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Assessment of the immunological surveillance value of humoral and lymphocyte assays in severe human cystic echinococcosis.

Thirty cystic echinococcosis (CE) patients in Uruguay with severe bone or secondary disseminated echinococcosis were immunologically assessed using cellular (lymphocyte transformation assay, LTA) and humoral (specific antibody and subclass responses, circulating antigen and circulating immune-complexes) immunological assays during the course of chemotherapy (albendazole and/or praziquantel). CE patients were divided into 4 groups, according to clinical treatment and outcome: (I) surgery and chemotherapy, (II) chemotherapy with outcome unchanged, (III) chemotherapy with outcome improved, and (IV) chemotherapy considered cured. Increased circulating antigen was of prognostic value in some severe CE cases where levels remained high and/or increased. The lymphoproliferative response in vitro to Echinococcus granulosus antigen was statistically greater in all patient groups compared to normal individuals but at lower levels in improved or cured CE patients. Levels of non-specific LTA response were significantly lower than controls for all groups during albendazole treatment (P < 0.001) but returned to normal levels in cured patients, a result consistent with parasite-induced suppression of cellular responses. This study suggests that, at least in severe osseous and secondary CE, immunosurveillance by specific antibodies, especially total specific immunoglobulin, was overall of more practical use than antigen-specific in-vitro lymphocyte transformation assays.

Adult↗

The emerging epidemic of echinococcosis in Kazakhstan.

Since independence from the Soviet Union in 1991 the annual surgical incidence of cystic echinococcosis in Kazakhstan has increased from 1.4 cases/100,000 in 1991 to 5.9 cases/100,000 in 2000. In some regions the annual surgical incidence is now over 10 cases/100,000. Twenty-nine percent of recorded cases in 2000 were in children aged < 14 years, which indicates recent transmission. Most of the cases are occurring in the regions where the sheep industry is concentrated, indicating that the zoonotic sheep strain of Echinococcus granulosus is the likely cause of the problem. The gross domestic product (GDP) of Kazakhstan has declined by nearly 50% since independence. Concurrently there has been decreased health spending with decreases in the numbers of hospitals, hospital beds and physicians. This situation suggests that an increase in the diagnosis of echinococcosis is an unlikely explanation for the epidemic but that there is an increase in transmission to the human population.

Adolescent↗

Immunoblot evaluation of the species-specificity of Em18 and Em16 antigens for serodiagnosis of human alveolar echinococcosis.

An immunoblot study to confirm the species-specificity of the diagnostic antigens Em18 and Em16 of Echinococcus multilocularis protoscolex extract showed that both antigens cross-reacted with sera from cystic echinococcosis (CE) patients. The 18 kDa component was detectable by 75% of the sera from active alveolar echinococcosis (AE) patients, while only 31% detected Em16. Western blot analysis also showed that AE sera recognized a band in the 18 kDa region of E. granulosus protoscolex extract, which was different from the 16/17 kDa subunit of antigen B. The results suggested that Em18 antigen is present in E. granulosus as well as E. multilocularis, and that some CE patients may have serum antibody against this antigen.

Antigens, Helminth↗

Long-term mebendazole therapy may be parasitocidal in alveolar echinococcosis.

Long-term chemotherapy of human alveolar echinococcosis with benzimidazole compounds (mebendazole, albendazole) has been shown to be primarily parasitostatic, but its curative (parasitocidal) efficacy is debated. This article reports on a 67-year-old male patient with non-resectable alveolar echinococcosis of the liver who had been continuously treated for 13 years with mebendazole (approximately 45-48 mg/kg body weight per day) and who was closely monitored according to a specific protocol. At the age of 80 years the patient died of oesophageal variceal bleeding. During treatment the hepatic lesion had decreased markedly in size in association with progression of perifocal calcification. At autopsy, a well-demarcated, necrotic, partially calcified, parasite-induced lesion of the right liver lobe and secondary biliary cirrhosis were found. Remnants of parasite tissue obtained from the periphery of the lesion showed a small-cystic structure, but it was not viable, as evidenced by transplantation of tissue blocks to rodents. The case is suggestive for a parasitocidal efficacy of mebendazole treatment carried out for 13 years, and is discussed in context with conflicting literature data.

Aged↗

A study of cystic echinococcosis in slaughter animals in three selected areas of northern Turkana, Kenya.

In an attempt to establish the prevalence of cystic echinococcosis, a study was conducted in slaughter animals in three divisions of northern Turkana, Kenya. A total of 5752 goats, 588 sheep, 381 cattle and 70 camels were examined at slaughter. Echinococcus granulosus metacestodes were found in 19.4% of the cattle, 3.6% of sheep, 4.5% of goats and 61.4% of camels. The prevalence of cystic echinococcosis in cattle, sheep and goats was higher in Lokichogio than in either Kakuma or Central divisions. On the other hand, the prevalence of the disease in camels was higher in Central (84.6%) than either Lokichogio (70.6%) or Kakuma (50%). The differences in prevalence rates in different study areas are attributed to differences in environmental conditions, livestock stocking intensity and cross-border migration of livestock.

Animals↗

Coproantigens: early detection and suitability of an immunodiagnostic method for echinococcosis in dogs.

In the present study immunodiagnostic tests for Echinococcus granulosus-specific coproantigens have been evaluated. The techniques are based on polyclonal antisera collected from dogs experimentally infected with E. granulosus protoscoleces. ELISA, Countercurrent immunoelectrophoresis (CCIEP) and Immunodot were evaluated for their application in coprodiagnosis. The level of coproantigens was detectable on day 7 post-infection and reached a maximum level on day 56 as detected by ELISA. Very high O.D values were obtained when faecal samples of 7-8 weeks post-infection were used. Besides this, immunodot and CCIEP were also tested and the 4th week post-infection samples gave significant reactions. It is evident from the results that ELISA was more sensitive and detected the coproantigens as early as the first week post-infection whereas immunodot and CCIEP detected coproantigens later. The latter methods are rapid, cost-effective and can be used to diagnose suspect cases of echinococcosis under field conditions. Thus, it is suggested that future studies should be aimed at early detection of echinococcosis by a rapid and cost-effective immunodot test.

Animals↗

Usefulness of contrast-enhanced wide-band Doppler ultrasonograpy to diagnose alveolar echinococcosis of the liver and evaluate the effect of the treatment.

Alveolar echinococcosis is a rare parasitic disease caused by Echinococcus multicularis and most commonly involves the liver. Early diagnosis and accurate evaluation of the effect of the treatment are essential to improve the prognosis of patients with alveolar echinococcosis of the liver (AEL). The aim of this study was to demonstrate the characteristic imaging of AEL by contrast-enhanced Dynamic Flow (CE-DF) employing a wide-band Doppler technique for the diagnosis and the accurate evaluation of the effect of the treatment. Four patients with five AEL lesions before treatment or during medication were examined by CE-DF. All of the five AEL lesions examined by CE-DF revealed a defect with an irregular and distinct margin like a worm-eaten defect appearance, which was never observed on other hepatic lesions, in liver perfusion image during post-vascular phase. In addition, CE-DF made it possible to measure the size of AEL lesions accurately because the margin was detected distinctly. These data suggest that CE-DF is clinically useful for the diagnosis of AEL and the evaluation of the effect of the treatment.

Aged↗

Bronchobiliary fistulae due to echinococcosis.

OBJECTIVE: A bronchobiliary fistula (BBF) is a rare complication of echinococcosis due to rupture of hydatid cysts located at the upper surface of the liver to the bronchial tree. We present our experience in treating this uncommon and dangerous entity. MATERIAL: During the last 20 years, 21 patients, ten men and 11 women ranging in age from 26 to 83 years with a BBF were treated in our department. They presented dyspnea, biloptysis, cough or fever. Diagnostic imaging studies have been very helpful in identifying the communication and in delineating its location. The disease was limited to the liver in 11 cases, whereas in the rest ten cases, both liver and lung were involved. RESULTS: Right thoracotomy was the approach of choice. Our strategy consisted of adequate evacuation of the intrahepatic cysts, obliteration of the cyst space, freeing the adherent lung, dissection and closure of the BBF. Two deaths occurred due to anaphylactic shock and cardiac insufficiency. Follow up at 7-12 years did not reveal any recurrence. CONCLUSION: Although the incidence of echinococcosis has been decreased, the BBF still remains a serious complication with a high morbidity and mortality. Early diagnosis and management of septic associated complications are essential.

Adult↗

Serodiagnostic potential of chemically synthesized glycosphingolipid antigens in an enzyme-linked immunosorbent assay for alveolar echinococcosis.

In the serodiagnosis of alveolar echinococcosis, the detection of specific reactions against not only protein but also carbohydrate antigen is useful and both antigens supplement each other. Though recombinant protein antigens have recently advanced, the preparation of carbohydrate antigen still depends on extraction from crude antigens. In the latter case, it is not conventional to obtain carbohydrate antigen as a single component for examination and research. Therefore, chemically synthesized carbohydrate antigens were prepared for serodiagnosis by the enzyme-linked immunosorbent assay (ELISA). Four antigens with the structure of glycosphingolipids from Echinococcus multilocularis were examined and one antigen, Galbeta1-6(Fucalpha1-3)Galbeta1-6Galbeta1-ceramide, was found to show significant serodiagnostic potential in differentiating alveolar from cystic echinococcosis.

Animals↗

Serodiagnosis of cystic echinococcosis in naturally infected camels.

An ELISA was developed for serological detection of Echinococcus granulosus infection in dromedary camels. Antigen B (AgB) partially purified from hydatid cyst fluid of camels or sheep naturally infected with cystic echinococcosis (CE) due to E. granulosus, as well as a recombinant antigen B product (r-AgB) were used in an ELISA to screen panels of serum samples from slaughtered camels naturally infected with CE. Native hydatid cyst fluid antigen preparations were able to detect antibodies in sera from a significant proportion of camels with CE, as confirmed at post-mortem. Seroreactivity however, was variable. ELISA specificity for sera from naturally infected camels versus inspection-negative animals ranged from 90 to 99%. Native antigen B gave the highest sensitivity (97%) in ELISA for camel CE confirmed at slaughter. In contrast, r-AgB gave lower sensitivity for camel (84%) and sheep (28%) CE. The r-AgB-ELISA was, however, highly specific (90 and 95%) respectively for both camel and sheep natural CE infection. These results indicate that an ELISA based on serum antibody detection to AgB could be developed for immunodiagnosis of cystic echinococcosis in camels.

Animals↗

Characterization of excretory-secretory products from protoscoleces of Echinococcus granulosus and evaluation of their potential for immunodiagnosis of human cystic echinococcosis.

This study describes, for the first time, the characterization of excretory-secretory antigens (ES-Ag) from Echinococcus granulosus protoscoleces, evaluating their usefulness in the immunodiagnosis of human cystic echinococcosis. ES-Ag were obtained from the first 50 h maintenance of protoscoleces in vitro. This preparation contained over 20 major protein components which could be distinguished by 1-dimensional SDS-PAGE with apparent masses between 9 and 300 kDa. The culture of of protoscoleces from liver produced a greater variety of excretory-secretory protein components than those from lung. Determination of enzymatic activities of secreted proteins revealed the presence of phosphatases, lipases and glucosidases, but no proteases. These findings were compared to those obtained from somatic extracts of protoscoleces and hydatid cyst fluid products. Immunochemical characterization was performed by immunoblotting with sera from individuals infected by cystic echinococcosis (n = 15), non-hydatidic parasitoses (n = 19), various liver diseases (n = 24), lung neoplasia (n = 16), and healthy donors (n = 18). Antigens with apparent masses of 89, 74, 47/50, 32, and 20 kDa showed specificity for immunodiagnosis of human hydatidosis. The 89 and 74 kDa components corresponded to antigens not yet described in E. granulosus, whereas proteins of 41-43 kDa and 91-95 kDa were recognized by the majority of the non-hydatid sera studied.

Animals↗

Serum cytokine detection in the clinical follow up of patients with cystic echinococcosis.

The relation of serum cytokine levels and outcome of chemotherapy was evaluated in 15 patients with cystic echinococcosis. Serum IL-4, IL-10 and interferon-gamma (IFN-gamma) concentrations were determined by ELISA before and after a 3-month course of albendazole treatment: at least one serum sample per patient from 13 patients (87%) contained measurable amounts of IL-4; samples from five patients (33%) measurable amounts of IL-10 and samples from only two patients (13%) measurable amounts of IFN-gamma. Clinical assessment at 1 year after the end of therapy showed that 11 of the 15 patients had responded clinically. Seven of these patients had lower IL-4 serum concentrations, two had unchanged and two undetectable amounts (pre- versus post-therapy, n = 11, P = 0.008). Conversely, of the patients who did not respond, three had higher and one patient unchanged serum IL-4 concentrations. Serum IL-10 10 levels also decreased in all patients who responded (3/5) and increased in all patients who did not (2/5). No association was found between cytokine concentrations and cyst characteristics or antibody levels. Overall these data suggest that serum IL-4 detection may be useful in the follow up of patients with cystic echinococcosis.

Adult↗

Experimental investigations on the B and T cell immune response in primary alveolar echinococcosis.

Susceptibility/resistance of the intermediate host to alveolar echinococcosis (AE) seems to be based on hitherto unknown immunological mechanisms, possibly involving the activation of different CD4+ T cell immune responses (Th1/Th2). Mice of two strains previously characterized as 'susceptible' (C57BL/6 J) and 'resistant' (C57BL/10 J) to secondary AE were orally infected with eggs of Echinococcus multilocularis and the course of infection was analysed by macroscopical, pathohistological and immunohistochemical examinations of the lymphocytes and cytokines participating in the periparasitic granulomas and by serological examinations of cytokines and E. multilocularis-specific antibodies. Although differences in the extent of parasitic growth were seen between the two groups, the composition of the granulomas was quite similar with CD4+ cells being the dominant lymphocyte subpopulation, succeeded by B cells and CD8+ cells. Interferon (IFN)-gamma-, interleukin (IL)-2- and IL-4-expressing cells could not be detected in the lesions of the early phase of the infection, possibly indicating the host's immunosuppression, but were present at the end. IL-10 was the most prominent cytokine throughout the course of the disease. Serological analyses of the cytokine concentrations revealed small amounts at the beginning and high levels at the end of the infection. The pattern of cytokine response was similar for IL-4 in both strains, but different for IL-2 and IL-10 in the late phase, when the C57BL/10 J strain developed higher levels than the C57BL/6 J strain. Correspondingly only small amounts of immunoglobulin (Ig)M, IgG1, IgG2a and IgG3 could be detected at the beginning of disease, followed by higher levels at the end. The courses of antibody titres were similar in both groups except IgG3, which was more pronounced in the C57BL/10 J strain. Parasite-specific IgG2b could neither be detected in the C57BL/6 J nor in the C57BL/10 J strain by the test system used. The results of the study suggest both subsets of CD4+ T cells (Th1 and Th2) being involved in murine primary alveolar echinococcosis. A strict differentiation of mice in susceptible and resistant animals based on the activation of different CD4+ T cell immune responses (Th1 'resistant' and Th2 'susceptible') should be avoided.

Animals↗

An enzyme-linked immunosorbent assay for detection of IgG1 antibodies specific to human cystic echinococcosis in Egypt.

Human cystic hydatidosis (cystic echinococcosis) is a chronic zoonotic disease that results from infection with the dog tapeworm Echinococcus granulosus. In Egypt, cystic echinococcosis (CE) is recognized in slaughtered livestock by veterinarians, however, there is little information about human CE infection rates. We describe an immunological assay useful for the diagnosis of human cystic hydatidosis. Sera were collected from surgically confirmed hydatid cases (34), nonendemic subjects free from parasitic infection (20) and from subjects (109) infected with other helminths (Hymenolepis nana, Schistosoma mansoni, Fasciola hepatica and Ancylostoma duodenale). Hydatid cyst fluid (HCF) of camel origin was used as antigen in an ELISA format to measure total E. granulosus specific IgG antibodies and IgG subclasses. Sensitivity measurements of total IgG, and IgG1-4 were 100, 100, 79.4, 61.8 and 55.9%, respectively, whereas respective specificity reached 65.1, 97.7, 98.4, 96.1 and 83. 7%. The diagnostic value of measuring IgG1 (97.7%), as assessed by a rating index (J) for combined sensitivity and specificity, was superior to total IgG (65.1%) and IgG2-4 (77.8, 57.9 and 39.6%, respectively). These findings set the stage for field evaluation of the IgG1 assay in areas endemic with human cystic hydatidosis.

Adolescent↗

HASTE MRCP and MRI findings in alveolar echinococcosis of the liver.

Alveolar echinococcosis is a rare mass-producing inflammatory process of the liver. Experience with MRI, and particularly magnetic resonance cholangiopancreatography (MRCP), demonstrates that features of this disease are limited. The HASTE (half-Fourier acquisition single-shot turbo spin echo) MRCP and MRI findings of alveolar echinococcosis of the liver are presented in this report. HASTE MRCP was used to define the biliary system and the biliary system-mass relationship. It was found that results were comparable with those of invasive techniques such as endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography.

Adolescent↗

[Surgical therapy of cystic echinococcosis of the liver].

This study analyses the results of a surgical deroofing technique that was used for the treatment of cystic echinococcosis of the liver in our institution during the last 18 years. The deroofing technique was used on 106 of 132 patients from January 1981 to December 1998. Other operative techniques (pericystectomy, hemihepatectomy) were performed on 26 patients. In 12 cases (9%) the operative procedure was completed by interventions at the extrahepatic bile ducts. 99 patients (75%) showed one or two cysts, and the remaining 33 patients (25%) had three or more cysts in the liver. 18 (14%) patients had to be reoperated on account of complications: in 5 cases a postoperative hemorrhage, in 11 cases a bile duct leakage and in 2 cases an intraabdominal abscess had to be treated operatively. The follow-up of 74 patients (81%) revealed recurrent disease in 14 (19%) cases. Surgical deroofing of cystic echinococcosis of the liver is easy to perform and in contrast to other minor surgical interventions universally applicable. The recurrence rate and the rate of postoperative complications are comparable to other minor surgical techniques. Therefore in our view this procedure represents the therapy of choice.

Adolescent↗

[Isolated intracerebral cystic echinococcosis. Unusual presentation of a rare disease].

HISTORY AND CLINICAL FINDINGS: A 46-year-old woman was admitted with a first generalised tonic-clonic seizure. Past medical history was unremarkable. She reported no travels abroad within the past five years. INVESTIGATIONS: Brain MRI demonstrated disseminated cerebral and cerebellar focal lesions. Cerebrospinal fluid analysis showed a mild eosinophilic pleocytosis. Extensive imaging investigations and serological tests revealed no hints for a systemic parasitic disease. A stereotactic brain biopsy detected no pathogenic agent. 10 months following the initial admission, brain MRI showed multiple cystic lesions with ring-like enhancement following Gd-DTPA administration. At that time serological tests were positive for an infection with Echinococcus granulosus. DIAGNOSIS: The diagnosis was based on positive sequential serological tests and the typical MRI findings in conjunction with an eosinophilic cerebrospinal fluid pleocytosis. TREATMENT AND CLINICAL COURSE: An antihelmintic therapy with Albendazole was initiated. Following two-months of oral Albendazole administration, brain MRI revealed a clear reduction in size and number of the hydatid lesions. The patient was free of complaints and the clinical examination was unremarkable. CONCLUSION: Isolated intracerebral manifestation of cystic echinococcosis is very rare. Compared to the typical presentation with a solitary cerebral hydatid cyst, the dissemination of hydatid cysts is quite uncommon in cystic echinococcosis. Diagnosis should be based on the typical MRI findings and serological tests. The present case demonstrates that the later may be negative over a long period within the clinical course of the disease offering a real challenge to the clinician.

Albendazole↗

[Cystic echinococcosis of the liver--problems of ultrasound diagnosis].

The authors examined 100 patients with a total of 119 cysts of the liver. The diagnosis was subsequently confirmed via scintigraphy, radiology and laparotomy. This paper reports on a sonographic analysis of cystic echinococcosis of the liver, its sonographically demonstrable types, structures and complications and their differential diagnosis. In 58% of the cases the classical aspect of cystic echinococcosis was seen (Type A). 22.7% of the cases pointed toward a sediment within the cyst (Type B). 8.4% of the cysts were septated (Type C), whereas 6.7% had daughter cysts (Type D). However, only 4.2% of the cysts were important for differential diagnosis, since they had to be set off against other space-occupying growths on account of their solid tumorous structure.

Biliary Fistula↗