Echinococcus multilocularis

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Bruno Gottstein - One of the best experts on this subject based on the ideXlab platform.

  • Echinococcus multilocularis first european haplotype identified in the united states an emerging disease
    Clinical Infectious Diseases, 2020
    Co-Authors: Louis B Polish, Bruno Gottstein, Bobbi S Pritt, Thomas F E Barth, Elise M Oconnell, Pamela C Gibson
    Abstract:

    Background Echinococcus multilocularis is one of the most severe and lethal parasitic diseases of humans most often reported in Europe and Asia. Only one previous case has been documented in the contiguous United States from Minnesota in 1977. European haplotypes have been identified in carnivores and domestic dogs as well as recently in patients in Western and Central Canada. Methods We used immunohistochemical testing with the monoclonal antibody (Mab) Em2G11 and a species specific ELISA affinity purified antigen Em2 as well as COX1 gene sequencing. Results Using pathology, immunohistochemical staining, specific immunodiagnostic testing and COX1 gene sequencing we were able to definitively identify Echinococcus multilocularis as the causative agent of our patient's liver and lung lesions that clustered most closely with the European haplotype. Conclusion We have identified the first case of a European haplotype Echinococcus multilocularis in the United States and the first case of this parasite infection east of the Mississippi River. Given the identification of this haplotype in Canada this appears to be an emerging infectious disease in North America.

  • immunoregulation in larval Echinococcus multilocularis infection
    Parasite Immunology, 2016
    Co-Authors: Junhua Wang, Bruno Gottstein
    Abstract:

    Alveolar echinococcosis (AE) is a clinically very severe zoonotic helminthic disease, characterized by a chronic progressive hepatic damage caused by the continuous proliferation of the larval stage (metacestode) of Echinococcus multilocularis. The proliferative potential of the parasite metacestode tissue is dependent on the nature/function of the periparasitic immune-mediated processes of the host. Immune tolerance and/or down-regulation of immunity are a marked characteristic increasingly observed when disease develops towards its chronic (late) stage of infection. In this context, explorative studies have clearly shown that T regulatory (Treg) cells play an important role in modulating and orchestrating inflammatory/immune reactions in AE, yielding a largely Th2-biased response, and finally allowing thus long-term parasite survival, proliferation and maturation. AE is fatal if not treated appropriately, but the current benzimidazole chemotherapy is far from optimal, and novel options for control are needed. Future research should focus on the elucidation of the crucial immunological events that lead to anergy in AE, and focus on providing a scientific basis for the development of novel and more effective immunotherapeutical options to support cure AE by abrogating anergy, anticipating also that a combination of immuno- and chemotherapy could provide a synergistic therapeutical effect.

  • The brown hare (Lepus europaeus) as a novel intermediate host for Echinococcus multilocularis in Europe
    Parasitology research, 2015
    Co-Authors: Valérie Chaignat, Patrick Boujon, Caroline F. Frey, Brigitte Hentrich, Norbert Müller, Bruno Gottstein
    Abstract:

    A typical multivesiculated metacestode tissue has been found in the liver of a European brown hare (Lepus europaeus) originating from a northern area of Switzerland. In this study, the causative species was identified as Echinococcus multilocularis by appropriate histological and molecular analyses and corresponding DNA sequencing. This is the first confirmation of larval E. multilocularis from hares in central Europe. The metacestode tissue contained protoscolices, suggesting that the hare may contribute to the transmission of E. multilocularis in Switzerland.

  • hepatic alveolar hydatid disease Echinococcus multilocularis in a boxer dog from southern ontario
    Canadian Veterinary Journal-revue Veterinaire Canadienne, 2014
    Co-Authors: Alicia Skelding, Bruno Gottstein, Andrew Brooks, Margaret Stalker, Nicola J Mercer, Eileen De Villa, Andrew S Peregrine
    Abstract:

    A 2-year-old boxer dog from southern Ontario was evaluated because of acute onset lethargy. Exploratory laparotomy revealed a hemorrhagic, destructive, liver mass. Histology, immunohistochemistry, and polymerase chain reaction confirmed Echinococcus multilocularis as the cause of the hepatic mass. This constitutes the first description of endemic E. multilocularis in Ontario.

  • alveolar hydatid disease Echinococcus multilocularis in the liver of a canadian dog in british columbia a newly endemic region
    Canadian Veterinary Journal-revue Veterinaire Canadienne, 2012
    Co-Authors: Andrew S Peregrine, Emily J. Jenkins, Brian Barnes, Shannon Johnson, Lydden Polley, Ian K Barker, Bradley De Wolf, Bruno Gottstein
    Abstract:

    An adult dog that lived in central British Columbia was examined because of a history of lethargy and vomiting. Histology, immunohistochemistry, and polymerase chain reaction (PCR) examination of a hepatic mass confirmed the presence of an alveolar hydatid cyst, the first description of Echinococcus multilocularis in British Columbia. We provide recommendations for case management and remind practitioners in endemic areas of western Canada that dogs can serve as definitive and, rarely, intermediate hosts for E. multilocularis.

Peter Deplazes - One of the best experts on this subject based on the ideXlab platform.

  • Long-term (35 years) cryopreservation of Echinococcus multilocularis metacestodes.
    Parasitology, 2020
    Co-Authors: Teivi Laurimäe, Philipp A Kronenberg, Cristian A. Alvarez Rojas, Theodor W Ramp, Johannes Eckert, Peter Deplazes
    Abstract:

    The metacestode of Echinococcus multilocularis is the etiological agent of alveolar echinococcosis. The metacestode stage used for research is maintained in rodents by serial passages. In order to determine whether cryopreservation of E. multilocularis metacestodes would be suitable for long-term maintenance and replace serial passages, isolates of different geographic origin were cryopreserved in 1984–1986. The aim of the current study was to test the viability of cryopreserved isolates following long-term cryopreservation (up to 35 years) and to determine the phylogenetic clades these isolates belonged to. Cryopreserved isolates were tested for viability in vitro and in vivo in gerbils. In vitro results of 5 isolates indicated protoscolex survival in 13 of 17 experiments (76%) and metacestode survival in 5 of 12 (42%) in vivo experiments. In vivo results showed ‘abortive lesions’ in 13 of the 36 animals, 15 were negative and 8 harboured proliferating metacestode tissue containing protoscoleces. Genetic analysis confirmed the isolates belonged to European, Asian and North-American clades. In conclusion, the results of the current study indicate that metacestodes of E. multilocularis are able to survive long-term cryopreservation. Therefore, cryopreservation is a suitable method for long-term storage of E. multilocularis metacestode isolates and reduces the number of experimental animals.

  • Albendazole increases the inflammatory response and the amount of Em2-positive small particles of Echinococcus multilocularis (spems) in human hepatic alveolar echinococcosis lesions.
    Public Library of Science (PLoS), 2017
    Co-Authors: Franz J Ricken, Peter Deplazes, Beate Grüner, Juliane Nell, Julian Schmidberger, Tanja Kaltenbach, Wolfgang Kratzer, Andreas Hillenbrand, Doris Henne-bruns, Peter Moller
    Abstract:

    Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. The inflammatory response to this infection is influenced by the interaction of the parasite with the host. We aimed to analyze human liver lesions infected with Echinococcus multilocularis and the changes of the cellular infiltrates during albendazole (ABZ) treatment.We analyzed liver tissue samples from 8 untreated patients, 5 patients treated with two daily doses of 400 mg ABZ for up to two months and 7 patients treated for more than two months with the same ABZ therapy. A broad panel of monoclonal antibodies was used to characterize the lesion by immunohistochemistry. A change in the cellular infiltrate was observed between the different chemotherapy times. During the initial phases of treatment an increase in CD15+ granulocytes and CD68+ histocytes as well as in small particles of Echinococcus multilocularis (spems) was observed in the tissue surrounding the metacestode. Furthermore, we observed an increase in CD4+ T cells, CD20+ B cells and CD38+ plasma cells during a longer duration of treatment.ABZ treatment of AE leads to morphological changes characterized by an initial, predominantly acute, inflammatory response which is gradually replaced by a response of the adaptive immune system

  • human wildlife interactions and zoonotic transmission of Echinococcus multilocularis
    Trends in Parasitology, 2015
    Co-Authors: Daniel Hegglin, Fabio Bontadina, Peter Deplazes
    Abstract:

    The life cycle of the zoonotic cestode Echinococcus multilocularis depends on canids (mainly red foxes) as definitive hosts and on their specific predation on rodent species (intermediate hosts). Host densities and predation rates are key drivers for infection with parasite eggs. We demonstrate that they strongly depend on multi-faceted human–wildlife interactions: vaccination against rabies, elimination of top predators, and changing attitude towards wildlife (feeding) contribute to high fox densities. The absence of large canids, low hunting pressure, and positive attitudes towards foxes modify their anti-predator response (‘landscape of fear’), promoting their tameness, which in turn facilitates the colonization of residential areas and modifies parasite transmission. Such human factors should be considered in the assessment of any intervention and prevention strategy.

  • control of Echinococcus multilocularis strategies feasibility and cost benefit analyses
    International Journal for Parasitology, 2013
    Co-Authors: Daniel Hegglin, Peter Deplazes
    Abstract:

    Echinococcus multilocularis, the zoonotic agent of human alveolar echinococcosis, has considerably extended its range and became more prevalent in many parts of the endemic areas. Accordingly, there is an increasing demand for measures to prevent human infections. Rising public awareness of this zoonosis and individual protective actions should be part of every prevention program. Considering the high reproduction of E. multilocularis in domestic dogs which live in close contact to humans, a monthly deworming scheme for domestic dogs with access to rodents is likely to be of high importance. This holds true if only low prevalences in domestic dogs are recorded, as high densities of these pets can easily outweigh low infections rates. Thus, in central Europe their estimated contribution to environmental contamination with E. multilocularis eggs ranges between 4% and 19%. The estimated contribution of domestic cats is insignificant (<0.3%) due to low parasite reproduction in this species. Control of the parasite by reducing its main wildlife hosts (foxes, vole species) is barely achievable on a larger scale and is generally not well accepted due to ecological considerations and animal welfare concerns. In general, the frequency of the parasite sharply decreases when anthelmintic baits are regularly distributed to foxes. However, eradication of the parasite is unlikely and long-term baiting campaigns are actually the most effective tool to significantly lower the infection pressure with parasite eggs. Regarding the long latency of 5–15 years of alveolar echinococcosis, however, such measures can only be cost effective if they are pursued for several decades and concentrate on restricted areas which are most relevant for the transmission of alveolar echinococcosis such as highly endemic areas in densely populated zones. Thus, the implementation of this approach strongly depends on factors such as public attitude, available financial resources and priority setting of political decision-makers.

  • age season and spatio temporal factors affecting the prevalence of Echinococcus multilocularis and taenia taeniaeformis in arvicola terrestris
    Parasites & Vectors, 2011
    Co-Authors: Pierre Burlet, Peter Deplazes, Daniel Hegglin
    Abstract:

    Background Taenia taeniaeformis and the related zoonotic cestode Echinococcus multilocularis both infect the water vole Arvicola terrestris. We investigated the effect of age, spatio-temporal and season-related factors on the prevalence of these parasites in their shared intermediate host. The absolute age of the voles was calculated based on their eye lens weights, and we included the mean day temperature and mean precipitation experienced by each individual as independent factors.

Klaus Brehm - One of the best experts on this subject based on the ideXlab platform.

  • the unique stem cell system of the immortal larva of the human parasite Echinococcus multilocularis
    Evodevo, 2014
    Co-Authors: Theresa Rauschendorfer, Uriel Koziol, Luis Zanon Rodriguez, Georg Krohne, Klaus Brehm
    Abstract:

    Background It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis, the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal.

  • emtip a t cell immunomodulatory protein secreted by the tapeworm Echinococcus multilocularis is important for early metacestode development
    PLOS Neglected Tropical Diseases, 2014
    Co-Authors: Justin Komguep Nono, Manfred B Lutz, Klaus Brehm
    Abstract:

    Background Alveolar echinococcosis (AE), caused by the metacestode of the tapeworm Echinococcus multilocularis, is a lethal zoonosis associated with host immunomodulation. T helper cells are instrumental to control the disease in the host. Whereas Th1 cells can restrict parasite proliferation, Th2 immune responses are associated with parasite proliferation. Although the early phase of host colonization by E. multilocularis is dominated by a potentially parasitocidal Th1 immune response, the molecular basis of this response is unknown.

  • Echinococcus multilocularis as an experimental model in stem cell research and molecular host parasite interaction
    Parasitology, 2010
    Co-Authors: Klaus Brehm
    Abstract:

    Totipotent somatic stem cells (neoblasts) are key players in the biology of flatworms and account for their amazing regenerative capability and developmental plasticity. During recent years, considerable progress has been made in elucidating molecular features of neoblasts from free-living flatworms, whereas their role in parasitic species has so far merely been addressed by descriptive studies. Very recently, however, significant advances have been made in the in vitro culture of neoblasts from the cestode Echinococcus multilocularis. The isolated cells proved capable of generating mature metacestode vesicles under laboratory conditions in a manner that closely resembles the oncosphere-metacestode transition during natural infections. Using the established neoblast cultivation protocols, combined with targeted manipulation of Echinococcus genes by RNA-interference, several fundamental questions of host-dependent parasite development can now be addressed. Here, I give an overview of current cultivation techniques for E. multilocularis neoblasts and present experimental approaches to study their function. Furthermore, I introduce the E. multilocularis genome sequencing project that is presently in an advanced stage. The combined input of data from the E. multilocularis sequencing project, stem cell cultivation, and recently initiated attempts to genetically manipulate Echinococcus will provide an ideal platform for hypothesis-driven research into cestode development in the next years.

  • long term in vitro cultivation of Echinococcus multilocularis metacestodes under axenic conditions
    Parasitology Research, 2004
    Co-Authors: Markus Spiliotis, Dennis Tappe, Lukas Sesterhenn, Klaus Brehm
    Abstract:

    We report here on the development of an in vitro system for the long-term cultivation of Echinococcus multilocularis larvae under axenic conditions. In the absence of feeder cells from the host, long-term survival of the parasite depended strictly on low oxygen conditions and the presence of reducing agents in the medium. Host serum supported survival of the parasite but the growth of metacestode vesicles and differentiation towards the protoscolex stage only occurred in the presence of culture medium that was preconditioned by hepatoma cells or several other immortal cell lines. On the basis of this in vitro system, future analyses on the identification of host-derived growth factors for E. multilocularis will be greatly facilitated.

Akira Ito - One of the best experts on this subject based on the ideXlab platform.

  • Echinococcus multilocularis identification and functional characterization of cathepsin b like peptidases from metacestode
    Experimental Parasitology, 2011
    Co-Authors: Yasuhito Sako, Kazuhiro Nakaya, Akira Ito
    Abstract:

    Cysteine peptidases have potent activities in the pathogenesis of various parasitic infections, and are considered as targets for chemotherapy and antigens for vaccine. In this study, two cathepsin B-like cysteine peptidases (EmCBP1 and EmCBP2) from Echinococcus multilocularis metacestodes were identified and characterized. Immunoblot analyses demonstrated that EmCBP1 and EmCBP2 were present in excretory/secretory products and extracts of E. multilocularis metacestodes. By immunohistochemistry, EmCBP1 and EmCBP2 were shown to localize to the germinal layer, the brood capsule and the protoscolex. Recombinant EmCBP1 and EmCBP2 expressed in Pichia pastoris, at optimum pH 5.5, exhibited substrate preferences for Z-Phe-Arg-MCA, Z-Val-Val-Arg-MCA, and Z-Leu-Arg-MCA, and low levels of hydrolysis of Z-Arg-Arg-MCA. Furthermore, recombinant enzymes degraded IgG, albumin, type I and IV collagens, and fibronectin. These results suggested that EmCBP1 and EmCBP2 may play key roles in protein digestion for parasites' nutrition and in parasite-host interactions.

  • geographic pattern of genetic variation in the fox tapeworm Echinococcus multilocularis
    Parasitology International, 2009
    Co-Authors: Minoru Nakao, Yasuhito Sako, Ning Xiao, Munehiro Okamoto, Tetsuya Yanagida, Akira Ito
    Abstract:

    Intraspecific genetic variation of Echinococcus multilocularis, the etiologic agent of human alveolar echinococcosis, has been evaluated among 76 geographic isolates from Europe, Asia and North America by using sequence data of mitochondrial and nuclear DNA. Relatively low genetic variation was found only in the mitochondrial DNA sequence consisting of 3 protein-coding genes. Pairwise divergence among the resultant 18 haplotypes ranged from 0.03 to 1.91%. Phylogenetic trees and parsimony network of these haplotypes depicted a geographic division into European, Asian and North American clades, but 1 haplotype from Inner Mongolia was unrelated to other haplotypes. The coexistence of the Asian and North American haplotypes could be seen, particularly on the St. Lawrence Island in the Bering Sea. These data suggest an evolutionary scenario in which distinct parasite populations derived from glacial refugia have been maintained by indigenous host mammals. The nuclear DNA sequence for the immunodominant B cell epitope region of ezrin/radixin/moesin-like protein (elp) was extremely conservative, indicating that the elp antigen is available for immunodiagnosis in any endemic areas.

  • isolation of polymorphic microsatellite loci from the tapeworm Echinococcus multilocularis
    Infection Genetics and Evolution, 2003
    Co-Authors: Minoru Nakao, Yasuhito Sako, Akira Ito
    Abstract:

    Two microsatellites were isolated from a genomic library of Echinococcus multilocularis. The microsatellites, designated EMms1 and EMms2, consist of tandem repeats of CAC-trinucleotide unit. Southern blot hybridization suggests that each of them is a single locus. Using fox-derived wild tapeworms (N=104), PCR-amplification of microsatellites was performed to assess the usefulness of these loci. We found four alleles of EMms1 and two alleles of EMms2. The heterozygosities observed were 10.6% in EMms1 and 7.7% in EMms2. The result suggests that both selfing and outcrossing occur in the adult stage of E. multilocularis.

  • the complete mitochondrial dna sequence of the cestode Echinococcus multilocularis cyclophyllidea taeniidae
    Mitochondrion, 2002
    Co-Authors: Minoru Nakao, Yasuhito Sako, Noriko Yokoyama, Masahito Fukunaga, Akira Ito
    Abstract:

    Abstract The 13,738 bp mitochondrial DNA from the cestode Echinococcus multilocularis has been sequenced. It contains two major noncoding regions and 36 genes (12 for proteins involved in oxidative phosphorylation, two for rRNAs and 22 for tRNAs) but a gene for ATPase subunit 8 is missing. All genes are transcribed in the same direction. Putative secondary structures of tRNAs indicate that most of them are conventional cloverleaves but the dihydrouridine arm is unpaired in tRNASer(AGN), tRNASer(UCN), tRNAArg and tRNACys. The base composition at the wobble positions of fourfold degenerate codon families is highly biased toward U and against C.

  • comparison of the antigenicity of protoscoleces and microvesicles of Echinococcus multilocularis prepared from rats
    Journal of Helminthology, 2001
    Co-Authors: Akira Ito, Minoru Nakao, T Kanazawa, Yasuhito Sako, Yuji Ishikawa, Kazuhiro Nakaya
    Abstract:

    Rats are known to be relatively resistant to infection with Echinococcus multilocularis. However, when rats are inoculated with the parasite tissues, E. multilocularis proliferates slowly at first but after 6 months the cysts increase in size considerably and contain large numbers of protoscoleces. As rats survive for 18 months or longer, approximately 100 ml of packed protoscoleces can be produced from each rat. A comparison of the antigenicity of the protoscoleces and microvesicles by immunoblot methods showed that both Em18 and Em16 are shared components between both protoscoleces and microvesicles, although the latter have some additional antigenic components. In antigens prepared from protoscoleces, the banding patterns around Em18 were much simpler than those from microvesicles. Therefore, for serodiagnosis of E. multilocularis, antigens should be carefully prepared from protoscoleces rather than microvesicles from the rat.

Andrew S Peregrine - One of the best experts on this subject based on the ideXlab platform.

  • Echinococcus multilocularis infection southern ontario canada
    Emerging Infectious Diseases, 2019
    Co-Authors: Jonathon D Kotwa, Nicola J Mercer, Olaf Berke, Mats Isaksson, Claire M Jardine, Douglas G Campbell, David L Pearl, Eva Ostermanlind, Andrew S Peregrine
    Abstract:

    Alveolar echinococcosis, the disease caused by infection with the intermediate stage of the Echinococcus multilocularis tapeworm, is typically fatal in humans and dogs when left untreated. Since 2012, alveolar echinococcosis has been diagnosed in 5 dogs, 3 lemurs, and 1 chipmunk in southern Ontario, Canada, a region previously considered free of these tapeworms. Because of human and animal health concerns, we estimated prevalence of infection in wild canids across southern Ontario. During 2015-2017, we collected fecal samples from 460 wild canids (416 coyotes, 44 foxes) during postmortem examination and analyzed them by using a semiautomated magnetic capture probe DNA extraction and real-time PCR method for E. multilocularis DNA. Surprisingly, 23% (95% CI 20%-27%) of samples tested positive. By using a spatial scan test, we identified an infection cluster (relative risk 2.26; p = 0.002) in the western-central region of the province. The cluster encompasses areas of dense human population, suggesting zoonotic transmission.

  • Echinococcus multilocularis in a wild free living eastern chipmunk tamias striatus in southern ontario a case report and subsequent field study of wild small mammals
    Veterinary Parasitology: Regional Studies and Reports, 2018
    Co-Authors: Shannon K French, Andrew S Peregrine, Jonathon D Kotwa, Douglas G Campbell, Sarah Jajou, Hugh Y Cai, Claire M Jardine
    Abstract:

    Southern Ontario has recently been identified as a risk area for Echinococcus multilocularis, based on surveys of foxes (Vulpes vulpes) and coyotes (Canis latrans) which act as definitive hosts of the parasite. In this manuscript, we describe the first detection of E. multilocularis in an eastern chipmunk (Tamias striatus) in North America. This case, submitted to the Canadian Wildlife Health Cooperative (CWHC) in August 2016 as part of ongoing wildlife disease surveillance activities, represents the first report of alveolar echinococcosis in a wild, free living, intermediate host from southern Ontario, providing further evidence of an established sylvatic cycle of E. multilocularis in this region. The finding prompted a field investigation to identify additional cases of alveolar echinococcosis in small mammals in the summer of 2017. Echinococcus multilocularis was not detected in any of the 196 small mammals submitted to the CWHC from across southern Ontario or in any of the 43 small mammals trapped in the area where the infected chipmunk was found. However, given the suspected low prevalence and patchy distribution of E. multilocularis in small mammals, our negative results do not preclude the established presence of the parasite. This case emphasizes the importance of passive surveillance networks for monitoring new and emerging diseases in wildlife populations.

  • hepatic alveolar hydatid disease Echinococcus multilocularis in a boxer dog from southern ontario
    Canadian Veterinary Journal-revue Veterinaire Canadienne, 2014
    Co-Authors: Alicia Skelding, Bruno Gottstein, Andrew Brooks, Margaret Stalker, Nicola J Mercer, Eileen De Villa, Andrew S Peregrine
    Abstract:

    A 2-year-old boxer dog from southern Ontario was evaluated because of acute onset lethargy. Exploratory laparotomy revealed a hemorrhagic, destructive, liver mass. Histology, immunohistochemistry, and polymerase chain reaction confirmed Echinococcus multilocularis as the cause of the hepatic mass. This constitutes the first description of endemic E. multilocularis in Ontario.

  • alveolar hydatid disease Echinococcus multilocularis in the liver of a canadian dog in british columbia a newly endemic region
    Canadian Veterinary Journal-revue Veterinaire Canadienne, 2012
    Co-Authors: Andrew S Peregrine, Emily J. Jenkins, Brian Barnes, Shannon Johnson, Lydden Polley, Ian K Barker, Bradley De Wolf, Bruno Gottstein
    Abstract:

    An adult dog that lived in central British Columbia was examined because of a history of lethargy and vomiting. Histology, immunohistochemistry, and polymerase chain reaction (PCR) examination of a hepatic mass confirmed the presence of an alveolar hydatid cyst, the first description of Echinococcus multilocularis in British Columbia. We provide recommendations for case management and remind practitioners in endemic areas of western Canada that dogs can serve as definitive and, rarely, intermediate hosts for E. multilocularis.