Lymphatic filarial (LF) parasites have been under anti-filarial drug pressure for more than half a century. Currently, annual mass drug administration (MDA) of diethylcarbamazine (DEC) or ivermectin in combination with albendazole (ALB) have been used globally to eliminate LF. Long-term chemotherapies exert significant pressure on the genetic structure of parasitic populations. We investigated the genetic variation among 210 Wuchereria bancrofti populations that were under three different chemotherapy strategies, namely MDA with DEC alone (group I, n = 74), MDA with DEC and ALB (group II, n = 60) and selective therapy (ST) with DEC (group III, n = 34) to understand the impact of these three drug regimens on the parasite genetic structure. Randomly amplified polymorphic DNA profiles were generated for the three groups of parasite populations; the gene diversity, gene flow and genetic distance values were determined and phylogenetic trees were constructed. Analysis of these parameters indicated that parasite populations under ST with a standard dose of DEC (group III) were genetically more diverse (0.2660) than parasite populations under MDA with DEC alone (group I, H = 0.2197) or with DEC + ALB (group II, H = 0.2317). These results indicate that the MDA may reduce the genetic diversity of W. bancrofti populations when compared to the genetic diversity of parasite populations under ST.
A safer, more effective adulticidal treatment and a safe method for reducing microfilaremia and breaking transmission of heartworm disease early in the treatment are needed. The present study evaluated efficacy of ivermectin (IVM) and doxycycline (DOXY) alone or together (with or without melarsomine [MEL]) in dogs with induced adult heartworm infection and assessed the ability of microfilariae from DOXY-treated dogs to develop to L3 in Aedes aegypti mosquitoes and subsequently to become reproductive adults in dogs. Thirty beagles were each infected with 16 adult heartworms by intravenous transplantation. Six weeks later, dogs were ranked by microfilarial count and randomly allocated to 6 groups of 5 dogs each. Beginning on Day 0, Group 1 received IVM (6 mcg/kg) weekly for 36 weeks. Group 2 received DOXY (10 mcg/(kgday)) orally Weeks 1-6, 10-11, 16-17, 22-25, and 28-33. Groups 3 and 5 received IVM and DOXY according to doses and schedules used for Groups 1 and 2. At Week 24, Groups 3 and 4 received an intramuscular injection of MEL (2.5 mg/kg), followed 1 month later by two injections 24h apart. Group 6 was not treated. Blood samples were collected for periodic microfilaria counts and antigen (Ag) testing (and later immunologic evaluation and molecular biology procedures). Radiographic and physical examinations, hematology/clinical chemistry testing, and urinalysis were done before infection, before Day 0, and periodically during the treatment period. At 36 weeks, the dogs were euthanized and necropsied for worm recovery, collection of lung, liver, kidney, and spleen samples for examination by immunohistochemistry and conventional histological methods. All dogs treated with IVM + DOXY (with or without MEL) were amicrofilaremic after Week 9. Microfilarial counts gradually decreased in dogs treated with IVM or DOXY, but most had a few microfilariae at necropsy. Microfilarial counts for dogs treated only with MEL were similar to those for controls. Antigen test scores gradually decreased with IVM + DOXY (with or without MEL) and after MEL. Antigen scores for IVM or DOXY alone were similar to controls throughout the study. Reduction of adult worms was 20.3% for IVM, 8.7% for DOXY, 92.8% for IVM + DOXY + MEL, 100% for MEL, and 78.3% for IVM + DOXY. Mosquitoes that fed on blood from DOXY-treated dogs had L3 normal in appearance but were not infective for dogs. Preliminary observations suggest that administration of DOXY+IVM for several months prior to (or without) MEL will eliminate adult HW with less potential for severe thromboembolism than MEL alone.
Whole-kernel corn was treated with 10 mg ivermectin per 0.45 kg corn and fed at rate of approximately .45 kg/deer per day to white-tailed deer confined in the treatment pasture, whereas deer in an adjacent control pasture received a similar ration of untreated corn. Treatments were dispensed from February through September of 1992 and 1993, and free-living populations of lone star ticks. Amblyomma americanum (L.), were monitored in both pastures using dry-ice traps to quantify nymphs and adults and flip-cloths to assay the relative abundance of larval masses. Control values that were calculated for all ticks collected in both pastures during 1993 showed 83.4% fewer adults, 92.4% fewer nymphs and 100.0% fewer larval masses in the treatment versus control pasture. Serum ivermectin concentrations in treated deer averaged 21.7 and 28.3 ppb during 1992 and 1993, respectively. These values compared favorably with the goal concentration of 30.0 ppb which was anticipated under ideal conditions. This study demonstrates that a freely consumed, systemically active acaricidal bait ingested by white-tailed deer under nearly wild conditions can significantly reduce the abundance of all stages of free-living long star ticks.
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The cytotoxicity and genotoxicity of abamectin, chlorfenapyr, and imidacloprid have been evaluated on the Chinese hamster ovary (CHOK1) cells. Neutral red incorporation (NRI), total cellular protein content (TCP), and methyl tetrazolium (MTT) assays were followed to estimate the mid-point cytotoxicity values, NRI50, TCP50, and MTT50, respectively. The effects of the sublethal concentration (NRI25) on glutathione S-transferase (GST), glutathione reductase (GRD), glutathione peroxidase (GPX), and total glutathione content have been evaluated in the presence and absence of reduced glutathione (GSH), vitamin C, and vitamin E. The genotoxicity was evaluated using chromosomal aberrations (CA), micronucleus (MN) formation, and DNA fragmentation techniques in the presence and absence of the metabolic activation system, S9 mix. Abamectin was the most cytotoxic pesticide followed by chlorfenapyr, while imidacloprid was the least cytotoxic one. The glutathione redox cycle components were altered by the tested pesticides in the absence and presence of the tested antioxidants. The results of genotoxicity indicate that abamectin, chlorfenapyr, and imidacloprid have potential genotoxic effects on CHOK1 cells under the experimental conditions.
We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Three hundred and thirty eight residents were examined, representing 69% of the total population of the five communities. Only 1 case of scabies was found, in an adult who had recently returned from the mainland. The prevalence of active impetigo was 8.8% overall and 12.4% in children aged 12 years or less.
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An 80-year-old female with severe RA developed erythroderma followed by hyperkeratosis, widespread scaling over the trunk, arms, hands and limbs, and crusted lesions on her scalp. She was on TCZ (8 mg/kg per month) with prednisone (20 mg/d). Several hypotheses were evoked (i.e., vasculitis, psoriasis or paraneoplasic syndrome) but a microscopic examination of the skin surprisingly demonstrated numerous scabies mites and eggs leading to the diagnosis of crusted (Norwegian) scabies. After repeated use of ivermectin and application of topical piperonyl butoxide cream, scabies disappeared. However, there had been outbreak of scabies among two individuals in the staff and two patients. TCZ was stopped after four infusions because of a severe infectious pneumonia and failure.
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There appears to be a clear need to retrain middle cadre ivermectin workers in trachoma rapid assessment and SAFE strategy intervention methods in order to further impact blindness prevention in these 'onchocerciasis-endemic' zones.
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Eprinomectin is a new endectocide of the avermectin chemical group developed for use in cattle. To establish its effectiveness against Cooperia spp., Dictyocaulus viviparus, Haemonchus contortus, Nematodirus helvetianus, Oesophagostomum radiatum, Ostertagia ostertagi, Trichostrongylus axei and Trichostrongylus colubriformis (immature infections only), six trials were conducted in Europe at two trial sites. In each trial, animals were artificially infected with a number of nematode species and treated with eprinomectin. In three trials, the nematodes were expected to be at the fourth larval stage of development at the time of treatment, and at the adult stage at the time of treatment in the other three trials. When compared with the untreated control groups, efficacy against the adult and immature nematode infections was > 99% for all the nematode species examined. There was no difference in efficacy between groups of animals with clipped hair at the application site, and those with long hair. Subsequent examination of the application sites, both visual and by palpation, showed no gross reactions to the applied treatments.
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We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock.
The commercial formulation of ivermectin used in this study can be administered SC to sheep on the basis of a nearly complete bioavailability. In addition, the maximum plasma concentration and interval from SC injection until maximum plasma concentration is obtained are higher than those reported by other authors who used other routes of administration.
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A total of 1,083 participants were screened and the overall parasite prevalence was 1.6% with mf intensities ranging from 0 to 59 per 100 μl and geometric mean intensity of 1.1 mf per ml of blood. Of the 564 mosquitoes collected, 350 (62.1%) were Anopheles spp., from which 310 (88.6%) were An. funestus and 32 (9.1%) An. gambiae. Six anopheline mosquitoes (1.7%) were found infected with L₁, but no larva was observed in any of the mosquitoes maintained up to 13 days. Molecular studies showed all An. gambiae s.l. to be An. gambiae s.s., of which 21 (70%) were of the M molecular form.
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For children with W bancrofti microfilaraemia, combined treatment with ivermectin and albendazole was more effective than treatment with ivermectin only, with no measurable increase in severity of adverse reactions.
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Three groups of 10 weaned Romney-cross lambs were treated either with an oral dose of ivermectin (0.2 mg/kg), or a benzimidazole/levamisole (BZ/LEV) combination (4.75 albendazole and 7.5 mg/kg levamisole), or were left untreated. Ten days later, animals were necropsied, and adult worms recovered and identified from the abomasa and small intestines. Pre- and post-treatment faecal nematode egg counts (FEC) were recorded, and larval cultures were performed.
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BZ-resistant gastrointestinal nematodes were found on all 25 farms with a previous history of BZ use. High levels of resistance (>40 % of hatching) were recorded on 36 % of these farms, and low levels (<20 % of hatching) on 40 % of farms. IVM-resistant populations were found on 13 out of 21 sheep farms using this drug. Of these 13 farms with AR to IVM, low levels of resistance (<30 % development) were recorded on 84.6 % of farms and high levels (>30 % development) on 15.4 % of farms. No resistance to IVM was recorded on 38.1 % of farms. Multi-drug resistance was detected on five farms out of 13 (38.5 %) using both classes of drugs.
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The cytochrome P450 monooxygenase Ema1 from Streptomyces tubercidicus R-922 and its homologs from closely related Streptomyces strains are able to catalyze the regioselective oxidation of avermectin into 4"-oxo-avermectin, a key intermediate in the manufacture of the agriculturally important insecticide emamectin benzoate (V. Jungmann, I. Molnár, P. E. Hammer, D. S. Hill, R. Zirkle, T. G. Buckel, D. Buckel, J. M. Ligon, and J. P. Pachlatko, Appl. Environ. Microbiol. 71:6968-6976, 2005). The gene for Ema1 has been expressed in Streptomyces lividans, Streptomyces avermitilis, and solvent-tolerant Pseudomonas putida strains using different promoters and vectors to provide biocatalytically competent cells. Replacing the extremely rare TTA codon with the more frequent CTG codon to encode Leu4 in Ema1 increased the biocatalytic activities of S. lividans strains producing this enzyme. Ferredoxins and ferredoxin reductases were also cloned from Streptomyces coelicolor and biocatalytic Streptomyces strains and tested in ema1 coexpression systems to optimize the electron transport towards Ema1.
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Ivermectin is a member of the macrocyclic lactone family widely used in livestock, pets, and humans as a potent parasiticide. Slight differences in formulation may change the plasma kinetics and efficacy of these compounds. The aim of the study is to evaluate the ability of a liposomal formulation of ivermectin to generate an efficient exposure of the animal to the drug. Ten rabbits were subcutaneously administered with 0.3 mg kg(-1) of ivermectin using Ivomec (n=5) or a liposomal formulation (n=5). The areas under serum concentration-time curve were similar after both treatments, indicating the same bioavailability for the two formulations. However, the liposomal formulation gave a higher C(max) value (33.33 ng ml(-1)) compared with Ivomec (20.82 ng ml(-1)) and a significantly faster absorption as indicated by the T(max) of 0.23 days compared with 1.13 days for the Ivomec formulation. The use of liposomal formulation shows promise as this system improves the efficacy of ivermectin and related drugs.
Oxfendazole is recommended as the drug of choice for treating porcine cysticercosis. The drug does not kill brain cysts and is not registered for use in pigs. Latest its safety in the recommended dose has been questioned. The aim of this study was to investigate two alternative anthelminthics. The efficacy of praziquantel and ivermectin was compared to oxfendazole In Vitro on Taenia solium. Cysts of T. solium were isolated from infected pork and incubated in culture media together with the drugs. The degree of evagination was used as effect measurement and determined after 6 hours. Praziquantel had a half maximal effective concentration (EC(50)) of value 0.006 ± 0.001 μg/mL. Ivermectin did not show any impact on the evagination in concentrations from 0.001 to 30 μg/mL and neither did oxfendazole in concentrations from 0.001 to 50 μg/mL.
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Loa loa is currently considered as a major pathogen in man. The clinical repercussions of this filariasis have been clearly established and treatment is considered essential. Ivermectin, administered alone or with diethylcarbamazine presents interesting therapeutic possibilities. The review of vector control methods show that trapping is the only effective measure of protection. In order to reduce the endemicity of loaiasis, mass treatment with ivermectin could be envisaged immediately. However, the development of this filariasis is directly related to the development of the Central African forest region.
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The persistent efficacy of some anthelmintics brings advantages in nematode control in domestic animals. However, scientific assessment of persistent efficacy is relatively new, and a feature of published data has been variability in the reported endpoint for this activity. Trial design and method of calculating efficacy have a large bearing on the results obtained. Three types of studies used to evaluate the persistent efficacy of anthelmintics are briefly discussed and compared. In the first type of study, animals are treated followed by a single infection at 7, 14 or more days after treatment. The reduction in worm counts compared to an untreated control group gives a good indication of the persistent efficacy of the product at each time point. One control group can be used for several time points. In the second type of study, the animals are treated and then infected daily from day 1 until 7 days, 14 days or longer after treatment. The animals are slaughtered approximately 3 weeks after the last infection. This approach may better mimic a natural infection but the results obtained are an average reduction over the whole infection period. At the end of the evaluated period, the actual protection may be considerably lower than the average. From this test, it is difficult to define when the protection decreases or disappears. In this test, a control group is required for each period. In the third type of study, a modification of the second, the animals are treated and infected as before but animals are slaughtered soon (2-5 days) after the last infection. Based on the reduction of, for example, the different Ostertagia stages a more specific determination of the persistent efficacy 0-3 days (L3), 3-7 (EL4), 7-14 (LL4 + EL5) and more than 14 days (LL5 + adults) before slaughter can be obtained. Only two groups of animals are required to cover a 3 week period and the average efficacies can be reduced to about one week.
Scabies is found worldwide among people of all groups and ages. It is curable with scabicide medications. This study aimed to compare the efficacy and safety of oral ivermectin vs malathion 0.5% lotion for the treatment of scabies. In total, 148 patients with scabies were enrolled and randomized into two groups: the first group received a single dose of oral ivermectin 200 sg/kg body weight, and the second was treated with two applications of topical lindane lotion 1%, with a 1-week interval between applications. Treatment was evaluated at intervals of 2 and 4 weeks, and if there was treatment failure at the 2-week follow-up, treatment was repeated. A single dose of ivermectin provided a cure rate of 60.8% at the 2-week follow-up, which increased to 89.1% at the 4-week follow-up after repeating the treatment. Treatment with two applications oflindane lotion 1%, with a 1-week interval between them, was effective in 47.2% of patients at the 2-week follow-up, which increased to 72.9% at the 4-week follow-up after this treatment was repeated. A single dose of ivermectin was as effective as two applications of lindane lotion 1% at the 2-week follow-up. After repeat treatment, ivermectin was superior to lindane lotion 1% at the 4-week follow-up. The delay in clinical response with ivermectin suggests that it may not be effective against the parasite at all stages in the life cycle.