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PubMed1997

Immunoaffinity column cleanup procedure for analysis of ivermectin in swine liver.

A simple and sensitive method for the analysis of ivermectin (22,23-dihydroavermectin B1) in swine liver based on immunoaffinity column cleanup is described. The immunosorbent was prepared by coupling polyclonal anti-ivermectin antibodies to carbonyl diimidazole-activated Sepharose CL-4B. After extraction with methanol, ivermectin was cleaned up on an immunoaffinity column, and determined by reversed-phase liquid chromatography with UV absorbance detection at 245 nm. Recoveries of ivermectin from fortified samples of 5-10 micrograms kg-1 levels ranged 85-102%, with coefficients of variation of 6-12%. The limit of detection was 2 micrograms kg-1 in a 5-g samples.

Animals↗
PubMed2003

[Ivermectin use in tropical medicine].

Ivermectin is a major breakthrough for the treatment of onchocerciasis, strongyloidosis, scabies and cutaneous larva migrans. Combined with albendazole, ivermectin is highly efficient for treating lymphatic filariasis and intestinal worms. Ivermectin shows very few side-effects but its use in children below 5 and during pregnancy is discussed. Ivermectin tolerance could be related to mdr1 gene expression. Additional studies are needed to assess its efficiency for pediculosis.

Antiparasitic Agents↗
PubMed1992

Efficacy of ivermectin against Parastrongylus malaysiensis infection in rats.

The efficacy of ivermectin on experimental infections of P. malaysiensis in rats was determined. Ivermectin was 99.4% and 97.9% effective at a dosage of 400 meg and 800 meg respectively at seven days post-infection. The same two dosages of ivermectin when given at 14 days post infection had an efficacy of 100%. However, as an adulticide it had only 40.7% efficacy. Ivermectin may therefore be useful for the treatment of parastrongyliasis due to the larval stages of the worm which can cause significant pathology in man and animals.

Angiostrongylus↗
PubMed1993

An ion-sensitive microelectrode study on the effect of a high concentration of ivermectin on chloride balance in the somatic muscle bag cells of Ascaris suum.

Ivermectin has been shown to increase chloride conductances of invertebrate cells. On the muscle cells of the parasitic nematode Ascaris, ivermectin acts as both a GABA receptor antagonist and a chloride channel opener. In this study, ion-sensitive microelectrodes were used to investigate the effect of ivermectin on intracellular Cl- concentration of the somatic muscle bag cells of Ascaris suum. Incubation of muscle cells with ivermectin (10 microM in 1% dimethyl sulphoxide vehicle for 60 min) increased intracellular Cl- by 2.9 mM or 15% compared to controls (P < 0.01, n = 6).

Animals↗
PubMed2002

Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment.

A pleomorphic neoplasm (PN) is described from sections of Onchocerca volvulus worms in nodules excised from Cameroonian patients. PN is confined to older, non-fecund, female worms, and those classed as moribund/dead. It is mainly composed of small, roundish, basophilic cells of diverse sizes, often forming a 'rosette' pattern around amorphous eosinophilic centres. The cells have a high nuclear/cytoplasmic ratio and up to 2-3 mitoses/high-power field; some become grossly enlarged, highly polymorphic and contain large, irregular blocks of chromatin. The eukaryotic PN cells first appear posteriorly in the pseudocoelom, probably from ovarian cells; they spread anteriorly, invading or compressing the uteri. Ivermectin treatment increased the prevalence PN from 3.7% of 1422 female worms in 637 patients before treatment to 17.5% of 1134 worms in 511 patients after 3 years treatment. Ivermectin at 400-800 microg/kg annually, or at 150 microg/kg or 400-800 microg/kg 3-monthly, over 3 years, did not increase the PN prevalence significantly, as compared with standard doses of 150 microg/kg annually. In other small series of African patients, PN prevalence increased in worms 2, 4, 6 and 10 months after ivermectin treatment; but there was no increase after treatment with amocarzine, albendazole or diethylcarbamazine and suramin. PN may partly account for the increased macrofilaricidal action of ivermectin on female O. volvulus in patients treated for 3 years at 3-monthly intervals.

Adult↗
PubMed2004

Genetic variability of glutamate-gated chloride channel genes in ivermectin-susceptible and -resistant strains of Cooperia oncophora.

The glutamate-gated chloride channels (GluCls) are members of the ligand-gated ion channel superfamily that are thought to be involved in the mode of action of ivermectin and mechanism of resistance. Using reverse-transcriptase PCR techniques, 2 full-length GluCl cDNAs, encoding GluClalpha3 and GluClbeta subunits, were cloned from Cooperia oncophora, a nematode parasite of cattle. The two sequences show a high degree of identity to similar subunits from other nematodes. The C. oncophora GluClalpha3 subunit is most closely related to the Haemonchus contortus GluClalpha3B subunit, while C. oncophora GluClbeta subunit shares high sequence identity with the H. contortus GluClbeta subunit. Using single-strand conformation polymorphism, the genetic variability of these two genes was analysed in an ivermectin-susceptible isolate and an ivermectin-resistant field isolate of C. oncophora. Statistical analysis suggested an association between the C. oncophora GluClalpha3 gene and ivermectin resistance. No such association was seen with the GluClbeta gene.

Amino Acid Sequence↗
PubMed2000

Ivermectin alone or in combination with benzyl benzoate in the treatment of human immunodeficiency virus-associated scabies.

In order to establish a safe and reliable treatment for human immunodeficiency virus (HIV)-associated scabies, we have treated 60 episodes of scabies in this setting, occurring in 39 patients, with one of the following regimens: (i) topical treatment with benzyl benzoate solution; (ii) single-dose oral treatment with ivermectin alone; and (iii) combination therapy with benzyl benzoate solution and oral ivermectin, employing the same regimens as single-agent therapy. Patients were stratified according to the severity score of the disease and the outcome (eradication, relapse, failure). We found that both benzyl benzoate and ivermectin alone were quite effective in mild to moderate scabies, but they were both associated with an unacceptable rate of relapse and failure in severe or crusted scabies. In contrast, combined treatment produced an optimal rate of success, without significant treatment-related side-effects. Therefore, we consider that combination treatment with benzyl benzoate solution and oral ivermectin is preferable to single-agent therapy in crusted scabies occurring in HIV/acquired immune deficiency syndrome patients.

AIDS-Related Opportunistic Infections↗
PubMed2002

Treatment of 18 children with scabies or cutaneous larva migrans using ivermectin.

In addition to onchocerciasis and other filarial diseases, ivermectin has been used for the treatment of scabies, head lice, larva migrans and gnathostomiasis. However, there is concern regarding the safety of its use in children under 5 years of age or weighing less than 15 kg. We present our experience in 18 children (aged 14 months to 17 years), with scabies or cutaneous larva migrans successfully treated with ivermectin. They included four cases of crusted scabies associated with immunosuppression and seven cases of common scabies four of whom had associated clinical mental retardation, immunosuppression or hypomobility. A further seven patients had cutaneous larva migrans. Fifteen patients were cured with a single dose of ivermectin, and three patients with crusted scabies required a second dose. None of our patients suffered significant adverse effects. We believe that ivermectin is a safe and effective alternative treatment of cutaneous parasitosis in children.

Adolescent↗
PubMed1996

A community trial of ivermectin for onchocerciasis in Sierra Leone: compliance and parasitological profiles after three and a half years of intervention.

We have studied the compliance patterns and the long-term effects of repeated ivermectin at various dosing intervals in a randomized controlled trial. The setting for the trial was six neighbouring communities hyperendemic for onchocerciasis in southern Sierra Leone. A total of 335 subjects attended a survey 18 months after the fifth treatment round. Of those randomized to ivermectin, over 85% had received at least three doses. There was no evidence that women of childbearing age were consistently under-treated, despite the criteria for exclusion from treatment. An intention-to-treat analysis showed that a 6-monthly ivermectin treatment regime satisfactorily suppressed microfilarial loads. Microfilarial repopulation was significantly slower over an 18-month period after multiple doses compared to a single dose. Further analysis of microfilarial repopulation suggests that there is a cumulative suppressive effect after at least the first three doses of ivermectin, and that an annual treatment interval is as effective for short-term microfilarial suppression as a 6-monthly interval.

Adolescent↗
PubMed1996

Ultrasonographic assessment of the adulticidal efficacy of repeat high-dose ivermectin in bancroftian filariasis.

Since diethylcarbamazine, the drug recommended for treatment of lymphatic filariasis, seems only partially effective against the adult worm, intense interest persists in identifying a macrofilaricidal drug for this infection. To evaluate directly in vivo the macrofilaricidal activity of repeat high-dose ivermectin, 15 men who had living adult Wuchereria bancrofti detected in the scrotal area by ultrasound were treated with 400 micrograms/kg of ivermectin at 2-week intervals for 6 months (total dose, 4.8 mg/kg). Serial ultrasound examinations were performed before, during, and for 6 months after treatment. Profound suppression of microfilaraemia followed the first dose of ivermectin, but movements characteristic of the adult worm on ultrasound remained unchanged both in location and pattern. Even when given in total doses of 4.8 mg/kg, ivermectin appears to have no observable activity against adult W. bancrofti, although its ability to suppress microfilaraemia makes it potentially useful for the control of lymphatic filariasis.

Adult↗
PubMed1997

Immunohistological studies on macrophages in lymph nodes of onchocerciasis patients after treatment with ivermectin.

The role of macrophages in the killing and elimination of microfilariae (mf) was studied immunohistologically in 14 lymph nodes from 10 patients with generalized onchocerciasis 20-68 h after treatment with a single oral dose of 150 microg/kg ivermectin. Mf with signs of damage at light microscopical level were surrounded by a cellular infiltrate comprising macrophages, eosinophils and neutrophils, whereas light microscopically intact mf mostly showed no cellular reaction. Resident mature macrophages expressing the CD 68 epitope usually neither migrated nor attached to damaged mf, especially on the first and second day after ivermectin treatment. However, many young invading macrophages labelled for the L1 protein (antibodies 27 E 10, MAC 387, S 36.48 and 8.5C2) were found within the cellular infiltrate around damaged mf and in adherence to the mf in all lymph nodes after ivermectin treatment. Free L1 protein was observed on the cuticle of the mf. The attacking macrophages contained increased amounts of the enzymes lysozyme, alpha-1-antichymotrypsin and alpha-1-antitrypsin compared to resident macrophages. Free enzymes were found on the cuticle of the mf and around them, indicating a role of these enzymes in the inflammatory reaction to the parasites. The attacking macrophages were strongly labelled for human HLA-DR and they showed further an increased expression of the complement receptors CR1 (CD 35) for C3b and CR3 (CD 11b) for C3 bi in comparison to resident macrophages and thus were considered as activated macrophages. Rarely fragments of mf were seen within multinuclear macrophages. We conclude that young activated macrophages play a major role in the elimination of mf transported to the regional lymph nodes after ivermectin treatment. The immunohistological findings are in accordance with the assumption that these activated macrophages together with granulocytes contribute to the killing of the damaged mf. They also help to limit the damage of the host tissue by release of alpha-1-antichymotrypsin and alpha-1-antitrypsin.

Adult↗
PubMed1998

Willingness to pay for community-based ivermectin distribution: a study of three onchocerciasis-endemic communities in Nigeria.

OBJECTIVE: To determine the willingness to pay (WTP) for local ivermectin distribution in a community financing framework. METHOD: Contingent valuation in three communities in Nigeria, using randomly selected household heads. WTP was elicited using a bidding game, and for collecting information on the households' socio-economic status, level of knowledge, priority ranking and perception of risk of contracting the disease, structured questionnaires were used. Ordinary least squares (OLS) multiple regression analysis was used to analyse factors associated with WTP. RESULTS: Between 92.1% and 93.3 % of respondents were willing to pay amounts ranging from 5 Naira (US$ 0.06) to 100 Naira (US$ 1.25) (median: 20 Naira, US$ 0.25) in the three communities, more than three times the modelled unit direct cost of distributing ivermectin by the communities themselves. Occupation of the respondent, marital status, average monthly expenditure on health care, manifestations of onchocerciasis, the type of savings scheme embarked on by the respondent, age-group, level of education and type of property were statistically significant (P < 0.05) variables affecting WTP. CONCLUSION: This study shows that there is WTP for local ivermectin distribution in the three study communities, and that it should be assessed before instituting community-directed treatment with ivermectin.

Adult↗
PubMed2002

Efficacy of ivermectin delivered via a controlled-release capsule against small lungworms (Protostrongylidae) in sheep.

To evaluate the efficacy of an ivermectin controlled-release capsule (CRC), which delivers 1.6 mg ivermectin per day intraruminally for 100 days to sheep weighing 40-80 kg (IVOMEC Maximizer CR Capsule for adult sheep, Merial), against small lungworms two studies with 48 naturally infected adult female Merino Landrace sheep were conducted. The sheep were allocated by restricted randomization based on bodyweight to untreated controls or received an ivermectin CRC. Eight sheep per group were necropsied 35, 70 or 105 days post-treatment. Lungworms were recovered by dissection or peptic digestion of the lungs. Baermann/Wetzel technique was used for faecal lungworm larval counts at weekly intervals. The efficacy of treatment was 100% against Dictyocaulus filaria and Protostrongylus rufescens (P < 0.05) at each necropsy day. The efficacy against Protostrongylus brevispiculum, Cystocaulus ocreatus and Neostrongylus linearis increased from 35 to 105 days after administration of the CRC and was found to be 100% (P < 0.01), 96.6% (P < 0.01) or 99% (P < 0.01), respectively, at 105 days post-treatment. The reductions of Muellerius capillaris counts varied and were 96.2% (P < 0.05) at 70 days post-treatment and 44.6% (P > 0.1) at 105 days post-treatment. Faecal lungworm larvae disappeared nearly completely from at least 3 weeks after the ivermectin CRC administration for all protostrongylid species including M. capillaris so that pasture infectivity will be subsequently significantly reduced.

Administration, Oral↗
PubMed2002

Ivermectin used in percutaneous drug injection method for the treatment of liver hydatid disease in sheep.

BACKGROUND & AIMS: Ivermectin is a macrocyclic lactone (avermectins) produced by the actinomycete Streptomyces avermitilis. In this experimental study, the effectiveness of intracystic injection of ivermectin was studied as a new approach of percutaneous treatment of cystic echinococcosis. METHODS: Twelve naturally infected sheep were selected and divided into 2 subgroups: treatment group (n = 9) and control group (n = 3). In the treatment group, approximate volume of ivermectin solution needed to achieve an intracystic concentration of 10 microg/mL was injected into cysts, but in the control group, sterile distillated water was applied. No reaspiration was performed at all. RESULTS: In the following period of 6 months, repeated sonography revealed a significant decrease in cyst sizes and progressive solidification of the cysts in the treatment group. In the control group, volumes of the cysts were increased. No major complications occurred during or after the procedure. After 6 months, all sheep were killed and examined for macroscopic and microscopic changes. Pathologic examination in the treatment group showed pericyst hyalinization, inflammatory cells in the cyst wall, degeneration of laminated and germinal membrane, and necrotic material in the cyst cavity. No viable protoscolices or daughter cysts were observed. CONCLUSIONS: Percutaneous treatment of cystic echinococcosis with ivermectin as a scolicidal agent seems to be effective in this animal model.

Administration, Cutaneous↗
PubMed2000

Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin.

The fruit fly Drosophila melanogaster was used to examine the mode of action of the novel insecticide and acaricide nodulisporic acid. Flies resistant to nodulisporic acid were selected by stepwise increasing the dose of drug in the culture media. The resistant strain, glc(1), is at least 20-fold resistant to nodulisporic acid and 3-fold cross-resistant to the parasiticide ivermectin, and exhibited decreased brood size, decreased locomotion, and bang sensitivity. Binding assays using glc(1) head membranes showed a marked decrease in the affinity for nodulisporic acid and ivermectin. A combination of genetics and sequencing identified a proline to serine mutation (P299S) in the gene coding for the glutamate-gated chloride channel subunit DmGluClalpha. To examine the effect of this mutation on the biophysical properties of DmGluClalpha channels, it was introduced into a recombinant DmGluClalpha, and RNA encoding wild-type and mutant subunits was injected into Xenopus oocytes. Nodulisporic acid directly activated wild-type and mutant DmGluClalpha channels. However, mutant channels were approximately 10-fold less sensitive to activation by nodulisporic acid, as well as ivermectin and the endogenous ligand glutamate, providing direct evidence that nodulisporic acid and ivermectin act on DmGluClalpha channels.

Animals↗
PubMed1998

Treatment of microfilaraemia in asymptomatic brugian filariasis: the efficacy and safety of the combination of single doses of ivermectin and diethylcarbamazine.

Although combinations of ivermectin and diethylcarbamazine (DEC) have been shown to be superior to either drug alone in the suppression of bancroftian microfilariae, their efficacy against infections with Brugia malayi has never been investigated. The present, open trial is the first on the efficacy and safety of a combination of single doses of ivermectin and DEC when used against microfilaraemias of brugian filariasis. Twenty-one, asymptomatic but microfilaraemic (109-6934 microfilariae/ml blood, with a median of 841/ml) men, aged 18-48 years, each received oral doses of ivermectin (400 micrograms/kg) and DEC (6 mg/kg) as a single treatment. Twelve hours post-treatment, 96.5%-100% of the microfilariae in each subject had been cleared and 12 of the subjects were amicrofilaraemic. A further reduction in microfilarial counts was evident 1 month post-treatment (mean clearance = 99.0%) and the counts continued to fall at least until the last follow-up, at 1 year post-treatment, when the mean clearance was 99.9% and 13 (68.4%) of the 19 subjects then investigated were amicrofilaraemic. All subjects experienced adverse reactions of one form or another, lasting for up to 48 h post-treatment; these included fever, myalgia, headache, and lethargy. Postural hypotension was recorded in two subjects and dilated, inflamed lymphatic channels were seen in another two. The combination of ivermectin and DEC demonstrated a microfilaricidal effect superior to that of either drug used alone, both in the initial rapid clearance of microfilariae and in sustaining the effect for 1 year. This finding has important implications for the control of lymphatic filariasis.

Adolescent↗
PubMed1999

Efficacy of albendazole and its combinations with ivermectin or diethylcarbamazine (DEC) in the treatment of Trichuris trichiura infections in Sri Lanka.

The efficacy of the drugs currently available for treatment of infection with Trichuris trichiura is low compared with that of the drugs used against roundworm and hookworm. Single-dose combinations of albendazole with ivermectin or of albendazole with diethylcarbamazine (DEC) have recently been seen to produce raid and sustained reductions in Wuchereria bancrofti microfilaraemia. This observation prompted the present study, on the efficacy of these combinations against trichuriasis. The drug regimens tested were albendazole (400 mg) alone, albendazole (400 mg) with ivermectin (200 micrograms/kg), and albendazole (400 mg) with DEC (6 mg/kg). Most (155) of the 176 children (4-14 years of age) who each provided a single, pre-treatment, stool sample were found positive for Trichuris ova. These 155 were each randomly allocated to one of the three treatment groups and checked for infection 3 weeks post-treatment, again by a single stool examination. Single-dose therapy with albendazole plus ivermectin produced a 'cure rate' (79.3%) and an egg-reduction rate (93.8%) which were significantly higher than the corresponding rates produced by albendazole alone or albendazole plus DEC (P < 0.01 for each). The efficacies of albendazole with DEC and of albendazole alone were statistically equivalent. Single-dose treatment with the albendazole-ivermectin combination appears to be highly effective against trichuriasis and could prove valuable for routine use.

Adolescent↗
PubMed2005

Confirmation of resistance to ivermectin by Cooperia curticei in sheep.

AIM: To investigate the occurrence of resistance to a full dose of oral ivermectin by Cooperia curticei in sheep. METHODS: Twelve lambs on a sheep and cattle property in the North Island of New Zealand were randomly allocated to one of two equal-sized groups. One group was treated orally with a single dose of ivermectin at the manufacturer's recommended dose rate of 0.2 mg/kg, while the other remained as an untreated control. Worm counts were carried out post mortem on the abomasa and small intestines of all animals in both groups 7 days after treatment. RESULTS: While treatment with ivermectin reduced the numbers of all other worm genera to almost zero, those of Ostertagia(= Telodorsagia) circumcincta and C. curticei were reduced by only 37% and 19%, respectively. CONCLUSIONS: These results provide clear evidence of resistance to ivermectin by O. circumcincta and C. curticei. They also appear to represent the first record of macrocylic lactone (ML) resistance in C. curticei in sheep in New Zealand or elsewhere.

Abomasum↗