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Current Opinion in Infectious Diseases Oct 2020Giardiasis remains a common cause of diarrhea and intestinal enteropathy globally. Here we give an overview of clinical treatment studies and discuss potential... (Review)
Review
PURPOSE OF REVIEW
Giardiasis remains a common cause of diarrhea and intestinal enteropathy globally. Here we give an overview of clinical treatment studies and discuss potential mechanisms and molecular targets for in-vitro testing of drug resistance.
RECENT FINDINGS
Giardia is a cause of disease both in diarrheal and nondiarrheal cases. The prevalence of treatment refractory giardiasis is increasing. Recent studies reveal 5-nitroimidazole refractory infection occurs in up to 50% of cases. Mechanisms of drug resistance are not known. Placebo controlled studies of drug efficacy, taking the self-limiting course of giardiasis into account, has not been reported. No randomized controlled trials of treatment of refractory infection have been performed the last 25 years. Based on the clinical studies reported, combination treatment with a 5-nitroimidazole and a benzimidazole is more effective than repeated courses of 5-nitroimidazole or monotherapies in refractory cases. Quinacrine is effective in refractory cases, but potentially severe side effects limit its use.
SUMMARY
A combination of a 5-nitroimidazole and albendazole or mebendazole, and quinacrine monotherapy, are rational choices in nitroimidazole refractory infections, but randomized controlled studies are needed. Further research into more recent clinical isolates is necessary to uncover mechanisms for the increase in metronidazole refractory giardiasis observed during the last decade.
Topics: Adult; Albendazole; Antiprotozoal Agents; Benzimidazoles; Child; Diarrhea; Drug Resistance; Drug Therapy, Combination; Female; Giardia; Giardiasis; Humans; Male; Mebendazole; Metronidazole; Nitroimidazoles; Quinacrine
PubMed: 32773501
DOI: 10.1097/QCO.0000000000000668 -
The Urologic Clinics of North America May 2022Patients using nutraceuticals represent a diverse patient population with a keen potential interest and/or adherence to healthy lifestyle changes. BPH nutraceuticals,... (Review)
Review
Patients using nutraceuticals represent a diverse patient population with a keen potential interest and/or adherence to healthy lifestyle changes. BPH nutraceuticals, including saw palmetto were as safe, but not more effective than placebo in the STEP and CAMUS clinical trials, but another high-quality saw palmetto product could be tested in a phase 3 trial. Several other BPH supplements need more recent robust clinical data, environmental oversight, or safety data. ED supplements, including Panax ginseng, and the notable nitric oxide (NO) enhancing amino acids arginine and citrulline have positive preliminary short-term efficacy data with and without PDE-5 inhibitors, but herbal quality control (QC) or safety signals with some of these agents in specific patient populations need to be resolved. "Less is more" should be the current mantra in the prostate cancer milieu, and potentially in some men with male infertility based on the FAZST trial because it is plausible some antioxidants are exhibiting prooxidant activity in some settings. Some prescription anthelmintic medications are being studied, others are being purchased over-the-counter (OTC), but their preliminary safety and efficacy against cancer have been concerning and questionable. In fairness, ongoing additional objective clinical trial data should become available soon, especially with mebendazole. DHEA or DHEA enhancing products have multiple concerns including HDL reductions, and their questionable use in men with BPH or prostate cancer based on the limited data. Some of these concerns should also be addressed in long-term robust clinical trials of prescription testosterone agents. Regardless, more attention should be directed toward heart-healthy lifestyle changes for most urologic men's health conditions, whether they are used in a preventive or synergistic setting with other acceptable clinical treatment options.
Topics: Antioxidants; Dehydroepiandrosterone; Dietary Supplements; Female; Humans; Life Style; Male; Men's Health; Phytotherapy; Prostatic Hyperplasia; Prostatic Neoplasms; Reactive Oxygen Species; Urologic Diseases
PubMed: 35428430
DOI: 10.1016/j.ucl.2021.12.006 -
Cancers Aug 2022Resistance to conventional chemotherapy remains a huge challenge in the clinical management of hepatoblastoma, the most common liver tumor in childhood. By integrating...
Resistance to conventional chemotherapy remains a huge challenge in the clinical management of hepatoblastoma, the most common liver tumor in childhood. By integrating the gene expression data of hepatoblastoma patients into the perturbation prediction tool Connectivity Map, we identified the clinical widely used anthelmintic mebendazole as a drug to circumvent chemoresistance in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner. The combination of mebendazole and cisplatin revealed a strong synergistic effect, which was comparable to the one seen with cisplatin and doxorubicin, the current treatment for high-risk hepatoblastoma patients. Moreover, mebendazole treatment resulted in reduced colony and tumor spheroid formation capabilities, cell cycle arrest, and induction of apoptosis of hepatoblastoma cells. Mechanistically, mebendazole causes blockage of microtubule formation and transcriptional downregulation of genes encoding the unwindosome, which are highly expressed in chemoresistant tumors. Most importantly, mebendazole significantly reduced tumor growth in a subcutaneous xenograft transplantation mouse model without side effects. In conclusion, our results strongly support the clinical use of mebendazole in the treatment of chemoresistant hepatoblastoma and highlight the potential theranostic value of unwindosome-associated genes.
PubMed: 36077733
DOI: 10.3390/cancers14174196 -
Acta Tropica Feb 2022Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are the two most important global parasitic infectious diseases caused by species of Echinococcus granulosus... (Review)
Review
Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are the two most important global parasitic infectious diseases caused by species of Echinococcus granulosus and E. multilocularis, respectively. Although numerous trials have been performed in search of novel therapeutic options to curb the neglected zoonosis, no other nonsurgical options are currently available to replace the licensed anti echinococcal drugs albendazole (ABZ) and mebendazole (MBZ). A safer and more effective treatment plan for echinococcosis is therefore urgently needed to compensate for this therapeutic shortfall. Here, we present a review of the literature for state-of-the-art valuable anti-parasitic compounds and novel strategies that have proved effective against CE and AE, which includes details about the pharmaceutical type, practical approach, experimental plan, model application and protoscolecidal effects in vivo and in vitro. The content includes the current application of traditional clinical chemicals, the preparation of new compounds with various drug loadings, repurposing findings, combined programs, the prospects for Chinese herbal medicines, non-drug administrations and the exploration of target inhibitors based on open-source information for parasitic genes. Next the conventional experimental projects and pharmacodynamic evaluation methods are systematically summarized and evaluated. The demands to optimize the construction of the echinococcosis model and improve the dynamic monitoring method in vivo are also discussed given the shortcomings of in vivo models and monitoring methods.
Topics: Albendazole; Animals; Echinococcosis; Echinococcus granulosus; Echinococcus multilocularis; Mebendazole
PubMed: 34808118
DOI: 10.1016/j.actatropica.2021.106252 -
BioMed Research International 2021Soil-transmitted helminths (STHs) and are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and...
BACKGROUND
Soil-transmitted helminths (STHs) and are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and eliminate the infection in endemic countries including Ethiopia. Although periodic deworming is conducted in endemic areas, the prevalence of the infection is high in the country. In addition, periodic evaluation of the efficacy of the anthelminthic drug is limited.
OBJECTIVE
This study is aimed at checking the efficacy of mebendazole and praziquantel with the respective STHs and parasites.
METHODS
A longitudinal study was conducted from February to March 2018 among 422 schoolchildren. Stool samples were collected at baseline and at 2 and 4 weeks posttreatment and were processed using the Kato-Katz technique. Schoolchildren positive for STHs were treated with mebendazole and those positive for with praziquantel. After two weeks, a second round of stool was collected and examined, and then, single-dose redosing was given to each positive child. Lastly, the third stool sample was collected two weeks after the initiation of the redosing and checked for STHs and parasites. A close follow-up of students who were treated was done. All the data were entered and analyzed using SPSS version 20 for analysis. Descriptive statistics was used to compute the cure rate and egg reduction rate of mebendazole and praziquantel.
RESULTS
Among 422 participants, the prevalence of STHs, hookworm, , and was 44.7%, 35.1%, 21.1%, and 13.9%, respectively. The cure rate of mebendazole against increased from 60% in the single dose to 100% in redosing after two weeks. The cure rate of mebendazole against hookworm also increased from 32.4% in the single dose to 91.0% in the redosing. The cure rate of praziquantel against -infected children was 91.5% in the first round and 100% in the redosing phase. There was a 98.6-100% egg reduction rate in the redosing regimen of both drugs.
CONCLUSION
The cure and egg reduction rates of single-dose mebendazole in the treatment of hookworm and are lower at week two than at redosing, while cure and egg reduction rates of single-dose praziquantel are satisfactory to treat . Therefore, single-dose praziquantel to and redosing of single-dose mebendazole to and hookworm infections can be used for treatment purposes.
Topics: Adolescent; Animals; Child; Ethiopia; Female; Geography; Helminthiasis; Helminths; Humans; Male; Mebendazole; Ovum; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Schools; Soil; Students; Treatment Outcome
PubMed: 34327236
DOI: 10.1155/2021/6682418 -
The Cochrane Database of Systematic... Apr 2020Ascaris lumbricoides is a common infection, and mainly affects children living in low-income areas. Water and sanitation improvement, health education, and drug... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ascaris lumbricoides is a common infection, and mainly affects children living in low-income areas. Water and sanitation improvement, health education, and drug treatment may help break the cycle of transmission, and effective drugs will reduce morbidity.
OBJECTIVES
To compare the efficacy and safety of anthelmintic drugs (albendazole, mebendazole, ivermectin) for treating people with Ascaris infection.
SEARCH METHODS
We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, three other databases, and reference lists of included studies, without language restrictions, up to 4 July 2019.
SELECTION CRITERIA
Randomized controlled trials (RCT) that compared albendazole, mebendazole, and ivermectin in children and adults with confirmed Ascaris infection.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed risk of bias, and extracted data from the included trials. A third review author checked the quality of data extraction. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) to compare dichotomous outcomes in treatment and control groups. We used the fixed-effect model for studies with low heterogeneity and the random-effects model for studies with moderate to high heterogeneity. We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative cure rates in the comparison groups.
MAIN RESULTS
We included 30 parallel-group RCTs, which enrolled 6442 participants from 17 countries across Africa, Asia, Central America and the Caribbean, and South America. Participants were from 28 days to 82 years of age, recruited from school, communities, and health facilities. Twenty studies were funded or co-funded by manufacturers, while 10 studies were independent of manufacturer funding. Twenty-two trials had a high risk of bias for one or two domains (blinding, incomplete outcome data, selective reporting). Single dose of albendazole (four trials), mebendazole (three trials) or ivermectin (one trial) was compared to placebo. Parasitological cure at 14 to 60 days was high in all the studies (illustrative cure of 93.0% in the anthelmintic group and 16.1% in the placebo group; RR 6.29, 95% CI 3.91 to 10.12; 8 trials, 1578 participants; moderate-certainty evidence). Single dose of albendazole is as effective as multiple doses of albendazole (illustrative cure of 93.2% with single dose, 94.3% with multiple doses; RR 0.98, 95% CI 0.92 to 1.05; 3 trials, 307 participants; high-certainty evidence); or as single dose of mebendazole (illustrative cure of 98.0% with albendazole, 96.9% with mebendazole; RR 1.01, 95% CI 1.00 to 1.02; 6 trials, 2131 participants; high-certainty evidence). Studies did not detect a difference between a single dose of albendazole and a single dose of ivermectin (cure rates of 87.8% with albendazole, 90.2% with ivermectin; RR 0.99, 95% CI 0.91 to 1.08; 3 trials, 519 participants; moderate-certainty evidence). Across all the studies, failure after single dose of albendazole ranged from 0.0% to 30.3%, mebendazole from 0.0% to 22.2%, and ivermectin from 0.0% to 21.6%. The egg reduction rate (ERR) measured up to 60 days after the treatment was high in all treated groups, regardless of the anthelmintic used (range 96% to 100%). It was not possible to evaluate parasitological cure by classes of infection intensity. No included trials reported complication or serious adverse events. Other adverse events were apparently similar among the compared anthelmintic groups (moderate- to low-certainty evidence). The most commonly reported other adverse events were nausea, vomiting, abdominal pain, diarrhoea, headache, and fever.
AUTHORS' CONCLUSIONS
Single-dose of albendazole, mebendazole, and ivermectin all appeared effective against Ascaris lumbricoides infection, yielding high parasitological cure and large reductions in eggs excreted, with no differences detected between them. The drugs appear to be safe to treat children and adults with confirmed Ascaris infection. There is little to choose between drugs and regimens in terms of cure or adverse events.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albendazole; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Child; Child, Preschool; Humans; Infant; Ivermectin; Mebendazole; Middle Aged; Parasite Egg Count; Placebos; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32289194
DOI: 10.1002/14651858.CD010599.pub2 -
Membranes Sep 2022The idea of using drugs from the benzimidazole group as potential antitumor agents is becoming increasingly popular and widespread in research. However, their use as...
The idea of using drugs from the benzimidazole group as potential antitumor agents is becoming increasingly popular and widespread in research. However, their use as antiparasitics and in cancer treatment will increase their already recorded occurrence in the aquatic environment. In this study, the removal of the anthelmintic mebendazole from aqueous solution was investigated using nanofiltration and reverse osmosis membranes, adsorption on granular activated carbon (GAC), and photolytic degradation. The dense NF90 and reverse osmosis XLE membranes showed almost complete removal (>97.7%), while the NF270 membrane showed a large dependence of removal on initial concentration from 41.9% to 96.6%. Adsorption in the column resulted in complete removal of mebendazole at the highest GAC height used (40 cm) from the solution with the lowest concentration (1 mg/L). Photolytic degradation by artificial light for 2 and 12 h resulted in photodegradation of mebendazole in the range of 23.5−61.4%, forming a new degradation or transformation compound with an m/z ratio of 311. Mebendazole is a photosensitive drug whose photodegradation follows first-order kinetics and depends on the drug concentration. Toxicity was studied with Vibrio fischeri before and after photolysis, and showed a decrease in inhibition after 12 h.
PubMed: 36135907
DOI: 10.3390/membranes12090888 -
Oncotarget Jul 2021The five-year survival rate for metastatic pancreatic cancer is currently only 3%, which increases to 13% with local invasion only and to 39% with localized disease at...
The five-year survival rate for metastatic pancreatic cancer is currently only 3%, which increases to 13% with local invasion only and to 39% with localized disease at diagnosis. Here we evaluated repurposed mebendazole, an approved anthelminthic drug, to determine how mebendazole might work at the different stages of pancreatic cancer formation and progression. We asked if mebendazole could prevent initiation of pancreatic intraepithelial neoplasia precursor lesions, interfere with stromal desmoplasia, or suppress tumor growth and liver metastasis. In both the ; -Cre (KC) mouse model of caerulein-induced inflammatory pancreatitis and the ; ; -Cre (KPC) mouse model of advanced pancreatic cancer, mebendazole significantly reduced pancreas weight, dysplasia and intraepithelial neoplasia formation, compared to controls. Mebendazole significantly reduced trichrome-positive fibrotic connective tissue and α-SMA-positive activated pancreatic stellate cells that heralds fibrogenesis. In the aggressive KPC model, mebendazole significantly suppressed pancreatic tumor growth, both as an early and late intervention. Mebendazole reduced the overall incidence of pancreatic cancer and severity of liver metastasis in KPC mice. Using early models of pancreatic cancer, treatment with mebendazole resulted in less inflammation, decreased dysplasia, with the later stage model additionally showing a decreased tumor burden, less advanced tumors, and a reduction of metastasis. We conclude that mebendazole should be investigated further as a component of adjuvant therapy to slow progression and prevent metastasis, and well as for primary prevention in the highest risk patients.
PubMed: 34262644
DOI: 10.18632/oncotarget.28014 -
Microorganisms Jan 2022For the last four decades, knowledge about human toxocariasis with regard to its epidemiology, pathophysiology, clinical spectrum, and imaging or laboratory diagnosis...
For the last four decades, knowledge about human toxocariasis with regard to its epidemiology, pathophysiology, clinical spectrum, and imaging or laboratory diagnosis has substantially progressed. Knowledge about specific therapy with anthelmintics has lagged behind. To date, only four drugs are registered for human use, and their efficacy has rarely been assessed in prospective controlled trials. It is likely that the repurposing of potent anthelmintics from veterinary medicine will improve this situation. Due to its wide availability and a lack of major side effects during short regimens, albendazole has become the drug of choice. However, its efficacy should be more precisely assessed. The role of anthelmintics in the treatment of neurological or ocular toxocariasis remains to be clarified. Prophylactic measures in humans or companion animals are efficient and represent first-line treatments for the control of this zoonosis. Unfortunately, their implementation in areas or countries where toxocariasis epidemiology is driven by poverty is quite difficult or unrealistic.
PubMed: 35208697
DOI: 10.3390/microorganisms10020241 -
Food Additives & Contaminants. Part A,... May 2022As a typical and broad-spectrum benzimidazole, mebendazole (MBZ) has long been used in human and veterinary medicine to treat parasitic infestations, and is widely...
As a typical and broad-spectrum benzimidazole, mebendazole (MBZ) has long been used in human and veterinary medicine to treat parasitic infestations, and is widely employed in the aquaculture of Japanese pufferfish (). However, there have been no studies examining the pharmacokinetic characteristics of MBZ in Japanese pufferfish. Furthermore, the presence of MBZ and its metabolites in animal-derived raw food represents a notable safety concern. Here, we investigated the metabolism of MBZ using a UPLC-Q-TOF system. Additionally, we evaluated the pharmacokinetics of MBZ and two metabolites, 2-amino-5(6)-benzoylbenzimidazole (MBZ-NH) and 5-hydroxymebendazole (MBZ-OH), in Japanese pufferfish following intramuscular injection of 20 mg/kg MBZ. We detected three metabolites of MBZ (M1-M3), among which, 2-amino-5(6)-(a-hydroxybenzyl) benzimidazole (M3) was detected in an aquatic animal for the first time. The plasma dispositions of MBZ, MBZ-NH, and MBZ-OH were characterized by low plasma clearance, medium distribution volume, and long terminal half-life. Moreover, these compounds were widely distributed in the muscle, from which they were rapidly cleared. The pharmacokinetics and metabolism of mebendazole in Japanese pufferfish are described for the first time in this study. Our findings provide a basis for the rational application of MBZ in Japanese pufferfish farming and contribute to our understanding of the metabolism of MBZ in cultured fish.
Topics: Animals; Benzimidazoles; Mebendazole; Muscles; Takifugu
PubMed: 35442868
DOI: 10.1080/19440049.2022.2052974