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PubMed2004

The cost-effectiveness of ivermectin vs. albendazole in the presumptive treatment of strongyloidiasis in immigrants to the United States.

The presumptive treatment of parasitosis among immigrants with albendazole has been shown to save both money and lives, primarily via a reduction in the burden of Strongyloides stercoralis. Ivermectin is more effective than albendazole, but is also more expensive. This coupled with confusion surrounding the cost-effectiveness of guiding therapy based on eosinophil counts has led to disparate practices. We used the newly arrived year 2000 immigrant population as a hypothetical cohort in a decision analysis model to examine the cost-effectiveness of various interventions to reduce parasitosis among immigrants. When the prevalence of S. stercoralis is greater than 2%, the incremental cost-effectiveness ratios of all presumptive treatment strategies were similar. Ivermectin is associated with an incremental cost-effectiveness ratio of 1700 dollars per QALY gained for treatment with 12 mg ivermectin relative to 5 days of albendazole when the prevalence is 10%. Any presumptive treatment strategy is cost-effective when compared with most common medical interventions.

Albendazole↗
PubMed2002

Residue study of ivermectin in plasma, milk, and mozzarella cheese following subcutaneous administration to buffalo (Bubalus bubalis).

The distribution of ivermectin in buffalo plasma and milk after administration of a single subcutaneous dose (0.2 mg kg(-)(1) b.w.) was studied. Ivermectin reached the maximal concentration in plasma (28.5 +/- 1.7 ng mL(-)(1)) and milk (23.6 +/- 2.6 ng mL(-)(1)) after 2.4 +/- 0.32 and 2.8 +/- 0.44 days, respectively. The drug showed a parallel disposition in milk and plasma, with a ratio of 1.12 +/- 0.16. Ivermectin concentrations were detected in mozzarella cheese obtained from milk collected on days 1, 3, 4, and 20 following administration. The highest values (81.4 +/- 3.26 ng g(-)(1)) were found in the cheese produced on day 3 and were 4-fold higher than those present in the milk.

Animals↗
PubMed1999

Ivermectin in reindeer feces: determination by HPLC.

An assay method for the determination of ivermectin in reindeer feces was developed. Ivermectin was quantified by high-performance liquid chromatography and fluorescence detection after extraction (acetone, isooctane), cleanup (C-18 solid-phase extraction column), and derivatization to a fluorescent derivative using N-methylimidazole and trifluoroacetic anhydride. Concentration calculations were based on calibration lines found from analyses of standards prepared in feces. Abamectin was used as internal standard. Ivermectin was determined over a wide concentration range in a single sample preparation and HPLC run for each sample. The recovery from fortified samples was greater than 95% over the concentration range 5-2000 ng/g wet weight feces.

Animals↗
PubMed1998

Evaluation of the role of P-glycoprotein in ivermectin uptake by primary cultures of bovine brain microvessel endothelial cells.

The P-glycoprotein efflux system located on the apical membrane of brain capillary endothelial cells functions as part of the blood-brain barrier. In this study, primary cultures of bovine brain microvessel endothelial cells (BMECs) were investigated for the presence of a P-glycoprotein system and its contribution in regulating ivermectin distribution across the blood-brain barrier. Results of rhodamine 123 uptake studies with cyclosporin A and verapamil as substrates indicated that a functional efflux system was present on BMECs. Immunoblot analysis with the C219 monoclonal antibody to the product of the multidrug resistant member 1(MDR1) gene also confirmed the expression of MDR1 in the BMECs. Unbound ivermectin was shown to significantly increase the uptake of rhodamine 123 in BMECs, however, the drug only modestly enhanced the transcellular passage of rhodamine. The results of these studies affirmed that unbound ivermectin is an inhibitor of the MDR1 efflux system in BMECs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Ivermectin and onchocerciasis: is it all solved?

The donation of ivermectin by Merck and Co. Inc. has led to one of the most effective private-public partnerships controlling a disease of major public health importance particularly in Africa. The up scaling of ivermectin distribution during the last 15 years has been remarkable with almost 40 million people treated in 2003, many already on their regular annual dose. The tools that have been developed particularly by the APOC programme have been instrumental in this increase. However, ivermectin is a microfilaricide and does not kill the adult worms. Distribution will be needed for at least 25 years and latest estimates indicate that 90 million people need annual treatment if onchocerciasis is to be eliminated as a public health problem. In spite of this incredible progress it is difficult to see how the programme will be sustained, especially after the closure of APOC in 2010. A macrofilaricide destroying adult worms and safe for mass distribution would solve the problem of onchocerciasis.

Community Health Services↗
PubMed1996

Evolution of a specific fluorogenic derivatization of ivermectin for bioanalytical applications. A review.

The evolution of the fluorogenic derivatization of ivermectin is traced through a series of continual modifications that have resulted in improvements in speed and sensitivity. Since the original development of this selective analytical technique, the reaction time has been shortened from 24 h at 100 degrees C to < 30 s at room temperature and, through modifications of the derivatization reagent and catalyst, the sensitivity has also been increased 50-fold to 20 pg of analyte with no significant decrease in precision. A procedure is reported, based on the use of fluorescence derivatization, which eliminates the use of solid-phase columns for sample preparation and fluorophore isolation, and is faster and less cumbersome than previous methods. The method was evaluated with cattle and canine plasma samples over the concentration range 1.0-40 ng ml-1 of ivermectin. It has an accuracy of 1.9% (mean relative error) over this concentration range and a precision of 5.6% (RSD) at the 1 ng ml-1 ivermectin concentration level in a 1 ml plasma sample.

Animals↗
PubMed2003

Direct production of ivermectin-like drugs after domain exchange in the avermectin polyketide synthase of Streptomyces avermitilis ATCC31272.

Ivermectin, a mixture of 22,23-dihydroavermectin B1a9 with minor amounts of 22,23-dihydroavermectin B1b 10, is one of the most successful veterinary antiparasitic drugs ever produced. In humans, ivermectin has been used for the treatment of African river blindness (onchocerciasis) resulting in an encouraging decrease in the prevalence of skin and eye diseases linked to this infection. The components of ivermectin are currently synthesized by chemical hydrogenation of a specific double bond at C22-C23 in the polyketide macrolides avermectins B1a 5 and B1b 6, broad-spectrum antiparasitic agents isolated from the soil bacterium Streptomyces avermitilis. We describe here the production of such compounds (22,23-dihydroavermectins B1a 9 and A1a 11) by direct fermentation of a recombinant strain of S. avermitilis containing an appropriately-engineered polyketide synthase (PKS). This suggests the feasibility of a direct biological route to this valuable drug.

Blotting, Southern↗
PubMed1997

Effect of mass treatments with ivermectin, with only partial compliance, on prevalence and intensity of O. volvulus infection in adults and in untreated 4 and 5 year-old children in Burundi.

Between 1991 and 1994, 4 annual treatments with ivermectin were offered to the population of an area hyperendemic for onchocerciasis in the province of Bururi (Burundi). In one place, Kinama, the annual coverage ranged between 40 and 49% of the population. Of 151 persons who were examined there in 1987 and again in 1994, 4 months after the last treatment round, 43 took ivermectin all 4 times, 34 took it 3 times, 35 twice and 17 only once. Although the compliance in this population was incomplete and far from regular, the prevalence of infection in a sample of untreated 4 and 5 year-old children dropped from 60.0% in 1987 to 23.7% in 1994 (a reduction of 60.5%, P < 0.01) and their microfilarial load (geometric mean number of microfilariae in scarification slides) from 3.0 to 0.4 (a reduction of 86.7%, P < 0.01). It appears that even a suboptimal mass distribution of ivermectin can reduce the microfilarial load to a level where the transmission of O. volvulus becomes seriously affected.

Adult↗
PubMed2002

Factors associated with coverage in community-directed treatment with ivermectin for onchocerciasis control in Oyo State, Nigeria.

Community-directed distribution with ivermectin (CDTI) has been adopted by the African Programme for Onchocerciasis Control (APOC) as its main strategy for achieving sustained high coverage in endemic communities. This article describes the coverage results achieved when CDTI was introduced in four local government areas of Oyo State, Nigeria. Using a household survey after the second distribution, researchers documented that 68.6% of the community overall received the drug, and as did 85.0% of those who were eligible (not pregnant, not sick and at least 5 years of age). Six factors were associated with having received ivermectin. Four were personal characteristics: being male, being at least 35 years of age, belonging to the Fulani ethnic minority, having taken the drug at a previous distribution. Two village characteristics were smaller size, as measured by number of houses, and use of the central place mode of distribution as opposed to house-to-house. In-depth interviews with village leaders and volunteer community-directed distributors (CDDs) and focus group discussions among villagers provided qualitative data to help interpret the findings. Women in many villages felt excluded from decision making. The concerns of migrant farm workers living in Yoruba farm settlements were not well understood by health staff or the majority population. The main factor associated with receiving the ivermectin was having received it before, and qualitative comments about side-effects and beliefs about orthodox drugs indicated that issues of personal preferences, not addressed in a household coverage survey, need to be explored further. The findings can provide guidance in re-orienting health workers to the importance of fostering participation and cohesion among all segments of the community, especially the inclusion of women and minority groups.

Adolescent↗
PubMed2000

Management of endemic outbreaks of scabies with allethrin, permethrin, and ivermectin.

BACKGROUND: At three residences for the elderly, recurrent scabies infestations became out of control. Due to the failure of repeated, nonsynchronized therapeutic efforts with conventional external anti-scabies treatments, an eradication program had to be developed. We describe a protocol for the management of outbreaks of scabies. METHODS: According to the clinical examination and microscopically identified mites, all individuals of the population (IOP: patients, staff, and family members) were divided into two groups: (a) healthy and infested IOP; and (b) cases with crusted scabies. The first group was treated simultaneously once with external scabicides (allethrin or permethrin). All others were hospitalized and treated either with systemic ivermectin or with the latter in combination with permethrin. RESULTS: In 252 IOP living in three residences for the elderly, clinical signs of scabies were reported in 91.5%, 78.5%, and 15.4% of the patients (age 55-97 years; mean, 80.5 years), 54.1%, 32.9%, and 16.6% of staff members, and in 7%, 3%, and 0% of family members. The infested IOP showed crusted scabies (index cases) in 5.3%, 5.0%, and 1.7%, common scabies in 43.1%, 36.7%, and 7.1%, and postscabiotic dermatitis in 10.3%, 7.6%, and 3.5%. In 99.2% of the synchronously treated IOP in group (a) (n = 240), the conventional treatment with permethrin cream 5% or allethrin spray was effective. Group (b) (n=12) received ivermectin (12 mg) once (n=5) or twice (n= 7) after an interval of 8 days. One index case received permethrin three times. CONCLUSIONS: Outbreaks of scabies in populations of elderly people require special management for disease control. Synchronous treatment with external permethrin cream 5% or allethrin spray, including all IOP once, and close control offers a time-saving, cheap, and reliable method. Crusted scabies should be treated by oral administration of ivermectin once or twice after an interval of 8 days. Additional applications of permethrin and mechanical clearing of hyperkeratotic subungual areas shorten the course.

Aged↗
PubMed2003

Demodex infestation in a child with leukaemia: treatment with ivermectin and permethrin.

BACKGROUND: Demodex mites are almost ubiquitous on older adult skin but are infrequent in young children. In immunocompromised patients, demodicosis may be more frequent and severe, and systemic therapy may be needed to achieve clinical resolution. CASE REPORT: A six-year-old boy having maintenance chemotherapy for acute lymphoblastic leukemia presented with widespread erythema and scaling of the face. Skin scrapings were negative and the eruption worsened despite the completion of chemotherapy and the use of topical corticosteroids. Pustules developed on the face and around the eyelids, associated with bilateral blepharitis and lower lid chalazia. Skin biopsy then revealed heavy infestation with Demodex folliculorum. The child was treated with a combination of topical permethrin and oral ivermectin, with a total of four doses of ivermectin given over 6 weeks. The facial eruption had completely resolved 3 months after initiation of this combined treatment. COMMENT: Demodex infestation can cause dramatic facial and eyelid inflammation in immunocompromised patients. Oral ivermectin, in combination with topical permethrin, can be a safe and effective treatment for severe demodicosis.

Animals↗
PubMedDate not supplied

Crusted scabies in an immunocompetent child: treatment with ivermectin.

An 11-year-old girl presented to our clinic with recalcitrant crusted scabies despite repeated applications of topical scabicides. She had no history of corticosteroid use prior to onset of the eruption and no evidence of immunodeficiency. A combination of oral ivermectin, topical lindane, and keratolytics cleared the infestation. Our patient is exceptional in that she had no risk factors commonly associated with a propensity to develop crusted scabies. While topical therapy remains the first-line treatment for children with classic scabies, in the unusual instance of a child with recalcitrant, crusted scabies, ivermectin may offer an efficacious alternative, although it should be used with caution. We discuss the use of oral ivermectin for treatment of crusted scabies and the challenging comprehensive management needed for this socially stigmatizing condition.

Administration, Oral↗
PubMed1987

[Ivermectin and the reduction of the rate of infection of simuliids in a forest focus of human onchocerciasis].

Eight patients from a forest onchocercian area "Grandes rivières", in Ivory Coast, were treated with a single oral dose of ivermectin (12 mg). The density of dermic microfilariae was estimated at days 0, 7 and 180; the mean numbers of ingested microfilariae and of developing larvae in the vectors S. soubrense-S. sanctipauli, engorged on the treated patients were recorded. Comparisons were made with non treated patients, having a similar density of microfilariae than the 8 treated patients at day 7. Results confirm the reduction induced by ivermectin of the dermic microfilarial density and the resulting reduction of the infection of the simuliids. Furthermore 7 days after treatment, a new phenomenon is demonstrated: for a similar dermic microfilarial density, simuliids take up a number of microfilariae 100 times lower from treated than from untreated patients. To explain this phenomenon, it is suggested that ivermectin induces a change in the microfilarial distribution in the layers of the dermis. Six months after treatment, this low uptake of microfilariae by the vectors had disappeared, and the infection rate of the engorged similiids was much higher than at day 7 although the dermic microfilarial density was similar.

Animals↗
PubMed1992

Ivermectin in human onchocerciasis: a clinical-pathological study of skin lesions before and three days after treatment.

Findings are presented from an histological study of 360 skin-snips (from iliac crests, calves, ankles) taken from 30 Ivory Coast onchocerciasis patients before and three days after an oral dose of ivermectin (200 micrograms/kg). This dose causes a nearly complete disappearance of the intralymphatic microfilariae and, surprisingly, of the "extra-vascular" ones. That shows the difficulty to localize the microfilariae on histological sections; these microfilariae are in fact inside the lymphatic pre-capillaries. There was no intensification of acute skin lesions after the treatment, thus showing that, contrary to diethylcarbamazine (DEC), ivermectin does not induce an exit of microfilariae into the extralymphatic connective tissue. Under the influence of ivermectin, paralyzed microfilariae may be carried passively towards the deep sub-cutaneous lymphatics, and then destroyed inside the regional lymph nodes, without producing major changes in the skin.

Animals↗
PubMed2001

A controlled prospective trial of the prophylactic effect of a single dose of ivermectin against Onchocerca volvulus.

A clinical trial was conducted in Cameroon in order to evaluate in humans the possible effect of a single dose of ivermectin (150 micrograms per kg) on the pre-adult stages of Onchocerca volvulus. The incidence of the skin microfilariae was measured in two groups of patients who initially had negative biopsies, and who were subsequently treated, immediately after the seasonal peak of transmission of O. volvulus, either with a combination of ivermectin + ferrous sulphate, or with ferrous sulphate alone. One year after the treatment, i.e. 14 months after the start of the transmission period, the proportion of patients with positive skin biopsies, and their mean microfilarial loads, did not differ significantly between the two groups. Thus a single dose of ivermectin does not seem to have any perceptible prophylactic effect against O. volvulus.

Adolescent↗
PubMed1999

Effect of repeated ivermectin treatments on ocular onchocerciasis: evaluation after six to eight doses.

In 26 villages (1987 population 12,302), hyperendemic for savanna onchocerciasis in North Cameroon, ivermectin was distributed annually between 1987/89 and 1995. Each year until 1992, ophthalmologic examinations were performed before treatment. A final examination was made in 1995. The effects of ivermectin on ocular onchocerciasis were assessed by following (a) the ophthalmologic indices in three cohorts of males recruited before treatment in 1987, 1988 and 1989, who were treated and examined annually, and (b) the indices recorded yearly in the cross-section of males aged 15-19 years. The indices in 1995 from patients who had received up to eight doses were compared with those calculated before treatment in individuals of similar age. In the cohorts, the prevalences of microfilariae in the anterior chamber (MFAC) and of punctate keratitis (PK) recorded in 1995 were markedly reduced; there was a non-significant decrease in sclerosing keratitis (SK), and a significant worsening in the fundus indices in the cohorts. The cross-sectional analysis showed significant decreases in the prevalences of MFAC, PK and SK, and a significant increase in the mean visual acuity; there was no significant change in any fundus index. The findings suggest that repeated ivermectin treatment does not prevent the appearance of initial retinal lesions or the worsening of existing retinal lesions.

Adolescent↗
PubMed1986

Response of laboratory-adapted human hookworm and other nematodes to ivermectin.

The activity of ivermectin was examined in Necator americanus, a human hookworm, adapted to the laboratory hamster. A dose of 30 mg kg-1 X 1 or 10 mg kg-1 X 2 was required for complete clearance of pre-adult N. americanus; however, hamsters carrying adult N. americanus were completely cured of infection by doses of 15 mg kg-1 or 7.5 mg kg-1 X 2. The doses of ivermectin required for complete elimination of N. americanus were much higher than those reported for other intestinal nematodes. The probable reasons for these higher doses are discussed. Tests were also carried out with other rodent parasites, namely Nematospiroides dubius, Strongyloides ratti and Trichuris muris. Doses as low as 0.3 mg kg-1 X 1 completely eliminated adult N. dubius from mice, whereas++ S. ratti needed a repeated dose (0.3 mg kg-1 X 2). None of the mice was cured of T. muris infection even at doses of 10 mg kg-1 X 2, although some degree of cure was apparent at the toxic dose. It thus appears that ivermectin is in no way superior in its activity against N. americanus and T. muris than the existing anthelmintics.

Animals↗
PubMed1992

Ivermectin for the treatment of periodic malayan filariasis: a study of efficacy and side effects following a single oral dose and retreatment at six months.

Ivermectin, a new antifilarial drug and currently the drug of choice for the treatment of onchocerciasis, has been shown to be effective in bancroftian filariasis. We report here, for the first time, the efficacy and safety of the drug in the treatment of filariasis caused by periodic Brugia malayi. Sixty male, asymptomatic microfilaraemics of Alleppey district, Kerala, South India, received single oral doses of ivermectin in a double blind study. Four dosages were used: 20, 50, 100 and 200 micrograms kg-1 body weight. Clearance of microfilariae, which was not complete, began as early as 12 hours post-treatment and was maximal at the end of one month. Microfilaria levels began to rise thereafter and reached 20-50% of pretreatment levels at six months. The two higher doses (100 and 200 micrograms kg-1) were more effective in suppressing microfilaraemia at six months (P < 0.05). After six months, 32 patients were retreated using the same dose of ivermectin that they had received initially. The pattern of clearance was essentially similar to that seen during the first treatment phase and microfilaria levels were 10-35% of pretreatment levels at the end of the next six months. Twenty-eight individuals who were not retreated at six months continued to have increasing levels of microfilariae, reaching 60% of pretreatment levels at the end of the next six months. Side effects (such as fever, headache, myalgia), which were mild to moderate, were seen in most patients and were unrelated to the dose (P > 0.05) or pretreatment levels of microfilariae.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗