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Adverse reactions after community treatment of onchocerciasis with ivermectin in Guatemala.

Male and female residents on a Guatemalan coffee plantation where Onchocerca volvulus infections were hyperendemic were offered oral ivermectin (100-200 micrograms/kg) as part of a community-wide treatment programme for onchocerciasis. Forty-five persons were treated and then questioned daily for 28 d about changes in their health. Those with complaints were monitored until all signs and symptoms had resolved. Sixty-seven percent complained of some adverse event after treatment; 60% developed observable adverse reactions attributed clinically to ivermectin. No reaction was life-threatening; the most common were oedema (53%) and fever (47%). Expulsion of intestinal helminths was reported by 38%. Almost all reactions began 24-48 h after treatment; their mean duration was 5 d, despite treatment with acetaminophen and antihistamines. Three patients had oedematous changes lasting over 2 weeks. Incidence, but not severity, of reactions was related to the pretreatment density of microfilariae in skin.

Adolescent↗

The impact of five years of annual ivermectin treatment on skin microfilarial loads in the onchocerciasis focus of Asubende, Ghana.

Following the registration of ivermectin (Mectizan) for human use in the treatment of onchocerciasis, in 1987 the Onchocerciasis Control Programme in West Africa (OCP) begun a series of trials in order to determine the safety of the drug when used on a large scale and its potential for morbidity control. This paper reports the changes in skin microfilarial loads during the first 5 years of annual treatment in the holoendemic focus of Asubende in Ghana, which was the largest trial area and which also had the longest series of follow-up surveys. The general observed pattern was a marked reduction of microfilarial loads shortly after each treatment followed by a steady repopulation of the skin until a subsequent treatment round. The overall reduction of microfilarial loads observed between the base line survey and one year after the last treatment was 90% for the total population examined and over 93% for a cohort which received the drug at all 5 treatment rounds. In contrast, there was only a very gradual decrease in the prevalence of infection in the population after subsequent treatments. The study further emphasizes that even a single treatment with ivermectin has a significant medium-term impact on microfilarial loads. Microfilarial counts barely increased after 14-16 months of treatment and stabilized around 55% of pre-treatment counts 2-4 years after a single treatment.

Animals↗

Advantages of ivermectin at a single dose of 400 micrograms/kg compared with 100 micrograms/kg for community treatment of lymphatic filariasis in Polynesia.

In April and October in 1991-1993, 5 supervised single doses of ivermectin were given to inhabitants aged > or = 3 years in a Polynesian district: the first 3 treatments were with 100 micrograms/kg and the 2 latter with 400 micrograms/kg. At each treatment, about 97% of the eligible population (899) were treated and blood samples were collected just before treatment from 96% of the 613 inhabitants aged > or = 15 years. Following the 5 successive treatments, adverse reactions were observed in, respectively, 23.8, 13, 6.2, 13.6 and 7.9% of the microfilariae (mf) carriers, and in less than 1% of amicrofilaraemic subjects. Neither the frequency nor the intensity of adverse reactions was significantly different between single doses of 100 micrograms/kg and 400 micrograms/kg. Although the geometric mean microfilaraemia (GMM) was reduced, the mf carrier prevalence remained unchanged before and after 3 mass treatments with 100 micrograms/kg (21.4 and 20.7% respectively), and the mf recurrence rate 6 months after each dose of 100 micrograms/kg was roughly stable (respectively, 34.3%, 21.6% and 31.2% of the initial GMM). In contrast, after one dose round of 400 micrograms/kg, the mf carrier prevalence decreased significantly to 14.9% (P < 10(-6)), and the mf recurrence rate dropped to 9.9% (P < 10(-3)) of the initial GMM. These results confirm the safety and the effectiveness of 400 micrograms/kg of ivermectin for lymphatic filariasis control.

Adolescent↗

Effects of ivermectin on the activity of enzymes in mammalian cells in vitro.

The effects of ivermectin on the activities of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glucose-6-phosphatase have been estimated in IB-RS-2 cells in vitro. A 72-hr time course following ivermectin exposure indicated a decrease in the activity of lactate dehydrogenase. The activities of glucose-6-phosphate dehydrogenase and glucose-6-phosphatase remained essentially unchanged.

Animals↗

Knowledge, attitudes and perceptions (KAP) of onchocerciasis: a survey among residents in an endemic area in Guatemala targeted for mass chemotherapy with ivermectin.

If ivermectin distribution programs are to have maximum impact on the morbidity and transmission of human onchocerciasis there must be broad and sustained acceptance within the endemic communities. Educational activities, developed with careful consideration of community attitudes, should promote positive treatment seeking behavior while simultaneously addressing local reservations about the control effort. To better understand the ambient knowledge, attitudes, and practices concerning onchocerciasis in the context of ivermectin use in Guatemala, we conducted a survey among 145 heads of households in five endemic communities. Given the country's long-standing nodulectomy program, it was not surprising that 100% of persons interviewed had heard of the disease 'la filaria', which they defined as a skin nodule that could cause blindness. Ninety-five percent of respondents identified surgery as the only cure for the condition. Relatively few (39%) knew that la filaria was caused by a worm, although slightly more (50%) knew that the condition was acquired by the bite of an insect. The term microfilaria was not broadly recognized. We also determined that onchocerciasis was not perceived as a serious health problem: few persons (12%) mentioned la filaria when requested to provide a complete list of illnesses that occurred in the community, and the gravity of infection (based on rank ordering of common illnesses) was similar to that of a bad cold. Recommendations were made which might assist long-term acceptance of a national chemotherapy initiative against onchocerciasis in Guatemala.

Adolescent↗

The infectivity of surviving Psoroptes ovis (Hering) on cattle treated with ivermectin.

Ivermectin, 22,23-dihydroavermectin B1 (Merck MK-933), injected intramuscularly at the rate of 200 microgram kg-1 body wt., completely eliminated Psoroptes ovis populations from 6 Hereford cattle within 2 weeks after treatment. However, mites surviving 1, 3, and 5 days after treatment were viable and infective when transferred to untreated cattle. Mites surviving 7 days after treatment did not cause scabies or establish a colony of mites when transferred to untreated cattle. These results indicate that cattle treated with ivermectin for control of psoroptic scabies should be isolated from other cattle for at least 5 days after treatment.

Animals↗

The efficacy of ivermectin against nematode parasites of White Fulani calves.

Ivermectin was evaluated for anthelmintic activity in calves naturally infected with gastrointestinal helminths. Five of 10 calves were treated subcutaneously with ivermectin at 200 micrograms per kg body weight. One-hundred percent efficacy was indicated against adult and immature Haemonchus, Trichostrongylus, Bunostomum phlebotomum and Oesophagostomum radiatum. Adult Cooperia were also completely eliminated, and a 95.5% reduction was obtained for the immature forms; an 88.7% reduction was obtained for Trichuris spp.

Ancylostomatoidea↗

Treatment of inhibited Dictyocaulus viviparus in cattle with ivermectin.

Fifteen calves, each infected with approximately 3000 third stage larvae, were used to compare the tendencies of two strains of Dictyocaulus viviparus to inhibit at the fifth larval stage and to evaluate the efficacy of ivermectin. There were notable differences between the strains. While greater than 99% of worms developing from infection with an Alpine strain remained inhibited 42 days after infection, only 0-26% of those recovered following infection with a U.K. laboratory strain were arrested. Neither adult nor immature D. viviparus were present in the lungs of animals treated with ivermectin subcutaneously at 200 micrograms/kg body weight 28 days after infection with the Alpine larvae.

Animals↗

Efficacy of ivermectin against mange and gastrointestinal nematodes of buffalo (Bubalus bubalis).

The incidence of mange in dairy buffalo in India has increased significantly in recent years. The authors record an outbreak of mange affecting a dairy herd stocking about 30,000 buffalo and 1000 cows. The mange mites were either Sarcoptes scabiei or Psoroptes ovis, or a mixed infestation of both. The morbidity rate was 5-30% varying from group to group, with 100% in a severely affected group. Signs noticed were progressive dermatitis, alopecia, keratinization, skin thickened and wrinkled, intense itching and marked loss of condition often ending in death. Great losses of young animals from mange and gastrointestinal nematodes are very common in dairy herds in India. In view of their economic importance, the activity of ivermectin against naturally occurring mange and parasitic infections of adult buffalo and buffalo calves was determined. Ivermectin was administered by subcutaneous injection (IVOMEC 1% w/v - MSD AGVET) at a dose of 200 mcg kg-1 body weight. The efficacy was ascertained from the disappearance of mites from skin scrapings and the reduction in numbers of worm eggs in the faeces. The results of the treatment were dramatic: the mites disappeared within 2 weeks of the drug being administered in the majority of animals, with marked improvement in skin lesions. Four buffalo which had their entire body surface affected with mange needed a second dose on Day 28 for complete recovery. The effect on the nematodes was equally spectacular, with infections of Neoascaris vitulorum, Trichostrongylidae, Oesophagostomum spp. and Bunostomum being eliminated within 1 week of treatment.

Animals↗

Anthelmintic activity of ivermectin against experimental Ascaridia galli infection in chickens.

The efficacy of ivermectin against Ascaridia galli infection was evaluated in chickens under controlled laboratory conditions in two separate experiments. In each experiment 22 White Leghorn chicks were randomly assigned to three groups of 10 (infected-treated), 9 (infected-control) and 3 (uninfected-control) birds. Each bird in the former two groups was orally infected with 1,500 embryonated A. galli eggs. The chicks in the treated group were subcutaneously injected with ivermectin at a dose of 0.3 mg kg-1 body weight on Day 10 (Experiment 1) and Day 35 post-infection (Experiment 2) for immature and adult infections, respectively. The treated birds had 0.9% (Experiment 1) and 0.4% (Experiment 2) worm recovery compared with 8.7 and 8% in the infected-untreated controls of the respective experiments. The fall in post-treatment faecal egg counts was 81 and 92% in birds treated on Days 10 and 35, respectively. The drug was found to be 90 and 95% effective against immature and adult worms, respectively. The lower lesion score and post-treatment near-normal haematobiochemical picture in treated birds confirmed these observations. The treated birds also had a better growth rate than the untreated chickens. The mature worms in the intestinal lumen of the host were more sensitive to the treatment than the immature stages of the parasite in the tissue phase.

Animals↗

Effect of ivermectin treatment on anti-hypodermin C titers of Asturiana cattle naturally infected with Hypoderma lineatum.

The collagenase (hypodermin C) from soluble crude extracts of Hypoderma lineatum 1st-instar larvae was purified by reverse-phase HPLC and used in a new indirect ELISA test. This pure protein had several advantages over the use of crude larval extracts allowing a much better discrimination between infested and non-infested cattle. The anti-hypodermin C titers of 19 Asturiana cattle were estimated over the course of a natural H. lineatum infestation cycle, in which the effect of ivermectin treatment was also investigated. The results showed differences in the onset and ending of the infestation with respect to those described for other European countries. The ivermectin treatment proved to be very effective and treated animals had relatively low anticollagenase titers.

Animals↗

Effects of tactical late-season treatments with ivermectin on calves naturally exposed to trichostrongyles.

This study was conducted to evaluate the effects of tactical treatments with ivermectin against trichostrongyles in first-season grazing heifer calves in the Danish marshland. A group of Black-Pied Friesian calves was turned out in early May on a permanent pasture naturally infected with trichostrongyle larvae. In late July, when high herbage infectivity started to appear, the pasture was divided into two plots of equal size, which from then and until housing in late October were each grazed by half of the original group of calves. One of these groups was given three anthelmintic treatments with ivermectin at 4-week intervals starting in late July. The other group served as non-treated controls. Ostertagia ostertagi and Cooperia oncophora were the predominant trichostrongyles. Nematodirus helvetianus was observed on few occasions. Although the animals were exposed to a high herbage infectivity from July onwards, the anthelmintic treatments conferred a significant reduction in trichostrongyle loads, as evidenced by an almost complete cessation of egg excretion and a significant lowering of pepsinogen and gastrin levels in the blood. This was reflected in higher weight gains.

Animals↗

Effect of ivermectin delivered from a sustained-release bolus on the productivity of beef cattle in Oregon.

The effect of ivermectin delivered from a sustained-release bolus (I-SRB) on the weight gain of beef cattle through a grazing season was evaluated using 20 yearling beef steer calves randomly divided into two groups of ten animals each. Calves in the control group each received a placebo bolus, while those in the treatment group each received an I-SRB designed to release 12 mg ivermectin day-1 for approximately 90 days. All animals were weighted and samples of feces were collected from the rectum at monthly intervals, beginning on Day 0, until trial termination (Day 148). Pasture larval counts were also conducted on herbage collected on each sampling date. On Day 119, two control and two treated calves were removed from pasture, housed in isolation for 3 weeks, then necropsied for recovery of gastrointestinal nematodes. Three sets of parasite-naive tracer calves were utilized to evaluate the initial, interim and final levels of pasture contamination by nematode larvae. A fourth set was used to evaluate the level of pasture contamination the following spring. The use of the I-SRB resulted in a greater than 99% reduction in fecal egg counts of trichostrongyles and numbers of gastrointestinal nematodes in the treated principals, as well as an average daily gain advantage of 0.114 kg over the 148 day period. A 67-98% reduction in pasture larval nematode contamination occurred on pastures grazed by the treated animals, as indicated by the parasite burden in tracer calves and pasture larval counts. The treatment effect was eventually lost by the following spring since tracer calves on the treated pasture had only 33% fewer nematodes than those on the control pasture.

Animals↗

Effect of parasitism with Nematodirus battus on the pharmacokinetics of levamisole, ivermectin and netobimin.

The pharmacokinetics of levamisole, ivermectin and netobimin administered orally and by subcutaneous injection were compared in lambs exposed to a moderate challenge with Nematodirus battus and in parasite naive lambs. There were no significant differences (P greater than 0.05) in the bioavailability of any of the anthelmintics tested between parasitized and non-parasitized animals. Levamisole reduced nematode faecal egg output by more than 99% when administered by either route. Ivermectin was also highly effective (greater than 99%). Orally administered netobimin reduced egg output by more than 98% seven days after administration. However egg output was only reduced by 89% 21 days after administration, suggesting poor activity against the early parasitic stages of N. battus. Netobimin was not effective against N. battus when administered by the subcutaneous route and this was probably because very low plasma concentrations of its active albendazole metabolites were achieved.

Administration, Oral↗

Treatment of stephanofilariosis ('earsore') with ivermectin.

Thirty-four adult male buffaloes with clinical signs of 'earsore' were used to determine the efficacy of ivermectin against Stephanofilaria zaheeri. On the basis of parasite counts in skin scrapings, ivermectin was effective as a microfilaricide. Adult parasite counts were reduced, but removal of adults was incomplete. Clinical improvement was recorded in more than half of the treated buffaloes, but constant reinfection meant that meaningful interpretations were not possible.

Animals↗

Influence of ivermectin and clorsulon treatment on productivity of a cow-calf herd on the southern Oregon coast.

The reproductive performance of beef cows and the weight gain of their calves was evaluated after oral administration of clorsulon or clorsulon in combination with the subcutaneous administration of ivermectin. One hundred and fifty pregnant cows harboring infections of Fasciola hepatica were assigned to one of three treatment groups: Group 1 comprising 50 unmedicated controls; Group 2, 50 cows treated with clorsulon orally at 7 mg kg-1; Group 3, 50 cows treated with clorsulon orally at 7 mg kg-1 and ivermectin subcutaneously at 200 micrograms kg-1. Weights and body condition scores of the cows were measured and fecal and blood samples were taken at trial initiation and days 158 and 270. Pregnancy status was also determined at day 270. Weights and body condition scores were measured for the calves at days 158 and 270. Adjusted 205 day weaning weight of the calves was calculated and analyzed for differences between treatment groups. Four sets of tracer calves were used periodically throughout the trial to monitor the helminth challenge to the herd. Both gastro-intestinal nematodes and liver flukes were transmitted to the tracer calves during the entire trial. Even in the face of continual helminth challenge, beef cows treated with combined clorsulon/ivermectin conceived approximately 2 weeks earlier than their untreated counterparts and their calves had better body condition scores and weights than untreated calves.

Administration, Oral↗

Haemonchus contortus resistance to ivermectin and netobimin in Brazilian sheep.

Suffolk, Texel, Hampshire Down and Ile de France sheep from the municipalities of Porto Amazonas, Piraquara and Araucaria in the State of Paraná, and Bagé in the State of Rio Grande do Sul were brought to Sobral, State of Ceará, to be used in a cross-breeding project. On arrival they had clinical signs of nematode parasitosis, and one Suffolk female died. The animals were treated orally with ivermectin (0.2 mg kg-1) and fifteen days later with netobimin (20.0 mg kg-1). Neither drug reduced the egg counts (measured in eggs per gram, EPG) significantly, and this suggested that the nematodes in the sheep were resistant to the anthelmintics used. Haemonchus contortus was the species involved. The egg counts were reduced after oral treatment with trichlorfon (100.0 mg kg-1). Haemonchus contortus larvae obtained from these animals before trichlorfon treatment and passaged through two nematode-free sheep were used in a further experiment. Twenty 6- to 9-month-old nematode-free lambs were infected with the H. contortus larvae (10,000 per animal) and after the infection was confirmed, were randomly divided into four groups of five animals. Group I was orally treated with ivermectin at 0.2 mg kg-1, Group II with oral netobimin at 20.0 mg kg-1, Group III with oral trichlorfon at 100.0 mg kg-1 and Group IV was a non-treated control. Egg counts and faecal cultures were taken before dosing on the day of treatment and seven days later when all animals were necropsied and the nematodes were collected from the abomasa and counted.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Laboratory selection for ivermectin resistance in Haemonchus contortus.

A strain of Haemonchus contortus, susceptible to ivermectin (IVM), was submitted to a selection procedure using IVM at 0.02 mg kg-1 during nine successive passages in lambs. Treatment reduced worm egg counts (epg) by more than 99% up to the seventh passage, but thereafter there was no significant reduction in epg. The efficacy of ivermectin against the ninth selected generation compared with the original susceptible strain was assessed. The results showed that animals infected with the selected strain and treated with IVM did not show any significant reduction (P > 0.05) in epg compared with a 99.9% reduction in the susceptible group. At necropsy, post-treatment worm burdens confirmed that the selection pressure applied to the original strain had been successful in stimulating resistance to IVM.

Animals↗