A phase 1 study of mebendazole with bevacizumab and irinotecan in high-grade gliomas.

BACKGROUND: High-grade gliomas (HGG) have a dismal prognosis despite multimodal therapy. Mebendazole is an anti-helminthic benzimidazole that has demonstrated efficacy in numerous in vitro cancer models, and is able to cross the blood-brain barrier. We conducted a phase 1 trial (NCT01837862) to evaluate the safety of mebendazole in combination with bevacizumab and irinotecan in children and young adults with HGG. OBJECTIVE: To determine the maximally tolerated dose of mebendazole when given in combination with bevacizumab and irinotecan in children with HGG; to describe the progression-free survival (PFS) and overall survival (OS) for this group. DESIGN/METHOD: Patients between 1 and 21 years of age with HGG were enrolled in a 3 + 3 design to escalating doses of mebendazole in combination with bevacizumab (10 mg/kg/dose) and irinotecan (150 mg/m2 /dose). Subjects were eligible upfront after completion of radiation or at the time of progression. Mebendazole was taken orally twice per day continuously, and bevacizumab and irinotecan were given intravenously on Days 1 and 15 of 28-day cycles. RESULTS: Between 2015 and 2020, 10 subjects were enrolled at mebendazole doses of 50 mg/kg/day (n = 3), 100 mg/kg/day (n = 4), and 200 mg/kg/day (n = 3). One subject assigned to 100 mg/kg/day was not evaluable. Seven subjects had a diagnosis of diffuse midline glioma, one subject had anaplastic astrocytoma, and one subject had a spinal HGG. All subjects received radiation. There were no dose-limiting toxicities. The most frequent G3/4 adverse events were neutropenia (n = 3) and lymphopenia (n = 4). The overall response rate was 33%, with two subjects achieving a partial response and one subject achieving a complete response sustained for 10 months. The mean PFS and OS from the start of study treatment were 4.7 and 11.4 months, respectively. CONCLUSION: Mebendazole was safe and well tolerated when administered with bevacizumab and irinotecan at doses up to 200 mg/kg/day. Further studies are needed to determine the efficacy of this treatment.

Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma.

BACKGROUND: Relapsed high-grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in-vitro and in-vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma. METHODS: We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re-irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1-5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination. FINDINGS: 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%). INTERPRETATION: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU.

Hepatotoxicity caused by mebendazole in a patient with Gilbert's syndrome.

WHAT IS KNOWN AND OBJECTIVE: Mebendazole (MBZ) is a broad-spectrum antihelminthic agent of the benzimidazole type. Although MBZ has been reported to cause hepatic injury, case reports of severe hepatic injury are very rare. We report a case of severe hepatitis after administration of MBZ in a patient with Gilbert's syndrome affected by pinworms infestation. CASE SUMMARY: Differently from other cases of hepatitis due to MBZ reported in the scientific literature, our patient received standard doses of MBZ for a short period of time. After 18 days from the start of therapy, he developed hepatomegaly, and increases in hepatic enzymes and bilirubin. Hepatic enzymes returned to normal over the following 5 weeks. WHAT IS NEW AND CONCLUSION: This is the first case report of important liver injury after administration of MBZ in a patient with Gilbert's syndrome. We suspected that a diminished hepatic glucuronidation of MBZ due to the reduced activity of the glucuronosyltransferase enzyme in our patient could have caused an increase in unconjugated toxic metabolites of MBZ and the consequent liver damage.

Systematic review of exposure to albendazole or mebendazole during pregnancy and effects on maternal and child outcomes, with particular reference to exposure in the first trimester.

Soil-transmitted helminth infections cause an important burden of morbidity worldwide, primarily from blood loss and malabsorption of nutrients. Where STH endemicity ≥20%, the World Health Organization (WHO) recommends preventive chemotherapy with single dose anthelminthic drugs: albendazole or mebendazole. Although WHO recommends that women of reproductive age, including pregnant women after the first trimester, be included in large-scale deworming programs, there are concerns related to the use of anthelminthic drugs during pregnancy, especially inadvertent use in the first few weeks when the pregnancy may not yet be confirmed. We therefore conducted a systematic review using the MEDLINE database with the aim of appraising all peer-reviewed evidence, published up to July 1, 2018, on the association between exposure to albendazole or mebendazole and outcomes in pregnant women, including those in the first trimester of pregnancy, and their children. From a yield of 205 papers based on titles alone, 58 papers, reporting results from 46 originator studies conducted in pregnant populations, constituted the initial evidence base. Among the nine originator observational studies which had included women in the first trimester of pregnancy within their study population, five compared birth outcomes between women exposed in the first trimester with women who were not exposed, and none reported higher rates of adverse birth outcomes in the exposed group. Due to heterogeneity in terms of study design, sample size, deworming drug, dosage and outcomes measured, data from these studies could not be pooled. Based on this cumulative evidence, it is unlikely that inadvertent exposure to albendazole or mebendazole in the first trimester carries an additional risk of adverse birth outcomes. To optimize relevance for policy making, future research in pregnant populations should aim to provide data disaggregated by trimester and to report on maternal and child adverse events, whenever possible.

Preclinical toxicity and pharmacokinetics of a new orally bioavailable flubendazole formulation and the impact for clinical trials and risk/benefit to patients.

BACKGROUND: Flubendazole, originally developed to treat infections with intestinal nematodes, has been shown to be efficacious in animal models of filarial infections. For treatment of filarial nematodes, systemic exposure is needed. For this purpose, an orally bioavailable amorphous solid dispersion (ASD) formulation of flubendazole was developed. As this formulation results in improved systemic absorption, the pharmacokinetic and toxicological profile of the flubendazole ASD formulation have been assessed to ensure human safety before clinical trials could be initiated. METHODS & FINDINGS: Safety pharmacology, toxicity and genotoxicity studies have been conducted with the flubendazole ASD formulation. In animals, flubendazole has good oral bioavailability from an ASD formulation ranging from 15% in dogs, 27% in rats to more than 100% in jirds. In in vivo toxicity studies with the ASD formulation, high systemic exposure to flubendazole and its main metabolites was reached. Flubendazole, up to high peak plasma concentrations, does not induce Cmax related effects in CNS or cardiovascular system. In repeated dose toxicity studies in rats and dogs, flubendazole-induced changes were observed in haematological, lymphoid and gastrointestinal systems and in testes. In dogs, the liver was an additional target organ. Upon treatment cessation, at least partial recovery was observed for these changes in dogs. In rats, the No Observed Adverse Effect Level (NOAEL) was 5 mg (as base)/kg body weight/day (mg eq./kg/day) in males and 2.5 mg eq./kg/day in females. In dogs, the NOAEL was lower than 20 mg eq./kg/day. Regarding genotoxicity, flubendazole was negative in the Ames test, but positive in the in vivo micronucleus test. CONCLUSIONS: Based on these results, in combination with previously described genotoxicity and reproductive toxicity data and the outcome of the preclinical efficacy studies, it was concluded that no flubendazole treatment regimen can be selected that would provide efficacy in humans at safe exposure.

The public health benefit and burden of mass drug administration programs in Vietnamese schoolchildren: Impact of mebendazole.

BACKGROUND: Mass anthelmintic drug administration is recommended in developing countries to address infection by soil-transmitted helminthiases (STH). We quantified the public health benefit of treatment with mebendazole in eight million Vietnamese children aged 5-14 years from 2006 to 2011. This was compared to the environmental impact of the pharmaceutical supply chain of mebendazole, as the resource use and emissions associated with pharmaceutical production can be associated with a public health burden, e.g. through emissions of fine particulate matter. METHODOLOGY: Through Markov modelling the disability due to STH was quantified for hookworm, Ascaris lumbricoides and Trichuris trichiura. For each worm type, four levels of intensity of infection were included: none, light, medium and heavy. The treatment effect on patients was quantified in Disability-Adjusted Life Years (DALYs). The public health burden induced by the pharmaceutical supply chain of mebendazole was quantified in DALYs through Life Cycle Assessment. PRINCIPAL FINDINGS: Compared to 'no treatment', the modelled results of five-year treatment averted 116,587 DALYs (68% reduction) for the three worms combined and largely driven by A. lumbricoides. The main change in DALYs occurred in the first year of treatment, after which the results stabilized. The public health burden associated with the pharmaceutical supply chain was 6 DALYs. CONCLUSIONS: The public health benefit of the Mass Drug Administration (MDA) averted substantially more DALYs than those induced by the pharmaceutical supply chain. These results were verified in a sensitivity analysis. The starting prevalence for each worm was the most sensitive model parameter. This methodology is useful for policymakers interested in a holistic approach towards the public health performance of MDA programs, enveloping both the treatment benefit received by the patient and the public health burden associated with the resource consumption and environmental emissions of the pharmaceutical production and supply chain.

Safety of Mebendazole Use During Lactation: A Case Series Report.

INTRODUCTION: Mebendazole is an effective drug widely used in the treatment of parasitic infections. Although theoretically considered as safe during lactation, no studies have evaluated its potential adverse effects in infants of breastfeeding mothers. OBJECTIVES: We aimed to evaluate the safety of mebendazole in infants of lactating women treated with the drug. METHODS: Women referred for consultation regarding mebendazole use were invited to participate in the study. Overall 45 lactating women treated with various protocols of mebendazole were recruited in this case series study. RESULTS: Regardless of the treatment protocol used (single or repeated doses) mebendazole was well tolerated and was not associated with any adverse effects in infants of lactating mothers. There was mild GI irritability in two treated women. CONCLUSION: This study provides first evidence in humans as to the safety of mebendazole in breastfeeding.

Adverse Events from a Randomized, Multi-Arm, Placebo-Controlled Trial of Mebendazole in Children 12-24 Months of Age.

Large-scale deworming interventions, using anthelminthic drugs, are recommended in areas where the prevalence of soil-transmitted helminth infection is high. Anthelminthic safety has been established primarily in school-age children. Our objective was to provide evidence on adverse events from anthelminthic use in early childhood. A randomized multi-arm, placebo-controlled trial of mebendazole, administered at different times and frequencies, was conducted in children 12 months of age living in Iquitos, Peru. Children were followed up to 24 months of age. The association between mebendazole administration and the occurrence of a serious or minor adverse event was determined using logistic regression. There was a total of 1,686 administrations of mebendazole and 1,676 administrations of placebo to 1,760 children. Eighteen serious adverse events (i.e., 11 deaths and seven hospitalizations) and 31 minor adverse events were reported. There was no association between mebendazole and the occurrence of a serious adverse event (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 0.47, 3.09) or a minor adverse event (OR = 0.84; 95% CI = 0.41, 1.72). Results from our trial support evidence of safety in administering mebendazole during early childhood. These results support World Health Organization deworming policy and the scaling up of interventions to reach children as of 12 months of age in endemic areas.

The Comparative Double-Blind Clinical Study in Antihelmintic Efficacy Between Thai Traditional Herbal Formulae and Mebendazole.

This study was carried out in Mahasarakham Primary Healthcare Centre, Mahasarakham province in the area of Northeastern of Thailand. The experiment was randomized controlled trial in the clinical study to examine the efficacy of Thai Traditional Herbal Formula (TTHF) in the treatment of antihelmintic activity of mixed worm infections in human. The 2 experimental groups consisted of 10 patients, and 5 patients for control group with inclusion and exclusion criteria, who were screened by the selection of mixed worm infection symptom samples. The investigation and extraction of worm eggs per gram (EPG) of patient feces method were performed with Ether-Formalin Sedimentation test. The percentage of reduction of EPG of patient feces were collected, counted, and confirmed by parasitologist, and the clinical efficacy was investigated by the physician and the pharmacist. The percent EPG data were collected before and after the treatment with TTHF and with mebendazole. The result showed that TTHF had higher efficacy in antihelmintic activity than mebendazole and placebo, which had the percent reduction of EPG of feces as 93.69 in TTHF and percent reduction of EPG of feces as 87.50 in mebendazole. The suggestion of this study should increase the number of samples of worm-infected patients, which the samples can be identified with the specific helminths genus and species to obtain the efficacy by the treatment using TTHF and mebendazole comparatively.

Clinical assessment of coded Unani formulation D-worm and mebandazole for the treatment of hook worm, roundworm and whip worm.

A case control, multicenter, prospective randomized two arm parallel group clinical trials was conducted on 190 patients. The main objective of this study is to provide comparative efficacy results of both trialed medicines. The comparison was done in between herbal medicine D-Worm and Mebandazole allopathic drug for the treatment of helminthiasis. All the rules of GCP (Good Clinical Practices) were followed including clinical history, clinical presentation, examination findings and stool tests. Stool D/R and Parasite antigen tests were performed before and after treatment. The comparison of symptoms were also done including the improvement in abdominal pain, worms in stool, anal itching, nausea and vomiting, loss of appetite, and fatigue etc. The data on clinical proforma was gathered and subjected to statistical analysis. Parasite specific antigen test and stool D/R is considered as gold standard test for the diagnosis and confirmation of helminthes infection. Different parameter i.e. age, sex, and other clinical sign and symptoms were studied and compared between two treatment groups (Control and Test groups) at baseline and end of therapeutic application. Consent of patient was taken at first before the start of examination. Majority of the patients (90%) included in this study group get cured after herbal treatment. The statistical analysis used for the assessment of the effect of the treatment also showed significant improvement after treatment.

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 trial.

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.

Efficacy and safety of praziquantel, tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.

BACKGROUND: Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths. METHOD: We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment. RESULTS: 156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel. CONCLUSION: Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55086560.

Oxantel pamoate-albendazole for Trichuris trichiura infection.

BACKGROUND: Infections with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) are widespread and often occur concomitantly. These parasitic-worm infections are typically treated with albendazole or mebendazole, but both drugs show low efficacy against T. trichiura. Albendazole is the drug of choice against hookworm. METHODS: In this double-blind trial conducted on Pemba Island, Tanzania, we randomly assigned children, 6 to 14 years of age, to receive one of four treatments: oxantel pamoate at a dose of 20 mg per kilogram of body weight, plus 400 mg of albendazole, administered on consecutive days; oxantel pamoate at a single dose of 20 mg per kilogram; albendazole at a single dose of 400 mg; or mebendazole at a single dose of 500 mg. We assessed the efficacy and safety profile of oxantel pamoate-albendazole when used in the treatment of T. trichiura infection (primary outcome) and concomitant soil-transmitted helminth infection (secondary outcome). Efficacy was determined by means of assessment of the cure rate and egg-reduction rate. Adverse events were assessed four times after treatment. RESULTS: Complete data were available for 458 children, of whom 450 were infected with T. trichiura, 443 with hookworm, and 293 with A. lumbricoides. The cure rate of T. trichiura infection was significantly higher with oxantel pamoate-albendazole than with mebendazole (31.2% vs. 11.8%, P=0.001), as was the egg-reduction rate (96.0% [95% confidence interval {CI}, 93.5 to 97.6] vs. 75.0% [95% CI, 64.2 to 82.0]). The cure rate with albendazole (2.6%) and the egg-reduction rate with albendazole (45.0%; 95% CI, 32.0 to 56.4) were significantly lower than the rates with mebendazole (P=0.02 for the comparison of cure rates). Oxantel pamoate had low efficacy against hookworm and A. lumbricoides. Adverse events (mainly mild) were reported by 30.9% of all children. CONCLUSIONS: Treatment with oxantel pamoate-albendazole resulted in higher cure and egg-reduction rates for T. trichiura infection than the rates with standard therapy. (Funded by the Medicor Foundation and the Swiss National Science Foundation; Current Controlled Trials number, ISRCTN54577342.).

[Up-to-date approaches in treatment of hydatid disease of the liver in childhood].

Sixty children (age 3-15 years) with hydatid disease of the liver were treated. The patients were divided into 2 equal groups (control and main groups).The hydatid disease of the liver was revealed in 22 (33.6%) patients, combined hydatid disease of the liver and lung were noted in 38 (66.4%) patients. The "capitonnage" of the residual cavity was applied in the control group and omentoplasty--in the main group. Chemotherapy with Nemazol (dose 10-15 mg/kg/day) was carried out. In order to reduce the negative influence of Nemazol on patients and to accelerate reparation processes of liver parenchyma Vobenzyme (2-3 pills/3 times/day) was applied. The number of complications was 23.2 % in the control group. The adhesive bowel obstruction was noted in 6.6% of patients, bleeding and jaundice in 3.3%, the residual cavity suppuration in 10%. Complications were registered in the main group in 6.6% of children (the adhesive bowel obstruction in 3.3%, preservation of the residual cavity after a year in 3.3%). The number of relapses in the control group was 6 (12%), there were no relapses in the main group. Thus the procedure of preoperative and postoperative chemotherapy allowed avoidance of the development of relapses of hydatid disease of the liver. Omentoplasty is the most rational method of treatment of residual cavity in surgery of hydatid disease of the liver in children.

Exposure to mebendazole and pyrvinium during pregnancy: a Danish nationwide cohort study.

PURPOSE: Families with children are frequently exposed to pinworm infection and treatment involves the whole family. Information on consequences of exposure during, pregnancy is limited. The aim of this study was to investigate the exposure to pyrvinium and mebendazole before, during, and after pregnancy in a Danish nationwide cohort. METHODS: From nationwide administrative registers, we identified 718,900 births in Denmark between January 1997 and December 2007 as well as maternal prescription data of anthelmintics and maternal characteristics. Redemption of a prescription for pyrvinium or mebendazole was used to identify exposure. RESULTS: 4715 women redeemed a prescription for pyrvinium or mebendazole during pregnancy; 1606 for pyrvinium, 2575 for mebendazole, and 534 for both drugs. Having >2 children compared to having no previous children was associated with exposure to pyrvinium (OR: 7.1, 95% CI: 5.8-8.7) and mebendazole (OR: 20.8, 95% CI: 17.3-24.9). CONCLUSION: 4715 pregnant women redeemed a prescription for either mebendazole or pyrvinium. We believe the exposure to be even higher since pyrvinium is also sold over-the-counter. Limited information on birth outcomes is available at present time, and considering the number of exposed pregnancies, we recommend that studies are to be undertaken to assess the safety of pyrvinium and mebendazole during pregnancy.

Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR.

BACKGROUND: Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. METHODOLOGY: We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n=100) and mebendazole (n=100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21-23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. PRINCIPAL FINDINGS: Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2-0.8; P=0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively). CONCLUSIONS/SIGNIFICANCE: Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN29126001.

The acceptability and safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and soil-transmitted helminthiasis in children aged 1-4 years in Uganda.

OBJECTIVE: There is limited information on the acceptability and safety of praziquantel for treatment of schistosomiasis in children below the age of four years. In addition, although mebendazole has been extensively used together with praziquantel against infections with schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged children, no specific acceptability or safety studies have been published on this drug combination in younger children. METHODS: A randomized clinical trial was conducted to determine the safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and STH in children aged 1 to 4 years. RESULTS: A total of 596 children from Bwondha fishing community in Mayuge district and Wang-Kado fishing community in Nebbi district were investigated using duplicate Kato-Katz thick smears of two stool samples and 130 (21·8%) were found infected with S. mansoni. Of these, 19·2% (25) had heavy intensity of infections. Of the infected children, 82 were included and randomised into praziquantel (40 mg/kg) + mebendazole (500 mg) or praziquantel (40 mg/kg) alone. CONCLUSION: Many symptoms were reported before treatment while very few were reported after treatment and all on treatment day. No serious adverse events were reported or observed after treatment. Praziquantel with or without mebendazole was well tolerated in small children in the study area.

Meningoencefalitis por Loa loa secundaria a tratamiento con mebendazol / Loa loa meningoencephalitis secondary to treatment with mebendazol

No disponible