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Preventive chemotherapy of schoolchildren against soil-transmitted helminths (STHs) is widely implemented in Rwanda. However, data on its actual efficacy are lacking. We assessed prevalence, associated factors and manifestation of STH infection among schoolchildren in southern highland Rwanda as well as cure and reinfection rates.
The binding and inhibitory properties of 11 benzimidazoles for bovine brain tubulin were investigated. The effects of the benzimidazoles on the initial rates of microtubule polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (I50) for nocodazole, oxibendazole, parbendazole, mebendazole and fenbendazole ranged from 1.97 . 10(-6) to 6.32 . 10(-6) M. Benomyl, cambendazole and carbendazim had I50 values from 5.83 . 10(-5) to 9.01 .10(-5) M. Thiabendazole had an I50 value of 5.49 . 10(-4) M. Inhibitor constants (Ki) were determined by the colchicine binding assay. Oxibendazole, fenbendazole, and cambendazole had Ki values of 3.20 . 10(-5), 1.73 . 10(-5) and 1.10 . 10(-4) M, respectively. Oxibendazole and fenbendazole were competitive inhibitors of colchicine. In contrast, cambendazole was a noncompetitive inhibitor of colchicine. The ability of these benzimidazoles to inhibit microtubule polymerization and the mode of action for the anthelmintic benzimidazoles is discussed.
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Brugia malayi microfilaraemic patients were treated with either mebendazole 500 mg thrice daily for 21 days or a combination of a similar dose of mebendazole with levamisole hydrochloride 2.5 mg/kg weekly for 3 weeks. Although both regimes were effective, the addition of low doses of levamisole to mebendazole hastened the conversion of all patients to amicrofilaraemia, this being achieved by the second post-treatment week. No serious side reaction was encountered in the use of this high dose of mebendazole. Further experimental studies are necessary to determine whether the drug is adulticidal or only embryostatic.
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The number of children per family and the frequency of washing linen and cleaning bedclothes were the most important factors for transmission of pinworm infection among the groups surveyed.
The secretion of acetylcholinesterase (AChE) by female and male Heligmosomoides polygyrus was studied in different in vitro culture media. AChE secretion was increased in the presence of fetal calf serum or bovine serum albumin (BSA). In the absence of crowding effects, specific AChE activity in excretion/secretion products was higher for male (2.41 +/- 0.07 mumol min-1 l-1 mg-1) than for female (0.56 +/- 0.04 mumol min-1 mg-1) worms but on a per nematode basis both sexes showed comparable rates of secretion. Acetylthiocholine iodide was the favoured substrate of the enzyme. When the nematodes were incubated in vitro with albendazole (ABZ), ricobendazole (RBZ), mebendazole (MBZ), levamisole (LVM), morantel (MRT) or ivermectin (IVM), at concentrations from 1 mM to 10 nM, in RPMI medium for 2 or 6 h and then transferred to a drug-free medium (RPMI medium supplemented with 0.5% BSA) for 24 h or continuously exposed to the drugs in supplement-free medium (24 h), the concentration- and time-dependent inhibitory effects on AChE secretion were observed. The continued exposure to the drugs for all incubation periods (with a single exception for LVM 1 mM) produced the highest levels of inhibition. Under these conditions, the concentrations inhibiting the secretion of AChE by 50% (IC50) relative to drug-free controls were estimated. The IC50 values ranged from 0.012 microM (IVM) to 2.96 microM (MRT). The potential of this bioassay for the selective primary evaluation of new compounds with broad-spectrum anti-nematodal activity is discussed.
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The charts of 39 consecutive patients who underwent surgery between 1979 and 1989 with a diagnosis of alveolar hydatid disease (AHD) of the liver were reviewed. The analysis of these cases from eastern Anatolia, which is the endemic region in Turkey, was undertaken to determine the current experience for AHD lesions. Of these patients, 33 (84.6%) had unresectable disease and the remaining six patients (15.4%) were treated by hepatic resection of the primary lesion. In the unresectable cases, laparotomy with biopsy was the most commonly used surgical procedure (56.4%), followed by tube drainage of the necrotic cavity (18.0%), marsupialization (5.1%), and cystojejunostomy (5.1%). Diagnostic studies and operative findings were useful in detecting the AHD lesions. Differential diagnosis was established mainly by histopathologic examination of a biopsy specimen or resected tissue. Pulmonary metastases were seen in two cases, and mortality occurred due to brain metastases in two other cases. Mebendazole was administered postoperatively to 19 patients with indications for 1) advanced AHD, 2) adjuvant therapy to radical and palliative surgical procedures, and 3) recurrences of disease after hepatic resection. The patients were treated with daily doses of approximately 50 mg/kg for periods of one and six years (median 3.2 years). Encouraging results were obtained in 11 of nineteen patients. Five-year survival was seen in 8 of the patients with AHD in this series. There were 18 deaths (46.2%) in our 39 patients. Long-term follow-up was not possible in four cases, and 17 patients (43.6%) were still living. The causes of mortality were advanced AHD in 14 cases, brain metastases in two, and acute myocardial infarction in another two.(ABSTRACT TRUNCATED AT 250 WORDS)
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A 13-yr-old boy was admitted because of persistent fever, abdominal pain and diarrhea for 3 mo. Abdomen CT revealed hepatomegaly and multiple nodular low-density pathological changes. At laparotomy considerable yellow and turbid ascites were seen in the abdominal cavity and miliary nodules were noted on the surface of the omentum majus, liver, and small intestine wall. Histological examination revealed parenchymal tubercles containing several worms. Pathological diagnosis was parasitic granuloma. These parasites were identified as Porocephalus taiwana sp.nov. The patient made an uneventful recovery after therapy and was discharged. Moreover, another 17 cases of human pentastomiasis reported from China were reviewed. Human pentastomiasis is an extremely rare disease and this is only the second case of human Porocephalus taiwana sp.nov infection. Pentastomiasis should be considered in differential diagnosis of patients with a history of abdominal symptoms and eating of poorly-cooked snakes.
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Resistance to benzimidazoles (BZs) in parasitic nematodes has recently been shown to be due to a reduction in the ability of BZs to bind the structural protein, tubulin, in resistant isolates. Based on these observations the development and standardisation of a routine diagnostic assay has been undertaken by measuring the binding of tritiated mebendazole to crude supernatants of L3 larvae. The assay is rapid, requiring less than 2 h, and is robust, highly reproducible and sensitive to minor changes in the resistance status of parasite populations. Investigation of the routine application and validity of this assay has been documented using 24 isolates of known resistance status from the species Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia circumcincta: In all cases the observed binding and calculated susceptibility factors were in accordance with their respective resistance status.
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Mansonella perstans filariasis is widely present in Africa and equatorial America and its pathogenicity has recently been reconsidered. Effective treatment is lacking and there is no consensus on the optimal therapeutic approach. The aim of this study was to compare the effects of different drug regimens on M. perstans infection. Six different anthelminthic therapeutic protocols were undertaken on 165 subjects with M. perstans infection and their effects on microfilariae burden were evaluated. Diethylcarbamazine (DEC) was able to reduce microfilariae density in the majority of cases, but it seldom eliminated infection after a single treatment. Mebendazole appeared to be more active than DEC in eliminating the infection, with a comparable rate of overall responses. Ivermectin and praziquantel showed no modification of microfilariae concentration. Thiabendazole showed a small but significant activity against the infection. Combination treatments (DEC plus mebendazole) resulted in a significantly higher activity than the single drugs.
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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The prevalence of soil-transmitted helminth (STH) infection was reduced in the treatment group (n = 615), with significant differences between treatment and control groups (n = 575) in the levels of Ascaris and Trichuris. No impact was found on haemoglobin (Hb) levels, nor any significant impact on concentration levels or on educational test scores.
Chemotherapy of cystic echinococcosis became a treatment option 25 years ago, when new anthelminthic drugs were introduced. Benzimidazole carbamates were shown to kill the entire metacestode stage of the parasite, and praziquantel exhibited an effect on protoscoleces. Continuous or intermittent treatment with albendazole is recommended for a period of up to 6 months, and praziquantel may enhance the effect, in particular in the case of cyst spillage. Degenerative changes in the cysts occur in approximately 75% of the patients by the end of the treatment period. Benzimidazoles have to be applied in high daily doses, and adverse effects are observed, such as leucopenia, elevation of liver transaminases, and alopecia. Unfortunately, prospective randomized trials on the efficacy of chemotherapy versus surgery are not available. New treatment methods, such as percutaneous puncture, aspiration, injection of scolicidal agents and re-aspiration (PAIR) or modified PAIR-based techniques, have received much attention, and in experienced hands these approaches yield rates of cure and relapse equivalent to those following surgery. Adjunct treatment with benzimidazoles is the cornerstone of the interdisciplinary approach in cystic echinococcosis.
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Anthelmintic efficacies of ivermectin, febantel, fenbendazole, and mebendazole were compared in 45 adult gray foxes (Urocyon cinereoargenteus) naturally infected with helminth parasites. Fecal specimens were examined one week before treatment and one week and 3 weeks after treatment with each anthelmintic, using a sucrose flotation technique. Compared with pretreatment, fewer foxes in all groups were infected with helminths one week and 3 weeks after treatment. Ivermectin, febantel, and fenbendazole more effectively eliminated helminths than did mebendazole. Parasites found were Ancylostoma sp, Capillaria aerophila, and Aelurostrongylus abstrusus and/or Filaroides osleri.
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Giardiasis infection may be asymptomatic, or can cause diarrhoea (sometimes severe), weight loss, malabsorption, and, in children, failure to thrive. It is usually treated with metronidazole given three times daily for five to 10 days.
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Gemcitabine-(C4-amide)-[anti-HER2/neu] in dual combination with benzimidazoles can produce enhanced levels of cytotoxic anti-neoplastic activity and potentially provide a basis for treatment regimens with a wider margin-of-safety. Such benefits would be possible through the collective properties of; [i] selective "targeted" gemcitabine delivery; [ii] relatively lower toxicity of benzimidazoles compared to many if not most conventional chemotherapeutics; [iii] reduced total dosage requirements faciliated by additive or synergistic anti-cancer properties; and [iv] differences in sequelae for gemcitabine-(C4-amide)-[anti-HER2/neu] compared to benzimidazole tubulin/microtubule inhibitors.
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Benzimidazole anthelmintics have reported anti-neoplastic effects both in vitro and in vivo. The purpose of this study was to evaluate the in vitro chemosensitivity of three canine glioma cell lines to mebendazole and fenbendazole. The mean inhibitory concentration (IC50 ) (±SD) obtained from performing the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay after treating J3T, G06-A, and SDT-3G cells for 72 h with mebendazole were 0.030 ± 0.003, 0.080 ± 0.015 and 0.030 ± 0.006 μM respectively, while those for fenbendazole were 0.550 ± 0.015, 1.530 ± 0.159 and 0.690 ± 0.095 μM; treatment of primary canine fibroblasts for 72 h at IC50 showed no significant effect. Immunofluorescence studies showed disruption of tubulin after treatment. Mebendazole and fenbendazole are cytotoxic in canine glioma cell lines in vitro and may be good candidates for treatment of canine gliomas. Further in vivo studies are required.
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This paper presents our experience with mebendazole, a new broad-spectrum anthelmintic, in 91 cases with ascariasis, 71 cases with necatoriasis 54 cases with trichuriasis and 10 cases with T. saginata infection. Various dosage schedules were evaluated. In ascariasis, a single dose of 200 mg was effective in totally clearing the infection in 100 per cent cases. In necatoriasis 200 mg twice daily for four days was found to be the most effective dose. With this dose total eradication of the infection was seen in 92 per cent cases. In trichuriasis, 200 mg twice daily for four days totally eradicated the infection in 90 per cent cases. In T. saginata infection, the drug was totally ineffective. The anthelminitic activity of the drug was demonstrated by the recovery of roundworms, hookworms and whipworms from the stools. The drug was well tolerated. No side effects or toxic effects were seen in any of the cases.
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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Mice infected with protoscoleces of Echinococcus granulosus for 8-9 months were treated ig with mebendazole (Meb) 50 mg.kg-1.d-1, albendazole (Alb) 300 mg.kg-1.d-1 or albendazole sulfoxide (AlbSO) 150 mg.kg-1.d-1 for 1-7 d. The glycogen contents of cyst wall in each drug groups were 1.0 +/- 0.6 - 1.8 +/- 0.9 mg/g, 1.1 +/- 0.9 - 1.8 +/- 0.8 mg/g and 0.8 +/- 0.5 - 1.5 +/- 0.9 mg/g, respectively, which were less than those 2.2 +/- 1.3 - 2.8 +/- 1.3 mg/g of corresponding control groups with respective glycogen reduction rates of 38-55%, 36-51% and 46-62%. After prolongation of treatment course to 10-14 d, the glycogen contents of cyst wall in Meb and AlbSO groups were further decreased, which resulted in glycogen reduction rates of 73% and 69%, respectively. No further decrease of glycogen contents in Alb groups was seen as the glycogen reduction rates sustained in 32%. Histochemical observation showed that the glycogen contents in germinal layer of the cysts decreased significantly or even disappeared during the treatment of Meb, Alb or AlbSO. The results suggested that the effects of Meb and AlbSO on mice infected with secondary cysts of E granulosus were superior to Alb as evaluated by glycogen reduction rate of cyst wall.
We previously reported the short period cure rate of mebendazole (MBZ) treatment to strongyloidiasis. We are now reporting the long period cure rate of the treatment. The results were as follows: 1) The cure rate was 73.9% (17/23) in single use of MBZ (100 mg twice daily for 28 days). 2) The cure rate was 100.0% (22/22) in combination therapy (thiabendazole 500 mg three times a day for 5 days and after that, MBZ 100 mg twice daily for 9 days). Before we obtained the cure rate of 6 months after the treatment described above, we concluded that MBZ could be used for the treatment of strongyloides infection because of the lack of severe side effects and suitable intervals between courses would prevent liver injury. Thus, in this study, 47 patients were treated with 100 mg of MBZ twice a day for 5 days and this treatment was repeated 1, 3 and 4 weeks later on the same schedules (group 1). But because of liver injury, 13 patients were interrupted and moved to the 4th course (group 2). The following results were obtained: 1) Out of a total of 60 patients, the cure rate was 88.1% (52/59) after 2 courses, 92.3% (12/13) after 3 courses and 100.0% (46/46) after the 4 courses were finished. 2) Diarrhea (10.6%), arthralgia and lumbago (8.5%) were observed in group 1. No side effects were observed in group 2. 3) The incidence of liver injury occurred 48.9% (23/47) in group 1 and 30.8% (4/13) in group 2. 4) Positive rate of HTLV-I antibody was 40.0% (24/60).(ABSTRACT TRUNCATED AT 250 WORDS)
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The main purpose of this work was to accomplish a comparative study about cyclodextrins complexation equilibria with three benzimidazolic antihelmintics: albendazole (Alb), mebendazole (Meb) and thiabendazole (Thiab). The complexation process with four different cyclodextrins (alpha-, beta-, gamma-, and HP-beta-CDs) was investigated under various temperatures and different reaction media (aqueous solution buffered at pH 7.5, dimethylsulfoxide (DMSO) and DMSO/water at 25/75, 50/50, 75/50 (w/w) mixtures). It was studied by electronic absorption and 1H NMR (NOESY) spectroscopy. Binding constants were determined by electronic absorption spectroscopic method, the DeltaH and DeltaS complexation values were evaluated and discussed according to the diverse factors that affect the chemical interactions in these systems. Solubility has also been determined by the Higuchi and Connors method. In general, albendazole and mebendazole exhibit similar complexation behavior, while thiabendazole acts differently. Classic and non-classic solvophobic effects are mainly the driving and stabilizing forces for complex formation, with the exception in some Thiab-CDs interactions. In all cases, DMSO, an aprotic solvent, should be considered as an active component of the reaction systems.
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We studied gastrointestinal parasites in symptomatic Cambodian children attending a provincial hospital in Siem Reap, Cambodia between 2006 and 2011. A total of 16 372 faecal samples were examined by direct microscopy. Parasites were detected in 3121 (19.1%) samples and most common were Giardia lamblia (8.0% of samples; 47.6% disease episodes), hookworm (5.1%; 30.3%) and Strongyloides stercoralis (2.6%; 15.6%). The proportion of infected children increased, and the number of disease episodes effectively treated with a single dose of mebendazole decreased, over the 5-year period.
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Ascaris Lumbricoides Infestation (ALI) is one of the most common helmintic disease of the gastrointestinal tract, and may cause severe surgical complications, especially in children. ALI is frequent in tropical and subtropical countries. We present our experience with a case of a 5-years old pakistan girl treated in Italy for acute abdomen in which ALI was detected during surgical exploration.
Germinal cells isolated from Echinococcus granulosus cysts harbored in mice have been maintained in an in vitro culture system containing RPMI 1640 supplemented by 20% calf serum, and used as a model for screening anti-hydatid drugs. When the germinal cells were maintained in the medium for 6 days, the cell proliferation rate was rather high in the first four days but declined in the last two days. In screening drugs, 1.4 x 10(6) germinal cells were exposed to known effective drugs against metacestodes of E. granulosus in mice, such as mebendazole (Meb), albendazole (Alb) or praziquantel (Pra) at various concentrations. One to three days after exposure, cell counts were made daily in 3 samples of each drug concentration. The mean cell number of each group was compared with that of the control and the inhibition rate of the cell was then calculated. The results showed that the minimal effective concentrations of Meb, Alb and Pra, were 1.0 (48 h), 2.5 (24 h) and 10.0 (72 h) micrograms/ml, respectively, while the inhibition rates of the cell were 34.1, 55.7 and 18.5%. Interestingly, the in vitro effects of Meb, Alb and Pra were consistent to those obtained from the in vivo tests, ie Meb > Alb > Pra. Nevertheless, after exposure of germinal cells to Meb at 2.5 micrograms/ml for 24 h, the cells appeared in roughness, indistinction, shrunk or swelling, collapse, deformation and hole-like feature detected by light microscopy and scanning electron-microscopy, while the ultrastructure alterations of the cells noted by transmission electron-microscopy were lysis in cytoplasm, disruption or disappearance of nucleus and even darkness of the whole cell.(ABSTRACT TRUNCATED AT 250 WORDS)