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PubMed1997

Required duration of combined annual ivermectin treatment and vector control in the Onchocerciasis Control Programme in west Africa.

In the extension areas of the Onchocerciasis Control Programme in West Africa, aerial larviciding is supplemented with annual ivermectin treatment, mainly to achieve better control of morbidity. The purpose of this study is to determine whether and to what extent the addition of annual ivermectin treatment permits earlier cessation of vector control than originally recommended. The effectiveness of combined ivermectin distribution and vector control was assessed using an epidemiological model. Model predictions suggest that, dependent on the pre-control endemicity of the area and the proportion of persons treated during each ivermectin round, large-scale annual treatment permits a considerable reduction in the duration of vector control. Taking into account uncertainty about the efficacy of ivermectin, our results indicate that, provided treatment coverage is at least 65% and there is no importation of infection from elsewhere, 12 years of combined control will be sufficient to reduce the risk of recrudescence to below 1% in even the most afflicted areas.

Adolescent↗
PubMed2004

Dermal safety study with imidacloprid/moxidectin topical solution in the ivermectin-sensitive collie.

A study was conducted to determine the safety of the dermal application of 10% imidacloprid/2.5% moxidectin topical solution in ivermectin-sensitive collies. Each milliliter of this solution contains 100mg of imidacloprid and 25mg of moxidectin. A total of 21 collies were prescreened for ivermectin-sensitivity and heartworm negative status prior to selection for the study. Animals were assigned based on the maximum ivermectin-sensitivity score demonstrated during the prestudy screening. Treatment groups included a 3x and 5x test article group, and a 3x and 5x mineral oil control group. The 3x and 5x doses were administered at three and five times, respectively, the 1x dose based on the animal's body weight. On day 0, 3 of the 21 dogs were treated with dermal applications of a preliminary dose of 3x test article to screen for unexpected signs of toxicity with the remaining 18 dogs being treated with 3x mineral oil to blind for the volume of liquid applied. After no signs of toxicity were observed, these same three dogs were treated with 3x of test article and 2x mineral oil on days 28 and 56. The remaining 18 animals were equally allocated to either a 5x test article group or a 5x control group and were each treated on days 28, 56, and 84. Personnel performing observations were blinded to treatment. Observations were made for clinical signs of ivermectin sensitivity twice daily during non-dosing days. On treatment days, dogs were observed hourly for the first 4h post-treatment and at 6, 8, 12, 18 and 24h. Signs of toxicosis were not observed in any of the dogs throughout the observation period. This study demonstrated the safety of imidacloprid/moxidectin, when administered to collies testing positive for ivermectin sensitivity at dosages up to five times the maximum recommended dose.

Administration, Topical↗
PubMed1989

Utilisation of the persistent anthelmintic activity of ivermectin in a preventive drenching programme for dairy calves.

A study was undertaken to assess whether the persistent anthelmintic effect of ivermectin in cattle would allow an extension of the drenching interval in the currently recommended preventive drenching programme for the control of gastrointestinal nematode infection in dairy calves. A comparison was made of the parasitological and production responses of treatment groups of calves, grazing replicated plots, receiving either six drenches of oxfendazole at four-weekly intervals or four subcutaneous treatments with ivermectin at six-weekly intervals. Compared with the levels of infective larvae on pasture grazed by untreated control calves, mean larval numbers on pasture grazed by ivermectin and oxfendazole treated calves were 94.3% and 98.3% lower, respectively, during the period of maximum larval availability (March-May). Mean liveweight gains (December-August) of the treated groups (101.4kg and 110.2kg respectively) were not significantly different, but both were highly significantly different from that of the untreated controls (57.4kg). Mean plasma pepsinogen levels for the ivermectin, oxfendazole and control groups over the period of maximum values (June-August) were 1.92 i.u., 1.72 i.u. and 5.53 i.u., respectively. The difference between the treated groups was not statistically significant but both were highly significant different from the control group. The present results indicate that four treatments with ivermectin (subcutaneously) at six-weekly intervals achieved a similar level of prophylactic control to that effected by six treatments with oxfendazole at four-weekly intervals.

Journal Article↗
PubMed2000

Ivermectin-resistant Ostertagia circumcincta from sheep in the lower North Island and their susceptibility to other macrocyclic lactone anthelmintics.

AIM: To confirm the ivermectin resistance status of a strain of Ostertagia circumcincta which was isolated from a sheep farm in the lower North Island of New Zealand and to assess the susceptibility of this strain to other macrocycliclactone anthelmintics. METHODS: Twenty-five lambs housed indoors were each infected with 12,000 L3 larvae of the above parasite strain. Approximately 3 weeks after infection the lambs were allocated to 1 of 4 treatment groups (3 groups of 6, and 1 group of 7 lambs), one of which remained untreated while the others were drenched orally with ivermectin, moxidectin or abamectin at 0.2 mg/kg liveweight. Faecal egg counts (FECs) before and after treatment, and post-mortem worm burdens 10 days after treatment were examined to assess efficacies of each anthelmintic. RESULTS: Treatment with ivermectin reduced the mean FEC by only 18% and the mean worm burden by only 42%, whereas moxidectin and abamectin reduced FECs by 92% and worm burdens by 95%. CONCLUSION: These results, together with a similar case described recently from the South Island , confirm the emergence of ivermectin resistance in nematode parasites of sheep in New Zealand. The superior efficacy of moxidectin and abamectin in this case indicates that, following the emergence of resistance to ivermectin, some short-term practical use may still be made of these other anthelmintics. However, their continued use will undoubtedly result in increased levels of resistance and eventual therapeutic failure of these products also.

Journal Article↗
PubMed2003

Serious adverse events following treatment with ivermectin for onchocerciasis control: a review of reported cases.

This paper presents a summary of reported cases of Serious Adverse Events (SAEs) following treatment with Mectizan(R) (ivermectin, Merck, Sharpe & Dohme) in onchocerciasis mass treatment programs from January 1, 1989 to December 31, 2001 through a passive surveillance system. A total of 207 SAE cases were reported out of approximately 165 million reported treatments delivered during the period under review, giving rise to a cumulative incidence of 1 reported SAE per 800,000 reported treatments. The mean age was 40 years and 70% of the cases were males. The mean time between ivermectin intake and onset of illness was 1 day. For 57% of the cases (n = 118), that was their first exposure to ivermectin. The majority of cases were reported from Cameroon (n = 176; 85%) with peaks in the incidence of SAE reporting in 1989-1991 and 1994-1995 when the program expanded to ivermectin-naïve populations. Fifty-five percent of the cases from Cameroon (i.e. 97 out of 176 cases) were encephalopathic and were reported from the central-southern region of the country; two-thirds of these cases were 'probable' or 'possible' cases of Loa loa encephalopathy temporally related to ivermectin treatment. Reporting bias may explain some but not all of the differences in SAE reporting between the 34 onchocerciasis-endemic countries that have, or have had, mass treatment programs. Further research is needed to understand the apparent clustering of encephalopathy cases in central-southern Cameroon since L. loa infection alone probably does not explain the increased incidence of this type of SAE from this region.

Journal Article↗
PubMed2003

Ivermectin: does P-glycoprotein play a role in neurotoxicity?

The macrocyclic lactone ivermectin (Mectizan(R)) is widely used for the control of human filarial infections, particularly as a donated product for onchocerciasis and lymphatic filariasis. In the case of control of lymphatic filariasis in Africa, it is used in combination with donated albendazole. In areas co-endemic for Onchocerciasis and Loa loa, serious adverse reactions have been observed in patients with apparently high microfilaria counts of Loa loa. Recent findings suggest that the severe central nervous system side effects seen in various vertebrates following ivermectin treatment may be due to an absence of, or functional deficiency in P-glycoprotein. P-glycoprotein is expressed in the apical membrane of brain capillary epithelial cells and is responsible for limiting the brain penetration of a range of compounds. Toxicity of ivermectin in some collie dogs may be explained by a 4-bp deletion mutation of the mdr1 gene resulting in a frame shift, generating stop codons that prematurely terminate synthesis of P-glycoprotein. Additionally, sub-populations of CF-1 identified as expressing reduced levels of P-glycoprotein exhibit increased toxicity to substrates of this transporter. Furthermore, while the traditional view of drug-drug interactions is alteration in drug clearance mediated through a change in hepatic drug metabolism, some of these changes may arise through competition for binding sites on P-glycoprotein in the blood-brain barrier, resulting in reduced extracellular efflux and enhanced CNS toxicity. In conclusion, P-glycoprotein is an integral component of the human blood brain barrier and plays a central role in limiting drug uptake into the brain. Altered expression or function of p-glycoprotein could conceivably allow elevation of brain concentrations of ivermectin and produce severe neurotoxicity. This might arise through a genetic polymorphism in p-glycoprotein or co-administration of ivermectin with a drug or foodstuff that might inhibit this efflux transporter.

Journal Article↗
PubMed2004

The scourge of sarcoptes: oral ivermectin for scabies.

OBJECTIVE: To review the use of the oral antiparasitic ivermectin in the treatment of scabies, with an emphasis on its use in the elderly and in long-term care settings. DATA SOURCE: A MEDLINE/PUBMED search was conducted to identify pertinent studies, case reports, letters, and reviews in the English language. All articles published from 1980 to October 2003 were reviewed. Additional references were obtained from the bibliographies of these articles. STUDY SELECTION: All studies evaluating ivermectin in the context of scabies mite infestation. DATA SYNTHESIS: The semisynthetic macrocyclic lactone ivermectin has been available since the early 1980s as a broad-spectrum antiparasitic agent in animals and humans. This agent, which works by suppressing motor nerve conduction leading to parasite paralysis and death, was first used in ectoparasitic diseases (i.e., those caused by lice and mites) shortly after commercial introduction. A large body of literature, mainly uncontrolled case reports and series, has since evolved. However, these reports and results of the small number of placebo- and/or active-controlled studies have demonstrated the favorable response of both classic and crusted scabies to single- and multiple-dose oral ivermectin. Adverse reactions to the drug are uncommon, with the exception of a transient, new onset, or mild increase in existing pruritus soon after drug ingestion, which is thought to be a hypersensitivity reaction to dead mites and/or their products. CONCLUSION: Oral ivermectin may prove to be a time- and labor-saving alternative to topical scabicide treatments, especially in the institutional setting where labor shortages make the management of scabies outbreaks a true challenge. However, the use of this agent does not change the need to decontaminate the environment (clothing, bedding, bed clothes, and, in selected cases, floors and walls) in order to truncate an outbreak and prevent reinfestation.

Journal Article↗
PubMed2004

Selective mass treatment with ivermectin to control intestinal helminthiases and parasitic skin diseases in a severely affected population.

OBJECTIVE: To assess the short-term and long-term impact of selective mass treatment with ivermectin on the prevalence of intestinal helminthiases and parasitic skin diseases in an economically depressed community in north-east Brazil. METHODS: An intervention was carried out in a traditional fishing village in north-east Brazil where the population of 605 is heavily affected by ectoparasites and enteroparasites. The prevalence of intestinal helminths was determined by serial stool examination and the prevalence of parasitic skin diseases by clinical inspection. A total of 525 people out of a target population of 576 were treated at baseline. The majority of these were treated with ivermectin (200 microg/kg with a second dose given after 10 days). If ivermectin was contraindicated, participants were treated with albendazole or mebendazole for intestinal helminths or with topical deltamethrin for ectoparasites. Follow-up examinations were performed at 1 month and 9 months after treatment. FINDINGS: Prevalence rates of intestinal helminthiases before treatment and at 1 month and 9 months after mass treatment were: hookworm disease 28.5%, 16.4% and 7.7%; ascariasis 17.1%, 0.4% and 7.2%; trichuriasis 16.5%, 3.4% and 9.4%; strongyloidiasis 11.0%, 0.6% and 0.7%; and hymenolepiasis 0.6%; 0.4% and 0.5%, respectively. Prevalence rates of parasitic skin diseases before treatment and 1 month and 9 months after mass treatment were: active pediculosis 16.1%, 1.0% and 10.3%; scabies 3.8%, 1.0% and 1.5%; cutaneous larva migrans 0.7%, 0% and 0%; tungiasis 51.3%, 52.1% and 31.2%, respectively. Adverse events occurred in 9.4% of treatments. They were all of mild to moderate severity and were transient. CONCLUSION: Mass treatment with ivermectin was an effective and safe means of reducing the prevalence of most of the parasitic diseases prevalent in a poor community in north-east Brazil. The effects of treatment lasted for a prolonged period of time.

Adult↗
PubMed1999

Haemonchus contortus: characterization of a glutamate binding site in unselected and ivermectin-selected larvae and adults.

A specific ivermectin-sensitive, glutamate binding site has been identified in the parasitic nematode Haemonchus contortus. Glutamate binding in H. contortus was saturable and occurred in a single class of high-affinity binding sites which appeared to have pharmacological properties different from those of mammalian glutamate receptors. Adult and larval forms of H. contortus had dramatically different glutamate binding kinetics, the larvae showing nearly up to 200-fold higher Bmax values and up to 9-fold increases in Kd values compared to adults. Treatment of adult H. contortus with the anthelmintic, ivermectin, decreased the Bmax value for glutamate binding in the susceptible strain but not in the resistant parasites. Furthermore, selection for ivermectin resistance was associated with a significant increase in Bmax for glutamate binding in adults and a similarly significant increase in glutamate binding affinity in larvae. These results suggest that the H. contortus glutamate binding site identified in this study may be involved in the phenomenon of ivermectin resistance.

Animals↗
PubMed1992

Efficacy of topically applied ivermectin against sarcoptic mange (Sarcoptes scabiei var. bovis) of cattle.

A total of 12 adult cattle with sarcoptic mange were included in a study to confirm the efficacy of ivermectin applied topically at 500 micrograms/kg against Sarcoptes scabiei var. bovis. Animals were allocated by restrictive randomization according to mite counts to serve as untreated controls or were treated with a topical formulation of ivermectin applied along the backline on healthy skin. Mites were counted in epidermal scrapings made prior to treatment and at 7, 14, 21, 28, 42 and 56 days thereafter. Except for three mites recovered from one animal on day 28, no mites were found after day 14 over the remainder of the trial in scrapings from animals treated with ivermectin. Differences in the numbers of mites recovered from animals treated with ivermectin and those found on controls were significant (P less than 0.05) for counts carried out on days 14-56. Clinical signs of mange resolved following treatment, whereas the extent of lesions and severity of clinical signs increased in the control animals over the trial period.

Administration, Topical↗
PubMedDate not supplied

Ivermectin dosing based on physical appearance.

Ivermectin is a safe and effective microfilaricide which has been shown to have a beneficial impact on some onchocercal eye lesions. Current requirements for the distribution of ivermectin are that patients be weighed, and that their dose be determined according to their weight. This requirement increases the cost of distributing the drug to communities in need of treatment and, when scales breakdown, may lead to the suspension of distribution. Data are presented on a simple, alternative method of dose assessment based on the physical appearance of the patient. Fifteen assessors achieved an overall level of agreement with the weight-based schedule of 86% on a sample of 6420 patients. The level of agreement varied between assessors, from 73% to 95%. About 6% of the population would have received doses outside the range of the current weight-based schedule. We believe that the current insistence that each individual's dose of ivermectin be determined by weighing will hamper efforts to distribute the drug to those most in need of it and that our data indicate that workers can be trained to distribute ivermectin safely without weighing every individual. We would welcome confirmation of our findings from other populations.

Adult↗
PubMed2005

Assessment of a liposomal formulation of ivermectin in rabbit after a single subcutaneous administration.

Ivermectin is a member of the macrocyclic lactone family widely used in livestock, pets, and humans as a potent parasiticide. Slight differences in formulation may change the plasma kinetics and efficacy of these compounds. The aim of the study is to evaluate the ability of a liposomal formulation of ivermectin to generate an efficient exposure of the animal to the drug. Ten rabbits were subcutaneously administered with 0.3 mg kg(-1) of ivermectin using Ivomec (n=5) or a liposomal formulation (n=5). The areas under serum concentration-time curve were similar after both treatments, indicating the same bioavailability for the two formulations. However, the liposomal formulation gave a higher C(max) value (33.33 ng ml(-1)) compared with Ivomec (20.82 ng ml(-1)) and a significantly faster absorption as indicated by the T(max) of 0.23 days compared with 1.13 days for the Ivomec formulation. The use of liposomal formulation shows promise as this system improves the efficacy of ivermectin and related drugs.

Animals↗
PubMed2006

Environmental impact of ivermectin excreted by cattle treated in autumn on dung fauna and degradation of faeces on pasture.

The effect of ivermectin excreted in faeces of treated cattle on dung fauna and dung degradation on pasture during autumn was evaluated. Two groups of calves were used. One group was treated subcutaneously with ivermectin while the other remained as untreated control. Faeces deposited on 1, 3, 7, 14 and 21 days post-treatment (dpt) were removed on 1, 3, 7, 14, 21, 30 and 60 days post-deposition (dpd) and were used to determine the concentration of ivermectin and the percentage of organic matter and for the collection of colonising organisms. Samples from 1 and 3 dpt contained the highest drug concentration and percentage of organic matter compared to the control group (p<0.05). Faeces from the treated group showed lesser abundance and diversity of arthropods (p<0.05) than the control group. A reduction in numbers and diversity of dung fauna in faecal samples from treated animals was most remarkable at 1, 3 and 7 dpt, coinciding with the highest concentration of ivermectin and organic matter percentage.

Animals↗
PubMed1996

Efficacy of ivermectin and moxidectin injection against larvae of Wohlfahrtia magnifica (Diptera: Sarcophagidae) in sheep.

The therapeutic efficacies of ivermectin (Ivomec injection, Merck Sharp & Dohme B.V.) and moxidectin (Cydectin 1% injection, American Cyanamid Company) were evaluated in sheep naturally infested with larvae of Wohlfahrtia magnifica. Sheep were randomly allocated to one of the 2 groups, each consisting of 19 animals. Sheep in one group received ivermectin and those in the other, moxidectin by subcutaneous injection at a dose of 0.2 mg/kg body weight. Evaluation was performed at 19, 24, 28, 39, 43, 48, 52, 63, 67, 72, 87, 96, 120, 144 and 168 h after treatment. At 144 and 168 h post-treatment, late third-instar larvae were collected from wounds of four sheep in both groups and from untreated, infested sheep. These larvae were reared in the laboratory to assess adult emergence. Neither ivermectin nor moxidectin was effective as a rapid acting treatment or as a long-term, or even short-term, prophylactic. Despite the treatment, 30-40% of sheep had live larvae at every evaluation. Although larvae disappeared from the wounds of some sheep in both groups after the treatment, the wounds in these animals failed to recover and were reinfested by larvae of W. magnifica. On day 7 post-treatment the trial had to be finished because the majority of treated sheep were severely infested by Wohlfahrtia maggots. The average number of infested sheep in the two groups and the number of adults that were produced from larvae collected from treated sheep indicate that ivermectin and moxidectin did not differ significantly in efficacy.

Animals↗
PubMed1999

Effects of the multidrug-resistance-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds (Meriones unguiculatus).

The development of anthelmintic resistance is making parasite control in small ruminants problematic. Following the discovery that the drug transporter P-glycoprotein may be involved in macrocyclic lactone resistance in Haemonchus contortus, we determined the effect of two multidrug-resistance modulators, verapamil and CL347,099, on the efficacy of ivermectin and moxidectin against unselected and drug-selected strains of H. contortus. CL347,099 is an analog of verapamil that has multidrug-resistance properties but weaker calcium-channel-blocking activity than the parent drug. The combinations of verapamil with either ivermectin or moxidectin significantly reduced worm counts of the selected strains as compared with the untreated controls, whereas ivermectin or moxidectin alone did not significantly reduce worm counts as compared with the untreated controls. The CL347,099 plus moxidectin combination was significantly more efficacious than moxidectin alone against the ivermectin-selected strain. The drug-combination regimes were without adverse effect on the jirds. However, higher levels of verapamil (> or =40 mg/kg) produced some toxicity.

Animals↗
PubMed2002

Efficacy of ivermectin for chronic strongyloidiasis: two single doses given 2 weeks apart.

We assessed the efficacy and adverse effects of ivermectin for the treatment of chronic strongyloidiasis. Fifty patients were treated with a single dose of ivermectin at approximately 200 microg/kg, and the dose was repeated 2 weeks later. The eradication rate was 96% (48 of 50 patients) at 2 weeks after the first dose and 98% at 2 weeks after the second dose (49 of 50 patients). In the latter cases, no recurrence was noted at the end of the 4-month post-treatment follow-up period. The gastrointestinal symptoms observed most frequently before the treatment were borborygmus, constipation, and diarrhea. These symptoms improved in the majority of patients after the treatment. Side effects, including nausea and vomiting, occurred in 1 patient (2%), but these were mild and transient. Although abnormal values in laboratory tests were observed in 4 patients (8%), they were mild, and no particular clinical care was required. Thus, ivermectin showed an excellent antihelminthic effect, with little toxicity. Our results indicate that a regimen of two single doses of 200 microg/kg ivermectin, given 2 weeks apart, is clinically suitable for the treatment of chronic strongyloidiasis.

Adult↗
PubMed1994

Chemotherapy of experimental filariasis: enhancement of activity profile of ivermectin with immunomodulators.

The effect of certain immunopotentiators (Freund's complete adjuvant, picroliv, tuftsin and CDRI Compound 86/448) was evaluated on exertion of antifilarial activity of ivermectin at different dose levels in cotton rats experimentally infected with Litomosoides carinii. Ivermectin alone (up to 250 micrograms/kg p.o. x 5 days) caused sterilization of most of the surviving female parasites, but had no lethal effect on adult worms. In combination with immunomodulators, ivermectin brought about significant lethal effect on adult parasites even at a dose of 1 microgram/kg x 5 days. Nevertheless, in animals receiving FCA alone, sterility was caused in > 50% of female parasites. Other immunomodulators used alone had a suppressive effect on microfilaraemia only. Immunomodulators alone or in combination with ivermectin also caused enhanced filaria-specific antibody response.

Adjuvants, Immunologic↗
PubMed1991

Fecundity of anthelmintic resistant adult Haemonchus contortus after exposure to ivermectin or benzimidazoles in vivo.

A strain of Haemonchus contortus resistant to the benzimidazoles, ivermectin and salicylanilides was used to study the effect of exposure to ivermectin or oxfendazole on the number of eggs produced by adult female parasites. After anthelmintic administration there was a reduction in the faecal egg count of the infected lambs. Ivermectin caused a reduction in the number of eggs within adult parasites for up to 72 hours but this returned to higher than pre-treatment levels at 168 hours after treatment. After oxfendazole treatment there was an increase in the number of eggs stored in the adult parasites at 24 hours and then a significant reduction in the number of eggs for over 168 hours. This suggested that both ivermectin and oxfendazole have a deleterious effect on the reproductive potential of female H contortus although the parasites are resistant to these drugs. These results confirm the importance of allowing up to 10 days to elapse between the time of administration of an anthelmintic and the collecting of faecal samples when using the faecal egg count reduction test to identify anthelmintic resistance, especially when using benzimidazoles. The more prolonged effect on fecundity produced by oxfendazole may reflect the antimitotic action of the benzimidazole anthelmintics.

Animals↗