Effect of plasma mebendazole concentrations in the treatment of human echinococcosis

High oral doses of mebendazole were given for a mean period of 23 months to 22 patients with inoperable alveolar or cystic echinococcosis (Echinococcus multilocularis n = 18, E. granulosus n = 4). Clinical, morphological, biochemical and serological findings and plasma mebendazole levels were monitored. Clinical and biochemical improvement or stabilization was observed in 17 patients but the parasitic lesions did not decrease in size in most instances. One patient died shortly after onset of therapy with hemorrhage of esophageal varices. Three patients with alveolar and one with cystic echinococcosis had evidence of progressive disease such as increase of cholestasis, destruction of lumbar vertebrae and growth of an intraperitoneal cyst. The plasma mebendazole levels (4 hr after the morning dose) of the latter 4 patients were 0.09 +/- SD 0.02 mumol/l, while in those with clinical stabilization or improvement it was 0.30 +/- SD 0.14 mumol/l (P less than 0.001). These preliminary data indicate 1) a good clinical response to chemotherapy in most patients despite unchanged size of the parasitic lesions, and 2) a direct correlation of clinical response with plasma mebendazole levels.     

Chemotherapy of human cystic echinococcosis: comparative efficacy of mebendazole and albendazole.

The relative efficacy of mebendazole (MEB) and albendazole (ALB) was tested by treating 51 patients with single, multiple and multi-organ hydatid cysts; 28 patients were treated with MEB, 50-70 mg kg-1 body weight daily for six to 24 months, and 23 with ALB, 10 mg kg-1 body weight daily in four courses of 30 days with 15-day intervals between courses. The therapeutic effect during the follow-up was assessed by ultrasonography, computerized tomography and chest X-ray. The criteria used when assessing the results were: 'success', evidence of effect on all cysts; 'partial success', evidence of effect on some of the cysts; and 'no success', no changes in cyst morphology. Treatment with MEB was successful in eight cases (28.6%), partially successful in eight (28.6%) and unsuccessful in 12 (42.8%). Treatment with ALB was successful in 10 cases (43.5%), partially successful in 10 (43.5%) and unsuccessful in three (13.0%).     

甲苯咪唑治疗12例囊型包虫病的效果观察

近20年兴起的包虫病化疗,开始时用甲苯咪唑(MBZ),后来逐渐由丙硫咪唑(ABZ)取代。这二种药是苯并咪唑类化合物的衍生物,为WHO认可的治疗包虫病首选药物。为了不完全摒弃MBZ的应用,特小结1982～1992年间用MBZ治疗12例囊型包虫病(CE)的随访结果。材料与方法1　临床资料12例CE中,男9例,女3例。年龄20～26岁者7例,最大1例58岁,8～9岁小儿3例,最幼1例3岁。肝CE7例中,单发4例,多发3例。肺CE5例中,单发3例,多发2例。2　药物剂量和疗程MBZ由比利时杨森(Janssen)制药公司提供,片剂,每片含量500mg,批号J51346-01087。成人每次量500mg,小儿…     

The efficacy of chemotherapy with mebendazole in human cystic echinococcosis: long-term follow-up of 52 patients.

Sixty patients with Echinococcus granulosus infection of the liver, lungs, bone and/or soft tissues were treated for several months with oral mebendazole (50-60 mg kg-1 day-1), in divided doses after fat-rich meals, either without surgery (WS), post-surgery (PS) or pre- and post-surgery (PPS). Long-term follow-up, possible for 52 of the patients, showed that WS, PS and PPS patients have so far remained disease-free following treatment for (means +/- standard deviations) 65.5 +/- 37.7, 82.5 +/- 37.0 and 84.1 +/- 28.3 months, respectively. Ultrasound and computed tomography scans were similar in WS and PPS patients post-treatment. Blood eosinophil levels, which were sometimes elevated initially, returned to normal in all patients and this decrease indicated cyst degeneration before this was evident on the scans. Treatment of patients with cystic echinococcosis may no longer require surgery.     

A pediatric case of disseminated cystic echinococcosis successfully treated with mebendazole

We report a 4-year-old girl with disseminated cystic echinococcosis in the lung and the liver and a solitary cyst in the left kidney. Mebendazole therapy produced complete resolution of the lung and kidney cysts. In the liver, most of the smaller cysts disappeared, whereas the larger cysts showed only partial response and required surgical excision. Our experience reinforce the finding in previous reports that long term medical treatment of cystic echinococcosis with mebendazole can be lifesaving in cases that are unmanageable by surgical treatment.     

Benzimidazole treatment of cystic echinococcosis

Hydatidosis (cystic echinococcosis, CE) constitutes a serious public health problem worldwide. Total surgical removal of a hydatid cyst is still considered the gold standard treatment for CE. Percutaneous treatment (PAIR), using either hypertonic saline or alcohol as a larvacidal agent, appears to be an additional effective form of treatment. Benzimidazoles (albendazole, ABZ; mebendazole, MBZ), given either alone or combined with praziquantel (PZ) are currently used for the treatment of non-surgical cases and as a supplementary treatment prior and post-surgery. Combined chemotherapy was found to be more effective than either of the agents given alone. ABZ is easily absorbed and more effective than MBZ. ABZ (12-15 mg/kg/day) and MBZ (30-70 mg/kg/day) given for 14-20 days prior to surgery and continued for an additional 3-24 months in a cyclic monthly form were found effective against the disease. Either increased or decreased circulating antigen levels, which consequently cause changes in the humoral (IgG, IgG1, IgG4, IgE) immune responses, have a prognostic value in successfully treated CE cases. However, although the cellular immune response to echinococcal antigens decreased in improved or cured CE patients, it was not considered of practical use in determining treatment efficacy. In certain cases successful treatment was also followed by elevated eosinophilia and erythrocyte sedimentation rates. In the present article, the mechanism of drug activities as well as the development of resistance against the drugs available are further discussed.     

Surgical treatment of multiple cystic echinococcosis

BackgroundMultiple hydatid disease is a complex surgical problem, and its treatment can follow either conservative principles (drainage or obliteration of the cavity) or radical principles (cystoperi-cystectomy or liver or lung resection).MethodsA total of 220 patients with multiple cystic echinococcosis (428 cysts) were managed between 1967 and 1998 with conservative operations (group A) or radical operation (group B). There were 90 men and 130 women, with a mean age of 52 years (range 18–77 years). There were two cysts in 124 patients, three cysts in 40 patients, four in 15 and more than four in 41 patients. These multiple cysts were located at one anatomical site (n=140) or at more than one site (n=80). Multiple (2–3) hepatic cysts occurred in 142 patients, multiple (2–3) lung cysts in 15 and multiple peritoneal cysts in 13 patients. Hepatic cysts co-existed with lung cysts in another 32 patients, with peritoneal cysts in 14 patients and once each with splenic, splenic plus lung cysts and renal cysts, one retroperitoneal cyst coincided with small peritoneal cysts.ResultsThe operative procedure employed was dependent on the type and site of the parasite and the condition of the host. Three of 208 patients operated conservatively (group A) died postoperatively as opposed to receiving radical treatment. Morbidity rates were 8.8% and 12.5% in group A and B and mean hospital stay was 15.8 and 15.1 days, respectively. In group A there was an 8.6% recurrence rate, and recurrent disease was finally managed in each group the overall result could be considered satisfactory.DiscussionWe conclude that conservative surgery can provide good results in multiple cystic echinococcosis. Radical surgery, with its time-consuming major procedures, is ideal but only in properly selected cases.     

Albendazole-soybean oil emulsion for the treatment of human cystic echinococcosis: evaluation of bioavailability and bioequivalence

A single 12.5 mg/kg dose of albendazole (Abz) in tablet form (AbzT) followed 2 weeks later by an equivalent dose of Abz emulsified in 30% soybean oil (AbzE) was administered orally 2 h after the first morning meal to 7 male adult patients with cystic echinococcosis caused by Echinococcus granulosus. Serum samples were taken 1, 3, 5, 7, 8, 9, 11, 14, 18, 24, 36, and 48 h post medication from each patient to measure the serum concentrations of albendazole sulfoxide (AbzSOX), the principal bioactive metabolite of Abz. AbzSOX concentrations were measured by reverse phase HPLC. The data were subjected to pharmacokinetic analysis to compare the relative bioavailability and bioequivalence of AbzT and AbzE. The results demonstrated that the mean peak concentrations (C(max)) for AbzT and AbzE were 1.06+/-0.38 mg/l and 1.71+/-0.47 mg/l, respectively; the area under the concentration-time curves (AUC) were 13.24+/-4.93 mg x h/l and 21.01+/-7.54 mg x h/l, respectively. The relative bioavailability of AbzE was F(Flu)=1.59. Two one-sided tests procedure and (1-2 alpha) 90% confidence interval methods were used to evaluate the bioequivalence of AbzE and AbzT. The results demonstrated that the bioavailability of AbzE was greater than AbzT.     

Human cystic hydatid disease: treatment with interrupted courses of mebendazole

Ten patients suffering from intra-abdominal cystic hydatid disease, confirmed by serological tests and CT scan were treated with mebendazole. Each received 1800 mg day-1 either as a continuous therapy for 18 weeks, or as interrupted 6-week courses for a minimum of three courses, with intervals of 19-22 weeks between the courses. One patient dropped out of the study because of the development of jaundice 11 days after initiation of treatment. Nine patients were treated and followed up for the minimum of 20 months; of these, three patients received continuous therapy and six received interrupted therapy. One patient from the continuous therapy group showed progressive regression of his cyst, one showed minimal radiological changes only, while the third patient showed minimal radiological changes plus per-operative evidence of partial destruction of the cyst. Of those treated with interrupted therapy, one patient showed continuous progression in the size of the cyst with the appearance of a new cyst, although there was radiological and operative evidence of partial destruction of the cyst. One patient initially showed regression, but later progression of his cyst, while four patients showed no benefit from the treatment.     

阿苯达唑脂质体和阿苯达唑片治疗囊型包虫病的临床疗效及安全性

目的 观察阿苯达唑脂质体(L-ABZ)和阿苯达唑片(T-ABZ)治疗囊型包虫病的临床疗效及安伞性.方法 收集1998-2008年我院门诊收治及下乡现场普查发现的囊型包虫病患者269例,采用回顾性病例对照方法,纳入符合病例218例,其中经L-ABZ治疗的患者110例,经T-ABZ治疗的患者108例.依据随访的临床症状及影像和血清学化验结果对比分析药物的疗效及不良反应.短期为服药3个月,长期为服药6个月.囊型包虫病患者分为单囊型(CE1)、多子囊型(CE2)和内囊塌陷坏死型并囊内可见活性子囊(CE3).用χ2检验分析计量资料、计数资料;用Wilcoxon秩和检验分析等级资料;统计学检验均为双侧检验,统计数据均用SPSS13.0及PEMS3.1医学统计软件分析完成.结果 短期疗效评价中,L-ABZ组与T-ABZ组总有效率及治愈率分别为77.9%和49.1%,28.4%和13.9%,两组比较,χ2值分别为19.581、6.877,P值均<0.05,差异有统计学意义.长期疗效评价中,L-ABZ组与T-ABZ组总有效率及治愈率分别为81.7%和49.0%,47.6%和20.6%,两组比较,χ2值分别为20.977、15.049,P值均<0.05,差异有统计学意义.T-ABZ组不同类型包虫囊肿疗效比较:对于短期治愈率、短期总有效率、长期治愈率、长期总有效率,CE1组分别为50.0%(15/30)、56.7%(17/30)、58.3%(7/12)、75.0%(9/12);CE2组分别为8.8%(8/91)、35.2%(32/91)、28.6%(12/42)、69.0%(29/42);CE3组分别为33.3%(7/21)、61.9%(13/21)、70.0%(7/10)、100.0%(10/10).CE1组、CE3组分别与CE2组的短期疗效(治愈率和总有效率)比较,χ2值分别为24.887、4.329、8.860、5.076,P值均<0.05,差异有统计学意义;L-ABZ组不同类型包虫囊肿疗效比较:对于短期治愈率、短期总有效率、长期治愈率、长期总有效率,CE1组分别为47.4%(18/38)、92.1%(35/38)、79.3%(23/29)、96.6%(28/29).CE2组分别为12.2%(12/98)、65.3%(64/98)、35.9%(23/64)、84.40/0(54/64).CE3组分别为61.5%(8/13)、92.3%(12/13)、50.0%(3/6)、100%(6/6).CE1组、CE3组分别与CE2组的短期疗效(治愈率、总有效率)比较,χ2值分别为19.648、9.930、18.880、3.876,P值均<0.05,差异有统计学意义;在安全性评价中,T-ABZ组和L-ABZ组药物相关的不良反应发生率分别为11.1%(12/108)、12.7%(14/110),两组比较,χ2=0.155,P>0.05,差异无统计学意义.结论 L-ABZ及T-ABZ均是有效的抗包虫药物,但L-ABZ临床疗效更佳.

Abstract：

Objective To explore and compare the clinical effect and safety of liposomal albendazole (L-ABZ) and tablet-albendazole (T-ABZ) in the treatment of cystic echinococcosis (CE1, CE2, and CE3). Methods A total of 269 cases treated with cystic echinococcosis (CE) in Xinjiang Medical University the First Affilicated Hospital from 1998 to 2008 were reviewed. 51 cases were excluded and 218 cases were enrolled in this research by retrospective case-control method. Among 110 cases were treated with L-ABZ and 108 cases were treated with T-ABZ for short-term (3 months) and long-term courses (6 months) respectively. The effects and safety of the two medicines were compared by analyzing the clinical symptoms, imaging check and serologic test results. Results In short-term effect evaluation, the total effective rates and curative rates of L-ABZ group and T-ABZ group were 77.9% and 49.1% vs 28.4% and 13.9%, respectively. The effects of L-ABZ group was better than that of T-ABZ group, with remarkable difference in total effective rates and curative rates ( χ2 value was 19.581, 6.877, respectively, P < 0.05). In long-term effect evaluation, the total effective rates and curative rates of L-ABZ and T-ABZ group were 81.7% and 49.0% vs 47.6% and 20.6%, respectively. There was significant difference between L-ABZ group and T-ABZ group in total effective rates and curative rates (χ2 value was 20.977, 15.049, respectively, P < 0.05). In T-ABZ group the short-term curative rates were 50.0% (15/30), 8.8% (8/91) and 33.3% (7/21) respectively in CE1, CE2, and CE3, the short-term total effctive rates were 56.7% (17/30), 35.2% (32/91) and 61.9% (13/21) respectively in CE1, CE2, and CE3. The long-term curative rates were 58.3% (7/12), 28.6% (12/42) and 70.0% (7/10) respectively in CE1, CE2 and CE3, the long-term total effctvie rates were 75.0% (9/12), 69.0% (29/42) and 100.0% (10/10) respectively in CE1, CE2, and CE3. When compared with CE2, differences existed in CE1 ( χ2 = 24.887,4.329; P < 0.05) and CE3 groups ( x 2 = 8.860, 5.076; P < 0.05) in terms of short-term effects. In L-ABZ group, the short-term curative rates were 47.4% (18/38), 12.2% (12/98) and 61.5% (8/13) respectively in CE1, CE2 and CE3, the short-term total effctive rates were 92.1% (35/38), 65.3% (64/98) and 92.3% (12/13) respectively in CE1, CE2 and CE3, the long-term curative rates were 79.3% (23/29), 35.9% (23/64) and 50.0% (3/6) respectively in CE1, CE2 and CE3, the long-term total effective rates were 96.6% (28/29),84.4% (54/64) and 100% (6/6) respectively in CE1, CE2 and CE3. When compared with CE2, there were significant differences in CE1 (χ2 = 19.648, 9.930; P < 0.05) and CE3 groups ( χ2 = 18.880, 3.876; P < 0.05) in terms of short-term effect. In L-ABZ and T-ABZ groups, the durg-related adverse effects were 11.1% (12/108) and 12.7% (14/110) respectively without significant difference ( χ2 = 0.155, P > 0.05). Conclusion L-ABZ and T-ABZ were both effective anti-echinococcosis drugs without dominant sideeffects. The clinical effect of L-ABZ was better than that of T-ABZ.     

Treatment of human echinococcosis with mebendazole. Preliminary observations in 28 patients

Preliminary results of a long-term, prospective therapeutic trial with mebendazole in 28 patients mainly with inoperable echinococcosis are reported. The course of disease was monitored closely and plasma mebendazole levels were checked regularly. A major problem is the lack of reliable methods for defining and measuring early success or failure of therapy. Most of the patients improved clinically. No marked change of parasitic lesions was observed except in one patient with constantly low plasma mebendazole levels who deteriorated. No serious side effects occurred. The preliminary results are encouraging and suggest that mebendazole has a "parasitostatic" effect on larval growth.     

肝包虫病的外科治疗

目的 分析、探索肝囊型包虫病(cystic echinococcosis,CE)手术治疗的方式、适应证及其疗效。方法 分析我院2009-2013年手术治疗的肝囊型包虫患者216例。结果 内囊摘除术(A组) 术后平均住院d数、带管时间、术后残腔并发症等均显著高于其他3组(P＜0.01);手术D组的手术耗时及出血量、住院费用等均显著高于其他3组(P＜0.01)。结论 ①肝包虫外囊完整剥除术治疗可根除因内囊摘除术导致包虫复发和胆瘘等并发症;同肝切除相比具有创伤较小、并发症减少的特点,故可为CE手术治疗的首选;②对于邻近大血管、重要脏器组织或周围解剖层次不清的肝包虫,外囊次全切除术可在有效消灭残腔的同时,减少手术难度及外囊剥除术所引发手术风险。     

Hepatic cystic echinococcosis:Percutaneous treatment as an outpatient procedure

Objective:To demonstrate utility and safety of the puncture aspiration injection and reospiration(PAIR)technique for outpatients.Methods:Percutaneous treatment with US guidance was applied to 33 patients for 44 cysts.Patients treated with the PAIR technique,were outpatients.PAIR and catheterization technique were evaluated for efficacy and safety of procedure and complication rates.Results:Thirty-five of 44 cysts were treated with the PAIR and 9 of 44 were treated with the catheterization technique.The success rate of the cysts Gharbi type 1(CEI)and type 2(Ct3a)treated with the PAIR technique was 1009.hi the follow up of 9 cysts treated with the catheterization technique,2 of them(22%)developed cyst infection and 1(11%)developed a biliary fistula.Conclusions:The PAIR technique was found to be an effective and safe approach in order to treat Gharbi type 1 and type 2 cysts percutaneously for outpatients.It has a very low complication rate in comparison with the catheterization technique.So every effort should be mode to finish the treatment with PAIR technique.     

Native and recombinant antigens in the immunodiagnosis of human cystic echinococcosis

To evaluate the diagnostic sensitivity and specificity of immunoelectrophoresis (IEP), indirect haemagglutination (IHA), enzyme-linked immunosorbent assay (ELISA) and immunoblotting (IB), we compared their ability in detecting IgG antibodies to a hydatid fluid fraction (HFF) and to native and recombinant antigen B of Echinococcus granulosus. We tested sera from patients who had cystic echinococcosis (CE) grouped according to their type of cysts (n = 204), from patients with other parasitic diseases (n = 21), lung or liver carcinomas (n = 6) or serous cysts (n = 26) and from healthy controls (n = 90). HFF-IB gave the highest sensitivity (80%) followed by ELISA (72%), IHA (54%) and IEP (31%), respectively. The diagnostic sensitivity significantly (P < 0.01) decreased as cysts matured from type I-II to type VII. Recombinant and native antigen B-IB yielded similar sensitivity (74%). A large number of clinically or surgically confirmed CE patients (20%) resulted negative. In these patients' sera, IB to assess the usefulness of the recombinant E. granulosus elongation factor-1 beta/delta in detecting IgE antibodies yielded 33% of positivity. Our findings underline the need to standardize techniques and antigenic preparations and to improve the performance of immunodiagnosis by characterizing new antigens and detecting distinct immunoglobulin classes.     

Agranulocytosis--a complication of the chemotherapy of echinococcosis with mebendazole]

Only two of the 75 patients with echinococcosis, treated with mebendazole in a dose of 50 mg/kg b. m. for 30 days (single course) and administered from 1 to 13 courses with intervals of 1 to 3 months, developed agranulocytosis eventuating in death in one female patient. Analysis of blood levels of mebendazole and its metabolites permits a hypothesis that high concentrations thereof may have a toxic effect on the bone marrow, inducing its hypoplasia, in subjects sensitive to these substances.     

Liver cystic echinococcosis and human host immune and autoimmune follow-up:A review

Cystic echinococcosis(CE) is an infectious disease caused by the larvae of parasite Echinococcus granulosus(E.granulosus).To successfully establish an infection,parasite release some substances and molecules that can modulate host immune functions,stimulating a strong anti-inflammatory reaction to carry favor to host and to reserve self-survival in the host.The literature was reviewed using MEDLINE,and an open access search for immunology of hydatidosis was performed.Accumulating data from animal experiments and human studies provided us with exciting insights into the mechanisms involved that affect all parts of immunity.In this review we used the existing scientific data and discuss how these findings assisted with a better understanding of the immunology of E.granulosus infection in man.The aim of this study is to point the several facts that challenge immune and autoimmune responses to protect E.granulosus from elimination and to minimize host severe pathology.Understanding the immune mechanisms of E.granulosus infection in an intermediate human host will provide,we believe,a more useful treatment with immunomodulating molecules and possibly better protection from parasitic infections.Besides that,the diagnosis of CE has improved due to the application of a new molecular tool for parasite identification by using of new recombinant antigens and immunogenic peptides.More studies for the better understanding of the mechanisms of parasite immune evasion is necessary.It will enable a novel approach in protection,detection and improving of the host inflammatory responses.In contrast,according to the "hygiene hypothesis",clinical applications that decrease the incidence of infection in developed countries and recently in developing countries are at the origin of the increasing incidence of both allergicand autoimmune diseases.Thus,an understanding of the immune mechanisms of E.granulosus infection is extremely important.     

Chemotherapy of echinococcosis with mebendazole: clinical observations of 7 patients.

The effect of high dosage therapy with Mebendazole was studied in 5 patients with cystic echinococcosis and 2 patients with alveolar echinococcosis involving several organs. Follow-up studies at regular intervals from 7 to 20 months indicated an improvement of the pathological findings initially observed. This could clearly be demonstrated by the radiographic findings in cases with pulmonary involvement. The desintegration or dissolution of pulmonary cysts was observed within a few months after treatment with Mebendazole had begun. However, consolidation of previously emptied cysts occurred during the follow-up later. Allergic reactions were observed after commencement of drug therapy in two cases. These were probably due to spillage of antigenic material. The following treatment periods were tolerated well. No serious toxic side effects were observed in the other cases described here.