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Twenty-four beagles were randomly allocated into four groups of six and housed in separate cages. Each dog was infested with 25 Ctenocephalides canis and 25 Ctenocephalides felis felis and two days later (day 0) the dogs in groups 1, 2 and 3 received a spot-on application of selamectin (6 mg/kg), imidacloprid (10 mg/kg), or fipronil (6-7 mg/kg), respectively, while the dogs in group 4 were not treated. The dogs were combed 48 hours later, the fleas were removed, counted and their species were determined. All the dogs were reinfested with the same number of the two species of fleas on days 7, 14, 21, 28 and 35, and the efficacy of the treatments was calculated 48 hours after each infestation. The mean numbers of fleas on the control dogs were 19.8 C. canis and 14.7 C. felis felis. The three treatments were effective for the full 35 days of the trial; over the first 28 days, the efficacy of selamectin ranged from 81 to 100 and 92 to 99 per cent against C. felis felis and C canis, respectively, the efficacy of imidacloprid ranged from 98 to 100 per cent and the efficacy of fipronil was 100 per cent against both species. There were no significant differences between the three treatments.
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Ivermectin is the first oral treatment available for scabies. It is however not licensed for use in Belgium. In this article, we review its mechanism of action, its preferential indications among which crusted scabies and institutional outbreaks, its contra-indications and its advantages in comparison with topical treatments.
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This study shows that there is WTP for local ivermectin distribution in the three study communities, and that it should be assessed before instituting community-directed treatment with ivermectin.
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IRE/CTVM19 cells were treated with different concentrations of ivermectin (0, 11, 22 or 33 μM) and incubated for 10 days. Evaluation of viability and relative expression of ABCB1, ABCB6, ABCB8 and ABCB10 genes were carried out at day 10 post treatment. Cell viability ranged between 84% and 92% with no significant differences between untreated and treated cells. qRT-PCR showed that ABC pump expression was not significantly modulated by ivermectin treatment. Expression of the ABCB8 PgP subfamily revealed a biphasic trend, based on the ivermectin concentration. ABCB6 and ABCB10 gene expression was not modulated by ivermectin treatment and ABCB1 expression was not detected.
Five Ndama bulls aged between 1.5 and 2 years and 20 Djallonke rams aged between 6 to 18 months were dewormed as follows: the bulls were dewormed in November (beginning of the dry season), the sheep were divided into four groups dewormed in November, January, March and May respectively. The animals were kept on naturally infected pastures prior to and throughout the experiment. Gastrointestinal nematode egg excretion was measured weekly after starting the treatment. Egg excretion stayed practically nil for all animals except for the series of sheep treated in May which started excreting eggs on month after the first rain. The bulls were slaughtered in June and the sheep were slaughtered nine weeks after they had been initially dewormed. A complete parasitological post mortem examination confirmed the absence of any pathologically consequent reinfection by gastro-intestinal nematodes of Gambian cattle during the dry season. This confirms the strategic importance of the application of a dewormer also efficient against immature trichostrongylids at the beginning of the dry season and renders complementary deworming between November and May superfluous.
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Prevalence rates of intestinal helminthiases before treatment and at 1 month and 9 months after mass treatment were: hookworm disease 28.5%, 16.4% and 7.7%; ascariasis 17.1%, 0.4% and 7.2%; trichuriasis 16.5%, 3.4% and 9.4%; strongyloidiasis 11.0%, 0.6% and 0.7%; and hymenolepiasis 0.6%; 0.4% and 0.5%, respectively. Prevalence rates of parasitic skin diseases before treatment and 1 month and 9 months after mass treatment were: active pediculosis 16.1%, 1.0% and 10.3%; scabies 3.8%, 1.0% and 1.5%; cutaneous larva migrans 0.7%, 0% and 0%; tungiasis 51.3%, 52.1% and 31.2%, respectively. Adverse events occurred in 9.4% of treatments. They were all of mild to moderate severity and were transient.
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A 9-year old German Shepherd bitch was presented with a recent onset of seborrhoea oleosa, hyperpigmentation, erythema, pruritus and alopecia along the neck, thorax, ventrum and the dorsal area of the carpus. The skin changes were believed to be caused by Dirofilaria immitis infection. A combination of topical and parenteral anti-heartworm therapy led to the resolution of the lesions.
Twelve Holstein calves were used to determine the prophylactic efficacy of ivermectin against challenge exposure with gastrointestinal and pulmonary nematodes. Two groups of 6 calves (mean body weight, 205 kg) each were formed by restricted randomization according to body weight. Group-1 calves served as nonmedicated controls. Each calf of group 2 was orally given one prototype sustained-release bolus designed to deliver ivermectin at a continuous daily dose of 8 mg. Third-stage nematode infective larvae were given to the calves on posttreatment days 28 and 42. The calves were euthanatized 77 or 78 days after treatment. Ivermectin was 100% effective (P less than 0.05) in preventing the establishment of infection by Haemonchus placei, Ostertagia ostertagi, Cooperia spp (C punctata, C oncophora, C surnabada), Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus and was greater than 99% effective against Trichostrongylus axei. Incidental infection by Trichuris spp was reduced by 94% (P = 0.08).
Scabies is a contagious parasitic dermatitis that is a significant cause of morbidity, especially outside of the United States. Scabies is diagnosed most often by correlating clinical suspicion with the identification of a burrow. Although scabies should be on the differential for any patient who presents with a pruritic dermatosis, clinicians must consider a wide range of diagnostic possibilities. This approach will help make scabies simultaneously less over- and underdiagnosed by clinicians in the community. Atypical or otherwise complex presentations may necessitate the use of more definitive diagnostic modalities, such as microscopic examination of KOH prepared skin scrapings, high-resolution digital photography, dermoscopy, or biopsy. Scabies therapy involves making the correct diagnosis, recognizing the correct clinical context to guide treatment of contacts and fomites, choosing the most effective medication, understanding how to use the agent properly, and following a rational basis for when to use and reuse that agent. Although the development of new therapeutic agents is always welcome, tried and true treatments are still effective today. Permethrin is the gold standard therapy, with malathion being an excellent topical alternative. Ivermectin is an effective oral alternative that is especially useful in crusted scabies, patients who are bed ridden, and in institutional outbreaks. Despite the availability of effective therapeutics, treatment failures still occur, mostly secondary to application error (ie, failure to treat the face and scalp or close contacts, failure to reapply medication) or failure to decontaminate fomites. Because increasing resistance to scabies treatments may be on the horizon, we propose that standard of care for scabies treatment should involve routine treatment of the scalp and face and re-treating patients at day 4 on the basis of the scabies life cycle to ensure more efficient mite eradication. Practitioners should attempt to treat all close contacts simultaneously with the source patient. To eradicate mites, all fomites should be placed in a dryer for 10 minutes on a high setting, furniture and carpets vacuumed, and nonlaunderables isolated for a minimum of 2 days, or, for those who wish to be rigorous, 3 weeks.
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A young woman with history of asthma presented with complaints of nausea, vomiting, abdominal pain, wheezing, and dry cough. Physical examination revealed diffuse expiratory wheezing and mild diffuse abdominal pain without rebound or guarding. Laboratory results showed leukocytosis with eosinophilia. Stool studies showed Strongyloides stercoralis. Imaging revealed ground-glass opacities in the right upper and lower lobe along with an infiltrate in the lingular lobe on the left side. Bronchoscopy showed Strongyloides stercoralis. The patient was diagnosed with hyperinfection syndrome due to Strongyloides stercoralis most probably exacerbated by prednisone given for her asthma. Steroids were then discontinued and the patient was started on ivermectin. The patient improved with treatment. Repeat stool examination was negative for Strongyloides stercoralis.
Serum samples from 953 reindeer (Rangifer t. tarandus) calves-of-the-year from 21 reindeer herding co-operatives in Finland in slaughter season 2006/2007 were assayed for antibodies against Hypodermin C by an ELISA detecting IgG. Data on presence of Hypoderma tarandi larvae on 12,327 reindeer hides from 17 of the 21 herding co-operatives in slaughter season 2005/2006 were included for support. ELISA showed a seroprevalence of 60.9%, with no significant difference between females and males, and increase with latitude (southernmost and northernmost co-operatives examined, Pudasjärvi and Kaldoaivi, 11.8 and 100% of seropositives, respectively). The proportion of larva positive hides (range 0.5-60% per co-operative) was low compared to the proportion of seropositives. Also the proportion of larva positive hides increased with latitude. Our findings indicated that high latitude combined with open landscape, presence of low vegetation and high reindeer density provided more favorable conditions for sustaining of high degree of warble fly infestation, and furthermore, that any possible effect of ivermectin treatment on infestation rate was ruled out by the higher effect by the above factors.
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Spirocerca lupi is a nematode mainly affecting dogs but has been found in other animals, particularly carnivores. Anatomical areas of typical and aberrant migration vary. This report describes four cases of Spirocerca lupi causing neurological symptoms, similar to thoracolumbar disc syndrome, as a result of aberrant migration of the nematode into the spinal canal. In two of the cases, the nematode could be demonstrated intraoperatively. The third was discovered on post-mortem examination, while the fourth case displayed compelling evidence of Spirocerca lupi involvement. Surgical removal of the Spirocerca lupi nematode would be the treatment of choice in cases of spinal migration, with therapeutic and preventive treatment with doramectin instituted to treat remote sites and prevent re-infection. In areas endemic for spirocercosis, Spirocerca lupi should be considered as an important differential diagnosis in cases that are presented with clinical signs suggestive of a spinal cord lesion.
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Collies with mild to severe reactions to ivermectin challenge (120 mg/kg; 20 times the recommended dose for heartworm prevention) were used. Six replicates of 4 dogs each were formed on the basis of body weight and severity of reaction to ivermectin test dose. Within replicates, each dog was randomly allocated to treatment with oral administration of 30, 60, or 90 microg of moxidectin/kg or was given a comparable volume of placebo tablet formulation. Dogs were observed hourly for the first 8 hours and twice daily thereafter for 1 month for signs of toxicosis.
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The plasma concentration profiles of four randomly chosen ivermectin (IVM) generic formulations (IVM G1-G4) were compared after their subcutaneous (SC) administration to healthy calves. The disposition of other avermectin-type endectocide compounds, doramectin (DRM) and abamectin (ABM), was also assessed in the same pharmacokinetic trial. Forty-two parasite-free Aberdeen Angus male calves were randomly allocated into six treatment groups. Animals in each group (n = 7) received SC treatment (200 microg/kg) with one of the commercially available endectocide formulation used in the trial. Blood samples were taken into heparinised vacutainer tubes from the jugular vein prior to and up to 35 days post-treatment. The recovered plasma was analysed by HPLC with fluorescence detection. Large kinetic differences were observed among the DRM, ABM and IVM formulations under evaluation. The DRM plasma concentration profiles were higher than those measured for ABM and all the IVM generic formulations. The higher and sustained plasma concentrations of DRM accounted for greater area under concentration-time curve (AUC) and longer mean residence time (MRT) values compared to those obtained for both ABM and the IVM generic preparations. The pattern of IVM absorption from the site of subcutaneous administration showed differences among the generic formulations under evaluation. The IVM G2 preparation showed higher peak plasma concentration and AUC values (P < 0.05) compared to those obtained after the administration of the IVM G1 formulation. Longer (P < 0.05) MRT values were obtained after the administration of the IVM G3 compared to other IVM generic preparations. The kinetic behaviour of ABM did not show significant differences with that described for most of the IVM formulations. This study demonstrates that major differences on drug kinetic behaviour may be observed when using different endectocide injectable formulations in cattle.
Ivermectin administered orally to Spanish goats, Capra hircus (L.), or to white-tailed deer, Odocoileus virginianus (Zimmerman), was highly effective against lone star ticks, Amblyomma americanum (L.). For Spanish goats, daily oral doses of 20 micrograms/kg resulted in greater than or equal to 2 ppb ivermectin in the blood. This level was sufficient to cause greater than 95% reduction of estimated larvae from feeding ticks. A bioassay with horn flies, Haematobia irritans (L.), was developed to estimate oral intake of ivermectin. Probit analysis of dose-mortality data indicated that a 50% reduction in adult horn fly emergence can be expected when the manure from goats treated orally with ivermectin at 10, 20, 35, and 50 micrograms/kg/d was mixed with untreated cow manure at a rate of 0.345, 0.110, 0.100, and 0.092%, respectively. In studies with white-tailed deer, daily oral doses of 35 and 50 micrograms/kg/d provided 100% control of adult and about 90% control of nymphs that were placed on treated fawns. A single oral dose of 50 micrograms/kg gave greater than 90% control of adult and nymphal ticks attached to treated fawns at the time of drug administration and 70% control of ticks placed on treated deer three days thereafter. When ticks were placed on fawns treated with a single dose of ivermectin (50 micrograms/kg) the engorgement period was longer, ticks were lighter in weight, and females laid fewer eggs than ticks detaching from control fawns. A single oral dose of ivermectin at 20 micrograms/kg prevented about 60% of the adult and nymphal ticks attached at the time of drug administration from engorging, but did not affect other ticks placed on the animals after treatment.
During March of 1991 and 1992, four trials were carried out in the central area of Argentina to evaluate the efficacy of ivermectin in the prevention of myiasis caused by Cochliomya hominivorax larvae. In the first trial 24 steers were artificially wounded, in the second and third trial, 36 and 20 bull calves were castrated while in the fourth trial, 30 newborn calves were used. On day 0, half of the animals of each trial was treated with ivermectin (200 micrograms/kg) and the rest remained as untreated controls. None of the treated animals sustained a screw-worm larva infestation, but 3 of 12 (25%), 8 of 18 (44%), 5 of 10 (50%) and 8 of 15 (53%) of the controls developed active myiasis in trials 1 to 4 respectively.
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The observed inhibition of RH123 cell exclusion ranged from little or no effect (digoxin, indinavir, fexofenadine) up to a nearly 10-fold increase in RH 123 accumulation (ivermectin, terfenadine). No correlation between P-gp and CYP3A4 inhibition was observed. The rank order in P-gp inhibitory potency for terfenadine, verapamil, ritonavir. and indomethacin was identical in both LS180V and Caco-2 models. Ritonavir and St. John's wort extract showed a concentration-dependent P-gp induction, with good correlation between western blot analysis and RH123 accumulation.
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The veterinary parasiticide ivermectin was selected as a case study compound within the project ERAPharm (Environmental Risk Assessment of Pharmaceuticals). Based on experimental data generated within ERAPharm and additional literature data, an environmental risk assessment (ERA) was performed mainly according to international and European guidelines. For the environmental compartments surface water, sediment, and dung, a risk was indicated at all levels of the tiered assessment approach. Only for soil was no risk indicated after the lower tier assessment. However, the use of effects data from additional 2-species and multispecies studies resulted in a risk indication for collembolans. Although previously performed ERAs for ivermectin revealed no concern for the aquatic compartment, and transient effects on dung-insect populations were not considered as relevant, the present ERA clearly demonstrates unacceptable risks for all investigated environmental compartments and hence suggests the necessity of reassessing ivermectin-containing products. Based on this case study, several gaps in the existing guidelines for ERA of pharmaceuticals were shown and improvements have been suggested. The action limit at the start of the ERA, for example, is not protective for substances such as ivermectin when used on intensively reared animals. Furthermore, initial predicted environmental concentrations (PECs) of ivermectin in soil were estimated to be lower than refined PECs, indicating that the currently used tiered approach for exposure assessment is not appropriate for substances with potential for accumulation in soil. In addition, guidance is lacking for the assessment of effects at higher tiers of the ERA, e.g., for field studies or a tiered effects assessment in the dung compartment.
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This paper presents a summary of reported cases of Serious Adverse Events (SAEs) following treatment with Mectizan(R) (ivermectin, Merck, Sharpe & Dohme) in onchocerciasis mass treatment programs from January 1, 1989 to December 31, 2001 through a passive surveillance system. A total of 207 SAE cases were reported out of approximately 165 million reported treatments delivered during the period under review, giving rise to a cumulative incidence of 1 reported SAE per 800,000 reported treatments. The mean age was 40 years and 70% of the cases were males. The mean time between ivermectin intake and onset of illness was 1 day. For 57% of the cases (n = 118), that was their first exposure to ivermectin. The majority of cases were reported from Cameroon (n = 176; 85%) with peaks in the incidence of SAE reporting in 1989-1991 and 1994-1995 when the program expanded to ivermectin-naïve populations. Fifty-five percent of the cases from Cameroon (i.e. 97 out of 176 cases) were encephalopathic and were reported from the central-southern region of the country; two-thirds of these cases were 'probable' or 'possible' cases of Loa loa encephalopathy temporally related to ivermectin treatment. Reporting bias may explain some but not all of the differences in SAE reporting between the 34 onchocerciasis-endemic countries that have, or have had, mass treatment programs. Further research is needed to understand the apparent clustering of encephalopathy cases in central-southern Cameroon since L. loa infection alone probably does not explain the increased incidence of this type of SAE from this region.
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These results confirm the important role of the arachidonic acid metabolic pathway in DEC's mechanism of action in vivo and show that in addition to its effects on the 5-lipoxygenase pathway, it targets the cyclooxygenase pathway and COX-1. Moreover, we show for the first time that inducible nitric oxide is essential for the rapid sequestration of microfilariae by DEC.
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The anthelmintic efficacy of ivermectin, a combined solution of the B1a and B1b fractions of avermectin, was assessed in a controlled trial. Twenty-four yearling calves experiencing naturally acquired, clinical gastrointestinal helminthiasis were evenly divided on the basis of weight into two 12-animal groups. The medicated group was given (subcutaneously) ivermectin at the dose rate of 200 microgram/kg of body weight. The control animals were given the vehicle alone, at an equivalent rate. All animals were killed 14 days later. At necropsy of the calves, gastrointestinal helminth arithmetic means were 178,626 and 575 for the control and the treated groups, respectively, an overall reduction of 99.7%. Nematodes which were present at substantial levels were Ostertagia ostertagi, O lyrata, Trichostrongylus axei, Cooperia punctate, C oncophora, C mcmasteri, and Oesophagostomum radiatum. Anthelmintic activity of ivermectin was excellent regardless of nematode species, sex, or stage of development.
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The study was conducted in August 2002 in Kigoyera parish in Kyenjojo district, where ivermectin treatment had been the strategy to control onchocerciasis since 1991 and was later supplemented with Simulium neavei control in 1995 and subsequent elimination; and in July 2003 in Kicece parish in Kamwenge district, where ivermectin treatment alone had been the strategy used to control onchocerciasis since 1991. Our objective was to examine and compare the impact of ivermectin treatment alone and when in parallel with S. neavei elimination on nodule and microfilariae carrier rates and on onchocercal dermatitis to provide baseline data that could be used to monitor the trends of microfilariae carrier rates for decision-making on when to discontinue ivermectin treatment. The combined interventions had significantly reduced onchocercal dermatitis from 34% pre-control to 2.9% (P < 0.001), microfilariae carrier rate from 88 to 7.5% (P < 0.001) and nodule prevalence from 49 to 19.2% (P < 0.001). Ivermectin treatment alone had also reduced onchocercal dermatitis prevalence from 34.2% pre-control to 9.5% (P < 0.001), the microfilariae carrier rate from 78 to 27.8% (P < 0.001) and nodule prevalence from 49.1 to 14.2% (P < 0.001). None of the children under 10 years were nodule or microfilariae carriers in both study areas. Histological examination of eight nodules extirpated from patients in Kigoyera identified five male and 12 female adult worms that were all old and alive. Five live and one dead female worms and one live male worm were identified from nodules extirpated from patients in Kicece. There was no female worm with embryogenesis from the nodules obtained from Kigoyera while two female worms from five nodules obtained from Kicece still showed a few embryos. Two female worms in each of the study area had sperms in uteri indicating that male worms were still active. Ivermectin treatment in parallel with vector elimination had a greater impact on onchocercal dermatitis and microfilariae carrier rates than ivermectin treatment alone. It would be worthwhile considering supplementation of ivermectin treatment with vector elimination in all isolated foci with S. neavei transmission to hasten the elimination of onchocerciasis as a public health and socio-economic problem in those foci.
A 9-week-old miniature mule foal presented to the Veterinary Medical Teaching Hospital for acute blindness, ataxia, and depression following an overdose of an over-the-counter ivermectin-based de-worming medication. Ophthalmic examination and electrodiagnostic evaluation eliminated outer retinal abnormalities as the primary cause of the bilateral blindness, implicating instead a central neurologic effect of the drug. With symptomatic and supportive care, the foal recovered fully and regained its vision.
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Calves were matched for body weight and randomly allocated to remain untreated or to receive an ivermectin sustained-release bolus before turnout on day 0. Calves were grazed by treatment group on B pastures (4 replicates). Body weights and fecal egg counts were recorded on days- 1 and 28, and then at 28-day intervals until day 168.
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Three groups of ten 4-month-old red deer (Cervus elaphus) calves naturally infected with lungworm (Dictyocaulus viviparus) were treated with either oral ivermectin (200 microg/kg), topical (pour-on) ivermectin (500 microg/kg) or oral oxfendazole (5 mg/kg). Faecal larval counts for lungworm were undetectable or very low for 14 days after treatment with oxfendazole, 28 days after treatment with oral ivermectin and for 49 days after treatment with topical ivermectin. This pilot study suggests that the topical formulation of ivermectin was very effective against lungworm and had a more persistent action than the oral ivermectin formulation in young red deer.
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Mosquitoes of different ages and blood meal history died at different frequencies after ingesting ivermectin. Mortality was lowest in 2-day old mosquitoes exposed on their first blood meal and highest in 6-day old mosquitoes exposed on their second blood meal. Twenty-four hours following ivermectin ingestion, 101 and 187 genes were differentially-expressed relative to control blood-fed, in 2 and 6-day groups, respectively. Transcription patterns of select genes were similar in membrane-fed, colonized, and naturally-fed wild vectors. Transcripts from several unexpected functional classes were highly up-regulated, including Niemann-Pick Type C (NPC) genes, peritrophic matrix-associated genes, and immune-response genes, and these exhibited different transcription patterns between age groups, which may explain the observed susceptibility differences. Niemann-Pick Type 2 genes were the most highly up-regulated transcripts after ivermectin ingestion (up to 160 fold) and comparing phylogeny to transcriptional patterns revealed that NPCs have rapidly evolved and separate members respond to either blood meals or to ivermectin.
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Dictyocaulus viviparus cause severe lung infections and are endemic in some areas of temperate and tropical countries. Treatment is based on strategic nematode control programs using potent compounds with no reports of drug failure. Macrocyclic lactones (MLs) are available at different concentrations and combinations and have being used heavily by producers. The objective of this work was to determine the efficacy of the MLs ivermectin, moxidectin, doramectin, and abamectin, and the combination ivermectin plus abamectin in naturally infected calves (n=70). Initial infection was determined by necropsy of tracer animals. Faecal larval counts determined that none of the compounds used was able to eliminate D. viviparus for up to 28 days after treatment. The "Area Nova" strain was isolated for future work.
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Ivermectin is generally well tolerated in infants. The 80% rate of healing observed in infants who had failed to respond to at least two other topical treatments suggests that ivermectin could be considered for treatment of infants with recalcitrant or relapsing scabies.
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Ivermectin, a modified avermectin, is widely known to be an ectoparasiticidal agent in animals but its effect on human ectoparasites is not known.