Long-term albendazole therapy for diffuse parenchymal neurocysticercosis in an immunocompetent patient:A case report

Rationale:Neurocysticercosis is a neglected tropical disease caused by the larvae of Taenia solium and may occur in immunocompetent people.We report a case of diffuse parenchymal neurocysticercosis mimicking tuberculous meningitis in an immunocompetent patient.Patient concerns:A 24-year-old immunocompetent woman presented with serial focal to generalized seizure,left body weakness,left abducens palsy,chronic cough,and body weight loss.She came from an area where she was unlikely to have contact with Taenia solium.Diagnosis:Diffuse parenchymal neurocysticercosis.Intervention:Valproic acid,dexamethasone and 15 months of albendazole therapy.Outcome:Complete recovery without any neurological sequelae.

对Albendazole治疗脑豚囊虫病的疗效评价

<正> 在我国脑豚囊虫病的发病率并不低,且致残率亦较高,因此,研究治疗脑豚囊虫病的药物是个重要课题,既往有报告用吡喹酮治疗,但结果不太理想。本文试用

Formulation and evaluation of Albendazole microcapsules for colon delivery using chitosan

Objective:To formulate and evaluate Albendazole microcapsules using chitosan,a natural polymer for colon-specific delivery for better treatment of helminthiasis,filariasis,colorectal cancer,avoiding the side effects.Methods:The Albendazole microcapsules were prepared by the use of different concentrations of sodium alginate,chitosan and hydroxypropyl methylcellulose(HPMC).The polysaccharides chitosan reacted with sodium alginate in the presence of calcium chloride to form microcapsules with a polyelectrolyte complex membrane by electrostatic interactions between the two oppositely charged polymers.The microcapsules were then studied for entrapment efficiency,drug-polymer compatibility and surface morphology. In vitro drug release study in presence and absence of cecal content were also studied.Further, kinetic modellings were employed to find out release mechanisms.Results:Albendazole loaded microspheres showd high entrapment efficiency(72.8%) and the microcapsules were free flowing,non aggregated and spherical,between 600 and 1 000μm in diameter.The surface of microcapsules were found to be porous and wavy.The FT-IR spectrum showed that there is no interaction between the polymer and the drug.The in vitro drug release study found to be affected by change in chitosan,sodium alginate and HPMC concentration.The microcapsules with 2.5% sodium alginate and 0.4% chitosan shown minimum release in gastrointestinal simulated condition but shows maximum drug release at the end of 24th hour in presence of cecal content.The rate of drug release follows Korsmeyer-peppas model that was the drug release is by diffusion and erosion.Conclusions:The study reveals that Albendazole loaded chitosanalginate based microsphere can be used effectively for the colon targeting.

Current status of the efficacy and effectiveness of albendazole and mebendazole for the treatment of Ascaris lumbricoides in North-Western Indonesia

Objective:To investigate the efficacy and effectiveness of albendazole and mebendazole in the treatment of Ascaris lumbricoides(A.lumbricoides) in the North-Western Indonesia.Methods: 229 primary school children who were positive for A.lumbricoides in their stool were recruited in the study.123 children received single-dose of 400 mg albendazole and 106 children received single-dose 500 mg of mebendazole.After 1 week,their stools were examined for the cure rate (CR) and egg reduction rate(ERR).Egg culture was also performed and observation was made on week-1,-3,-4.Results:have shown a non-significant difference in CR 96.7%vs.100%:and ERR of 99.3%vs.100.0%for albendazole and mebendazole groups respectively(P】0.05).In-vitro egg culture has shown trends of decrease in the percentage of the unfertilized eggs and in≥2 cell eggs in both treatment groups(P【0.05).The embryonated eggs from the albendazole groups has shown an increase from 7.3%on week-1 to 13.8%on week-4,whilst the mebendazole group has shown a constant increase during the whole 4 weeks of culture from 7.5%to 28.3%(P【0.01). Conclusions:No evidence of drug resistance is noted so far from the area of North-Western part of Indonesia.In addition,although both drugs showed incomplete ovicidal effects,single-dose albendazole is better than mebendazole in sterilizing A.lumbricoides eggs.

Study on the inclusion interaction of methylated-β-cyclodextrins with albendazole by spectrofluorimetry and its application

The inclusion interaction between three types of methylated-β-cyclodextrins （Me-β-CDs） and albendazole （ABZ） was studied by spectrofluorimetry. The result showed that Me-β-CDs reacted with ABZ to form an inclusion complex, 1： 1 stoichiometry for Me- β-CDs-ABZ complex was established and its association constant have been determined from fluorescence data by Benesi- Hildebrand＇s method （double reciprocal plots）. It was noted that 2,6-DM-β-CD exhibited stronger binding ability than other Me-β- CDs. Based on the significant enhancement of fluorescence intensity of inclusion complex, a simple and highly sensitive fluorimetric method is proposed for the determination of ABZ in the presence of 2,6-DM-β-CD. The proposed method was successfully applied to the determination of ABZ in tablets and human urine.

Liquid chromatography-tandem mass spectrometry method for simultaneous determination of albendazole and albendazole sulfoxide in human plasma for bioequivalence studies

An improved high performance liquid chromatography-tandem mass spectrometry（LC-MS/MS） method has been developed for sensitive and rapid determination of albendazole（ABZ） and its active metabolite,albendazole sulfoxide（ABZSO）,in the positive ionization mode.The method utilized solid phase extraction（SPE） for sample preparation of the analytes and their deuterated internal standards（ISs） from100 μL human plasma.The chromatography was carried out on Hypurity C_（18） column using acetonitrile-2.0 mM ammonium acetate,pH 5.0（80：20,v/v） as the mobile phase.The assay exhibited a linear response over the concentration range of 0.200-50.0 ng/mL for ABZ and 3.00-600 ng/mL for ABZSO.The recoveries of the analytes and ISs ranged from 86.03%-89.66%and 89.85%-98.94%,respectively.Matrix effect,expressed as IS-normalized matrix factors,ranged from 0.985 to 1.042 for the both analytes.The method was successfully applied for two separate studies in healthy subjects using single dose of 400 mg conventional tablets and 400 mg chewable ABZ tablets,respectively.

Effects of albendazole,artesunate,praziquantel and miltefosine,on Opisthorchis viverrini cercariae and mature metacercariae

Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicidal activities of albendazole(A1),artesunate(Ar),praziquantel(Pzq) and miltefosine(Mf) on O.viverrini cercariae and mature metacercariae were investigated.Lethal concentrations(LC_(50) and LC_(95)) of these drugs were determined.Mature metacercariae previously exposed to various concentrations of the drugs were administered to hamsters.Worms were harvested 30 d post infection and worm recovery rates calculated.Al,Ar,Pzq and Mf produced morphological degeneration and induced shedding tails of cercariae after 24 h exposure.Results:The LC_(50) and LC_(95) of Al,Ar,Pzq and Mf on cercariae were 0.720 and 1.139,0.350 and 0.861,0.017 and 0.693,and 0.530 and 1.134 ppm,respectively.LC_(50) and LC_(95) of Ar on mature metacercariae were 303.643 and 446.237 ppm and of Mf were 289.711 and 631.781 ppm,respectively but no lethal effect in Pzq-and Al-treated groups(up to 1 ppt).No worms were found in hamsters administered Pzq-treated metacercariae.The adult worms from Al-treated metacercariae were significantly bigger in size compared to the control group(P<0.05).Fecundity and body width were greater in adults from Mf-treated metacercariae compared to the control group(P<0.05).Conclusions:The larvicidal effects of these drugs were high efficacy to O.viverrini cercariae but lesser efficacy to metacercariae.It should be further studied with the eventual aim of developing a field-based control program.

Inhibition of Albendazole and Oxfendazole on the Activity of Fumaric Reductase in Cysticercus cellulosae

The activity of fumaric reductase in Cysticercus cellulosae tissue homogenate with albendazole and oxfendazole individually was detected. Results showed that the two kinds of drugs both could inhabite the activity of fumaric reductase. The results indicate that the mechanism of action of benzimidazole carbamate drugs is probably inhabiting the complex of fumaric reductase noncompetently, thus lead to the exhaostion of energy and death.

Effect of Albendazole and Mebendazole on Hydatid Cyst of Mice

In the current study, hydatid cysts from livers and lungs of camels were obtained from Tambool slaughter house and protoscoleces were separated aseptically. 36-weeks-old Swiss mice (25 - 30 gram body weight males and females) were divided into two groups of 6 each: a prophylactic group dosed with 150 ml/kg of albendazole and mebendazole was given directly after injection with 2000 protoscoleces intraperitoneally for 10 consecutive days. The treated group was given a dose of 300 ml/kg of albendazole and mebendazole for 24 days with 4 days interval separated by 2 days and after 6 months of inoculation with protoscoleces, the two groups in addition to the control group were sacrificed and necropsied. The results revealed a significant difference in the development of hydatid cyst (p < 0.01). Inside the mice, small number of cysts was noticed in the group treated with albendazole and mebendazole compared to the control group, however, albendazole was highly efficacious than the mebendazole where the efficiency of albendazole reached 97% while the mebendazole efficiency rate was almost 50% which indicates that albendazole could be considered the drug of choice in the treatment of hydatid cyst.

Praziquantel and Albendazole Pills Can Cure Cancer

Objective:To prevent and treat various types of cancer safely,reliably,and at low cost.Method:Early and mid-stage cancer patients took praziquantel and albendazole every day,late cancer patients only took albendazole every day,while with the traditional Chinese medicine“ginseng jade bamboo particle”to eliminate the adverse reactions and side effects caused by the above two western medicines,continue for more than three months.Conclusion:Praziquantel and albendazole have good therapeutic and cancer prevention effects in actual clinical trials.

Protective Effects of Vitamin E on Albendazole Adverse Effects

The present study was conducted to determine the effect of albendazole alone or in combination with vitamin E on antioxidant activity and histopathological, changes on the liver and kidney. Following oral administration of albendazole of 0.25 mg/kg body weight and Vitamin E of 0.01 mg/kg body weight used for 21 successive days to broiler chicken, the experiment was done on fifteen broiler chickens divided into three groups: group one was non-treated, group two was treated with albendazole of 0.25 mg/kg body weight and group three was treated in combination with vitamin E of 0.01 mg/kg body weight. The blood sample and tissue were taken at the end of experiment 12 hrs after the last dose. The experimental result revealed that the significant decrease of liver enzymes caused by albendazole like serum Alanine Aminotransferase (ALP), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALT), when compared with the control group, the experimental result significant decrease in kidney parameters like urea creatinine level caused by albendazole and finally there was a significant increase in antioxidant enzymes activity like CAT, SOP, GPX and a significant decrease in MDA. Histopathology results in liver-treated animals with albendazole in combination with vitamin E showed dilated, congested Portal Blood Vessels (PBV, arrow), mild to moderate Biliary Proliferation (BP, arrow), portal Round Cells Aggregation (RCA, arrow), and focal Hepatocellular Degeneration (HCD, arrow). Histopathology results of kidney-treated animals with al- bendazole in combination with vitamin E showing a mild Per Tubular Edema (PTE arrow), focal Tubular Degeneration (TD arrow), Tubular Regeneration (TR, arrow), glomerular lobulation and atrophy (GL arrow), and beside interstitial cells aggregation (RCA arrow), H & EX 200. Therefore, vitamin E should be taken by albendazole to decrease its effect.

In vivo therapeutic effects of albendazole in combination with IFN-on cystic echinococcosis in mice

Objective:This study was aimed to evaluate the in vivo therapeutic effects of the combination of ABZ with interferon(IFN)-αon cystic echinococcosis(CE)in mice.Methods:After 5-month secondary infection with protoscolices,Balb/c mice were randomly divided into four groups:ABZtreated group,IFN-α-treated group,ABZ+IFN-αgroup and untreated control group.Drugs in different treated groups were respectively administered for 2 months.Blood was respectively taken from caudal veins in mice at treatment time points of 0 d,7 d,14 d,28 d,36 d,48 d and 60 d,in order to detect the changes in the level of antibodies in the serum.Mice were then sacrificed after the end of treatment,and related indicators were detected to evaluate the therapeutic effects.Results:In comparison with untreated control group(p<.01)and ABZ-treated group(p<.05),ABZ+IFN-αgroup showed a more significant decrease in the number of cysts,cyst size and cyst weight.After transmission electron microscopy(TEM)of the cysts in different treated groups,it was found that,there was an obvious change in cyst ultrastructure in ABZ+IFN-αgroup.ELISA experimental results showed that,in ABZ+IFN-αgroup,there was a significant decrease in IL-10 in serums and splenocytes(p<.01);In comparison with untreated control group,ABZ+IFN-αgroup showed a more significant decrease in the levels of IgE,IgG and its subtypes(p<.01).Conclusions:In this study,the combination of ABZ with IFN-αwas proved to be an effective CE treatment option.

Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study

Background Mass drug administration(MDA)program of albendazole to at-risk populations as preventive chemo-therapy is the core public health intervention to control soil-transmitted helminths(STHs).Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing reinfection.We assessed the effcacy of albendazole against STH parasite infection and reinfection status after cure.Methods A total of 984 schoolchildren infected with at least one type of STH parasite(hookworm,Ascaris lumbri-coides,Trichuris trichiura)in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March 2019.Stool exams at week-4 and at week-8 of post-MDA were done using Kato Katz technique.The primary outcome was effcacy assessed by cure rate(CR)and fecal egg reduction rates(ERRs)at four weeks of post-MDA.The secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of post-MDA.Group comparisons in CR and related factors were assessed with chi-square or Fisher's exact tests.Predictors of CR were examined through univariate and multi-variate regression analyses.Results The overall CR and ERR for hookworm infection were 97.2%(95%CI:94.6-99.4)and 97.02%,respectively.The overall CR and ERR for A.lumbricoides were 71.5%(95%CI:68.3-74.6)and 84.5% respectively.The overall CR and ERR and for T.trichiura were 49.5%(95%CI:44.8-54.2)and 68.3%,respectively.The CR among moderate T.trichiura infec-tion intensity was 28.6%.Among children cured of hookworm,A.lumbricoides and T.trichiura at week 4 post-MDA,4.6%,18.3% and 52.4% became reinfected at week-8 post-MDA,respectively.Significantly lower CR(36.6%)and higher reinfection after cure(60.6%)among A.lumbricoides and T.trichiura coinfected children than A.lumbricoides only(CR=69.6%,reinfection rate=15.1%)or T.trichiura only infected children(CR=55.6%,reinfection rate=47.1%)was observed.Pre-treatment coinfection with≥two types of STH parasites was significantly associated with re-infec-tion after cure.Conclusion Albendazole MDA is efficacious against hookworm but has reduced efficacy against A.lumbricoides and is not effective against T.trichiura.The low drug efficacy and high reinfection rate after cure underscore the need for alternative treatment and integration of other preventive measures to achieve the target of eliminating STHs as a public health problem by 2030.

A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver

Although nanotechnology has been rapidly developed and applied in tumor targeting, the outcome of chemotherapy remains greatly restricted by the toxicity of cytotoxic drugs in normal tissues and cells. Therefore, the development of alternative delivery systems, with few side effects in normal cells, has attracted increasing attention. Energy restriction is a novel and promising approach to cancer treatment, which can restrict tumor growth via inhibition of cellular energy metabolism. In this study, a novel tumor targeting system, based on folate-conjugated bovine serum albumin （BSA）, was developed to co-deliver albendazole and nanosilver simultaneously, to restrain the energy metabolism of tumor cells. This nanosystem showed stronger anti-tumor efficacy than those using nanoparticles without folic acid modification, nanosilver, or albendazole, both in vitro and in vivo. This nanosystem depleted cellular ATP via direct inhibition of glycolytic enzymes and mitochondrial damage, resulting in inhibition of proliferation, cell-cycle arrest, and apoptosis of tumor cells. The enhanced anti-tumor activity contributed to the tumor-targeting ability of this system, resulting in specific energy inhibition in tumor cells. Toxicity evaluation was performed to confirm the safety of this system. This nanosystem provides an efficient and safe strate~ for tumor therapy.

Continuous long-term albendazole therapy in intraabdominal cystic echinococcosis

To assess the therapeutic effects of long-term albendazole therapy in intraabdominal cystic echinococcosis Methods Fifteen patients with a total of 45 cysts were treated with albendazole with dosage regimen of 20 *!mg·kg -1 ·d -1 for an average of 2 5 years Repeated CT and ultrasound scannings (US) were performed after the end of therapy The duration of follow-up was 3 6 years on average The number, size and morpiology of cysts were compared before and after treatment Results The hydatid cysts were classified according to location and CT patterns into hepatic simple cysts, hepatic cysts with daughter cysts, hepatic/abdominal cysts and splenic cysts The hepatic simple cysts responded most favorably to albendazole therapy, with an overall cure rate of 88 7% The disappearance of cysts was observed in 43 0% of cases (15/35) Sixteen cysts (45 7%) became solidified or calcified, among which 8 cysts were completely calcified, 6 showed egg shell-like calcification of the cystic walls, and 2 showed solidification and calcification of cyst contents Four patients had large hepatic cysts containing daughter cysts; the daughter cysts all disappeared after treatment, but one patient relapsed with the reappearance of daughter cysts at 4-year follow-up Two splenic cysts also calcified Two patients had peritoneal cysts; one calcified and the other one reduced in size Among 15 patients treated, 9 were cured and 6 were improved There was no serious toxic reactions with continuous long-term therapy in a small series of patients Conclusions Continuous long-term albendazole treatment of intraabdominal cystic echinococcosis is safe and effective in the treatment of hepatic simple cysts, and some daughter cysts, peritoneal secondary cysts and splenic cysts No serious toxic reactions were found

Reevaluation of effect of albendazole on Echinococcus multilocularis infection in mice and gerbils

Abstract Objective To study the effect for albendazole therapy for alveolar echinococcus infection in gerbils and mice. Methods Mice and gerbils were infected of metacestode tissues by intraperitoneal (IP) transplantation and treated with albendazole medicated feeds. The effects were evaluated by comparison of the treated and control groups in terms of host mortality, larval metastases to lungs and liver, final larval weight, histopathological and ultrastructural examination of metacestode tissues. Viability of metacestode tissues at necropsy of treated animals was tested by intraperitoneal transplantation into uninfected animals. Results Albendazole medicated feeds significantly inhibited larval growth of Echinococcus multilocularis (E. multilocularis) both in mice and gerbils with markedly reduced host mortality and pulmonary and liver metastsaes. Viability test showed that albendazole therapy was parasiticidal in early stage of experimental infection. Light microscopic and ultrastructural examination of metacestode tissues of the treated animals revealed severe destruction and massive necrosis with marked calcification of protoscoleces and residual tissues. Conclusion Continuous long term albendazole therapy in animal models is parasiticidal against larval E. multilocularis especially in early stage of infection.

Spectrophotometric Determination of Albendazole Drug in Tablets： Spectroscopic Characterization of the Chargetransfer Solid Complexes

Simple, rapid and reliable method for the determination of albendazole （ABZ） was described. This includes the utility of some π-acceptors such as 2,3-dichloro-5,6-dicyano-p-benzoquinone （DDQ） and 3,6-dichloro-2,5-dihydroxy-p-benzoquinone （p-CLA） for estimation of ABZ drug （act as donor）. The experimental conditions were optimized and the system obeys Beer＇s law for 7.50-80 and 10.00-85.00 ug·mL-1 of ABZ using DDQ and p-CLA, respectively. The molar absorptivity and Sandell sensitivity were calculated to be 1.83× 10^3 and 1.12× 10^3 L·mol ·cm -1 and 2.60 and 3.40 ng·cm -2 using DDQ and p-CLA, respectively. The limits of detection and quantification were calculated to be （7.42 and 6.73） and （9.94 and 4.13） ug·mL-1 using DDQ and p-CLA, respectively. The proposed methods were successfully applied to the determination of ABZ in commercially available dosage forms. The reliability of the assays was established by parallel determination by the official method and recovery studies. The chemical structures of the solid charge-transfer （CT） complexes formed via reaction between ABZ under study and π-acceptors, have been elucidated using elemental analyses （C, H and N）, IR, 1H NMR and mass spectra.

CSF-VP shunt placement and albendazole therapy for cerebral cysticercosis

ZHU Liping , WENG Xinhua , SHI Yaozhong, PAN Xiaozhang and MO Ling Department of Infectious Diseases, Hua Shan Hospital, Fudan University, Shanghai 200040, China (Zhu LP, Weng XH, Shi YZ, Pan XZ and Mo L)

Current status of diagnosis and treatment of hepatic echinococcosis

Echinococcus granulosus(E.granulosus) and Echinococcus multilocularis(E.multilocularis) infections are the most common parasitic diseases that affect the liver.The disease course is typically slow and the patients tend to remain asymptomatic for many years.Often the diagnosis is incidental.Right upper quadrant abdominal pain,hepatitis,cholangitis,and anaphylaxis due to dissemination of the cyst are the main presenting symptoms.Ultrasonography is important in diagnosis.The World Health Organization classification,based on ultrasonographic findings,is used for staging of the disease and treatment selection.In addition to the imaging methods,immunological investigations are used to support the diagnosis.The available treatment options for E.granulosus infection include open surgery,percutaneous interventions,and pharmacotherapy.Aggressive surgery is the first-choice treatment for E.multilocularis infection,while pharmacotherapy is used as an adjunct to surgery.Due to a paucity of clinical studies,empirical evidence on the treatment of E.granulosus and E.multilocularis infections is largely lacking;there are no prominent and widely accepted clinical algorithms yet.In this article,we review the diagnosis and treatment of E.granulosus and E.multilocularis infections in the light of recent evidence.

The Target of Benzimidazole Carbamate Against Cysticerci cellulosae

To study the target of benzimidazole carbamate drugs against Cysticerci cellulosae and give a theoretical basis for type evolution and new drug design, the changes of key enzyme activities and metabolite contents in the pathway of energy metabolism in C. cellulosae in vitro and in vivo were tested with albendazole and oxfendazole, respectively. Both albendazole and oxfendazole inhibited the pathways of anaerobic glycolysis, partial inversed tricarboxylic acid cycle of Taenia Solium oncosphere, immature and mature Cysticerci in vitro, and immature and mature Cysticerci in vivo to a certain degree, and enhanced fat decomposing, amino acid decomposing, xanthine decomposing metabolism, and on the other hand, the absorption of glucose was hindered; furthermore, both albendazole and oxfendazole inhibited the activities of the fumaric reductase （FR） complex noncompetently in vitro. Benzimidazole carbamate drugs could inhibit the activities of FR complex noncompetently and hinder the absorption of glucose.