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Biomolecules Feb 2020Infections caused by and are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that... (Review)
Review
Infections caused by and are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that might be considered as initiators of infection-associated carcinogenesis. Chemotherapy for these helminthic infections relies on a single drug, praziquantel, (PZQ) that mainly targets the parasite. Additionally, PZQ has some major drawbacks as inefficacy against juvenile form and alone it is not capable to counteract pathologies associated to infections or prevent carcinogenesis. There is an urgent need to develop novel therapeutic approaches that not only target the parasite but also improve the pathologies associated to infection, and ultimately, counteract or/and prevent the carcinogenesis processes. Repurposing the drug in combination of compounds with different modes of action is a promising strategy to find novel therapeutics approaches against these helminthic infections and its pathologies. Here, we emphasized that using antioxidants either alone or combined with anthelmintic drugs could ameliorate tissue damage, infection-associated complications, moreover, could prevent the development of cancer associated to infections. Hence, antioxidants represent a potential adjuvant approach during treatment to reduce morbidity and mortality. Despite the success of some strategies, there is a long way to go to implement novel therapies for schistosomiasis.
Topics: Animals; Anthelmintics; Antioxidants; Drug Discovery; Drug Repositioning; Drug Therapy, Combination; Humans; Neoplasms; Opisthorchiasis; Opisthorchis; Praziquantel; Schistosoma; Schistosomiasis
PubMed: 32106428
DOI: 10.3390/biom10030350 -
Parasites & Vectors Apr 2023The use of applications involving single nucleotide polymorphisms (SNPs) has greatly increased since the beginning of the 2000s, with the number of associated techniques...
A duplex tetra-primer ARMS-PCR assay to discriminate three species of the Schistosoma haematobium group: Schistosoma curassoni, S. bovis, S. haematobium and their hybrids.
BACKGROUND
The use of applications involving single nucleotide polymorphisms (SNPs) has greatly increased since the beginning of the 2000s, with the number of associated techniques expanding rapidly in the field of molecular research. Tetra-primer amplification refractory mutation system-PCR (T-ARMS-PCR) is one such technique involving SNP genotyping. It has the advantage of amplifying multiple alleles in a single reaction with the inclusion of an internal molecular control. We report here the development of a rapid, reliable and cost-effective duplex T-ARMS-PCR assay to distinguish between three Schistosoma species, namely Schistosoma haematobium (human parasite), Schistosoma bovis and Schistosoma curassoni (animal parasites), and their hybrids. This technique will facilitate studies of population genetics and the evolution of introgression events.
METHODS
During the development of the technique we focused on one of the five inter-species internal transcribed spacer (ITS) SNPs and one of the inter-species 18S SNPs which, when combined, discriminate between all three Schistosoma species and their hybrid forms. We designed T-ARMS-PCR primers to amplify amplicons of specific lengths for each species, which in turn can then be visualized on an electrophoresis gel. This was further tested using laboratory and field-collected adult worms and field-collected larval stages (miracidia) from Spain, Egypt, Mali, Senegal and Ivory Coast. The combined duplex T-ARMS-PCR and ITS + 18S primer set was then used to differentiate the three species in a single reaction.
RESULTS
The T-ARMS-PCR assay was able to detect DNA from both species being analysed at the maximum and minimum levels in the DNA ratios (95/5) tested. The duplex T-ARMS-PCR assay was also able to detect all hybrids tested and was validated by sequencing the ITS and the 18S amplicons of 148 of the field samples included in the study.
CONCLUSIONS
The duplex tetra-primer ARMS-PCR assay described here can be applied to differentiate between Schistosoma species and their hybrid forms that infect humans and animals, thereby providing a method to investigate the epidemiology of these species in endemic areas. The addition of several markers in a single reaction saves considerable time and is of long-standing interest for investigating genetic populations.
Topics: Animals; Adult; Humans; Schistosoma haematobium; Schistosoma; Polymerase Chain Reaction; DNA; Mutation; Senegal
PubMed: 37029440
DOI: 10.1186/s13071-023-05754-9 -
Frontiers in Immunology 2020The hygiene hypothesis states that improved hygiene and the resulting disappearance of once endemic diseases is at the origin of the enormous increase in immune related... (Review)
Review
The hygiene hypothesis states that improved hygiene and the resulting disappearance of once endemic diseases is at the origin of the enormous increase in immune related disorders such as autoimmune diseases seen in the industrialized world. Helminths, such as , are thought to provide protection against the development of autoimmune diseases by regulating the host's immune response. This modulation primarily involves induction of regulatory immune responses, such as generation of tolerogenic dendritic cells and alternatively activated macrophages. This points toward the potential of employing helminths or their products/metabolites as therapeutics for autoimmune diseases that are characterized by an excessive inflammatory state, such as multiple sclerosis (MS), type I diabetes (T1D) and inflammatory bowel disease (IBD). In this review, we examine the known mechanisms of immune modulation by , explore preclinical and clinical studies that investigated the use of an array helminthic products in these diseases, and propose that helminthic therapy opens opportunities in the treatment of chronic inflammatory disorders.
Topics: Animals; Antigens, Helminth; Autoimmune Diseases; Humans; Immunotherapy; Schistosoma mansoni; Therapy with Helminths
PubMed: 32903582
DOI: 10.3389/fimmu.2020.01821 -
Critical review of methods for isothermal amplification of nucleic acids for environmental analysis.Journal of Microbiological Methods Dec 2020The past 30 years have seen the emergence and proliferation of isothermal amplification methods (IAMs) for rapid, sensitive detection and quantification of nucleic... (Review)
Review
The past 30 years have seen the emergence and proliferation of isothermal amplification methods (IAMs) for rapid, sensitive detection and quantification of nucleic acids in a variety of sample types. These methods share dependence on primers and probes with quantitative PCR, but they differ in the specific enzymes and instruments employed, and are frequently conducted in a binary, rather than quantitative format. IAMs typically rely on simpler instruments than PCR analyses due to the maintenance of a single temperature throughout the amplification reaction, which could facilitate deployment of IAMs in a variety of environmental and field settings. This review summarizes the mechanisms of the most common IAM methods and their use in studies of pathogens, harmful algae and fecal indicators in environmental waters, feces, wastewater, reclaimed water, and tissues of aquatic animals. Performance metrics of sensitivity, specificity and limit of detection are highlighted, and the potential for use in monitoring and regulatory contexts is discussed.
Topics: Animals; Bacteria; DNA Primers; Environmental Monitoring; Harmful Algal Bloom; Nucleic Acid Amplification Techniques; Nucleic Acids; Real-Time Polymerase Chain Reaction; Schistosoma; Wastewater; Water Microbiology
PubMed: 33159993
DOI: 10.1016/j.mimet.2020.106099 -
Frontiers in Cellular and Infection... 2021Schistosomiasis (Bilharziasis), a neglected tropical disease that affects more than 240 million people around the world, is caused by infection with the helminth... (Review)
Review
Schistosomiasis (Bilharziasis), a neglected tropical disease that affects more than 240 million people around the world, is caused by infection with the helminth parasite . As part of their secretome, schistosomes release extracellular vesicles (EVs) that modulate the host immune response. The EV-harbored miRNAs upregulate the innate immune response of the M1 pathway and downregulate the differentiation toward the adaptive Th2 immunity. A schistosomal egg-derived miRNA increases the percentage of regulatory T cells. This schistosomal-inducible immunoediting process generates ultimately a parasitic friendly environment that is applied carefully as restrained Th2 response is crucial for the host survival and successful excretion of the eggs. Evidence indicates a selective targeting of schistosomal EVs, however, the underlying mechanisms are unclear yet. The effects of the schistosomes on the host immune system is in accordance with the hygiene hypothesis, attributing the dramatic increase in recent decades in allergy and other diseases associated with imbalanced immune response, to the reduced exposure to infectious agents that co-evolved with humans during evolution. Deciphering the bioactive cargo, function, and selective targeting of the parasite-secreted EVs may facilitate the development of novel tools for diagnostics and delivered therapy to schistosomiasis, as well as to immune-associated disorders.
Topics: Animals; Extracellular Vesicles; Humans; Immunity; MicroRNAs; Schistosoma; Schistosomiasis
PubMed: 33869080
DOI: 10.3389/fcimb.2021.649480 -
The Lancet. Planetary Health Jul 2020Agrochemical pollution of surface waters is a growing global environmental challenge, especially in areas where agriculture is rapidly expanding and intensifying.... (Review)
Review
BACKGROUND
Agrochemical pollution of surface waters is a growing global environmental challenge, especially in areas where agriculture is rapidly expanding and intensifying. Agrochemicals might affect schistosomiasis transmission through direct and indirect effects on Schistosoma parasites, their intermediate snail hosts, snail predators, and snail algal resources. We aimed to review and summarise the effects of these agrochemicals on schistosomiasis transmission dynamics.
METHODS
We did a systematic review of agrochemical effects on the lifecycle of Schistosoma spp and fitted dose-response models to data regarding the association between components of the lifecycle and agrochemical concentrations. We incorporated these dose-response functions and environmentally relevant concentrations of agrochemicals into a mathematical model to estimate agrochemical effects on schistosomiasis transmission. Dose-response functions were used to estimate individual agrochemical effects on estimates of the agrochemically influenced basic reproduction number, R, for Schistosoma haematobium. We incorporated time series of environmentally relevant agrochemical concentrations into the model and simulated mass drug administration control efforts in the presence of agrochemicals.
FINDINGS
We derived 120 dose-response functions describing the effects of agrochemicals on schistosome lifecycle components. The median estimate of the basic reproduction number under agrochemical-free conditions, was 1·65 (IQR 1·47-1·79). Agrochemical effects on estimates of R for S haematobium ranged from a median three-times increase (R 5·05, IQR 4·06-5·97) to transmission elimination (R 0). Simulations of transmission dynamics subject to interacting annual mass drug administration and agrochemical pollution yielded a median estimate of 64·82 disability-adjusted life-years (DALYs) lost per 100 000 people per year (IQR 62·52-67·68) attributable to atrazine use. In areas where aquatic arthropod predators of intermediate host snails suppress transmission, the insecticides chlorpyrifos (6·82 DALYs lost per 100 000 people per year, IQR 4·13-8·69) and profenofos (103·06 DALYs lost per 100 000 people per year, IQR 89·63-104·90) might also increase the disability burden through their toxic effects on arthropods.
INTERPRETATION
Expected environmental concentrations of agrochemicals alter schistosomiasis transmission through direct and indirect effects on intermediate host and parasite densities. As industrial agricultural practices expand in areas where schistosomiasis is endemic, strategies to prevent increases in transmission due to agrochemical pollution should be developed and pursued.
FUNDING
National Science Foundation, National Institutes of Health.
Topics: Agrochemicals; Animals; Environmental Pollutants; Environmental Pollution; Food Chain; Host-Parasite Interactions; Humans; Schistosoma; Schistosomiasis
PubMed: 32681899
DOI: 10.1016/S2542-5196(20)30105-4 -
PloS One 2023Traditional diagnostic tests for schistosome infections are suboptimal, particularly when the parasite burden is low. In the present review we sought to identify...
Diagnostic performances of Schistosoma haematobium and Schistosoma mansoni recombinant proteins, peptides and chimeric proteins antibody based tests. Systematic scoping review.
BACKGROUND
Traditional diagnostic tests for schistosome infections are suboptimal, particularly when the parasite burden is low. In the present review we sought to identify recombinant proteins, peptides, and chimeric proteins with potential to be used as sensitive and specific diagnostic tools for schistosomiasis.
METHODS
The review was guided by PRISMA-ScR guidelines, Arksey and O'Malley's framework, and guidelines from the Joanna Briggs Institute. Five databases were searched: Cochrane library, PubMed, EMBASE, PsycInfo and CINAHL, alongside preprints. Identified literature were assessed by two reviewers for inclusion. A narrative summary was used to interpret the tabulated results.
RESULTS
Diagnostic performances were reported as specificities, sensitivities, and AUC. The AUC for S. haematobium recombinant antigens ranged from 0.65 to 0.98, and 0.69 to 0.96 for urine IgG ELISA. S. mansoni recombinant antigens had sensitivities ranging from 65.3% to 100% and specificities ranging from 57.4% to 100%. Except for 4 peptides which had poor diagnostic performances, most peptides had sensitivities ranging from 67.71% to 96.15% and specificities ranging from 69.23% to 100%. S. mansoni chimeric protein was reported to have a sensitivity of 86.8% and a specificity of 94.2%.
CONCLUSION
The tetraspanin CD63 antigen had the best diagnostic performance for S. haematobium. The tetraspanin CD63 antigen Serum IgG POC-ICTs had a sensitivity of 89% and a specificity of 100%. Peptide Smp_150390.1 (216-230) serum based IgG ELISA had the best diagnostic performance for S. mansoni with a sensitivity of 96.15% and a specificity of 100%. Peptides were reported to demonstrate good to excellent diagnostic performances. S. mansoni multi-peptide chimeric protein further improved the diagnostic accuracy of synthetic peptides. Together with the advantages associated with urine sampling technique, we recommend development of multi-peptide chimeric proteins urine based point of care tools.
Topics: Animals; Schistosoma haematobium; Schistosoma mansoni; Tetraspanin 30; Peptides; Blood Group Antigens; Recombinant Proteins; Recombinant Fusion Proteins; Immunoglobulin G
PubMed: 36862712
DOI: 10.1371/journal.pone.0282233 -
ACS Infectious Diseases May 2023In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the... (Review)
Review
In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and challenges associated with treating schistosomiasis. The aim of this meeting was to discuss the need for new treatments in view of the clinical situation and to ascertain what the key requirements would be for any potential new anti-schistosomals. This information will be essential to inform ongoing drug discovery efforts for schistosomiasis. We also discussed the potential drug discovery pathway and associated criteria for progressing compounds to the clinic. To date, praziquantel (PZQ) is the only drug available to treat all species causing schistosomiasis, but it is often unable to completely clear parasites from an infected patient, partially due to its inactivity against juvenile worms. PZQ-mediated mass drug administration campaigns conducted in endemic areas (e.g., sub-Saharan Africa, where schistosomiasis is primarily prevalent) have contributed to reducing the burden of disease but will not eliminate the disease as a public health problem. The potential for to develop resistance towards PZQ, as the sole treatment available, could become a concern. Consequently, new anthelmintic medications are urgently needed, and this Perspective aims to capture some of the learnings from our discussions on the key criteria for new treatments.
Topics: Animals; London; Schistosomiasis; Praziquantel; Anthelmintics; Schistosoma
PubMed: 37083395
DOI: 10.1021/acsinfecdis.3c00081 -
Acta Tropica Feb 2023Schistosomiasis, an ancient and neglected tropical disease, which poses a huge threat to over 200 million people globally. It is necessary to have a general summary of...
BACKGROUND
Schistosomiasis, an ancient and neglected tropical disease, which poses a huge threat to over 200 million people globally. It is necessary to have a general summary of schistosomiasis research after the new roadmap 2021-2030 issued by WHO. This study analyzes the current status of schistosomiasis research from the perspective of the One Health concept by analyzing important research literature published from 2011 to 2020, while further highlighting research priorities, difficulties, and research directions in order to propose suggestions for tropical disease studies research.
METHODS
Published literature related to schistosomiasis was searched from the Web of Science Core Collection (WoSCC) database. Focusing on a visual analysis of the main research literature in the field of schistosomiasis, CiteSpace software was used to conduct co-occurrence analysis with keywords, countries, institutions, and authors. Moreover, clustering and burst analyses of keywords and co-citation analysis of authors, publications, and journals were performed.
RESULTS
A total of 6638 schistosomiasis-related articles were published from 2011 to 2020, all of which can be sourced from the WoSCC database. The publication of schistosomiasis research has remained stable over the past 10 years, and contains studies in the area of human epidemiology, animal surveillance and the environment. The top five high-frequency keywords included Schistosoma mansoni, schistosomiasis, infection, praziquantel, and Schistosoma japonicum. The keywords formed nine clusters, including praziquantel, epidemiology, Schistosoma japonicum, helminths, protein, diagnosis, schistosomiasis, response, and haematobium. In recent years, most research studies focused on the mechanism of liver fibrosis, eliminating schistosomiasis, controlling risk factors, and the relationship between schistosomiasis infection and host immunity. The most productive countries include the United States, China, and Brazil, and the most productive institutions are the University of Basel, the Swiss Tropical and Public Health Institute, and the University of São Paulo. Highly productive authors include Jürg Utzinger and Donald P. McManus. At the time of writing, the author with the highest co-citation frequency (993 times) was Peter Hotez, and the journal with the highest co-citation frequency (3,720 times) was PLoS Neglected Tropical Diseases. Human schistosomiasis, published by Colley et al. (2014), was the most frequently co-cited publication (494 times).
CONCLUSIONS
This study provides a preliminary description of the current status of schistosomiasis research and an initial exploration of future research directions. The One Health concept was applied in the field of schistosomiasis control, as confirmed by this bibliometric analysis. Our study provides guidance for the development of research on schistosomiasis and other neglected tropical diseases.
Topics: Animals; Humans; United States; Praziquantel; Retrospective Studies; Schistosomiasis; Bibliometrics; Schistosoma japonicum; Neglected Diseases
PubMed: 36372254
DOI: 10.1016/j.actatropica.2022.106750 -
International Journal For Parasitology.... Aug 2020Human schistosomiasis is a disease which globally affects over 229 million people. Three major species affecting humans are Schistosoma mansoni, S. haematobium and S....
Human schistosomiasis is a disease which globally affects over 229 million people. Three major species affecting humans are Schistosoma mansoni, S. haematobium and S. japonicum. Previous treatment of S. mansoni includes the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The OXA activating enzyme was identified and crystallized, as being a S. mansoni sulfotransferase (SmSULT). S. haematobium and S. japonicum possess homologs of SmSULT (ShSULT and SjSULT) begging the question; why does oxamniquine fail to kill S. haematobium and S. japonicum adult worms? Investigation of the molecular structures of the sulfotransferases indicates that structural differences, specifically in OXA contact residues, do not abrogate OXA binding in the active sites as previously hypothesized. Data presented argue that the ability of SULTs to sulfate and thus activate OXA and its derivatives is linked to the ability of OXA to fit in the binding pocket to allow the transfer of a sulfur group.
Topics: Animals; Molecular Structure; Oxamniquine; Schistosoma; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomicides; Sulfotransferases
PubMed: 32315953
DOI: 10.1016/j.ijpddr.2020.04.001