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PubMed2006

New screening test to predict the potential impact of ivermectin-contaminated cattle dung on dung beetles.

According to European Union recommendations, a test method has been developed to evaluate the effects of veterinary pharmaceuticals on dung feeding insects. This test method was evaluated with the dung beetle Aphodius constans by using fecal residues of ivermectin after a pour-on administration. Dung of different age (and thus containing different concentrations of ivermectin) as well as mixtures of highly-contaminated spiked dung with untreated control dung were studied in five test runs in two laboratories. The concentration of ivermectin (active substance; a.s.) in the dung samples was verified analytically. The main test endpoint was the survival of first instar larvae. The LC50 using dung directly obtained from treated cattle ranged from 470 to 692 microg a.s. kg(-1) dung (dry weight; d.w.) and 67 to 97 microg a.s. kg(-1) dung (fresh weight; f.w.). Using mixtures, the outcome of two tests was almost identical: 770 to 781 microg a.s. kg(-1) dung (d.w.); 109 to 132 microg a.s. kg(-1) dung (f.w.). In comparison to the LC50 values obtained when ivermectin was spiked in control dung at several concentrations (LC50 880-985 microg a.s. kg(-1) dung (d.w.)), the LC50 values were again very similar. Three conclusions can be drawn from these results. The proposed test method seems to be robust and allows for the initiation of an international validation process (including ringtesting). Because of only small differences found in tests in which the test substance was spiked into control dung and those in which dung from treated cattle was applied, the use of a standard test method is proposed. The effects of ivermectin on ecologically relevant dung beetles obtained in a standardised test method reflect the results from field studies and are in the range of environmentally relevant concentrations.

Animals↗
PubMed2004

Efficacy of ivermectin in a patient population concomitantly infected with intestinal helminths and ectoparasites.

Ivermectin (CAS 70288-86-7) is a potent antiparasitic drug. However, studies have not been published evaluating the efficacy of ivermectin in a patient population concomitantly infected with intestinal helminths and ectoparasites. Here the results of an open trial on the efficacy of ivermectin in a heavily poly-parasitized population in northeast Brazil are presented. Two hundred and fifty-one patients were enrolled. Two doses of ivermectin (200 microg/kg) were given at an interval of 10 days. The cure rates for intestinal helminthiases were: 100% for strongyloidiasis and enterobiasis, 99% for ascariasis, 84% for trichuriasis, 68% for hookworm disease, and 50% for hymenolepiasis. Cure rates for ectoparasitoses were: 100% for cutaneous larva migrans, 99% for pediculosis, 88% for scabies and 64% for tungiasis. The results show that two doses of ivermectin are highly efficacious for most intestinal helminths and ectoparasites simultaneously present in an impoverished population. The drug seems to be particularly useful when polyparasitism is expected to occur or when public health measures aim to reduce both intestinal helminthiases and parasitic skin diseases by mass chemotherapy.

Adolescent↗
PubMed2001

Involvement of women in community-directed treatment with ivermectin for the control of onchocerciasis in Rukungiri district, Uganda: a knowledge, attitude and practice study.

A study of knowledge, attitudes and practice was carried out in the Rukungiri district of Uganda, in order to investigate the involvement of women in community-directed treatment with ivermectin (CDTI), for the control of onchocerciasis. The data analysed came from interviews with 260 adult women (one from each of 260 randomly-selected households in 20 onchocerciasis-endemic communities), community informants, and participatory evaluation meetings (PEM) in eight communities. The women who had been treated with ivermectin in 1999 generally had more knowledge of the benefits of taking ivermectin, were more likely to have attended the relevant health-education sessions and were more involved in community decisions on the method of ivermectin distribution than the women who had not received ivermectin in that year. There were fewer female community-directed health workers (CDHW) than male CDHW in the communities investigated. The reasons for not attending health-education sessions, not participating in community meetings concerning the CDTI, and the reluctance of some women to serve as CDHW were investigated. The most common reasons given were domestic chores, a reluctance to express their views in meetings outside their own kinship group, suspicions that other women might take advantage of them, and a lack of interest. Most of the women interviewed (as well as other community members) felt that there were relatively few women CDHW. The women attributed this to a lack of interaction and trust amongst themselves, which resulted in more men than women being selected as CDHW. The rest of the community members were not against women working as CDHW. It is recommended that communities be encouraged to select women to serve as CDHW in the CDTI, and that the performances of male and female CDHW be compared.

Community Health Workers↗
PubMed1986

The chemotherapy of onchocerciasis. XI. A double-blind comparative study of ivermectin, diethylcarbamazine and placebo in human onchocerciasis in northern Ghana.

Fifty-nine onchocerciasis patients with ocular involvement were randomly assigned to receive either 12 mg of ivermectin in a single dose or 1300 mg of diethylcarbamazine over eight days or matching placebo capsules. Detailed standardized follow-up examination was carried out for one year. Both ivermectin and diethylcarbamazine rapidly reduced skin microfilarial counts to a similar extent over six months, after which counts increased significantly more with diethylcarbamazine. Diethylcarbamazine rapidly eliminated microfilariae from the eye, while ivermectin did so over six months. Reactions to treatment were more severe with diethylcarbamazine, which also produced clinical ocular deficiency in two patients. Ivermectin produced intra-uterine sequestration and degeneration of microfilariae in adult worms, which may account for its ability to produce prolonged suppression of skin microfilariae. Ivermectin proved superior to diethylcarbamazine in safety, tolerance and efficacy, but further work is needed to assess fully its effects in patients with heavy intraocular microfilarial loads.

Adolescent↗
PubMed1996

Onchocerca volvulus and O. lienalis: the microfilaricidal activity of moxidectin compared with that of ivermectin in vitro and in vivo.

The activity of the veterinary drug moxidectin against Onchocerca volvulus and On. lienalis microfilariae (mf), both in vitro and in experimentally infected CBA/Ca mice, was compared with that of ivermectin. The in-vitro results demonstrated that both compounds (at a concentration of 10(-7) M) significantly reduced the mf motility index (MI) throughout the 7-day culture period and that this reduction was similar for the two compounds. Mice were treated with moxidectin and ivermectin by subcutaneous injection (sc) or orally (po); the two routes were equally efficacious. When mice infected with On. lienalis were treated with one of the drugs at 3.2, 1.6, 0.8, 0.4 or 0.2 micrograms/kg.day on days 3-7 post-infection, with necropsy on day 18, moxidectin cleared more mf than ivermectin at all of the doses examined. In mice treated with a single dose (on day 3 post-infection), 150 or 15 micrograms/kg moxidectin completely cleared the mf whereas 1.5 micrograms/kg produced a 90%-96% reduction in mf recoveries. Following ivermectin treatment at the same doses, mf were virtually cleared at 150 micrograms/kg, with a 98% reduction at 15 micrograms/kg but no significant effect at 1.5 micrograms/kg. When mice with On. volvulus infections were treated with a single dose of moxidectin at 15 or 1.5 micrograms/kg, there were reductions in mf recoveries of 96% and 23%, respectively, compared with only a 48% reduction with 15 micrograms ivermectin/kg and a 2% increase with 1.5 micrograms ivermectin/kg. In order to examine the persistence and activity of each drug, mice were treated with a single dose of 150 micrograms/kg up to 28 days before infection. Moxidectin was found to be more efficacious (with subsequent 99.9% reduction in mf when given 28 days pre-infection and a 100% reduction when give 16 or 4 days before or 3 days after infection) than ivermectin (giving reductions of 57.1%, 66.7%, 100% and 100%, respectively). The further evaluation of moxidectin and its potential usefulness for the treatment of human onchocerciasis are discussed.

Animals↗
PubMed1997

The entry of ivermectin and suramin into Onchocerca ochengi nodules.

No currently available drug, which is safe for mass treatment, effectively kills adults of Onchocerca volvulus, the causal agent of onchocerciasis in humans, or of O. ochengi, a cattle parasite used as a model of O. volvulus. Since adults of both of these filarial nematodes are found in well developed nodules, the lack of efficacy of these drugs may be a result of their poor penetration into the nodules. To check if this was the problem, the distributions of the microfilaricide, ivermectin, and the partial macrofilaricide, suramin, in plasma, skin, nodule capsules and nodule contents were determined in cattle naturally infected with O. ochengi in Cameroon. The cattle were treated with either a single, subcutaneous injection of 500 micrograms ivermectin/kg, or with intravenous injections of [14C]-labelled suramin, each of 10 mg/kg, given one a day for 6 days. Concentrations of ivermectin and suramin in various tissues were then assayed by high-pressure liquid chromatography and scintillation counting, respectively. On day 7 post-treatment (pt), suramin concentrations were consistently highest in the nodule, contents and capsule wall (11.0 and 8.9 nCi/g, respectively) and significantly less in skin and plasma (1.2 and 1.4 nCi/g, respectively; P < 0.05). The distribution of ivermectin on day 7 pt was similar, with the highest concentrations in the capsule wall, nodule contents and plasma (58.4 ng/g, 43 ng/g and 48.6 ng/ml, respectively; P > 0.05) and the concentration in the skin (6.4 ng/g) significantly lower than those in the capsule or plasma (P < 0.05). High intra-nodular concentrations of both drugs were maintained for 5-7 days at least and those of ivermectin would be expected to kill nematodes other than filariae. It is apparent that failure of ivermectin and suramin to kill adult Onchocerca spp. is not because the drugs penetrate nodules inadequately.

Animals↗
PubMed1998

A method to determine the coverage of ivermectin distribution in onchocerciasis-control programmes.

Onchocerciasis is a human filarial infection responsible for an estimated 750,000 blind and severely visually disabled people. In some African countries, this disease represents the main cause of blindness, with considerable socio-economic impact on the affected communities. Since the introduction of ivermectin as a microfilaricidal agent, there is hope that visual loss from onchocerciasis can be eliminated through community-based ivermectin-distribution programmes. The African Programme for Onchocerciasis Control (APOC) has now been initiated, by the World Health Organization and World Bank, to distribute ivermectin in 19 African countries where onchocerciasis is endemic. Estimates of ivermectin coverage in distribution programmes for onchocerciasis control have so far been based on the number of treatments given, in any one year, to a target population. There is a need for a standardized method to evaluate, measure and monitor coverage over time. In April 1996, a cluster random-sampling method was used to calculate coverage with ivermectin in an urban population of 30,000 people in the Central African Republic. The method was adapted from that used to determine coverage by the WHO Expanded Programme on Immunization. It proved to be inexpensive and easy to perform, requiring only local equipment and personnel. The method used and results obtained in Bossangoa and the potential use of the technique in other distribution programmes are discussed.

Adult↗
PubMed1998

Identification of cytochrome P4503A4 as the major enzyme responsible for the metabolism of ivermectin by human liver microsomes.

1. Ivermectin was extensively metabolized by human liver microsomes to at least 10 metabolites. The structure of many of them (mostly hydroxylated and demethylated) was determined by 1H-NMR and LC/MS. 2. To determine which human cytochrome P450 isoform(s) is responsible for the metabolism of ivermectin, chemical inhibitors including sulphaphenazole, quinidine, furafylline, troleandomycin (TAO) and diethyldithiocarbamate (DDC) were used to evaluate their effect on ivermectin metabolism. TAO, a specific inhibitor of cytochrome P4503A4, was the most potent inhibitor, inhibiting the total metabolism as well as formation of each metabolite. Metabolism was also inhibited by an anti-human cytochrome 3A4 antibody by 90%. 3. When ivermectin was incubated with microsomes from cells expressing CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 at 4 mg/ml protein concentrations, metabolic activity was only detected with the microsomes containing CYP3A4. The metabolic profile from cDNA-expressed CYP3A4 microsomes was qualitatively similar to that from human liver microsomes. 4. Thus, cytochrome P4503A4 is the predominant isoform responsible for the metabolism of ivermectin by human liver microsomes.

Chromatography, High Pressure Liquid↗
PubMed1991

Community-based treatment of onchocerciasis with ivermectin: safety, efficacy, and acceptability of yearly treatment.

The safety, acceptability, and efficacy of ivermectin during community-based mass treatment of onchocerciasis was assessed. Ivermectin was distributed three times, 1 year apart, to the population of a rubber plantation (14,000 people) in Liberia where greater than 80% of adults have Onchocerca volvulus infection. In a sample of adults, the microfilarial density was reduced by 84% after 2 years of treatment. Acceptance was as high as 98% during the third year. Adverse reactions occurred in 6-13 in 1000 people after first treatment and in only 3-4 in 1000 receiving their second or third annual dose of ivermectin; severe adverse reactions were not seen. These data show that community-based treatment with ivermectin is safe, well accepted, and effective in reducing microfilarial loads and suggest that ivermectin is the first practical drug suitable for mass treatment campaigns to control human onchocerciasis.

Adolescent↗
PubMed1994

C-reactive protein and interleukin-6 are elevated in onchocerciasis patients after ivermectin treatment.

Ivermectin treatment of onchocerciasis can induce adverse reactions. Mechanisms underlying these reactions are poorly understood but may include activation of neutrophils. This study investigated the acute-phase response in onchocerciasis patients during 2 days after ivermectin treatment. The acute-phase protein C-reactive protein (CRP) and cytokines that mediate the acute-phase response (tumor necrosis factor-alpha [TNF alpha] and interleukin-6 [IL-6]) were measured in 144 skin snip-positive onchocerciasis patients and 12 skin snip-negative controls who received one dose of ivermectin (150 micrograms/kg). No elevated TNF alpha levels were found, but IL-6 and CRP were elevated in 25.7% and 50.7% of the patients, respectively, after ivermectin treatment. Most patients (89.2%) with raised IL-6 also had raised CRP. Such increases were not observed in controls and in patients were correlated with adverse reactions and microfilarial densities. These findings suggest a possible role of the acute-phase response in microfilarial destruction following ivermectin treatment.

Biomarkers↗
PubMed1989

Susceptibility of Ornithodoros parkeri (Cooley) (Acari: Argasidae) and Dermanyssus gallinae (DeGeer) (Acari: Dermanyssidae) to ivermectin.

Ivermectin was injected into hosts and evaluated for effectiveness against the argasid tick Ornithodoros parkeri (Cooley) and the chicken mite Dermanyssus gallinae (DeGeer). O. parkeri second stage nymphs (N2s) showed a marked increase in mortality when fed on mice injected intraperitoneally with ivermectin at a dose between 0.1 and 0.2 mg/kg host body weight. For adult O. parkeri and D. gallinae, 0.4 and 0.5 mg, respectively, per kilogram of host body weight were necessary for an increase in mortality over controls. These latter findings are comparable to those reported for other tick species but differ from those reported for the northern fowl mite, Ornithonyssus sylviarum (Canestrini & Fanzago). Further testing narrowed the effective dose range for O. parkeri adults to between 0.425 and 0.450 mg/kg host body weight. The time interval (4, 8, and 24 h) between ivermectin injection of the host and tick feeding had only a slight influence on the overall effectiveness of the drug. In O. parkeri, doses of 0.0125 to 0.1000 mg/kg body weight did not affect fecundity, hatchability, gross morphology of the reproductive system and synganglion, or histology of the reproductive system. Contrary to reports of irreversibility of effects of ivermectin on gamma aminobutyric acid-mediated neurotransmission, many ivermectin-paralyzed ticks recovered partial mobility over time.

Animals↗
PubMed1991

Effect of ivermectin on the ovarian development of Aedes aegypti (Diptera: Culicidae).

The effect of ivermectin (0.1 microgram/ml) on blood digestion, ovarian development, and ovipositional attributes of Aedes aegypti was studied using standard morphological and histological techniques. Uncoordinated movements and paralysis were observed in most ivermectin-treated females within 1 h after ingestion of blood containing the chemical. Eight days after the blood meal, 23.5% of the treated females had died, whereas no mortality occurred in controls. Formation of the peritrophic membrane and digestion of the blood meal were delayed in the surviving treated mosquitoes. The most striking effect of ivermectin on Ae. aegypti at this dosage was on ovarian development. Changes observed among ivermectin-treated mosquitoes included: blood digestion without development of ovarian follicles; degeneration of primary follicles and formation of ovarian dilatations within 24 h after ingestion of the chemical; significant reduction in the rate of vitellogenesis and follicle development; decreased egg production; reduced egg hatching; abnormal egg size and shape; and increased percentages of unhatched embryonated and sterile eggs. Although the precise action of ivermectin on Ae. aegypti is unknown, our studies indicate that the chemical directly or indirectly affects at least three major organ systems (nervous, digestive, and reproductive).

Aedes↗
PubMed2006

Crusted scabies in an adult T-cell leukemia/lymphoma patient successfully treated with oral ivermectin.

We report an adult T-cell leukemia/lymphoma (ATL) patient whose crusted scabies was successfully treated with oral ivermectin. This 63-year-old man had previously been treated with oral prednisolone, sobuzoxane and etoposide for approximately 1 year. When he developed crusted scabies, he received two doses of oral ivermectin (200 microg/kg) 10 days apart and the concomitant topical application of crotamiton containing 30% benzyl benzoate. This produced remarkable results, suggesting that oral ivermectin should be considered for the treatment of crusted scabies even in immunocompromised patients. While ivermectin may be useful for treating intractable scabies, attention must be paid to the possible appearance of ivermectin-resistant mites.

Administration, Oral↗
PubMed2000

The use of ivermectin in controlling an outbreak of scabies in a prison.

BACKGROUND: Ivermectin is a potentially useful treatment for scabies. OBJECTIVES: We aimed to evaluate the efficacy of ivermectin in the treatment of scabies in an institutional environment. METHODS: A single dose of ivermectin 150 microg kg-1 was given under supervision to 1153 prisoners in a prison in northern Tanzania where there was an outbreak of scabies. RESULTS: Thirty per cent of the prisoners were cured after 1 week, 88% after 4 weeks and 95.5% after 8 weeks. Of 16 prisoners with crusted scabies, seven (44%) still had scabies after 8 weeks. Those who were not cured were then treated with 1% lindane lotion topically, as were the prison staff who had scabies. This regimen eradicated scabies from the prison for the next 2 years. CONCLUSIONS: Ivermectin is an effective and safe treatment for scabies, particularly in a closed community, such as a prison, where it is easy to administer and avoids problems with compliance. It was of limited efficiency in crusted scabies as a single dose and we recommend that for such patients oral ivermectin is used in combination with a topical scabicide.

Adolescent↗
PubMed2007

Pharmacokinetics of a new long acting endectocide formulation containing 2.25% ivermectin and 1.25% abamectin in cattle.

The objective of this study was to determine the kinetic parameters of a new formulation that contained 2.25% ivermectin combined with 1.25% abamectin in bovine plasma. The results for 2.25% ivermectin: Cmax (37.11 ng/mL +/- 7.42), Tmax (16 days +/- 5.29), T(1/2) (44.62 days +/- 53.89), AUC (928.2 ng x day/mL +/- 153.83) and MRT (36.73 days +/- 33.64), and for 1.25% abamectin: Cmax (28.70 ng/mL +/- 9.54), Tmax (14 days +/- 4.04), T(1/2) (15.40 days +/- 11.43), AUC (618.05 ng x day/mL +/- 80.27) and MRT (20.79 days +/- 8.43) suggest that this combination of 2.25% ivermectin + 1.25% abamectin possesses properties that give this pharmaceutical formula a longer activity time than two of the commercial products tested (1% ivermectin and 1% abamectin), and showed similarity to 3.15% ivermectin.

Animals↗
PubMed2006

Reduction in the prevalence and intensity of infection in Onchocerca volvulus microfilariae according to ethnicity and community after 8 years of ivermectin treatment on the island of Bioko, Equatorial Guinea.

Bioko is the only island known in the world with endemic onchocerciasis. The island's rural communities consist of villages and cocoa plantations inhabited by Bubi and Fang ethnic groups. The aim of this study was to evaluate the impact of 8 years of vertical ivermectin distribution on the prevalence and intensity of Onchocerca volvulus infection in the rural population by means of pre- (1989) and post-long term treatment (1998) epidemiological surveys. In both surveys, the entire population of 12 randomly selected communities (1723 and 1082 individuals) was examined. The mean ivermectin therapeutic coverage for the 8 years was 53.2%. Iliac crest skin snips were used for differential diagnosis between O. volvulus and Mansonella streptocerca. The crude O. volvulus infection prevalence before ivermectin intervention was 74.5% (1284/1723); after the intervention it was 38.4% (415/1082). The Community Microfilarial Load (CMFL) before and after ivermectin intervention was 28.29 microfilariae/snip vs. 2.32 microfilariae/snip. The reduction in prevalence and CMFL after eight annual rounds of ivermectin treatment corroborates the drug microfilaricidal activity and good tolerability. In the pre-treatment survey, the prevalence was higher in the Bubi group (77.1%, 1126/1461); post-treatment it was higher among the Fang (51.1%, 92/180). The reduction in prevalence and intensity of O. volvulus infection differed between ethnic groups and communities.

Adolescent↗
PubMed1984

Ivermectin interactions with benzodiazepine receptors in rat cortex and cerebellum in vitro.

The anthelmintic macrolide, ivermectin, enhances the binding of benzodiazepine agonist ( [3H]-diazepam) and antagonist ( [3H] beta-carboline ethyl ester) ligands to rat cortical and cerebellar membrane preparations. Enhancement of benzodiazepine agonist binding is partially additive with that of gamma-aminobutyric acid (GABA) and is inhibited by etazolate, bicuculline, and the steroid GABA antagonist R5135. Ivermectin-stimulated benzodiazepine antagonist binding is enhanced by bicuculline and inhibited by GABA and etazolate. The modulatory effects of bicuculline are chloride-dependent. The stimulatory effects of ivermectin, while quantitatively different in cortex and cerebellum, are qualitatively similar in both brain regions and are reduced in the presence of chloride. Ivermectin effects on benzodiazepine ligand binding to the benzodiazepine receptor complex and the differences in the effects of GABA, bicuculline, and R5135 on ivermectin-stimulated agonist and antagonist binding may provide evidence for distinct differences in the recognition sites for the two classes of benzodiazepine receptor ligand and their interactions with other components of the receptor complex.

Animals↗
PubMed1998

Comparative effects of abamectin and two formulations of ivermectin on the survival of larvae of a dung-breeding fly.

OBJECTIVES: To compare the survival of larvae of a dung-breeding fly in the faeces of cattle treated either with an injectable formulation of abamectin, or with oral or injectable formulations of ivermectin. DESIGN: Replicated bioassays were conducted on larvae of the bush fly, Musca vetustissima, using faeces collected before and at intervals after drug treatment. ANIMALS: Two cows and their calves were allocated to each of three drug treatments and dosed according to individual weights. PROCEDURES: Differences in the proportions of larvae pupariating were used as measures of the toxicity of drug residues. RESULTS: Development of fly larvae was inhibited in all faeces collected 1 to 4 days after treatment. In cattle treated with oral ivermectin, there was reduced larval survival in faeces collected 8 and 16 days after treatment, but by day 32, survival was equivalent to that recorded in the faeces of untreated cattle. With injectable ivermectin, there was no survival at day 8, limited survival at day 16 and, at day 32, survival was not significantly affected. With injectable abamectin, survival was completely suppressed until day 32, at which time the number of pupariating larvae did not differ significantly from that recorded in faeces from untreated animals. CONCLUSION: The oral formulation of ivermectin is eliminated more rapidly than the injectable formulation and, as a consequence, is likely to be less harmful to dung-feeding insects. Abamectin and ivermectin appear to equally toxic larvae of M vetustissima.

Administration, Oral↗