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1
Pila, Emmanuel A., Michelle A. Gordy, Valerie K. Phillips, Alethe L. Kabore, Sydney P. Rudko, and Patrick C. Hanington. "Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host." Proceedings of the National Academy of Sciences 113, no. 19 (April 25, 2016): 5305–10. http://dx.doi.org/10.1073/pnas.1521239113.
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Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni. Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.
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SCHOLZ, TOMÁš. "Keys to the Trematoda. Volume II (ed. Jones, A., Bray, R. A. and Gibson, D. I.), pp. 768. Commonwealth Agricultural Bureau International (CABI Publishing), UK and The Natural History Museum, London, UK, 2005. ISBN 0 85199 587 X. £150.00." Parasitology 132, no. 1 (January 2006): 153–54. http://dx.doi.org/10.1017/s0031182005229670.
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Trematodes (flukes or digeneans) are by far the most abundant group of parasitic flatworms (Neodermata), and their importance for human and animal health is indisputable. In addition, they exhibit a variety of unique adaptations to parasitism and, probably most remarkably, possess extraordinarily complicated life-cycles. Classification of trematodes represents a very difficult task due to the huge number of existing species and variety of morphological forms, sites of infection within invertebrate and vertebrate hosts and ability to infect a wide spectrum of animals. Therefore, identification of any trematode may represent a problem even for an experienced specialist. This is the reason why I appreciated so much the publication of the first volume of the Keys to the Trematoda in 2002.
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McManus, Donald P. "Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines." Vaccines 8, no. 3 (September 22, 2020): 553. http://dx.doi.org/10.3390/vaccines8030553.
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Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe disability; hinder growth, productivity and cognitive development; and can end in death. Children are often disproportionately affected. F. hepatica and F. gigantica are also the most important trematode flukes parasitising ruminants and cause substantial economic losses annually. Mass drug administration (MDA) programs for the control of these liver and blood fluke infections are in place in a number of countries but treatment coverage is often low, re-infection rates are high and drug compliance and effectiveness can vary. Furthermore, the spectre of drug resistance is ever-present, so MDA is not effective or sustainable long term. Vaccination would provide an invaluable tool to achieve lasting control leading to elimination. This review summarises the status currently of vaccine development, identifies some of the major scientific targets for progression and briefly discusses future innovations that may provide effective protective immunity against these helminth parasites and the diseases they cause.
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OGAWA, K. "Diseases of cultured marine fishes caused by Platyhelminthes (Monogenea, Digenea, Cestoda)." Parasitology 142, no. 1 (July 7, 2014): 178–95. http://dx.doi.org/10.1017/s0031182014000808.
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SUMMARYMariculture is a rapidly developing industrial sector. Generally, fish are maintained in net cages with high density. Cage culture systems allow uncontrolled flow of sea water containing potentially infectious stages of fish parasites. In such culture conditions, prevention of such parasitic infections is difficult for parasites with life cycles that complete within culture sites, among which monogeneans and blood flukes are the most important platyhelminthes. Intense monogenean infections induce respiratory and osmo-regulatory dysfunctions. A variety of control measures have been developed, including freshwater bath treatment and chemotherapy. The potential to control monogenean infections through selective breeding, modified culture techniques to avoid infection, and general fish health management are discussed. It should be noted that mariculture conditions have provided some host-specific monogeneans with a chance to expand their host ranges. Blood flukes sometimes induce mass mortality among farmed fish. In-feed administration of praziquantel is the best solution to treat infected fish. Some cases are described that show how international trade in marine fish has resulted in the spread of hitherto unknown parasites into indigenous farmed and wild fish.
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González-Miguel, J., M. A. Valero, M. Reguera-Gomez, C. Mas-Bargues, M. D. Bargues, F. Simón, and S. Mas-Coma. "NumerousFasciolaplasminogen-binding proteins may underlie blood-brain barrier leakage and explain neurological disorder complexity and heterogeneity in the acute and chronic phases of human fascioliasis." Parasitology 146, no. 3 (September 24, 2018): 284–98. http://dx.doi.org/10.1017/s0031182018001464.
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AbstractHuman fascioliasis is a worldwide, pathogenic food-borne trematodiasis. Impressive clinical pictures comprising puzzling polymorphisms, manifestation multifocality, disease evolution changes, sequelae and mortality, have been reported in patients presenting with neurological, meningeal, neuropsychic and ocular disorders caused at distance by flukes infecting the liver. Proteomic and mass spectrometry analyses of theFasciola hepaticaexcretome/secretome identified numerous, several new, plasminogen-binding proteins enhancing plasmin generation. This may underlie blood-brain barrier leakage whether by many simultaneously migrating, small-sized juvenile flukes in the acute phase, or by breakage of encapsulating formations triggered by single worm tracks in the chronic phase. Blood-brain barrier leakages may subsequently occur due to a fibrinolytic system-dependent mechanism involving plasmin-dependent generation of the proinflammatory peptide bradykinin and activation of bradykinin B2 receptors, after different plasminogen-binding protein agglomeration waves. Interactions between diverse parasitic situations and non-imbalancing fibrinolysis system alterations are for the first time proposed that explain the complexity, heterogeneity and timely variations of neurological disorders. Additionally, inflammation and dilation of blood vessels may be due to contact system–dependent generation bradykinin. This baseline allows for search of indicators to detect neurological risk in fascioliasis patients and experimental work on antifibrinolytic treatments or B2 receptor antagonists for preventing blood-brain barrier leakage.
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JEDLIČKOVÁ, LUCIE, HANA DVOŘÁKOVÁ, MARTIN KAŠNÝ, JANA ILGOVÁ, DAVID POTĚŠIL, ZBYNĚK ZDRÁHAL, and LIBOR MIKEŠ. "Major acid endopeptidases of the blood-feeding monogenean Eudiplozoon nipponicum (Heteronchoinea: Diplozoidae)." Parasitology 143, no. 4 (February 18, 2016): 494–506. http://dx.doi.org/10.1017/s0031182015001808.
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SUMMARYIn parasitic flatworms, acid endopeptidases are involved in crucial processes, including digestion, invasion, interactions with the host immune system, etc. In haematophagous monogeneans, however, no solid information has been available about the occurrence of these enzymes. Here we aimed to identify major cysteine and aspartic endopeptidase activities in Eudiplozoon nipponicum, an invasive haematophagous parasite of common carp. Employing biochemical, proteomic and molecular tools, we found that cysteine peptidase activities prevailed in soluble protein extracts and excretory/secretory products (ESP) of E. nipponicum; the major part was cathepsin L-like in nature supplemented with cathepsin B-like activity. Significant activity of the aspartic cathepsin D also occurred in soluble protein extracts. The degradation of haemoglobin in the presence of ESP and worm protein extracts was completely inhibited by a combination of cysteine and aspartic peptidase inhibitors, and diminished by particular cathepsin L, B and D inhibitors. Mass spectrometry revealed several tryptic peptides in ESP matching to two translated sequences of cathepsin L genes, which were amplified from cDNA of E. nipponicum and bioinformatically annotated. The dominance of cysteine peptidases of cathepsin L type in E. nipponicum resembles the situation in, e.g. fasciolid trematodes.
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Dalton, John P., Patrick Skelly, and David W. Halton. "Role of the tegument and gut in nutrient uptake by parasitic platyhelminths." Canadian Journal of Zoology 82, no. 2 (February 1, 2004): 211–32. http://dx.doi.org/10.1139/z03-213.
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The ease of procuring nutrient is probably the main selection pressure that drives and maintains the host–parasite relationship. The feeding activities of the ectoparasitic monogeneans exhibit similarities with the predatory turbellarians, with certain monopisthocotylean members feeding by means of a protrusible pharynx. These parasites degrade fish skin by secreting enzymes extracorporeally, but most of the digestion is carried out intracellularly in cells lining a well-differentiated gut. Some polyopisthocotylean monogeneans, however, living within the vascularized gill chamber, took advantage of the availability of a more highly nutritious, consistent, and renewable diet in the form of blood, and this represented a major step in the evolution of endoparasitism. Blood provides a rich source of carbohydrates for the production of energy and amino acids and fatty acids for the synthesis of parasite molecules and for egg production. The external surfaces of all parasitic flatworms depart from turbellarian character and are composed of a multifunctional syncytial tegument that is permeable to a variety of small organic solutes. Glucose and amino acid transporter molecules situated in the tegumental surface and basal membranes of trematodes and cestodes function in the uptake of these molecules and their distribution to the parasite tissues. Cestodes are bereft of any vestige of a gut, but their tegument has become elaborated into a highly efficient digestive–absorptive layer that competes with the vertebrate mucosa for nutrients. The patterns of energy metabolism in adult flatworm parasites are generally anaerobic and based on glycogen, with abbreviated metabolic pathways and the loss of biosynthetic capacities. In contrast to the tegument, the role of the gut is to digest host macromolecules and subsequently absorb the soluble products. However, the switch to blood as the major source of nutrient necessitated development of a means of overcoming the problems of blood clotting, attack by immune effector mechanisms, and the intracellular accumulations of haematin pigment. Digenean trematode, in contrast to monogeneans, digest blood extracellularly and their secretions include molecules capable of lysing erythrocytes and preventing blood clotting. Digestion of the ingested proteins is generally rapid, involving a range of cathepsin-like cysteine and aspartic proteases, which reduce the blood meal to absorbable peptides that are most likely further catabolized to amino acids by intracellular aminopeptidases. The parasites dispose of accumulated haematin by simply emptying the contents of their blind-ended gut.
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Wilson, R. Alan, Xiao Hong Li, and William Castro-Borges. "Schistosome vaccines: problems, pitfalls and prospects." Emerging Topics in Life Sciences 1, no. 6 (December 22, 2017): 641–50. http://dx.doi.org/10.1042/etls20170094.
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Human schistosomiasis caused by parasitic flatworms of the genus Schistosoma remains an important public health problem in spite of concerted efforts at control. An effective vaccine would be a useful addition to control strategies that currently rely on chemotherapy, but such a product is not imminent. In this review, likely causes for the lack of progress are first considered. These include the strategies used by worms to evade the immune response, concepts that have misdirected the field, an emphasis on internal antigens, and the use of the laboratory mouse for vaccine testing. On a positive note, recent investigations on self-cure by the rhesus macaque offer the most promising context for vaccine development. The identification of proteins at the parasite–host interface, especially those of the esophageal glands involved in blood processing, has provided an entirely new category of vaccine candidates that merit evaluation.
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Mughal, Mudassar, Qing Ye, Lu Zhao, Christoph Grevelding, Ying Li, Wenda Di, Xin He, Xuesong Li, Robin Gasser, and Min Hu. "First Evidence of Function for Schistosoma japonicum riok-1 and RIOK-1." Pathogens 10, no. 7 (July 8, 2021): 862. http://dx.doi.org/10.3390/pathogens10070862.
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Protein kinases are known as key molecules that regulate many biological processes in animals. The right open reading frame protein kinase (riok) genes are known to be essential regulators in model organisms such as the free-living nematode Caenorhabditis elegans. However, very little is known about their function in parasitic trematodes (flukes). In the present study, we characterized the riok-1 gene (Sj-riok-1) and the inferred protein (Sj-RIOK-1) in the parasitic blood fluke, Schistosoma japonicum. We gained a first insight into function of this gene/protein through double-stranded RNA interference (RNAi) and chemical inhibition. RNAi significantly reduced Sj-riok-1 transcription in both female and male worms compared with untreated control worms, and subtle morphological alterations were detected in the ovaries of female worms. Chemical knockdown of Sj-RIOK-1 with toyocamycin (a specific RIOK-1 inhibitor/probe) caused a substantial reduction in worm viability and a major accumulation of mature oocytes in the seminal receptacle (female worms), and of spermatozoa in the sperm vesicle (male worms). These phenotypic alterations indicate that the function of Sj-riok-1 is linked to developmental and/or reproductive processes in S. japonicum.
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Fabiano, Marco, Alfonso Califano, Francesco Chiancone, Antonio D’Antonio, Francesco Maiorino, Davide Simeone, Gianmarco Silvestre, and Vincenzo Altieri. "Bladder schistosomiasis in Italy: A case report." Urologia Journal 87, no. 4 (March 5, 2020): 191–93. http://dx.doi.org/10.1177/0391560320910647.
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Introduction: Human schistosomiasis is a snail-borne disease caused by parasitic blood-dwelling flukes. A long-term infection can lead to the risk of liver damage, kidney failure, infertility, or bladder cancer. The most common sign is hematuria with the blood first seen in the terminal urine, but in severe cases the whole urine sample can be dark colored. We analyze the case of a healthy African child living in Italy since birth, harboring a hidden debilitating disease that was picked up during ultrasonography. Case Report: A 11-year-old African child was admitted to our emergency department with macroscopic hematuria, dysuria, and frequency for 2 months. Ultrasonography revealed a solid mass involving bladder’s right wall. Non-contrast and contrast-enhanced scans of computerized tomography showed a mass of 45 mm x 15 mm on the right bladder wall. A bipolar transurethral resection of bladder was performed. The pathological examination showed findings consistent with Schistosoma haematobium. Discussion: The clinical manifestations of schistosomiasis depend on the inflammatory response to the parasitic infection. In particular, it can manifest in the bladder as painless dysuria, urinary incontinence and urinary frequency, hematuria, or even urinary retention if the trigone is involved. Utilization of ultrasonography for diagnostic evaluation of schistosomiasis is mandatory. For treatment, the World Health Organization recommends praziquantel which has an efficacy of up to 90%.
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BROUWERS, Jos F. H. M., Cornelis VERSLUIS, Lambert M. G. van GOLDE, and Aloysius G. M. TIELENS. "5-Octadecenoic acid: evidence for a novel type of fatty acid modification in schistosomes." Biochemical Journal 334, no. 2 (September 1, 1998): 315–19. http://dx.doi.org/10.1042/bj3340315.
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The lipid metabolism of schistosomes is characterized by several intriguing adaptations to a parasitic way of living. The surface of the parasite consists of two closely apposed phospholipid bilayers, a structure unique to blood flukes. Schistosomes do not synthesize fatty acids de novo, but are able to modify fatty acids, which they obtain from the host, by chain elongation. Here we present evidence that schistosomes are capable of another type of fatty acid modification, resulting in the formation of 5-octadecenoic acid [C18:1(5)]. This highly unusual fatty acid, which is absent in the blood of the host, was shown to be almost exclusively located in the outer membrane complex of the schistosome. Within these membranes, it was almost exclusively present in one molecular phospholipid species, 1-palmitoyl-2,5-octadecenoyl phosphatidylcholine [C16:0–18:1(5)PtdCho]. Apart from dipalmitoyl phosphatidylcholine, this was the most abundant phosphatidylcholine species in the outer membrane complex. The specific synthesis by the schistosome of C18:1(5) and the highly specific localization of this fatty acid to the tegumental membranes suggest an important tegument-mediated role for this lipid.
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Yonis, Abdal Gadir, Al Safi Ahmed Abdallash, Mona Ahmed, and Ashraf Mustafa Mohammed Osman. "ASSESSMENT OF PATHOLOGICAL CHANGE OF SCHISTOSOMA MANSONI INFECTIONIN THE LIVER USING ULTRASOUNOGRAPHY." International Journal of Research -GRANTHAALAYAH 7, no. 7 (July 31, 2019): 125–31. http://dx.doi.org/10.29121/granthaalayah.v7.i7.2019.738.
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Background: Schistosomiasis is a tropical parasitic disease caused by blood flukes of the genus Schistosoma, causes periportal fibrosis and portal hypertension in approximately 13%-18% of those afflicted with the disease in the Gezira irrigated areas of Sudan. This a prospective study compromise of 360 consecutive patients at North Gezira State between 2016 to 2019 aimed to assessment of pathological change in schistosomiasismansoni infection using B-mode grayscale ultrasound, The images done by portable Sono Scape- A6 machine using convex probe with frequency range from 3.5 to 5 MHz and the data analyzed by SPSS version 15. The result showed that the majority of patients were male and periportal fibrosis had high incidence associated with schistosomiasismansoni, Out of 360 patients with schistosomal PPF under study there were no PPF noted in 56 (15.6%) , while the remaining had mild in106 (29.4%), moderate in166 (46.1%), and severe PPF in 32 (8,9%) The study concluded that the B- mode Gray scale portable ultrasound machine is the most frequently used imaging modality to assess patients for the presence of periportalfibrosis especially in the endemic area.
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Xiong, Qingming, Hannah Bekebrede, Pratibha Sharma, Luis G. Arroyo, John D. Baird, and Yasuko Rikihisa. "An Ecotype of Neorickettsia risticii Causing Potomac Horse Fever in Canada." Applied and Environmental Microbiology 82, no. 19 (July 29, 2016): 6030–36. http://dx.doi.org/10.1128/aem.01366-16.
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ABSTRACTNeorickettsia(formerlyEhrlichia)risticiiis an obligatory intracellular bacterium of digenetic trematodes. When a horse accidentally ingests aquatic insects containing encysted trematodes infected withN. risticii, the bacterium is transmitted from trematodes to horse cells and causes an acute and often fatal disease called Potomac horse fever (PHF). Since the discovery ofN. risticiiin the United States in 1984, using immunofluorescence and PCR assays, PHF has been increasingly recognized throughout North America and South America. However, so far, there exist only a few stableN. risticiiculture isolates, all of which are from horses within the United States, and the strain diversity and environmental spreading and distribution of pathogenicN. risticiistrains remain poorly understood. This paper reports the isolation ofN. risticiifrom the blood of a horse with acute PHF in Ontario, Canada. IntracellularN. risticiicolonies were detected in P388D1cells after 47 days of culturing and 8 days after the addition of rapamycin. Molecular phylogenetic analysis based on amino acid sequences of major surface proteins P51 and Ssa1 showed that this isolate is distinct from any previously sequenced strains but closely related to midwestern U.S. strains. This is the first Canadian strain cultured, and a new method was developed to reactivate dormantN. risticiito improve culture isolation.IMPORTANCENeorickettsia risticiiis an environmental bacterium that lives inside flukes that are parasitic to aquatic snails, insects, and bats. When a horse accidentally ingests insects harboring flukes infected withN. risticii, the bacterium is transmitted to the horse and causes an acute and often fatal disease called Potomac horse fever. Although the disease has been increasingly recognized throughout North and South America,N. risticiihas not been cultured outside the United States. This paper reports the first Canadian strain cultured and a new method to effectively culture isolateN. risticiifrom the horse blood sample. Molecular analysis showed that the genotype of this Canadian strain is distinct from previously sequenced strains but closely related to midwestern U.S. strains. Culture isolation ofN. risticiistrains would confirm the geographic presence of pathogenicN. risticii, help elucidateN. risticiistrain diversity and environmental spreading and distribution, and improve diagnosis and development of vaccines for this dreadful disease.
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SKELLY, P. J., and C. B. SHOEMAKER. "The Schistosoma mansoni host-interactive tegument forms from vesicle eruptions of a cyton network." Parasitology 122, no. 1 (January 2001): 67–73. http://dx.doi.org/10.1017/s0031182000007071.
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During trans-dermal invasion of the vertebrate host, larval schistosomes (cercariae) transform into schistosomula and become enveloped by a double lipid bilayered, tegumental membrane. The glucose transporter protein SGTP4 is found exclusively in these host-interactive tegumental membranes and in membranous vesicles proposed to be their precursor. In this study, we monitored the appearance and migration of this tegumental marker protein during larval transformation to test the current model of tegumental membrane biosynthesis in parasitic blood flukes. Only minutes after transformation was initiated, SGTP4 began accumulating in a previously unrecognized, bilaterally symmetrical, ‘cyton network’ beneath the peripheral muscle. Approximately 30min after the initiation of transformation the marker protein was seen in tubules connecting the network to the surface and erupting onto the surface in discrete patches. After 1h the patches were regularly arrayed over the schistosomula body and began to cover the anterior organ. By 3h the staining has largely resolved into a contiguous layer of fluorescence covering most of the worm surface. These findings confirm earlier suggestions, based on electron microscopy, that the parasite's surface tegumental membranes are derived from the migration of membranous vesicles produced within cytons and reveal a new subtegumental architecture interconnecting the cytons.
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YOSHINO, TIMOTHY P., NATHALIE DINGUIRARD, and MARINA DE MORAES MOURÃO. "In vitro manipulation of gene expression in larval Schistosoma: a model for postgenomic approaches in Trematoda." Parasitology 137, no. 3 (December 7, 2009): 463–83. http://dx.doi.org/10.1017/s0031182009991302.
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SUMMARYWith rapid developments in DNA and protein sequencing technologies, combined with powerful bioinformatics tools, a continued acceleration of gene identification in parasitic helminths is predicted, potentially leading to discovery of new drug and vaccine targets, enhanced diagnostics and insights into the complex biology underlying host-parasite interactions. For the schistosome blood flukes, with the recent completion of genome sequencing and comprehensive transcriptomic datasets, there has accumulated massive amounts of gene sequence data, for which, in the vast majority of cases, little is known about actual functions within the intact organism. In this review we attempt to bring together traditional in vitro cultivation approaches and recent emergent technologies of molecular genomics, transcriptomics and genetic manipulation to illustrate the considerable progress made in our understanding of trematode gene expression and function during development of the intramolluscan larval stages. Using several prominent trematode families (Schistosomatidae, Fasciolidae, Echinostomatidae), we have focused on the current status of in vitro larval isolation/cultivation as a source of valuable raw material supporting gene discovery efforts in model digeneans that include whole genome sequencing, transcript and protein expression profiling during larval development, and progress made in the in vitro manipulation of genes and their expression in larval trematodes using transgenic and RNA interference (RNAi) approaches.
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Rehman, Abdur, Sajjad Ahmad, Farah Shahid, Aqel Albutti, Ameen S. S. Alwashmi, Mohammad Abdullah Aljasir, Naif Alhumeed, Muhammad Qasim, Usman Ali Ashfaq, and Muhammad Tahir ul Qamar. "Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis." Vaccines 9, no. 6 (June 16, 2021): 658. http://dx.doi.org/10.3390/vaccines9060658.
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Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium are the main pathogenic species that infect humans. In this research, core proteomics was combined with a subtractive proteomics pipeline to identify suitable antigenic proteins for the construction of a multi-epitope vaccine (MEV) against human-infecting Schistosoma species. The pipeline revealed two antigenic proteins—calcium binding and mycosubtilin synthase subunit C—as promising vaccine targets. T and B cell epitopes from the targeted proteins were predicted using multiple bioinformatics and immunoinformatics databases. Seven cytotoxic T cell lymphocytes (CTL), three helper T cell lymphocytes (HTL), and four linear B cell lymphocytes (LBL) epitopes were fused with a suitable adjuvant and linkers to design a 217 amino-acid-long MEV. The vaccine was coupled with a TLR-4 agonist (RS-09; Sequence: APPHALS) adjuvant to enhance the immune responses. The designed MEV was stable, highly antigenic, and non-allergenic to human use. Molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MMGBSA) analysis were performed to study the binding affinity and molecular interactions of the MEV with human immune receptors (TLR2 and TLR4) and MHC molecules (MHC I and MHC II). The MEV expression capability was tested in an Escherichia coli (strain-K12) plasmid vector pET-28a(+). Findings of these computer assays proved the MEV as highly promising in establishing protective immunity against the pathogens; nevertheless, additional validation by in vivo and in vitro experiments is required to discuss its real immune-protective efficacy.
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Tedla, Bemnet A., Darren Pickering, Luke Becker, Alex Loukas, and Mark S. Pearson. "Vaccination with Schistosoma mansoni Cholinesterases Reduces the Parasite Burden and Egg Viability in a Mouse Model of Schistosomiasis." Vaccines 8, no. 2 (April 3, 2020): 162. http://dx.doi.org/10.3390/vaccines8020162.
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Schistosomiasis is a neglected tropical disease caused by parasitic blood flukes of the genus Schistosoma, which kills 300,000 people every year in developing countries, and there is no vaccine. Recently, we have shown that cholinesterases (ChEs)—enzymes that regulate neurotransmission—from Schistosoma mansoni are expressed on the outer tegument surface and present in the excretory/secretory products of larval schistosomula and adult worms, and are essential for parasite survival in the definitive host, highlighting their utility as potential schistosomiasis vaccine targets. When treated in vitro with anti-schistosome cholinesterase (SmChE) IgG, both schistosomula and adult worms displayed significantly decreased ChE activity, which eventually resulted in parasite death. Vaccination with individual SmChEs, or a combination of all three SmChEs, significantly reduced worm burdens in two independent trials compared to controls. Average adult worm numbers and liver egg burdens were significantly decreased for all vaccinated mice across both trials, with values of 29–39% and 13–46%, respectively, except for those vaccinated with SmAChE1 in trial 1. Egg viability, as determined by egg hatching from liver homogenates, was significantly reduced in the groups vaccinated with the SmChE cocktail (40%) and SmAChE2 (46%). Furthermore, surviving worms from each vaccinated group were significantly stunted and depleted of glycogen stores, compared to controls. These results suggest that SmChEs could be incorporated into a vaccine against schistosomiasis to reduce the pathology and transmission of this debilitating disease.
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Haji, Kassim H., and Prashath K. Guddeti. "Prevalence and knowledge, attitude and practices related to schistosomiasis among primary school children in Chaani village, North “A” District, Zanzibar." International Journal of Research in Medical Sciences 9, no. 9 (August 25, 2021): 2761. http://dx.doi.org/10.18203/2320-6012.ijrms20213420.
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Background: Schistosomiasis is a chronic, parasitic disease caused by blood flukes (Schistosoma species). It has been for along time a neglected tropical disease in most of the sub-Saharan countries.Methods: A cross sectional descriptive study was conducted between June 2015 to July 2015 at Chaani village in North “A” District. The school children were interviewed to identify activities which expose them frequently to water contact. Study subjects were selected by using stratified random sampling technique. The selected school children were asked to collect urine sample in well-labeled container. The samples were processed in the laboratory by using standard microbiological techniques (syringe filtration then examined by microscopy) and results were recorded, the data was analyzed.Results: Out of 170 School children 62 were infected with Schistosoma haematobium which is the predominant Schistosoma species found in that area. Among the 62, 45 (57.6%) were male and 17 (42.4%) were female. The level of knowledge of respondents on Schistosomiasis transmission is that 70% of school children have high knowledge, 18% have moderate knowledge and 12% have low knowledge. Other parameters were also assessed like bathing habits and knowledge and functions of Schistosomiasis control drug.Conclusions: Males were significantly more affected by the disease than females. Provision of safe water coupled with education of the communities regarding the modes of transmission of the disease and the way to prevent oneself, as well as provision of sanitary facilities, such as latrines may decrease the disease burden.
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Lee, Jayhun, Tracy Chong, and Phillip A. Newmark. "The esophageal gland mediates host immune evasion by the human parasiteSchistosoma mansoni." Proceedings of the National Academy of Sciences 117, no. 32 (July 31, 2020): 19299–309. http://dx.doi.org/10.1073/pnas.2006553117.
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Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease affecting over 200 million people. Schistosomes develop multiple body plans while navigating their complex life cycle, which involves two different hosts: a mammalian definitive host and a molluscan intermediate host. Their survival and propagation depend upon proliferation and differentiation of stem cells necessary for parasite homeostasis and reproduction. Infective larvae released from snails carry a handful of stem cells that serve as the likely source of new tissues as the parasite adapts to life inside the mammalian host; however, the role of these stem cells during this critical life cycle stage remains unclear. Here, we characterize stem cell fates during early intramammalian development. Surprisingly, we find that the esophageal gland, an accessory organ of the digestive tract, develops before the rest of the digestive system is formed and blood feeding is initiated, suggesting a role in processes beyond nutrient uptake. To explore such a role, we examine schistosomes that lack the esophageal gland due to knockdown of a forkhead-box transcription factor,Sm-foxA, which blocks development and maintenance of the esophageal gland, without affecting the development of other somatic tissues. Intriguingly, schistosomes lacking the esophageal gland die after transplantation into naive mice, but survive in immunodeficient mice lacking B cells. We show that parasites lacking the esophageal gland are unable to lyse ingested immune cells within the esophagus before passing them into the gut. These results unveil an immune-evasion mechanism mediated by the esophageal gland, which is essential for schistosome survival and pathogenesis.
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Abdisa, Tagesu. "Rev iew on Ovine Fasciolosis in Ethiopia." Open Access Journal of Veterinary Science & Research 2, no. 2 (2017): 1–10. http://dx.doi.org/10.23880/oajvsr-16000132.
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Fasciolosis is one of the major constraint factors for ovine production development in Ethiopia by inflecting direct and indirect loss at different parts of the country. Ovine fasciolosis is an economically important parasitic disease of sheep caused by tr ematodes species of the genus Fasciola , which migrate in the hepatic parenchyma and establish and develops in the bile ducts. In Ethiopia, both species co - exist at different altitudes. The snails of the genus lymnae are mainly involved as an intermediate host in the life cycle of fasciolosis. Ovine fascioliasis in Ethiopia were losses annually estimated at 48.4 million Ethiopian birr due to mortality, productivity (weight loss and reproductive wastage), and liver condemnation at slaughter. This fasciola di sease has three phases of clinical sign acute, sub - acute and chronic forms. Acute fasciolosis occurs as disease outbreak following a massive, but relatively short - term, intake of metacercariae. Death usually results from blood loss due to hemorrhage and ti ssue destruction caused by the migratory juvenile flukes in the live resulting in traumatic hepatitis. Diagnosis of Fasciolosis is based on clinical sign, grazing history, and seasonal occurrence, examination of feces by laboratory tests and post mortem ex amination. Treatment of infected animals will largely depend on the correct use of appropriate and registered anthelmintic. Triclabendazole is the most effective anthelmintic drug which can be destroys or kills all stage of fasciola. Fasciolosis may be con trolled by reducing the populations of the intermediate snail host, or by appropriate anthelminthic treatment and the population of snail should be destroyed by applying Molluscicide and destroying the environment that suit for snail’s reproduction.
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Rahman, M. M., A. Kabir, S. Ahmed, M. K. Islam, M. S. Rahman, A. Alam, M. A. A. Mubeen, et al. "NITROXYNIL UNCOUPLES OXIDATIVE PHOSPHORYLATION IN THE CELL MITOCHONDRIA AND A DRUG WHEREVER INJECTABLES ARE PREFERRED OVER DRENCHES." Bangladesh Journal of Veterinary Medicine 15, no. 1 (September 20, 2017): 45–49. http://dx.doi.org/10.3329/bjvm.v15i1.34054.
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In the absence of effective vaccines and because of practical limitations in management options to control the snail intermediate hosts, the control of liver fluke infection and disease in livestock relies heavily on the use of flukicidal anthelmintics. Nitroxynil is a nitrate derivative from benzene compounds and presents a flukicide effect and is commonly used as the one with best spectrum from all the nitrate derivative trematocides. The drug is in fact, a low spectrum anthelmintic effective against fascioliasis, an important parasitic disease caused by flukes like Fasciola hepatica, Fasciola gigantica, affecting significantly the ruminant production by means of reducing the growth, conversion rate, milk production, quality and quantity of meat and reproduction. Nitroxynil also does hold efficacy against few roundworms mainly blood-sucking species as well as certain myiasis. It is not effective against most of the tape worms or external parasites. It is chemically constitute of yellow benzene crystals, slightly soluble in water and soluble in organic solvents, almost odorless and is characterized for being a stable solution, but it precipitates in presence of calcium and other salts. It is marketed as bright orange-red injectable solution due that by this route is six times more efficient than by oral route. Nitroxynil is a safe drug and it can be used at any stage of pregnancy. It does not affect fertility, gestation or fetus formation and in no way impede the reproductive performance of stallions. Its presented as two salts, nitroxynil megaglumine and nitroxynil eglumine. The nitroxynil in salt is hydrosoluble having neutral pH and is exclusively administered to animals by subcutaneous route. The flukicide resistance phenomenon is already present in many countries in the same way that resistance against other anthelmintic drugs is spreading around worldwide. Because of the absence of new drugs against fluke infections, it is necessary to prove and compare the efficacy of the anthelmintics to prevent resistance development. In view of that we endeavored elucidating the latest progress of one such widely used flukicide nitroxynil.
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Mu, Yi, Donald P. McManus, Nan Hou, and Pengfei Cai. "Schistosome Infection and Schistosome-Derived Products as Modulators for the Prevention and Alleviation of Immunological Disorders." Frontiers in Immunology 12 (February 22, 2021). http://dx.doi.org/10.3389/fimmu.2021.619776.
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Parasitic helminths, comprising the flatworms (tapeworms and flukes) and nematodes (roundworms), have plagued humans persistently over a considerable period of time. It is now known that the degree of exposure to these and other pathogens inversely correlates with the incidence of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. Accordingly, there has been recent increased interest in utilizing active helminth worm infections and helminth-derived products for the treatment of human autoimmune and inflammatory diseases and to alleviate disease severity. Indeed, there is an accumulating list of novel helminth derived molecules, including proteins, peptides, and microRNAs, that have been shown to exhibit therapeutic potential in a variety of disease models. Here we consider the blood-dwelling schistosome flukes, which have evolved subtle immune regulatory mechanisms that promote parasite survival but at the same time minimize host tissue immunopathology. We review and discuss the recent advances in using schistosome infection and schistosome-derived products as therapeutics to treat or mitigate human immune-related disorders, including allergic asthma, arthritis, colitis, diabetes, sepsis, cystitis, and cancer.
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Stroehlein, Andreas J., Pasi K. Korhonen, Teik Min Chong, Yan Lue Lim, Kok Gan Chan, Bonnie Webster, David Rollinson, Paul J. Brindley, Robin B. Gasser, and Neil D. Young. "High-quality Schistosoma haematobium genome achieved by single-molecule and long-range sequencing." GigaScience 8, no. 9 (September 1, 2019). http://dx.doi.org/10.1093/gigascience/giz108.
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AbstractBackgroundSchistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease affecting >100 million people worldwide. Chronic infection with this parasitic trematode can lead to urogenital conditions including female genital schistosomiasis and bladder cancer. At the molecular level, little is known about this blood fluke and the pathogenesis of the disease that it causes. To support molecular studies of this carcinogenic worm, we reported a draft genome for S. haematobium in 2012. Although a useful resource, its utility has been somewhat limited by its fragmentation.FindingsHere, we systematically enhanced the draft genome of S. haematobium using a single-molecule and long-range DNA-sequencing approach. We achieved a major improvement in the accuracy and contiguity of the genome assembly, making it superior or comparable to assemblies for other schistosome species. We transferred curated gene models to this assembly and, using enhanced gene annotation pipelines, inferred a gene set with as many or more complete gene models as those of other well-studied schistosomes. Using conserved, single-copy orthologs, we assessed the phylogenetic position of S. haematobium in relation to other parasitic flatworms for which draft genomes were available.ConclusionsWe report a substantially enhanced genomic resource that represents a solid foundation for molecular research on S. haematobium and is poised to better underpin population and functional genomic investigations and to accelerate the search for new disease interventions.
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Wendt, George R., Julie NR Collins, Jimin Pei, Mark S. Pearson, Hayley M. Bennett, Alex Loukas, Matthew Berriman, Nick V. Grishin, and James J. Collins. "Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni." eLife 7 (March 20, 2018). http://dx.doi.org/10.7554/elife.33221.
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Schistosomes infect more than 200 million people. These parasitic flatworms rely on a syncytial outer coat called the tegument to survive within the vasculature of their host. Although the tegument is pivotal for their survival, little is known about maintenance of this tissue during the decades schistosomes survive in the bloodstream. Here, we demonstrate that the tegument relies on stem cells (neoblasts) to specify fusogenic progenitors that replace tegumental cells lost to turnover. Molecular characterization of neoblasts and tegumental progenitors led to the discovery of two flatworm-specific zinc finger proteins that are essential for tegumental cell specification. These proteins are homologous to a protein essential for neoblast-driven epidermal maintenance in free-living flatworms. Therefore, we speculate that related parasites (i.e., tapeworms and flukes) employ similar strategies to control tegumental maintenance. Since parasitic flatworms infect every vertebrate species, understanding neoblast-driven tegumental maintenance could identify broad-spectrum therapeutics to fight diseases caused by these parasites.
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Arunsan, Patpicha, Wannaporn Ittiprasert, Michael J. Smout, Christina J. Cochran, Victoria H. Mann, Sujittra Chaiyadet, Shannon E. Karinshak, et al. "Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity." eLife 8 (January 15, 2019). http://dx.doi.org/10.7554/elife.41463.
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Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed liver fluke granulin (Ov-GRN-1) in pre-malignant lesions by undertaking programmed CRISPR/Cas9 knockout of the Ov-GRN-1 gene from the liver fluke genome. Deep sequencing of amplicon libraries from genomic DNA of gene-edited parasites revealed Cas9-catalyzed mutations within Ov-GRN-1. Gene editing resulted in rapid depletion of Ov-GRN-1 transcripts and the encoded Ov-GRN-1 protein. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult flukes, but the infection resulted in reduced pathology as evidenced by attenuated biliary hyperplasia and fibrosis. Not only does this report pioneer programmed gene-editing in parasitic flatworms, but also the striking, clinically-relevant pathophysiological phenotype confirms the role for Ov-GRN-1 in virulence morbidity during opisthorchiasis.
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Akbar, Hairil. "Faktor Risiko Kejadian Schistosomiasis di Dataran Tinggi Lindu Kabupaten Sigi Sulawesi Tengah." Jurnal Ilmiah Keperawatan Stikes Hang Tuah Surbaya 13, no. 1 (January 22, 2019). http://dx.doi.org/10.30643/jiksht.v13i1.18.
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Schistosomiasis, known as snail fever is a parasitic disease caused byinfection with trematode worms of the genus Schistosomajaponica Sp (blood flukes) that live in the mesenterica vein or veins of the bladder. The purpose of this study was to determine epidemiological determinants in the incidence of Schistosomiasis in Lindu Plateau, Sigi Regency. The study applied observational analytic with case control method. The sample size used in this study consisted of 82 people representing 41 people for cases and 41 people for controls obtainedwith Simple Random Sampling. The result indicated that there were significant influence of the history of Schistosomiasis, with p value 0,000 (p < 0,05) and the utilization of health programs with p value of 0,020 (p < 0,05). While variable jobs p value 0,165 (p > 0,05), income p value 1,000 (p > 0,05) there is no influence on the incidence of Schistosomiasis. Based on the findings above, it can be inferred that the prevalence of the Schistosomiasis was still high, these disease is closely related to the behaviors or habits of the community.Keywords: Community Behavior, Lindu, Schistosomiasis,
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Tiongco, R. E., N. A. Paragas, M. J. Dominguez, S. L. Lasta, J. K. Pandac, and M. R. Pineda-Cortel. "ABO blood group antigens may be associated with increased susceptibility to schistosomiasis: a systematic review and meta-analysis." Journal of Helminthology 94 (December 11, 2018). http://dx.doi.org/10.1017/s0022149x18001116.
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Abstract Schistosomiasis or bilharzia is a widespread parasitic disease caused by blood flukes of the genus Schistosoma. Some factors have been investigated previously regarding their effect on the pathophysiological mechanism of human schistosomiasis, but the possible influence of the ABO blood group on the severity of Schistosoma infection has been the most promising. Hence, we performed a systematic review and meta-analysis to further investigate the association of the ABO blood group with schistosomiasis susceptibility. Selected publications were retrieved from PubMed up to 21 August 2018, for related studies written in English. Number of cases (with schistosomiasis) and controls (without schistosomiasis) were extracted across all ABO blood types. Odds ratios (OR) and 95% confidence intervals (CI) were computed, pooled and interpreted. Subgroup analysis by the species of Schistosoma infecting the population and the participants’ ethnicity was also performed. The overall analysis revealed heterogeneity in the outcomes, which warranted the identification of the cause using the Galbraith plot. Post-outlier outcomes of the pooled ORs show that individuals who are not blood type O are more susceptible (OR: 1.40; 95% CI: 1.17–1.67; PA < 0.001) to schistosomiasis than those who are blood type O (OR: 0.71; 95% CI: 0.60–0.85; PA < 0.001). Subgroup analysis yielded the same observations regardless of the species of schistosome and the ethnicity of the participants. Results of this meta-analysis suggest that individuals who are blood type B and A are more susceptible to schistosomiasis than those who are blood type O. However, more studies are needed to confirm our claims.
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Ulrychová, Lenka, Pavel Ostašov, Marta Chanová, Michael Mareš, Martin Horn, and Jan Dvořák. "Spatial expression pattern of serine proteases in the blood fluke Schistosoma mansoni determined by fluorescence RNA in situ hybridization." Parasites & Vectors 14, no. 1 (May 22, 2021). http://dx.doi.org/10.1186/s13071-021-04773-8.
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Abstract Background The blood flukes of genus Schistosoma are the causative agent of schistosomiasis, a parasitic disease that infects more than 200 million people worldwide. Proteases of schistosomes are involved in critical steps of host–parasite interactions and are promising therapeutic targets. We recently identified and characterized a group of S1 family Schistosoma mansoni serine proteases, including SmSP1 to SmSP5. Expression levels of some SmSPs in S. mansoni are low, and by standard genome sequencing technologies they are marginally detectable at the method threshold levels. Here, we report their spatial gene expression patterns in adult S. mansoni by the high-sensitivity localization assay. Methodology Highly sensitive fluorescence in situ RNA hybridization (FISH) was modified and used for the localization of mRNAs encoding individual SmSP proteases (including low-expressed SmSPs) in tissues of adult worms. High sensitivity was obtained due to specifically prepared tissue and probes in combination with the employment of a signal amplification approach. The assay method was validated by detecting the expression patterns of a set of relevant reference genes including SmCB1, SmPOP, SmTSP-2, and Sm29 with localization formerly determined by other techniques. Results FISH analysis revealed interesting expression patterns of SmSPs distributed in multiple tissues of S. mansoni adults. The expression patterns of individual SmSPs were distinct but in part overlapping and were consistent with existing transcriptome sequencing data. The exception were genes with significantly low expression, which were also localized in tissues where they had not previously been detected by RNA sequencing methods. In general, SmSPs were found in various tissues including reproductive organs, parenchymal cells, esophagus, and the tegumental surface. Conclusions The FISH-based assay provided spatial information about the expression of five SmSPs in adult S. mansoni females and males. This highly sensitive method allowed visualization of low-abundantly expressed genes that are below the detection limits of standard in situ hybridization or by RNA sequencing. Thus, this technical approach turned out to be suitable for sensitive localization studies and may also be applicable for other trematodes. The results suggest that SmSPs may play roles in diverse processes of the parasite. Certain SmSPs expressed at the surface may be involved in host–parasite interactions. Graphic abstract
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Hoekstra, Pytsje T., Govert J. van Dam, and Lisette van Lieshout. "Context-Specific Procedures for the Diagnosis of Human Schistosomiasis – A Mini Review." Frontiers in Tropical Diseases 2 (August 5, 2021). http://dx.doi.org/10.3389/fitd.2021.722438.
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Schistosomiasis is a parasitic disease caused by trematode blood flukes of the genus Schistosoma, affecting over 250 million people mainly in the tropics. Clinically, the disease can present itself with acute symptoms, a stage which is relatively more common in naive travellers originating from non-endemic regions. It can also develop into chronic disease, with the outcome depending on the Schistosoma species involved, the duration and intensity of infection and several host-related factors. A range of diagnostic tests is available to determine Schistosoma infection, including microscopy, antibody detection, antigen detection using the Point-Of-Care Circulating Cathodic Antigen (POC-CCA) test and the Up-Converting Particle Lateral Flow Circulating Anodic Antigen (UCP-LF CAA) test, as well as Nucleic Acid Amplification Tests (NAATs) such as real-time PCR. In this mini review, we discuss these different diagnostic procedures and explore their most appropriate use in context-specific settings. With regard to endemic settings, diagnostic approaches are described based on their suitability for individual diagnosis, monitoring control programs, determining elimination as a public health problem and eventual interruption of transmission. For non-endemic settings, we summarize the most suitable diagnostic approaches for imported cases, either acute or chronic. Additionally, diagnostic options for disease-specific clinical presentations such as genital schistosomiasis and neuro-schistosomiasis are included. Finally, the specific role of diagnostic tests within research settings is described, including a controlled human schistosomiasis infection model and several clinical studies. In conclusion, context-specific settings have different requirements for a diagnostic test, stressing the importance of a well-considered decision of the most suitable diagnostic procedure.