Albendazole Group Research Articles

Albendazole-ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial.

Treatments for soil-transmitted helminthiases face challenges, especially in addressing Trichuris trichiura. Combination regimens, particularly of ivermectin and albendazole, are promising. We aimed to assess the safety, efficacy, and palatability of a combination tablet for the treatment of T trichiura, hookworm, and Strongyloides stercoralis infections among school-aged children in Ethiopia, Kenya, and Mozambique. We conducted an adaptive phase 2/3, randomised, parallel-group, active-controlled, superiority trial in 15 schools in Ethiopia, Kenya, and Mozambique. Eligible participants for both phases were aged 5-18 years, weighed at least 15 kg, and were infected with T trichiura, hookworms, or S stercoralis. Participants were randomly assigned via a computer-generated sequence to either a single dose of a fixed-dose combination (FDC×1) of albendazole (400 mg) plus ivermectin (9 mg or 18 mg), three consecutive daily doses of an FDC (FDC×3) of albendazole (400 mg) plus ivermectin (9 mg or 18 mg), or a single dose of albendazole alone (400 mg) via block randomisation, stratified by soil-transmitted helminth species. Participants and those administering the treatments were not masked to treatment assignment, but those assessing the outcomes were masked. The primary outcome of phase 2 (conducted in Kenya only) was safety during the first 3 h after the intervention and for 7 days, and the primary outcome of phase 3 was efficacy (ie, the proportion of individuals cured at day 21 out of the total number infected at baseline) for T trichiura; both primary outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT05124691, and is terminated. Between Jan 20, 2022, and March 24, 2023, 1001 participants were recruited (465 [46%] were female and 536 [54%] were male). 636 (64%) were infected with T trichiura, 360 (36%) with hookworm, and 104 (10%) with S stercoralis; 94 (9%) of 1001 participants had co-infections and were included in the analysis of each infecting species. A total of 243 participants were allocated to the albendazole group, 381 to the FDC×1 group, and 377 to the FDC×3 group. In both phase 2 and 3, gastrointestinal symptoms were the most common mild-to-moderate adverse events in the FDC groups, but resolved within 48 h without intervention. At least one treatment-related adverse event occurred in 34 (14%) of 243 participants in the albendazole group, 75 (20%) of 381 participants in the FDC×1 group, and 88 (23%) of 377 participants in the FDC×3 group. No serious adverse events occurred. For T trichiura, both FDC groups had a higher cure rate (97·2% [95% CI 95·2- 99·3] for FDC×3 and 82·9% [78·2-87·5] for FDC×1) than albendazole (35·9% [27·7-44·1]), with absolute differences of 61·3% (98% CI 50·2-71·2) and 47·0% (34·7-58·1), respectively. For hookworms, FDC×3 had a higher cure rate (95·0% [95% CI 91·1-98·9]) than albendazole (65·1% [56·0-74·2]), with absolute differences of 29·9% (98% CI 17·2-42·4), whereas FDC×1 had a similar cure rate (79·8% [72·8-86·9]) to albendazole. The sample size for efficacy evaluation of S stercoralis was not met. An FDC of albendazole plus ivermectin has a similar safety profile but superior efficacy to albendazole alone against T trichiura infection and hookworms. These findings open opportunities for control of all soil-transmitted helminth species of interest, including potentially S stercoralis. Evaluation of safety in larger populations and implementation scenarios are the next steps for this innovation to promote its incorporation into programmatic activities. The European and Developing Clinical Trials Partnership. For the Portuguese translation of the abstract see Supplementary Materials section.

Tea Saponins: a Novel Stabilizer for Enhancing the Oral Bioavailability of Albendazole Nanocrystals.

Albendazole serves as a broad-spectrum anthelmintic medication for treating hydatid cysts and neurocysticercosis. However, its therapeutic effectiveness is limited by poor solubility. Nanocrystals offer a promising technology to address this limitation by enhancing drug solubility. The objective of this study is to evaluate an effective stabilizer for creating an albendazole nanocrystal formulation to improve oral absorption. Among different surfactants and polymers examined, tea saponins were used as the stabilizer to develop a nanosuspension with the particle size of 180nm through a wet grinding approach. The physical characteristics of the nanocrystals were assessed using SEM, DSC, and XRPD. The nanocrystals significantly enhanced solubility by 2.9-2602 fold in different media and showed significant enhancement in dissolution rate compared to albendazole crystals in both pH 1.0 and pH 6.8 medium. Everted gut sacs experiments demonstrated that the nanocrystals increased Papp by 3.60-fold in duodenum, 3.76-fold in jejunum, 3.71-fold in ileum, and 5.26-fold in colon, respectively. Furthermore, pharmacokinetic studies revealed that the nanocrystals significantly enhanced oral bioavailability, resulting in a 4.65-fold increase in plasma AUC0-t value of albendazole sulfoxide (the primary active metabolite of albendazole) compared to the albendazole group. The present data indicates that tea saponins are potential natural stabilizers for preparing nanocrystals with enhanced oral bioavailability for insoluble drugs.

Investigating the therapeutic effects of curcumin nanocapsules in hydatid cyst-infected mice

Background/objectiveThe primary treatment for cysts is surgery, including removing the cyst and administering the appropriate chemical drugs. Herbal remedies have gained popularity as a viable and secure alternative to conventional pharmaceuticals. It may be advantageous to use nanocapsules to overcome the bioavailability challenges associated with herbal remedies like curcumin. The present study aims to provide insights into the effectiveness of curcumin nanocapsules in treating hydatid infections. MethodsCurcumin-loaded oil-in-water surfactant-based biocompatible nanomicelles were developed from dissolving Curcumin in 1% (w/w) solutions of ethyl butyrate oil by dissolving an amount of fatty acid sodium caprylate (SC, 0.09 g) and F127 (0.009 g), phosphate-buffered saline (PBS at pH 7.4) under vigorous stirring at a fixed ethyl butyrate-to-surfactant molar ratio of 10 and final total volume of 50 mL. The excess of free PHT was eliminated by dialysis for 24 h. Following five months after infection, 45 mice were divided into six groups. Groups 1, 2, and 3 were treated daily with curcumin nanocapsules (0.5, 0.25, 0.125 mg/ml) for one month. Group 4 was treated with curcumin (0.5 mg/ml), group 5 was treated with albendazole (150 mg/kg), and group 6 was the negative control group without treatments (only received saline). A detailed analysis of the cysts' physical characteristics, including their size and weight, has been conducted. ResultsThe mean zeta potential spectrum of the nanocapsules was −33.96 mV. Regarding the total cyst numbers, all three nanocapsule groups had significantly lower total cyst numbers than the curcumin, albendazole, and negative control groups. Regarding the total cyst weight, all three nanocapsule groups had a significantly lower total cyst weight than the curcumin and negative control groups. Regarding the cyst with the maximum size, nanocapsules groups 1 and 2 had a significantly smaller size than the curcumin, albendazole, and negative control groups. ConclusionThe current study found that encapsulation positively affects curcumin efficacy as a superior alternative to chemical drugs, offering both biological advantages and environmental benefits.

Efficacy and safety of emodepside compared with albendazole in adolescents and adults with hookworm infection in Pemba Island, Tanzania: a double-blind, superiority, phase 2b, randomised controlled trial

Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections. We conducted a double-blind, superiority, phase 2b, randomised controlled clinical trial comparing emodepside and albendazole. Participants in the emodepside group received six 5 mg tablets of emodepside (totalling 30 mg) and one placebo; participants in the albendazole group received one 400 mg tablet of albendazole and six placebos. Participants were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania. Participants aged 12-60 years were eligible for treatment if they were positive for hookworm infection, and they had 48 or more eggs per gram from four Kato-Katz thick smears and at least two slides had more than one hookworm egg present. Participants' treatment allocation was stratified by infection intensity and efficacy was measured by cure rate: participants who were hookworm positive and became hookworm negative after treatment. Adverse events were reported at 3 h, 24 h, 48 h, and 14-21 days post-treatment. The trial is registered at ClinicalTrials.gov, NCT05538767. From Sept 15 to Nov 8, 2022, and from Feb 15 to March 15, 2023, 1609 individuals were screened for hookworm. Of these, 293 individuals were treated: 147 with albendazole and 146 with emodepside. Emodepside demonstrated superiority, with an observed cure rate against hookworm of 96·6%, which was significantly higher compared with albendazole (cure rate 81·2%, odds ratio 0·14, 95% CI 0·04-0·35; p=0·0001). The most common adverse event in the emodepside treatment group was vision blur at 3 h after treatment (57 [39%] of 146). Other common adverse events were vision blur at 24 h after treatment (55 [38%]), and headache and dizziness at 3 h after treatment (55 [38%] for headache and 43 [30%] for dizziness). In the emodepside treatment group, 298 (93%) of the 319 adverse events were mild. The most commonly reported adverse events in the albendazole treatment group were headache and dizziness at 3 h after treatment (27 [18%] of 147 for headache and 14 [10%] for dizziness). No serious adverse events were reported. This phase 2b clinical trial confirms the high efficacy of emodepside against hookworm infections, solidifying emodepside as a promising anthelmintic candidate. However, although the observed safety events were generally mild in severity, considerations must be made to balance the strong efficacy outcomes with the increased frequency of adverse events compared with albendazole. European Research Council.

In vivo anthelmintic effect of Artemisia annua L. on oxyurid nematodes of laboratory mice

Oxyurids are common intestinal parasites of mammals, and they are the cause of recurrent helminthic infections, especially in children Hence natural herbal compounds are necessary for a repeatable cure. This study aimed to investigate the antinematodal effect of Artemisia annua L. n-hexane extract on oxyurids in vivo. In this study, A. annua L. n-hexane extract was applied to mice naturally infected with Syphacia obvelata and Aspiculuris tetraptera species orally at 300, 600, and 1200 mg/kg doses for seven days and the change occurring in the number of oxyurid eggs was investigated by the fecal flotation method. The nematodes in the necropsy were compared on the 8th day in all groups in terms of number, gender, and species. Albendazole (ABZ) was applied at a 5 mg/kg dose for three days as positive drug control, and corn oil was used as solvent control. The arithmetic mean of oxyurid eggs counted in fecal flotation 43.51% decrease in the drug control ABZ group and showed a 21.12% increase in the A. annua 1200 mg/kg group on the last day of application. When compared with the corn oil group, a 34.08%, 34.76% and 36.91% decrease in ABZ 5 mg/kg, A. annua 300 mg/kg and A. annua 1200 mg/kg group respectively were found in their necropsies in terms of nematode number. Non-polar compounds of A. annua L., very low concentration of ABZ and as a dilution solvent corn oil are probably responsible for this result.

Influence of fasting on the efficacy of anthelminthics in naturally infected sheep

The aim of this study was to verify the effect of fasting on the anti-helminthic efficiency of ivermectin-albendazole-levamisole (IAL) combination (first stage) and the closantel and albendazole (second stage) in sheep naturally infected with gastrointestinal nematodes. To this end, fecal samples from young (4 to 6 months), male and female sheep were evaluated seven and 14 days after the treatments, using the Egg count Per Gram of feces (EPG) and the Fecal Egg Count Reduction Test (FECRT). In the first stage of the experiment, the mean EPG of the animals treated and fasted beforehand was lower than the mean EPG of the animals treated, but not fasted 14 days after treatment. Moreover, the group of fasted animals exhibited a better reduction in fecal egg count rate. In the second stage, there was no significant decrease in the mean EPG of the animals in any group (closantel and albendazole) and the efficiency calculated by FECRT was low for the closantel group and zero for the albendazole group. However, the decrease in EPG in animals treated with closantel after fasting was 326.8% greater than the decrease in EPG in animals treated without prior fasting. It was evident that fasting had a positive influence on the reduction of the genera Haemonchus, Cooperia, Trichostrongylus and Oesophagostomum in the animals treated with closantel. The anthelminthic effect of closantel, albendazole and ivermectin-albendazole-levamisole (IAL) combination in sheep was significantly enhanced by previous fasting. Therefore, it is strongly recommended to withhold solid food for a minimum of 12 hours before administering these treatments.

An in vivo appraisal of Punica granatum peel extract's ultrastructural effect on cystic echinococcosis in mice.

In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.

Emodepside for Trichuris trichiura and Hookworm Infection

BackgroundCurrent treatments for soil-transmitted helminth infections in humans have low efficacy against Trichuris trichiura. Emodepside — a drug in veterinary use and under development for the treatment of onchocerciasis in humans — is a leading therapeutic candidate for soil-transmitted helminth infection.MethodsWe conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against T. trichiura and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom T. trichiura or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of T. trichiura or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato–Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo.ResultsA total of 266 persons were enrolled in the T. trichiura trial and 176 in the hookworm trial. The predicted cure rate against T. trichiura in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events.ConclusionsEmodepside showed activity against T. trichiura and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.)

Physical Fitness, Growth and Appetite of Kenyan School Boys with Hookworm, Trichuris trichiura and Ascaris lumbricoides Infections are Improved Four Months after a Single Dose of Albendazole

We studied physical fitness with the Harvard Step Test, growth, and appetite in primary school boys infected with hookworm (96% baseline prevalence), Trichuris trichiura (98% prevalence) and Ascaris lumbricoides (41% prevalence) who received a single 600-mg dose of albendazole or an identical placebo. Boys were examined, allocated at random within pairs by descending hookworm egg count to placebo (n = 26) or albendazole (n = 27) groups, treated, and re-examined 4 mo later. Four months after treatment, the albendazole group showed highly significant improvements in fitness score, resting heart rate, and heart rates at 1, 2, 3 and 4 min after the Harvard Step Test, whereas the placebo group had not changed significantly. The albendazole group also exhibited significantly more rapid growth judged by weight gain (1.0 kg greater than the placebo group, P < 0.0002), height increment (0.6 cm more, P < 0.003), arm circumference (0.3 cm more, P < 0.0002), and triceps and subscapular skinfolds (1.0 mm more, P < 0.0002), and showed improved appetite with objective and subjective measures. We conclude that single-dose treatment with albendazole can allow improved physical fitness, growth, and appetite in school-age children in areas where these helminths and poor growth are highly prevalent.

Assessment of Oral Albendazole and Fumagillin in the Treatment of Pseudoloma neurophilia in Adult Zebrafish.

Pseudoloma neurophilia (Pn), the causative agent of the most commonly reported disease of zebrafish, is a microsporidianparasite that confounds research by inducing behavioral and physiologic changes in zebrafish. Although a treatmentfor P. neurophilia has not been documented in zebrafish, albendazole (ALB) and fumagillin (FUM) have been used to treatmicrosporidian infections of other fish species. To investigate the efficacy of oral ALB and FUM in the treatment of Pn, weperformed a pilot study that demonstrated the safety and palatability of novel gel-based diets containing FUM or ALB inadult AB zebrafish. In a subsequent study, approximately 250 adult AB zebrafish (previously infected with Pn) were treatedwith these medicated diets for 4 wk. At 4 different time points (weeks 0, 5, 10, and 16 of the study), fish were euthanized andwhole-body qPCR was performed to assess Pn prevalence across treatment and control groups. There was no statisticallysignificant association between treatment group and Pn prevalence at any time point, although potential biologically relevantreductions in Pn prevalence occurred in the combination therapy group at weeks 5 and 16 and in the ALB group at week 5.Based on high-performance liquid chromatography analyses, the medicated diets contained less ALB and more FUM thanexpected, highlighting the importance of validating medicated feed concentrations to ensure safety, efficacy, and consistency.While Pn remains challenging to eradicate and control, results of this study warrant further investigation into the utility ofALB and FUM as potential treatments for this pathogen.

Efficiacy of albendazole and paromomycin treatments against natural Giardia spp. infection in calves

The aim of the present study was to evaluate and compare the efficiacy of albendazole and paromomycine treatments against natural Giardia spp. infection in calves. The calves were divided in two groups of six animals each with similar parasitic loads of Giardiaspp. cysts. Albendazole (20 mg/kg) and paromomycin (50 mg/kg) were administrated orally to group A and group P, respectively, for three consecutive days. The efficiacies of drugs evaluated by analyzing the reduction in cyst excretion in native fecal examinations on days 0, 3, 7, 10, 14, 21 and 28. In addition, percentages of reduction for days 3, 7, 10, 14, 21 and 28 according to day 0 were evaluated. The geometric mean of fecal cyst excretion in both groups started to decrease from the 3rd day, in paromomycin group the decrease continued steadily throughout the examination days starting from the 3rd day, despite that in the albendazole group the cyst amount increased in the 7th day and then decreased again. Cyst excretion reached zero in all animals at the 21st and 28th days in group P and group A, respectively. The percentage of reduction started with a high rate of 47.72% on the third day and reached 100% on the 21st day in the paromomycin group. In the albendazole group, the percentage of reduction started with a rate of 35.29% on the third day and reached 100% on the 28th day. As a result, paromomycin was found to be more effective compared to albendazole in terms of both the regularity of the mean cyst reduction and the time it takes for the cyst excretion to reach zero.

Histopathological and Biochemical Evaluation of Albendazole in the Treatment of Infected Mice with Hydatid Cyst

Introduction: Hydatidosis, caused by the larval stage of Echinococcus granulosus, is a prevalent parasitic disease affecting both humans and animals. Albendazole is currently the most effective drug for treating hydatid cysts. This research aimed to investigate the histopathological and biochemical effects of Albendazole on the liver, lung, and kidney of mice experimentally infected by hydatid cysts.&#x0D; Materials and methods: A total of 20 mice weighing approximately 220 g were used. The rats were randomly divided into the Albendazole group (100 mg/kg/day) and the control group (infected Rats without treatment). At the end of the experiment, tissue samples from the liver, lung, and kidney were collected for histopathological evaluation. Liver blood tests were used to assess liver functions or liver injury (alkaline phosphatase, alanine aminotransferase, and bilirubin).&#x0D; Results: After 30 days of daily treatment, the total numbers of cysts, size, and weight of the largest cyst were significantly lower in the Albendazole group, compared to the control group. The study addressed histopathological changes in the liver, kidneys, and lungs caused by hydatid cysts, such as tissue necrosis, hemorrhage, and local inflammation, indicating the potential for serious complications and significant damage to these organs. The group treated with Albendazole showed severe histopathological changes in the liver, kidneys, and lungs, compared to the control group. This suggests that Albendazole may trigger a more aggressive response in these organs to the cysts, leading to increased tissue damage. In addition, alkaline phosphatase, alanine aminotransferase, and bilirubin concentrations revealed a significant increase in the Albendazole group.&#x0D; Conclusion: While Albendazole is an effective drug for treating hydatidosis, it can also cause severe side effects on various organs in the body. Therefore, alternative treatment strategies need to be developed to minimize these adverse effects.

Improvements of cognitive functions in mice heavily infected by Angiostrongylus cantonensis after treatment with albendazole, dexamethasone, or co-therapy.

Angiostrongylus cantonensis, the causative agent of human eosinophilic meningitis and eosinophilic meningoencepalitis, has been reported to cause cognitive impairments in the host. To determine whether drug treatment improves the cognitive functions, BALB/c mice infected with 50 third-stage larvae were treated with albendazole, dexamethasone, or co-therapy since day 7 or 14 post-infection for one or two weeks. Abilities of spatial memory and learning of these animals were assessed with the Morris water maze. Our results showed that body weight was significant higher then infected group in the albendazole and combined therapy groups. Significantly lower worm recovery rates were found in mice treated with the same groups. The mice treated with dexamethasone since day 7 for 14 day had significant longer time in the remaining groups were found in forced swimming test. The animals treated with albendazole and combined therapy since day 7 for 14 days was demonstrated to have significantly shorter latencies to the platform in learning memory on day 3 and 4. Mice in these two groups were demonstrated to have significantly higher sores in spatial memory tests. These results indicate that treatment with albendazole or combined therapy may be more efficient in preventing brain damages and depression as well as preserving their capabilities in learning and memory. Therefore, administration of albendazole alone or combined with dexamethasone should have higher efficacies than dexamethasone alone in treatment of BALB/c mice infected with a heavy dose of 50 third-stage larvae of A. cantonensis.

Comparison of Albendazole and Mebendazole on Soil-Transmitted Helminth Infections among School-Aged Children

BACKGROUND: Anthelmintics, such as albendazole and mebendazole, are widely used to treat soil-transmitted helminths (STHs). With its extensive usage and administration along with other medical prescriptions, different environmental conditions, etc., some studies have reported unsatisfactory efficacy from albendazole to treat STHs. AIM: To observe the efficacy of albendazole and mebendazole as a single dose in treating STH infections in elementary school children. METHODS: An open randomized clinical trial was conducted in Batubara, North Sumatra, comparing the efficacy of albendazole and mebendazole. Samples were 6−12-year-old children infected with STHs based on Kato-Katz examination. A Chi-square test was performed to compare the cure rate and a t-test was done to compare the number of eggs per gram (EPG) feces in both groups. RESULT: A total of 199 children from 426 met the study criteria. There was a significant difference (p &lt; 0.05) in the cure rate of Ascaris lumbricoides infections at 87.5% and 31% for albendazole and mebendazole groups, respectively. The cure rate of Trichuris trichiura infection at 61.5% and 65.6% with albendazole and mebendazole, respectively, and there was no significant difference (p &gt; 0.05). There was a significant reduction in the number of eggs of all STHs after the treatment either with albendazole or mebendazole. CONCLUSION: Single-dose albendazole has better efficacy against Ascaris lumbricoides infection than mebendazole. Meanwhile, both albendazole and mebendazole have high efficacy in reducing the number of eggs.

Efficacy of Combination Therapy of Albendazole and Praziquantel vs Albendazole Monotherapy in Children With Persistent Neurocysticercosis: A Randomized Controlled Trial.

To compare the efficacy of combined albendazole and praziquantel therapy vs albendazole monotherapy in a placebo-controlled, double-blinded, randomized trial in children with persisting neurocysticercosis. Children with persistent neurocysticercosis were randomized into 3 groups-albendazole (n = 19), albendazole and praziquantel (n = 21), and placebo (n = 20)-for 30 days and followed up at 3 and 6 months for resolution and recurrence of seizures. Mean age of children was 9.3 ± 2.9 years (range 3-14). At baseline, the majority of lesions were ring-enhancing (70%), colloidal (97%), with scolex (68%) and perilesional-edema (45%), and located in the parietal (58%) lobe. One case each in albendazole and placebo groups had a recurrence of seizure in the first month of treatment. The majority (62%) of children in the combination therapy group showed complete resolution of the persisting lesion at the end of 6 months compared to the albendazole alone group (26.3%, P = .02). Percentage reduction in the lesion's mean area at 6 months was highest in the combination group compared with other groups (P = .006). Rate of calcification was identical in all 3 groups (10%). None of the patients required interruption of therapy. Our study demonstrates the safety and efficacy of albendazole and praziquantel in combination for complete radiologic resolution in children with persistent neurocysticercosis when compared with albendazole monotherapy or placebo. The combination therapy did not result in increased seizure recurrence or adverse drug reaction compared with albendazole monotherapy.

Efficacy and safety of co-administered ivermectin and albendazole in school-aged children and adults infected with Trichuris trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania: a double-blind, parallel-group, phase 3, randomised controlled trial

Preventive chemotherapy with albendazole or mebendazole remains one of the cornerstones of soil-transmitted helminth control. However, these drugs are less effective against Trichuris trichiura. Combined ivermectin-albendazole is a promising treatment alternative, yet robust evidence is lacking. We aimed to demonstrate superiority of co-administered ivermectin-albendazole over albendazole monotherapy in three distinct epidemiological settings. We conducted a double-blind, parallel-group, phase 3, randomised controlled trial in community members aged 6-60 years infected with T trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania, between Sept 26, 2018, and June 29, 2020. Participants with at least 100 T trichiura eggs per g of stool at baseline were randomly assigned (1:1) using computer-generated randomisation sequences in varying blocks of four, six, and eight, stratified by baseline T trichiura infection intensity, to orally receive either a single dose of ivermectin (200 μg/kg) plus albendazole (400 mg) or albendazole (400 mg) plus placebo. Patients, field staff, and outcome assessors were masked to treatment assignment. The primary outcome was cure rate against T trichiura, defined as the proportion of participants with no eggs in their faeces 14-21 days after treatment, assessed by Kato-Katz thick smears, and analysed in the available-case population according to intention-to-treat principles. Safety was a secondary outcome and was assessed 3 h and 24 h after drug administration. The trial is registered at ClinicalTrials.gov, NCT03527732. Between Sept 13 and Dec 18, 2019, Jan 12 and April 5, 2019, and Sept 26 and Nov 5, 2018, 3737, 3694, and 1435 community members were screened for trial eligibility in Côte d'Ivoire, Laos, and Pemba Island, respectively. In Côte d'Ivoire, Laos, and Pemba Island, 256, 274, and 305 participants, respectively, were randomly assigned to the albendazole group, and 255, 275, and 308, respectively, to the ivermectin-albendazole group. Primary outcome data were available for 722 participants treated with albendazole and 733 treated with ivermectin-albendazole. Ivermectin-albendazole showed significantly higher cure rates against T trichiura than albendazole in Laos (66% [140 of 213]vs 8% [16 of 194]; difference 58 percentage points, 95% CI 50 to 65, p<0·0001) and Pemba Island (49% [140 of 288]vs 6% [18 of 293], 43 percentage points, 36 to 49, p<0·0001) but had similar efficacy in Côte d'Ivoire (14% [32 of 232]vs 10% [24 of 235], 4 percentage points, -2 to 10, p=0·24). No serious adverse events were reported; observed events were mostly classified as mild (95% [266 of 279] in the albendazole group and 91% [288 of 317] in the ivermectin-albendazole group), and all were transient in nature. Treatment with ivermectin-albendazole resulted in higher efficacy against trichuriasis than albendazole alone in Laos and Pemba Island but not in Côte d'Ivoire. We recommend implementation of this combination therapy for soil-transmitted helminth control in countries with high T trichiura prevalence and proven enhanced efficacy of this treatment, particularly where ivermectin is beneficial against other endemic helminthiases. Bill & Melinda Gates Foundation.

In vitro evaluation of albendazole-loaded nanostructured lipid carriers on Echinococcus granulosus microcysts and their prophylactic efficacy on experimental secondary hydatidosis.

To enhance the therapeutic effects of albendazole (ABZ) on Echinococcus granulosus protoscoleces and metacestodes, ABZ-loaded nanostructured lipid carriers (ABZ-NLCs) are prepared by the hot high-speed homogenization method. Protoscoleces and microcysts were treated in vitro with free ABZ and ABZ-NLCs (concentrations of 1, 5, and 10μg/ml), and the corresponding effects were monitored by methylene blue exclusion test and scanning and transmission electron microscopy. Chemoprophylactic treatment was performed on Balb/C mice 1day before intraperitoneal injection of viable protoscoleces. The drugs were administered daily by intragastric inoculation for a period of 30days. The prophylactic efficacy was assessed based on the number and weight of cysts developed in treated mice. The ultrastructural alterations in cysts were examined by transmission electron microscopy. After 18days, all the protoscoleces incubated with 10μg/ml ABZ-NLCs were killed, while 51.25 ± 4.03% of the protoscoleces incubated with 10μg/ml free ABZ were still viable. Microcysts treated with ABZ-NLCs underwent degenerative alterations in a shorter time than when free ABZ was applied. The mean weight of the cysts recovered from mice of ABZ-NLCs group was significantly lower than that of the free ABZ group (P < 0.05), yielding prophylactic efficacy of 92.45% and 38.53%, respectively. The cysts treated with ABZ-NLCs showed marked ultrastructural changes in the germinal layer. This study demonstrated that both in vitro and in vivo treatments with ABZ-NLCs are significantly more efficient than treatment with free ABZ against E. granulosus protoscoleces, metacestodes, and prevention of cyst development in mice.

The effects of levamisole and albendazole on spermatological parameters, testosterone levels, and sperm DNA damage in Saanen bucks.

This study aimed to investigate the effect of levamisole and albendazole on spermatological parameters, testosterone levels, and sperm DNA damage in Saanen bucks. For this purpose, twenty-four Saanen bucks were divided into three groups as control, levamisole, and albendazole administration group. The control group received only water (20ml, oral), the levamisole group received 7.5mg/kg of levamisole (2 oral tablets once daily for 2days) + water (20ml, oral), and the albendazole group received 7.5mg/kg of albendazole (1 oral tablet) + water (20ml, oral). Semen and blood samples were collected from all animals, both before drug application (day 0) and within a 2-day interval after drug application between day 1 (day of the treatment) and day 11. Spermatological parameters were evaluated immediately after collection. Testosterone levels were also measured from the blood samples with ELISA. Sperm DNA damage was determined with comet assay. The present research showed that especially albendazole administration decreased spermatological parameters and levamisole administration decreased testosterone levels. Significant sperm DNA damage was seen after both albendazole and levamisole administration. As a result, albendazole and levamisole administration should be used carefully on Saanen bucks, especially during the breeding season.

Radical versus conservative surgical management for liver hydatid cysts: A single-center prospective cohort study.

Background and AimWe prospectively compared the clinical outcomes of radical and conservative surgical procedures for primary liver hydatid cysts, additionally radical surgical procedures with and without the two‐month administration of albendazole after the operation were compared.MethodsOverall, 90 patients undergoing open surgical treatment for liver hydatid cysts were divided into three surgical groups: first group, patients who underwent radical surgery (pericystectomy) followed by albendazole treatment for 2 months following the operation group; second group, patients who underwent radical surgery(pericystectomy) without receiving albendazole after surgery group; third group, patients, who underwent conservative surgery (partial cystectomy) with albendazole treatment after surgery. The clinical outcomes and rate of recurrence were analyzed in follow‐up period.ResultsThe mean surgery duration in the Radical groups was significantly longer in comparison to the Conservative surgery + Albendazole group. (212.0 and 202.5 min vs. 173.2 min; p < 0.05). Blood loss in the Radical groups was significantly higher in comparison to the Conservative surgery + Albendazole group (218.3 and 174.6 ml vs. 67.2 ml; p < 0.05). However, postoperative complication rate in the Radical group was significantly lower in comparison to Conservative surgery + Albendazole group (13.3% [n = 4] and 6.7% [n = 2] vs. 36% [n = 11]; p < 0.05). The postoperative hospital stay in both Radical groups was significantly lower in comparison to the Conservative surgery + Albendazole group (7.9 and 7.4 days vs. 11.3 days; p < 0.05).ConclusionIn comparison to conservative surgery, radical surgery is a preferable treatment modality for patients with active liver hydatid cysts. Postoperative albendazole treatment is preferable, regardless of the type of surgical procedure.

Nephrotoxicity of Albendazole and Albendazole Loaded Solid Lipid Nanoparticles in Mice with Experimental Hydatidosis.

Purpose: Cystic echinococcosis (CE) is a serious contemporary public health problem. Different CE treatment methods are of considerable importance, with albendazole (ABZ) being one of the most preferred drugs for CE treatment and prophylaxis. In this study, we evaluated the nephrotoxicity caused by ABZ and ABZ-loaded solid lipid nanoparticles (SLNs) in mice with experimental hydatid cyst. Methods: ABZ-loaded SLNs were produced by micro-emulsification and a high shear homogenization technique. Thereafter, we evaluated the physicochemical characterization of the product. Live protoscolices were injected into mice to induce experimental hydatidosis. Mice were then treated with ABZ and ABZ-loaded SLNs. The nephrotoxicity effects were evaluated by biochemical and histopathological surveys. Results: Significantly different blood urea nitrogen (BUN) levels were observed between the two infected groups (ABZ treatment and ABZ-loaded SLN treatment) and the control group. The kidney malondialdehyde (MDA) and glutathione (GSH) levels of the infected groups were not significantly different from those of the control group. The histopathological study revealed nephropathic and pathologic changes in the ABZ and ABZ-loaded SLN groups. Conclusion: ABZ formulated for ABZ-loaded SLNs had a more prominent chemoprophylactic efficacy on CE and fewer side effects than ABZ alone. Neither ABZ nor ABZ-loaded SLNs caused significant biochemical and histopathological defects on the kidney, and all functional biochemical markers stayed within the normal range. Therefore, ABZ-loaded SLNs could be a potential new product for CE treatment.