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Roger K. Prichard - One of the best experts on this subject based on the ideXlab platform.
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prevalence and intensity of onchocerca volvulus infection and efficacy of Ivermectin in endemic communities in ghana a two phase epidemiological study
The Lancet, 2007Co-Authors: John O. Gyapong, Daniel A. Boakye, Mike Y Oseiatweneboana, Roger K. PrichardAbstract:Summary Background Ivermectin has been used for onchocerciasis control since 1987. Because of the long-term use of this drug and the development of resistance in other nematodes, we have assessed Onchocerca volvulus burdens, effectiveness of Ivermectin as a microfilaricide, and its effect on adult female worm reproduction. Methods For the first phase of the study, 2501 individuals in Ghana, from 19 endemic communities who had received six to 18 annual rounds of Ivermectin and one Ivermectin naive community, were assessed for microfilarial loads 7 days before the 2004 yearly Ivermectin treatment, by means of skin snips, and 30 days after treatment to assess the Ivermectin microfilaricidal action. For the second phase, skin snips were taken from 342 individuals from ten communities, who were microfilaria positive at pretreatment assessment, on days 90 and 180 after treatment, to identify the effects of Ivermectin on female worm fertility, assessed by microfilaria repopulation. Findings 487 (19%) of the 2501 participants were microfilaria positive. The microfilaria prevalence and community microfilarial load in treated communities ranged from 2·2% to 51·8%, and 0·06 microfilariae per snip to 2·85 microfilariae per snip, respectively. Despite treatment, the prevalence rate doubled between 2000 and 2005 in two communities. Microfilaria assessment 30 days after Ivermectin treatment showed 100% clearance of microfilaria in more than 99% of people. At day 90 after treatment, four of ten communities had significant microfilaria repopulation, from 7·1% to 21·1% of pretreatment counts, rising to 53·9% by day 180. Interpretation Ivermectin remains a potent microfilaricide. However, our results suggest that resistant adult parasite populations, which are not responding as expected to Ivermectin, are emerging. A high rate of repopulation of skin with microfilariae will allow parasite transmission, possibly with Ivermectin-resistant O volvulus , which could eventually lead to recrudescence of the disease.
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Prevalence and intensity of Onchocerca volvulus infection and efficacy of Ivermectin in endemic communities in Ghana: a two-phase epidemiological study
Lancet, 2007Co-Authors: Mike Y. Osei-atweneboana, Jeffrey Kl Eng, John O. Gyapong, Daniel A. Boakye, Roger K. PrichardAbstract:Background: Ivermectin has been used for onchocerciasis control since 1987. Because of the long-term use of this drug and the development of resistance in other nematodes, we have assessed Onchocerca volvulus burdens, effectiveness of Ivermectin as a microfilaricide, and its effect on adult female worm reproduction. Methods: For the first phase of the study, 2501 individuals in Ghana, from 19 endemic communities who had received six to 18 annual rounds of Ivermectin and one Ivermectin naive community, were assessed for microfilarial loads 7 days before the 2004 yearly Ivermectin treatment, by means of skin snips, and 30 days after treatment to assess the Ivermectin microfilaricidal action. For the second phase, skin snips were taken from 342 individuals from ten communities, who were microfilaria positive at pretreatment assessment, on days 90 and 180 after treatment, to identify the effects of Ivermectin on female worm fertility, assessed by microfilaria repopulation. Findings: 487 (19%) of the 2501 participants were microfilaria positive. The microfilaria prevalence and community microfilarial load in treated communities ranged from 2·2% to 51·8%, and 0·06 microfilariae per snip to 2·85 microfilariae per snip, respectively. Despite treatment, the prevalence rate doubled between 2000 and 2005 in two communities. Microfilaria assessment 30 days after Ivermectin treatment showed 100% clearance of microfilaria in more than 99% of people. At day 90 after treatment, four of ten communities had significant microfilaria repopulation, from 7·1% to 21·1% of pretreatment counts, rising to 53·9% by day 180. Interpretation: Ivermectin remains a potent microfilaricide. However, our results suggest that resistant adult parasite populations, which are not responding as expected to Ivermectin, are emerging. A high rate of repopulation of skin with microfilariae will allow parasite transmission, possibly with Ivermectin-resistant O volvulus, which could eventually lead to recrudescence of the disease. © 2007 Elsevier Ltd. All rights reserved.
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Haemonchus contortus: effects of glutamate, Ivermectin, and moxidectin on inulin uptake activity in unselected and Ivermectin-selected adults.
Experimental Parasitology, 1999Co-Authors: J.-p. Paiement, Leger C, Paula Ribeiro, Roger K. PrichardAbstract:Abstract Paiement, J-P, Leger, C., Ribeiro, P., and Prichard, R. K. 1999. Haemonchus contortus: Effects of glutamate, Ivermectin, and moxidectin on inulin uptake activity in unselected and Ivermectin-selected adults. Experimental Parasitology92, 193–198. Using [3H]inulin uptake as a measure of pharyngeal pumping activity, we have investigated and compared the effects of glutamate, Ivermectin, and moxidectin on inulin uptake in susceptible and Ivermectin-selected Haemonchus contortus. Inulin uptake is inhibited by glutamate, Ivermectin, and moxidectin, at biologically relevant concentrations. Glutamate influences the responses to both Ivermectin and moxidectin, suggesting that these three substances share a common mechanism of action. The effects of Ivermectin on inulin uptake, but not moxidectin, are significantly altered as a result of selection with Ivermectin. These results suggest that Ivermectin and moxidectin may differ, to some extent, in their mode of action responses or mechanisms of resistance.
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Ivermectin resistance in nematodes may be caused by alteration of p glycoprotein homolog
Molecular and Biochemical Parasitology, 1998Co-Authors: Ming Xu, Paula Ribeiro, Marcelo Beltrao Molento, William J Blackhall, Robin N Beech, Roger K. PrichardAbstract:Abstract Resistance to Ivermectin and related drugs is an increasing problem for parasite control. The mechanism of Ivermectin resistance in nematode parasites is currently unknown. Some P-glycoproteins and multidrug resistance proteins have been found to act as membrane transporters which pump drugs from the cell. A disruption of the mdr1a gene, which encodes a P-glycoprotein in mice, results in hypersensitivity to Ivermectin. Genes encoding members of the P-glycoprotein family are known to exist in nematodes but the involvement of P-glycoprotein in nematode Ivermectin-resistance has not been described. Our data suggest that a P-glycoprotein may play a role in Ivermectin resistance in the sheep nematode parasite Haemonchus contortus . A full length P-glycoprotein cDNA from H. contortus has been cloned and sequenced. Analysis of the sequence showed 61–65% homology to other P-glycoprotein/multidrug resistant protein sequences, such as mice, human and Caenorhabditis elegans . Expression of P-glycoprotein mRNA was higher in Ivermectin-selected than unselected strains of H. contortus . An alteration in the restriction pattern was also found for the genomic locus of P-glycoprotein derived from Ivermectin-selected strains of H. contortus compared with unselected strains. P-glycoprotein gene structure and/or its transcription are altered in Ivermectin-selected H. contortus . The multidrug resistance reversing agent, verapamil, increased the efficacy of Ivermectin and moxidectin against a moxidectin-selected strain of this nematode in jirds ( Meriones unguiculatus ). These data indicate that a P-glycoprotein may be involved in resistance to Ivermectin and other macrocyclic lactones in H. contortus .
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Anthelmintics.
Veterinary parasitology, 1993Co-Authors: Roger K. Prichard, S RanjanAbstract:Anthelmintics remain the principal means for the prevention and control of subclinical and clinical ostertagiasis. The selection of an appropriate anthelmintic depends on whether one is controlling or preventing Type I ostertagiasis (caused by the establishment of adult worms derived from recently acquired infective larvae), preventing Type II (treating pre-Type II or inhibited larvae) or controlling Type II ostertagiasis (caused by the development of inhibited larvae to adults), or using the anthelmintic as part of an epidemiologically based plan to reduce pasture contamination with infective Ostertagia ostertagi larvae. In the latter case, the choice of an anthelmintic may depend on whether the targets for treatment are only adult worms and developing larvae or whether the targets include hypobiotic larvae. Thus for Ostertagia control, anthelmintics must be divided into those that normally control all stages, such as the avermectin group (Ivermectin, abamectin and moxidectin) and some of the benzimidazoles (albendazole, oxfendazole and fenbendazole at appropriate dose rates), and those that only control adult worms and developing larvae (levamisole, morantel, coumaphos, phenothiazine and thiabendazole).
R M Gopal - One of the best experts on this subject based on the ideXlab platform.
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efficacy of abamectin against Ivermectin resistant strain of trichostrongylus colubriformis in sheep
Veterinary Parasitology, 2004Co-Authors: R M Gopal, Kanwarjit Singh Sandhu, P K SidhuAbstract:Abstract The efficacy of two formulations of abamectin, i.e. oral and injectable was determined against Ivermectin-resistant strain of T. colubriformis in sheep. Twenty-four lambs were infected with 10,000 third stage larvae of Ivermectin-resistant strain of T. colubriformis. Twenty-four days post-infection, the lambs were divided randomly into four groups of six animals each according to egg counts. The first group was left untreated and kept as a control. The second group was treated with Ivermectin (oral) at 0.2 mg kg−1 body weight. The third group was treated with oral formulation of abamectin at 0.2 mg kg−1 body weight. The fourth group was treated with injectable formulation of abamectin at 0.2 mg kg−1 body weight. Fecal egg count and controlled slaughter tests were employed to determine the efficacy of abamectin (oral and injection) against Ivermectin-resistant strain of T. colubriformis in sheep. Reduction in arithmetic mean fecal egg counts achieved by Ivermectin (oral), abamectin (oral) and abamectin (injection) was 66, 98 and 76%, respectively 10 days after treatment. Ivermectin (oral), abamectin (oral) and abamectin (injection) reduced arithmetic mean worm burden by 63, 97 and 74%, respectively. The findings demonstrated that abamectin oral formulation was more effective than abamectin injection against Ivermectin-resistant strain of T. colubriformis in sheep.
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resistance of field isolates of trichostrongylus colubriformis and ostertagia circumcincta to Ivermectin
International Journal for Parasitology, 1999Co-Authors: R M Gopal, W E Pomroy, D M WestAbstract:Abstract Twelve Romney lambs and 10 Angora goats were infected with 7000 infective third-stage larvae (89% Trichostrongylus, 11% Ostertagia) collected from goats suspected of harbouring Ivermectin-resistant nematodes. On 28 days p.i., the lambs and goats were divided into treatment and control groups of six and five animals, respectively. The animals in the treatment groups were treated with Ivermectin (0.2 mg/kg) and necropsied 35 days p.i. Faecal egg counts were estimated on days 28 and 35 p.i. and larval development assays (LDAs) were conducted on 22, 24, 26, 28, 30, 32, 34 and 35 days p.i. The Ivermectin treatment reduced Trichostronglus colubriformis burdens by 39% and 13% and Ostertagia circumcincta by 33% and 0% in lambs and goats, respectively. When compared with a susceptible strain, the LDAs indicated a resistance factor before treatment in lambs for T. colubriformis of 2.6 and 1.5 with Ivermectin and avermectin B2, respectively, which rose to 3.4 and 2.0 after treatment. The LD50 values of the two control groups were relatively constant throughout the experiment. Prior to Ivermectin treatment the LD50 values of the treated groups were similar (P>0.05) to the control groups but following Ivermectin treatment their LD50 values increased steadily until the animals were killed on 35 days p.i. The LD50 values for Ivermectin and avermectin B2 of sheep were always slightly higher and significantly different (P
T Gopalakrishnan V Nair - One of the best experts on this subject based on the ideXlab platform.
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a comparative study of oral Ivermectin and topical permethrin cream in the treatment of scabies
Journal of The American Academy of Dermatology, 2000Co-Authors: V Usha, T Gopalakrishnan V NairAbstract:Abstract Background: The conventional antiscabietics have poor compliance. Ivermectin, an oral antiparasitic drug, has been shown to be an effective scabicide and could be a useful substitute. Objective: This study compares the efficacy of oral Ivermectin with topical permethrin cream in the treatment of scabies. Methods: Eighty-five consecutive patients were randomized into 2 groups. Forty patients and their family contacts received 200 μg/kg body weight of Ivermectin, and another 45 patients and their family contacts received a single overnight topical application of 5% permethrin cream. Patients were followed up at intervals of 1, 2, 4, and 8 weeks. Results: A single dose of Ivermectin provided a cure rate of 70%, which increased to 95% with 2 doses at a 2-week interval. A single application of permethrin was effective in 97.8% of patients. One (2.2%) patient responded to 2 applications at a 2-week interval. Permethrin-treated patients recovered earlier. Conclusion: A single application of permethrin is superior to a single dose of Ivermectin. Two doses of Ivermectin is as effective as a single application of permethrin. The temporal dissociation in clinical response suggests that Ivermectin may not be effective against all the stages in the life cycle of the parasite. (J Am Acad Dermatol 2000;42:236-40.)
Kenneth C Lasseter - One of the best experts on this subject based on the ideXlab platform.
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safety tolerability and pharmacokinetics of escalating high doses of Ivermectin in healthy adult subjects
The Journal of Clinical Pharmacology, 2002Co-Authors: Cynthia Guzzo, Christine I Furtek, Arturo G Porras, Cong Chen, Robert Tipping, Coleen M Clineschmidt, David Sciberras, John Y K Hsieh, Kenneth C LasseterAbstract:Safety and pharmacokinetics (PK) of the antiparasitic drug Ivermectin, administered in higher and/or more frequent doses than currently approved for human use, were evaluated in a double-blind, placebo-controlled, dose escalation study. Subjects ( n= 68) were assigned to one of four panels (3:1, Ivermectin/placebo): 30 or 60 mg (three times a week) or 90 or 120 mg (single dose). The 30 mg panel (range: 347-594 µg/kg) also received a single dose with food after a 1-week washout. Safety assessments addressed both known Ivermectin CNS effects and general toxicity. The primary safety endpoint was mydriasis, accurately quantitated by pupillometry. Ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose of 200 µg/kg. All dose regimens had a mydriatic effect similar to placebo. Adverse experiences were similar between Ivermectin and placebo and did not increase with dose. Following single doses of 30 to 120 mg, AUC and Cmax were generally dose proportional, with tmax ~4 hours and t1/2 ~18 hours. The geometricmean AUC of 30 mg Ivermectin was 2.6 times higher when administered with food. Geometricmean AUC ratios (day 7/day 1) were 1.24 and 1.40 for the 30 and 60 mg doses, respectively, indicating that the accumulation of Ivermectin given every fourth day is minimal. This study demonstrated that Ivermectin is generally well tolerated at these higher doses and more frequent regimens.
Bart J Currie - One of the best experts on this subject based on the ideXlab platform.
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first documentation of in vivo and in vitro Ivermectin resistance in sarcoptes scabiei
Clinical Infectious Diseases, 2004Co-Authors: Bart J Currie, Pearly Harumal, Melita Mckinnon, Shelley F WaltonAbstract:Ivermectin is increasingly being used to treat scabies, especially crusted (Norwegian) scabies. However, treatment failures, recrudescence, and reinfection can occur, even after multiple doses. Ivermectin resistance has been documented for some intestinal helminths in animals with intensive Ivermectin exposure. Ivermectin resistance has also been induced in arthropods in laboratory experiments but, to date, has not been documented among arthropods in nature. We report clinical and in vitro evidence of Ivermectin resistance in 2 patients with multiple recurrences of crusted scabies who had previously received 30 and 58 doses of Ivermectin over 4 and 4.5 years, respectively. As predicted, Ivermectin resistance in scabies mites can develop after intensive Ivermectin use
