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A patient with chronic liver disease was treated with large doses of mebendazole for a hepatic hydatid cyst. Eighteen days after beginning treatment he developed marrow aplasia which reverted to normal after the drug was stopped. This is the marrow aplasia which reverted to normal after the drug was stopped. This is the sixth patient described as developing marrow aplasia when treated with large doses of mebendazole. We suggest that the aplasia is related to the dose of the drug, and that the patient's chronic liver disease was an important factor in its genesis. Patients treated with large doses of mebendazole should have their blood counts monitored during treatment.
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Intestinal parasites are common among labourers from foreign countries and in immigrants. Some worm-infections like ascaridiasis or enterobiasis occur in children quite often even in the cold climates. In cases of ascaridiasis only a heavy infection causes clinical symptoms. The diagnosis is made through the detection of eggs in the stools, as all the other worm-infections are diagnosed from the stool-test. Piperazine-derivatives are highly effective against ascaris; another useful drug is Pyrantel-Pamoate. Toxocara canis, which affects normally only dogs, can occur occasionally in humans. Its larvae migrate in the body and cause granulomas. The main clinical symptom of threadworms (enterobiasis) is itching around the anus. This parasite can be eradicated through Pyrvinium-Pamoate. The first symptom a patient notices in cases of taeniasis are proglottides--parts of the worms--which are passed with the stools. The drug of choice against all kinds of tapeworms is Niclosamide. Hookworms are rampant in tropical countries. Heavy infections can cause severe anemias, especially in children. Bephenium-Naphthoate and Bitoscanate are effective drugs against this parasite. The whipworm (Trichuris trichura) is very common in the warm countries. It can be treated by Tiabendazole and nowadays also with Mebendazole, which is virtually atoxic. Infections with Strongyloides stercoralis are difficult to eradicate, as there are different ways of reinfection. In case an infection with strongyloides is accompanied by other serious diseases cachexia and even fatal outcome has been seen.
Female filariae of the species Brugia malayi and Litomosoides carinii were investigated by means of electron microscopy after in vivo treatment with flubendazole. The earliest fine-structure alteration in both species was the disappearance of microtubuli from the intestinal cells as soon as 6 h after treatment. There was no further disintegration of intestinal cells for several days. Microtubuli disappeared from the outer zone of the hypodermal cytoplasm 24 h after treatment. At this time, marked alterations were also observed in the oogonia and in the embryonic cells. Many of these were swollen; their nuclear envelope was partly resolved and the chromatin was condensed, but no spindle apparatus was formed. The early fine-structure alterations observed after in vivo treatment with flubendazole consisted of the disappearance of microtubuli from various tissues. This led to the interruption of cell division in oogonia and embryonic cells and, and subsequently, to the disintegration of most other filarial tissues. These morphological alterations differed considerably from those observed after treatment with benzothiazole derivatives, which do not affect the microtubuli of the filariae.
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Albendazole is the first-choice treatment in patients with univesicular cysts. PAIR or combined injection of alcohol with polidocanol is indicated when pain is intractable or albendazole fails. In patients with multivesicular cysts, PEVAC is a better choice. Surgery is the first-choice treatment only when the expertise of percutaneous treatment is not available or when percutaneous treatment fails.
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A simple high-performance liquid chromatographic method for the determination of mebendazole in eel muscle tissue was developed. It is applicable for concentrations of 10 micrograms/kg and higher. Muscle tissue was extracted with ethyl acetate, and the extract, after addition of hexane, was concentrated and cleaned up on a silica gel solid-phase extraction column. Mebendazole was eluted from the column with 3% acetic acid in methanol. The eluate, after reconstitution in the chromatographic mobile phase, was analysed on a LiChrosorb RP-8 column with acetonitrile-0.05 M ammonium phosphate buffer (pH 6.2) (3:7, v/v) as the mobile phase. Detection was performed at 311 nm. The average mebendazole recovery over the concentration range 10-5000 micrograms/kg eel muscle tissue was 72 +/- 6.4%. The calibration curve for spiked samples was linear throughout the range 10-10,000 micrograms/kg (r = 0.999).
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Ascaris lumbricoides worm counts were examined as the outcome products of exposure proxy variables. A survey of 663 children, 4-10 yr old, living in southeastern Madagascar revealed prevalences of 93% for A. lumbricoides, 55% for Trichuris trichiura, and 27% for hookworm. Worm expulsions were conducted on 428 of these children; the data revealed an overdispersed distribution of A. lumbricoides, with an arithmetic mean of 19.2 worms per child. A concurrent socioeconomic household survey was conducted by visitation and interview. Exposure to infection was assessed by environmental, demographic, behavioral, and socioeconomic indicators. Ascaris lumbricoides aggregations were associated with gender, housing style, ethnicity, and agricultural factors. The results suggest that exposure and infection are ubiquitous in this child population, and that A. lumbricoides intensity is influenced by gender-related behavioral and environmental factors that contribute to exposure.
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Stool samples from 840 children attending 14 primary schools in Jimma, Ethiopia were pooled (pool sizes of 10, 20, and 60) to evaluate the infection intensity of STHs. In addition, the efficacy of a single dose of mebendazole (500 mg) in terms of fecal egg count reduction (FECR; synonym of egg reduction rate) was evaluated in 600 children from two of these schools. Individual and pooled samples were examined with the McMaster egg counting method. For each of the three STHs, we found a significant positive correlation between mean fecal egg counts (FECs) of individual stool samples and FEC of pooled stool samples, ranging from 0.62 to 0.98. Only for A. lumbricoides was any significant difference in mean FEC of the individual and pooled samples found. For this STH species, pools of 60 samples resulted in significantly higher FECs. FECR for the different number of samples pooled was comparable in all pool sizes, except for hookworm. For this parasite, pools of 10 and 60 samples provided significantly higher FECR results.
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We provide the first soil-transmitted helminthiasis risk profile for entire Côte d'Ivoire, based on a robust Bayesian geostatistical framework. Our model-based estimates of treatment needs and risk maps on health district level may guide the national control program in spatial targeting of annual interventions.
The situation in the chemotherapy of nematode infections. in both human and veterinary medicine, is currently satisfactory. There are different drugs available: the benzimidazoles, levamisole, pyrantel, and the different macrocyclic lactones (Tables 1. 2, 3, 4). In human medicine, mebendazole and albendazole are mainly used against the intestinal nematodes. while ivermectin and diethylcarbamazine are microfilaricidal drugs used in prophylaxis against onchocercosis and filarial infections. The situation in veterinary medicine is, however, governed by the great resistance problem in some animal hosts against all important anthelmintics. There are various reports of resistance against benzimidazoles, levamisole, pyrantel, and macrocyclic lactones in trichostrongylides in small ruminants (sheep, goats) and also Strongylides in horses. Resistance against ivermectin is now arising in cattle (Coles 2001; Sangster 2001). There are no reports of resistance problems in dogs and cats. Thus, there is always an urgent need in veterinary medicine for new anthelmintics with a new mode of action, which can easily break resistance against the existing anthelmintics. The situation in the chemotherapy of filarial infections in human medicine is not satisfactory. There is an urgent need for a new macrofilaricidal drug with only slight side-effects. Today, the only way is the prophylactic control of Onchocerca vovulus infections and treating lymphatic filariosis with ivermectin, diethylcarbamacine, ivermectin/diethylcarbamazine. or ivermectin/albendazole combinations.
Parasite infestation is still associated with significant morbidity and mortality. Hookworm infestation is a very rare cause of pancreatitis. This parasitic infestation might be asymptomatic. Acute pancreatitis as a result of the hookworms migrating into the ampulla of Vater with chronic inflammation was a very rare complication. Were port a case of hookworm infestation that was associated with significant complication of recurrent pancreatitis. The patient was treated with mebendazole. He was asymptomatic and had gained weight at the 3-month follow-up. Our case demonstrates that pancreatitis secondary to hookworm infection can occur and may resolve after anthelmintic treatment.
In an experimental larval infection of Ancylostoma caninum in mice, the efficacy of various anthelmintics against the larvae migrated and established in the brain is reported for the first time. Albendazole and flubendazole were the most effective drugs. Thiabendazole, benacil, phenacizole, oxfendazole and mebendazole showed significant larvicidal activity. Tetramisole, levamisole, fenbendazole, Sch 18099, pyrantel pamoate, morantel tartrate and oxantel pamoate did not show any significant activity even at relatively high dose levels.
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Helminthic parasites usually cause uncomplicated infections of the intestine. Complications can arise from nutritional competition between parasite and host, mechanical obstruction of the intestine or common bile duct (in ascariasis), and an overwhelming, fatal infection among immunocompromised hosts (in strongyloidiasis). Diagnosis is made by testing stool samples, except for Enterobius, which can often be seen in the perianal area. Treatment in uncomplicated cases is straightforward and easy. Several drugs are available, and the regimen depends on which parasites are present. However, none is safe for use in pregnant women.
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A series of 6 experiments was conducted to test the efficacy of mebendazole in eliminating naturally occurring pinworm infections from mice. Subjects treated with from 40-500 mg/kg of the drug harbored markedly fewer parasites than untreated controls. Treatment at 10 mg/kg appeared to be less effective. No mortality or overt signs of toxicity were observed in any of the experimental subjects.
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Government owned plantations in low-country regions of Sri Lanka with poor sanitary facilities.
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UMF-078, methyl (+/-)-[5-(alpha-amino-4-fluorobenzyl)benzimidazol-2-yl]carba mate, is a new antifilarial compound being developed by the World Health Organization. In the present study, a HPLC method for the simultaneous estimation of UMF-078 and its metabolites (flubendazole, decarbamoylated flubendazole, UMF060 and decarbamoylated UMF-060) in plasma was developed, validated and applied to pharmacokinetic studies. Linearity was observed between 20 and 1000 ng/ml for decarbamoylated UMF-060 and between 10 and 500 ng/ml for other analytes. Recoveries were consistent over the concentration ranges studied for all the analytes. Variations in intra- and inter-batch accuracy and precision were within acceptable limits of +/-20% at the lowest limit of quantitation, whereas at higher concentrations it was +/-15%. The analytes showed stability up to two freeze-thaw cycles in plasma. No degradation was observed for any of the analytes even after 72 h of storing the dry plasma extracts at -30 degrees C. The assay method was employed to study the pharmacokinetics of hydrochloride salt of UMF-078 in rats. The parent compound and its metabolites viz: decarbamoylated UMF-060, UMF-060 and flubendazole were quantitated in serum and the compounds could be monitored up to 168 h post-dose.
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Trichuris vulpis was identified in two children from urban slums. Both of them had nonspecific abdominal pain and one had episodes of diarrhea. Clinical recovery was good after treatment with mebendazole.
Nucleotide sequences of the beta-tubulin gene were generated by PCR using degenerate primers, specific primers and DNA from worms and eggs of T. trichiura and worms of Trichuris spp. from baboons. The ITS2 region was amplified using adult Trichuris spp. from baboons. PCR products were sequenced and analysed. The beta-tubulin fragments were studied for SNPs in codons 167, 198 or 200 and the ITS2 amplicons were compared with GenBank records of T. trichiura.
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Adult Necator americanus infection in laboratory hamsters (the hamster-hookworm model) was examined as an anthelminthic screening system. Three reference anthelminthics--pyrantel (PYTL), mebendazole (MBZ) and ivermectin (IVRN)--were used to assess the sensitivity of adult N. americanus and also to investigate the value of the hamster-hookworm model for predicting clinical results. Serial drug dosages were used, and the ED50 was determined from the resulting cure rates. In addition, percentage worm reductions were calculated by reference to the worm burdens in control groups. The results showed that the hamster-hookworm model was able to differentiate anthelminthics on their efficacy. Absolute activity (100% worm reduction) followed treatment with 8 mg kg-1 MBZ, 38-40 mg kg-1 PYTL and 18 mg kg-1 IVRN. Based on ED50 data of PYTL and MBZ, adult N. americanus appeared to be two to five times more sensitive than pre-adult stages. However, with IVRN the reverse appeared true. MBZ appeared to be most active and PYTL least active in terms of curing infected animals, but there were no obvious differences between the rates of worm reductions following single or multiple doses of anthelminthics. It is considered that the hamster-hookworm model will prove of value in identifying and characterizing possible new anthelminthics.
This study investigated the influence of moisture and heat on the stability of mebendazole polymorph C in tablets. The polymorphic forms of mebendazole display significant differences in solubility and therapeutic efficacy and form C is preferred clinically due to its optimal bioavailability and reduced toxicity. An accelerated stability study of the polymorphs revealed that the Johnson-Mehl-Avrami-Erofeyev-Kolmogorov (JMAEK) model best described the kinetics of the solid-state transformation of form C to A. Rate constants obtained using this model was used to calculated half-lives and shelf lives of products stored under ICH conditions of 30 degrees C + 65% RH and 40 degrees C + 75% RH. Results showed that form C was converted to the thermodynamic stable, least soluble form A with increased temperatures and moisture, and at constant temperature and relative humidity this transformation was significantly increased when trace amounts of form A was present in the tablets. Four out of the seven products tested contained trace amounts of form A. In some tablets, the transformation to form A was so quick that it reduced the shelf life to less than 1 month. The tablet dissolution of these products was reduced to such an extent that it did not comply with USP and FDA specifications.
Flubendazol is a veterinary antiparasitic agent which acts toxically on both adult and larval stages of round worms. It is nearly insoluble in water and it influences not only the selection of the dosage form, but also its biological availability. Its solubility can be increased by adding solutizers and tensides, or by complex-formation with cyclodextrins. In the published experimental paper the method of complex-formation of flubendazol with 2-hydroxypropyl-beta-cyclodextrin was employed and the effect of temperature on the resultant solubility of the active ingredient was examined. The final dosage form was pellets produced with the use of the method of extrusion and spheronisation.
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With an ever increasing number of international travelers, physicians should be aware of the diseases that have rarely been encountered in their home countries. Cystic echinococcosis (CE) caused by Echinococcus granulosus is seldom seen in Japan despite frequent occurrence of the other type of echinococcosis, alveolar echinococcosis (AE) caused by E. multilocularis, in its northern parts. However, CE is prevalent in many parts of the world including the United Kingdom, Mediterranean basin, Middle East, South America, and Australia, and is supposed to be resurgent in several parts of the world. The disease is acquired by the oral ingestion of the eggs of E. granulosus passed into the feces of several definitive host animals carrying tapeworms, mostly dogs. These definitive hosts are infected by cannibalizing intermediate host animals including sheep and cattle whose livers and/or lungs are affected by cystic lesions that contain protoscoleces. In endemic areas the diagnosis of CE is not considered to be complicated; typical morphological features composed of cysts as revealed by ultrasonography and/or computerized tomography (CT) scan. The diagnosis is also aided by serological methods detecting serum antibodies. However, imaging procedures show a variety of features that could often lead to misdiagnosis as other diseases. Moreover, serological assays are sometimes difficult to interpret because of their incomplete sensitivities and specificities. Hence, a comprehensive understanding of a spectrum of imaging features and the application of serological methods with better sensitivities and specificities are indispensable. The mainstay of treatment of the disease is still surgical removal of cysts that has the potential to lead to a complete cure. Recently, the less invasive method PAIR (Puncture of cysts percutaneously, Aspiration of fluid, Introduction of protoscolicidal agent, and Reaspiration) was introduced with considerable success, and could be a promising alternative to surgery. Lastly, medical treatment with oral mebendazole or albendazole, especially the latter, can be beneficial not only as a adjunctive to surgery or PAIR, but as a sole treatment in cases in which invasive methods are not indicated. Here we report a Jordanian patient with CE whose diagnosis was substantiated by a novel immunoblot assay and who showed a rapid improvement during albendazole therapy.
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The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China.
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Between 1978 and 2002, 15 patients (mean age, 23.0 +/- 8.5 years) with cardiac and pericardial echinococcosis were treated surgically. The cysts were located in the right atrium in 3 patients, on the anterior myocardium in 7, and pericardially in 5. The 3 patients with right atrial cysts were operated on using cardiopulmonary bypass. There were 4 recurrences requiring re-operation after a mean of 12 months. All other patients received mebendazole treatment and exhibited no recurrence during follow-up. One late death due to chronic right heart failure occurred after 10 months of follow-up. The serologic test is an effective method of diagnosis in undeveloped and developing countries.
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Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer therapeutic is warranted. A number of possible combinations with other drugs are discussed in the Appendix.
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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.