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Concept: Schistosomiasis

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Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma. The disease remains a serious public health problem in endemic countries and affects at least 207 million people worldwide. A definite diagnosis of the disease plays a key role in the control of schistosomiasis. The detection of schistosome circulating antigens (CAs) is an effective approach to discriminate between previous exposure and current infection. Different methods have been investigated for detecting the CAs. However, the components of the schistosome CAs remain unclear. In this study, we analyzed the CAs in sera of patients infected with Schistosoma japonicum.

Concepts: Epidemiology, Medical terms, Schistosomiasis, Schistosoma, Digenea, Flatworm, Schistosoma japonicum, Trematoda

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BACKGROUND: Schistosoma mansoni is one of the causative agents of schistosomiasis, a neglected tropical disease that affects about 237 million people worldwide. Despite recent efforts, we still lack a general understanding of the relevant host-parasite interactions, and the possible treatments are limited by the emergence of resistant strains and the absence of a vaccine. The S. mansoni genome was completely sequenced and still under continuous annotation. Nevertheless, more than 45% of the encoded proteins remain without experimental characterization or even functional prediction. To improve our knowledge regarding the biology of this parasite, we conducted a proteome-wide evolutionary analysis to provide a broad view of the S. mansoni’s proteome evolution and to improve its functional annotation. RESULTS: Using a phylogenomic approach, we reconstructed the S. mansoni phylome, which comprises the evolutionary histories of all parasite proteins and their homologs across 12 other organisms. The analysis of a total of 7,964 phylogenies allowed a deeper understanding of genomic complexity and evolutionary adaptations to a parasitic lifestyle. In particular, the identification of lineage-specific gene duplications pointed to the diversification of several protein families that are relevant for host-parasite interaction, including proteases, tetraspanins, fucosyltransferases, venom allergen-like proteins, and tegumental-allergen-like proteins. In addition to the evolutionary knowledge, the phylome data enabled us to automatically re-annotate 3,451 proteins through a phylogenetic-based approach rather than solely sequence similarity searches. To allow further exploitation of this valuable data, all information has been made available at PhylomeDB (http://www.phylomedb.org). CONCLUSIONS: In this study, we used an evolutionary approach to assess S. mansoni parasite biology, improve genome/proteome functional annotation, and provide insights into host-parasite interactions. Taking advantage of a proteome-wide perspective rather than focusing on individual proteins, we identified that this parasite has experienced specific gene duplication events, particularly affecting genes that are potentially related to the parasitic lifestyle. These innovations may be related to the mechanisms that protect S. mansoni against host immune responses being important adaptations for the parasite survival in a potentially hostile environment. Continuing this work, a comparative analysis involving genomic, transcriptomic, and proteomic data from other helminth parasites, other parasites, and vectors will supply more information regarding parasite’s biology as well as host-parasite interactions.

Concepts: Immune system, DNA, Gene, Genetics, Evolution, Schistosomiasis, Parasitism, Gene duplication

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Schistosomiasis is a parasitic disease that is highly prevalent, especially in developing countries. Biomphalaria tenagophila is an important invertebrate host of Schistosoma mansoni in Brazil, with some strains (e.g. Cabo Frio) being highly susceptible to the parasite, whereas others (e.g. Taim) are completely resistant to infection. Therefore, B. tenagophila is an important research model for studying immune defense mechanisms against S. mansoni. The internal defense system (IDS) of the snail comprises hemocytes and hemolymph factors acting together to recognize self from non-self molecular patterns to eliminate the threat of infection. We performed experiments to understand the cellular defenses related to the resistance and/or susceptibility of B. tenagophila to S. mansoni. During the early stages of infection, fibrous host cells of both snail strains were arranged as a thin layer surrounding the sporocysts. However, at later stages of infection, the cellular reactions in resistant snails were increasingly more intense, with thicker layers surrounding the parasites, in contrast to susceptible strains. All parasites were damaged or destroyed inside resistant snails after 10 h of infection. By contrast, parasites inside susceptible snails appeared to be morphologically healthy. We also performed experiments using isolated hemocytes from the two strains interacting with sporocysts. Hemocyte attachment started as early as 1 h after initial infection in both strains, but the killing of sporocysts was exclusive to hemocytes from the resistant strain and was time course dependent. The resistant strain was able to kill all sporocysts. In conclusion, our study revealed important aspects of the initial process of infection related to immune defense responses of strains of B. tenagophila that were resistant to S. mansoni compared with strains that were susceptible. Such information is relevant for the survival or death of the parasites and so is important in the development of control measures against this parasite.

Concepts: Immune system, Schistosomiasis, Schistosoma mansoni, Parasitism, Biomphalaria, Biomphalaria tenagophila, Biomphalaria glabrata, Biomphalaria straminea

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Poyang Lake, the largest fresh water lake in China, is the major transmission site of Schistosoma japonicum in China. Epidemics of schistosomiasis japonica have threatened the health of residents and stunted social-economic development there.

Concepts: Epidemiology, Mathematics, Physics, Schistosomiasis, Schistosoma, Digenea, Freshwater, Schistosoma japonicum

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Upon infection with Schistosoma, antibody responses are mounted that are largely directed against glycans. Over the last few years significant progress has been made in characterizing the antigenic properties of N-glycans of Schistosoma mansoni. Despite also being abundantly expressed by schistosomes, much less is understood about O-glycans and antibody responses to these have not yet been systematically analyzed. Antibody binding to schistosome glycans can be analyzed efficiently and quantitatively using glycan microarrays, but O-glycan array construction and exploration is lagging behind because no universal O-glycanase is available, and release of O-glycans has been dependent on chemical methods. Recently, a modified hydrazinolysis method has been developed that allows the release of O-glycans with free reducing termini and limited degradation, and we applied this method to obtain O-glycans from different S. mansoni life stages. Two-dimensional HPLC separation of 2-aminobenzoic acid-labeled O-glycans generated 362 O-glycan-containing fractions that were printed on an epoxide-modified glass slide, thereby generating the first shotgun O-glycan microarray containing naturally occurring schistosome O-glycans. Monoclonal antibodies and mass spectrometry showed that the O-glycan microarray contains well-known antigenic glycan motifs as well as numerous other, potentially novel, antibody targets. Incubations of the microarrays with sera from Schistosoma-infected humans showed substantial antibody responses to O-glycans in addition to those observed to the previously investigated N- and glycosphingolipid glycans. This underlines the importance of the inclusion of these often schistosome-specific O-glycans in glycan antigen studies and indicates that O-glycans contain novel antigenic motifs that have potential for use in diagnostic methods and studies aiming at the discovery of vaccine targets.

Concepts: Immune system, Antibody, Schistosomiasis, Schistosoma mansoni, Schistosoma, Digenea, Antigen, Strigeidida

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Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.

Concepts: Immune system, Schistosomiasis, Schistosoma mansoni, Schistosoma, Digenea, Strigeidida, Oxamniquine

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Intestinal schistosomiasis due to Schistosoma mansoni was first reported in Oman in 1979. We describe the trend in parasitological and serological prevalence of human infection with S. mansoni in the endemic area over the period 1982-2014, and the compliance of data generated by the national monitoring and evaluation system with schistosomiasis elimination criteria set by the Ministry of Health of Oman.

Concepts: Epidemiology, Schistosomiasis, Schistosoma mansoni, Schistosoma, Digenea, Strigeidida, Oxamniquine

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The antischistosomal pro-drug oxamniquine is activated by a sulfotransferase (SULT) in the human parasite Schistosoma mansoni Of the three main human blood fluke species, only S. mansoni is sensitive to oxamniquine therapy despite the presence of SULT orthologs in S. haematobium and S. japonicum The reason for this species-specific drug action has remained a mystery for decades. Here we present the crystal structures of S. haematobium and S. japonicum SULTs, including S. haematobium SULT in complex with oxamniquine. Our finding that all three enzymes show activity toward oxamniquine in vitro reveals differences in catalytic efficiency that implicate kinetics as the determinant for species-specific toxicity. These results support the initiative for designing oxamniquine derivatives to treat infection caused by all species of blood fluke to combat emerging resistance to current therapy.

Concepts: Parasites, Schistosomiasis, Schistosoma mansoni, Schistosoma, Digenea, Schistosoma haematobium, Schistosoma japonicum, Strigeidida

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Despite control efforts, human schistosomiasis remains prevalent throughout Africa, Asia, and South America. The global schistosomiasis burden has changed little since the new anthelmintic drug, praziquantel, promised widespread control.

Concepts: Schistosomiasis, Praziquantel, Pacific Ocean, South America, Americas, Natural reservoir, Anthelmintic, Emodepside

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Targeting the cellular Ca(2+) channels and pumps that underpin parasite Ca(2+) homeostasis may realize novel antihelmintic agents. Indeed, the antischistosomal drug praziquantel (PZQ) is a key clinical agent that has been proposed to work in this manner. Heterologous expression data has implicated an action of PZQ on voltage-operated Ca(2+) channels, although the relevant in vivo target of this drug has remained undefined over three decades of clinical use. The purpose of this review is to bring new perspective to this issue by discussing the potential utility of free-living planarian flatworms for providing new insight into the mechanism of PZQ action. First, we discuss in vivo functional genetic data from the planarian system that broadly supports the molecular data collected in heterologous systems and the ‘Ca(2+) hypothesis’ of PZQ action. On the basis of these similarities we highlight our current knowledge of platyhelminth voltage operated Ca(2+) channels, their unique molecular pharmacology and the downstream functional PZQ interactome engaged by dysregulation of Ca(2+) influx that has potential to yield novel antischistosomal targets. Overall the broad dataset underscore a common theme of PZQ-evoked disruptions of Ca(2+) homeostasis in trematodes, cestodes and turbellarians, and showcase the utility of the planarian model for deriving insight into drug action and targets in parasitic flatworms.

Concepts: Schistosomiasis, Schistosoma, Praziquantel, Target Corporation, Flatworm, Anthelmintic, Platyhelminthes, Planarian