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Lancet (London, England) Sep 2006Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus Schistosoma. The transmission cycle requires contamination of surface water by excreta,... (Review)
Review
Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus Schistosoma. The transmission cycle requires contamination of surface water by excreta, specific freshwater snails as intermediate hosts, and human water contact. The main disease-causing species are S haematobium, S mansoni, and S japonicum. According to WHO, 200 million people are infected worldwide, leading to the loss of 1.53 million disability-adjusted life years, although these figures need revision. Schistosomiasis is characterised by focal epidemiology and overdispersed population distribution, with higher infection rates in children than in adults. Complex immune mechanisms lead to the slow acquisition of immune resistance, though innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is mostly seen in travellers after primary infection. Chronic schistosomal disease affects mainly individuals with long-standing infections in poor rural areas. Immunopathological reactions against schistosome eggs trapped in the tissues lead to inflammatory and obstructive disease in the urinary system (S haematobium) or intestinal disease, hepatosplenic inflammation, and liver fibrosis (S mansoni, S japonicum). The diagnostic standard is microscopic demonstration of eggs in the excreta. Praziquantel is the drug treatment of choice. Vaccines are not yet available. Great advances have been made in the control of the disease through population-based chemotherapy but these required political commitment and strong health systems.
Topics: Animals; Anthelmintics; Female; Humans; Male; Praziquantel; Schistosoma; Schistosomiasis
PubMed: 16997665
DOI: 10.1016/S0140-6736(06)69440-3 -
Seminars in Immunopathology Jun 2020Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other... (Review)
Review
Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other mammalian) water contact with surface water contaminated by faeces or urine, as well as specific freshwater snails acting as intermediate hosts. The main disease-causing species are S. haematobium, S. mansoni and S. japonicum. According to the World Health Organisation, over 250 million people are infected worldwide, leading to considerable morbidity and the estimated loss of 1.9 million disability-adjusted life years (DALYs), a likely underestimated figure. Schistosomiasis is characterised by focal epidemiology and an over-dispersed population distribution, with higher infection rates in children. Complex immune mechanisms lead to the slow acquisition of immune resistance, but innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is most evident in travellers following a primary infection. Chronic schistosomiasis affects mainly individuals with long-standing infections residing in poor rural areas. Immunopathological reactions against schistosome eggs trapped in host tissues lead to inflammatory and obstructive disease in the urinary system (S. haematobium) or intestinal disease, hepatosplenic inflammation and liver fibrosis (S. mansoni and S. japonicum). An effective drug-praziquantel-is available for treatment but, despite intensive efforts, no schistosomiasis vaccines have yet been accepted for public use. In this review, we briefly introduce the schistosome parasites and the immunopathogenic manifestations resulting from schistosomiasis. We then explore aspects of the immunology and host-parasite interplay in schistosome infections paying special attention to the current status of schistosomiasis vaccine development highlighting the advancement of a new controlled human challenge infection model for testing schistosomiasis vaccines.
Topics: Animals; Anthelmintics; Child; Humans; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis; Vaccines
PubMed: 32076812
DOI: 10.1007/s00281-020-00789-x -
Trends in Parasitology Dec 2022Intravascular schistosomes may control immune and hemostatic responses by regulating the nature and amount of selected host purinergic signaling molecules - such as... (Review)
Review
Intravascular schistosomes may control immune and hemostatic responses by regulating the nature and amount of selected host purinergic signaling molecules - such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and nicotinamide adenine dinucleotide (NAD) - surrounding them. Such metabolites are collectively known as the worm's 'purinergic halo'. Host-interactive, membrane-bound, tegumental ectonucleotidases, notably SmATPDase1, SmNPP5, SmAP and SmNACE, can degrade proinflammatory, prothrombotic and immunomodulatory purinergic metabolites like those listed. A common catabolic product is the anti-inflammatory metabolite adenosine that can additionally be taken in by the worms as food. We envision the tegumental ectonucleotidases as having a twofold role at the worm surface: first, they degrade potentially harmful host signaling molecules, and second, they generate vital nutrients around the worms from where these can be conveniently imported.
Topics: Animals; Schistosoma mansoni
PubMed: 36182536
DOI: 10.1016/j.pt.2022.09.001 -
PLoS Pathogens Dec 2021Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to... (Review)
Review
Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to dampen host immune responses are described in this review. Adult worms express a collection of host-interactive tegumental ectoenzymes that can cleave host signaling molecules such as the "alarmin" ATP (cleaved by SmATPDase1), the platelet activator ADP (SmATPDase1, SmNPP5), and can convert AMP into the anti-inflammatory mediator adenosine (SmAP). SmAP can additionally cleave the lipid immunomodulator sphingosine-1-phosphate and the proinflammatory anionic polymer, polyP. In addition, the worms release a barrage of proteins (e.g., SmCB1, SjHSP70, cyclophilin A) that can impinge on immune cell function. Parasite eggs also release their own immunoregulatory proteins (e.g., IPSE/α1, omega1, SmCKBP) as do invasive cercariae (e.g., Sm16, Sj16). Some schistosome glycans (e.g., LNFPIII, LNnT) and lipids (e.g., Lyso-PS, LPC), produced by several life stages, likewise affect immune cell responses. The parasites not only produce eicosanoids (e.g., PGE2, PGD2-that can be anti-inflammatory) but can also induce host cells to release these metabolites. Finally, the worms release extracellular vesicles (EVs) containing microRNAs, and these too have been shown to skew host cell metabolism. Thus, schistosomes employ an array of biomolecules-protein, lipid, glycan, nucleic acid, and more, to bend host biochemistry to their liking. Many of the listed molecules have been individually shown capable of inducing aspects of the polarized Th2 response seen following infection (with the generation of regulatory T cells (Tregs), regulatory B cells (Bregs) and anti-inflammatory, alternatively activated (M2) macrophages). Precisely how host cells integrate the impact of these myriad parasite products following natural infection is not known. Several of the schistosome immunomodulators described here are in development as novel therapeutics against autoimmune, inflammatory, and other, nonparasitic, diseases.
Topics: Animals; Helminth Proteins; Humans; Immunologic Factors; Schistosoma; Schistosomiasis
PubMed: 34969052
DOI: 10.1371/journal.ppat.1010064 -
Brain Pathology (Zurich, Switzerland) Jan 1997Schistosomiasis is an infection caused by digenetic trematode platyhelminths of the genus Schistosoma. These blood flukes use man and other mammals as definitive hosts... (Review)
Review
Schistosomiasis is an infection caused by digenetic trematode platyhelminths of the genus Schistosoma. These blood flukes use man and other mammals as definitive hosts and aquatic and amphibious snails as intermediate hosts. Of the schistosomal species, S. mansoni, S haematobium and S. japonicum are the most important to man and the most widely distributed. The infection affects about 200 million individuals in 74 countries of Latin America, Africa and Asia. Far less commonly, schistosomes reach the central nervous system (CNS). This may occur at any time from the moment the worms have matured and the eggs have been laid. For this reason, CNS involvement may be observed with any of the clinical forms of schistosomal infection. The presence of eggs in the CNS induces a cell-mediated periovular granulomatous reaction. When eggs reach the CNS during the early stages of the infection or during evolution of the disease to its chronic forms, large necrotic-exudative granulomas are found. In-situ egg deposition following the anomalous migration of adult worms appears to be the main, if not the only, mechanism by which Schistosoma may reach the CNS in these stages. The mass effect produced by the heavy concentration of eggs and the presence of large granulomas in circumscribed areas of the brain and spinal cord explains, respectively, 1) the signs and symptoms of increased intracranial pressure and focal neurological signs; and 2) the signs and symptoms of rapidly progressing transverse myelitis, usually affecting the lumbosacral segments of the spinal cord. Most of the cases of CNS involvement associated with the hepatosplenic and cardiopulmonary chronic forms, or with severe urinary schistosomiasis, though more frequent, are asymptomatic. In the patients with these clinical forms, the random and sparse distribution of eggs in the CNS indicates that the embolization of eggs from the portal mesenteric system to the brain and spinal cord constitutes the main route of CNS invasion by Schistosoma. The discrete inflammatory reaction elicited by the sparsely distributed eggs in the CNS explains the lack of neurological symptoms that could be produced by egg deposition.
Topics: Animals; Brain Diseases; Host-Parasite Interactions; Humans; Schistosoma; Schistosomiasis; Spinal Cord Diseases
PubMed: 9034571
DOI: 10.1111/j.1750-3639.1997.tb01080.x -
PLoS Neglected Tropical Diseases Apr 2020Schistosomes are parasitic blood flukes that infect >200 million people around the world. Free-swimming larval stages penetrate the skin, invade a blood vessel, and... (Review)
Review
Schistosomes are parasitic blood flukes that infect >200 million people around the world. Free-swimming larval stages penetrate the skin, invade a blood vessel, and migrate through the heart and lungs to the vasculature of the liver, where maturation and mating occurs. From here, the parasite couples migrate to their preferred egg laying sites. Here, we compare and contrast what is known about the migration patterns within the definitive host of the three major species of human schistosome: Schistosoma mansoni, S. japonicum, and S. haematobium. We conclude that intravascular schistosomes are inexorable colonizers whose migration and egg laying strategy is profligate; all three species (and their eggs) can be found throughout the mesenteric venules, the rectal venous plexus, and, to a greater or lesser extent, the urogenital venous plexuses. In addition, it is common for parasite eggs to be deposited in locations that lack easy access to the exterior, further demonstrating the relentless exploratory nature of these intravascular worms.
Topics: Animals; Blood Vessels; Humans; Life Cycle Stages; Locomotion; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis haematobia; Schistosomiasis japonica; Schistosomiasis mansoni
PubMed: 32240157
DOI: 10.1371/journal.pntd.0007951 -
International Journal For Parasitology.... Aug 2020Ion channels underlie electrical excitability in cells and are essential for a variety of functions, most notably neuromuscular and sensory activity. They are also... (Review)
Review
Ion channels underlie electrical excitability in cells and are essential for a variety of functions, most notably neuromuscular and sensory activity. They are also validated targets for a preponderance of approved anthelmintic compounds. Transient receptor potential (TRP) channels constitute an ion channel superfamily whose members play important roles in sensory signaling, regulation of ion homeostasis, organellar trafficking, and other key cellular and organismal activities. Unlike most other ion channels, TRP channels are often polymodal, gated by a variety of mechanisms. Furthermore, TRP channels fall into several classes or subtypes based on sequence and structure. Until recently, there had been very little investigation of the properties and functions of TRP channels from parasitic helminths, including schistosomes, but that situation has changed in the past few years. Indeed, it is now clear that at least some schistosome TRP channels exhibit unusual pharmacological properties, and, intriguingly, both a mammalian and a schistosome TRP channel are activated by praziquantel, the current antischistosomal drug of choice. With the latest release of the Schistosoma mansoni genome database, several changes in predicted TRP channel sequences appeared, some of which were significant. This review updates and reassesses the TRP channel repertoire in S. mansoni, examines recent findings regarding these potential therapeutic targets, and provides guideposts for some of the physiological functions that may be mediated by these channels in schistosomes.
Topics: Animals; Anthelmintics; Genes, Helminth; Genome, Helminth; Humans; Ion Channels; Phylogeny; Praziquantel; Schistosoma; Schistosoma mansoni; Schistosomiasis; TRPA1 Cation Channel; TRPV Cation Channels; Transient Receptor Potential Channels
PubMed: 32250774
DOI: 10.1016/j.ijpddr.2020.02.002 -
Molecular and Biochemical Parasitology Oct 2019Nuclear receptors (NRs) belong to a large protein superfamily which includes intracellular receptors for secreted hydrophobic signal molecules, such as steroid hormones... (Review)
Review
Nuclear receptors (NRs) belong to a large protein superfamily which includes intracellular receptors for secreted hydrophobic signal molecules, such as steroid hormones and thyroid hormones. They regulate development and reproduction in metazoans by binding to the promoter region of their target gene to activate or repress mRNA synthesis. Isolation and characterization of NRs in the parasitic trematode Schistosoma mansoni identified two homologues of mammalian thyroid receptor (TR). This was the first known protostome exhibiting TR homologues. Three novel NRs each possess a novel set of two DNA binding domains (DBD) in tandem with a ligand binding domain (LBD) (2DBD-NRs) isolated in Schistosoma mansoni revealed a novel NR modular structure: A/B-DBD-DBD-hinge-LBD. Full length cDNA of several NRs have been isolated and studied in the parasitic trematodes S. mansoni, S. japonicum and in the cestode Echinococcus multilocularis. The genome of the blood flukes S. mansoni, S. japonicum and S. haematobium, the liver fluke Clonorchis sinensis and the cestode Echinococcus multilocularis have been sequenced. Study of the NR complement in parasitic Platyhelminths will help us to understand the role of NRs in regulation of their development and understand the evolution of NR in animals.
Topics: Animals; Clonorchis sinensis; Echinococcus multilocularis; Evolution, Molecular; Helminth Proteins; Phylogeny; Platyhelminths; Receptors, Cytoplasmic and Nuclear; Schistosoma; Schistosoma mansoni
PubMed: 31470045
DOI: 10.1016/j.molbiopara.2019.111218 -
Frontiers in Immunology 2020Human schistosomes combat the unique immune systems of two vastly different hosts during their indirect life cycles. In gastropod molluscs, they face a potent innate... (Review)
Review
Human schistosomes combat the unique immune systems of two vastly different hosts during their indirect life cycles. In gastropod molluscs, they face a potent innate immune response composed of variable immune recognition molecules and highly phagocytic hemocytes. In humans, a wide variety of innate and adaptive immune processes exist in proximity to these parasites throughout their lifespan. To survive and thrive as the second most common parasitic disease in humans, schistosomes have evolved many techniques to avoid and combat these targeted host responses. Among these techniques are molecular mimicry of host antigens, the utilization of an immune resistant outer tegument, the secretion of several potent proteases, and targeted release of specific immunomodulatory factors affecting immune cell functions. This review seeks to describe these key immune evasion mechanisms, among others, which schistosomes use to survive in both of their hosts. After diving into foundational observational studies of the processes mediating the establishment of schistosome infections, more recent transcriptomic and proteomic studies revealing crucial components of the host/parasite molecular interface are discussed. In order to combat this debilitating and lethal disease, a comprehensive understanding of schistosome immune evasion strategies is necessary for the development of novel therapeutics and treatment plans, necessitating the discussion of the numerous ways in which these parasitic flatworms overcome the immune responses of both hosts.
Topics: Adaptive Immunity; Animals; Gastropoda; Host-Parasite Interactions; Humans; Immunity, Innate; Immunomodulation; Life Cycle Stages; Lung; Molecular Mimicry; Mucins; Oocysts; Proteome; Schistosoma; Schistosomiasis mansoni; Transcriptome
PubMed: 33613562
DOI: 10.3389/fimmu.2020.624178 -
Trends in Parasitology Sep 2021Schistosomes cause one of the most devastating neglected tropical diseases, schistosomiasis. Their transmission is accomplished through a complex life cycle with two... (Review)
Review
Schistosomes cause one of the most devastating neglected tropical diseases, schistosomiasis. Their transmission is accomplished through a complex life cycle with two obligate hosts and requires multiple radically different body plans specialized for infecting and reproducing in each host. Recent single-cell transcriptomic studies on several schistosome body plans provide a comprehensive map of their cell types, which include stem cells and their differentiated progeny along an intricate developmental hierarchy. This progress not only extends our understanding of the basic biology of the schistosome life cycle but can also inform new therapeutic and preventive strategies against the disease, as blocking the development of specific cell types through genetic manipulations has shown promise in inhibiting parasite survival, growth, and reproduction.
Topics: Animals; Host-Parasite Interactions; Humans; Life Cycle Stages; Schistosoma; Schistosomiasis; Stem Cells; Transcriptome
PubMed: 33893056
DOI: 10.1016/j.pt.2021.03.005