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In a large-scale Bulgarian study, 122 patients with abdominal and/or lung echinococcosis were randomly selected for treatment with albendazole or mebendazole. The main aims were to evaluate the effect of each drug on the hydatid cysts, to follow the changes in cyst morphology during and after treatment, and to determine how quickly each drug produced the first, detectable, degenerative changes in the cysts. Follow-up was based on periodic ultrasonography, chest radiography and computed tomography. The abdominal cysts were categorised as small (<5 cm in diameter) or large. As albendazole treatment had effects that were almost identical to those of mebendazole treatment, the results for the two drugs were combined. In the lungs and, particularly, in the abdomen, the size of the cysts being treated influenced the character and timing of the degenerative changes seen in them. The initial change seen in each abdominal cyst was detachment of the endocyst, which occurred 1-3 months (small cysts) or 2-5 months (large cysts) after the initiation of treatment (P<0.05). The abdominal cysts then developed a hyper-echoic/hyper-dense appearance, became smaller, and finally disappeared 3.3-9.3 months (small cysts) or 5.6-13.9 months (large cysts) after treatment began (P<0.05). The first degenerative change noted in the lung cysts was cyst rupture, which occurred as early as day 10 of therapy but was generally observed 1 or 2 months after treatment began. After their complete evacuation, the ruptured lung cysts shrank and became deformed, some disappearing within 5-9 months of the initiation of treatment. The degenerative changes recorded, which began significantly earlier in the lung cysts than in abdominal cysts, indicate serious damage to the cysts and the parasiticidal, curative effect of each of the two benzimidazoles employed.
To document the occurrence of primary pelvic hydatid cyst as one of the hidden causes of lower limb weakness and foot drop, and to recommend inclusion of the pelvic cavity when assessing sciatica and foot drop.
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Flubendazole has been given at a daily dosage of 50 mg/kg for 16 months (extremes 10 and 24 months) to 10 patients with hepatic alveolar echinococcosis. Clinical, morphological and immunological evaluations have been performed every 2 months during the treatment, and in 6 patients after discontinuation of the drug for 24 months. Jaundice persisted or occurred in 7 patients; infectious complications were observed in 4 patients; portal hypertension appeared in 5 patients; metastatic spread was suspected in 2 patients. Subjective improvement and weight gain were reported by 6 patients during the first 4 months of treatment. Severe complications occurring during the period of FZ therapy or within 2 months after withdrawal of the drug led to surgery in 6 patients, and death occurred in 3 cases. These observations demonstrate the inefficacy of FZ in this series of 10 patients with alveolar echinococcosis, possibly related to the extremely poor bioavailability of FZ. Higher plasma concentrations obtained with mebendazole and albendazole could explain the better efficacy of these two drugs despite their similar chemical structures and experimental toxicity upon larval cestodes.
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We reported a 14-year-old girl who had been admitted to our clinic due to the appearance of red macules on her extremities and face, vomiting, and pain in the abdomen and joints. The patient was initially diagnosed with Henoch-Schönlein purpura. At the end of the fourth week of illness, larvae of Strongyloides stercoralis were detected in stool samples. The patient was therefore treated with mebendazole, after which all symptoms permanently withdrew. About a month later laboratory examinations were repeated demonstrating increasing signs of renal damage. Kidney biopsy was performed, showing mesangioproliferative glomerulonephritis with crescents and IgA and C3 positive staining in the mesangium. Upon reviewing the clinical presentation, biochemically demonstrated progressive renal damage and biopsy results, the patient was diagnosed with HSP nephritis.
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In this work, four different supercapacitive microbial fuel cells (SC-MFCs) with carbon brush as the anode and an air-breathing cathode with Fe-Aminoantipyrine (Fe-AAPyr) as the catalyst have been investigated using galvanostatic discharges. The maximum power (Pmax) obtained was in the range from 1.7 mW to 1.9 mW for each SC-MFC. This in-series connection of four SC-MFCs almost quadrupled Pmax to an operating voltage of 3025 mV and a Pmax of 8.1 mW, one of the highest power outputs reported in the literature. An additional electrode (AdHER) connected to the anode of the first SC-MFC and placed in the fourth SC-MFC evolved hydrogen. The hydrogen evolution reaction (HER) taking place at the electrode was studied on Pt and two novel platinum group metal-free (PGM-free) catalysts: Fe-Aminoantipyrine (Fe-AAPyr) and Fe-Mebendazole (Fe-MBZ). The amount of H2 produced was estimated using the Faraday law as 0.86 mMd(-1)cm(-2) (0.132 L day(-1)) for Pt, 0.83 mMd(-1)cm(-2) (0.127 L day(-1)) for Fe-AAPyr and 0.8 mMd(-1)cm(-2) (0.123 L day(-1)) for Fe-MBZ. Hydrogen evolution was also detected using gas chromatography. While HER was taking place, galvanostatic discharges were also performed showing simultaneous H2 production and pulsed power generation with no need of external power sources.
A 41-year old man of Brazilian origin, suffering from AIDS for one year, fell ill with pyrexia of over 39 degrees C, dyspnoea, chest pain and deterioration in his general condition. At the same time he noted a discrete skin eruption, mainly on the upper limbs. Diarrhoea began later. A chest radiograph revealed bilateral infiltrates. The blood showed leucocytosis (11,000/microliters) with pronounced increase of eosinophil granulocytes (47.5%). Alkaline phosphatase was raised to 170 U/l. Suspicion of strongyloidiasis was confirmed by the discovery of numerous Strongyloides stercoralis larvae in the faeces. A few days after starting treatment with mebendazole, 400 mg daily, he felt better and the diarrhoea stopped. However, as the lung infiltrates remained unchanged and hilar lymph node enlargement now appeared, the dose of mebendazole was raised to 2500 mg daily. The abnormal findings then cleared up: Strongyloides stercoralis larvae ceased to be demonstrable and the patient gained 10 kg in weight.
Community in Pemba Island, Zanzibar.
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These findings demonstrate that MBZ-OS is a promising new formulation of MBZ for treatment of hydatid diseases without showing significantly liver toxicity.
The rat lungworm (Angiostrongylus cantonensis) is the principal cause of eosinophilic meningitis or meningoencephalitis worldwide. It is endemic in Taiwan and the Asia Pacific area. We report the case of a 10-year-old boy who was referred to us suffering from intermittent headache, low-grade fever and blurred vision of 4-5 days' duration. He had been treated for gastroenteritis just prior to referral. The patient's history was unremarkable, except that he raised snail (Ampullarium canaliculatus) as pet at home. On physical examination, the patient's consciousness was alert and well oriented. No papilledema was found on fundal examination. The neurological examination revealed normal cranial nerve function, mild weakness of both lower limbs and normal deep tendon reflexes, but positive Babinski and Kernig signs. Laboratory findings showed peripheral eosinophilia, elevated immunoglobulin E level, cerebrospinal fluid eosinophilic pleocytosis and the presence of stage 3 A. cantonensis larvae, which confirmed the diagnosis of eosinophilic meningitis. A 2-week course of mebendazole combined the glucocorticosteroids was beneficial in relieving headache, paresthesia and the other eosinophilic meningitis symptoms in the patient.
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There were 78 patients (41 females, 37 males). All age groups were involved with an age range of 8-70 years. The main clinical presentation was upper abdominal discomfort, heaviness and mild pain. Ultrasonography and indirect hemagglutination test diagnosed more than 90% of cases. All patients were operated upon and received a postoperative prophylactic course of mebendazole. We reported a recurrence rate of less than 3%. Excessive loss of hair as a side effect to mebendazole therapy occurred in 2 young female patients.
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Iron deficiency anaemia is a common condition in rural Aboriginal children. Poor nutrition and helminth infections are the common causes of this morbidity. This study aims to evaluate the impact of annual single dose mebendazole 300-500 mg (albendazole unavailable) in preventing anaemia and the impact of iron and mebendazole in treating anaemia in a population of remote Aboriginal children in Arnhemland.
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The effects of the anthelmintics praziquantel (PZQ), levamisole (LEV), mebendazole (MBZ), fenbendazole (FBZ) and albendazole (ABZ), on the morphology and the histology of a digenetic trematode, Cotylophoron cotylophorum, were studied. Scanning electron micrographs of the drug-treated worms revealed that PZQ was the most effective drug inducing surface damages to a great extent. The parasite exposed to PZQ for 6 h, showed smaller blebs on the oral sucker region as well as on the sensory papillae. These blebs enlarged in size after 24 h and ruptured after 30 h of exposure. The worms treated with LEV showed a few smaller blebs on the ventrolateral margin. In MBZ- and FBZ-treated worms the blebs appeared between the oral and genital sucker after 6 h of incubation. The changes were not apparent in the ABZ-treated worms.
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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Onchocerciasis is a major cause of blindness, and much of the blindness due to onchocerciasis is caused by chorioretinitis. Little is known about the progression of lesions in the posterior segment in either untreated or treated disease. The authors studied the progression of onchocercal chorioretinitis in 57 patients from 1 to 3 years. Changes were documented from detailed ocular examinations, fundus photographs, and fluorescein angiograms, and included live intraretinal microfilariae, intraretinal hemorrhages, cotton-wool opacities, intraretinal pigment, white and shiny intraretinal deposits, retinal pigment epithelial window defects, and atrophy. Depigmentation at the edge of chorioretinal scarring progressed at a rate of up to 200 microns per year. Ivermectin or mebendazole treatment did not appear to alter the progress of depigmentation at the edge of chorioretinal scars. These observations suggest that onchocercal chorioretinitis is associated with early changes in the retina and retinal pigment epithelium, and that disease in the posterior segment may progress rapidly.
This national survey investigated the prices and affordability of 25 key essential medicines for children in private sector pharmacies using the WHO/Health Action International (HAI) medicine price methodology. Data were collected from a representative sample of 48 private sector pharmacies selected from 8 Provinces using a multistage clustered approach. At each pharmacy prices of originator brand (OB) and lowest priced generics (LPG) of the selected medicines were collected. Medicine prices were compared with international reference prices to obtain a median price ratio (MPR). Income of the lowest paid unskilled government worker was used to establish the affordability.
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The molecular basis for the resistance of the sheep parasitic nematode Haemonchus contortus to the benzimidazole (BZ) group of anthelmintics was investigated. Three BZ-susceptible and three resistant populations from different geographical locations were characterized with respect to the egg-hatch assay with thiabendazole (TBZ), mebendazole (MBZ) binding tests and restriction fragment length polymorphism (RFLP) after Southern blotting. Cloned H. contortus alpha- and beta-tubulin genes were used as probes to analyze the RFLPs of genomic DNA prepared from mixtures of infectious larvae (L3) or adults. The susceptible populations showed, with both alpha- and beta-tubulin probes, 2 to 6 different fragments, depending on the restriction enzyme used. The three resistant populations showed as many fragments with the alpha-tubulin probe as the susceptible populations, but when probed with beta-tubulin only 1 or 2 fragments were visible, but always less than in the susceptible populations. An in vitro selection experiment was carried out using a susceptible population that was isolated in the laboratory before BZ came on the market. The results showed that after two selections with increasing amounts of TBZ, the population had become resistant, according to the egg-hatch assay values and MBZ binding assay. Using RFPL, the number of beta-tubulin probe reactive DNA fragments was reduced from 5 to 1. Analysis of the DNA of individual male adults of susceptible populations indicated a heterogeneity among the individual worms regarding the number of beta-tubulin probe reactive fragments (1 to 4) and frequency of the specific fragments. Usually, only one specific fragment (9 kb) was found in the resistant individuals. This 9-kb fragment was already present in some individuals in the susceptible population although it was in combination with other fragments. This would imply that genes conferring BZ resistance were present in H. contortus populations before BZ came on the market, and could explain the fast selection for BZ resistance in the field.
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Wistar rats were infected with 600 embryonated eggs of C. hepatica administered by gavage and treated with ivermectin and mebendazole in separate groups at PIDs 10, 12, 15, 17 or 20. Rats from each group and their nontreated controls, were killed and examined 40 days after the end of treatment.
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Women on their first visit to antenatal clinics of the University Obstetrics Unit, General Hospital Colombo North, Ragama, during July-August 1995, were recruited for the study. Demographic details, duration of pregnancy and a history of using anthelmintics during the current pregnancy were noted. A stool sample was obtained and examined using modified Kato-Katz technique.
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We searched the literature and the animal health marketed products and pipeline for potential drug development candidates. Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials. For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI) statements, European Public Assessment Reports (EPAR) and published literature). Concomitantly, we developed a target product profile (TPP) against which the products were compared.
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Clinical assessment of the symptoms and plain chest X-ray led to the correct diagnosis in 228 cases (95%). In six (2.5%), imaging studies such as ultrasonography, computed tomography and nuclear magnetic resonance were required, and in the remaining six cases (2.5%), the diagnosis was established intraoperatively or in the subsequent histopathological study. One hundred and seventy patients (70.8%) presented a solitary lung cyst, while the remaining 70 (29.2%) were found to have multiple cysts in one or more lobes of one or both lungs. In addition, 45 patients (18.7%) presented hepatic cysts and 25 (10.4%) had cysts in other locations. After 18 years of follow-up, the survival rate was 94.6%. Of the surviving patients, 98.3% were free of pulmonary hydatid disease and 95.1% were free of hydatid disease.
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Cutaneous larva migrans (CLM), a zoonotic helminthiasis imported to Canada by travelers to the tropics, causes morbidity due to severe, intractable pruritus. Treatment in Canada is only available through the Special Access Program (SAP) of Health Canada, thus, many patients are prescribed ineffective courses of non-targeted therapy.
A six-year-old aboriginal girl living in northeast Taiwan, was admitted via Emergency Service with the chief complaint of epigastralgia for one day. Fever, leucocytosis, hyponatremia, acidosis and unilateral pleural effusion were noted. The serum amylase was 2976 U/L. Image studies including abdominal sonography and computerized tomography revealed a swollen and edematous pancreas. There was no evidence of previous trauma, drug using, hereditary problems, nor biliary tract stone; the patient was noted to have adult worms and eggs of Ascaris lumbricoides in stool and vomitus. Ascariasis associated with pancreatitis was suspected. She recovered completely after antihelmintic therapy (mebendazole) and supportive treatment. Fourteen ascarides and 20 trichurides were expelled during nine days of admission.
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The present work is concerned with study of the effects of praziquantel, thiabendazole, mebendazole, cyclophosphamide and cortisone on histopathology of the small intestine (during intestinal phase) and skeletal muscles (during muscular phase), in addition to T. lymphocytes count and serum IgG estimation in experimental trichinosis in albino rats. Praziquantel has no effect on the histopathology of small intestine or skeletal muscles. Thiabendazole and mebendazole treatment resulted in complete eradication of Trichinella spiralis worms of small intestine and marked reduction of larval infection (mild infection) of skeletal muscle. Praziquantel, thiabendazole and mebendazole did not affect significantly the T. lymphocytes count of the host during the intestinal phase. Cyclophosphamide and cortisone suppressed the cellular immunity (T. lymphocytes) and accordingly enhanced the parasitic infection in histopathology of both phases. All the drugs tested induced significant reduction of T. lymphocytes in muscular phase (which may be due to parasitic infection itself) and insignificant effect on IgG level in both phases.
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Patent infections of adult dogs with Toxocara canis induced by transplantation of immature, intestinal stages were examined for their suitability for testing of anthelmintics. Each of 5 dogs were infected four times by transplantation of 80 immature, intestinal stages of Toxocara canis. The dogs were treated with various anthelmintics of well established efficacy (pyrantel, nitroscanate, mebendazole, piperazine) 20 dpi. All anthelmintics tested showed the same efficacy as had been assessed earlier by treatment of dogs infected prenatally with Toxocara canis.
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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.