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PubMed2003

Efficacy of different dosages of ivermectin injectable against the Hypoderma spp. in yaks.

A chemotherapy trial was conducted to determine the lowest dosage of injectable preparation of ivermectin against Hypoderma spp. infestation in yaks in Tibetan areas in Tianzhu county, Gansu province, in northwest of China. One hundred and sixty yaks were randomly divided into four groups of 40 yaks for the trial. The first three groups were treated by subcutaneous injection in the neck with 0.1% ivermectin (respectively, 1, 5, 10 microg/kg body weight). The fourth group was not treated and considered as control group. All the experiments were performed in November 2000 and the animals were examined for the presence of warbles in the next March and May. The results indicated that there was no warbles found on the back of treated animal while third stage larvae were palpated on back of some of the yaks in control group. It is concluded that dosage of 1 microg/kg ivermectin injectable was sufficient to kill or stop development of larvae of Hypoderma spp. in naturally infected yaks if administrated in November.

Animals↗
PubMed2005

Rapid selection for ivermectin resistance in Haemonchus contortus.

Lambs infected with two isolates, one British and one American, of Haemonchus contortus were treated with increasing doses of ivermectin. Eggs from the highest dose that had not eliminated the infection were cultured and larvae used to infect another lamb. After three generations the H. contortus was resistant to 0.2 mg/kg ivermectin. The results stress the ease with which ivermectin resistance can be selected if high selection pressure is applied.

Animals↗
PubMed2005

Disposition of 3H-selamectin and 3H-ivermectin in the brain of the cat flea Ctenocephalides felis felis using micro-image analysis.

In addition to intrinsic potency and metabolic stability, the disposition of an antiparasitic drug within the target parasite plays a major role in determining drug activity. A novel technique that allows the disposition of radiolabelled drugs to be visualised within the body of the cat flea (Ctenocephalides felis felis) is described. The concentrations of two macrocyclic lactones, (3)H-selamectin and (3)H-ivermectin, within the supra- and sub-oesophageal ganglia of the flea brain following in vitro feeding of fleas on different doses of drug solubilised in calf blood have been measured. Drug disposition was visualised in cryostat sections of fleas using a micro-image analysis (MIA). A relationship between the concentration of radioactivity in the ganglia and the dose of drug in the blood meal was obtained. The concentration of selamectin in the ganglia was significantly higher than ivermectin at all doses investigated. The enhanced concentration of selamectin, at a site rich in glutamate-gated chloride channels may, in part, explain the higher potency of selamectin against fleas compared to ivermectin.

Animals↗
PubMed2001

Onchocerciasis control in Nigeria: will households be able to afford community-directed treatment with ivermectin?

OBJECTIVES: To determine the level of affordability of community-directed treatment with ivermectin (CDTI) to households living in two onchocerciasis endemic Nigerian communities namely Toro in the north and Nike in the south. METHODS: The proportion of the cost of treating people with ivermectin will deplete in average monthly/projected annual household expenditure on food and health care, and on average monthly and projected annual household income were respectively calculated and used to determine the level of affordability of CDTI. Questionnaires administered to heads of households or their representatives were used to collect information on the household expenditures and income. The suggested unit CDTI cost of $0.20 was used. However, as a test of sensitivity, we also used the unit cost of $0.056 which some community based distributors are charging per treatment. RESULT: Using $0.20 as the unit treatment cost, this will consume less than 0.05% of average annual household income in both communities. It will equally deplete 0.05% of combined annual household expenditures on food and health care in both communities. However, using $0.056 as the unit treatment cost, then 0.02% of average annual household expenditure on health care, 0.01% average annual expenditure on combined health care and food, and 0.01% of average annual household income will be depleted. CONCLUSION: The households living in both communities may be able to afford CDTI schemes. However, the final decision on levels of affordability lies with the households. They will decide whether they can afford to trade-off some household income for ivermectin distribution.

Adult↗
PubMed1997

An improved dosing schedule for ivermectin as a microfilaricidal agent against onchocerciasis.

The introduction of ivermectin therapy has proved to be the most important advance in the management and control of onchocerciaisis. By using the standard dosing schedule (150 micrograms/kg) in a mass chemotherapy campaign in Awhum, Nigeria, 128 (14.6%) of 875 eligible subjects used in this study were underdosed while 696 (79.6%) and 51 (5.8%) were overdosed and correctly dosed, respectively. Since underdosing is more serious than overdosing, an improved dosing schedule (300 micrograms/kg) is hereby suggested, bearing in mind that ivermectin is safe at doses well in excess of the standard dose. 824 (94.2%) And 51 (5.8%) of these eligible subjects would be overdosed and correctly dosed respectively, if this improved dosing schedule (< 15 kg, 0 mg (0 tablet); 15-20 kg, 6 mg (1 tablet); 21-40 kg, 12 mg (2 tablets); 41-60 kg, 18 mg (3 tablets); > 60 kg, 24 mg (4 tablets)) were to be employed. This dosing schedule is worth adopting and an investigation of the effects of these high single doses of ivermectin on adult Onchocerca volvolus worms is advocated. Furthermore 'non-responders' may be investigated for doses administered.

Adolescent↗
PubMed1990

Ocular involvement in patients with onchocerciasis after repeated treatment with ivermectin.

We assessed ocular changes after therapy at six and 12 months with ivermectin (150 micrograms/kg of body weight) in a 12-month prospective study of 29 patients with ocular onchocerciasis and 15 patients with onchocerciasis without ocular involvement. The patients lived in a hyperendemic area in Sierra Leone, West Africa, where no vector control was instituted. Five months after initial treatment, the microfilarial load in skin and eyes had decreased significantly (P less than .0000), but 28 of 44 (63%) patients had positive skin-snip test results and nine of 29 (31%) patients with ocular involvement had active ocular disease. Twelve months after initial treatment, 15 of 41 (37%) patients had positive skin-snip test results and eight of 26 (31%) showed active ocular involvement. All patients with persistent ocular disease after therapy showed evidence of active onchocerciasis at that time, which suggests that a dose of ivermectin at six-month intervals is not sufficient for intensely infested patients with severe ocular disease. We developed an ocular involvement score to evaluate the patient's total ocular status and observed a significant relation between the pretreatment severity of ocular involvement and the persistence of active ocular disease after treatment with ivermectin.

Adolescent↗
PubMed2003

MDR1-deficient genotype in Collie dogs hypersensitive to the P-glycoprotein substrate ivermectin.

Multidrug resistance (MDR) phenotypes in cancer cells are associated with overexpression of the drug carrier P-glycoprotein. The antiparasitic drug ivermectin, one of its substrates, abnormally accumulates in the brain of transgenic mice lacking the P-glycoprotein, resulting in neurotoxicity. Similarly, an enhanced sensitivity to ivermectin has been reported in certain dogs of the Collie breed. To explore the basis of this phenotype, we analyzed the canine P-glycoprotein-encoding MDR1 gene, and we report the first characterization of the cDNA for wild-type (Beagle) P-glycoprotein. The corresponding transcripts from ivermectin-sensitive Collies revealed a homozygous 4-bp exonic deletion. We established, by genetic testings, that the MDR1 frame shift is predictable. Accordingly, no P-glycoprotein was detected in the homozygote-deficient dogs. In conclusion, we characterized a unique case of naturally occurring gene invalidation. This provides a putative novel model that remains to be exploited in the field of human therapeutics and that might significantly affect tissue distribution and drug bioavailability studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Co-endemicity of loiasis and onchocerciasis in the South West Province of Cameroon: implications for mass treatment with ivermectin.

Encephalopathy has been reported in Cameroon in individuals heavily infected with Loa loa microfilariae who were treated with ivermectin against onchocerciasis. Prior to the initiation of the community-directed treatment of onchocerciasis with ivermectin (CDTI) in the South West Province of Cameroon, an epidemiological survey of loiasis was conducted (in July 1998-July 1999) to ascertain the intensity of the disease. Thick blood films were made from 1228 blood samples collected during the day. Rapid epidemiological assessment (REA) of onchocerciasis was conducted among 614 individuals in the Upper Bayang area. Sixteen percent of the population examined were carriers of L. loa microfilariae. More males (20.1%) than females (12.4%) were infected. The community mean microfilaraemias of the different villages were low (< 1100 mf/mL). However, 1 person was found harbouring 174,000 mf/mL of blood and 1% of the study population (12) had microfilaraemia > 8100 mf/mL. Results of the REA of onchocerciasis show that 31.3% of the population investigated in the Upper Bayang area have this disease. These findings show that loiasis and onchocerciasis are co-endemic in the area, but the risk of developing encephalopathy after taking ivermectin is small.

Adolescent↗
PubMedDate not supplied

Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations.

Adolescent↗
PubMedDate not supplied

Ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana: follow-up after re-treatment with the combination.

The efficacy of re-treatment with the combination of ivermectin (150-200 micrograms/kg bodyweight) and albendazole (400 mg) on Wuchereria bancrofti microfilaraemia was assessed in 1997-99 in 4 groups of individuals from coastal Ghana, which 1 year previously had received a primary treatment with placebo (n = 38), albendazole (n = 39), ivermectin (n = 34) or combination of albendazole and ivermectin (n = 42), respectively. One year after the re-treatment, an overall mean reduction in microfilarial intensity of 76.2% in relation to the intensity before re-treatment was observed, with no statistical significant difference between the 4 groups. The groups given primary treatment with placebo or the drug combination showed re-treatment reductions which were lower (72.5% and 69.8%, respectively) but not statistically significantly different from the reduction observed 1 year after the primary treatment with the combination (86.7%). The efficacy of the combination treatment thus appeared to be largely independent of the type of primary treatment given and multiplicative when used repeatedly.

Adolescent↗
PubMedDate not supplied

Control of bancroftian filariasis in an endemic area of Polynesia by ivermectin 400 micrograms/kg.

Community treatment with ivermectin was implemented in Opoa, French Polynesia from April 1991 to October 1993. All consenting inhabitants aged 3 years or more were treated with twice-yearly single doses of ivermectin, pregnant women excepted. A dosage of 100 microgram/kg was used for the 3 first treatments and then abandoned because it did not reduce the prevalence of microfilariae (mf) carriers. With a dosage of 400 micrograms/kg dosage, this prevalence decreased dramatically from 21% to 7%, and the mf level in carriers dropped to only 0.5% of its initial value after 3 treatments. The 400 micrograms/kg dosage was well tolerated and compliance was excellent. The twice-yearly single dose strategy with ivermectin at 400 micrograms/kg is safe and highly effective for filariasis control in an endemic area.

Animals↗
PubMed2003

Preliminary studies of offspring exposure to phenylbutazone and ivermectin during the perinatal period in a Holstein cow-calf model.

The pregnant Holstein cow and her newborn calf were evaluated as an animal model to study in utero and for lactational drug transfer and offspring exposure. A nonsteroidal antiinflammatory drug, phenylbutazone, and an antiparasitic drug, ivermectin, were tested in the model. Prior to parturition, pregnant cows were dosed orally to steady state with phenylbutazone at 4 g/day or given a single subcutaneous injection of 200 microg ivermectin/kg body wt. The level of drug transferred to calves exposed in utero, in utero combined with lactational exposure, and via lactational exposure only, was measured from days 1 through 7 postpartum. At birth the plasma level in phenylbutazone-exposed calves was approximately one-half the dam's steady-state level. For ivermectin-exposed calves, plasma levels were at or below the limit of quantitation (0.5 ng/ml) at birth, suggesting that placental transfer of ivermectin is limited in the cow. For both drugs, rapid accumulation of the drug in calf plasma occurred with lactational exposure to a mean daily dose of 2 microg ivermectin/kg body wt or 0.1 mg phenylbutazone/kg body wt/day for the first 7 days of life. The accumulation observed in the newborn calf is attributed to the lipid solubility and long elimination half-lives of these drugs. These results demonstrate that drug transfer and offspring exposure can be studied using the cow-calf model. The data also highlight the importance of considering not only the dose but also physicochemical characteristics and pharmacokinetics of the drug in the offspring when evaluating the safety of a newborn's exposure to a drug in breast milk.

Animals↗
PubMed2003

Effects of the antibacterial agents tiamulin, olanquindox and metronidazole and the anthelmintic ivermectin on the soil invertebrate species Folsomia fimetaria (Collembola) and Enchytraeus crypticus (Enchytraeidae).

Veterinary pharmaceutical products such as antibacterial agents and antiparasitics are widely used to control diseases and promote production in the agricultural sector. Exposure of non-target organisms are a likely result of using manure from treated live stocks or from dung dropped on the field by grazing animals. The aim of this study was to determine the toxic threshold levels of three antibacterial agents (tiamulin, olanquindox and metronidazole) and one anthelmintic (ivermectin) to two species of soil dwelling organisms (springtails and enchytraeids), that are often found in bio-solids such as manure or dung. The antibacterial agents were not toxic to adults and effects on reproduction occurred generally above concentrations normally found in soil or dung. The threshold values for toxicity (10% reduced reproduction or EC10 values) were in the range of 61-111 mg kg(-1) dry soil for springtails and 83-722 mg kg(-1) dry soil for enchytraeids. Ivermectin was significantly more toxic with EC10 values of 0.26 mg kg(-1) dry soil for the springtails and 14 mg kg(-1) dry soil for the enchytraeids. A comparison of these results with rough estimates of likely and worse case environmental concentrations indicates a potential risk of ivermectin to non-target species such as springtails and enchytraeids, whereas direct toxic effect of antibacterial agents is very unlikely to occur at environmental realistic concentrations. However, indirect effects of antibacterial agents driven through changes in the food web cannot be abolished at this stage.

Animals↗
PubMed2002

Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial.

BACKGROUND: At present, control of onchocerciasis depends almost entirely on yearly treatments with 150 microg/kg ivermectin. We aimed to compare the effect of higher doses, more frequent doses, or both with the standard regimen on adult Onchocerca volvulus. METHODS: We randomly allocated 657 patients who had onchocerciasis to 150 microg/kg ivermectin yearly (reference group), 150 microg/kg every 3 months, 400 then 800 microg/kg yearly, or 400 then 800 microg/kg every 3 months. We took skin snip samples from every patient before, and 3 years and 4 years after the first dose, and, at the same time excised one subcutaneous O volvulus nodule, which was examined histologically. The primary outcome was the vital status of the female worms. Analysis was done per protocol. FINDINGS: We obtained nodules from 511 patients. After 3 years of treatment, more female worms had died in the groups treated every 3 months than in the reference group (odds ratio=1.84 [95% CI 1.23-2.75], p=0.003 for 150 microg/kg; and 2.17 [1.42-3.31], p<0.001 for high doses). Female worms were also less fertile in these groups than in the reference group (0.24 [0.14-0.43], p<0.0001; and 0.14 [0.06-0.29], p<0.0001, respectively). No difference was recorded between groups treated yearly (p=0.83 for the proportion of dead females). Unexpected side-effects consisted of mild, temporary, subjective visual changes in patients on high-dose regimens. INTERPRETATION: Treatment with 3-monthly ivermectin could greatly reduce the number of female worms and acute itching and skin lesions; lower transmission of O volvulus; and change the duration of control programmes.

Adult↗
PubMed1998

Randomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes.

BACKGROUND: WHO has targeted lymphatic filariasis for elimination. Studies of vector-parasite relations of Wuchereria bancrofti suggest that a reduction in the microfilarial reservoir by mass chemotherapy may interrupt transmission and thereby eliminate infection. However, no field data exist on the impact of chemotherapy alone on vector efficiency and transmission intensity of W bancrofti. We compared the impact of an annual community-wide single-dose treatment with diethylcarbamazine alone or with ivermectin on rate and intensity of microfilaraemia, and transmission intensity in an area of Papua New Guinea endemic for intense W bancrofti transmission. METHODS: We carried out clinical and parasitological surveys in 14 communities in matched pairs. People aged 5 years or older in seven communities received randomly assigned diethylcarbamazine 6 mg/kg and people in the other seven communities received diethylcarbamazine 6 mg/kg plus ivermectin 400 micrograms/kg. We made physical examinations for hydroceles and leg oedema and investigated microfilarial densities by membrane filtration before and after treatment. We selected five communities for monthly entomological surveys between September, 1993, and September, 1995. Mosquitoes were collected in these communities by the all-night landing catch method and were individually dissected to identify rates of infection and infectiveness. FINDINGS: 2219 (87.6%) of 2534 eligible people received treatment. Microfilarial rate and density had decreased 1 year after treatment in all 14 communities; this decrease was significantly higher in communities given combined therapy than in those given diethylcarbamazine alone (mean decreases 57.5% and 30.6%, respectively; p = 0.0013). Greater decreases were also seen in community-specific microfilarial intensity with combined therapy (mean reductions 91.1% and 69.8%, respectively; p = 0.0047). The rate of leg oedema was not altered, but the frequency of advanced hydroceles decreased by 47% with combined therapy and 56% with diethylcarbamazine alone. 26,641 Anopheles punctulatus mosquitoes were caught during 499 person-nights of landing catches. Exposure to infective third-stage larvae decreased in all monitored five communities. Annual transmission potential decreased by between 75.7% and 98.8% in combined-therapy communities and between 75.6% and 79.4% in communities given diethylcarbamazine alone. Transmission was almost interrupted in two communities treated with combined therapy. INTERPRETATION: Annual single-dose community-wide treatment with diethylcarbamazine alone or with ivermectin is effective for the control of lymphatic filariasis in highly endemic areas, but combination therapy brings about greater decreases in rates and intensity of microfilaraemia.

Adolescent↗
PubMed2005

[Demodecidosis in a patient infected by HIV: successful treatment with ivermectin].

INTRODUCTION: Demodex is a saprophyte parasite in mammals. In Man, it is associated with differing clinical profiles (rosacea-like dermatitis, folliculitis and blepharitis). We report a case of demodecidosis in an HIV-infected patient that was successfully treated with ivermectin. CASE REPORT: A man from Laos, infected by HIV and treated for glandular tuberculosis, presented with a prurigenous eruption on the face and the pre-sternal and interscapular areas. Direct examination of scraped product and histopathological examinations confirmed the diagnosis of demodecidosis. Clinical cure was obtained after 2 single cures of ivermectin a one month's distance. DISCUSSION: The features of demodecidosis are often similar to those of rosacea. In immunodeficient patients, the semiology remains the same but the eruption is more abundant. During HIV-infection, demodecidosis occurs at the AIDS stage or with a CD4 count lower than 200/mm3. Many anti-dust mite molecules are used to treat the disease but frequently lead to irritation. Administration of a single cure of ivermectin, repeated if necessary, appears to be an interesting alternative to contact anti-dust mite agents.

Adult↗
PubMed2000

Effects of psoroptes ovis infection and its control with an ivermectin controlled-release capsule on growing sheep. 1. Evaluation of weight gain, feed consumption and carcass value.

To evaluate the prophylactic and therapeutic effects of an ivermectin controlled-release capsule (IVM-CRC) on the productivity of growing sheep infested with Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed based on sex and Day 0 body weight. Within each replicate animals were randomly allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is designed to deliver ivermectin at a minimum dose of 20 microg/kg per day for 100 days. The lambs were infested with 50-60 P. ovis mites each on Days 14 and 21. Mites in skin scrapings were counted on Days 70, 84, 98, 112 and 126. Body weight and feed consumption were measured every 2 weeks from Day 0 to 126. The animals were slaughtered on Day 127 and their carcasses evaluated. The IVM-CRC treatment on Day 0 prevented the establishment of P. ovis. All untreated lambs became infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards. The lambs treated on Day 0 had significantly (p<0.05) greater body weight gain from Day 0 to 84 (13.9 kg) and Day 0 to 126 (20.9 kg) than the untreated controls (9.6 and 12.8 kg, respectively) and the sheep treated on Day 84 (8.4 and 14.9 kg, respectively). Feed consumption (Days 0-126) for sheep treated with the IVM-CRC on Day 0 was higher than for sheep treated on Day 84 (p<0.05) and for the untreated controls (p<0.1). The carcasses of sheep treated with the IVM-CRC on Day 0 had significantly (p<0.05) higher warm and cold weights, carcass yield, rib eye area and back fat thickness than the untreated control group and the sheep treated with the IVM-CRC on Day 84. The sheep treated with the ivermectin CRC on either Day 0 or 84 had significantly (p<0.05) better muscle scores and lower muscle pH 1h post-slaughter than the untreated controls. There was no significant (p>0.1) difference between warm and cold carcass weights, carcass yield and rib eye area between sheep treated on Day 84 and untreated controls.

Animals↗
PubMed2001

Nematocidal activities of thiabendazole and ivermectin against the larvae of Strongyloides ratti and S. venezuelensis.

With the aim of developing therapeutic agents for strongyloidosis, the disease caused by infection with Strongyloides stercoralis, we established a novel assay technique using S. ratti and S. venezuelensis as models for S. stercoralis. The newly developed assay technique was found to more accurately represent treatment-induced larval paralysis than existing assays. Our method uses paper disks impregnated with the test solution, which even allows materials that are sparingly soluble in water to be tested. An inverted microscope was used to observe the larval states, and these states were recorded using a digital camera. We observed the activities of ivermectin and thiabendazole against larvae and calculated larval motility and velocity. These two factors were then combined to determine the overall viability of larvae at selected concentrations. The activities of the anthelmintics were compared by calculating the concentrations at which 50% viability was demonstrated, or in other words, the concentration at which paralysis was caused in 50% of the individuals (50% paralysis concentration; PC(50)). Evaluations after 24h of exposure yielded the following reproducible PC(50) values for ivermectin and thiabendazole, respectively: S. ratti, 2.4 and 140 microM; and S. venezuelensis, 2.3 and 190 microM. After treatment with ivermectin, there was a tendency for larval motility to be greater than that of the controls at low concentrations, a result that might be associated with its mechanism of action.

Animals↗