scholarly journals Targeting the Laminated Layer of Echinococcus multilocularis as a Potential Therapeutic Strategy

Pharmacology ◽  
2021 ◽  
Vol 106 (1-2) ◽  
pp. 1-2
Author(s):  
Richard D. Cummings ◽  
Stephan von Gunten
2002 ◽  
Vol 88 (9) ◽  
pp. 822-828 ◽  
Author(s):  
Bruno Gottstein ◽  
Wen Dai ◽  
Mirjam Walker ◽  
Marianne Stettler ◽  
Norbert Müller ◽  
...  

1998 ◽  
Vol 72 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Y. Sato ◽  
M. Nakao ◽  
K. Nakaya ◽  
A. Ito

AbstractExperimental infection of larval Echinococcus multilocularis in the rodent brain was attempted to establish a murine model for cerebral alveolar echinococcosis. Balb/c mice and jirds were injected intracranially with 10% of a homogenated hydatid cyst mass. Small cystic larvae were observed macroscopically in the cranial cavity 1, 2 and 5 months post-infection in both mice and jirds. Some larval cysts from both rodents contained mature or immature protoscoleces. In mice, the laminated layer was found in the lateral ventricle 2 months post-infection but without protoscoleces. At five months post-infection, larger larval cysts were found in the cranial cavity of a mouse, which also demonstrated partial palsy of the legs. A laminated layer with mature protoscoleces was observed in the third ventricle and the mouse also harboured, in the left lung, a larval cyst containing protoscoleces surrounded by lymphocytes. Jirds were also found to be infected with metacestodes in the cranial cavity, but neither unusual behaviour nor establishment of cysts inside the brain was observed in jirds during the course of infection.


2021 ◽  
Vol 15 (2) ◽  
pp. e0009155 ◽  
Author(s):  
Johannes Grimm ◽  
Julian Krickl ◽  
Annika Beck ◽  
Juliane Nell ◽  
Monika Bergmann ◽  
...  

Background Alveolar echinococcosis (AE) is caused by metacestode larva of the tapeworm Echinococcus multilocularis. AE diagnostics currently rely on imaging techniques supported by serology, but unequivocal detection of AE is difficult. Although polymerase chain reaction (PCR)-based methods to detect tapeworm DNA in biopsies have been suggested for several species, no validated protocol adhering to accepted guidelines has so far been presented for AE diagnostics. We herein established a PCR protocol for metacestode biopsies and technically evaluated the method using isolated parasite DNA and cells, biopsies of clinically relevant material, and formalin fixed paraffin-embedded (FFPE) human tissue blocks. We compared the results with an immunochemical (IHC) approach using the monoclonal antibody Em2G11 specific for the antigen Em2 of E. mulitlocularis. Methodology/Principal findings Based on tapeworm 12S rDNA sequences we established and validated a PCR protocol for robust detection of as little as 50 parasite cells per specimen and report 127 cases of positive identification of Echinococcus species in samples from humans and animals. For further validation, we analyzed 45 liver, heart, brain, and soft tissue samples as well as cytological probes of aspirates of FFPE-material from 18 patients with clinically confirmed AE. Of each patient we analyzed (i) fully viable lesions with laminated layer; (ii) tissue with mAbEm2G11-positive small particles of E. multilocularis (spems); (iii) mAbEm2G11-negative tissue adjacent to the main lesion; and (iv) lymph node tissue with mAbEm2G11-positive spems. To identify the areas for the PCR-based approach, we performed IHC-staining with the monoclonal antibody Em2G11. Micro-dissected tissue of these areas was then used for PCR-analysis. 9 of 15 analyzed samples with viable E. multilocularis lesions with laminated layer were positive by PCR. Of this group, all samples preserved for less than 6 years (6/6) were tested positive. 11 of 15 samples of spems and 7 of 9 samples of the control group mAbEm2G11-negative tissue were negative by PCR. We further show that all probes from lymph nodes with spems are PCR negative. Conclusions/Significance We present a sensitive PCR method for the detection of E. multilocularis in human tissue, particularly in fresh biopsy material and tissue blocks stored for less than 5 years. While the diagnostic sensitivity of material containing only spems was higher using IHC, PCR detection was possible in IHC negative liver tissue and in patients with negative serology. Our results support the view that spems do not contain parasitic DNA or viable cells of the parasite. spems thus most probably do not directly contribute to metastasis formation during AE.


Parasitology ◽  
1998 ◽  
Vol 116 (5) ◽  
pp. 463-469 ◽  
Author(s):  
J. MATSUMOTO ◽  
K. YAGI ◽  
N. NONAKA ◽  
Y. OKU ◽  
M. KAMIYA

The kinetics of serum antibody response against infection with Echinococcus multilocularis eggs was evaluated in AKR mice. The animals were infected by oral inoculation with 300 parasite eggs, and necropsied at 1, 2, 4, 6, 9, 12 and 16 weeks post-infection (p.i.), respectively. The parasite formed the laminated layer at 4 weeks p.i., the brood capsule with a massive proliferation of germinal cells at 9 weeks p.i. and protoscoleces at 16 weeks p.i. Serum antibody responses of the mice to antigen preparations from metacestodes of different stages and protoscoleces were evaluated by ELISA, immunoblotting and immunohistochemistry. In ELISA, the antibody responses began to increase at 4 weeks and became more apparent at 9 weeks p.i. and thereafter. Immunoblots using sera collected at 16 weeks p.i. showed some common bands among the 3 different antigen preparations. In addition to this, the germinal cells and brood capsules of mature metacestodes were stained strongly in an immunohistochemical study. From above, it is suggested that some antigen molecules are expressed in the parasite through these stages and stimulated host antibody responses.


Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 634 ◽  
Author(s):  
Johannes Grimm ◽  
Annika Beck ◽  
Juliane Nell ◽  
Julian Schmidberger ◽  
Andreas Hillenbrand ◽  
...  

Alveolar echinococcosis (AE) is caused by the intermediate stage of Echinococcus multilocularis. We aimed to correlate computed tomography (CT) data with histology to identify distinct characteristics for different lesion types. We classified 45 samples into five types with the Echinococcus multilocularis Ulm Classification for Computed Tomography (EMUC-CT). The various CT lesions exhibited significantly different histological parameters, which led us to propose a progression model. The initial lesion fit the CT type IV classification, which comprises a single necrotic area with the central located laminated layer, a larger distance between laminated layer and border zone, a small fibrotic peripheral zone, and few small particles of Echinococcus multilocularis (spems). Lesions could progress through CT types I, II, and III, characterized by shorter distances between laminated layer and border zone, more spems inside and surrounding the lesion, and a pronounced fibrotic rim (mostly in type III). Alternatively, lesions could converge to a highly calcified, regressive state (type V). Our results suggest that the CT types mark sequential stages of the infection, which progress over time. These distinct histological patterns advance the understanding of interactions between AE and human host; moreover, they might become prognostically and therapeutically relevant.


2004 ◽  
Vol 72 (1) ◽  
pp. 527-536 ◽  
Author(s):  
Mirjam Walker ◽  
Adriana Baz ◽  
Sylvia Dematteis ◽  
Marianne Stettler ◽  
Bruno Gottstein ◽  
...  

ABSTRACT Echinococcus multilocularis metacestodes are fluid-filled, vesicle-like organisms, which are characterized by continuous asexual proliferation via external budding of daughter vesicles, predominantly in the livers of infected individuals. Tumor-like growth eventually leads to the disease alveolar echinococcosis (AE). We employed the monoclonal antibody (MAb) E492/G1, previously shown to be directed against a carbohydrate-rich, immunomodulatory fraction of Echinococcus granulosus, to characterize potentially related components in E. multilocularis. Immunofluorescence studies demonstrated that MAb E492/G1-reactive epitopes were found predominantly on the laminated layer and in the periphery of developing brood capsules. The respective molecules were continuously released into the exterior medium and were also found in the parasite vesicle fluid. The MAb E492/G1-reactive fraction in E. multilocularis, named Em492 antigen, was isolated by immunoaffinity chromatography. Em492 antigen had a protein/carbohydrate ratio of 0.25, reacted with a series of lectins, and is related to the laminated layer-associated Em2(G11) antigen. The epitope recognized by MAb E492/G1 was sensitive to sodium periodate but was not affected by protease treatment. Anti-Em492 immunoglobulin G1 (IgG1) and IgG2 and, at lower levels, IgG3 were found in sera of mice suffering from experimentally induced secondary, but not primary, AE. However, with regard to cellular immunity, a suppressive effect on concanavalin A- or crude parasite extract-induced splenocyte proliferation in these mice was observed upon addition of Em492 antigen, but trypan blue exclusion tests and transmission electron microscopy failed to reveal any cytotoxic effect in Em492 antigen-treated spleen cells. This indicated that Em492 antigen could be modulating the periparasitic cellular environment during E. multilocularis infection through as yet unidentified mechanisms and could be one of the factors contributing to immunosuppressive events that occur at the host-parasite interface.


2006 ◽  
Vol 43 (2) ◽  
pp. 76-80 ◽  
Author(s):  
M. Miterpáková ◽  
D. Antolová ◽  
Z. Ševčíková ◽  
M. Stanko ◽  
A. Dinkel ◽  
...  

AbstractInfection with the larval stage of Echinococcus multilocularis was diagnosed in musk rat (Ondatra zibethicus) in the Slovak Republic. At necropsy, massively enlarged liver with numbers of abscess-like lesions up to 1.5 cm in diameter was found. Histological examination shoved the presence of typical multivesicular cysts with multiple protoscoleces and typical laminated layer. Polymerase chain reaction confirmed the diagnosis. According to our knowledge, this is the first documentation of Echinococcus multilocularis in naturally infected rodent in territory of the Slovak Republic.


Nitric Oxide ◽  
2004 ◽  
Vol 10 (3) ◽  
pp. 150-155 ◽  
Author(s):  
M.Amparo Andrade ◽  
Mar Siles-Lucas ◽  
Elsa Espinoza ◽  
José Luis Pérez Arellano ◽  
Bruno Gottstein ◽  
...  

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