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The efficacy of formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica) and gastro-intestinal nematodes in cattle and sheep and sucking lice species in cattle.

OBJECTIVE: To assess the efficacy of two formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica), gastro-intestinal nematodes and sucking louse species in cattle and sheep. PROCEDURE: A study of 540 cattle and 428 sheep at 18 sites throughout Victoria and New South Wales was undertaken. At each site, one group of cattle or sheep was treated with a combined formulation (Fasimec Cattle or Fasimec Sheep), another received ivermectin and triclabendazole separately. In trials on lice infestation, an additional group remained untreated. Samples for faecal egg counts were collected on days -7, 0 (treatment day), +7, +14 and +21 after treatment. Lice assessments were carried out on days -7, 0, +7, +14, +28, +42 and +56. RESULTS: Both treatments were highly efficacious (> 98% efficacy) against liver fluke in cattle and sheep, against three sucking lice species of cattle and against gastro-intestinal nematodes in sheep. There was also no significant difference between treatments in efficacy. Against gastro-intestinal nematodes, Fasimec Cattle was significantly (P < 0.01) more effective than the separately applied ivermectin and triclabendazole treatment. Mean efficacy for the Fasimec Cattle and Ivomec/Fasinex 120 groups respectively, was 97.6% and 94.2% on Day +7, 98.9% and 91% on Day +14 and 98.5% and 92.6% on Day +21. CONCLUSION: The efficacy of Fasimec' Cattle and Fasimec Sheep was at least equal to that of currently registered products (with the same active ingredients) used to control these parasites.

Administration, Oral↗

The effects of ivermectin on transmission of Onchocerca volvulus.

Ivermectin, given to onchocerciasis patients as a single oral dose of 200 micrograms per kilogram of body weight, substantially reduced the uptake of Onchocerca volvulus microfilariae by Simulium yahense, an efficient black fly vector of the parasite in the tropical rain forests of West Africa. Three months after treatment, patients given ivermectin infected flies at a significantly lower rate than those who had received diethylcarbamazine or placebo, thereby reducing the number of developing larvae in the vector population. This diminished rate of infectiousness was also evident 6 months after treatment. These results strongly suggest that ivermectin could be effective in interrupting transmission of Onchocerca volvulus for epidemiologically important periods of time.

Humans↗

Comparison of vaccination and ivermectin treatment in the prevention of bovine lungworm.

Three groups of calves were put out to graze on separate paddocks within a field known to be infected with Dictyocaulus viviparus and were also given a small initial trickle infection of the parasite. The first group were untreated controls, the second were immunised with live irradiated lungworm vaccine and the third were injected three times with ivermectin; the injections taking place after they had grazed for three, eight and 13 weeks. The subsequent infections of D viviparus were estimated by grazing a series of parasite-free tracer calves in the paddocks used by each group. The first group of such calves grazed from July 17 until August 7, the second from August 22 to September 29. During the first half of the grazing season all the untreated and three of the six immunised calves were observed to excrete D viviparus larvae, in contrast to none of the ivermectin-treated group. As a result all the tracer calves on the areas occupied by the untreated and immunised calves became infected with the parasite whereas only one worm was found in one of the 10 tracer calves grazing the area occupied by the ivermectin-treated calves.

Animals↗

Efficacy of topically administered ivermectin against chorioptic and sarcoptic mange of cattle.

The efficacy of topically administered ivermectin against Chorioptes bovis and Sarcoptes scabiei var bovis on cattle was evaluated in five studies involving a total of 68 cattle. Treatment with ivermectin solution at a dose rate of 500 micrograms/kg bodyweight topically once was fully effective against C bovis and S scabiei when applied to healthy skin. Efficacy against S scabiei was impaired when the formulation was applied over areas of severe lesions caused by this parasite, presumably due to reduced absorption of ivermectin.

Administration, Topical↗

Evaluation of the persistence of the effect of ivermectin and abamectin against gastrointestinal and pulmonary nematodes in cattle.

The persistence of the effect of ivermectin and abamectin against gastrointestinal nematodes and lungworm in cattle was evaluated in two trials, each involving 28 animals. Groups of seven cattle either remained untreated, or were treated topically with ivermectin at 500 micrograms/kg bodyweight or subcutaneously with either ivermectin or abamectin at 200 micrograms/kg bodyweight. Starting on the day of treatment the cattle were given daily trickle infections with various infective nematode larvae for two weeks (Haemonchus species, Trichostrongylus axei and Cooperia species), three weeks (Ostertagia ostertagi and Oesophagostomum radiatum) and four weeks (Dictyocaulus viviparus). The cattle were killed 49 to 51 days after treatment and their worm burdens measured. An efficacy of > 99 per cent was recorded in all the groups demonstrating that the products controlled Haemonchus species, T axei, C oncophora, C punctata and C surnabada for at least two weeks, O ostertagi and O radiatum for at least three weeks and D viviparus for at least four weeks.

Administration, Topical↗

Efficacy of an ivermectin controlled-release capsule against nematode and arthropod endoparasites in sheep.

Five controlled trials were conducted in Germany or in the United Kingdom, using 74 female sheep of merino or Dorset horn breeds, to evaluate the efficacy of an ivermectin controlled-release capsule against naturally acquired or induced infections of gastrointestinal nematodes, lungworms and nasal bot larvae and against incoming infections with gastrointestinal and pulmonary nematodes. Half of the animals were treated with one ivermectin controlled-release capsule that delivered ivermectin at the rate of 1.6 mg per day for 100 days while the other half remained untreated. Parasites were counted 21, 28, 35 or 56 days after administration of the capsule. The treatment was highly effective (> or = 99 per cent) against established parasites of the following species: Haemonchus contortus (adults and fourth-stage larvae), Ostertagia circumcincta, O pinnata, O trifurcata, Ostertagia species fourth-stage larvae, Trichostrongylus axei, T colubriformis, T vitrinus, Cooperia curticei, Nematodirus battus, N filicollis, Strongyloides papillosus, Chabertia ovina, Oesophagostomum venulosum, Trichuris ovis, Tr skrjabini, Dictyocaulus filaria, Protostrongylus rufescens and Oestrus ovis (larvae). The treatment prevented the establishment of the gastrointestinal nematodes H contortus, O circumcincta, T axei, T colubriformis, C curticei, N battus, N filicollis, Ch ovina, Oe vennulosum and the establishment of the lungworm D filaria by > 99 per cent compared with untreated controls (P < or = 0.01).

Animals↗

Evaluation of the dosage of ivermectin in falcons.

Twelve groups of falcons, each containing three female gyrfalcon-peregrine falcon hybrids (Falco rusticolus x Falco peregrinus) were injected intramuscularly with a single dose of ivermectin ranging from 0.2 mg/kg to 11 mg/kg bodyweight, and a control group was injected with water. Doses of ivermectin between 0.2 and 5 mg/kg failed to produce clinical signs of illness in the birds. Four birds which received either 6, 7 or 8 mg/kg showed slight clinical signs, and all the birds receiving 9 to 11 mg/kg showed more or less severe clinical signs of anorexia, apathy and sedation. Slight changes in the mean plasma activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase (AP) were detected in the group dosed with 5 mg/kg, and higher dosages caused marked changes in these enzymes as well as in the mean plasma activity of lactate dehydrogenase. The mean activity of AP decreased, and the activities of the other enzymes increased. A dosage of 2 to 3 mg/kg ivermectin is recommended as a safe and effective antiparasitic drug for falcons and it has been used successfully to treat infestations of Serratospiculum species.

Alanine Transaminase↗

Using ivermectin-treatment coverage among schoolchildren monitored by schoolteachers as a proxy of population coverage in areas of Uganda where onchocerciasis is endemic.

In the control of onchocerciasis using mass treatment with ivermectin, coverage needs to be monitored regularly so that communities with poor or insufficient coverage can be identified and timely and appropriate interventions then instituted. The aim of the present study was to assess whether ivermectin-treatment coverage in schoolchildren, as monitored by schoolteachers, could be used as a proxy of population coverage. Although the coverages estimated in schoolchildren were found to be significantly correlated with estimates based on household surveys (P=0.01), there was poor correlation between either school and household-survey coverage and the values recorded in community registers. Although the community-register figures are the ones which the district health services normally use to report treatment coverage, they may be unreliable. Ivermectin-treatment coverage in schoolchildren monitored by schoolteachers could give a good and more accurate approximation of total population coverage. Further, large-scale studies, that take into consideration the cost-effectiveness of the various methods available to validate reported treatment coverage, are recommended.

Adolescent↗

Implementing community-directed treatment with ivermectin for the control of onchocerciasis in Uganda (1997-2000): an evaluation.

Over the period 1997-2000, an evaluation was made, in 10 districts of Uganda, of the onchocerciasis-control programme based on community-directed treatment with ivermectin (CDTI). This programme is supported by the Ministry of Health, the African Progamme for Onchocerciasis Control (APOC) and The Carter Center Global 2000 River Blindness Programme. The data analysed came from: (1) monthly and annual reports; (2) annual interviews, in randomly-selected communities in selected districts, with heads of household, community leaders and ivermectin distributors; (3) participatory evaluation meetings (PEM); (4) participant observation studies; and (5) key informants. The percentage of treated communities in the 10 study districts achieving satisfactory treatment coverage [i.e. > or = 90% of the annual treatment objective (ATO)] rose from 46.0 in 1997 to 86.8 in 2000. This improvement was largely attributable to the adoption of collective CDTI decision-making by community members, avoidance of paving monetary incentives to the ivermectin distributors, and the satisfaction with the programme of those who had been treated. Coverage improved as the numbers of community members who were involved in choosing the method of distribution and in selecting their own community-directed health workers (CDHW) increased. Health education was also critical in improving individual members' involvement in decision-making, and in mobilizing other community members to take part in CDTI. Involvement of kinship groups, as well as educated community members as supervisors of CDHW, also helped to increase coverage. In a regression model, satisfaction with the programme was revealed as a significant predictor of the achievement of the target coverage (P<0.001). Cost per person, as an indicator for sustainability, varied with the size of the population under treatment, from at least U.S. $0.40 when the district ATO was <15,000 people, to U.S. $0.26 with an ATO of 15,000-40,000 and less than U.S. $0.10 when the district ATO exceeded 40,000 people. These results cast doubt on the validity of the current APOC indicator for sustainability, of a cost of no more than U.S. $0.20/person for all CDTI projects, whatever the size of the population to be treated. Although some women were involved in decision-making, their current involvement as supervisors or CDHW was minimal. Most of the present data were obtained through monitoring and operational-research activities that have been carried out, in an integrated fashion, within the Ugandan CDTI programme since its launch. It is recommended that assessment, monitoring and evaluation be widely used within all CDTI efforts. Operational research should remain focused and appropriate and directly involve the personnel who are executing the programme.

Community Health Services↗

[Nosocomial outbreak of scabies in a psychiatric hospital--epidemiological assessment and prophylactic treatment with oral ivermectin].

OBJECTIVES: To evaluate the effectiveness of mass treatment with ivermectin of scabies outbreak in institutional settings. To determine the factors, such as host susceptibility and scabetic exposure level associated with the onset of scabies. METHODS: The authors investigated a nosocomial scabies outbreak in a close psychiatric ward. The index case was a man with steroid-induced localized crusted scabies. Twenty-six patients were diagnosed with scabies, 4 of them had relapse of scabies, while no staff was infested. Despite frequent surveillance and treatment of symptomatic patients with 1% gamma-benzenehexachloride (gamma-BHC: Lindane), new cases were observed. Thus, all 69 patients in the ward were treated with ivermectin (200 microg/kg) simultaneously on day 105 of the outbreak (the mass treatment). Patients who had scabies were compared with patients who had no scabies in terms of age, body weight, diabetes, physical functions, topical administration of corticosteroid, proximity to the index patient, and problematic behavior. RESULTS: The mass treatment was implemented without a significant adverse event. Although two patients developed symptoms of scabies after the mass treatment, no patient in the ward had been diagnosed with scabies since the 98th day of the treatment. Regarding factors associated with the scabies onset, the only statistically significant factor was proximity to the index patient with crusted scabies. CONCLUSIONS: Oral ivermectin was safe and effective for controlling scabies in institutional settings. The exposure level to scabetic mites was more important than host susceptibility in determining the risk of scabies onset.

Administration, Oral↗

Efficacy of ivermectin against Setaria microfilariae in calves and cerebrospinal setariosis in sheep and goats.

Ten calves harboring microfilariae (Mf) were injected with ivermectin at a single dose of 200 micrograms/kg body weight. Thereafter, the number of calves harboring Mf was gradually reduced to 7, 2 and 0 by 1, 4 and 12 weeks, respectively and remained negative for microfilariae by 16 weeks after injection. Furthermore, none of 221 goats and sheep injected twice with ivermectin at a dose of 200 micrograms/kg body weight developed setariosis while 17 out of 303 non-injected animals suffered from that disease. Therefore, ivermectin was much effective for the eradication of Mf in calves and the prevention of setariosis in sheep and goats.

Animals↗

Efficacy of ivermectin against live mites and eggs of Sarcoptes scabiei in pigs.

Sows infested with Sarcoptes scabiei var. suis (ssvs) were treated with 75, 150 and 300 micrograms/kg of ivermectin by a single subcutaneous injection at the neck region. Compared to the numbers of mites and eggs just before injection, those on post treatment weeks (PTW) 1, 2 and 4 showed significant decreases. Especially at 300 micrograms/kg, the counts showed almost all mites and eggs were eradicated on PTW 1, manifesting ivermectin to possess potential effect on ssve without apparent abnormal side effect. Potential mitocide effect of ivermectin on ssvs was revealed.

Animals↗

[Treatment of experimental infection by Strongyloides venezuelensis in rats, with the use of injectable ivermectin and levamisole].

For the therapy of human strongyloidiasis, are necessary effective drugs to eliminate both larvae and adult worm parasitism, which may also be used by parenteral route, to obviate the particular conditions presented by many patients. A study based on the experimental infection by Strongyloides venezuelensis in rats was done, administering injectable ivermectin or levamisole. Both drugs were shown to be active, when used in single doses of 0.2 to 0.5 mg/kg of ivermectin, or 26 mg/kg for levamisole. Ivermectin was slightly more effective as far as larval stage of the infection is concerned, and the same happened for levamisole for the adult worm stage. Promising perspectives are visualized to improve the therapy of patients with serious disseminated infection by Strongyloides stercoralis.

Animals↗

Effects of ivermectin on Culex quinquefasciatus larvae.

The effects of ivermectin, a semi-synthetic drug widely used for treatment of livestock parasite diseases, were observed on Culex quinquefasciatus larvae. Toxic effects and mortality evaluation were carried out after 5, 15, 30 and 60 minutes of exposure to 1, 5 or 10 ppm of ivermectin solutions. Observations were made 24 and 48 hours after the beginning of the experiment, and loss of mobility, progressive paralysis and high mortality of larvae were recorded. The observed effects of ivermectin on the mosquito larvae is probably correlated with chloride channel activation on cell membranes.

Animals↗

Attempt to control ticks (Acari: Ixodidae) on deer on an isolated island using ivermectin-treated corn.

We report an attempt by an offshore island community to control the vector tick of Lyme disease by providing ivermectin-treated corn to an isolated herd of free-ranging white-tailed deer, Odocoileus virginianus Zimmerman. Medicated corn was supplied in troughs within the island village and from automatic feeders at remote sites during 5 consecutive fall and spring adult tick questing seasons. Acaricide consumption was monitored by assaying its presence in fresh deer pellets and its concentration in deer sera. Its effectiveness was evaluated by recording the number of adult ticks collected from the hides of deer, the number of females becoming sufficiently engorged to oviposit, and the success of subsequent oviposition and eclosion. Entomologic risk was monitored by collecting immature ticks from hosts and adult ticks from vegetation. Estimates based on a subsequent deer reduction program indicated that up to twice as many deer had been present during the project as originally presumed. For this and other reasons related to deer behavior, target levels of serum ivermectin were achieved in a minority of deer. Nevertheless, > 90% control of female tick infestation, subsequent oviposition, and larval eclosion was obtained in those 8 of 16 sampled deer with serum ivermectin levels of > or = 15 ng/ml. In addition, the ratio of females to males, the numbers of females engorging > 10 mg body weight, and the numbers of those eventually hatching, were all significantly less among ticks from island deer in comparison with ticks from untreated deer. No consistent changes in the numbers of ticks found on immature-stage hosts or removed from vegetation were noted within 3 yr of the cessation of treatment.

Animal Feed↗

Ivermectin toxicosis in a chameleon (Chamaeleo senegalensis) infected with Foleyella furcata.

Both male and female Foleyella furcata were found in the subcutaneous tissue and abdominal cavity of an adult male wild-caught Senegalese chameleon (Chamaeleo senegalensis). This nematode species is endemic to Madagascar but has never been recorded from the continent of Africa. Prior to the chameleon's death, a migrating worm was seen under the skin in the abdominal and thoracic region. Huge numbers of small, sheathed microfilariae were detected in the blood smears. The chameleon was treated with a single dose (0.2 mg/kg s.c.) of ivermectin. Serious adverse reactions (complete inertia) developed within 24 hr after injection and lasted for 7 days, indicating either ivermectin toxicity or a systemic reaction involving the release of endotoxins from the microfilariae dying in the bloodstream as a result of parasiticide therapy. Therefore, ivermectin treatment of chameleons infected with Foleyella should be avoided.

Animals↗

Comparison of ivermectin, doramectin, selamectin, and eleven intermediates in a nematode larval development assay.

Chemical substitutions at pharmacologically relevant sites such as C-5, C-13, C-22,23, and C-25 were examined in ivermectin, doramectin, selamectin, and a series of 11 other intermediates using a larval development assay with Haemonchus contortus. A range of activities spanning 5 orders of magnitude were manifest with small changes in the substituents to the 14 avermectins. Within this compound series, there was no major potency advantage or disadvantage to a disaccharide over a monosaccharide substituent at C-13. Ivermectin and doramectin were each fully effective at a concentration of 0.001 microg/ml, and both were similar to their respective monosaccharide homologs. Specific patterns emerged among the analogs with substituents at C-5. Analogs possessing hydroxyl groups at C-5 were superior in activity by several orders of magnitude over those with oxo substituents. Replacement of the oxo with an oxime (NOH) restored activity to some degree but did not restore it to the level of those possessing the hydroxyl substituent. Consequently, ivermectin and doramectin that possess hydroxyl moieties at C-5 were superior against H. contortus to those like selamectin that have oxime substituents. There was no advantage for analogs with a single or double bond at C-22,23 within the cyclohexyl series, and these analogs had equivalent activity as those with a single bond at C-22,23 in the sec-butyl/isopropyl series. However, there was superior activity for the analog series that possessed the combination of a double-bond at C-22,23 and a sec-butyl/isopropyl substituent at C-25. As a result, the most potent compound in this test was not any of the 3 commercialized avermectins but was a monosaccharide with a double bond at C-22,23, an hydroxyl at C-5, and a sec-butyl/isopropyl moiety at C-25.

Animals↗

Effects of ivermectin and albendazole against Anisakis simplex in vitro and in guinea pigs.

The activity of ivermectin and albendazole against larval Anisakis simplex was tested in vitro and in experimentally infected guinea pigs. Before drug exposure the medium for half of the larvae was adjusted to pH 2.0 with 1 N HCl, whereas the other half was held at pH 7.0. To these solutions, ivermectin was added to full concentrations of 1, 2, 5, 10, 50, 100, or 200 microg/ml, and for albendazole, 300, 400, and 500 microg/ml. Animals from group I were given 0.1 ml of 1% (3.3 mg/kg) ivermectin, whereas guinea pigs from group II were each given 5-7 mg (16.6-23.3 mg/kg) of albendazole orally. The efficacy of both drugs against L, A. simplex was high in vitro and in vivo against the larvae in different organs of guinea pigs.

Albendazole↗