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Efficacy of ivermectin in controlling Strongyloides westeri infections in foals.

Twenty-eight foals whose dams were treated IM with ivermectin (200 micrograms/kg of body weight) on the day of parturition were compared with 35 foals whose dams were administered only the vehicle. The effect of ivermectin on the vertical transmission of Strongyloides westeri and foal heat diarrhea was determined by a comparison of results obtained in the 2 groups. Foals from treated mares had significantly fewer S westeri eggs per gram of feces from 17 to 28 days postpartum. There were no differences observed in the frequencies of severity of foal heat diarrhea between the treated and control groups. In another experiment, using the same foals, 32 foals were treated IM with ivermectin (200 micrograms/kg) at 21 days of age and were compared with 31 foals administered only the vehicle. Significantly fewer S westeri eggs were recovered from the ivermectin-treated foals on day 26 to day 32, the completion day of the trial.

Animals↗

Toxicity and efficacy of ivermectin in chelonians.

Five red-footed tortoises (Geochelone carbonaria) treated for intestinal nematode parasitism with a single IM injection of ivermectin (0.4 mg/kg) were found in a state of extreme paresis or flaccid paralysis. One tortoise recovered normal motor function over the next 7 to 10 days. The remaining tortoises died within 3 days of receiving the ivermectin. The only consistent postmortem finding was a marked fatty change in the liver. Studies in the red-footed tortoise showed that some paresis will occur with dosages as low as 0.05 mg/kg. At least 3 other species of chelonians were found to be susceptible to ivermectin toxicosis at similar dosages (0.1 mg/kg or less). The leopard tortoise (Geochelone pardalis) appeared to be the most susceptible of the species tested, consistently developing mild paresis with a dosage of 0.025 mg/kg. Death occurred with dosages as low as 0.3 mg/kg. A dosage of 0.05 mg/kg was found to be safe in red-footed tortoises, provided that treatment was not repeated at intervals of less than 7 days. Shedding of nematode larvae and eggs in the feces of parasitized red-footed tortoises was prevented with 2 to 6 weekly IM injections of ivermectin at a dosage of 0.05 mg/kg, but limited necropsy findings indicated that elimination of adult nematodes from the intestines was incomplete.

Animals↗

Controlled tests of ivermectin against migrating Strongylus vulgaris in ponies.

Twelve pony foals were reared worm-free and inoculated with Strongylus vulgaris. On day 7 after inoculation, 6 ponies were given ivermectin IM at a dose of 200 micrograms/kg of body weight and on day 28 were necropsied. Ivermectin was effective in eliminating early 4th-stage S vulgaris larvae and reducing clinical signs associated with acute arteritis. After administrative ivermectin was effective against early 4th-stage Strongylus vulgaris larvae in ponies when administered at 100, 300, or 800 micrograms/kg of body weight. The purpose of the present study was to report on a more extensive trial, using a single dosage of ivermectin.

Animals↗

Efficacy of ivermectin against inhibited larvae of Ostertagia ostertagi.

The efficacy of ivermectin against inhibited early 4th-stage larvae of ostertagia ostertagi and other nematodes of the abomasum and intestinal tract was determined in naturally infected yearling beef cattle. The time when large numbers of inhibited larvae were acquired was determined by monthly slaughter of monitor cattle, beginning in January. In April, 12 animals were removed from pasture and maintained free of further helminth exposure until slaughter (21 days). At 9 days after the cattle were removed from pasture, ivermectin was administered to the principals by subcutaneous injection (200 micrograms/kg); the other 6 animals were given subcutaneous injections of the ivermectin vehicle. both groups were klled and necropsied at 12 days after treatment. Mean numbers of O ostertagi in the 6 controls were: adults, 41,906; developing 4th stage, 73,813; and early 4th stage, 334,965. The mean proportion of early 4th-stage larvae was 73.7%. In the 6 principals (treated with ivermectin), the following reductions were observed: O ostertagi adults, 100%; developing 4th stage, 99.8%; and early 4th stage, 99,9%. Small numbers of dead and degenerated O ostertagi of all developmental stages were recovered from abomasal washings before fixation; few viable worms were recovered.

Abomasum↗

Anthelmintic efficacy of ivermectin given intramuscularly in horses.

The anthelmintic activity of ivermectin was evaluated in 18 female horses with naturally acquired parasitic infections. Horses were treated once (IM) with vehicle only (n = 6), 200 microgram/kg of body weight (n = 6), and 300 microgram/kg (n = 6). Efficacy of both dosages of ivermectin was greater than 99% against Gasterophilus spp, 100% against Trichostrongylus axei, Habronema muscae, H majus, and Draschia megastoma, 98% to 99% against adult cyathostomes, 86% to 97% against 4th-stage cyathostomes, and 100% against adult large strongyles. Although ivermectin was incomplete in its activity against arterial stages of Strongylus vulgaris, it was effective against microfilariae of Onchocerca spp. Adverse local or systemic reactions were not observed due to treatment with ivermectin.

Animals↗

Ivermectin: activity against larval Strongylus vulgaris and adult Trichostrongylus axei in experimental infections in ponies.

Activity of ivermectin, administered IM at the dosage rate of 200 micrograms/kg of body weight, was evaluated in controlled tests against migrating larvae of Strongylus vulgaris and adult Trichostrongylus axei in experimental infections in 6 ponies raised worm-free. Ponies were given 2,190 or 2,400 infective 3rd-stage larvae of S vulgaris at 7 days before treatment and 22,000 or 22,750 infective 3rd-stage larvae of T axei at 42 or 45 days before treatment. Three ponies were given ivermectin plus vehicle, and 3 ponies were given the vehicle only; the ponies were euthanatized 7 or 9 days after treatment. At necropsy, 4th-stage S vulgaris larvae were not recovered from visceral arteries of the 3 ivermectin plus vehicle-treated ponies, but 21 to 40 larvae were recovered from each of the 3 vehicle-treated ponies. Also at necropsy, adult T axei (140 specimens) were recovered from only 1 ot the 3 ivermectin plus vehicle-treated ponies, but 4,610 to 6,410 specimens were found in each of the 3 vehicle-treated ponies. Toxicosis was not observed after treatment.

Animals↗

A study on the prevention of prenatal and galactogenic Toxocara canis infections in pups by treatment of infected bitches with ivermectin or doramectin.

Investigations were carried out to test the efficacy of a two dose treatment with ivermectin or doramectin on reactivated larvae of Toxocara canis in bitches to prevent prenatal and galactogenic infections of their pups. Thirty pregnant bitches were treated by subcutaneous injection of ivermectin or doramectin on day 40 and 50 post conception (p.c.) each with a dose of 1 mg/kg body weight. The efficacy of the treatments was determined by faecal examinations and by comparing the number of infected pups and the onset of patency in each group of pups. 1. Patient infections with T. canis were seen in pups from untreated bitches from day 21 after birth and all pups were coproscopically positive one week later. To prevent severe clinical symptoms all pups in this group were treated with anthelmintics on day 42 after birth. 2. Pups from ivermectin treated bitches occasionally exhibited patent infections from day 28 after birth onwards; pups from doramectin group exhibited infections from day 56 after birth. The number of patently infected pups in both groups increased till 70 days after birth, probably because of postnatal infections. 3. 28 days after parturition, T. canis infections became patent in all untreated bitches. Single bitches in the ivermectin and doramectin groups developed patent infections after day 49 after parturition. All coproscopically positive bitches had patently infected pups in their litters. 4. The contamination of the environment with eggs of T. canis was calculated from the results of the faecal examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of suramin, ivermectin and CGP 20376 in a new macrofilaricidal drug screen, Onchocerca ochengi in African cattle.

To aid the development of a macrofilaricidal agent for Onchocerca volvulus, the African bovine parasite, O. ochengi, was evaluated as a drug screen by testing three known filaricidal drugs. Groups of five Zebu cattle, naturally infected with more than 15 palpable O. ochengi nodules in the ventral skin, were treated with either suramin (10 mg/kg/day i.v. for 6 days), ivermectin (200 micrograms/kg, s.c.), CGP 20376 (20 mg/kg orally) or left untreated as controls and examined at intervals up to 137 days post-treatment (d.p.t.). After ivermectin treatment, microfilarial densities in the skin decreased within one week to virtually zero and remained at a very low level. A similar rapid and profound reduction was seen after CGP 20376 treatment, but by 137 d.p.t. microfilarial skin densities were approaching pre-treatment levels. With suramin, skin microfilarial densities fell to very low levels after 12 weeks but rose slightly by 137 d.p.t. Effects on the macrofilariae were assessed by sequential nodulectomies at -3 and 28, 84 and 137 d.p.t. By 137 d.p.t. embryogenesis was almost completely interrupted in the CGP 20376 and ivermectin treated animals, although not in the suramin treated group, but in all three groups the majority of remaining intrauterine microfilariae were pathologically altered. Degenerating intrauterine microfilariae accumulated in the ivermectin and in the CGP 20376, but not in the suramin treated worms. The motility of male and female worms was not reduced by any treatment except for female worms at 84 d.p.t. with CGP 20376. Viability of the worms as indicated by the MTT-formazan reduction assay was not reduced in any of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa↗

Onchocerciasis and human immunodeficiency virus in western Uganda: prevalences and treatment with ivermectin.

Epidemiologic investigations were made to assess the interaction between onchocerciasis and human immunodeficiency (HIV) type 1 infection and the efficacy of ivermectin treatment. Among 1,910 Onchocerca volvulus carriers in a hyperendemic focus, 73 (3.8%) were concurrently infected with HIV and 20 (7.2%) of 276 persons without microfilariae (mf) were HIV-seropositive. A stratified analysis showed no epidemiologic association between onchocerciasis and HIV infection. Consistently, a microfilaria density of 11.9 mf/mg of skin in HIV-positive subjects and 17.7 mf/mg in HIV-negatives ones was observed. During mass treatment of onchocerciasis with a single dose of 150 micrograms/kg of ivermectin, no difference of the efficacy was detected between persons with or without HIV and side effects in the two groups were similar. Even in HIV-positive persons with a reduced ratio of CD4+:CD8+ cells and reduced numbers of CD4+ cells, a significant reduction of their microfilaria density was observed after treatment with ivermectin. Thus, in HIV-endemic areas, the usual dose of ivermectin can be administered during mass treatment.

Adolescent↗

Colonisation and degradation of dung pats after subcutaneous treatment of cattle with ivermectin or levamisole.

The fauna and degradation of dung pats from cattle treated with ivermectin or levamisole were examined in a field study conducted in southern Germany. Four groups of seven cattle each grazed on four paddocks. The cattle were treated subcutaneously with ivermectin (0.2 mg/kg) or levamisole (5 mg/kg) 3, 8 and 13 weeks after turnout. A total of 300 pats voided naturally before the first and third treatment and 3, 7, 14 and 28 days after treatment were evaluated. Half of them were used as sampling pats, in which adult and immature Coleoptera, larvae of Diptera and soil and dung nematodes were counted. Earthworms were weighed in samples taken on 8 occasions within 63 days after pat deposition. Dung degradation was investigated using 150 observation pats by measuring surface area, weight and organic matter content on six occasions within 63 days from deposition. A photographic record was also maintained. There was no difference between treatment groups as to the range of Coleoptera, nematodes and earthworms collected from the pats. No quantitative differences between groups were seen regarding the total number of adult and immature dung beetles, soil nematodes and earthworms isolated within 63 days after deposition. Populations of Diptera larvae in pats voided up to 28 days after treatment were reduced for the ivermectin treated group relative to the levamisole group. There were reductions in numbers of dung specific nematodes in pats from both groups and some species were reduced in pats deposited 3, 7, and to a lesser extent, 14 days after treatment for the ivermectin group compared with pats from the levamisole group. These effects on dung fauna had no impact on dung degradation. The results of serial measurement of pat area, photographic evaluation, and determination of remaining dung weight and organic matter showed no difference between treatment group.

Animals↗

[The effect of ivermectin on the transmission of Onchocerca volvulus in southern Mexico].

We assessed the transmission potential and the mean infected and infective biting density of S. ochraceum in an onchocerciasis endemic community in the southern Mexican state of Chiapas. In addition, the impact of first treatment of ivermectin during the peak of natural infection of host-seeking S. ochraceum populations was also evaluated. Monthly entomological sampling was carried out during the year before treatment to assess the seasonal biting behavior of parous host-seeking S. ochraceum females, and either infected (with whatever stage of O. volvulus) or infective females (with only third larval stage of O. volvulus). The mean of infective biting density was unimodal with the peak in February. Higher densities of infective females were detected from January to March. Annual infective biting density estimated was 95.2 and the annual transmission potential of 152.3. After treatment with ivermectin, entomological collections were carried out during the December-April period. In these months, the first ivermectin mass treatment produced a reduction of natural infection rates of 55 per cent in the mean infected females density (p < 0.001) and of 30 per cent in the transmission potential. However, significative differences were found in parity rates of biting females during the evaluation periods. Decrease of infection rates in vector populations was caused by immediate effect of ivermectin over the skin microfilariae. Microfilariae community load available for transmission declined significantly from 14 Dmg/mg to 5.9 Dmf/mg. These means were statistically different (p < 0.001) and were reduced by 58 per cent from the baseline value.

Animals↗

Determination of ivermectin in human plasma by high-performance liquid chromatography.

A specific reversed-phase HPLC-assay with sensitive fluorometric detection has been developed to measure the potent new antiparasitic agent ivermectin (CAS 70288-86-7) in human plasma (and urine). The lower limit of the method was 1 ng/ml and the intra-/interassay variability averaged 4.5/6.9%, respectively. The assay was applied for measuring plasma (urine) concentrations of ivermectin upto 56 (72 h) following a single oral dose of 6 and 12 mg. No unchanged or conjugated ivermectin could be detected in urine. Plasma concentrations increased linearly with dose but elimination half-life (12.6/13.4 h) was independent of the administered dose. Thus, the method is applicable for monitoring plasma levels during clinical and pharmacokinetic trials with ivermectin to evaluate its most efficacious dosage regimen.

Adult↗

The effects of ivermectin on the hydatid cyst of Echinococcus granulosus after direct injection at laparotomy.

The effect of ivermectin on the hydatid cysts of Echinococcus granulosus was studied in vivo. Jirds were infected with secondary hydatid cysts of E. granulosus by intraperitoneal passage. One to one and a half years postinfection a laparotomy was performed on each of 20 jirds and the hydatid cysts located. Ivermectin or the vehicle (1% dimethyl sulfoxide in sterile physiological saline) was injected into a single hydatid cyst in each animal (10 with ivermectin; 10 with vehicle as control). The jirds were killed 44-58 days postsurgery and necropsied. The integrity of each injected cyst was assessed and tissue samples were taken for microscopic examination. Treated cysts were discolored, collapsed, and had no viable protoscolices. The germinal layer of treated hydatid cysts was necrotic; the laminated layer was intact. The effects were restricted to the ivermectin-treated cysts. Treated cysts were not infective to naive jirds by intraperitoneal passage.

Animals↗

The chemotherapy of onchocerciasis XX: ivermectin in combination with albendazole.

Ivermectin is a potent microfilaricide that also blocks microfilarial release while albendazole is toxic to all intrauterine stages. We investigated whether their combination would permanently sterilize the adult worms. In the first open phase, all 69 patients received 150 micrograms/kg of ivermectin. In the second double-blind phase one week later, 35 patients were randomized to receive 800 mg of albendazole with a fatty breakfast for three consecutive days while 34 patients received matching placebo tablets. Detailed clinical and laboratory examinations were done before treatment and were repeated at intervals over one year. Nodules were excised at three and six months. There was a rapid reduction in skin microfilariae, maximal at four weeks (99.9%). Counts increased subsequently and were between 11 and 18% of initial values at one year. Nodule histology showed no macrofilaricidal activity of the combination. A high proportion of the stretched intrauterine microfilariae were degenerate in both groups. Anterior chamber microfilarial counts were unchanged until day 18 and then fell successively. Low levels persisted in several patients at one year. Dead corneal microfilariae and corneal punctate opacities increased initially, fell with time and then disappeared in most patients. Systemic and ocular reactions were mild to moderate and biochemical abnormalities were minor. A pronounced posttreatment eosinophilia subsided by day 30. There was no significant difference between the two groups in clinical and laboratory tolerance or in alterations in skin and ocular parasites and no important differences in the effect on the adult worms. The combination of ivermectin with albendazole given one week apart is well tolerated but produces no additional effect against Onchocerca volvulus when compared to ivermectin given alone.

Adolescent↗

Assessment of parasite control and weight gain after use of an ivermectin sustained-release bolus in calves.

OBJECTIVE: To assess parasite control and weight gain after administration of an ivermectin sustained-release bolus over 135 days to calves grazing in the midwestern United States. DESIGN: Replicated pasture study. ANIMALS: 56 Bos taurus calves. PROCEDURE: Calves were matched for body weight and randomly allocated to remain untreated or to receive an ivermectin sustained-release bolus before turnout on day 0. Calves were grazed by treatment group on B pastures (4 replicates). Body weights and fecal egg counts were recorded on days- 1 and 28, and then at 28-day intervals until day 168. RESULTS: Parasitism was not clinically evident prior to or during the study. In treated calves, mean fecal egg counts were at or near 0 at all posttreatment evaluations. Although the mean egg count exceeded 20 ova/g only once in control calves, the cumulative egg output was > 42 million/calf. For the treated group, it was < 0.1% of this number. Mean total weight gain was 33.9 kg (74.6 lb) greater for ivermectin-treated calves than for untreated control calves (P < 0.02): a 34% increase. CLINICAL IMPLICATIONS: Fecal trichostrongyle eggs from calves can accumulate over a grazing season to provide enormous potential for augmenting pasture infectivity. An ivermectin sustained-release bolus (administered to calves being placed on pasture) controls parasitism, limits pasture infectivity, and can substantially influence growth by limiting the impact of subclinical parasitism.

Animals↗

Efficacy of an in-feed formulation of ivermectin against somatic larvae of Strongyloides ransomi in pregnant swine.

OBJECTIVE: To confirm that ivermectin fed for 7 days to pregnant sows controls transmission of Strongyloides ransomi larvae to pigs via the colostrum or milk. ANIMALS: 24 mixed-breed sows. PROCEDURE: The sows were infected with 250,000 S ransomi larvae on 3 occasions (days 63, 64, or 65, days 71 or 73, and days 78, 79, or 80 of gestation). Eight sows received ivermectin at a dosage of 100 micrograms of ivermectin/kg of body weight/d from days 92 to 99 of gestation, and 8 sows were treated from days 103 to 110 of gestation; 8 remaining sows received unmedicated vehicle. Numbers of S ransomi larvae were counted in samples of colostrum or milk collected 1, 2, and 7 days after parturition. At 7 and 14 days after parturition, fecal samples were collected from each sow and from 4 pigs from each litter for determination of nematode egg counts; at the latter date, pigs were euthanatized and necropsied for worm counting. RESULTS: Pigs born to ivermectin-treated sows had significantly (P < 0.01) fewer adult S ransomi than did those born to control sows; efficacy was 100%. Treated sows had significantly (P < 0.05) fewer S ransomi larvae in colostrum/milk samples taken 1, 2, and 7 days after parturition than did control sows; efficacy was 100%, with the exception of 1 S ransomi larva found in a milk sample from 1 treated sow at 2 days after parturition. CONCLUSION AND CLINICAL RELEVANCE: Ivermectin fed to sows during the last third of gestation at a dosage of 100 micrograms/kg/d for 7 consecutive days is highly efficacious for control of transmission of infective S ransomi larvae to pigs via colostrum or milk.

Animals↗

Efficacy of ivermectin on the infectivity of Leishmania major promastigotes.

Ivermectin is widely used as an antiparasitic drug for livestock and recently used for some human parasites. The effect of ivermectin on the infectivity of Leishmania major promastigotes was studied in Syrian golden hamsters. The results showed that hamsters infected with promastigotes treated for one day with 100 micrograms/ml ivermectin in culture medium did not develop skin lesion at the site of infection. However, amastigotes were demonstrated in Giemsa stained splenic smears. On the other hand, promastigotes treated for two days with 90 micrograms/ml ivermectin did not acquired the infection. i.e. the promastigotes died or lost their infectivity.

Animals↗

Pharmacology of ivermectin.

Ivermectin is a semi-synthetic macrocyclic lactone (Fig. I) active in single low doses against many parasites - particularly nematodes and arthropods. It has been registered for animal health use since early 1985, and was earlier this year approved for human use by the French Directorate o f Pharmacy and Drugs. Of particular interest is ivermectin's potential as a micro filaricide for treatment o f onchocerciasis. Clinical trials leave little doubt about the potential o f ivermectin as a therapeutic tool for symptomatic relief from the effects o f infection with Onchocerca volvulus, and the drug is also recognized to have potential in reducing transmission o f the parasite. The manufacturers (Merck, Sharp and Dohme) recently arranged to provide the drug free o f charge to the WHO for mass trials against onchocerciasis in 12 African and Central American countries. In this article we focus on the pharmacological properties o f ivermectin, with a brief consideration of its absorption, fate, excretion and side-effects, and a discussion o f its micro filaricidal action.

Journal Article↗