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Jennifer Keiser - One of the best experts on this subject based on the ideXlab platform.
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Efficacy and Safety of a Single Dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections in Children: A Randomised, Double-blind Trial.
EClinicalMedicine, 2018Co-Authors: Marta S. Palmeirim, Jan Hattendorf, Shaali M. Ame, Said M. Ali, Jennifer KeiserAbstract:Abstract Background Single-dose Mebendazole is widely used in preventive chemotherapy against the soil-transmitted helminths (STHs) Ascaris lumbricoides, hookworm and Trichuris trichiura, yet it shows limited efficacy against hookworm and T. trichiura infections. The use of adapted treatment regimens might provide a strategy to control and eliminate STH infections in STH-persistent settings. We evaluated the safety and efficacy of the multiple dose Mebendazole regimen (3 days 100 mg bid) versus a single dose of 500 mg Mebendazole in a setting with high STH prevalence and high drug pressure. Methods This randomised, double-blind clinical trial took place in a primary school on Pemba Island, Tanzania, in school-aged children (6–12 years). Using a computer random number generator (block size 10), hookworm-positive children were randomly assigned (1:1) to either a single or multiple dose regimen of Mebendazole by an independent statistician. Two stool samples were collected at baseline and follow-up (18 to 22 days after treatment) for Kato-Katz analysis. The primary outcome was cure rate (CR) against hookworm. Secondary outcomes were egg reduction rate (ERR) against hookworm, CRs and ERRs against A. lumbricoides and T. trichiura, and tolerability assessed 3, 24 and 48 h post-treatment. Participants, investigators, caregivers, outcome assessors and the trial statistician were blinded. This trial is registered with ClinicalTrials.gov , number NCT03245398 . Findings 93 children were assigned to each treatment arm. 185 children completed treatment and provided follow-up stool samples. CR against hookworm was significantly higher in the multiple dose (98%) than in the single dose arm (13%, OR 389.1, 95% CI 95.2 to 2885.7%, p Interpretation The poor performance of single dose Mebendazole against hookworm infections was confirmed, but the multiple dose treatment regimen of Mebendazole showed high efficacy. Hence, multiple dose Mebendazole might provide a treatment strategy in given epidemiological situations to boost control and elimination of STH infections. Funding PATH.
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In Vitro and In Vivo Drug Interaction Study of Two Lead Combinations, Oxantel Pamoate plus Albendazole and Albendazole plus Mebendazole, for the Treatment of Soil-Transmitted Helminthiasis
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Noemi Cowan, Mireille Vargas, Jennifer KeiserAbstract:The current treatments against Trichuris trichiura, albendazole and Mebendazole, are only poorly efficacious. Therefore, combination chemotherapy was recommended for treating soil-transmitted helminthiasis. Albendazole-Mebendazole and albendazole-oxantel pamoate have shown promising results in clinical trials. However, in vitro and in vivo drug interaction studies should be performed before their simultaneous treatment can be recommended. Inhibition of human recombinant cytochromes P450 (CYPs) CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was tested by exposure to albendazole, albendazole sulfoxide, Mebendazole, and oxantel pamoate, as well as albendazole-Mebendazole, albendazole sulfoxide-Mebendazole, albendazole-oxantel pamoate, and albendazole sulfoxide-oxantel pamoate. A high-pressure liquid chromatography (HPLC)-UV/visible spectroscopy method was developed and validated for simultaneous quantification of albendazole sulfoxide, albendazole sulfone, Mebendazole, and oxantel pamoate in plasma. Albendazole, Mebendazole, oxantel pamoate, albendazole-Mebendazole, and albendazole-oxantel pamoate were orally applied to rats (100 mg/kg) and pharmacokinetic parameters calculated. CYP1A2 showed a 2.6-fold increased inhibition by albendazole-oxantel pamoate (50% inhibitory concentration [IC50] = 3.1 μM) and a 3.9-fold increased inhibition by albendazole sulfoxide-Mebendazole (IC50 = 3.8 μM) compared to the single drugs. In rats, Mebendazole's area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax) were augmented 3.5- and 2.8-fold, respectively (P = 0.02 for both) when coadministered with albendazole compared to Mebendazole alone. Albendazole sulfone was slightly affected by albendazole-Mebendazole, displaying a 1.3-fold-elevated AUC compared to albendazole alone. Oxantel pamoate could not be quantified, translating to a bioavailability below 0.025% in rats. Elevated plasma levels of albendazole sulfoxide, albendazole sulfone, and Mebendazole in coadministrations are probably not mediated by CYP-based drug-drug interaction. Even though this study indicates that it is safe to coadminister albendazole-oxantel pamoate and albendazole-Mebendazole, human pharmacokinetic studies are recommended.
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efficacy and safety of albendazole plus ivermectin albendazole plus Mebendazole albendazole plus oxantel pamoate and Mebendazole alone against trichuris trichiura and concomitant soil transmitted helminth infections a four arm randomised controlled t
Lancet Infectious Diseases, 2015Co-Authors: Benjamin Speich, Jan Hattendorf, Isaac I Bogoch, Rainer Alles, Jorg Huwyler, Marco Albonico, Jurg Utzinger, Jennifer KeiserAbstract:Summary Background Existing anthelmintic drugs (eg, albendazole and Mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus Mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or Mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than Mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus Mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to Mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus Mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for Mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus Mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for Mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.
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Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo
Parasites & Vectors, 2012Co-Authors: Jennifer Keiser, Lucienne Tritten, Roberto Adelfio, Mireille VargasAbstract:Background Soil-transmitted helminth (STH) infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority. Methods 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 ED_50 of the respective drugs. Results In vitro all 10 combinations of the standard anthelmintics tested against T. muris revealed synergistic behavior. We identified three drug combinations in vivo as strongly synergistic, namely Mebendazole-ivermectin (Combination index (CI)=0.16), Mebendazole-levamisole (CI=0.17) and albendazole-Mebendazole (CI=0.23). For albendazole-ivermectin, moderate synergism was observed (CI=0.81) and for albendazole-levamisole a nearly additive effect was documented (CI=0.93) in vivo . Five combinations (albendazole-pyrantel pamoate, Mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin) were antagonistic in vivo. Conclusion Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-Mebendazole should be studied in greater detail in preclinical studies.
Gregory J. Riggins - One of the best experts on this subject based on the ideXlab platform.
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Mebendazole inhibits tumor growth and prevents lung metastasis in models of advanced thyroid cancer
Endocrine-related Cancer, 2020Co-Authors: Tara Williamson, Thais Biude Mendes, Natalie Joe, Janete M Cerutti, Gregory J. RigginsAbstract:The most common thyroid malignancy is papillary thyroid cancer. While a majority respond to therapy and have a favorable prognosis, some papillary thyroid cancers persist. This subset may dedifferentiate to anaplastic thyroid cancer, an aggressive, highly invasive and rapidly fatal cancer. Thyroid cancer patients at risk for disease progression and metastasis need earlier, safer and more effective therapies. The purpose of this translational study was to determine if Mebendazole could be repurposed to effectively treat thyroid cancer, in particular before metastasis. In vitro, Mebendazole potently inhibited the growth of a panel of human papillary and anaplastic thyroid cancer cells. In papillary (B-CPAP) and anaplastic (8505c) cell lines, Mebendazole increased the percentage of cells in G2/M cell cycle arrest and induced late stage apoptosis by activation of the caspase-3 pathway. In aggressive 8505c cells, Mebendazole significantly repressed migratory and invasive potential in a wound healing and transwell invasion assay and inhibited expression of phosphorylated Akt and Stat3 and reduced Gli1. In vivo, Mebendazole treatment resulted in significant orthotopic thyroid tumor regression (B-CPAP) and growth arrest (8505c), with treated tumors displaying reduced expression of the proliferation maker KI67 and less vascular epithelium as indicated by CD31+ immunohistochemistry. Most importantly, daily oral Mebendazole prevented established thyroid tumors from metastasizing to the lung. Given the low toxicity and published anticancer mechanisms of Mebendazole, this novel preclinical study of Mebendazole in thyroid cancer has promising therapeutic implications for patients with treatment refractory papillary or anaplastic thyroid cancer.
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Mebendazole and radiation in combination increase survival through anticancer mechanisms in an intracranial rodent model of malignant meningioma
Journal of Neuro-oncology, 2018Co-Authors: Christine G Skibinski, Tara Williamson, Gregory J. RigginsAbstract:Meningiomas are a frequent tumor of the central nervous system. Although mostly benign, approximately 5% present as atypical or malignant tumors. Treatments for atypical meningiomas include gross total resection and radiotherapy, but about 33% of patients have recurrent tumors, sometimes as a higher grade. Recently, the brain penetrant anthelmintic drug, Mebendazole, has shown promise as an anticancer agent in rodent models of glioblastoma and medulloblastoma. The half maximal inhibitory concentration (IC50) effect on colony formation, cell proliferation, and caspase-3/7 markers of apoptosis of Mebendazole with and without radiation was measured in vitro. Mice intracranially implanted with KT21MG1 human meningioma were administered Mebendazole alone or in combination with radiation. Survival benefit was evaluated, while tumors were investigated by immunohistochemical staining for apoptosis, cell proliferation, and vascular density. In vitro experiments on meningioma cell lines showed the IC50 for Mebendazole in the range of 0.26–0.42 µM. Mebendazole alone induced cytotoxicity, however the combination had a greater reduction in colony formation and resulted in higher levels of cleaved caspase-3. The in vivo study showed both, Mebendazole alone and the combination, to have a survival benefit with an increase in apoptosis, and decreases in tumor cell and vascular proliferation. These preclinical findings indicate that Mebendazole alone or in combination with radiation can be considered for the treatment of malignant meningioma. The mechanism of action for this combination may include an increase in apoptosis, a reduction in proliferation and angiogenesis, or a combination of these effects.
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atnt 21preclinical and initial phase 1 experience for use of Mebendazole as up front therapy for high grade glioma
Neuro-oncology, 2015Co-Authors: Gregory J. Riggins, Renyaun Bai, Gary L GalliaAbstract:INTRODUCTION: Identifying drugs that can reach brain cancers in effective concentrations has been a serious challenge. There has been a body of evidence implicating anti-cancer mechanisms and utility for antihelminthics benzimidazoles, and preclinical and clinical development of repurposed Mebendazole is gaining momentum. Mebendazole has been used safely as an anti-parasitic drug, and in high doses, in humans starting in 1972. METHODS: Multiple intracranial models of glioblastoma and medulloblastoma have been used for efficacy studies on intracranial tumors. Studies with orally administered Mebendazole demonstrate favorable pharmacokinetics with 70 to 80% of Mebendazole serum levels measured in the in the mouse brain and brain tumors. RESULTS: Our laboratory serendipitously identified benzimidazole anti-cancer activity in brain cancers and found that of the approved benzimidazoles, Mebendazole showed the best survival benefit. We observe in preclinical testing it reaches effective concentrations in intracranial tumors, acts to prevent tubulin polymerization, has an additional anti-VEGR2 and anti-angiogenesis mechanisms and significantly improves survival in a variety of intracranial malignancy models. We have translated our preclinical findings into a Phase I trial, using Mebendazole for upfront therapy, concurrent with temozolomide therapy for newly diagnosed patients with a high grade glioma. We have further improved Mebendazole with drug combinations. CONCLUSION: The preclinical and phase 1 clinical findings are consistent with safe and possibly effective use of an improved formulation of oral Mebendazole. We provide evidence that continued optimization of Mebendazole based oral therapy and planning of future clinical trials may yield an additional tool for therapy of GBM and other intracranial tumors.
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Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model
Clinical Cancer Research, 2015Co-Authors: Verena Staedtke, Teresia Wanjiku, Avadhut D. Joshi, Michelle A. Rudek, Gary L Gallia, Gregory J. RigginsAbstract:Purpose: Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different Mebendazole polymorphs (A, B, and C) exist, and a detailed assessment of the brain penetration, pharmacokinetics, and antitumor properties of each individual Mebendazole polymorph is necessary to improve Mebendazole-based brain cancer therapy. Experimental Design and Results: In this study, various marketed and custom-formulated Mebendazole tablets were analyzed for their polymorph content by IR spectroscopy and subsequently tested in an orthotopic GL261 mouse glioma model for efficacy and tolerability. The pharmacokinetics and brain concentration of Mebendazole polymorphs and two main metabolites were analyzed by LC/MS. We found that polymorph B and C both increased survival in a GL261 glioma model, as B exhibited greater toxicity. Polymorph A showed no benefit. Polymorph B and C both reached concentrations in the brain that exceeded the IC 50 in GL261 cells 29-fold. In addition, polymorph C demonstrated an AUC 0–24h brain-to-plasma (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In contrast, polymorph A presented markedly lower levels in the plasma and brain. Furthermore, the combination with elacridar was able to significantly improve the efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice. Conclusions: Among Mebendazole polymorphs, C reaches therapeutically effective concentrations in the brain tissue and tumor with fewer side effects, and is the better choice for brain cancer therapy. Its efficacy can be further enhanced by combination with elacridar. Clin Cancer Res; 21(15); 3462–70. ©2015 AACR .
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Repurposing the antihelmintic Mebendazole as a hedgehog inhibitor
Molecular cancer therapeutics, 2014Co-Authors: Andrew R. Larsen, Gregory J. Riggins, Ren Yuan Bai, Jon Chung, Alexandra Borodovsky, Charles M. Rudin, Fred BunzAbstract:The hedgehog (Hh) signaling pathway is activated in many types of cancer and therefore presents an attractive target for new anticancer agents. Here, we show that Mebendazole, a benzamidazole with a long history of safe use against nematode infestations and hydatid disease, potently inhibited Hh signaling and slowed the growth of Hh-driven human medulloblastoma cells at clinically attainable concentrations. As an antiparasitic, Mebendazole avidly binds nematode tubulin and causes inhibition of intestinal microtubule synthesis. In human cells, Mebendazole suppressed the formation of the primary cilium, a microtubule-based organelle that functions as a signaling hub for Hh pathway activation. The inhibition of Hh signaling by Mebendazole was unaffected by mutants in the gene that encodes human Smoothened (SMO), which are selectively propagated in cell clones that survive treatment with the Hh inhibitor vismodegib. Combination of vismodegib and Mebendazole resulted in additive Hh signaling inhibition. Because Mebendazole can be safely administered to adults and children at high doses over extended time periods, we propose that Mebendazole could be rapidly repurposed and clinically tested as a prospective therapeutic agent for many tumors that are dependent on Hh signaling.
Jan Hattendorf - One of the best experts on this subject based on the ideXlab platform.
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Efficacy and Safety of a Single Dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections in Children: A Randomised, Double-blind Trial.
EClinicalMedicine, 2018Co-Authors: Marta S. Palmeirim, Jan Hattendorf, Shaali M. Ame, Said M. Ali, Jennifer KeiserAbstract:Abstract Background Single-dose Mebendazole is widely used in preventive chemotherapy against the soil-transmitted helminths (STHs) Ascaris lumbricoides, hookworm and Trichuris trichiura, yet it shows limited efficacy against hookworm and T. trichiura infections. The use of adapted treatment regimens might provide a strategy to control and eliminate STH infections in STH-persistent settings. We evaluated the safety and efficacy of the multiple dose Mebendazole regimen (3 days 100 mg bid) versus a single dose of 500 mg Mebendazole in a setting with high STH prevalence and high drug pressure. Methods This randomised, double-blind clinical trial took place in a primary school on Pemba Island, Tanzania, in school-aged children (6–12 years). Using a computer random number generator (block size 10), hookworm-positive children were randomly assigned (1:1) to either a single or multiple dose regimen of Mebendazole by an independent statistician. Two stool samples were collected at baseline and follow-up (18 to 22 days after treatment) for Kato-Katz analysis. The primary outcome was cure rate (CR) against hookworm. Secondary outcomes were egg reduction rate (ERR) against hookworm, CRs and ERRs against A. lumbricoides and T. trichiura, and tolerability assessed 3, 24 and 48 h post-treatment. Participants, investigators, caregivers, outcome assessors and the trial statistician were blinded. This trial is registered with ClinicalTrials.gov , number NCT03245398 . Findings 93 children were assigned to each treatment arm. 185 children completed treatment and provided follow-up stool samples. CR against hookworm was significantly higher in the multiple dose (98%) than in the single dose arm (13%, OR 389.1, 95% CI 95.2 to 2885.7%, p Interpretation The poor performance of single dose Mebendazole against hookworm infections was confirmed, but the multiple dose treatment regimen of Mebendazole showed high efficacy. Hence, multiple dose Mebendazole might provide a treatment strategy in given epidemiological situations to boost control and elimination of STH infections. Funding PATH.
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efficacy and safety of albendazole plus ivermectin albendazole plus Mebendazole albendazole plus oxantel pamoate and Mebendazole alone against trichuris trichiura and concomitant soil transmitted helminth infections a four arm randomised controlled t
Lancet Infectious Diseases, 2015Co-Authors: Benjamin Speich, Jan Hattendorf, Isaac I Bogoch, Rainer Alles, Jorg Huwyler, Marco Albonico, Jurg Utzinger, Jennifer KeiserAbstract:Summary Background Existing anthelmintic drugs (eg, albendazole and Mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus Mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or Mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than Mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus Mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to Mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus Mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for Mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus Mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for Mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.
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albendazole and Mebendazole administered alone or in combination with ivermectin against trichuris trichiura a randomized controlled trial
Clinical Infectious Diseases, 2010Co-Authors: Benjamin Speich, Stefanie Knopp, Khalfan A Mohammed, Simba I Khamis, Alipo Naim Khamis, Jan Hattendorf, Russell J StothardAbstract:Background. Single-dose albendazole and Mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a Mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 mug/kg), Mebendazole (500 mg) plus placebo, and Mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a Mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), Mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the Mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), Mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. 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. Trial registration. isrctn.org Identifier: ISRCTN08336605
Benjamin Speich - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of albendazole plus ivermectin albendazole plus Mebendazole albendazole plus oxantel pamoate and Mebendazole alone against trichuris trichiura and concomitant soil transmitted helminth infections a four arm randomised controlled t
Lancet Infectious Diseases, 2015Co-Authors: Benjamin Speich, Jan Hattendorf, Isaac I Bogoch, Rainer Alles, Jorg Huwyler, Marco Albonico, Jurg Utzinger, Jennifer KeiserAbstract:Summary Background Existing anthelmintic drugs (eg, albendazole and Mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus Mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or Mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than Mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus Mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to Mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus Mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for Mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus Mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for Mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.
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albendazole and Mebendazole administered alone or in combination with ivermectin against trichuris trichiura a randomized controlled trial
Clinical Infectious Diseases, 2010Co-Authors: Benjamin Speich, Stefanie Knopp, Khalfan A Mohammed, Simba I Khamis, Alipo Naim Khamis, Jan Hattendorf, Russell J StothardAbstract:Background. Single-dose albendazole and Mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a Mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 mug/kg), Mebendazole (500 mg) plus placebo, and Mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a Mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), Mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the Mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), Mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. 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. Trial registration. isrctn.org Identifier: ISRCTN08336605
Marco Albonico - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of albendazole plus ivermectin albendazole plus Mebendazole albendazole plus oxantel pamoate and Mebendazole alone against trichuris trichiura and concomitant soil transmitted helminth infections a four arm randomised controlled t
Lancet Infectious Diseases, 2015Co-Authors: Benjamin Speich, Jan Hattendorf, Isaac I Bogoch, Rainer Alles, Jorg Huwyler, Marco Albonico, Jurg Utzinger, Jennifer KeiserAbstract:Summary Background Existing anthelmintic drugs (eg, albendazole and Mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus Mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or Mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than Mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus Mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to Mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus Mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for Mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus Mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for Mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.
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Efficacy of Mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted Mebendazole treatment in Zanzibar
Bulletin of the World Health Organization, 2003Co-Authors: Marco Albonico, Quentin D. Bickle, Ramsan, Antonio Montresor, Lorenzo Savioli, Martin G. TaylorAbstract:OBJECTIVE: To evaluate the efficacy of and resistance to Mebendazole (500 mg) and levamisole (40 or 80 mg), alone or in combination, for the treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections on Pemba Island - an area exposed to periodic school-based Mebendazole treatment since 1994. METHODS: A randomized, placebo-controlled trial was carried out in 914 children enrolled from the first and fifth grades of primary schools. Stool samples collected at baseline and 21 days after treatment were examined by the Kato-Katz technique to assess the prevalence and intensity of helminth infection. FINDINGS: Efficacies of Mebendazole and levamisole as single treatments against intestinal nematode infections were comparable with those in previous trials, but Mebendazole treatment of hookworm infections gave significantly lower cure (7.6%) and egg reduction (52.1%) rates than reported in a study undertaken before the beginning of periodic chemotherapy (cure rate, 22.4%; egg reduction rate, 82.4%). Combined treatment with Mebendazole and levamisole had a significantly higher efficacy against hookworm infections (cure rate, 26.1%; egg reduction rate, 88.7%) than either drug given alone. No difference in Mebendazole efficacy was found in children who had been treated repeatedly compared with those who had not been treated previously. CONCLUSION: The overall efficacy of Mebendazole against hookworm infections after periodic chemotherapy is reduced. The efficacy of benzimidazoles in chemotherapy-based control programmes should be monitored closely. Combined treatment with Mebendazole and levamisole may be useful as a tool to delay the development of benzimidazole resistance.
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a randomized controlled trial comparing Mebendazole and albendazole against ascaris trichuris and hookworm infections
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1994Co-Authors: Marco Albonico, Pete Smith, Andrew Hall, Hababu M Chwaya, Kassim S Alawi, Lorenzo SavioliAbstract:The efficacies and side effects of single dose treatments with 500 mg Mebendazole (Janssen Pharmaceutica) and 400 mg albendazole (SmithKline Beecham) against intestinal nematodes were compared in a single-blind, randomized controlled trial among 2294 children aged 6 to 12 years on Pemba Island, Zanzibar, among whom infections with Ascaris, hookworms and Trichuris were highly prevalent. Both drugs were highly effective against Ascaris, with cure rates of over 97%. The cure rates for Trichuris were low, but Mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count. Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count. There was no difference in the frequency of side effects reported by heavily infected children treated with either drug. In a trial on 402 children, 500 mg Mebendazole (Janssen) was compared with a generic version of the drug, 500 mg Mebendazole (Pharmamed). No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied.