Special Issue "Alveolar Echinococcosis: Joining Hands to Tackle a Lethal Parasitosis"

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 15 January 2022.

Special Issue Editors

Dr. Beate Grüner
E-Mail Website
Guest Editor
Head of Division of Clinical Infectious Diseases, Department of Internal Medicine III, University Hospital Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Interests: clinical infectious diseases; infections of the immunocompromized host; HIV; parasitic diseases; alveolar and cystic echinococcosis; tuberculosis
Dr. Thomas Romig
E-Mail Website
Co-Guest Editor
Parasitology Unit 190p, Emil-Wolff-Str. 34, University of Hohenheim, 70599 Stuttgart, Germany
Interests: epidemiology of cestodes; alveolar and cystic echinococcosis; taeniosis; cysticercosis; wildlife parasitology

Special Issue Information

Dear Colleagues,

Human alveolar echinococcosis (AE) remains a challenge for clinicians and public health systems in affected countries. Experimental, epidemiological, and clinical research has given us some insight into one of the world’s most lethal parasitoses, yet we still are far from fully understanding this disease.

Therefore, we would like to invite you, as experts in this field, to add a piece to the puzzle and share your research results on Echinococcus multilocularis. Compiling and integrating our research will improve our ability to prevent, diagnose, and treat AE und hopefully reduce the burden of disease.

This Special Edition of Pathogens aims to share research with clinical implications from all AE-affected countries. More precisely, the focus lies on the following research questions:

  1. AE or not? How to make first diagnosis of AE easier.
    • What are simple and reliable biomarkers to identify AE?
    • How can new imaging techniques help to establish the diagnosis?
    • When is a biopsy required and how can the examination be conducted?
    • Histology, Immunohistology or Nucleic acid detection—quo vadis?
  1. Diagnosis prompts treatment—or not? How to strike the right balance between action and cautious restraint.
    • How can we separate active from inactive disease?
    • How can we evaluate treatment response?
    • Is the PNM classification a reliable prognostic tool?
    • When is it appropriate to delay or pause treatment?
  1. Therapy in AE: crossroads, dead-end or roadworks? How to choose a treatment option and overcome current limitations.
    • If benzimidazoles fail, what treatment options are left?
    • How does treatment differ in vulnerable groups, e.g., the immunocompromised?
    • When is conservative treatment and when is surgery the best choice?
    • What are the strengths and limitations of different surgical and interventional techniques?
    • How can resection margin and perioperative treatment with benzimidazoles affect the long-term outcome?
    • Liver transplantation as ultima ratio—quo vadis?
  1. From bench to bedside: How clinicians learn from basic research.
    • How does the host’s immune system control AE?
    • Which host factors contribute to a stable disease and which do not?
    • Is there a difference in the pathogenicity/infectivity of different genetic variants?
    • What are underlying mechanisms of benzimidazole intolerance or suspected resistance?
  1. Looking at the greater picture: How can we reduce the burden of disease?
    • Understanding the One Health dynamics of AE: what are risk factors for transmission?
    • What is the geographical distribution and relative frequency of different genotypes? Are there differences in host predilection?
    • Mass screening, baiting or hygiene promotion—what are successful and cost-effective public health strategies?

Dr. Beate Grüner
Guest Editor
Dr. Thomas Romig
Co-Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • Echinococcus multilocularis
  • human alveolar echinococcosis
  • AE
  • diagnosis
  • treatment and clinical management of AE
  • immunology
  • genotypes
  • epidemiology
  • public health

Published Papers (2 papers)

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Article
Maca against Echinococcosis?—A Reverse Approach from Patient to In Vitro Testing
Pathogens 2021, 10(10), 1335; https://doi.org/10.3390/pathogens10101335 - 15 Oct 2021
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Abstract
Drug-based treatment of alveolar echinococcosis (AE) with benzimidazoles is in most cases non-curative, thus has to be taken lifelong. Here, we report on a 56-year-old male AE patient who received standard benzimidazole treatment and biliary plastic stents, and additionally self-medicated himself with the [...] Read more.
Drug-based treatment of alveolar echinococcosis (AE) with benzimidazoles is in most cases non-curative, thus has to be taken lifelong. Here, we report on a 56-year-old male AE patient who received standard benzimidazole treatment and biliary plastic stents, and additionally self-medicated himself with the Peruvian plant extract Maca (Lepidium meyenii). After 42 months, viable parasite tissue had disappeared. Based on this striking observation, the anti-echinococcal activity of Maca was investigated in vitro and in mice experimentally infected with Echinococcus multilocularis metacestodes. Albendazole (ABZ)-treated mice and mice treated with an ABZ+Maca combination exhibited a significantly reduced parasite burden compared to untreated or Maca-treated mice. As shown by a newly established UHPLC-MS/MS-based measurement of ABZ-metabolites, the presence of Maca during the treatment did not alter ABZ plasma levels. In vitro assays corroborated these findings, as exposure to Maca had no notable effect on E. multilocularis metacestodes, and in cultures of germinal layer cells, possibly unspecific, cytotoxic effects of Maca were observed. However, in the combined treatments, Maca inhibited the activity of ABZ in vitro. While Maca had no direct anti-parasitic activity, it induced in vitro proliferation of murine spleen cells, suggesting that immunomodulatory properties could have contributed to the curative effect seen in the patient. Full article
(This article belongs to the Special Issue Alveolar Echinococcosis: Joining Hands to Tackle a Lethal Parasitosis)
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Morphological Characteristics of Alveolar and Cystic Echinococcosis Lesions in Human Liver and Bone
Pathogens 2021, 10(10), 1326; https://doi.org/10.3390/pathogens10101326 - 14 Oct 2021
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Abstract
Among echinococcoses diseases of human interest, two have a global public health impact: cystic and alveolar echinococcosis caused by Echinococcus granulosus sensu lato and Echinococcus multilocularis, respectively. Cystic and alveolar echinococcosis are neglected infectious diseases epidemiologically and are clinically vastly different with [...] Read more.
Among echinococcoses diseases of human interest, two have a global public health impact: cystic and alveolar echinococcosis caused by Echinococcus granulosus sensu lato and Echinococcus multilocularis, respectively. Cystic and alveolar echinococcosis are neglected infectious diseases epidemiologically and are clinically vastly different with distinct microscopic features. Because of the rareness of these zoonotic diseases, pathologists have limited diagnostic experience in the analysis of the lesions caused by Echinococcus tapeworms. Here, we describe the main microscopic features to be considered to characterize these lesions: laminated layer, central necrosis, growth pattern, and delineation from adjacent tissue. Moreover, immunohistology using monoclonal antibodies is of great diagnostic help in reaching a definitive diagnosis by identifying the laminated body and small particles of E. multilocularis (spems) and small particles of E. granulosus (spegs). Full article
(This article belongs to the Special Issue Alveolar Echinococcosis: Joining Hands to Tackle a Lethal Parasitosis)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Maca against echinococcosis? - A reverse approach from patient to in vitro testing
Authors: Tanja Karpstein1$, Sheena Chaudhry1$, Solange Bresson-Hadni2,3, Michael Hayoz4, Ghalia Boubaker1, Andrew Hemphill1, Reto Rufener1, Isabelle Schindler4, Yolanda Aebi4, Carlo Largiadèr4, Britta Lundströ
Affiliation: 1 Institute of Parasitology, Department of Infectious Diseases and Pathobiology (DIP), Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland 2 French National Reference Center for Echinococcosis, Besançon University Hospital, University Bourgogne Franche-Comté, 25000 Besançon, France. 3 Hepato-Gastroenterology and Tropical Medicine Units, University Hospital, 1205 Geneva, Switzerland. 4 Clinical Metabolomics Facility, Center of Laboratory Medicine, Bern University Hospital (Inselspital), 3010 Bern, Switzerland
Abstract: Echinococcus multilocularis causes the severe disease alveolar echinococcosis (AE) in humans and other mammals by proliferative growth of metacestodes (larval stage), mostly in livers of affected patients. Chemotherapy-based treatment with benzimidazoles is non-curative, thus has to be taken lifelong, and if treatment is discontinued due to intolerance, no alternative option is available for AE patients. We here report on a 56-year-old, male AE patient who received standard benzimidazole-treatment and a biliary plastic stent, and in addition self-medicated himself with the Peruvian plant extract Maca (Lepidium meyenii). Unexpectedly, the AE lesion completely disappeared in the patient. Based on this striking observation, the potential activity of Maca against AE was investigated in an AE mouse model and in vitro against E. multilocularis metacestodes. Secondary E. multilocularis-infected mice showed a significantly reduced parasite growth when treated with the standard benzimidazole treatment (200 mg/kg ABZ) or when treated with a combination of ABZ and Maca, but not when treated with Maca alone (33 mg/kg). Maca treatment did not have any effect on ABZ plasma levels in treated mice, as was assessed in a newly established UHPLC-MS/MS-based method for measurement of ABZ-metabolites in small plasma volumes. In vitro Maca (50 µg/ml) was tested alone and in combination with ABZ (10.6 µg/ml) against E. multilocularis metacestodes by the damage-marker PGI-assay, the alamar metacestode viability assay, the germinal layer cell viability assay, and transmission electron microscopy. In all tests, ABZ induced the expected damage of metacestodes within 12 days of treatment, whereas Maca did not. On isolated germinal layer cells, however, Maca had a direct, possibly unspecific, cytotoxic effect. Highly interestingly, Maca even slightly inhibited the activity of ABZ in vitro. Thus, no direct anti-parasitic activity of Maca could be proven in vitro or in an AE mouse model. Indirect effects through which Maca might have been active against AE in the presented patient could be of immunomodulatory nature. For this reason, we also tested the effect of Maca on splenocyte proliferation and could show that indeed it induced proliferation of these cells.

Title: Alveolar Echinococcosis – an old enemy who keeps presenting in new garment.
Authors: Jens Strohaeker 1*, Mihaly Sulyok 2, Falko Fend 2, Alfred Koenigsrainer 1 and Silvio Nadalin 1
Affiliation: 1 Department of General, Visceral and Transplantation Surgery, University Hospital of Tuebingen, Tuebingen, Germany 2 Department of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany.

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