A sequential biopsy sampling method was used to investigate oxidant and antioxidant gene responses in resistant sheep challenged with Haemonchus contortus larvae or a sham saline challenge. The expression of key sheep oxidant and antioxidant producing genes were measured in sequential samples removed from the abomasums at days 0, 1, 2, 3, 5, 7 and 28 post challenge. Gene expression levels at each time point were compared to expression at day 0, and levels of the various genes were also correlated to other markers of infection including immune cell counts and cytokine gene expression. The early response to larval challenge infection in resistant animals was marked by a divergence of two groups of host oxidant producing genes: the dual oxidase group (DUOX2/DUOXA2) showing increases in expression to day 7, while members of the phagocytic NADPH oxidase (PHOX) group showed significant decreases in expression. The change in DUOX2 expression between days zero and seven, when host resistance to infection is mediated, was negatively correlated to final worm burden suggesting NADPH oxidase expression may play a role in parasite expulsion. Expression of the DUOX group oxidants was positively correlated to expression of the Th2 cytokine IL4. Changes in host antioxidant pathways between different members of the glutathione peroxidase family (intestinal and plasma GPX) and genes involved in glutathione metabolism were also observed. This first study of the putative roles of oxidant production by the dual oxidase group, antioxidant glutathione pathways, immune cell populations, and cytokine profiles, in the development of resistance to infection by hyperimmune sheep are discussed.
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Ivermectin 1% cream (Soolantra(®); Rosiver™; Izefla(®)) is a novel topical agent indicated for the once-daily treatment of inflammatory lesions of rosacea. Ivermectin is a derivative of the avermectin family of macrocyclic lactone parasiticides. It displays anti-inflammatory properties as well as broad-spectrum anti-parasitic activity, both of which may contribute to its efficacy in treating rosacea. In phase III trials of 12 or 16 weeks' duration in adults with moderate to severe papulopustular rosacea, once-daily ivermectin 1% cream improved the symptoms of rosacea (as per Investigator Global Assessment and inflammatory lesion count) and health-related quality of life versus vehicle, and was more effective than twice-daily metronidazole 0.75% cream in terms of these measures. Ivermectin 1% cream continues to provide benefit for up to 52 weeks of treatment, according to extension studies, and is well tolerated, with the most common treatment-related adverse events (skin burning sensation, pruritus, dry skin and skin irritation) each occurring with low incidence (<2%). Thus, ivermectin 1% cream is an effective and well tolerated option for the topical treatment of inflammatory lesions of rosacea, with the convenience of once-daily application.
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Detailed epidemiological mapping of three isolated foci of hyperendemic blinding onchocerciasis was undertaken in three West African countries as part of community trials of ivermectin, a new microfilaricide for the treatment of human onchocerciasis. The results show that the geographical distribution of the prevalence and intensity of onchocerciasis infection in the community can be very different from what was expected on the basis of demographic and entomological information. The technique of detailed epidemiological mapping is an important tool for the identification of target populations for large scale ivermectin treatment of onchocerciasis. It is being used extensively in the Onchocerciasis Control Programme in West Africa.
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Community-directed treatment with ivermectin expanded from 1968 communities in 2001 to 39 100 communities by 2012 while the number of community-directed distributors (CDD) and health workers (HW) multiplied. By 2012, there were ratios of 1 CDD per 262 persons and 1 HW per 2318 persons at risk. More than 80% of the funding came from the fiduciary funds of the African Programme for Onchocerciasis Control. The cost of treatment per person treated fell from US$ 1.1 in 2001 to US$ 0.1 in 2012. The therapeutic coverage increased from 2.7% (2001) to 74.2% (2012); the geographical coverage, from 4.7% (2001) to 93.9% (2012). Geographical coverage fell in 2005 due to deaths in loiasis co-endemic areas, and the therapeutic coverage fell in 2008 due to insecurity.
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This study shows that the study area is now hypo-endemic for onchocerciasis, following 6 years of continuous treatment with ivermectin. Careful monitoring of onchocerciasis should however be continued to avoid that the area returns to its initial hyper endemicity.
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Ivermectin is an effective and safe treatment for scabies, particularly in a closed community, such as a prison, where it is easy to administer and avoids problems with compliance. It was of limited efficiency in crusted scabies as a single dose and we recommend that for such patients oral ivermectin is used in combination with a topical scabicide.
Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children.
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Infection with O. volvulus does not affect the pharmacokinetics of ivermectin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of depot formation in fat tissue.
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A new macrolactam, fluvirucin B0 (1), and two known macrolactams, Sch 38516/fluvirucin B1 (2) and Sch 39185/fluvirucin B3 (3), have been isolated from an acetone extract of a strain of Nonomuraea turkmeniaca. These compounds were isolated by bioassay-guided fractionation as part of our search for new anthelmintics. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported fluvirucins, and confirmed by 2D-NMR. 1approximately 3 exhibited in vitro activity (EC90 <1.0 approximately 1.7 microg/ml) against Haemonchus contortus larvae, but were ineffective in reducing worm counts in vivo against Heligmosomoides polygyrus in mice at 50 mg/kg dosed intramuscularly.
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Lymphatic filariasis continues to cause severe morbidity and economic loss. The World Health Assembly (WHA) has passed a resolution to eliminate this disease by 2020. The major thrust of the elimination strategy is interrupting transmission by anti-parasitic treatment of entire communities. However, both vector density and community microfilaria load (CMFL) influence the intensity of transmission. Therefore, using a logistic regression approach a relationship has been established between the Risk of Infection Index (RII), vector density and CMFL. The present analysis indicates that there is no risk of transmission as long as the CMFL is maintained below 5 microfilaria (mf)/60 mm3 and the vector density per man-hour (MHD) is 25 and CMFL is <5 mf/60 mm3. In situations where CMFL is very high, parasitic control by mass administration may be cost effective in interrupting transmission. But at lower level of CMFL (<4 mf) and higher level of vector density it might be more cost effective to use vector control methods. A RII value <0.2 is considered to be the threshold for confirming interruption of transmission. Thus, the relationship has been depicted in the form of a probability matrix, which could be used for selecting an appropriate control strategy.
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Ten 'high risk' communities along the River Mayo Douka system in Ngong Health District, at least 20 km from the nearest CDTI program were studied. Six hundred and forty-nine adults (over 20 years of age) and 561 children (under 10 years) were examined for nodules and microfilaria. A subsample of 334 adults was examined for onchocercal ocular morbidity. Simulium flies from 4 collection points were captured over 3 months annually for 2 years and dissected for larval stages of O. volvulus.
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Human myiasis is the parasitism of human tissues by fly larvae. Diagnoses are based on clinical pattern of tissue damage and presence of insect stages. Herein, a case myiasis is described in a seven-year-old female child. She presented with fever associated with abscessed scalp lesions containing exposed larvae. Severe pediculosis was also observed. The patient was hospitalized and treated with clindamycin, gentamicin (for bacterial secondary infections) and ivermectin (treatment for lice) after which the patient showed clinical improvement and was discharged four days later. Since human myiasis can be caused by a number of different species, larvae were collected from the patient and identified as those of Cochliomyia hominivorax (Diptera: Calliphoridae). Because other cases of coinfestation of flies and lice are on record, health workers are to be alerted about the possible pediculosis-myasis risk.
The normal time interval between treatment of horses with a macrocyclic lactone (ML) and reappearance of strongyle eggs in the feces, or 'Egg Reappearance Period (ERP)', is at its shortest 8 weeks for ivermectin (IVM) and 12 weeks for moxidectin (MOX). Nowadays, it is not uncommon to find shorter ERPs, potentially indicating the beginning of the development of drug resistance. Whether all cyathostomin species contribute equally to a shortened ERP is not known. In the present study a Reverse Line Blot (RLB) on individual infective larvae was used to compare species composition before and after ML-treatment in horses with either a normal or a shortened ERP. Species composition was determined for a total of 21 horses on 4 farms and was based on differentiation of approximately 40 larvae per horse per sampling day. After IVM treatment the shortest ERP was found to be 28-42 days. After MOX treatment the shortest ERP was found to be 42-56 days. The RLB showed that early egg shedding was dominated by species of the genus Cylicocyclus (Cyc.) (Cyc. ashworthi, Cyc. insigne, Cyc. leptostomum and Cyc. nassatus). Before treatment, species composition was generally more diverse with species from several other genera also present. Interestingly, on the farm with the overall shortest ERP and where all horses showed a shortened ERP, more species/genera were present during early egg excretion than on other farms. Results suggest that cyathostomin species within the genus Cylicocyclus contribute to a shortened ERP more than species from other genera. However, if shortening of ERP overall becomes more pronounced and widespread within a farm, species from other genera will also be present during early egg shedding.
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Loiasis, which is caused by the filarial nematode Loa loa, affects millions of persons living in the rainforest areas and savannah regions of central Africa. Typical manifestations are calabar swellings and the eyeworm. We report a case of loiasis with unusual clinical complications: a peripheral neuropathy and focal hypo-echogenic lesions of the spleen, which disappeared after treatment with albendazole and ivermectin. The literature reports that L. loa infection can be associated with various manifestations, some of them being serious. More information is needed to better characterize the protean manifestations of the disease in loiasis-endemic areas to evaluate the true incidence of loiasis.
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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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Since 2007 Sierra Leone has conducted mass drug administration (MDA) for the elimination of lymphatic filariasis (LF) implemented by unpaid community health volunteers (CHVs). Other health campaigns such as Mother and Child Health Weeks (MCHW) pay for services to be implemented at community level and these persons are then known as community health workers (CHWs). In 2010, the LF MDA in the 12 districts of the Southern, Northern and Eastern Provinces un-expectantly coincided with universal distribution of Long Lasting Insecticide Treated Nets (LLITNs) during the MCHW. In-process monitoring of LF MDA was performed to ensure effective coverage was attained in hard to reach sites (HTR) in both urban and rural locations where vulnerable populations reside.
Twelve naturally infected sheep were selected and divided into 2 subgroups: treatment group (n = 9) and control group (n = 3). In the treatment group, approximate volume of ivermectin solution needed to achieve an intracystic concentration of 10 microg/mL was injected into cysts, but in the control group, sterile distillated water was applied. No reaspiration was performed at all.
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We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis).
The present study aimed to evaluate the persistent efficacy of a 3.5% doramectin(*) (700 μg/kg) formulation compared to 3.15% ivermectin(**) (630 μg/kg) treatment, administered subcutaneously at a dose of 1 mL/50 kg body weight in cattle experimentally infected with gastrointestinal nematodes. Seventy-two male crossbred Holstein cattle that were negative for helminth infection were divided into nine groups. Treatments of 3.5% doramectin (Groups 2, 4, 6 and 8) and 3.15% ivermectin (Groups 3, 5, 7 and 9) were administered on days 49, 42, 35 and 28 prior to challenge with infectious nematode larvae (L3). Animals in the control group (Group 1) received saline solution on day 49 before challenge. Beginning on day zero, each animal received 50 mL orally of a mixed culture containing approximately 3,000 third stage larvae (L3) of Haemonchus (60%), Oesophagostomum (20%), Cooperia (15%) and Trichostrongylus (5%) for seven consecutive days, resulting in a total challenge of 21,000 larvae/animal. Due to the large number of cattle, autopsies were performed between days 28 and 35 after the last day of inoculation. The formulation containing doramectin (700 mcg/kg) achieved persistent efficacy against H. placei and C. punctata for 49 and 35 days, respectively. The persistent efficacy of ivermectin (630 mcg/kg) against H. placei lasted for 49 days, but this treatment was ineffective against C. punctata. Both formulations demonstrated persistent efficacy against T. axei for 49 days. The persistent efficacy of doramectin (700 mcg/kg) and ivermectin (630 mcg/kg) lasted for 49 and 42 days against O. radiatum, respectively.
Of the 40 Collies, 9 (22%) were homozygous for the normal allele (normal), 17 (42%) were heterozygous (carrier), and 14 (35%) were homozygous for the mutant allele (affected). Pedigree analysis revealed that some, but not all, affected dogs were related to each other within the 4 most recent generations.
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We treated 125 patients with strongyloidiasis (78 males and 47 females) by 2 oral doses of ivermectin (6 mg) at 2-week interval, and obtained the following results: 1. Eradication rate after treatment was 86.4% (108 of 125 patients), responsively. Out of the total 17 patients were resistant (non-responsive) to treatment, 8 patients received a further course of ivermectin and all Strongyloides stercoralis in their feces were eradicated. 2. Side effects were observed in 7.2% of the patients after the first dose treatment and in 3.2% after the second dose. But all symptoms were mild and self-limited. Although liver disfunction developed in 13.6% of the patients, no symptoms occurred and no special treatment was required. 3. Positive rate of anti-HTLV-I antibody in the resistant group was significantly higher (80.0%) than in the eradicated group (29.2%) and in the stool-negative group (0%). 4. Although eosinophils before treatment in the eradicated group was significantly higher than that of controls, there was no significant difference between the resistant group and controls. IgE levels in the resistant group was significantly lower than in the eradicated group. We would like to conclude that IVM is the best drug for treatment of the patient with Strongyloides stercoralis not only from this results but also our previous reports which had investigated the clinical efficacy on thiabendazole, mebendazole and albendazole.
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Ivermectin is a worldwide-used antiparasitic drug largely administered to cattle as a topical formulation (pour-on). The actual plasma and faecal disposition of pour-on ivermectin in cattle was documented using an original pharmacokinetic model, and taking into account the oral ingestion of the topical drug following physiological licking as a secondary route of exposure. Six pairs of monozygotic twin cattle received successively one i.v. and two pour-on administrations of ivermectin at a 3-5-month interval. For one pour-on administration, the twins were separated into an unrestrained group and a group where self- and allo-licking were prevented. Ivermectin concentrations in the plasma and faeces were determined by HPLC. Licking resulted in a high intra-and inter-individual variability of systemic exposure after topical application. By the means of pharmacokinetic modelling, we showed that 58-87% of the pour-on dose was ingested, while only 10% was absorbed percutaneously. Approximately 72% of the ingested ivermectin transited directly into the faeces, resulting in a 7-fold higher faecal excretion of the parent drug than in the non-lickers. We conclude that topical administration does not guarantee a controlled drug delivery in cattle. More importantly, the simulations revealed that non-treated cattle could get easily contaminated by allo-licking, raising the public health problem of unexpected drug residues in edible tissues.