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PubMed1995

Ivermectin detection in serum of onchocerciasis patients: relationship to adverse reactions.

Ivermectin treatment of onchocerciasis patients can be accompanied by adverse reactions. Not much is known concerning the pathogenesis of these reactions. Previous studies have demonstrated that the occurrence and extent of adverse reactions are related to infection intensity. However, some severely infected patients experience relatively few adverse effects. The aim of the present study was to investigate whether this seeming discrepancy could be due to diminished ivermectin absorption. Ivermectin concentrations one and two days after treatment were measured by high-performance liquid chromatography in sera of 71 skin snip-positive onchocerciasis patients (21 without reactions, 25 with mild reactions, 14 with moderate reactions, and 11 with severe reactions). The overall mean +/- SD ivermectin concentrations one and two days after a single oral dose (150 micrograms/kg) were 16.4 +/- 6.4 and 6.6 +/- 3.1 ng/ml, respectively. The overall mean +/- SD half-life was estimated to be 19.9 +/- 8.6 hr. The data presented did not show a relationship between ivermectin concentrations and the grade of adverse reactions.

Chromatography, High Pressure Liquid↗
PubMed1996

A comparative trial of a single-dose ivermectin versus three days of albendazole for treatment of Strongyloides stercoralis and other soil-transmitted helminth infections in children.

A randomized trial carried out in rural Zanzibar comparing a single dose of 200 micrograms/kg of ivermectin and 400 mg/day for three days of albendazole for treatment of strongyloidiasis and other intestinal nematodes is described. In 301 children with Strongyloides stercoralis infection, treatment with ivermectin or albendazole resulted in cure rates of 83% and 45%, respectively. While both drugs were very effective against Ascaris lumbricoides, Trichuris trichiura was cured only in 11% (ivermectin) and 43% (albendazole) of the subjects, although the mean eggload was reduced by 59% and 92%, respectively. Ivermectin was ineffective against hookworms, while albendazole resulted in a cure rate of 98%. No severe side effects were recorded and mild side effects were of transient nature for both treatments. Therefore, ivermectin provides a safe and a highly effective single dose treatment for S. stercoralis and A. lumbricoides, while it is not an alternative for the treatment of T. trichiura and hookworm infections.

Adolescent↗
PubMed2001

The Carter Center's assistance to river blindness control programs: establishing treatment objectives and goals for monitoring ivermectin delivery systems on two continents.

Periodic mass treatment with ivermectin in endemic communities prevents eye and dermal disease due to onchocerciasis. As part of an international global partnership to control onchocerciasis, The Carter Center's Global 2000 River Blindness Program (GRBP) assists the ministries of health in ten countries to distribute ivermectin (Mectizan, donated by Merck & Co.). The GRBP priorities are to maximize ivermectin treatment coverage and related health education and training efforts, and to monitor progress through regular reporting of ivermectin treatments measured against annual treatment objectives and ultimate treatment goals (e.g., full coverage, which is defined as reaching all persons residing in at risk villages who are eligible for treatment). Since the GRBP began in 1996, more than 21.2 million ivermectin treatment encounters have been reported by assisted programs. In 1999, more than 6.6 million eligible persons at risk for onchocerciasis received treatment, which represented 96% of the 1999 annual treatment objective of 6.9 million, and 78% of the ultimate treatment goal in assisted areas.

Africa↗
PubMed2006

Non-adherence to community directed treatment with ivermectin for onchocerciasis control in Rungwe district, southwest Tanzania.

BACKGROUND: Community directed treatment with ivermectin (CDTI) for onchocerciasis control was developed as a strategy for achieving sustained high coverage in endemic communities. This strategy for over a short period of time has radically altered the consequences of infection with Onchocerca volvulus. The present challenge is maintaining the high therapeutic coverage especially in some of the impoverished endemic countries. One of these challenges is non-adherence to ivermectin treatment and this provides compelling reason for data collection at community level. OBJECTIVE: To describe the factors associated with non-adherence to CDTI. DESIGN: Cross-sectional descriptive study. SETTING: Communities participating in CDTI activities in Ndubi village, Rungwe district, southwest Tanzania. RESULTS: A high proportion (66%) of respondents were aware of onchocerciasis, and this was more significant in males than females (X2 = 9.17; p< 0.002). Knowledge on causes of the disease was low, only 29.3% associated it with the bite of Simulium fly, 17% associated it with mosquitoes, 17.1% to houseflies, and 30% had completely no idea. Knowledge on signs and symptoms of onchocerciasis was also observed to be equally low (20.4%) among the respondents. Similarly, only 35.4% of the respondents knew itching, swelling of the body, diarrhoea and vomiting as associated side effects of ivermectin. There was, however, no sex difference in knowledge levels (X2 = 0.01; p>0.939). Low knowledge levels on causes of the disease, signs and symptoms and side effects of ivermectin were attributed to inadequate health education in the communities. However, some other factors associated with non-adherence were local beliefs and the lifestyle of alcoholism. CONCLUSIONS: Factors identified to affect programme implementation and associated with non-adherence were inadequate knowledge on causes of the disease and sign/symptoms, side effects of ivermectin, local beliefs and lifestyle of alcoholism in the communities.

Adult↗
PubMed1991

Control of Psoroptes cuniculi in captive white-tailed deer with ivermectin-treated corn.

Psoroptes cuniculi, the ear mite of domestic rabbits, was collected from captive white-tailed deer (Odocoileus virginianus). This is the first report of rabbit ear mite infestations in white-tailed deer in Oklahoma or Texas (USA). In addition to moderate infestations in their ears, two 4-yr-old bucks, two 3-yr-old does, and seven 4-yr-old does showed patchy areas of alopecia along the sides and brisket. Both bucks also had patchy areas of alopecia around the base of antlers. Ear mites were eradicated from all deer except from one doe by providing ivermectin-treated corn to the deer at a rate of 1,000 g (equivalent to 200 mcg/kg of ivermectin)/day/deer for several days. The ear mite infestation in the one doe was eradicated by intramuscularly injection with ivermectin at 400 mcg/kg. After treatment with the ivermectin and eradication of the mites, the alopecia improved and eventually was eliminated. The ivermectin-treated corn also controlled all internal nematode parasites in the deer.

Administration, Oral↗
PubMed2001

Experimental ivermectin treatment of sarcoptic mange and establishment of a mange-free population of Spanish ibex.

Ivermectin was used to treat sarcoptic mange in Spanish ibex (Capra pyrenaica hispanica). Its therapeutic effectiveness was analyzed when it was administered through subcutaneous injection, to sick animals in the consolidation stage of mange (third phase) and, with double injections to chronically affected animals (fourth phase) at a dosage of 0.2 or 0.4 mg/kg body weight (bw). Three wk after treatment, the animals in the third phase of mange treated with a high dose (0.4 mg/kg bw) of ivermectin were completely cured. The same result was achieved after 4 wk of treatment in those animals in phase 3 of mange when 0.2 mg/kg body weight was used. Double injection with ivermectin, even at high doses, did not guarantee the complete cure of all cases of sarcoptic mange in the chronic stage (phase 4); only three of six animals were free of Sarcoptes scabiei. The second experiment consisted on the application of a sanitation program in order to obtain a population of Spanish ibex free from S. scabiei, starting with free-ranging animals, some of them healthy and others sick. After capture the animals were classified as chronically ill, in which case they were excluded from the program, mite carriers and healthy specimens. All the animals were treated first topically with foxim (500 mg/l) and subcutaneously with ivermectin (0.4 mg/kg bw). The infected animals were housed in the treatment pen, and received two doses of ivermectin (0.2 mg/kg bw) at an interval of 15 days, then spent 15 days in the quarantine pen, where they received a further dose before they were included in the pool of healthy animals, and immediately were placed in the quarantine phase. The sanitation we implemented was fully effective in curing the affliction of Spanish ibex affected by S. scabiei.

Animals↗
PubMed1999

Behavioral effects of ivermectin in mice.

BACKGROUND AND PURPOSE: Ivermectin is a common anthelmintic drug, widely used in laboratory rodents for treatment of pinworm and mite infestations. We evaluated the action of ivermectin on sensitive behavioral tasks in mice during treatment for mites within a barrier facility. METHODS: A total of 21 (5 males, 16 females) mice (129/SvEv) were used for measuring body weight, open field locomotor activity, and rotarod motor coordination. For acoustic startle and prepulse inhibition, 20 C57BL/6J and 29 AKR/J mice were studied. For the Morris water task, the same 20 C57BL/6J mice were studied. Ivermectin (0.08% sheep drench) was administered in the drinking water of the home cage for 8 weeks. Control groups received normal tap water in identical bottles. RESULTS: Ivermectin did not affect general health, body weight, motor coordination, swimming behavior, or spatial learning in several inbred strains of mice. However, it induced a small but significant effect on some sensitive behaviors. CONCLUSIONS: A cautious approach to initiating ivermectin treatment in mice should be used for sensitive behavioral experiments.

Acoustic Stimulation↗
PubMed2003

[Clinical observation on the efficacy of ivermectin in the treatment of intestinal nematode infections].

OBJECTIVE: To observe the efficacy and side effects of ivermectin in the treatment of intestinal nematode infections. METHODS: A single dose of ivermectin 0.1, 0.2, 0.2 and 0.2 mg/kg was orally administered to cases with infection of Ascaris, hookworm, Trichuris and Enterobius respectively. A single dose of albendazole 400 mg was used as control. RESULTS: The egg negative conversion rates of ivermectin and albendazole were both 100% (34/34) for Ascaris infection, 17.6% (6/34) and 76.5% (26/34) respectively for hookworm infection, 67.6% (23/34) and 47.1% (16/34) respectively for Trichuris infection, 58.8% (20/34) and 100% (34/34) respectively for Enterobius infection. The worm discharge reached a peak in 1-2 days after treatment. The side effect of ivermectin was mild and transient showing no adverse effect on blood picture, liver function, renal function or ECG. CONCLUSION: Ivermectin shows similar effect on Ascaris with albendazole, better effect on Trichuris and poorer effect on hookworm and Enterobius than albendazole.

Adolescent↗
PubMed1992

The effect of repeated doses of ivermectin on adult female Onchocerca volvulus in Sierra Leone.

The effects of single and multiple doses of ivermectin on mortality and morphology were assessed in over 700 female Onchocerca volvulus worms and the effects on embryogenesis were assessed in 490. Nodules were surgically removed from Sierra Leoneans recruited from a double-blind placebo controlled study of ivermectin given at six-monthly intervals. Nodules were digested in collagenase to isolate whole adult worms. After four or five doses of ivermectin there were significant increases in the numbers of discoloured and calcified worms and possibly a trend towards increased mortality, but this was not seen consistently. There was no evidence of a prophylactic effect of the drug. Worms were then homogenised and embryograms constructed. A single dose of ivermectin produced large numbers of degenerating intrauterine microfilariae, but embryonic development occurred normally. After multiple doses we observed almost complete cessation of embryogenesis, with a highly significant decrease in the numbers of viable multicellular embryonic stages, while oocytes appeared to be produced normally. Development is probably impeded at the single cell stage, possibly because of reduced fertilization. In planning the future role of ivermectin as a control measure for onchocerciasis it is crucial to determine if these effects on embryogenesis are reversible.

Adolescent↗
PubMed1992

[Ivermectin or diethylcarbamazine in spaced dosages in Bancroft's filariasis: which protocol?].

58 apparently healthy Polynesian Wuchereria bancrofti carriers were randomly allocated to 5 treatment groups: 1) two annual doses of ivermectin 100 mcg/kg, 2) three semi-annual doses of ivermectin 100 mcg/kg, 3) two annual doses of diethylcarbamazine (DEC) 3 mg/kg, 4) semi-annual doses of DEC 3 mg/kg, 5) two annual doses of DEC 6 mg/kg. Results observed during the 12-month period which followed last treatment have confirmed that efficacy of ivermectin is higher than that of DEC in terms of immediate clearance or complete negativation of microfilaremia, but not in terms of sustained reduction and that efficacy of repeated single doses of either DEC 3 mg/kg or ivermectin 100 mcg/kg is much higher when given semi-annually than annually. They also have indicated that (i) 6 months after last treatment: 3 semi-annual doses of 100 mcg/kg of ivermectin have resulted in high reduction of microfilaremia (85%) and, 2 annual doses of 6 mg/kg and 3 semi-annual doses of 3 mg/kg of DEC have resulted in even greater reduction (96 and 98% respectively) and (ii): 12 months after last treatment, the greatest reductions of microfilaremia (95 and 92%) have been observed in carriers treated, respectively, with 3 semi-annual doses of 3 mg/kg or with 2 annual doses of 6 mg/kg of DEC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Compared efficacy of repeated annual and semi-annual doses of ivermectin and diethylcarbamazine for prevention of Wuchereria bancrofti filariasis in French Polynesia. Final evaluation.

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. Six months later again, all of the carriers received a last treatment dose similar to the initial one. The results observed during the 12-month period which followed this last treatment have confirmed that (i) in terms of immediate clearance or complete negativation of microfilaremia, the efficacy of ivermectin is higher than that of DEC (at dosage of 3 or 6 mg/kg), (ii) DEC is more effective than ivermectin in sustaining the reduction of microfilaremia over a longer period of time and (iii) the efficacy of repeated single doses of either DEC 3 mg/kg or ivermectin 100 mcg/kg is much higher when given semi-annually than annually.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

[Ivermectin].

Initial clinical trials in 1980 showed that ivermectin was remarkably effective against Onchocerca volvulus. Some 25 years after more than 50 million people are treated annually with Mectizan mainly within the framework of the African Programme for Onchocerciasis Control (APOC). This success has been possible thanks to Merck Mectizan Donation Program and to distribution through a novel strategy based on the strong involvement of endemic communities. In the last few years Mectizan has been used in combination with albendazole to control lymphatic filariasis on a large-scale basis in African countries. More recently ivermectin (under the tradename Stromectol) received market approval in France for treatment of gastrointestinal strongyloidiasis and scabies. Clinical trials are under way to evaluate the activity of ivermectin on nematodes (Loa loa, Mansonella sp., intestinal nematodes, cutaneous and visceral larva migrans) and ectoparasites (Pediculus humanus capitis, Phtirius pubis, Tunga penetrans, myiases). Trials are also ongoing to explain the mechanisms underlying the severe adverse events sometimes observed in patients presenting high Loa loa microfilaraemia and to develop preventive measures. Fundamental research will provide a better understanding of the mode of action of ivermectin at the molecular and cellular level, evaluate the risk of resistance of human parasites, and to determine the extent to which ivermectin could be used in association with other agents for the treatment of nonparasitic diseases.

Animals↗
PubMed2005

Tolerability of ivermectin in gnathostomiasis.

At present, no universally-accepted effective treatment for cutaneous gnathostomiasis is available. At the Hospital for Tropical Diseases, Mahidol University, albendazole 400 mg twice a day for 14 days is commonly prescribed for patients diagnosed with cutaneous gnathostomiasis. The efficacy of albendazole to induce outward migration of the parasite was less than or around 20% in 2 studies. Research for alternative, more efficacious treatment, is needed. In this prospective open-labeled study, we assessed the safety of ivermectin in 20 Thai patients diagnosed with cutaneous gnathostomiasis. Ivermectin, one time only, at dosages of 50, 100, 150, or 200 microg/kg bodyweight, was given orally to 4 groups of patients, 5 patients each group. Adverse events were recorded and laboratory tests were obtained before and after treatment. No serious adverse events occurred in this study. Forty adverse events were possibly related to ivermectin. The adverse events were malaise (35%), myalgia (30%), drowsiness (30%), pruritus (20%), nausea/vomiting (20%), dizziness (15%), diarrhea (15%), feeling of shortness of breath (10%), feeling of palpitations (10%), constipation (5%), anorexia (5%), and headache (5%). These adverse events were self-limited and not dose-related. Laboratory abnormalities were found in 3 patients (15%). Transient microscopic hematuria, pyuria, and mildly elevated liver enzymes were found in 1 patient each. Ivermectin single dose, of 50,100, 150, and 200 microg/kg bodyweight, is considered safe in Thai patients. Future trials of ivermectin on human gnathostomiasis may be performed using dosages up to 200 microg/kg bodyweight.

Adult↗
PubMed1990

Laboratory selection of a benzimidazole-resistant isolate of Trichostrongylus colubriformis for ivermectin resistance.

In vivo ivermectin resistance was selected in an isolate of Trichostrongylus colubriformis (TcR) already known to be benzimidazole resistant. This was accomplished in sheep by using levels of ivermectin calculated to reduce the fecal egg output from each generation of T. colubriformis by congruent to 95%. The first indication of ivermectin resistance was observed with the F10. A dosage-titration trial comparing the parent TcR with the ivermectin-selected F21 demonstrated that the latter was congruent to 20 times more resistant to oral ivermectin therapy in experimentally infected sheep than was the parent isolate. Treatment of the F16 generation with 50 mg/kg of thiabendazole resulted in only 54% egg reduction and confirmed that benzimidazole resistance was stable.

Animals↗
PubMed1989

A community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana. II. Adverse reactions.

A community trial of the microfilaricide ivermectin undertaken in an hyperendemic focus of blinding onchocerciasis in Ghana. One objective was to investigate the safety of this new drug when used in mass treatments. 14,911 persons (61.5% of the census population) were treated with ivermectin. Of these, 15% reported with adverse reactions which were generally similar to those reported in the clinical trials. However, cutaneous reactions were relatively less frequent while brawny oedema of the limbs and inguinal gland pain were important. The severe reactions consisted of 37 cases of Severe Symptomatic Postural Hypotension (SSPH), 13 cases of severe fever and two cases of severe dyspnoea. The latter two cases represented life threatening situations, but there was no evidence that they were complications of ivermectin treatment. Only four of the SSPH cases required treatment. All severe adverse reactions were managed successfully and recovered within one day, usually within a few hours. The incidence of adverse reactions was highest the first day after treatment. Thirteen cases of delayed reactions were reported during a four-week follow-up. There was a highly significant relationship between incidence of adverse reactions and intensity of infection but no relation with ivermectin dosage within the range of 130-200 mcg/kg. The results suggest that ivermectin is sufficiently safe to be used in mass treatments. However, mass distribution of this drug should not be undertaken without adequate monitoring.

Adolescent↗
PubMedDate not supplied

Comparative metabolic disposition of ivermectin in fat tissues of cattle, sheep, and rats.

In the study of the metabolic disposition of ivermectin in cattle, sheep, and rats, a group of nonpolar metabolites was detected in the fat tissues of these animals. Upon saponification or esterase treatment, these nonpolar metabolites gave rise to polar products that were similar to the ivermectin metabolites present in the liver. A hypothesis was thus proposed that the polar ivermectin metabolites produced in the liver were esterified and stored in the fat as nonpolar entities, which can be reconverted back to the polar metabolites chemically or enzymatically. To substantiate this hypothesis, the regeneration of polar metabolites from the nonpolar metabolites was studied and hydrolysis products were characterized to establish the basic structure of the alcohol portion of the metabolites. Furthermore, chromatographic comparisons were made between radiolabeled in vivo metabolites and synthetic fatty acid ester samples. These results established the general structural class of the ivermectin nonpolar metabolites and also confirmed the unusual metabolic pathway of ivermectin disposition in fat tissue.

Adipose Tissue↗
PubMed1988

Chemotherapy of onchocerciasis with high doses of diethylcarbamazine or a single dose of ivermectin: microfilaria levels and side effects.

Fifty adult male subjects with moderate to heavy onchocerciasis from the Liberian rain forest were selected for a double-blind placebo-controlled chemotherapy study. The effects of high doses of diethylcarbamazine (DEC) - 30 mg/kg/d - over one week preceded by a one week initial treatment with normal oral doses of DEC or DEC lotion were compared with a single dose of ivermectin (150 micrograms/kg) and placebo. During the initial treatment DEC tablets or lotion caused distinctly more frequent and severe reactions than did invermectin. The reactions to ivermectin did not differ from those of the placebo patients. High doses of DEC caused, in about half of the patients, headache, dizziness, nausea or vomiting. DEC markedly increased the number of corneal microfilariae and of corneal opacities compared to ivermectin. All changes resolved with a return to pretreatment findings two months after treatment. The three treatment groups showed no differences at the ten months follow-up. In all treated patients skin microfilaria counts fell almost to zero by the end of the two week therapy. In the ivermectin group microfilaria counts remained significantly lower than in the DEC patients at the two and ten months examinations. In summary, ivermectin was much better tolerated than DEC and had a longer lasting effect on the microfilariae in the skin. Since high doses of DEC were less effective and caused more frequent and severe side effects, this approach cannot be recommended for treatment of onchocerciasis.

Adult↗
PubMed1987

Infestivity of Psoroptes ovis on ivermectin-treated cattle.

Psoroptes ovis was not transmitted by natural contact to susceptible cattle which were exposed to infested, ivermectin-treated cattle 6, 12, 14, 16, and 18 days after treatment was given. However, clinical scabies did develop in 2 calves naturally exposed to P ovis-infested, ivermectin-treated calves at 10 days after treatment was given subcutaneously (200 micrograms/kg). Psoroptes ovis was transmitted to stanchioned cattle manually exposed to 200 to 300 ml of hair and skin scrapings from infested, ivermectin-treated cattle at 6, 10, 12, 14, and 16 days after treatment was given subcutaneously (200 micrograms/kg). Scabies did not develop in cattle exposed to skin scrapings obtained from infested, treated cattle at 18 and 20 days after they were treated with ivermectin. The 14-day isolation of P ovis-infested, ivermectin-treated cattle from susceptible cattle recommended by the US Department of Agriculture, although marginal, is adequate under natural conditions to prevent transmission of scabies from treated to noninfested cattle.

Animals↗