Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.

Echinococcoses require the involvement of specialists from nearly all disciplines; standardization of the terminology used in the field is thus crucial. To harmonize echinococcosis terminology on sound scientific and linguistic grounds, the World Association of Echinococcosis launched a Formal Consensus process. Under the coordination of a Steering and Writing Group (SWG), a Consultation and Rating Group (CRG) had the main missions of (1) providing input on the list of terms drafted by the SWG, taking into account the available literature and the participants’ experience; and (2) providing independent rating on all debated terms submitted to vote. The mission of the Reading and Review Group (RRG) was to give an opinion about the recommendation paper in terms of readability, acceptability and applicability. The main achievements of this process were: (1) an update of the current nomenclature of Echinococcus spp.; (2) an agreement on three names of diseases due to Echinococcus spp.: Cystic Echinococcosis (CE), Alveolar Echinococcosis (AE) and Neotropical Echinococcosis (NE), and the exclusion of all other names; (3) an agreement on the restricted use of the adjective “hydatid” to refer to the cyst and fluid due to E. granulosus sensu lato; and (4) an agreement on a standardized description of the surgical operations for CE, according to the “Approach, cyst Opening, Resection, and Completeness” (AORC) framework. In addition, 95 “approved” and 60 “rejected” terms were listed. The recommendations provided in this paper will be applicable to scientific publications in English and communication with professionals. They will be used for translation into other languages spoken in endemic countries.

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.

Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC) are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E.multilocularis, by excretory/secretory (E/S)-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. We established cultivation systems for exposing DC to live material from early (oncosphere), chronic (metacestode) and late (protoscolex) infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naïve T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The induction of CD4+CD25+Foxp3+ T cells through metacestode E/S-products suggests that these cells fulfill an important role for parasite persistence during chronic echinococcosis. Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host.

Alveolar and cystic echinococcosis, caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively, are life-threatening diseases and very difficult to treat. The introduction of benzimidazole-based chemotherapy, which targets parasite β-tubulin, has significantly improved the life-span and prognosis of echinococcosis patients. However, benzimidazoles show only parasitostatic activity, are associated with serious adverse side effects and have to be administered for very long time periods, underlining the need for new drugs. Very recently, the nuclear genomes of E. multilocularis and E. granulosus have been characterised, revealing a plethora of data for gaining a deeper understanding of host-parasite interaction, parasite development and parasite evolution. Combined with extensive transcriptome analyses of Echinococcus life cycle stages these investigations also yielded novel clues for targeted drug design. Recent years also witnessed significant advancements in the molecular and cellular characterisation of the Echinococcus 'germinative cell' population, which forms a unique stem cell system that differs from stem cells of other organisms in the expression of several genes associated with the maintenance of pluripotency. As the only parasite cell type capable of undergoing mitosis, the germinative cells are central to all developmental transitions of Echinococcus within the host and to parasite expansion via asexual proliferation. In the present article, we will briefly introduce and discuss recent advances in Echinococcus genomics and stem cell research in the context of drug design and development. Interestingly, it turns out that benzimidazoles seem to have very limited effects on Echinococcus germinative cells, which could explain the high recurrence rates observed after chemotherapeutic treatment of echinococcosis patients. This clearly indicates that future efforts into the development of parasitocidal drugs should also target the parasite's stem cell system.