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Toxocara canis and Toxocara cati do not transform in human organism into a mature form and they circulate reaching various organs and tissues causing characteristic symptoms. Activated eosinophils, which play a significant role in parasitic invasion, contain in their granules eosinophilic cationic protein (ECP) of strong pro-inflammatory activity. The aim of the study was to estimate the concentration of immunoglobulin E, peripheral blood eosinophilia and serum concentration of eosinophilic cationic protein in children treated for toxocariasis and the analysis of their value as the markers of active invasion and the therapy efficacy. The study included 45 children, aged from 3 to 18 years with Toxocara canis infection diagnosed for the first time. The children were diagnosed and treated at the Department of Gastroenterology, in the Outpatient Gastrointestinal and Allergologic Clinic, Institute Polish Mother Health Centre. T. canis larva infection was diagnosed based on serological investigation using immunoenzymatic ELISA test (Bordier Affinity Products, Switzerland). The tests (percentage of eosinophilia in peripheral blood, ECP, IgE) were performed after diagnosis and every 3 months since the beginning of the therapy. In children with toxocariasis its covert form was diagnosed and mebendazole was administered. Among the children with toxocariasis eosinophilia was found in 14 (31.1%) before therapy. Mean percentage of peripheral blood eosinophils was 5.58% in children with toxocariasis. The concentration of IgE was elevated in these children and was significantly higher than in the control group (p=0.002). Mean IgE concentration after 3-and 6-month therapy decreased IgE(I) vs IgE(III) (p=0.01), but it was still higher than normal value. In children with toxocariasis the ECP concentration was 30.19 microg/l before the therapy and was significantly higher than in the control group (p<0.05); after 6 months of the therapy it decreased significantly (p<0.05). Eosinophilic cationic protein and eosinophilia can be the markers of Toxocara canis infection activity. The determination of immunoglobulin E and eosinophilic cationic protein concentration may be useful for toxocariasis therapy monitoring.
In mice immunized with staphylococcal vaccine the arresting of graft-versus-host reaction under the influence of small doses of staphylococcal vaccine, hyperimmune antistaphylococcal serum, cyclophosphamide, antilymphocytic serum has been demonstrated. Small doses of staphylococcal vaccine stimulated the production of antibodies to staphylococci and dermal extract in the animals, previously immunized with this vaccine, with the simultaneous suppression of cell-mediated immune reactions to both antigens. Immunosuppressing agents have been found to inhibit humoral and cell-mediated immune response to microbial antigen and dermal extract. No influence of vermox and levamisole on the outcome of the graft-versus-host reaction has been registered; the latter preparation has been found to intensify cell-mediated immune reactions to microbial and tissue antigens.
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Toxocarosis is a consequence of human infection by Toxocara canis larvae. There are symptomatic (visceral, ocular) and asymptomatic courses of toxocarosis. The cerebral form is very rare.
Unilocular hydatid disease occurs in humans after oral intake of eggs of the dog tapeworm, Echinococcus granulosus. Cysts develop mostly in the liver, but sometimes also in the lung. The diagnosis of Echinococcus infection is based on history-taking, physical examination, ultrasound and CT examination and serological testing; the diagnosis is confirmed by parasitological examination of cystic fluid. Treatment until some 15 years ago consisted in operation. Subsequently, treatment with initially mebendazole, later with albendazole or with percutaneous drainage (puncture, aspiration, injection of a scolicidal, respiration (PAIR)), or with combinations of the same, became accepted forms of management. The PAIR method is reported to give high proportions of success, low proportions of recurrence and few complications. However, adequate evaluation is not yet possible because of the short follow-up period. For the prevention of leakage it is recommended to perform the PAIR method with a transhepatic puncture under continuous ultrasonographic or CT guidance; for avoidance of recurrences, one week's pretreatment and 1-4 weeks' after-treatment with albendazole are recommended. The results of albendazole monotherapy are hard to predict and highly variable: success: 30-88% (median: 71%); failure: 22-32% (median: 25%); recurrences: 9.5-31% (median: 16%). Both albendazole therapy and the PAIR management should be followed by protracted follow-up to check regression of cysts and detect recurrences. It is not clear which treatment is the best one.
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Ketoconazole, an orally active antifungal drug, is known to inhibit testicular androgen production both in vitro and in vivo. The aim of the present study was to examine the effect of ketoconazole and 13 other imidazole drugs on rat testicular microsomal 17 alpha-hydroxylase, 17,20-lyase, 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-I) and 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR). The order of decreasing inhibitory effect (determined from Ki values) on 17 alpha-hydroxylase (substrate [3H]progesterone; Km = 89 +/- 0.65 nmol/l; SEM, n = 8) was bifonazole (Ki = 86 +/- 3.3 nmol/l; SEM, n = 4) greater than ketoconazole (160 +/- 4.92) greater than clotrimazole (170 +/- 5.81) greater than miconazole (599 +/- 7.22) greater than econazole (688 +/- 6.98) greater than tioconazole (901 +/- 1.71) greater than isoconazole (1090 +/- 6.96) and on 17,20-lyase (substrate, [3H]17 alpha-hydroxyprogesterone; Km = 250 +/- 0.75 nmol/l; SEM, n = 8) was bifonazole (56.5 +/- 3.4) greater than clotrimazole (81.5 +/- 3.1) greater than ketoconazole (84 +/- 3.5) greater than miconazole (243 +/- 6.3) greater than econazole (325 +/- 5.1) greater than tioconazole (505 +/- 5.2) greater than isoconazole (610 +/- 6.34). However, these imidazole drugs did not inhibit the 3 beta-HSD-I or 17 beta-HSOR activities. A common structural feature of the imidazole drugs having an inhibitory effect was the presence of one or more aromatic rings on the imidazole side chain. In contrast, the imidazole drugs having the imidazole ring fused to a benezene ring, i.e. benzimidazoles (astemizole, mebendazole, thiabendazole) and those having an aliphatic side chain on the N-1 of the imidazole ring (carbimazole, metronidazole, nimorazole, tinidazole) did not inhibit 17 alpha-hydroxylase, 3 beta-HSD-I or 17 beta-HSOR enzyme activities. However some did inhibit 17,20-lyase activity but only at high concentrations. The results of the present study suggest that some imidazole drugs may be useful in clinical situations requiring the suppression of androgen production, for example in the treatment of hormone-dependent prostatic cancer.
Soil-transmitted helminths (STHs) are the most prevalent intestinal helminths of humans, and a major cause of morbidity in tropical and subtropical countries. The benzimidazole (BZ) drugs albendazole (ABZ) and mebendazole (MBZ) are used for treatment of human STH infections and this use is increasing dramatically with massive drug donations. Frequent and prolonged use of these drugs could lead to the emergence of anthelmintic resistance as has occurred in nematodes of livestock. Previous molecular assays for putative resistance mutations have been based mainly on PCR amplification and sequencing. However, these techniques are complicated and time consuming and not suitable for resource-constrained situations. A simple, rapid and sensitive genotyping method is required to monitor for possible developing resistance to BZ drugs.
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Plasma mebendazole levels were analysed retrospectively in patients treated for inoperable infections with Echinococcus multilocularis or granulosus. In 10 patients receiving mebendazole at 4 dose levels there was no relation between dose and plasma concentration. In 17 patients followed on the same dose for more than 18 months, the plasma levels varied with individual coefficients of variation ranging from 27 to 72%. The data reveal the limitations of single measurements of plasma mebendazole and emphasize the need for repeated monitoring. Coadministration of phenytoin and carbamazepine seemed to lower plasma levels, presumably as a result of enzyme induction. It was not possible appreciably to raise the mebendazole concentrations by inhibition of drug metabolizing enzymes with cimetidine.
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Benzimidazoles, namely albendazole (ABZ) and mebendazole, are the only drugs licensed for the treatment of inoperable alveolar echinococcosis. In addition, amphotericin B (AMB) has shown effect against Echinococcus multilocularis as salvage treatment in humans. Both benzimidazoles and AMB are only parasitostatic against E. multilocularis and toxicity may limit long-term use. In the present study we examined the effect of combined treatment between ABZ and AMB on E. multilocularis larvae in an in vitro model. Vesicles were grown in a tissue culture model of metacestodes and hepatocytes. Drugs were added to the culture and the destructive effect on the vesicles was visually observed. Sequential application of ABZ and AMB yielded effective destruction of vesicles which was faster than the application of AMB alone. However, simultaneous application of ABZ and AMB had an inhibitory effect on vesicle destruction. After discontinuation of drug application, regrowth of vesicles occurred, hereby proving the parasitostatic effect of combined treatment against E. multilocularis larvae. Due to an inhibitory effect between ABZ and AMB against E. multilocularis larvae, we discourage from the simultaneous application of both drugs. If our in vitro results hold true in vivo, sequential application of ABZ and AMB would be an effective means for long-term suppression of larval growth. Long-term tolerance of both drugs could be improved by a reduction of side effects.
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We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the Trichuris muris model. Drug combinations were first tested in vitro and additive and synergistic combinations investigated further in vivo in female mice using ratios based on the ED50 of the respective drugs.
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Praziquantel could reduce the motor activity of the worms rapidly which resulted in detachment of oral sucker from the well wall, curl of the worm body and emergence of vacuoles from the tegument. The minimal concentration of praziquantel to kill adult C. sinensis was 0.1 g/ml. After adult C. sinensis exposed to tribendimidine at concentrations of 0.5, 1 and 10 g/ml, they revealed in paralysis, looseness and stretch of the worm body rapidly or immediately. The minimal concentration of tribendimidine to kill adult worms was 0.05 g/ml. When worms exposed to levamisole at 10 and 20 g/ml, there was a gradual decrease in the worm's motor activity accompanied by looseness of the worm body. But 48 h post exposure, most worms showed apparently recovery of motor activity. In a higher levamisole concentration of 50 g/ml, all worms revealed in stretch and paralysis which was similar to that induced by tribendimidine. When adult C. sinensis were exposed to artemether or artesunate 10 and 50 g/ml, the motor activity of worm body and oral sucker reduced which accompanied by worm contraction, then followed by looseness of the worm body and emergence of vacuoles along the tegument. At 72h post exposure, the worm mortalities induced by the two concentrations of the two drugs were about half, respectively. In adult C. sinensis exposed to albendazole and mebendazole at concentrations of 10 and 50 g/ml, only stimulation of motor activity of oral sucker was seen which revealed in vigorous contraction within 24 h post exposure. During 72 h observation period, no any other changes in worm activity and morphology were seen.
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The need to identify improved therapy against cystic echinococcosis (CE) has motivated pharmacology-based research. The comparative pharmacological performances of the benzimidazole compounds flubendazole (FLBZ) and albendazole (ABZ) were addressed here. The goals of the work were as follows: (i) to evaluate the ex vivo activities of FLBZ, ABZ, and their respective metabolites against Echinococcus granulosus protoscoleces, (ii) to compare the plasma and cyst disposition kinetics for the two drugs in infected mice, and (iii) to compare the clinical efficacies of FLBZ and ABZ against CE in mice. For the ex vivo study, E. granulosus protoscoleces were incubated with FLBZ, reduced FLBZ (R-FLBZ), ABZ, and ABZ-sulfoxide (ABZSO) (10 nmol/ml). Protoscolex viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). For the pharmacokinetic study, BALB/c mice with CE were allocated to two different groups and orally treated with either FLBZ or ABZ (5 mg/kg of body weight), both formulated as a cyclodextrin-based solution. Blood and cyst samples were taken up to 12 h posttreatment and analyzed by high-performance liquid chromatography (HPLC). For the efficacy study, CE-infected BALB/c mice were divided into three groups: the unmedicated control group and the FLBZ- and ABZ-treated groups. Oral treatments were performed twice a day during 25 days. After treatment, all animals were killed and the weight of the cysts was recorded. Loss of protoscolex viability was observed after drug incubation. FLBZ was detected in plasma (area under the concentration-versus-time curve [AUC] = 1.8 μg · h/ml) and cysts (AUC = 0.3 μg · h/g) collected from treated infected animals. Conversely, ABZSO was the only active molecule measured in plasma (AUC = 4.4 μg·h/ml) and cysts (AUC = 1.5 μg·h/g) after ABZ treatment. FLBZ induced a 90% reduction in cyst weight in comparison to those collected from untreated control mice (P < 0.05). However, no differences in cyst weight were observed between the ABZ-treated (8.2 g) and unmedicated control (10.5 g) groups. Due to these results, we consider flubendazole to have great potential to become a drug of choice in the treatment of cystic echinococcosis.
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The effects of albendazole, its sulphone metabolite and mebendazole on the viability of Echinococcus granulosus protoscoleces in vitro were investigated. Significant reductions in viability occurred in cultures treated with albendazole parent compound at 100 micrograms/litre, but lower concentrations were ineffective. The sulphone metabolite of albendazole had no significant effect at concentrations of 50 and 100 micrograms/litre over periods of up to 71 days. Mebendazole induced significant reductions in viability at 100 micrograms/litre.
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Urupá, a rural community in Western Brazilian Amazon.
Intensity of Ascaris lumbricoides infection was measured in terms of egg counts and worm burden in children 2-10 years of age. The expulsion of A. lumbricoides with a 3-day treatment of mebendazole occurred over 8 days, beginning on the second day of treatment. Ninety-seven percent of the worms were expelled between the second and seventh days. A rapid means of estimating eggs per gram (epg) by the Kato Katz technique correlated well with the method described by Martin & Beaver (1968). In spite of apparent density dependence in egg production, A. lumbricoides egg counts correlated well with worm burdens. It is concluded that, within the context of community surveys, epg is a reasonable means of identifying heavily infected individuals and that epg can be estimated rapidly by a slight modification to the standard Kato Katz technique.
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The immunological responses in hamsters during treatment with mebendazole against Ancylostoma ceylanicum are studied. Indirect haemagglutination (IHA) counterimmunoelectrophoresis (CIEP), passive cutaneous anaphylaxis (PCA), foot pad swelling for immediate (ITH) and delayed (DTH) types of hypersensitivities were employed for measuring the responses. Serum antibody which was 1:32 before treatment increased to the maximum of 1:512 (control 1:128) on the 10th day and it declined subsequently. The CIEP test was positive for 10 days and then became negative. The PCA test was positive throughout the observation period both in the treated and untreated groups. Foot pad swelling for ITH and DTH responses were comparatively more prominent than in the untreated control up to the 20th day and then both decreased simultaneously. The immunological responses remained prominent for a longer period and decreased more slowly in the untreated control group.
Experimental study with a randomised design.
Levamisole and mebendazole, broad spectrum anthelminthic compounds were tested against microfilaria of Wuchereria bancrofti, and the results were compared with similarly treated diethylcarbamazine and untreated group. Levamisole at a dosage of 3 mg/kg daily for 8 days showed marked reduction in both microfilaria rate and microfilaria density and immediately thereafter mf-rate steadily increased almost up to pre-treatment level, the mf-density however showed only marginal increase. Mebendazole at dosage of 6 mg/kg daily for 10 days following 8 days treatment of levamisole also showed marginal increase of mf-rate but no increase of mf-density. Treatment with DEC at a dosage of 6 mg/kg daily for 12 days showed comparatively better results both in respect of reduction in mf-rate and mf-density. The reactions - severity and duration were more among levamisole treated groups as compared to DEC treated group. Thus with the dosages tried, DEC could be considered as a better drug than levamisole and mebendazole. Both the latter compounds had no or very limited effect on the adult worms of W. bancrofti.
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Anisakiasis is a very rare infection in Germany. In single cases, a history of the place of work may be helpful in diagnosis. Usually the larva penetrate into gastric or intestinal mucosa. The case presented here illustrates the possibility of an anisakiasis infection in severe and otherwise unexplainable segmental colitis, especially with a history of a possible ingestion of raw fish.
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Conservative management and long term follow up are proposed for the non-active or mebendazole-responsive patients. For the non-respondents or the cases with kidney destruction, surgery is the only hope for cure.
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All stray dogs (8) in the vicinity of the temple were treated, with mebendazole (100 mg) crushed and filled into sausages, 10 days before the commencement of festival in 2011. The same procedure was repeated a week later to ensure complete coverage. A cross-sectional study was conducted among 200 systematically selected devotees in August 2011 using an interviewer-administered questionnaire and the clinical examination of the skin. Baermann's technique was used for the recovery of nematode larvae from 40 soil samples collected from the temple premises. Ten samples of dog faeces collected from the same premises were also examined for nematode eggs. Prevalence of CLM among devotees in 2010 (Pre intervention) and 2011(Post intervention) were compared to test the hypothesis. Prevalence of CLM declined from 58% to 8% (Chi-square = 112.90, p<0.001) following the intervention. None of the subjects practiced new precautionary measures compared to the previous year. Soil and fecal samples were negative for parasites.
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Mebendazole, a benzimidazole carbamate compound, is currently in use for human medical practice against soil-transmitted helminthiasis (STH) and enterobiasis. However, it has been demonstrated that its spectrum of activity is broad and goes beyond those infections. Several studies provide evidence that this drug, taken at higher doses than used for STH and enterobiasis, could be sufficiently effective on some protozoa, nematodes and cestodes.
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The first part of this study was conducted between November 2005 and February 2006 in Miaoli County. 44,071 primary schoolchildren from 18 districts were examined by 2 consecutive-day adhesive cellophane perianal swabs to estimate the infection rate. The second part was performed between October 2006 and January 2007 in Taichung County. 24,382 primary schoolchildren from 14 districts were examined.
The efficacy of mebendazole and pyrantel pamoate was studied in two groups of 59 and 58 cases, respectively, of patients with polyparasitosis. Mebendazole had a cure rate of 96%, 82.2%, 71.4% and 66.6% in A. lumbricoides, hookworm, T. trichiura and S. stercoralis, respectively, while the corresponding figures for pyrantel pamoate were 92.6%, 85.7%, 19.4% and 0%. Pyrantel pamoate is considered to have no significant effect on T. trichiura and S. stercoralis. None of the drugs had any effect on T. saginata. Both drugs have been found to be equally effective against enterobiasis by various authors. It is recommended that pyrantel pamoate be the drug of choice in cases of multiple parasitic infections excluding T. trichiura and S. stercoralis whereas those with one or both of these in addition to others should be treated with mebendazole. Mebendazole can be prescribed for patients with clinical evidence of helminthic infections even where stool examination is not possible as it covers almost the whole range of common helminthic infections. The only limitation for poorer patients however is its cost. Pyrantel pamoate has a wider applicability for the poorer patients in spite of the fact that it is ineffective against trichurids and S. stercoralis.
The assessment of a ten-year clinical trial of continuous therapy in eight patients revealed further evidence of a significant therapeutic effect of mebendazole on alveolar hydatid disease. Life-expectancy was increased when compared to untreated historical controls, especially in the patients over 55 years of age. All symptomatic patients showed subjective improvement. In four patients, three had a 50% or greater reduction in the diameter of massive hepatic lesions, and in the fourth, progressively enlarging metastases were arrested. Fall in the IHA titre suggested that the causative organism had been destroyed in two additional patients. Of greater significance was the absence of progression of the disease process as measured by changes in the size of the hepatic lesion or lack of development of distant metastases in patients under therapy. In contrast, progressive enlargement of hepatic lesions or the appearance of distant metastases were cardinal features of untreated cases (15 of the 16 cases followed). In vivo determination of viability of tissues of the larval Echinococcus multilocularis from patients receiving long-term therapy was considered important in evaluating efficacy of the drug. Such tissues, obtained by autopsy from two patients under continuous therapy for four and ten years, failed to proliferate when inoculated into rodents (red-backed voles), whereas similar inoculations from untreated patients or those receiving 15 months' or less of therapy brought about production of vesicles in rodents in eight of 11 tests (73%). These two deaths, unrelated to therapy, resulted from late fibrotic constriction of end-stage parasitic lesions about the portal vein and major bile ducts. The clinical findings in combination with negative in vivo tests and other data indicate that the mebendazole therapy significantly alters the clinical course of alveolar hydatid disease. The evidence strongly indicates that long-term therapy may eventually have a lethal effect on the larval cestode in advanced disease.
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Three patients had viable, noninfected, echinococcal cysts of the lung unintentionally diagnosed by percutaneous transthoracic aspiration without deleterious effects. Although aspiration generally should be avoided in hydatid disease because of the possibility of allergic reaction or spread of disease, neither of these potentially adverse effects was seen. Cystobronchial communication was produced iatrogenically in all three cases. The patients were followed for up to 3 years 2 months. Two patients were treated with mebendazole. The pathologist should be alerted when clear colorless fluid is withdrawn from a chest mass because the scoleces of Echinococcus granulosus may be missed on routine staining.
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Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management.
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Curative surgery for AE is feasible if parasitic tissue is entirely removable. The benefit of palliative resections is uncertain because long-term results of conservative treatment are favorable. Palliative surgery is an option for complications not being manageable otherwise.