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PubMed2000

Activation of rat recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptor by the insecticide ivermectin.

In the present study, the activation of rat recombinant alpha(1)beta(2)gamma(2S) gamma-aminobutyric acid (GABA)-ergic Cl(-) channel expressed in human embryonic kidney (HEK) 293 cells by ivermectin was investigated. Maximal activation of the channel occurred with GABA concentrations of 10 mM or 20 microM ivermectin both achieving about the same current amplitudes. With those saturating concentrations, the currents rose with GABA within 1 ms to the maximal values, whereas the rise time for ivermectin was about 500 times longer. In contrast to activation with GABA, no desensitisation in the presence of the agonist was observed with ivermectin. With both agonists, two different open states were detected. On simultaneous application of GABA and ivermectin the current amplitudes and the kinetics were determined by the agonist applied in the concentration eliciting the higher open probability. It is concluded that GABA and ivermectin activated the channel independently resulting in different kinetic properties.

Animals↗
PubMed1992

Resistance to ivermectin by Haemonchus contortus in goats and calves.

Efficacy of ivermectin on susceptible or resistant populations of the parasitic nematode Haemonchus contortus was determined in cattle and goats held in a barn. Goats were each infected with 3000 infective, ivermectin-susceptible or -resistant H. contortus larvae on day 0 and reinfected with 2000 infective larvae on day 24. Goats were treated orally with 600 micrograms kg-1 ivermectin on day 31. No significant differences were detected in blood packed cell volume (PCV) or total protein (TP), prepatent period, or epg among the four groups of goats that were each infected with one of four parasite strains (one susceptible, three resistant). There were no differences among the four parasite strains in the numbers of infective larvae that developed to the third larval stage from fecal cultures or in the viability of cultured infective larvae when held in the laboratory at 27 +/- 1 degrees C for 14 weeks. After treatment with ivermectin, there were significant differences among the parasite strains in PCV, TP, and epg. Total worm counts were reduced by 94 to 97% with three times the recommended dose. Immature and adult Skrjabinema ovis were also present in two treated goats. In a second test, one goat infected once with 10,000 infective larvae of a resistant strain of H. contortus and then treated with nine doses of ivermectin, increasing from 500 to 2000 micrograms kg-1 over a period of 133 days, had 35 adult worms at necropsy. In a third test, three calves were readily infected with an ivermectin-resistant strain of H. contortus from goats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The efficacy of 22,23-dihydroavermectin B1 (Ivermectin) acting singly or in combination with a benzodiazepine on microfilariae of Onchocerca species and Brugia pahangi (an in vitro study).

An in vitro study of the antinematodal action of two groups of compounds which act on the receptor complex of the inhibitory neurotransmitter, Gamma-aminobutyric acid (GABA) in mammalian systems is described. The compounds, Ivermectin and two benzodiazepines, Diazepam and a water soluble Midazolam were tested singly or in combination against two microfilarial parasites Onchocerca lienalis (closely related to Onchocerca volvulus) and Brugia pahangi. The combination of ivermectin and diazepam at a concentration of 0.1 microgram/ml and 33 micrograms/ml respectively achieved the same effect on microfilarial motility as when ivermectin was given at 1 microgram/ml alone or diazepam at 66 micrograms/ml alone. Similarly when the combination of ivermectin at 0.1 microgram/ml and midazolam at 10 micrograms/ml was used it achieved the same effect as ivermectin at 1 microgram/ml alone or midazolam at 33 micrograms/ml alone. This showed that both benzodiazepines had a synergistic effect on the activity of ivermectin. The microfilariae of B. pahangi were insensitive to both groups of compounds at all concentrations used.

Animals↗
PubMed2003

Adverse reactions following annual ivermectin treatment of onchocerciasis in Nigeria.

OBJECTIVES: This study aims to document and underscore the need to monitor adverse reactions following repeated ivermectin treatment under the current dispensation of the implementation of the Community-directed Treatment with Ivermectin (CDTI) Program. As communities are empowered to distribute ivermectin, monitoring of adverse reactions by health care professionals is important in achieving the onchocerciasis control objectives through mass ivermectin therapy. METHODS: Eight hundred and ninety subjects from 204 randomly selected households (based on cluster of households) were interviewed using structured questionnaires and in-depth interviews. Responses concerning the adverse effects of ivermectin at the first and sixth rounds were obtained using self-report and treatment records. RESULTS: Of the 890 individuals, 40.67% presented with adverse reactions at the first round of treatment (TX(1)). This was reduced to 15.06% at the sixth (TX(6)) round of treatment. Pains in joints were more frequently reported at TX(1) and TX(6), 22.7% and 8.5%, respectively. CONCLUSION: The relatively mild adverse reaction rates observed at TX(1) did not affect future participation in community treatment with ivermectin, due to adequate community mobilization with health education messages. The current CDTI program has a good chance of achieving the onchocerciasis control program's objectives in Shao, Kwara State, Nigeria.

Adolescent↗
PubMed2006

Prolonged persistence of fecally excreted ivermectin from reindeer in a sub-arctic environment.

In December 2001 and 2002, feces from reindeer calves treated with ivermectin were distributed on plots established on two types of forested reindeer pasture in northern Finland. The ungrazed plots were on an enclosure that had been fenced to prevent reindeer access for the last 6 years. The grazed plots were on an area that had been heavily stocked by reindeer during the last 5 years. After enclosures had been established, reindeer and large wildlife were prevented from entering by a fence. Topsoil samples (feces, vegetation, and soil) were collected monthly during the summers of the following 2 years, over a period of from 25 to 95 weeks after deposition. The samples were analyzed for ivermectin using HPLC. Although ivermectin degradation rapidly took place during the first spring, considerable residual ivermectin could be measured throughout the sampling time, showing that ivermectin in feces on pasture may not be photodegraded as rapidly as previously believed. The results support the need for further environmental evaluation studies on the use of ivermectin to control reindeer parasites.

Animals↗
PubMed1997

Successful control of onchocerciasis with community-based ivermectin distribution in the Rio Santiago focus in Ecuador.

Onchocerciasis is a major blinding disease in equatorial Africa and Central and South America. Ivermectin is a safe and effective drug in the treatment of this disease and now forms the basis of disease control in most endemic areas. We report the findings of long-term control of this infection in the Río Santiago focus in Ecuador, between January 1990 and December 1996, using a strategy of giving ivermectin treatments biannually in hyperendemic communities and annually in meso- and hypoendemic communities. Ivermectin was administered by local health workers from each community. A high level of compliance to ivermectin was achieved, with 81.9% to 98.0% of those eligible receiving the drug at each treatment instance. The impact of ivermectin therapy was monitored using a cohort of 120 randomly selected infected individuals from 8 hyperendemic communities. The geometric mean microfilarial density of this group declined from 19.3 to 0 mf/mg over the 84-month observation period. Ivermectin had a significant impact on anterior segment ocular disease, acute onchodermatitis and sowda. The rate of infection of blackflies declined from 1.1% in 1989-0.08% in 1996, which is below the vectorial capacity of the Simulium vector and, as no new nodules were detected after 1994 and no children under 5 became infected over the observation period, it is likely that the transmission of this infection was interrupted in the study area.

Animals↗
PubMed2000

Tolerability and efficacy of single-dose diethyl carbamazine (DEC) or ivermectin in the clearance of Wuchereria bancrofti microfilaraemia in Pondicherry, south India.

In a double blind design the tolerability and efficacy of single-dose DEC (6 mg/kg/body weight) or ivermectin (400 microg/kg/body weight) was studied in 30 asymptomatic W. bancrofti parasite carriers each. Although both drugs were tolerated well, the adverse reaction score (DEC 0.5; ivermectin 1.5) and overall incidence (DEC 65.0%; ivermectin 93.3%) were significantly higher in the ivermectin group. Major adverse reactions were fever, headache and myalgia, all of which peaked on the second day post-therapy. Efficacy was measured in terms of proportion of cases clearing parasitaemia and reduction in mean parasite density compared to pre-therapy levels. Although at the end of one year the ivermectin group showed a significantly higher efficacy (34.8%, 97.0%) compared to DEC (8.3%, 83.8%), at the end of the second year there was no significant difference in efficacy between the drugs (73.7%, 99.5% for ivermectin; 47.8%, 98.9% for DEC). The tolerability and efficacy of the two drugs were not significantly different between gender, age and weight classes of patients.

Adult↗
PubMed1999

Oral ivermectin in the treatment of scabies.

One hundred and twenty scabietic patients attending the outpatient clinic of the Department of Dermatology, Mansoura University Hospital, voluntarily participated in this uncontrolled, open label study to evaluate ivermectin 20 microg/kg as a scabietic after they had given their consent. The scabietic subjects included in this study were otherwise healthy, mentally competent, aged more than 18 years, and used no topical antiscabietic treatment in the week before ivermectin treatment, or during the 4-week study period. Patients were also required to show clinical evidence of scabies, and the microscopically demonstrated presence of Sarcoptes scabiei, their eggs, or their fecal pellets (scybala). A thorough history was taken, and a physical examination was conducted that included measurement of the pulse, blood pressure, temperature, and weight. For each participant, the distribution of scabies lesions was plotted on a body diagram, and the severity of disease was recorded as mild (10 or fewer lesions), moderate (11-49 lesions), or severe (50 or more lesions). Skin scrapings were examined for mites, eggs, or scybala. Urinalysis, stool analysis, a complete blood count, prothrombin time, and serum chemistry studies (serum creatinine, alanine aminotransferase (ALT), and total bilirubin) were performed before treatment, and 2 and 4 weeks after the drug was given. Ivermectin was administered as scored 6-mg tablets with water, and the dose was designed to provide 200 micrograms/kg (ivermectin was provided by Delta Pharma, Tenth of Ramadan City, Egypt). The patients were instructed to have recently worn clothing, sheets, and towels washed in a hot cycle the day after treatment. The patients were interviewed 3 days after treatment about any symptoms or subjective evidence of adverse reactions. Follow-up examinations were carried out 2 and 4 weeks after intake of ivermectin, and all examination procedures and laboratory investigations were repeated. Cure criteria included absence of nocturnal itching as well as dermatologic evidence of scabies, and negative skin scraping. Patients showing evidence of active scabies or having new lesions during the follow-up visits were given a second dose of ivermectin. All members of the household and immediate family were treated with either topical 5% permethrin cream or 1% gamma benzene hexachloride to reduce the chance of reinfestation.

Administration, Oral↗
PubMed2002

Ivermectin is better than benzyl benzoate for childhood scabies in developing countries.

OBJECTIVE: To compare single dose oral ivermectin with topical benzyl benzoate for the treatment of paediatric scabies. METHODS: An observer-blinded randomized controlled trial was undertaken at Vila Central Hospital, Vanuatu. One hundred and ten children aged from 6 months to 14 years were randomized to receive either ivermectin 200 micro g/kg orally or 10% benzyl benzoate topically. Follow up was at 3 weeks post-treatment. Primary outcome measures were the number of scabies lesions, the itch visual analogue score and nocturnal itch. Secondary outcome measures were the skin's reaction to treatment, the passage of worms in stool and other side effects. RESULTS: Eighty patients completed the study protocol. There was no significant difference between the two treatments; both produced a significant decrease in the number of scabies lesions seen at follow up. Ivermectin cured 24 out of 43 patients (56%), and benzyl benzoate 19 out of 37 patients (51%) at 3 weeks post-treatment. No serious side effects were noted with either treatment, but benzyl benzoate was more likely to produce local skin reactions (P = 0.004, OR 6.4, 95% CI 1.6-25.0) CONCLUSIONS: Ivermectin is cheap and effective in the treatment of paediatric scabies. Ivermectin has minimal observed toxicity and has the additional beneficial effects of antiparasitic action in onchocerciasis, filariasis and strongyloidiasis. Ivermectin is better than benzyl benzoate for the treatment of paediatric scabies in developing countries.

Adolescent↗
PubMedDate not supplied

The negative effects of the residues of ivermectin in cattle dung using a sustained-release bolus on Aphodius constans (Duft.) (Coleoptera: Aphodiidae).

This paper reports the findings of two trials into the effects of the treatment of cattle with ivermectin slow-release (SR) bolus on the larval development of the dung beetle Aphodius constans Duft. Rectal faecal samples were collected prior to treatment and every 3 and 2 weeks in a first and second trial, respectively, and up to 156 days post-administration of the SR bolus. Faecal ivermectin concentration reached a peak at 63 days post-treatment (1427 ng g(-1)) and ivermectin was detected up to 147 days post-treatment in the first trial (7.2 ng g(-1)). First stage larvae of A. constans were reared with control or contaminated dung and adult beetles were counted after emergence. In the first trial, the comparison of pairwise samples showed that ivermectin prevented the development of larval A. constans until day 105, while at day 135 the rate of emergence was still significantly lower than the corresponding series of control (p < 0.05). In the second trial, the difference between control and treated series remained significant until 143 days post-treatment, with no emergence until 128 days post-administration of SR bolus to cattle. These results show the negative effect of ivermectin on the development of larval A. constans, even at a low concentration (38.4 ng g(-1)). The administration of ivermectin sustained-release bolus to cattle was highly effective in killing dung beetle larvae for approximately 143 days after treatment. The results were similar when dung was obtained from a single animal kept alone, or from a blending of faecal pats obtained from a group of animals kept in field conditions during the whole trial period.

Animals↗
PubMed1998

In-vitro uptake of ivermectin by adult male Onchocerca ochengi.

Ivermectin is not lethal to the adult worms of Onchocerca volvulus or to those of O. ochengi, a cattle parasite closely related to O. volvulus. Although ivermectin penetrates the nodules in which the adults of these nematodes live, it is not known what levels of the drug enter the worms. Adult male O. ochengi were incubated in [3H]ivermectin in a saturated solution of unlabelled ivermectin (11.44 microM), to measure uptake by the oral and transcuticular routes, and in [3H]inulin, to ascertain if oral ingestion occurs in vitro. Uptake of [3H]ivermectin was high [1040 disintegrations/min (d.p.m.) at 3 h, representing a mean total of 86 pmoles ivermectin/worm] and occurred predominantly by the transcuticular route. Viability of worms was not reduced by this exposure, and uptake continued for up to 12 h. Only low levels of [3H]inulin (four d.p.m.) were detected in worms, indicating that the gut is probably not functional in vitro. Scanning and transmission electron microscopy revealed that the epicuticle of both sexes had an irregular surface which was pitted with a honeycomb structure in males, and rough and abundantly folded in females. These structures greatly increased the absorptive surface of the worms. In conclusion, ivermectin is able to enter adult O. ochengi males at concentrations sufficient to kill non-filarial nematodes.

Animals↗
PubMed2006

Occurrence of ivermectin in bovine milk from the Brazilian retail market.

High-performance liquid chromatography (HPLC) with fluorescence detection was used for the quantification of ivermectin residues in bovine milk intended for human consumption. After liquid-liquid extraction of ivermectin and purification of the extract, the compound was derivatized with 1-methylimidazol in N,N-dimethyl formamide to form a fluorescent derivative, which was separated by HPLC, using reversed-phase C18, with methanol : water (96 : 4 v/v) mobile phase at a flow rate 0.7 ml min-1. The excitation and emission wavelengths of the fluorescence detector were adjusted at 360 and 470 nm, respectively. The linearity of the method was in the range 10-100 ng ivermectin ml-1. Based on a sample of 5.0 ml, the limit of detection and the limit of quantification for ivermectin in milk were 0.6 and 2 ng ml-1, respectively. The recovery rate varied from 76.4 to 87.2%, with an average of 77.9 +/- 3.2%, at four fortification levels. The inter-day precision of the method was 13% (n = 5). Of 168 samples analysed, 17.8% contained ivermectin above the limit of quantification. Nevertheless, none of the samples contained ivermectin above the maximum residue limit (10 ng ml-1) established by the Brazilian Ministry of Agriculture.

Animals↗
PubMed1997

avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans.

Ivermectin is a widely used anthelmintic drug whose nematocidal mechanism is incompletely understood. We have used Caenorhabditis elegans as a model system to understand ivermectin's effects. We found that the M3 neurons of the C.elegans pharynx form fast inhibitory glutamatergic neuromuscular synapses. avr-15, a gene that confers ivermectin sensitivity on worms, is necessary postsynaptically for a functional M3 synapse and for the hyperpolarizing effect of glutamate on pharyngeal muscle. avr-15 encodes two alternatively spliced channel subunits that share ligand binding and transmembrane domains and are members of the family of glutamate-gated chloride channel subunits. An avr-15-encoded subunit forms a homomeric channel that is ivermectin-sensitive and glutamate-gated. These results indicate that: (i) an ivermectin-sensitive chloride channel mediates fast inhibitory glutamatergic neuromuscular transmission; and (ii) a nematocidal property of ivermectin derives from its activity as an agonist of glutamate-gated chloride channels in essential excitable cells such as those of the pharynx.

Alternative Splicing↗
PubMed1998

Ivermectin distribution using community volunteers in Kabarole district, Uganda.

Ivermectin mass distribution for the control of onchocerciasis in Uganda began in 1991. This report describes a community based ivermectin distribution programme covering two foci in the Kabarole district which have an estimated 32,000 persons infected and another 110,000 at risk. Through nodule palpation in adult males, 143 villages were identified where nodule prevalence exceeded 20%. Skin snips were also taken from a sample of the population to measure changes in community microfilarial load (CMFL) with treatment. The delivery programme was integrated into the district health management structure, and used community volunteers supervised by medical assistants from adjacent health facilities for annual ivermectin distribution campaigns. After initial efforts by the community to support distributors in-kind proved inadequate, ivermectin distributors earned money retailing condoms as part of the social marketing component of district STD/AIDS programme. Reduction in the CMFL ranged from 40-62% twelve months after the second ivermectin treatment in three villages, and from 69-84% six months after the fourth round of treatment in two villages. After four years of treatment, 85% of eligible persons were receiving ivermectin from community volunteers in each treatment cycle. Drop out rates among volunteers did not exceed 20% over the four years reported here. The direct cost of treatment was US $0.29 per person. Among the reasons for low per-person treatment costs were the strong supervisory structure, the presence of health centres in the foci and a well developed and capable district Primary Health Care management team.

Adult↗
PubMed1991

Changes in circulating parasite antigen levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin.

This study assessed changes in circulating parasite antigen levels after diethylcarbamazine (DEC) and ivermectin treatment of bancroftian filariasis to determine effects of these drugs on adult Wuchereria bancrofti in vivo. Thirty adult Haitians with microfilaremia were treated with 1 mg of ivermectin to reduce counts of microfilariae. Later, subjects were treated with either one or two 200 micrograms/kg doses of ivermectin or with 12 daily 6 mg/kg doses of DEC. Macrofilaricidal activity of these drugs was indirectly monitored by measuring circulating W. bancrofti antigen by EIA. Antigen levels fell by 75% after DEC and by 34% after ivermectin. These results suggest that low-dose ivermectin treatment followed by a standard course of DEC is a more effective macrofilaricidal regimen for W. bancrofti than either of the multidose ivermectin regimens used in this study.

Animals↗
PubMed1994

A randomized trial of single- and two-dose ivermectin versus thiabendazole for treatment of strongyloidiasis.

A randomized trial is described comparing ivermectin and thiabendazole for treatment of chronic infection with Strongyloides stercoralis. Subjects received ivermectin (200 micrograms/kg) in a single dose, ivermectin (200 micrograms/kg) on 2 consecutive days, or thiabendazole (50 mg/kg/day) twice daily for 3 consecutive days. Most subjects (94%) had intermittent symptoms, including urticaria, epigastric pain, and diarrhea. Stools were examined 7 days and 1, 3, 6, 10, and 22 months after treatment. Fifty-three subjects completed at least 3 months of follow-up. Only 1 of 34 and 2 of 19 ivermectin and thiabendazole subjects, respectively, had a stool positive for larvae after treatment. Symptoms were relieved in all 3 groups and eosinophil levels returned to normal in 90% of all subjects by 12 months. Nearly 95% of thiabendazole subjects had short-term adverse effects during therapy versus only 18% of those treated with ivermectin. One dose of ivermectin provides safety and efficacy equivalent to thiabendazole with a much lower prevalence of side effects and, consequently, better compliance.

Adolescent↗
PubMed1989

Control of lone star ticks (Acari: Ixodidae) on Spanish goats and white-tailed deer with orally administered ivermectin.

Ivermectin administered orally to Spanish goats, Capra hircus (L.), or to white-tailed deer, Odocoileus virginianus (Zimmerman), was highly effective against lone star ticks, Amblyomma americanum (L.). For Spanish goats, daily oral doses of 20 micrograms/kg resulted in greater than or equal to 2 ppb ivermectin in the blood. This level was sufficient to cause greater than 95% reduction of estimated larvae from feeding ticks. A bioassay with horn flies, Haematobia irritans (L.), was developed to estimate oral intake of ivermectin. Probit analysis of dose-mortality data indicated that a 50% reduction in adult horn fly emergence can be expected when the manure from goats treated orally with ivermectin at 10, 20, 35, and 50 micrograms/kg/d was mixed with untreated cow manure at a rate of 0.345, 0.110, 0.100, and 0.092%, respectively. In studies with white-tailed deer, daily oral doses of 35 and 50 micrograms/kg/d provided 100% control of adult and about 90% control of nymphs that were placed on treated fawns. A single oral dose of 50 micrograms/kg gave greater than 90% control of adult and nymphal ticks attached to treated fawns at the time of drug administration and 70% control of ticks placed on treated deer three days thereafter. When ticks were placed on fawns treated with a single dose of ivermectin (50 micrograms/kg) the engorgement period was longer, ticks were lighter in weight, and females laid fewer eggs than ticks detaching from control fawns. A single oral dose of ivermectin at 20 micrograms/kg prevented about 60% of the adult and nymphal ticks attached at the time of drug administration from engorging, but did not affect other ticks placed on the animals after treatment.

Administration, Oral↗
PubMed1996

The abamectin derivative ivermectin is a potent P-glycoprotein inhibitor.

Among the compounds endowed with the capacity to reverse the P-glycoprotein (Pgp)-mediated multidrug resistance of cancer cells, a powerful agent was found to be the cyclosporin D derivative SDZ PSC 833. After in vivo treatment with SDZ PSC 833, mice showed a decreased tolerability to cyclosporin A (CsA), but also to ivermectin, a widely used polycyclic lactone pesticide of Streptomyces avermitilis origin. The sequels were suggestive of CsA- or ivermectin-induced central nervous system dysfunction; they were interpreted as caused by the neutralization of the Pgp at the blood-brain barrier level, implying that CsA and ivermectin were Pgp substrates. CsA was already known to display both Pgp substrate and Pgp inhibitor properties. It now appears that ivermectin may also inhibit Pgp function. When compared in short-term assays for Pgp function inhibition, which measure the restoration of the retention of two Pgp probes in multidrug-resistant (MDR) cells to their parental (Par) cell levels, ivermectin appeared only a few fold weaker that SDZ PSC 833 in the case of murine monocytic leukemia MDR-P388 cells and nearly as active as SDZ PSC 833 in the case of human lymphocytic leukemia MDR-CEM cells. Therefore, like CsA or FK-506, ivermectin may also be a substrate and an inhibitor of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗