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Evaluation of treatment and long-term follow-up in patients with hepatic alveolar echinococcosis.

BACKGROUND: Alveolar echinococcosis is a rare disorder, which makes a comparison of different treatment modalities within a clinical trial difficult to perform. Data prospectively recorded over a period of 25 years were used to evaluate three therapeutic strategies: benzimidazole therapy alone, complete 'curative' resection followed by 2 years of adjuvant benzimidazole treatment, and partial debulking resection followed by continuous administration of a benzimidazole. METHODS: Details of 113 patients with hepatic alveolar echinococcosis treated between 1976 and 2003 were analysed. Kaplan-Meier survival curves were constructed and, using a Cox regression model, patient age, year of initial treatment and PNM stage were entered as co-variates in the analysis. RESULTS: Kaplan-Meier overall survival curves stratified for treatment strategy indicated an improved long-term survival in patients undergoing the debulking procedure (P = 0.061) or curative resection (P = 0.002) compared with benzimidazole therapy alone. However, when PNM stage, patient age and year of initial treatment were introduced into the analysis, there was a trend for survival advantage only with curative resection (P = 0.07 versus benzimidazole alone). Debulking resulted in a higher rate of progression of hepatic echinococcosis than curative surgery (P = 0.008). The incidence of parasite-related complications was similar for debulking resection and benzimidazole therapy alone (P = 0.706). CONCLUSION: Debulking hepatic resections do not appear to offer any advantage in the treatment of patients with alveolar echinococcosis.

Adult↗

Epidemiology of echinococcosis.

BACKGROUND: Various species and infraspecific forms of the cestode genus Echinococcus are causative agents of human echinococcosis. Pathology, epidemiology and geographical occurrence vary widely between the different Echinococcus taxa. As a general rule, those forms of echinococcosis that are transmitted mainly by wild animals are rather rare, due to limited contact between humans and wildlife. This is the case with alveolar echinococcosis (AE) caused by Echinococcus multilocularis, the 'fox tapeworm' (except in regions where domestic dogs are heavily involved in the lifecycle), and for the South American endemic species E. oligarthrus and E. vogeli. On the other hand, most forms of cystic echinococcosis (CE) are transmitted in domestic lifecycles involving dogs and livestock and constitute an emerging public health problem, especially in regions with extensive livestock husbandry and non-supervised slaughter. METHOD: This review focuses on two fields where a wealth of new information became available in recent years. RESULTS AND CONCLUSIONS: New data demonstrate that ' E. granulosus', the causative agent of CE, is an assembly of several, rather diverse, species and genotypes that show fundamental differences, not only in their epidemiology, but also in their pathogenicity to humans. This fact may explain the unequal distribution of high-endemicity areas for human CE on regional scales, which previously, has been attributed to differences in human behaviour. In addition, new data suggest that E. multilocularis is expanding its geographical range in the northern hemisphere, and its transmission is intensifying, e.g. in central Europe. Moreover, the lifecycle (involving wild foxes and rodents) is rapidly becoming 'urbanised' due to the recent establishment of fox populations in cities and towns. This shift from sylvatic to synanthropic occurrence is likely to result in an increased pressure on the human population of infection from AE.

Animal Husbandry↗

Immunoblot evaluation of the 100 and 130 kDa antigens in camel hydatid cyst fluid for the serodiagnosis of human cystic echinococcosis in Libya.

Two high molecular weight antigens with molecular masses approximately 100 kDa and 130 kDa were identified by immunoblotting camel hydatid cyst fluid, with 94% sensitivity in sera from surgically confirmed Libyan cystic echinococcosis cases. 40% of sera from surgically confirmed alveolar echinococcosis cases cross-reacted with the 100 and 130 kDa antigens, as did 5.3% of sera from human Taenia solium cysticercosis patients. No cross-reaction occurred with sera from human schistosomiasis mansoni or onchocerciasis patients. In addition, all sera from patients with non-hydatid space-occupying lesions (i.e. simple liver cysts, kidney cysts, lung tuberculosis, pulmonary carcinoma, pulmonary empyema, and lung abscess) were seronegative against the same antigens, as were control serum samples from healthy individuals. The 100 and 130 kDa antigens were strongly recognized by sera from cystic echinococcosis patients when camel or horse hydatid cyst fluid was used in immunoblotting but were only weakly recognized if sheep or human hydatid cyst fluid was used. Camel hydatid cyst fluid could be an important source of diagnostic antigens for human cystic echinococcosis in the Middle East endemic region.

Animals↗

Hydatid disease in acute leukemia: effect of anticancer treatment on echinococcosis.

Echinococcosis, also known as hydatid disease or hydatidosis, is a zoonotic illness caused by the larval form of Echinococcus spp. It is highly prevalent in areas where the parasite is endemic such as the Mediterranean region. However, occurrence of echinococcosis and cancer together is rare. We treated and followed approximately 1200 patients with different hematologic neoplastic diseases between 1985 and 2003, and only one of these individuals had concomitant acute leukemia and liver hydatidosis. This report describes the case of a 19-year-old man who had both primary refractoriness of acute leukemia (AML-M4) and liver hydatidosis. Management is discussed. The patient had cystic echinococcosis (CE) of the liver that was classified as CE1 according to the system established by the World Health Organization's Informal Working Group on Echinococcosis. The patient underwent 3 months of treatment with agents that targeted the leukemia (daunorubicin, idarubicin, cytarabine, fludarabine) and its complications (amphotericin B, amphotericin B lipid complex, liposomal amphotericin B). Throughout this period, the size and the contents of the cyst did not change, Echinococcus titers remained unchanged, and the cyst classification remained CE1.

Adult↗

Epidemiological evaluations of the efficacy of slow-released praziquantel-medicated bars for dogs in the prevention and control of cystic echinococcosis in man and animals.

To assess the epidemiological efficacy of type SRP III slow-released praziquantel-medicated bars for dogs in the prevention and control of cystic echinococcosis in man and livestock, praziquantel-medicated bars were implanted subcutaneously in over 90% of dogs in villages in north Xinjiang, China, where cystic echinococcosis is highly endemic. After implantation, infection rate of Echinococcus granulosus in dogs, specific antibodies in children and prevalence of echinococcosis in one-year-old lambs were observed for 3 years. Coproantigen of E. granulosus was positive in 41.2% of the dogs at the start of experiment. In the second and third year after medicated-bar implantation, coproantigen was undetectable in any dogs examined, while 3.0% of dogs were positive at the end of the fourth year. The antibody positive rate in 7-year-old pupils, that was 41.2% before the experiment, declined gradually and it was 5.4% in the fourth year, while children in the non-intervention control area showed 30.6% seropositivity. The prevalence of hydatid disease in children aged 7-16 years also declined significantly. The prevalence of hydatidosis in lambs one year of age was 44.8% in the first year, dropping to 10.7% in the fourth year, while in the non-intervention control area the level of infection was 46.4%. These results demonstrated not only that the slow released praziquantel-medicated bars efficiently blocked reinfection in dogs at least for 2 years, but also the measure was effective in preventing transmission of cystic echinococcosis to both man and livestock.

Adolescent↗

Medical treatment of echinococcosis under the guidance of Good Clinical Practice (GCP/ICH).

Chemotherapy is one of the main components for the treatment of alveolar and cystic echinococcosis. Benzimidazoles are on the market since 30 years, and are used widely according to the recommendations of the 1996 WHO guidelines for treatment of cystic and alveolar echinococcosis [Bull WHO 1996; 74: 231-242.]. However, none of the two drugs (Albendazole or Mebendazole) would satisfy today the requirements for an approval by the relevant authorities, such as the European Agency for the Evaluation of Medicinal Products (EMEA) or the Food and Drug Administration (FDA). New anthelmithic drugs are in the pipeline, and some of them have already undergone preclinical testing. In addition, recent advances have been made in the definition of outcomes for clinical trials in alveolar echinococcosis. Thus, phase III studies with new active ingredients are needed to assess short- and long-term safety as well as the therapeutic value. The basic requirements for comparative drug testing are provided in the Note for Guidance on Good Clinical Practice (GCP), and are based upon the rules and regulations by International Conference on Harmonization (ICH) and the Clinical Trial Directive (Directive 2001/20/EC) of the European Commission. The application of these standards to new drug testing for echinococcosis will help to upgrade the level of evidence.

Anthelmintics↗

WHO classification of alveolar echinococcosis: principles and application.

Alveolar echinococcosis is caused by the larval stage of the fox tapeworm (Echinococcus multilocularis) and is frequently diagnosed as a space occupying lesion in the liver. The growth pattern resembles that of a malignant tumor with infiltration throughout the liver, spreading into neighbouring organs and metastases formation in distant organs. Thus, one of the prevailing differential diagnoses is liver cancer. Guided by the Tumor-Node-Metastasis (TNM) system of liver cancer, the European Network for Concerted Surveillance of Alveolar Echinococcosis and the WHO Informal Working Group on Echinococcosis proposed a clinical classification for alveolar echinococcosis. It was designated as PNM system (P = parasitic mass in the liver, N = involvement of neighbouring organs, and M = metastasis). As for TNM in oncology, single PNM categories were combined into four stages, I to IV. The system was developed by a retrospective analysis of 97 patients' records from two treatment centers (Besançon/France and Ulm/Germany). Recently, this WHO classification was applied to 222 patients in 4 clinical centers around the world (Besançon/France, n = 26; Urumqi/China, n = 46; Sapporo/Japan, n = 58; and Ulm/Germany, n = 92). All patients could be classified who had been diagnosed in the period from January 1998 to June 2005. The stage grouping indicated center differences, but appeared to segregate patients according to various treatment regimens. The WHO classification not only serves as a tool for the international standardization of disease manifestation but also aids to evaluate the outcome of a chosen diagnostic and treatment procedure in different treatment centers in Europe and Asia.

Animals↗

Field evaluation of a coproantigen enzyme-linked immunosorbent assay for diagnosis of canine echinococcosis in a rural Andean village in Peru.

One hundred and six dogs (61 males and 45 females) were examined for Echinococcus granulosus infection in a farming cooperative in the central highlands of Peru during November 1998. Canine echinococcosis was diagnosed using direct microscopic examinations of purged feces following arecoline purging and a coproantigen-detection enzyme-linked immunosorbent assay (ELISA) for E. granulosus. Mean age was 2 years with a range of 3 months to 9 years. The overall prevalence of canine echinococcosis using the ELISA test was 79% (84/106). Seventy-four dogs were successfully purged with arecoline. The frequency of canine echinococcosis was 82 (61/74) and 34% (25/74) by the coproantigen ELISA test and arecoline purging, respectively. The sensitivity and specificity of the coproantigen ELISA test was 88 and 95%, respectively. We found this assay to be especially advantageous in remote geographical areas. In future control programs against echinococcosis in Peru and other areas where E. granulosus is endemic the coproantigen ELISA should be used for the surveillance of the dog population.

Animals↗

Off-pump technique for the treatment of ventricular myocardial echinococcosis.

BACKGROUND: This study was planned to investigate the off-pump operability of ventricular myocardial Echinococcosis, which has no close relation with the cardiac chambers. METHODS: Twenty patients with cardiac echinococcosis, and 2 patients with isolated pericardial echinococcosis were operated on. Hydatid cysts were located in the ventricular wall in 17 patients and 10 of these 17 patients were operated without cardiopulmonary bypass. We present these 10 patients in this report. We used transesophageal echocardiography (TEE) and peroperative surface echocardiography (PSE) to determine the relation of cysts with cardiac chambers. The cysts were aspirated for diagnosis and to facilitate the dissection. Cyst cavities were left open in all cases. RESULTS: We did not observe any early complication and in long-term follow-up only one patient underwent reoperation 68 months after her first operation due to reoccurrence. CONCLUSIONS: Ventricular myocardial echinococcosis without relation with the cardiac chambers can be operated without using cardiopulmonary bypass with the aid of TEE, PSE, and controlled cyst fluid aspiration.

Adolescent↗

Echinococcosis--an international public health challenge.

This review aims to summarise some of the recent studies that have been undertaken on parasites of the genus Echinococcus and the diseases which they cause. Although the adult parasite, which inhabits the intestine of various carnivore species is not pathogenic, the larval or metacestode stages can be highly pathogenic, causing economic losses to livestock and various forms of echinococcosis in humans, some of which have a high fatality rate. There is growing evidence that there are at least 5 species of Echinococcus rather than the generally accepted 4 species. Within these species there are a number of genotypes or strains. This can have implications for surveillance and control. In some wealthy countries, cystic echinococcosis caused by Echinococcus granulosus has been successfully controlled or indeed eradicated. However, in most parts of the world it remains a serious threat to human health. In the former Soviet Union, the disease has rapidly increased in incidence after the end of communist administration. Human alveolar echinococcosis, caused by Echinococcus multilocularis, is more sporadic. However, in some Chinese communities there is a disturbingly high human prevalence and in Europe there has been an increase in the detection rate of E. multilocularis in animals in the last 10 years. Echinococcosis can present diagnostic challenges, particularly in the definitive host in areas of low endemicity. Much of the recent work relating to the use of coproantigen and PCR to overcome these difficulties is summarized. New ideas for controlling the parasite are becoming available and these include both the use of vaccination and the application of mathematical models to determine the most cost effective means of control. Effective measures that are affordable are vital if the parasite is to be controlled in poor countries.

Animals↗

Specific cellular and humoral immune responses induced by different antigen preparations of Echinococcus multilocularis metacestodes in patients with alveolar echinococcosis.

A specific proliferation of the peripheral blood mononuclear cells (PBMC) stimulated by antigens of Echinococcus sp. has been shown in patients with cystic as well as alveolar echinococcosis. However, the development of a major granulomatous reaction around the parasitic larvae is a characteristic feature of the local immune response to E. multilocularis while humoral immune responses seem to predominate in E. granulosus infection. The aim of this study was to analyse the specific proliferation of the PBMC from 36 patients with alveolar echinococcosis, and 23 controls, induced by a crude preparation of E. multilocularis (EmcAg) as well as by two E. multilocularis specific antigen preparations, the Em2 antigen and the protoscolex (ESAg) antigen. The significant correlation observed between the proliferation index either by Em2 and ES or by Emc suggests that both antigens account for an important part of the lymphocyte proliferative response. The strong effect of these species specific antigens on lymphocyte proliferation is confirmed by the comparison of the results obtained in this study to those obtained in a previous study of specific cellular immunity to E. granulosus antigens in patients with cystic echinococcosis. The proliferation indices were significantly elevated in all those 7 patients with a proven AE who were sero-negative using the Emc ELISA as well as in the 12 patients also seronegative, but using the Em2 ELISA. In 5 seronegative patients who had had a complete resection of the parasitic lesions two years before the lymphocyte proliferation evaluation, the PI was above the threshold value for two dilutions of EmcAg. PI under the threshold values were obtained only in patients with residual lesions. These results suggest that E. multilocularis specific antigens promote the proliferation of lymphocytes which could be TH1 cells, responsible for the intense periparasitic granulomatous reaction characteristic of alveolar echinococcosis.

Adult↗

Ultrasound wall-sign in pulmonary echinococcosis (new application).

PURPOSE: We report our experience in diagnosing pulmonary cystic echinococcosis using an ultrasound sign related to the cystic wall. MATERIALS AND METHODS: 40 patients with 46 cysts, suspected of pulmonary echinococcosis, based on plain chest radiographs and clinical findings, were examined by ultrasound over a 9-year period (1996 - 2004), and followed up until discharge. We applied our long experience with echinococcal cysts utilising the wall sign (WS) to diagnose pulmonary hydatid disease. All cysts were subject to surgical removal, and postoperative histopathology was the gold standard. RESULTS: There were 34 (74 %) unilocular and 12 (26 %) multivesicular echinococcal cysts. In the univesicular cysts, the WS was found in 20 cases (66.7 %) while it was present in all multivesicular cysts (100 %). Following surgical removal, echinococcosis was confirmed by histopathology in all cases. CONCLUSION: We conclude that a double layered border in univesicular and double layered internal septum in multivesicular pulmonary echinococcal cysts is a reliable indicator of pulmonary echinococcosis, with a specificity of 66 % and 100 %, respectively.

Adolescent↗

Benzimidazoles in the treatment of alveolar echinococcosis: a comparative study and review of the literature.

Mebendazole and albendazole are the drugs of choice for the treatment of alveolar echinococcosis. In this open-labelled observational study we present and evaluate the outcome of long-term treatment with these drugs and present results of different treatment regimens. Thirty-five patients were started on either mebendazole or albendazole at the beginning of 1992 and followed for an average of 39 months (range 12-79 months). Treatment was classed as successful if the disease had not progressed for >1 year and if there were no side-effects necessitating a change of treatment. Lack of progression was evaluated mainly using ultrasound and computed tomography and was further substantiated by laboratory tests and clinical findings. The overall success rate was 97%. An initial regimen for cases of alveolar echinococcosis was recurrence-free in 71% of those treated with mebendazole and in 78% of those treated with albendazole. Four out of five cases with progressive disease stabilized after the therapeutic regimen was changed. Seven patients received a continuous regimen with albendazole. These patients were observed over an average of 28 months (range 13-50 months) without signs of progression or significant side-effects. This open-labelled prospective study demonstrates the high therapeutic efficacy of both mebendazole and albendazole with similar response rates in the treatment of alveolar echinococcosis. Albendazole reduced costs by >40% and is easier for patients to take, further arguing in favour of its preferred use. Albendazole in alveolar echinococcosis is only licensed for intermittent application. None the less, continuous treatment is safe and well tolerated and showed promising results when applied to patients in whom other treatment regimens had failed. It should thus be strongly considered in inoperable cases or progressive disease.

Adolescent↗

CT in lobar atrophy of the liver caused by alveolar echinococcosis.

We reviewed the CT findings of 13 patients with histologically proved alveolar echinococcosis of the liver. Seven of these patients had hilar involvement, which caused dilatation of intrahepatic bile ducts and invasion of the portal vein or portal branches. In two of these patients we found marked atrophy of the right lobe and in one patient marked atrophy of the left lobe in addition to various CT findings previously reported for alveolar echinococcosis of the liver. The occurrence of lobar atrophy of the liver caused by alveolar echinococcosis has not been previously reported. We concluded that, when a mass lesion with hilar infiltration causing lobar atrophy is found in endemic areas, alveolar echinococcosis should be considered in the differential diagnosis in addition to malignant neoplasms.

Atrophy↗

Serological differentiation between cystic and alveolar echinococcosis by use of recombinant larval antigens.

Two recombinant antigens of the larval stages of Echinococcus granulosus and Echinococcus multilocularis, termed EG55 and EM10, respectively, were applied for serodiagnosis and serological differentiation between parasitic infections caused by the metacestode tissue of both tapeworms. Antigen EM10 is synthesized by E. multilocularis larvae. Antigen EG55 represents the recombinant form of the low-molecular-weight subunit of antigen B, which is an Echinococcus genus-specific antigen. Both recombinant antigens were expressed as glutathione S-transferase fusion proteins. A sandwich enzyme-linked immunosorbent assay with monoclonal antibodies against EM10 and EG55 as capture reagents for the recombinant antigens was established and was evaluated with 74 serum samples from patients with histologically confirmed alveolar echinococcosis and 63 serum samples from patients with histologically confirmed cystic echinococcosis. A sensitivity of 93.2% and a specificity of 96.8% were achieved for the serodiagnosis of alveolar echinococcosis. Cystic echinococcosis could be detected with a sensitivity of 89.1% and a specificity of 98.6%.

Animals↗

[Hepatic echinococcosis and its surgical treatment].

973 patients were operated for the period of 14 years for echinococcosis of the abdominal cavity. Echinococcosis of the liver was revealed in 742 (76.2%) patients. Complicated forms of echinococcosis were registered in 42.3% patients. Suppurative cyst was detected in 138 (43.9%) patients; perforation of the cyst into free abdominal cavity--in 22 (7%), into pleural cavity--in 14 (4.5%) patients, into bile ducts--in 62 cases (19.7%); biliary tracts compressing by the cyst with mechanical jaundice--in 29 (9.2%) patients; bilio-pulmonary bronchial fistula was revealed in 7 (2.3%) patients and calcification of the cysts--in 42 (13.4%). Radioisotope scanning, X-ray, ultrasound, Computed tomography and serological reactions were used for diagnosis. For differential diagnosis of parasitic cysts from non-parasitic cysts laparoscopic video technique was also used in three cases. Radical operations were carried out in 47 patients, 19 patients from them underwent total pericystectomy and 28 patients underwent resection of the liver. For echinococcosis of the liver complicated by mechanical jaundice: in this case echinococcectomia was done with the correction of the continuity of the bile duct. Ultrasound cavitation, CO2 laser, thermal or thermic means (70 degrees C solution of furaciline or instant steam treatment) were used for antiparasitic purposes.

Echinococcosis, Hepatic↗

Diagnosis and classification of hepatic echinococcosis by ultrasonography.

OBJECTIVE: To make an early and correct diagnosis of hepatic echinococcosis. METHODS: A total of 1092 patients with hepatic echinococcosis underwent operation in our hospital between 1984 and 1995. Of these patients, 427 (39.1%) were cases with complications, including secondary infection, rupture, obstructive jaundice, anaphylactic shock, disseminated implantation with resultant multiple echinococcosis and portal hypertension. The ultrasonic examination has been generally used in clinical practice for comprehensive evaluation which can dectedct the preoperative diagnostic accuracy rate. RESULTS: B-mode ultrasonography can be used not only to detect the location, dimension and pathological characteristics of hydatid cyst but also to show the pathological changes of various complications caused by echinococcosis. Seven patterns specific ultrasonic scanning images were revealed. In this series the diagnostic accuracy rate reached 98.8%. CONCLUSIONS: Ultrasonic examination is harmless to human body, and has been widely used in combination with immunological tests in clinical and epidemiological studies to detect the asymptomatic parasite carriers in early stage and to improve the preoperative diagnostic accuracy rate.

Echinococcosis, Hepatic↗

[The surgical treatment of echinococcosis of the diaphragmatic surface of the liver].

The results of surgical treatment of 628 patients aged 15-76 years operated on for echinococcosis of diaphragmatic surface of the liver have been analysed for period from 1976 to 1996. 333 patients had complicated echinococcosis, 124 combined pathology of other organs. Methods which have been applied for diagnosis of echinococcosis of the liver and its complications are described. Details of surgical treatment of the echinococcosis of the diaphragmatic surface of the liver are elucidated in time course aspects, as a staged treatment, during which various factors were used for antiparasitic treatment of cystic cavity as well as various methods of elimination of the residual cavity. Problems concerning application of laser and plasmatic scalpel during various stages of the operation, as well as low-intensity lasers and low-frequency ultrasound during the operation and in postoperative period are considered. Postoperative complications were detected in 99 (15.8%) patients, lethal outcomes were in 5 (0.8%) cases.

Adolescent↗