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Impact of mass treatment of onchocerciasis with ivermectin on the transmission of infection.

Onchocerciasis is a major blinding disease that, until recently, has been essentially untreatable. Ivermectin is a safe and effective drug for the mass treatment of onchocerciasis and when used on an individual basis, it reduces the ability of the treated person to transmit Onchocerca volvulus infection. In the present study, the effect of community-based ivermectin treatment on the degree of transmission within the community was assessed by determining the incidence of new infection in children. Ivermectin was distributed annually on three occasions to the eligible members of a population of approximately 14,000 people living on a rubber plantation in a forest area endemic for onchocerciasis. After 2 years, the prevalence of infection in 5-year-old children decreased by 21%. The annual incidence in an uninfected cohort of children decreased by 35% and, after age-specific adjustment, the reduction in incidence in 7- to 12-year-old children was 45%. Thus, community-based distribution of ivermectin led to a significant reduction in incidence of new infection. These findings suggest that ivermectin can be important in reducing the transmission of onchocerciasis.

Child↗

Ocular findings in a double-blind study of ivermectin versus diethylcarbamazine versus placebo in the treatment of onchocerciasis.

The effect of ivermectin, a new microfilaricide, was assessed in a double blind trial against diethylcarbamazine citrate (DEC) and placebo. Fifty-nine adult males with moderate to heavy infection with Onchocerca volvulus and with eye involvement were recruited from an area under Onchocerciasis Control Programme (OCP) vector control in Northern Ghana. They were randomly assigned to an eight-day treatment with ivermectin as a single dose of 12 mg on day 1 followed by placebo for the remaining seven days, or DEC, total dose 1.3 g, or placebo, and ophthalmological review was undertaken over a period of one year. DEC acted quickly to eliminate microfilariae from the eye and was associated with reactive ocular changes and in a few cases functional deficit. Ivermectin eliminated microfilariae slowly from the anterior chamber of the eye over a period of six months. The ocular inflammatory reaction was minimal and no functional deficit occurred. It is postulated that the observed slow action of ivermectin on the eye may be attributed in part to its instability to cross the blood-aqueous humour barrier because of its molecular size as a macrocyclic lactone causing microfilariae to leave the eye gradually along a newly created gradient. Ivermectin is an effective microfilaricide with minimal ocular adverse effect and could therefore be suitable for widespread application without strict supervision.

Adolescent↗

Comparison of ivermectin, oxfendazole and levamisole for use as anthelmintics during the periparturient period in sheep.

Ewes synchronised with progestin impregnated sponges to reduce the spread of lambing were treated during the periparturient period with anthelmintic. The suppression of nematode egg output in faeces was measured in ewes given ivermectin either by subcutaneous injection or orally, or oxfendazole or levamisole orally. Ivermectin and oxfendazole reduced the output of eggs in the faeces of the ewes significantly (P less than 0.05) and the period of suppressed egg output was extended when ivermectin was given by subcutaneous injection. Plasma pepsinogen activity was estimated as a measure of abomasal damage. Pepsinogen values were significantly (P less than 0.001) lower in those animals treated with ivermectin by subcutaneous injection than in control animals. Levamisole showed a poorer response in terms of the output of eggs in faeces than either ivermectin or oxfendazole.

Administration, Oral↗

Field efficacy of ivermectin, fenbendazole and pyrantel embonate paste anthelmintics in horses.

Three anthelmintic pastes were compared in terms of their ability to suppress the output of parasite eggs in the faeces of 108 grazing horses at four sites in Britain; the horses were treated once with either ivermectin, fenbendazole or pyrantel. At each site, the horses grazed together throughout the trials which took place during the summers of 1985 and 1986. The median periods before parasite eggs reappeared in faeces were 70 days for ivermectin, 14 days for fenbendazole and 39 days for pyrantel embonate. Geometric mean faecal egg counts in the groups treated with ivermectin and pyrantel were significantly less (P less than 0.05) than in the fenbendazole group on days 21, 28, 35 and 42 after treatment. On days 49, 56, 63 and 70 the mean egg counts in the ivermectin group were significantly lower (P less than 0.05) than those in either of the other groups. The results indicated that in order to ensure minimal contamination of pastures, grazing horses treated with ivermectin paste would have required a second treatment approximately 10 weeks after the first, and to achieve similar control with fenbendazole or pyrantel embonate, a second treatment would have been required after approximately two weeks and six weeks, respectively.

Animals↗

An evaluation of the potential effects of ivermectin on the decomposition of cattle dung pats.

The parasiticide ivermectin has been administered to domestic livestock since 1981 to control internal and external parasites, including insects; some of the ivermectin is excreted unchanged in faeces. Concerns over the effects of ivermectin on dung-utilising insect populations and the potential for consequent persistence of dung on pastures have been raised. This paper presents the results of a study over two grazing seasons of the rate of decomposition of cattle dung pats exposed to normal environmental influences. The cattle had been treated at therapeutic levels with either an injectable or a sustained release bolus formulation of ivermectin. It was concluded that the rate of decomposition of the dung pats, the extent of their avoidance by the cows, the organic matter content of the soil and the populations of earthworms in the pastures were not affected by the use of ivermectin.

Animals↗

Comparative studies of ivermectin and moxidectin in the control of naturally acquired cyathostome infections in horses.

The control of naturally acquired cyathostome infections in horses by treatments with ivermectin and moxidectin was evaluated in three field studies. In a first study the efficacy of both drugs was assessed in a faecal egg count reduction test. Both ivermectin and moxidectin demonstrated efficacies greater than 99 per cent for up to 60 days after treatment. In a second study, the period required for strongyle eggs to reappear was estimated in horses treated either with ivermectin or moxidectin. For the horses treated with ivermectin the period varied between 10 and approximately 13 weeks, and for moxidectin between 22 and approximately 24 weeks. With both drugs strongyle eggs started to reappear in the faeces significantly earlier in foals and young horses than in adults. In a third study, two prophylactic dosing schemes involving three ivermectin treatments at intervals of eight weeks, and two moxidectin treatments 12 weeks apart, were found to be highly effective in controlling strongyle infections of horses on pasture.

Animals↗

Gender issues in the community-directed treatment with ivermectin (CDTI) of the African Programme for Onchocerciasis Control (APOC).

This paper reviews the issues relating to compliance and participation among the men and women of three countries within the remit of the African Programme for the Control of Onchocerciasis (APOC): Cameroon, Nigeria and Tanzania. Project-monitoring data from 109 focus-group discussions, 6069 household-survey respondents and 89 interviews with ivermectin distributors were analysed to gain an insight into the attitudes and behaviours of men and women in relation to ivermectin treatment and their participation in the programme. Although there are no statistically significant gender differences in coverages for ivermectin treatment, culturally prescribed gender relationships influence the ways in which men and women express and experience treatment-related behaviours. Gender roles also affect participation in the programme. Decision-making in communities on the selection of distributors tends to follow socio-cultural hierarchies based upon patriarchy and gerontocracy. Relatively few ivermectin distributors (21%) are women. Although they receive less support than their male counterparts, the female distributors are just as willing to continue ivermectin distribution in the community, and they perform as well or better than men in this regard. The terms 'community-directed', 'community participation' and even 'compliance' obfuscate important gender differences that are inherent in the implementation of onchocerciasis control. Development of strategies that recognize these gender differences will have important implications for long-term adherence to treatment and for the overall quality and sustainability of the programme.

Cameroon↗

The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus.

Two randomized, double-blind, placebo-controlled trials, in which levamisole (2.5 mg/kg) was given alone or co-administered with ivermectin (200 microg/kg) or albendazole (400 mg), were conducted. In Trial 1, safety and drug-drug interaction were explored in 42 healthy male volunteers. During Trial 2, the safety of the same treatment regimens and their efficacy against the adult worms and microfilariae of Onchocerca volvulus were investigated in 66 infected subjects of both sexes. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. The pharmacokinetic parameters for levamisole alone and the combinations were determined in Trial 1 and then compared with historical data for ivermectin and albendazole, given as single agents, to determine if drug-drug interaction had occurred. The level of efficacy against the adult worms was determined by the examination of histology sections of nodules excised 6 months posttreatment and from the changes seen in the levels of microfilaridermia within a year of treatment. Microfilaricidal efficacy was estimated from the reductions in the levels of microfilaridermia between day 0 (1 day pre-treatment) and day 30. Although the regimens were generally well tolerated, there were unexpected adverse effects in both healthy volunteers and infected subjects. Clinically significant drug-drug interactions resulted in an increase in the bio-availability of ivermectin but a reduction in that of albendazole when these drugs were co-administered with levamisole. Levamisole given alone or with albendazole had little effect on O. volvulus. The combination of levamisole with ivermectin was neither macrofilaricidal nor more effective against the microfilariae and the adult worms than ivermectin alone. The pathogenesis of the adverse events and the drug-drug interactions are discussed.

Adolescent↗

Ivermectin treatment of a colony of guineapigs infested with fur mite (Chirodiscoides caviae).

Ivermectin was used for treating a breeding colony of guinea pigs heavily infested with fur mite Chirodiscoides caviae. In preliminary experiments on different dosages and routes of administration, spraying with diluted Ivomec (ivermectin 0.2 mg/ml) as well as applying undiluted ivermectin (10 mg/ml) drops on the fur proved effective and practical. The breeding colony was treated with diluted ivermectin aerosol and retreated two weeks later with undiluted ivermectin drops applied to the coat. After 3 months neither mites nor mite eggs were observed on microscopic examination. Two-and-a-half years later, the guinea pigs are still free of mites.

Animals↗

Experimental eradication of pinworms (Syphacia obvelata and Aspiculuris tetraptera) from mice colonies using ivermectin.

A spray administration of ivermectin was evaluated for the treatment of pinworm infection in mice. In this study, a spray of 0.1% ivermectin injectable solution over the entire cage once a week, for three consecutive weeks (one cycle treatment), was effective in eradicating both Syphacia obvelata and Aspiculuris tetraptera from mice under experimental conditions. In addition, no acute toxicity was observed in 105 mothers or 687 neonates treated with ivermectin, indicating that ivermectin does not affect murine reproduction. Finally, we attempted to eradicate pinworms from infected mice in our institute using this method. Two cycles of treatment were administered, with a two-week pause between cycles, resulting in complete eradication for at least one year. Treating mouse colonies with spray ivermectin is inexpensive, safe, requires very little labor and is very effective at eradicating pinworms from mice.

Animals↗

Assessment of ivermectin therapeutic efficacy on third-stage larvae of Lagochilascaris minor in mice experimentally infected.

In this study we evaluated the potential action of ivermectin on third-stage larvae, both at migratory and encysted phases, in mouse tissues after experimental infection with Lagochilascaris minor. Study groups I and II consisted of 120 mice that were orally administered 1,000 parasite eggs. In order to assess ivermectin action upon migratory larvae, group I (60 mice) was equally split in three subgroups, namely I-A, I-B, and I-C. On the 7th day after inoculation (DAI), each animal from the subgroup I-A was treated with 200 micrograms/Kg ivermectin while subgroup I-B was given 1,000 micrograms/Kg, both groups received a single subcutaneous dose. To assess the drug action on encysted larvae, group II was equally split in three subgroups, namely II-A, II-B, II-C. On the 45th DAI each animal was treated with ivermectin at 200 micrograms/Kg (subgroup II-A) and 1,000 micrograms/Kg (group II-B) with a single subcutaneous dose. Untreated animals of subgroups I-C and II-C were used as controls. On the 60th DAI all animals were submitted to larva search. At a dose of 1,000 micrograms/Kg the drug had 99.5% effectiveness on third-stage migratory larvae (subgroup I-B). Ivermectin efficacy was lower than 5% on third-stage encysted larvae for both doses as well as for migratory larvae treated with 200 micrograms/Kg.

Animals↗

Therapy of tungiasis: a double-blinded randomized controlled trial with oral ivermectin.

Tungiasis is an ectoparasitosis causing considerable pathology in endemic areas. Standard therapy consists of removing the embedded parasite with a sterile needle. There is no effective chemotherapy at hand. To fill this gap, a double-blinded randomized controlled trial with oral ivermectin was conducted. A total of 54 individuals (27 in the placebo group, 27 in the ivermectin group) was followed up for seven days. They presented a total of 192 lesions. Patients received either ivermectin (300 microg/kg body weight at a single dose, repeated after 24 h) or placebo. Outcome measures included the clinical stage of lesion, presence of erythema, pain, itching, signs of viability of the parasite, and total lysis of flea. The ratio of fleas with total lysis per total number of fleas was slightly higher in the ivermectin group; however, this difference was not statistically significant. There was no significant difference in any of the other outcome measures between the treatment and the placebo group. The results show that oral ivermectin is without any clinically significant efficacy against embedded sand fleas at the dose given.

Adolescent↗

Depletion rates of injected and ingested ivermectin from blood serum of penned white-tailed deer, Odocoileus virginianus (Zimmermann) (Artiodactyla: Cervidae).

Penned female and male white-tailed deer, Odocoileus virginianus (Zimmerman), were administered ivermectin both by direct subcutaneous injection and by ingestion of ivermectin-medicated whole kernel corn. Depletion rates of ivermectin were determined by biweekly and weekly assays of blood serum. No statistical differences were observed between mean peak ivermectin serum concentrations in deer (data of sexes combined) from injection and ingestion studies, and ivermectin concentrations decreased to below detectable within 21 d after injection and 14 d after ingestion.

Administration, Oral↗

Effect of refrigeration on the antinematodal efficacy of ivermectin.

Several observations have suggested that the anthelmintic ivermectin can affect nematodes by non-oral entry into the nematode body. To investigate this possibility further, we refrigerated Caenorhabditis elegans at 5 C to prevent its locomotion and to block the pharyngeal pumping that is so prominent a feature of its feeding. Worms were exposed to ivermectin (1-25 microg/ml) at that temperature for 1 hr, after which the medium was replaced by unmedicated medium at room temperature. After 1 hr at room temperature the worms were examined and counted to determine the degree to which irreversible immobilization had occurred. The drug was significantly less effective at 5 C than at room temperature. This reduction in potency could be attributed to a general cold-induced decline in the rate of the biochemical processes involved in drug action. Alternatively, the reduction could be attributed to the cold-induced blockade of pharyngeal pumping, which would suggest that the efficacy of ivermectin is partially the result of oral intake of drug. The fact that antinematodal efficacy was not entirely abrogated and reached a significant level despite blockade of pharyngeal pumping supports the former interpretation and is in accord with earlier indications that ivermectin can enter by non-oral routes. This conclusion is further supported by the observation that ivermectin is active against the nonfeeding third-stage larva of Haemonchus contortus.

Animals↗

Pharmacokinetics of a novel formulation of ivermectin after administration to goats.

OBJECTIVE: To evaluate the pharmacokinetics of a novel commercial formulation of ivermectin after administration to goats. ANIMALS: 6 healthy adult goats. PROCEDURE: Ivermectin (200 microg/kg) was initially administered IV to each goat, and plasma samples were obtained for 36 days. After a washout period of 3 weeks, each goat received a novel commercial formulation of ivermectin (200 microg/kg) by SC injection. Plasma samples were then obtained for 42 days. Drug concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. RESULTS: Pharmacokinetics of ivermectin after IV administration were best described by a 2-compartment open model; values for main compartmental variables included volume of distribution at a steady state (9.94 L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time curve (AUC; 143 [ng x d]/mL). Values for the noncompartmental variables included mean residence time (7.37 days), AUC (153 [ng x d]/mL), and clearance (1.43 L/kg/d). After SC administration, noncompartmental pharmacokinetic analysis was conducted. Values of the variables calculated by use of this method included maximum plasma concentration (Cmax; 21.8 ng/mL), time to reach Cmax (3 days), and bioavailability (F; 91.8%). CONCLUSIONS AND CLINICAL RELEVANCE: The commercial formulation used in this study is a good option to consider when administering ivermectin to goats because of the high absorption, which is characterized by high values of F. In addition, the values of Cmax and time to reach Cmax are higher than those reported by other investigators who used other routes of administration.

Animals↗

Effects of parenteral administration of doramectin or a combination of ivermectin and clorsulon on control of gastrointestinal nematode and liver fluke infections and on growth performance in cattle.

OBJECTIVE: To compare effects of an injectable doramectin preparation with those of an injectable ivermectin-clorsulon preparation on control of gastrointestinal nematodes and liver flukes and on growth performance in cattle. DESIGN: Randomized complete block design. ANIMALS: 60 crossbred calves. PROCEDURES: Calves (20/treatment group) were treated with doramectin or ivermectin-clorsulon or were not treated. Fecal samples were collected for nematode and Fasciola hepatica egg counts on day 0 and for up to 140 days after treatment. Cattle were weighed before treatment and at 28-day intervals until day 140. RESULTS: From day 7 through day 49, nematode egg counts for calves treated with doramectin or with ivermectin-clorsulon were significantly lower than those for untreated control calves. As the study progressed beyond day 56, the percentages of cattle with fluke eggs in their feces increased, but differences in regard to these percentages were not detected among the 3 groups. Average daily gain for the doramectin-treated cattle (0.79 kg/d [1.74 lb/d]) was significantly greater than that for the cattle treated with ivermectin-clorsuIon (0.71 kg/d [1.56 lb/d]); values for both groups were significantly greater than that for the control cattle (0.62 kg/d [1.37 lb/d]). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that doramectin had a greater impact on subclinical gastrointestinal tract parasitism in calves, as demonstrated by growth performance, than did ivermectin-clorsulon. In the Gulf Coast region of the United States, spring-born nursing beef calves may have minimal grazing exposure to F hepatica during the peak fluke transmission period; therefore, mature fluke burdens may be negligible at the beginning of the fall season.

Animals↗

Identification of foals infected with Parascaris equorum apparently resistant to ivermectin.

During September 2002, routine fecal examinations performed on 16 Thoroughbred foals residing on a farm outside Toronto, Ontario, Canada, revealed low to moderate numbers of Parascaris equorum eggs in feces from 9 of the 16. All foals were then treated with ivermectin at a dose of 220 to 280 microg/kg (100 to 127 microg/lb), p.o., and fecal egg counts were repeated 12 days later. Fecal P. equorum egg counts increased between the first and second fecal examination in 7 foals, were unchanged in 1, and decreased in 5. Fecal samples were collected 13 days after treatment from 21 additional foals that had been treated with ivermectin at the same dose, and P. equorum eggs were detected in 12 of the 21. For all 37 foals, high P. equorum egg counts (> or = 100 eggs/g of feces) 12 to 13 days after ivermectin treatment were significantly more likely in foals that had been regularly treated with ivermectin since birth and permanently resided on the farm, compared with foals that had been treated with other anthelmintics or had an unknown deworming history. Collectively, these data suggested that P. equorum in these foals was resistant to ivermectin administered at the recommended dose.

Animals↗

Ivermectin prophylaxis against experimental Onchocerca volvulus infection in chimpanzees.

Ivermectin was tested for possible prophylactic action against the third and fourth larval stages (L3 and L4) of Onchocerca volvulus inoculated into chimpanzees. The infective larvae (L3) were obtained from laboratory-raised black flies. Eighteen chimpanzees were inoculated, each with approximately 250 L3. Six were treated with ivermectin (200 micrograms/kg) on the day of inoculation, 6 were treated with ivermectin on day 28, and 6 were not treated. Monthly skin snips were taken for the next 30 months to detect patent infection. One of the chimpanzees treated with ivermectin on the day of infection developed a patent infection as did 4 of the 6 treated at day 28 and 4 of the 6 control animals. The results suggest that ivermectin may have a partial in vivo effect against the L3 of O. volvulus but has no effect against later larval stages of the parasite.

Animals↗