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PubMed2003

The prevalences of Wuchereria bancrofti antigenaemia in communities given six rounds of treatment with diethylcarbamazine, ivermectin or placebo tablets.

The ICT filariasis card test was used to determine the prevalences of Wuchereria bancrofti antigenaemia among villagers in India. Prior to the tests, those living in the 15 study villages had been treated six times, in six rounds of mass treatment (with 54%-75% coverage) spread over 6 years, with single doses of diethylcarbamazine (five villages), ivermectin (five villages) or placebo (five villages). The corresponding overall prevalences (and ranges) of filarial antigenaemia were 20.2% (13.7%-28.6%), 22.6% (15.3%-34.3%) and 25.9% (22.6%-29.3%), respectively. The overall prevalence of antigenaemia in the villages where diethylcarbamazine (DEC) had been distributed (but not that in the 'ivermectin' villages) was significantly lower than that recorded in the 'placebo' villages (z =2.56; P <0.05). The prevalences of antigenaemia among the villagers aged 1-5 years (18.9%, 15.6% and 22.4% in the DEC, ivermectin and placebo villages, respectively) did not differ significantly with treatment (P >0.05). The results indicate that annual mass treatments based on DEC or ivermectin, with 54%-75% treatment coverage, may have only a limited effect on the prevalence of infection with adult W. bancrofti. The possible reasons for the antigenaemias observed are discussed.

Animals↗
PubMed2004

Thirty-month follow-up of sub-optimal responders to multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

The pathogenesis of the sub-optimal response of Onchocerca volvulus to ivermectin was investigated in a 30-month follow-up of 28 individuals who, in a previous study, had been found to show a sub-optimal (N = 15) or adequate response (N = 13) to multiple treatments with the drug. Verbal informed consent was obtained before each subject was given a general clinical and ocular examination. Skin snips were taken from both iliac crests and both calves. Seventeen nodule carriers were hospitalized for nodulectomy. Adult worms were harvested, embryogrammes were constructed and all developmental stages were counted; degenerate, stretched microfilariae were noted separately. All the subjects were in good general health and all except one had received at least one additional treatment with ivermectin since the earlier study. A large proportion of the adult female worms in 10 out of the 11 sub-optimal responders who were nodule carriers were in full embryonic production but most of the stretched microfilariae they carried were degenerate. This picture is similar to that found in adult worms exposed to the first dose of ivermectin. In one subject who had no viable worms in his nodules, the existence of occult but actively reproductive worms was inferred from the high level of microfilaridermia observed less than 12 months after treatment. These observations confirm the existence of populations of adult female O. volvulus that respond poorly to repeated doses of ivermectin. The use of suramin in the treatment of the sub-optimal responders is discussed.

Adult↗
PubMed2005

Adverse reactions to the ivermectin treatment of onchocerciasis patients: does infection with the human immunodeficiency virus play a role?

To assess and compare the adverse effects resulting from ivermectin treatment of onchocerciasis patients with and without infection with human immunodeficiency virus (HIV-1), 1256 Ugandan cases of onchocerciasis were investigated as they were treated for the first time with the drug. Treatment followed the protocol of the Mectizan Expert Committee (i.e. a single dose of 150 mug/kg body weight). Adverse reactions to the ivermectin were determined, within 48 h of treatment, through questioning and clinical examinations during house-to-house visits. The HIV-1 status of each patient aged >15 years was initially determined using indirect ELISA, and any ELISA-positives were then confirmed in a western-blot assay. Among the cases aged >15 years, the frequency of adverse reactions to ivermectin was higher among those seropositive for HIV-1 (53.4%) than among the seronegative (45.7%) but the difference was not statistically significant (P = 0.25). The severity of the adverse reactions observed was, however, significantly lower in the HIV-1-positive patients than in the seronegative patients, with median scores of 1.37 and 1.68, respectively (P = 0.044). The conclusion is that ivermectin can be safely used for mass treatment in areas where the prevalences of onchocerciasis and HIV-1 infection are both high.

Adolescent↗
PubMedDate not supplied

Efficacy of ivermectin against the bloodsucking insect, Rhodnius prolixus (Hemiptera, Triatominae).

Ivermectin (0.2 mg/kg body weight) caused a high mortality in nymphs and adults of Rhodnius prolixus following a single meal in mice sub-cutaneously injected with the drug. This effect was more evident in nymphs of 1st-and 2nd-instar than in older nymphs and adults. Third-instar nymphs presented a high mortality when fed on mice treated with ivermectin 24 and 48 hours previously, while mortality was significantly reduced in nymphs fed on mice treated 72 hours before. Surviving 3rd-instar nymphs did not molt. When adult females were fed once on mice treated for 24 hours with ivermectin there was a considerable reduction in egg production. This inhibition was not reversed by a second feeding on normal mice. We concluded that sub-lethal doses of ivermectin caused toxic effects interfering in the neuro-endocrine control of development and reproduction of this bloodsucking insect.

Animals↗
PubMed2006

Ticks, ivermectin, and experimental Chagas disease.

Following an infestation of dogticks in kennels housing dogs used for long-term studies of the pathogenesis of Chagas disease, we examined the effect of ivermectin treatment on the dogs, ticks, trypanosome parasites, and also on triatomine vectors of Chagas disease. Ivermectin treatment was highly effective in eliminating the ticks, but showed no apparent effect on the dogs nor on their trypanosome infection. Triatominae fed on the dogs soon after ivermectin treatment showed high mortality, but this effect quickly declined for bugs fed at successive intervals after treatment. In conclusion, although ivermectin treatment may have a transient effect on peridomestic populations of Triatominae, it is not the treatment of choice for this situation. The study also showed that although the dogticks could become infected with Trypanosoma cruzi, this only occurred when feeding on dogs in the acute phase of infection, and there was no evidence of subsequent parasite development in the ticks.

Acute Disease↗
PubMed2006

Population growth rate and carrying capacity for springtails Folsomia candida exposed to ivermectin.

Forecasting the effects of stressors on the dynamics of natural populations requires assessment of the joint effects of a stressor and population density on the population response. The effects can be depicted as a contour map in which the population response, here assessed by population growth rate, varies with stress and density in the same way that the height of land above sea level varies with latitude and longitude. We present the first complete map of this type using as our model Folsomia candida exposed to five different concentrations of the widespread anthelmintic veterinary medicine ivermectin in replicated microcosm experiments lasting 49 days. The concentrations of ivermectin in yeast were 0.0, 6.8, 28.8, 66.4, and 210.0 mg/L wet weight. Increasing density and chemical concentration both significantly reduced the population growth rate of Folsomia candida, in part through effects on food consumption and fecundity. The interaction between density and ivermectin concentration was "less-than-additive," implying that at high density populations were able to compensate for the effects of the chemical. This result demonstrates that regulatory protocols carried out at low density (as in most past experiments) may seriously overestimate effects in the field, where densities are locally high and populations are resource limited (e.g., in feces of livestock treated with ivermectin).

Animals↗
PubMed1991

Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis.

Ivermectin, a derivative of avermectin B, is an orally effective microfilaricidal agent. It is the current drug of choice for treating patients infected with the nematode Onchocerca volvulus, which is a major cause of blindness in inhabitants of some tropical areas. Ivermectin is administered orally as a single dose of 150 micrograms/kg given annually. Skin and ocular microfilarial counts are dramatically reduced after the first dose, with some evidence for a resulting decrease in transmission of infection by the blackfly vector. With the exception of rare serious reactions such as severe systemic postural hypotension, ivermectin is generally well tolerated. The drug has the clear advantages of ease of administration and better tolerability compared with diethylcarbamazine and suramin, agents previously used to treat onchocerciasis. Thus, ivermectin is suitable for inclusion in mass treatment programmes and is the best therapeutic option presently available to combat onchocerciasis. As such it provides hope for many thousands of people at risk of becoming blind, and represents a major contribution to tropical medicine.

Animals↗
PubMed1993

Effects of ivermectin on reproductive functions in ewes.

In response to producers' concerns about possible detrimental effects of ivermectin on ewes during the breeding season, an evaluation of its effects on endocrinological, physiological, and behavioral measures of reproductive performance was made. Twenty cycling ewes were randomly assigned on d 10 (d 0 = estrus) to receive a single recommended oral dose of 200 micrograms/kg of BW of ivermectin or a control volume of water. Twelve hours after treatment, ewes received a luteolytic injection of 5 mg of PGF2 alpha and were introduced to fertile rams. On d 10 after mating, laparoscopies were performed to assess ovulation rate, and on d 18 conceptuses were surgically recovered. Blood samples were collected during the 92-h interval beginning immediately before ivermectin and control treatments and were assayed for LH. It was determined that 1) interval from PGF2 alpha-induced luteal regression to a) onset of estrus (36.1 +/- 1.4 vs 36.3 +/- 1.4 h) and b) onset of the preovulatory surge of LH (38.2 +/- 2.6 vs 44.2 +/- 2.6 h), 2) magnitude of the surge of LH (275.6 +/- 38.9 vs 199.8 +/- 38.9 ng/mL), 3) duration of the surge of LH (9.4 +/- .4 vs 9.0 +/- .4 h), 4) area under the curve of the surge of LH (54,321 +/- 7,419 vs 38,138 +/- 7,419 arbitrary units), 5) ovulation rate (2.1 +/- .4 vs 2.0 +/- .3 ovulations/ewe), 6) pregnancy rate (8/10 vs 5/10 ewes pregnant), and 7) conceptuses per ewe (1.75 +/- .37 vs 1.60 +/- .33) did not differ (all P > .1) between ivermectin- and control-treated ewes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

A study to evaluate the field efficacy of ivermectin, fenbendazole and pyrantel pamoate, with preliminary observations on the efficacy of doramectin, as anthelmintics in horses.

The efficacy of ivermectin, fenbendazole, pyrantel pamoate and doramectin was evaluated under field conditions at 2 sites in the Free State Province of South Africa. The study involved 25 horses at each site, divided into 5 groups of equal size. Ivermectin, fenbendazole and pyrantel pamoate were administered orally at doses of 0.2, 10 and 19 mg/kg respectively. Doramectin was administered by intramuscular injection at a dose of 0.2 mg/kg. Treatment efficacy was based on the mean faecal egg count reduction 14 days post treatment. At site A a faecal egg count reduction of 100% was found after treatment with ivermectin, fenbendazole and doramectin. A 96.1% reduction was found after treatment with pyrantel pamoate. At site B ivermectin and doramectin produced a 100% reduction in faecal egg counts, fenbendazole produced an 80.8% reduction and pyrantel pamoate a 94.1% reduction. Doramectin produced a 100% reduction in faecal egg counts at both sites, despite not being registered for use in horses. In addition, the results indicated reduced efficacy of fenbendazole at site B, which suggested benzimidazole resistance. Larval cultures showed that cyathostomes accounted for between 86 and 96% of pre-treatment parasite burdens at both sites. Other helminths identified in the faecal samples were Strongylus spp. and Trichostrongylus axei.

Animals↗
PubMed1989

The status of ivermectin in the treatment of human onchocerciasis.

Ivermectin is a macrocyclic lactone that has widespread antiparasitic activity. Numerous clinical trials have shown that ivermectin is safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction, as is seen with diethylcarbamazine treatment. The drug temporarily interrupts production of microfilaria but has not known long-lasting effects on the adult worms. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement. At this dose, ivermectin causes minimal side effects and is sufficiently free of severe reactions to be used on a mass scale. It promises to revolutionize the treatment of onchocerciasis.

Clinical Trials as Topic↗
PubMed1992

Effects of three-month doses of ivermectin on adult Onchocerca volvulus.

Onchocerca volvulus worms in nodules from Guatemalan patients treated with four, eight, or 11 single doses of ivermectin (150 micrograms/kg of body weight) that were given once every three months were examined by routine histologic techniques and compared with worms in control nodules from untreated persons living in the same location over the same time periods. All treated nodules were removed four months after the last dose of ivermectin, i.e., 13, 25, or 34 months after the start of the trial. At the 25th and 34th months, i.e., after the eighth or eleventh doses of ivermectin, there were excess mortalities in female worms of 25.5% and 32.6%, respectively, over and above the levels in controls. Furthermore, the proportions of live females still producing scanty embryos up to the gastrula stage were only 7.7% and 18.2%, and no females were producing microfilariae. Ivermectin given at 3-month intervals also reduced significantly the mean numbers of live male worms in nodules, as well as the proportions of inseminated females. This regimen was effective in preventing embryogenesis to the microfilarial stage while, at the same time, it caused a slow but steady attrition of the adult worms.

Adolescent↗
PubMed1992

Ivermectin: reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemalan communities.

Residents of five hyperendemic communities located in the central focus of onchocerciasis in Guatemala were treated with ivermectin (Mectizan) or placebo every six months for 30 months. The effects of treatment on prevalence and the intensity of skin infection (microfilarial skin density [MFD]) were evaluated. Significant and persistent reductions in both of these indices were achieved by coverage of 80.7% of the eligible populations. The highest proportionate reductions in both indicators of infection occurred after the first treatment, followed by more gradual decreases through the fourth treatment. In one community in which the mean coverage was 92.7%, prevalence decreased from 74.0% at pretreatment to 34.9% after four treatments, while the MFD decreased from 7.8 to 2.0; reductions of 52.8% and 74.3% from pretreatment values, respectively. In every ivermectin-treated community except one, in which drug acceptance was low, the mean community MFD values were reduced to the level associated with low infectiousness for the vector, Simulium ochraceum. Moreover, the category of MFD associated with high vector infectiousness was reduced at least ten-fold over the pretreatment level. One community had low participation during the first two treatments (32.8% and 22.7% of those eligible). This increased to 55.2% at the third treatment because of implementation of an educational program describing both the disease and the beneficial effects of ivermectin and because skin biopsies and nodulectomies were not performed. Secondary reaction rates for all communities were 29.5%, 9.9%, 10.3%, 8.2%, and 7.1% for the first through fifth treatments, respectively. Pruritus was the most common (34.0%) secondary reaction, followed by facial edema (31.8%). All reactions were classified as mild to moderate. Recommendations for mass distribution of ivermectin in Guatemala are given.

Adolescent↗
PubMed1993

Tolerance and efficacy of single high-dose ivermectin for the treatment of loiasis.

A study was carried out in southeastern Gabon to evaluate the tolerance and efficacy of single high doses of ivermectin in 31 Loa loa-infected subjects with low-to-moderate parasitemia (7-7,700 microfilaria/ml). The first group of 16 subjects received 300 micrograms/kg of ivermectin and, seven days later, a second group of 15 received 400 micrograms/kg. Complete clinical and biological monitoring was carried out during the first 10 days post-treatment and again after one and three months. All subjects continued with their usual activities during the study. The clinical tolerance of treatment was very good, and except in one case, only mild adverse reactions were observed, with pruritus being the most common symptom. There were no significant changes in blood or urine function test results or in hematologic results, except for a pronounced eosinophil reaction. The 400 micrograms/kg dose of ivermectin equaled or surpassed in tolerance that of 300 micrograms/kg dose. After treatment, L. loa microfilaremia decreased rapidly to less than 9% of the pretreatment value by day 10. This decrease was enhanced with the 400 micrograms/kg dose, although differences between the two groups diminished slightly with time. At 100 days post-treatment, the microfilaremia was still at less than 10% of the initial values in the two groups, which may indicate an effect of ivermectin on the adult worms.

Adult↗
PubMed1993

A randomized trial of ivermectin versus albendazole for the treatment of cutaneous larva migrans.

In an open study, we compared the efficacy of single doses of oral ivermectin (12 mg) and oral albendazole (400 mg) for the treatment of cutaneous larva migrans. Twenty-one patients were randomly assigned to receive ivermectin (n = 10) or albendazole (n = 11). All patients who received ivermectin responded and none relapsed (cure rate = 100%). All but one patient in the group receiving albendazole responded, but five relapsed after a mean of 11 days (cure rate = 46%; P = 0.017). No major adverse effects were observed. We conclude that a single 12-mg dose of ivermectin is more effective than a single 400-mg dose of albendazole for the treatment of cutaneous larva migrans.

Administration, Oral↗
PubMed1997

Clearance of Wuchereria bancrofti antigen after treatment with diethylcarbamazine or ivermectin.

The present study was undertaken to assess the relationship between microfilarial clearance and clearance of circulating filarial antigen from the blood of Wuchereria bancrofti-infected persons following chemotherapy with either diethylcarbamazine or ivermectin. Patients received either 12 weekly doses of 6 mg/kg of diethylcarbamazine (DEC), a single dose of 6 mg/kg of DEC, a single dose of 420 microg/kg of ivermectin, or 20 microg/kg of ivermectin, followed by 6 mg/kg of DEC five days later. Microfilarial clearance was marked in all groups, but was significantly less in the single-dose DEC. In contrast, as monitored by the Og4C3 monoclonal anitbody assay, clearance of circulating filarial antigen was highly variable, not only between groups but within each group. As a result, there were few statistically significant differences in antigen clearance between groups. In no instance did the antigen level fall to zero, even in individuals that remained microfilaria negative during two or three years of follow-up. These results suggest that living adult worms persist in almost all persons treated with DEC and/or ivermectin.

Adolescent↗
PubMed1998

Three probable cases of Loa loa encephalopathy following ivermectin treatment for onchocerciasis.

Over the past nine years, more than 12 million people exposed to Onchocerca volvulus infection have received at least one dose of ivermectin, almost all without serious adverse reactions. Since 1991, however, several cases with neurologic manifestations, including coma, have been reported after ivermectin treatment of persons infected with O. volvulus who also had concomitant Loa loa infection with very high microfilaremia (> 50,000 microfilariae/ml of blood). In 1995, four criteria were established to define probable cases of Loa encephalopathy temporally related to treatment with ivermectin (PLERI). The present paper describes three PLERI cases recorded in Cameroon and compares them with two others reported previously. Disorders of consciousness began 3-4 days after treatment. The objective neurologic signs were variable. The conditions improved favorably in three patients who benefited from early hospitalization and good nursing; their disorders of consciousness lasted only 2-3 days; the results of clinical examination became normal after one month and electroencephalographic abnormalities disappeared after 5-7 months. Conversely, late diagnosis and delay in proper management in two others probably led to worsening of the condition and to fatal outcome related to the usual complications of coma. In addition to these cases, patients w with high Loa microfilaremia also developed milder neurologic manifestations causing functional impairment lasting for at least one week after treatment. Before launching mass ivermectin distribution programs to control onchocerciasis in central Africa, communities in which the intensity of concomitant L. loa microfilaremia is high need to be identified, and specific educational measures and monitoring strategies should be developed and applied before they are treated.

Adolescent↗
PubMed1999

Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren.

This randomized, placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths (albendazole) and lymphatic filariasis (ivermectin). Children were infected with Ascaris (29.2%), Trichuris (42.2%), and hookworm (6.9%), with 54.7% of children having one or more of these parasites. Wuchereria bancrofti microfilaria were found in 13.3% of the children. Children were randomly assigned to treatment with placebo, albendazole, ivermectin, or combined therapy. Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone. Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone. Only combination therapy resulted in significantly greater gains in height (hookworm-infected children) or weight (Trichuris-infected children) compared with the placebo group. Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and resulted in nutritional benefits not found with either drug alone.

Albendazole↗
PubMed2001

Validation of reports of nodules dissolution after repeated ivermectin treatment of onchocerciasis in southeastern Nigeria.

OBJECTIVE: To ascertain the validity of the claims by villagers in endemic communities in southeastern Nigeria that repeated ivermectin treatment cause disappearance or dissolution of onchocercal nodules. DESIGN: From baseline epidemiological data, four communities (Amuro, Aku, Nzerem Ikpem and Awuchinimo) were randomly chosen as the study sites. A total of 324 adults (hitherto had onchocercal nodules), aged > or = 20 years from these communities were enlisted in the study. After clinical examination, each of the villager was interviewed with structured, pre-tested questionnaire. Also personal and focus group discussion was held. RESULTS: Sixty nine (21.30%) respondents; 16.67% from Amuro, 32.26% from Aku, 19.05% from Nzerem Ikpem and 15% from Awuchnimo claimed that their nodules gradually dissolved or disappeared. A significant (p < 0.05) proportion (82.61%) attributed this phenomenon to repeated doses of ivermectin; 4.35% claimed it was not due to ivermectin therapy while 13.04% were not sure of the cause. CONCLUSION: The results have opened challenges in our understanding of the role of ivermectin therapy in endemic communities and calls for further studies of nodule dissolution in other onchocerciasis endemic communities.

Dose-Response Relationship, Drug↗