Echinococcosis

Echinococcosis is a human disease caused by the larval form of Taenia echinococcus, which lives in the gut of the dog, wild canides and other carnivorous animals which represent the definitive hosts and involves as intermediate hosts both domestic and wild animals. Humans become accidental intermediate hosts by ingesting Taenia eggs. The main species pathogenic for man are E granulosus causing cystic echinococcosis with worldwide distribution and endemic in sheep and cattle breeding countries, and E multilocularis causing alveolar echinococcosis, with preferential distribution in the northern hemisphere. After ingestion of contaminated food, hexacanth embryos migrate by the portal system to liver and later lung, brain and other tissues. Symptoms are related to both cyst location and size. E granulosus infection of the central nervous system (CNS) may be primary or secondary and has been estimated to be low (2%). Sharply demarcated, spherical and intraparenchy-mal, cysts may reach a large size causing neurological symptoms. Spilling of cyst fluid due to trauma or surgery may trigger anaphylaxis as well as disseminated infection. Host reaction is minimal in the brain but a foreign giant cell reaction may develop. E multilocularis develops within the liver as a rapid invasive pseudomalignant growth and may metastasize to the CNS, where estimated incidence reaches 5%. Hydatid antigens induce an immune reaction in the host which is helpful for the diagnosis. DNA probes and PCR may be applied to differentiate between Echinococcus spp. Although the host develops an immunological protection from reinfection, the parasite evades host immune attack. A wide range of evasion mechanisms have been advanced, including a barrier for host cells due to hydatid cyst laminated cuticle, polyclonal activation of lymphocytes by parasite soluble antigens, and depression of host cell immune responses. Chronic stimulation of the host by cyst fluid antigens leads to increased specific IgG4 production, which might act as blocking antibodies against anaphlaxis suggestive of host response immuno-modulation.     

Specific IgG Responses to Recombinant Antigen B and Em18 in Cystic and Alveolar Echinococcosis in China

An understanding of the correlation of the specific antibody responses and the disease phase is essential in evaluating diagnostic values of immunological tests in human echinococcosis. In this study, 422 echinococcosis patients diagnosed by ultrasonography, including 246 with cystic echinococcosis (CE), 173 with alveolar echinococcosis (AE), and 3 with dual infection, were tested for specific IgG in sera against recombinant AgB (rAgB) and recombinant Em18 (rEm18) in an enzyme-linked immunosorbent assay. As a result, rAgB-specific antibody was detected in 77.6% of CE and 86.1% of AE patients, while rEm18-specific antibody was present in 28.9% of CE and 87.3% of AE patients. Additionally, all three patients with dual infection exhibited specific antibodies responding to rAgB and rEm18. Further analysis revealed that rAgB-specific antibody was elevated in a significantly greater proportion (87.3%) of CE patients with cysts at active or transitional stages (CE1, CE2, or CE3), compared to 54.8% of other patients with cysts at an early or an inactive stage (CL or CE4 or CE5). Furthermore, rAgB-specific antibody was detected in 95.6% of CE2 cases, which was statistically greater than that (73.7%) in CE1 patients. Although rEm18-specific antibody was elevated in 28.9% of CE patients, the positive reaction was much weaker in CE than in AE cases. Serum levels and concentrations of rEm18-specific antibody were further indicated to be strongly disease phase correlated in AE patients, with positive rates of 97.4% in cases with alveolar lesions containing central necrosis and 66.7% in patients with early alveolar lesions that measured ≤5 cm.Humans acquire the infection of echinococcosis by accidental ingestion of eggs excreted with feces of carnivores harboring the adult worms of Echinococcus spp. The eggs hatch in the small intestine of humans, releasing the oncosphere, which migrates via the portal system into various organs and then develops into the metacestode stage. The larval parasite can establish itself in any part of the human body but most frequently does so in the liver (32). Diagnosis of human echinococcosis is primarily based on the pathognomonic features in images obtained using imaging techniques including ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Of these techniques, B-ultrasound is much more widely applied, as CT and MRI are too expensive and largely inaccessible in most areas where echinococcosis is endemic. Criteria for classification of cystic echinococcosis (CE) and alveolar echinococcosis (AE) have been proposed based on stage-specific ultrasound images (20, 36). Briefly, on the basis of conformational features of cysts, CE lesions are differentiated into six types: CL, CE1, CE2, CE3, CE4, and CE5. The CL type refers to a cystic lesion of a parasite origin and without a clear rim, indicating the parasite is at a very early stage of development. The CE1 type describes a unilocular simple cyst with uniform anechoic content and, importantly, with a visible wall, while the CE2 type is characterized by multivesicular, multiseptated cysts in which daughter cysts may partially or completely fill the unilocular mother cyst. The presence of CE1 or CE2 cysts is indicative of an active stage of the disease. The CE3 type is distinguished by detachment of the cyst membrane and/or partial degeneration of cyst content, suggestive of a transitional parasite. A CE4 or CE5 type of cyst shows an involution, with a necrotic or inactive parasite, with the features of complete degeneration of cyst content for CE4 and a calcified cyst wall for CE5 (36). In contrast, AE lesions are characterized by a nonhomogenous hyperechoic tumor-like structure with a poorly defined verge and containing scattered calcifications and/or a central necrotic cavity (1), and they are further differentiated into three types and eight subtypes based on the features and sizes of lesions, including AE1, AE2, and AE3 (20). In detail, AE1 refers to alveolar lesions measuring ≤5 cm, normally without central necrosis detected, and the type is differentiated further as AE1s (single lesion) and AE1m (multiple lesion) subtypes and indicates an early stage of the disease. Alveolar lesions that measure >5 cm and ≤10 cm are classified as AE2 and include three subtypes, recorded as AE2s (single lesion), AE2m (multiple lesions), and AE2f (presence of central necrotic fluid, regardless of the number of lesions), suggestive of a developing parasite, while AE lesions that measure >10 cm in diameter are confirmed as AE3, indicative of an advanced stage of the disease; this type includes three subtypes, i.e., AE3s (single lesion), AE3m (multiple lesions), and AE3f (presence of central necrotic fluid).Meanwhile, several antigens, such as antigen B (AgB) (15, 23, 24, 26) for cystic echinococcosis and for Echinococcus multilocularis Em2a (8), II/3 (34), II/3-10 (27), EM10 (5), EM4 (9), and Em18 (12, 30), have been confirmed to be of potential use in serodiagnosis of human echinococcosis. However, relatively little information about the correlation between the specific antibody levels in humans and disease pathology or stage is available (29).In this study, serum levels and concentrations of specific IgG antibodies in human CE and AE patients at different stages were determined by enzyme-linked immunosorbent assay (ELISA) using recombinant antigen B (rAgB) and recombinant Em18 (rEm18) as antigens.     

Evaluation of a New Immunochromatographic Test Using Recombinant Antigen B8/1 for Diagnosis of Cystic Echinococcosis

Diagnosis of cystic echinococcosis (CE) is based on the identification of the cyst(s) by imaging, using immunodiagnostic tests mainly as complementary tools in clinical settings. Among the antigens used for immunodiagnosis, previous studies described a good performance of the recombinant antigen B8/1 (rAgB) in an enzyme-linked immunosorbent assay (ELISA) format; however, in remote parts of areas where the disease is endemic, the implementation of an ELISA is difficult, so a more simple, rapid, and reliable method such as the immunochromatographic test (ICT) is required. In this study, using a set of 50 serum samples from patients with surgically confirmed CE, we compared the performance of an ICT and that of an ELISA using the rAgB. The overall sensitivities of ICT and ELISA were not statistically different (78% versus 72%; P = 0.36). The overall agreement between both tests was moderate (κ = 0.41; P < 0.01). Concordance between ICT and ELISA was substantial or almost perfect for patients with liver involvement (κ = 0.65; P < 0.001) and patients with more than one hydatid cyst (κ = 0.82; P < 0.001), respectively. Moreover, specificity analysis using a total of 88 serum samples from healthy individuals (n = 20) and patients (n = 68) with other parasitic infections revealed that ICT had a specificity of 89.8%. ICT and ELISA had similar performance for the detection of specific antibodies to E. granulosus, and ICT had a high specificity, opening the possibility of using ICT as a screening tool in rural settings.     

Echinococcosis in Austria

In 1982, a research project on the prevalence of human echinococcosis in Austria was started. Within the period from 1982 to 1988, data on 188 patients with cystic (CE) and of 16 patients with alveolar (AE) echinococcosis were obtained. 15 out of 16 AE patients and 79 (= 42%) out of 188 CE patients were Austrian nationals, 1 AE patient was of Swiss nationality, and 94% of the 109 non-Austrian patients came from Mediterranean countries. Cases of (presumably autochthonous) cystic echinococcosis were found in Lower Austria, Vienna, Burgenland, Styria, Upper Austria, Carinthia, Salzburg and Vorarlberg, the eastern part of Austria being the main distribution area. Cases of (certainly autochthonous) alveolar echinococcosis were recorded in the Tyrol, in Carinthia and in Lower Austria. At the time of diagnosis, the average ages of Austrian patients with E. multilocularis (49 years) and with E. granulosus (55 years), respectively were significantly higher than those of foreign CE patients (34 years). The finding concerning the localisation of the infection (78% of E. granulosus cysts and 100% of E. multilocularis lesions were located in the liver) are consistent with previously published reports.     

Echinococcosis and allergy

The larval stages of Echinococcus granulosus and E. multilocularis are involved in parasitic diseases in humans: cystic echinococcosis (CE) ("hydatid disease") and alveolar echinococcosis (AE), respectively. Both diseases and parasites have tight links with allergy because of the immunological characteristics that contribute to maintain the larvae in their human host as well as their potential in inducing clinical anaphylactic reactions in some patients. Clinical observations in patients and data obtained from mass screenings in various countries have identified both forms of echinococcosis as "polar diseases," i.e., diseases where immunological background of the patients was related to the clinical presentation and course. In particular, abortive cases (i.e., spontaneous cures) have been found in many subjects in endemic areas. On the other hand, immune suppression was associated with severe disease. AE especially might be considered as an opportunistic infection. Experimental and clinical studies have shown that Th1-related immune response was associated with protection and Th2-related response was associated with parasite growth. Genetic characteristics of the host are related to both occurrence and severity of AE and are associated with the extent of IL-10 secretion, which is a major feature of chronic progressing echinococcosis. Anaphylactic reactions, including urticaria, edema, respiratory symptoms, and anaphylactic shock due to spontaneous or provoked rupture of the parasitic cyst, are well known in CE. Anaphylactic reactions in AE are far less frequent, and have been observed in rare cases at time of metastatic dissemination of the parasitic lesions. Echinococcus-specific IgE is present in most of the patients and associated with severity. Specific histamine release by circulating basophils stimulated with E. granulosus antigens is present in all patients with CE and AE. Echinococcus allergens include (1) AgB 12-kDa subunit, a protease inhibitor and a potent Th2 inducer; (2) Ag5, a serine protease; (3) EA 21, a specific cyclophilin, with a homology with other types of cyclophilins; (4) Eg EF-1 beta/delta an elongation factor, with a homology with Strongyloides stercoralis EF that shares the same IgE epitope. A clinical cross-reaction with Thiomucase, a mucopolysaccharidase used in arthritis treatment, has recently been published. However, despite the potential risk of allergic reactions, the dogma "never puncture a hydatid cyst" is no longer valid. International experience of therapeutic technique of "puncture, aspiration, injection, re-aspiration" of hydatid cysts developed at the beginning of the 1980s has proved to be successful in a variety of selected indications that have been reviewed by WHO recommendations. A better understanding of the immunological background of echinococcosis in humans has led to new therapeutic developments, such as immunomodulation using interferon alpha. Th2-driven immunological response and IL-10-related tolerance state are common characteristics of atopic allergy and echinococcosis. The example of echinococcosis stresses the ambiguous links that exist between parasitic and allergic diseases, and show the usefulness of comparing these diseases to better understand how immune deviation may lead to pathological events and to find new therapeutic and.or preventive agents.     

Usefulness of Hydatid Cyst Fluid of Echinococcus granulosus Developed in Mice with Secondary Infection for Serodiagnosis of Cystic Echinococcosis in Humans

The aim of this work was to assess the usefulness of hydatid cyst fluid (HCF) of Echinococcus granulosus, obtained from mice experimentally infected with hydatid cyst tissue homogenates, for the serodiagnosis of cystic echinococcosis (CE) in humans. The sensitivity and specificity of HCF obtained from mice for the detection of immunoglobulin G (IgG) antibodies in the sera of CE patients were compared with those of HCF from sheep and/or from a human CE patient by using immunoblotting (IB) and an enzyme-linked immunosorbent assay (ELISA). HCFs obtained from three different host species all were highly useful for immunoblotting, and sera from 19 (95%) of 20 CE patients equally recognized the antigen B subunit (approximately 8 kDa). HCF from mice showed a cross-reaction with 9 of 20 alveolar echinococcosis (AE) sera (45%), whereas HCFs from two other host species cross-reacted with 14 of the AE sera (70%). Although 2 (10%) of 20 sera from neurocysticercosis (NCC) patients were false positive with HCF from both sheep and humans, none of these sera showed a positive reaction with HCF from mouse origin. ELISAs with HCFs from both mouse and sheep origins detected all 20 CE and AE sera; however, these ELISAs showed 45% (9 of 20) and 60% (12 of 20) false-positive reactions with 20 NCC sera, respectively. The presence of nonspecific human IgG in HCF obtained from a CE patient prevented us from applying it to the ELISA. HCF of E. granulosus, obtained from laboratory mice with a secondary infection with hydatid cyst tissue homogenates, appears to be highly useful for the serodiagnosis of CE in humans and may be useful in domestic animals.     

Secondary Echinococcosis of Echinococcus granulosus

Ohne Zusammenfassung     

Cystic panfolliculoma

Panfolliculoma is a rare follicular neoplasm with differentiation toward both upper (infundibulum and isthmus) and lower (stem, hair matrix, and bulb) segments of a hair follicle. We present an unusual case of cystic panfolliculoma. A 33-year-old Hispanic woman presented with an 8-month history of a 3.0-cm cystic scalp mass. The lesion was excised, and the histologic sections showed a cystic follicular neoplasm that contained corneocytes in basket-woven and laminated array, trichohyalin granules of the inner root sheath, germinative cells, papillae, matrical cells, and "shadow" cells. Cytokeratin 903 and cytokeratin 5/6 immunostains uniformly highlight the tumor cells. Ber-EP4 strongly labels the germinative cells but not the follicular papillae. CD34 labels the surrounding fibrotic stroma and focally the epithelial component.