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Comparative cost-effectiveness of ivermectin versus topical organophosphate in feedlot yearlings.

A replicated-pen field trial was performed under commercial feedlot conditions in western Canada to determine the cost-effectiveness of administering ivermectin to yearling beef cattle upon entry to the feedlot after the grazing season, and to establish the level of trichostrongylid gastrointestinal parasite infection in this population, as estimated by fecal egg counts. Six thousand eight hundred and eighty-three, mixed breed, yearling steers were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: Ivermectin, which received topical ivermectin (0.5%) at the rate of 1.0 mL/10 kg body weight; or Fenthion, which received topical fenthion (20%) at the rate of 12 mL/295 kg body weight. There were 15 pens in each experimental group. Final weight, weight gain, average daily gain, and dry matter intake to gain ratio were significantly (P < 0.05) improved in the Ivermectin group as compared with the Fenthion group. There were no significant (P > or = 0.05) differences in initial weight, days on feed, or daily dry matter intake between the experimental groups. The geometric mean fecal egg counts at the time of allocation were 14.7 eggs/5 g and 16.6 eggs/5 g for the Ivermectin and Fenthion groups, respectively (P > or = 0.05). There were no significant (P > or = 0.05) differences in morbidity or mortality between the experimental groups. In the economic analysis, the significant improvements in feedlot performance in the Ivermectin group resulted in a net economic advantage of $4.20 CDN per animal.

Abattoirs↗

[Ivermectin and pregnancy in mass treatment in Mali].

During july 1989, we have done a retrospective study, in Koba's valley in a savanna onchocerciasis area of Mali, after a mass treatment in rural community with ivermectin. 435 women aged from 15 to 45 years, among 461 with can be submitted to ivermectin risk during their pregnancy period, was seen and overhauled. In 1987, the frequency of women who received ivermectin during their pregnancy period (treated by error), was 17.7%, and 17.3% in 1988. We have seen any difference, between exposed and not exposed women to this error ivermectin treatment, comparing their in utero-mortality, new born mortality an the level of malformations. In spite of careful clinical monitoring in the field, the risk to give ivermectin to pregnancy women in rural community, is very high during mass treatment. Because traditionally (taboos), pregnancy is a forbidden subject. Sociological and anthropological studies, pregnancy field laboratory test and health education, are needed in african rural community before mass treatment with ivermectin.

Adolescent↗

Adverse reactions to ivermectin treatment in Simulium neavei-transmitted onchocerciasis.

To assess adverse effects of ivermectin treatment in a Simulium neavei-transmitted focus of onchocerciasis, a study was conducted with 1,246 patients infected with Onchocerca volvulus in eight villages in western Uganda. Study participants were treated the first time with a single dose of 150 microg/kg of ivermectin. Adverse reactions to ivermectin were determined through questioning and clinical examination during house-to-house visits to the participants within 48 hours after ivermectin treatment. Overall adverse reactions were observed in 737 (59.1%) patients. Severe reactions were rare (10 patients, 1.4%). Our data show that adverse reactions to ivermectin in an S. neavei-transmitted onchocerciasis focus in western Uganda occur frequently. In spite of the fact that many patients showed adverse reactions to ivermectin, the drug was well accepted and appreciated by the population.

Adolescent↗

Field efficacy of ivermectin plus praziquantel oral paste against naturally acquired gastrointestinal nematodes and cestodes of horses in North America and Europe.

The efficacy of an oral formulation of ivermectin plus praziquantel in the reduction of nematode and cestode egg counts in horses was assessed in 273 horses under field conditions at 15 sites in North America (n = 6) and Europe (n = 9). Horses were confirmed by fecal examination to have natural infections of strongyles (100%) and tapeworms (76%). Replicates of four horses were formed at each site, and in each replicate three animals received ivermectin (0.2 mg/kg body weight) plus praziquantel (1 mg/kg body weight) oral paste and one animal remained untreated or received vehicle paste. Fecal samples were collected for fecal nematode and cestode egg counting before and 7, 8, 9, 14, 15, and 16 days after treatment. Horses treated with ivermectin plus praziquantel oral paste had significantly (P <.01) lower posttreatment strongylid and cestode egg counts (reductions of 98% or more) than controls. Combined site analyses revealed that 95% or 96% of the horses positive for cestode eggs before treatment that were treated with ivermectin plus praziquantel were negative for cestode eggs at each posttreatment fecal examination. No adverse reactions attributable to ivermectin plus praziquantel oral paste treatments were observed. The results of the studies demonstrated that ivermectin plus praziquantel paste was highly effective in reducing egg shedding by gastrointestinal nematodes and cestodes, and no adverse reactions were observed in horses treated under field conditions.

Administration, Oral↗

Efficacy of ivermectin as an anthelmintic in leopard frogs.

Ivermectin administered cutaneously at dosages of 2 mg/kg of body weight eliminated nematode infections in leopard frogs. Three clinical trials were conducted. In the first trial, 5 groups of 11 frogs were given ivermectin IM at dosages of 0, 0.2, 0.4, 2, or 20 mg/kg. All frogs given ivermectin IM at dosages of 2.0 mg/kg or greater died. In trial 2, 44 frogs, allotted to 5 groups, were given ivermectin cutaneously at 0, 0.2, 2, or 20 mg/kg. Cutaneously administered ivermectin was not toxic at dosages up to 20 mg/kg. In trial 3, nematode infections were eliminated in all 10 frogs treated cutaneously with ivermectin at 2.0 mg/kg.

Administration, Cutaneous↗

Single versus repeated doses of ivermectin and diethylcarbamazine for the treatment of Wuchereria bancrofti var. pacifica microfilaremia. Results at 12 months of a double-blind study.

In October 1989, 58 apparently healthy Polynesian Wuchereria bancrofti carriers in whom microfilarial (mf) density was greater than or equal to 100 mf/ml were randomly allocated to treatment groups receiving single doses of either ivermectin at 100 mcg/kg or diethylcarbamazine (DEC) at 3 and 6 mg/kg. Six months later, half of the carriers initially treated with ivermectin 100 mcg/kg or DEC 3 mg/kg were given a second similar dose while the rest were given a placebo. By day 360 (6 months after retreatment), comparison of adjusted geometric mean mf counts per group indicated that (i) among the 3 treatments given once a year the DEC 6 mg/kg dose resulted in the highest efficacy, (ii) nevertheless, regarding either ivermectin 100 mcg/kg or DEC 3 mg/kg, 2 successive doses resulted in higher efficacy than one annual dose and (iii) though no significant difference could be evidenced between efficacy of ivermectin 100 mcg/kg and DEC 3 mg/kg given twice a year, DEC seemed to sustain the mf reduction for a longer period of time. During the 3 days following retreatment, adverse reactions (mild to moderate) were observed in 46% of carriers treated with microfilaricidal drugs and in 20% of those treated with placebo. These results suggest that single dose therapy with either DEC or ivermectin is safe and effective for prevention of lymphatic filariasis due to Wuchereria bancrofti in French Polynesia. The real impact on transmission by the vector, Aedes polynesiensis, of the complete negativation of microfilaremia observed during the previous part of the trial in carriers treated with ivermectin should be evaluated in a community-based trial including entomological study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The embryogenesis of Onchocerca volvulus over the first year after a single dose of ivermectin.

Adult Onchocerca volvulus, extracted from nodules before, and at intervals of two weeks to 12 months after, a single 150 micrograms/kg dose of ivermectin, were examined longitudinally and by sequential transverse sections. The mean number of male worms per nodule fell, and the proportion of nodules with no male worm rose, within two weeks of ivermectin and remained so for 12 months. In female worms, at intervals after ivermectin, the percentages of the length of the lower genital tracts occupied by embryos at each stage of development, or by degenerating ova, embryos and microfilariae (mfs), were recorded: (a) in un(re-)inseminated worms whose original embryogenesis was continuing and in those in which it was completed; and (b) in worms, reinseminated post-ivermectin, in which a new embryogenesis had begun. The results indicated that: (a) the time needed for the zygotes of O. volvulus to develop to mfs is 8-12 weeks; (b) nearly 40 percent of females had not resumed mf production by 12 months after treatment; (c) many intrauterine mfs had not degenerated within the first two weeks of ivermectin; (d) some of the last embryos to mature to mfs did not degenerate but accumulated temporarily in the anterior uteri 8-16 weeks after ivermectin.

Animals↗

Effect of ivermectin on the immune response in mice.

To assess the effect of ivermectin on immune function (antibody production), male CD-1 mice were inoculated with an antigen the day after SC administration of ivermectin (0.2 mg/kg of body weight or 20 mg/kg). Responses were evaluated 5 days after inoculation of the antigen. Antibody production against sheep RBC, a T lymphocyte-, macrophage-dependent response, was enhanced by ivermectin treatment (P = 0.00049). In contrast, antibody production against dinitrophenyl-Ficoll, a T lymphocyte-independent, macrophage-dependent response, was not altered by ivermectin treatment. Results indicate that the immunostimulatory properties of ivermectin are associated with altered function of T lymphocytes, in particular, T-helper lymphocytes. The immunomodulating effects of ivermectin may provide an alternative approach for treatment of disease problems involving immunosuppression.

Animals↗

Viability of adult Onchocerca volvulus after six 2-weekly doses of ivermectin.

Ivermectin is a safe, effective microfilaricide and microfilarial suppressant for Onchocerca volvulus; but in single doses of 100-200 micrograms/kg body weight it has no macrofilaricidal action. The present trial aimed to determine whether 6 doses of 100 micrograms/kg ivermectin, given at 2-week intervals, would kill the adult worms. Eighty-two nodules from 28 otherwise healthy adult male Liberian patients treated with this ivermectin schedule, and 102 nodules from a similar group of 25 control patients, were removed four months after the last dose of ivermectin. They were coded and assessed in a masked fashion either by routine histology or by examination of whole worms extracted from the nodules after collagenase digestion. The drug had no visible effect on adult male worms. More adult female worms were assessed as moribund or dead in the ivermectin-treated group than in the control group (for the collagenase digests P = 0.09; for the histological assessment P = 0.47). The data suggest that repeated dosage with ivermectin may lead to a slow attrition of some female worms and this possibility should be investigated in patients receiving regular doses every 3, 6 or 12 months as part of onchocerciasis control programmes.

Adult↗

Ivermectin uptake and distribution in the plasma and tissue of Sudanese and Mexican patients infected with Onchocerca volvulus.

Ten Sudanese patients with Onchocerca volvulus infection were treated with a single oral dose of 150 micrograms/kg of ivermectin. Plasma samples were collected before treatment, 0.5, 1, 3, 4, 6, 12 hours and 1, 2, 3, 7, and 30 days. Four patients were selected for nodulectomies and skin biopsies at 6, 18 and 30 hours and 3 days post treatment. Using these samples O. volvulus worm fragments were dissected free of host nodular tissues for ivermectin extraction. Ivermectin was present in the nodular tissue at 6 hr and persisted for 3 days. It was also detected in an individual worm tissue extract at a concentration similar to the nodule, but in subcutaneous fascial tissue higher concentrations were sometimes found. Ivermectin was detected by radioimmunoassay in the plasma of all patients at 1 hr and peak concentrations were reached in an average of 5.6 hr. The drug persisted at detectable levels for 7 days in 70% of the studied patients. Plasma samples were also collected from 16 treated Mexican onchocerciasis patients before ivermectin treatment and 4 hr treatment and from six individuals who served as controls. The Mexican patients had concentrations of ivermectin in their plasma similar to those in the Sudanese patients.

Humans↗

Double blind study on efficacy and safety of single doses of ivermectin and diethylcarbamazine for treatment of Polynesian Wuchereria bancrofti carriers. Results at six months.

In 1989, a double-blind trial was implemented in Tahiti to compare both efficacy and tolerability of single doses of ivermectin and diethylcarbamazine (DEC) for treatment of Wuchereria bancrofti carriers. Of 58 carriers, in whom microfilarial (mf) density was greater than or equal to 100 mf/ml, 23, 24 and 11 were randomly allocated to treatment with respectively ivermectin 100 mcg/kg, DEC 3 and DEC 6 mg/kg. One week after treatment, clearance of microfilaremia was complete in 22 of the 23 carriers treated with ivermectin and in one only of the 35 treated with DEC. Adjusted geometric mean for mf densities was significantly lower (p less than 0.001) in carriers treated with ivermectin than in those treated with DEC at one, but neither at 3 (p = 0.26) nor at 6 months (p = 0.63). At 3 and 6 months, mf levels were 14 and 28%, 21.6 and 19.4%, and 10.2 and 8.4% of pretreatment mf levels in carriers treated respectively with ivermectin 100 mcg/kg, DEC 3 and DEC 6 mg/kg. Side effects were experienced by 51 carriers (88%) of whom only 8 (14%) suffered a grade 3 reaction. Onset and intensity of side effects were significantly associated (p less than 0.01) with both pretreatment mf densities and peripheral blood parasite clearance. Efficacy of ivermectin single dose was superior to that of DEC single dose in terms of immediate mf clearance but not in terms of sustained mf decrease at 6 months.

Adult↗

[Changes in the peripheral leukocytes of onchocerciasis patients treated with consecutive doses of ivermectin].

The purpose of this investigation, which utilized a single-blind study with placebo, was to evaluate the peripheral leukocyte count in onchocerciasis patients treated with ivermectin. Eighty-three male patients between the ages of 12 and 60, all with moderate or severe onchocerciasis infections (but otherwise in general good health), were selected from three villages from the southern onchocerciasis endemic area of Chiapas, Mexico. All onchocerciasis patients were randomly assigned to either the ivermectin group or a placebo group in a three to one ratio, respectively. Sixty-two patients from the ivermectin group received five single oral doses of ivermectin between 150 and 220 mcg/kg (one every six months), and placebo pills of identical appearance were given to 21 patients from the placebo group. Physical, ophthalmological, and laboratory exams were performed on all patients in this study. Skin and ocular microfilaria were stimulated in all patients. Results have indicated that ivermectin induced a decrease in the total number of peripheral leukocytes to the extent of about 300 to 500 cells after each drug intake. In the majority of the cases, the reduction was due to a decrease in the total number of eosinophils; the number of neutrophils, lymphocytes, and monocytes remained at the same level after treatment. These results strongly suggest that the eosinophilia observed in the prestudy of those individuals with onchocerciasis could have induced leukocytosis (the eosinophilia decreasing significantly after administering ivermectin).

Adolescent↗

Large scale ivermectin distribution and its epidemiological consequences.

Community trials were started to address questions concerning the safety of ivermectin during large scale treatment, its potential for transmission control, its effect in preventing ocular onchocercal disease, its acceptability and the organization of large scale treatment. A summary is presented of the major, latest results on the short-term epidemiological impact of large scale ivermectin treatment, as observed in eight community trials undertaken in the Onchocerciasis Control Programme in West Africa (OCP). Ivermectin treatment resulted in a 96%-99% reduction in the mean load of microfilariae (mf) in the skin in treated patients. The subsequent mf-repopulation of the skin was faster than in the clinical trials and after 12 months the mean loads had returned to more than 40% of the pre-treatment load. Ocular mf loads were also greatly reduced and a post-treatment regression of early lesions of the anterior segment of the eye was observed. The transmission of Onchocerca volvulus was reduced by some 60% during the first year after treatment in one trial but no additional reduction was observed after the second treatment round. These results, and other recent research findings, have been used to quantify an epidemiological model for the transmission and control of onchocerciasis. Preliminary results of computer simulations of the predicted long-term epidemiological impact of large scale ivermectin treatment indicate that ivermectin treatment may play a very important role in disease control but that it is unlikely to become a practical tool for transmission control in endemic foci. Ivermectin treatment appears to be the most appropriate method for control of recrudescence of infection in an area where the parasite reservoir has been virtually eliminated by vector control, such as in the core area of the OCP.

Africa, Western↗

Efficacy of ivermectin in oral drench and paste formulation against migrating larvae of experimentally inoculated Parascaris equorum.

Twenty-one mixed-breed pony foals, reared and maintained under parasite-free conditions, were used to test the efficacy of ivermectin in oral drench and paste formulations (200 micrograms/kg) against 11-day-old migrating larvae of Parascaris equorum. Three replicates of 4 foals and 3 replicates of 3 foals were formed on the basis of age. Foals in replicates of 4 were randomly allocated to be indicators, or to receive vehicle (control) or ivermectin paste or ivermectin liquid. Foals in replicates of 3 were randomly allocated to receive vehicle or ivermectin paste or ivermectin liquid. The recovery of larvae from the lungs, liver, and small intestines of the indicator foals showed that 99.9% of the larvae were in the lungs 11 days after inoculation (day 0 of treatment). The recoveries of larvae from lungs and small intestines of controls at 25 days after inoculation indicated that all larvae had migrated to the small intestine by this time. The mean length of larvae recovered from the lungs (11 days after inoculation) was 0.87 mm the mean length of those recovered from the small intestine (25 days after inoculation) was 3.65 mm. Using larvae recovered from small intestinal contents for calculations, ivermectin in both formulations was 100% effective against 11-day P equorum (P less than 0.01, compared with control group geometric mean of 1498.4).

Animals↗

Ivermectin for the treatment of Wuchereria bancrofti filariasis. Efficacy and adverse reactions.

Ivermectin treatment was evaluated for efficacy and side effects in 40 patients in South India who had microfilaremia and bancroftian filariasis. Ivermectin was administered once orally at four dose levels (range, 25 to 200 micrograms/kg), and at each it was found to be completely effective in clearing blood microfilariae within five to 12 days. In most patients, microfilariae reappeared by three months; by six months the levels averaged 14% to 32% of pretreatment values in the four study groups, and all groups showed equivalent efficacy. Detailed monitoring identified some side effects in almost all patients: usually fever, headache, light-headedness, myalgia, sore throat, or cough that occurred most prominently 18 to 36 hours after treatment. These were most frequent and severe in patients with the greatest microfilaremia, but only when treated with the two higher doses of ivermectin (100 and 200 micrograms/kg). The low-dose (25 micrograms/kg) ivermectin group, despite equivalent efficacy in parasite killing, had clinical reaction scores that were minimal and that were not correlated with parasitemia. Since efficacy and side effects of ivermectin therapy compare favorably with those reported for treatment with the standard antifilarial drug diethylcarbamazine citrate, the major advantage of single-oral-dose administration makes ivermectin the best candidate to replace diethylcarbamazine as the treatment of choice for bancroftian filariasis.

Adult↗

Efficacy of ivermectin in the oral paste formulation against naturally acquired adult and larval stages of Parascaris equorum in pony foals.

The efficacy of ivermectin in oral paste formulation at a dosage of 200 micrograms/kg of body weight was tested against naturally acquired larval and adult stages of Parascaris equorum, in a controlled study. Twenty infected pony foals 18 to 27 weeks of age were randomly allocated to 2 groups of 10 each and were placed in dry lots. Foals in 1 group were given ivermectin on day 0. Necropsies and parasite recoveries from small intestines and lung tissues were performed on 5 foals in each group at 2 weeks after treatment (WAT) and on the remaining foals at 5 WAT. Ivermectin was 100% effective against adult P equorum. At 2 WAT, ivermectin was 100% effective against lung larval stages and 91% effective against intestinal larvae of P equorum. Efficacy of ivermectin against all intestinal stages was 93%. Intestinal and lung larval populations were similar in ivermectin-treated and nontreated foals at 5 WAT, indicating that the foals had become reinfected from the contaminated drylots, with larvae repopulating in the tissues 2 to 5 WAT. Apparent increases in severity of lymphoproliferative and inflammatory tissue reactions were observed histologically in lung and liver tissues of treated foals. Clear differences in clinical conditions between foals in treated and nontreated groups were not observed. However, weight gains in foals were greatest after treatment.

Animals↗

Efficacy of repeated doses of levamisole, morantel, fenbendazole, and ivermectin against gastrointestinal nematodes in ewes.

Levamisole, morantel, fenbendazole, or ivermectin was administered at 2-week intervals from May 1 through Sept 14, 1985, to breeding ewes (20 ewes/drug) infected with various gastrointestinal nematodes. All ewes had fewer gastrointestinal nematode eggs per gram of feces (epg) after 2 treatments, compared with pretreatment epg counts. Ewes administered ivermectin continued to have a low mean epg (0 to 3) throughout the study. The mean epg counts of ewes treated with levamisole increased from 3 to 483 during the study. This increase was similar to that of ewes treated with morantel (7 to 485 epg). The mean epg count of fenbendazole-treated ewes increased from 4 to 192 during the study. By the end of the study, the mean epg counts when expressed as a percentage of the pretreatment epg counts were 4% (ivermectin), 249% (fenbendazole), 627% (levamisole), and 630% (morantel). With the exception of the ivermectin-treated ewes, the epg count increased almost linearly in the ewes after the 2nd anthelmintic treatment. These data indicate that the gastrointestinal nematodes (including Haemonchus contortus) may have developed more resistance to levamisole and morantel than to fenbendazole. On the basis of the epg counts, resistance to ivermectin did not develop during the 4.5-month treatment period. The percentage of ewes shedding eggs after 2, 4, and 6 anthelmintic treatments was lowest for ewes treated with ivermectin (20%) and was similar (40%) for ewes treated with 1 of the other 3 anthelmintics. At the conclusion of the study, most of the ewes (90%) were shedding at least a small number of eggs, regardless of the anthelmintic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ivermectin for the control of swine scabies: relative values of prefarrowing treatment of sows and weaning treatment of pigs.

Ivermectin given in a single subcutaneous dose (300 micrograms/kg of body weight) was tested for activity against swine scabies (Sarcoptes scabiei). Efficacy was determined by recoveries of mites from ear scrapings and by observations of clinical signs. Treatment of infected sows 8 to 37 days before farrowing eliminated scabies from the sows and prevented its transmission to their offspring. Pigs farrowed by ivermectin-treated sows remained noninfected throughout the study regardless of whether they were treated with ivermectin at weaning. Placebo-treated sows remained infected and transmitted scabies to their offspring. Ivermectin treatment of pigs at weaning eliminated the infection, whereas placebo treatment did not. The placebo-treated pigs remained infected while in the nursery, but ivermectin treatment eliminated the infection when they were moved to the growing and finishing floor at 12 weeks of age. It appears that an effective control program for swine scabies using ivermectin could be based on a single treatment of the sows before farrowing. Any infection (epizootic) appearing in growing pigs could be controlled by a single treatment of all in-contact pigs.

Animals↗