin, which ranged from 82.4% (1 wk) to 0.0% (4 wk). The potential for the use of these injectable endectocide formulations in the US Boophilus Eradication Program is discussed.

Animals↗
PubMed1990

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)

Aedes↗