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PLoS Neglected Tropical Diseases Mar 2021Most of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular transmission monitoring. However, the Kato-Katz technique has shown low sensitivity for the detection of light-intensity infections, and therefore highly sensitive diagnostic tools are urgently required to monitor prevalence of infection in low transmission settings. The objective of this systematic review was to evaluate and synthesize the performance of diagnostic tests for detecting Schistosoma japonicum and S. mekongi infection in people living in endemic areas.
METHODOLOGY/PRINCIPAL FINDINGS
We comprehensively searched these nine electronic databases and other resources until July 2019, with no language or publication limits: PubMed, EMBASE, MEDLINE, Web of Science, BIOSIS Citation Index, HTA, CINAHL PLUS, The Cochrane Library, and PsycINFO. We included original studies that assessed diagnostic performance using antibody, antigen, and molecular tests with stool examination test as a reference standard. Two reviewers independently extracted a standard set of data and assessed study quality. We estimated the pooled estimates of sensitivity and specificity for each index test. We used diagnostic odds ratio to determine the overall accuracy and hierarchical summary receiver operating characteristics (HSROC) curve to assess the index tests performance. Fifteen studies (S. japonicum [n = 13] and S. mekongi [n = 2]) testing 15,303 participants were included in the review. Five studies reported performance of enzyme-linked immunosorbent assay (ELISA), seven studies reported indirect hemagglutination assay (IHA), and four studies reported polymerase chain reaction (PCR) for detecting S. japonicum. The pooled sensitivity and specificity were 0.93 (95% CI: 0.84-0.98) and 0.40 (95% CI: 0.29-0.53) for ELISA, 0.97 (95% CI: 0.90-0.99) and 0.66 (95% CI: 0.58-0.73) for IHA, and 0.89 (95% CI: 0.71-0.96) and 0.49 (95% CI: 0.29-0.69) for PCR respectively. A global summary indicated the best performance for IHA, closely followed by ELISA. We were unable to perform meta-analysis for S. mekongi due to insufficient number of studies.
CONCLUSIONS/SIGNIFICANCE
IHA showed the highest detection accuracy for S. japonicum. Further studies are needed to determine the suitable diagnostic methods to verify the absence of transmission of S. mekongi and also to compare detection accuracy against more sensitive reference standards such as PCR.
Topics: Animals; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Polymerase Chain Reaction; Schistosoma; Schistosoma japonicum
PubMed: 33730048
DOI: 10.1371/journal.pntd.0009244 -
Infectious Diseases of Poverty Jan 2022Schistosomiasis remains an important public health problem, also among adults, and infected individuals not treated serve as a reservoir for continued transmission....
Prevalence of Schistosoma mono- and co-infections with multiple common parasites and associated risk factors and morbidity profile among adults in the Taabo health and demographic surveillance system, South-Central Côte d'Ivoire.
BACKGROUND
Schistosomiasis remains an important public health problem, also among adults, and infected individuals not treated serve as a reservoir for continued transmission. Despite this fact, evidence on the epidemiology of schistosomiasis in adults in Côte d'Ivoire is scanty. This study aimed to determine the prevalence and risk factors of Schistosoma infection and co-infection with other helminth species and Plasmodium among adults in the Taabo region in the south-central part of Côte d'Ivoire.
METHODS
A cross-sectional survey was carried out in April and May 2017 in the frame of the "Côte d'Ivoire Dual Burden of Disease Study" (CoDuBu). A total of 901 randomly selected individuals, aged 18-90 years, provided blood, stool and urine samples for the diagnosis of malaria and helminth infections. Stool samples were subjected to the Kato-Katz technique for detection of Schistosoma mansoni and soil-transmitted helminth eggs, while urine samples were examined for eggs of Schistosoma haematobium and circulating cathodic antigen of S. mansoni. Risk factors and morbidity profiles were assessed using health examination and questionnaires. Multinomial logistic regressions were employed to identify risk factors and morbidity patterns associated with S. mansoni mono- and co-infections.
RESULTS
The prevalence of S. mansoni and S. haematobium was 23.2% and 1.0%, respectively. Most S. mansoni were mono-infections (81.3%). Independent determinants of S. mansoni infection were young age, low socioeconomic status (mono- and co-infection) and poor hygiene practices (co-infection) (P < 0.05). S. mansoni infection was independently associated with higher pain and symptom scores (mono-infection), poor self-rated health and low healthcare use (co-infection) (P < 0.05).
CONCLUSIONS
This study showed that adults represent a substantial reservoir of S. mansoni. To sustain schistosomiasis control and improve people's wellbeing, it is important to expand preventive chemotherapy from school-aged children to adults, coupled with hygiene and health education.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Coinfection; Cote d'Ivoire; Cross-Sectional Studies; Feces; Humans; Middle Aged; Parasites; Prevalence; Risk Factors; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis mansoni; Young Adult
PubMed: 34983662
DOI: 10.1186/s40249-021-00925-1 -
Parasites & Vectors Dec 2022Glutamate carboxypeptidase 2 (GCP2) belongs to the M28B metalloprotease subfamily encompassing a variety of zinc-dependent exopeptidases that can be found in many...
BACKGROUND
Glutamate carboxypeptidase 2 (GCP2) belongs to the M28B metalloprotease subfamily encompassing a variety of zinc-dependent exopeptidases that can be found in many eukaryotes, including unicellular organisms. Limited information exists on the physiological functions of GCP2 orthologs in mammalian tissues outside of the brain and intestine, and such data are completely absent for non-mammalian species. Here, we investigate GCP2 orthologs found in trematodes, not only as putative instrumental molecules for defining their basal function(s) but also as drug targets.
METHODS
Identified genes encoding M28B proteases Schistosoma mansoni and Fasciola hepatica genomes were analyzed and annotated. Homology modeling was used to create three-dimensional models of SmM28B and FhM28B proteins using published X-ray structures as the template. For S. mansoni, RT-qPCR was used to evaluate gene expression profiles, and, by RNAi, we exploited the possible impact of knockdown on the viability of worms. Enzymes from both parasite species were cloned for recombinant expression. Polyclonal antibodies raised against purified recombinant enzymes and RNA probes were used for localization studies in both parasite species.
RESULTS
Single genes encoding M28B metalloproteases were identified in the genomes of S. mansoni and F. hepatica. Homology models revealed the conserved three-dimensional fold as well as the organization of the di-zinc active site. Putative peptidase activities of purified recombinant proteins were assayed using peptidic libraries, yet no specific substrate was identified, pointing towards the likely stringent substrate specificity of the enzymes. The orthologs were found to be localized in reproductive, digestive, nervous, and sensory organs as well as parenchymal cells. Knockdown of gene expression by RNAi silencing revealed that the genes studied were non-essential for trematode survival under laboratory conditions, reflecting similar findings for GCP2 KO mice.
CONCLUSIONS
Our study offers the first insight to our knowledge into M28B protease orthologs found in trematodes. Conservation of their three-dimensional structure, as well as tissue expression pattern, suggests that trematode GCP2 orthologs may have functions similar to their mammalian counterparts and can thus serve as valuable models for future studies aimed at clarifying the physiological role(s) of GCP2 and related subfamily proteases.
Topics: Animals; Mice; Trematoda; Fasciola hepatica; Schistosoma mansoni; Peptide Hydrolases; Mammals
PubMed: 36539882
DOI: 10.1186/s13071-022-05556-5 -
Revista Da Sociedade Brasileira de... 2022Schistosomiasis is a neglected acute and chronic tropical disease caused by intestinal (Schistosoma mansoni and Schistosoma japonicum) and urogenital (Schistosoma... (Review)
Review
Clustered Regularly Interspaced Short Palindromic Repeats/ CRISPR associated protein 9-mediated editing of Schistosoma mansoni genes: Identifying genes for immunologically potent drug and vaccine development.
Schistosomiasis is a neglected acute and chronic tropical disease caused by intestinal (Schistosoma mansoni and Schistosoma japonicum) and urogenital (Schistosoma haematobium) helminth parasites (blood flukes or digenetic trematodes). It afflicts over 250 million people worldwide, the majority of whom reside in impoverished tropical and subtropical regions in sub-Saharan Africa. Schistosomiasis is the second most common devastating parasitic disease in the world after malaria and causes over 200,000 deaths annually. Currently, there is no effective and approved vaccine available for human use, and treatment strongly relies on praziquantel drug therapy, which is ineffective in killing immature larval schistosomula stages and eggs already lodged in the tissues. The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9)-mediated gene editing tool is used to deactivate a gene of interest to scrutinize its role in health and disease, and to identify genes for vaccine and drug targeting. The present review aims to summarize the major findings from the current literature reporting the usage of CRISPR/Cas9-mediated gene editing to inactivate genes in S. mansoni (acetylcholinesterase (AChE), T2 ribonuclease omega-1 (ω1), sulfotransferase oxamniquine resistance protein (SULT-OR), and α-N-acetylgalactosaminidase (SmNAGAL)), and freshwater gastropod snails, Biomphalaria glabrata (allograft inflammatory factor (BgAIF)), an obligatory component of the life cycle of S. mansoni, to identify their roles in the pathogenesis of schistosomiasis, and to highlight the importance of such studies in identifying and developing drugs and vaccines with high therapeutic efficacy.
Topics: Acetylcholinesterase; Animals; CRISPR-Associated Protein 9; Humans; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Vaccine Development
PubMed: 35976333
DOI: 10.1590/0037-8682-0131-2022 -
Trends in Parasitology Aug 2020A precise timeframe to differentiate acute schistosomiasis (AS) and chronic schistosomiasis (CS) is not well defined. Based on recent published literature, lung nodular... (Review)
Review
A precise timeframe to differentiate acute schistosomiasis (AS) and chronic schistosomiasis (CS) is not well defined. Based on recent published literature, lung nodular lesions in AS and CS seem to have the same pathophysiology, that is, eggs laid in situ by adult worms, during an ectopic migration. Moreover, the occurrence of lung nodules due to clusters of eggs and the systemic immunoallergic reaction of AS (Katayama syndrome) may be two separate clinical entities, which may overlap during the early phase of infection. Consequently, the classical distinction between AS and CS loses much of its conceptual validity. If adult worms play a more important role in the early phase of the disease the clinical management of AS should probably be revised.
Topics: Acute Disease; Animals; Chronic Disease; Humans; Schistosoma; Schistosomiasis
PubMed: 32505540
DOI: 10.1016/j.pt.2020.05.009 -
PLoS Neglected Tropical Diseases Mar 2024Schistosomiasis is the second most widespread parasitic disease affecting humans. A key component of today's infection control measures is the diagnosis and monitoring... (Review)
Review
Schistosomiasis is the second most widespread parasitic disease affecting humans. A key component of today's infection control measures is the diagnosis and monitoring of infection, informing individual- and community-level treatment. However, newly acquired infections and/or low parasite burden are still difficult to diagnose reliably. Furthermore, even though the pathological consequence of schistosome egg sequestration in host tissues is well described, the evidence linking egg burden to morbidity is increasingly challenged, making it inadequate for pathology monitoring. In the last decades, omics-based instruments and methods have been developed, adjusted, and applied in parasitic research. In particular, the profiling of the most reliable determinants of phenotypes, metabolites by metabolomics, emerged as a powerful boost in the understanding of basic interactions within the human host during infection. As such, the fine detection of host metabolites produced upon exposure to parasites such as Schistosoma spp. and the ensuing progression of the disease are believed to enable the identification of Schistosoma spp. potential biomarkers of infection and associated pathology. However, attempts to provide such a comprehensive understanding of the alterations of the human metabolome during schistosomiasis are rare, limited in their design when performed, and mostly inconclusive. In this review, we aimed to briefly summarize the most robust advances in knowledge on the changes in host metabolic profile during Schistosoma infections and provide recommendations for approaches to optimize the identification of metabolomic signatures of human schistosomiasis.
Topics: Animals; Humans; Schistosoma; Schistosomiasis; Metabolome; Biomarkers; Morbidity
PubMed: 38512811
DOI: 10.1371/journal.pntd.0012009 -
Frontiers in Immunology 2020Blood flukes of the genus Schistosoma are covered by a protective heptalaminated, double lipid bilayer surface membrane. Large amounts of sphingomyelin (SM) in the outer... (Review)
Review
Blood flukes of the genus Schistosoma are covered by a protective heptalaminated, double lipid bilayer surface membrane. Large amounts of sphingomyelin (SM) in the outer leaflet form with surrounding water molecules a tight hydrogen bond barrier, which allows entry of nutrients and prevents access of host immune effectors. Excessive hydrolysis of SM to phosphoryl choline and ceramide activation of the parasite tegument-associated neutral sphingomyelinase (nSMase) with the polyunsaturated fatty acid, arachidonic acid (ARA) leads to parasite death, allowing exposure of apical membrane antigens to antibody-dependent cell-mediated cytotoxicity (ADCC), and accumulation of the pro-apoptotic ceramide. Surface membrane nSMase represents, thus, a worm Achilles heel, and ARA a valid schistosomicide. Several experiments conducted using larval, juvenile, and adult and documented ARA schistosomicidal potential. Arachidonic acid schistosomicidal action was shown to be safe and efficacious in mice and hamsters infected with and , respectively, and in children with light infection. A combination of praziquantel and ARA led to outstanding cure rates in children with heavy infection. Additionally, ample evidence was obtained for the powerful ARA ovocidal potential and against and liver and intestine eggs. Studies documented ARA as an endogenous schistosomicide in the final mammalian and intermediate snail hosts, and in mice and hamsters, immunized with the cysteine peptidase-based vaccine. These findings together support our advocating the nutrient ARA as the safe and efficacious schistosomicide of the future.
Topics: Animals; Antigens, Helminth; Arachidonic Acid; Cysteine Proteases; Disease Models, Animal; Host-Parasite Interactions; Humans; Parasite Egg Count; Schistosoma; Schistosomiasis; Schistosomicides; Treatment Outcome; Vaccination; Vaccines
PubMed: 33281832
DOI: 10.3389/fimmu.2020.609994 -
Parasites & Vectors Aug 2023Although schistosomiasis is a public health issue in Mali, little is known about the parasite genetic profile. The purpose of this study was to analyze the genetic...
BACKGROUND
Although schistosomiasis is a public health issue in Mali, little is known about the parasite genetic profile. The purpose of this study was to analyze the genetic profile of the schistosomes of Schistosoma haematobium group in school-aged children in various sites in Mali.
METHODS
Urine samples were collected from 7 to 21 November 2021 and subjected to a filtration method for the presence S. haematobium eggs. The study took place in two schistosomiasis endemic villages (Fangouné Bamanan and Diakalèl), qualified as hotspots according to the World Health Organization (WHO) definition. Molecular genotyping on both Cox1 and ITS2/18S was used for eggs' taxonomic assignation.
RESULTS
A total of 970 miracidia were individually collected from 63 school-aged children and stored on Whatman FTA cards for molecular analysis. After genotyping 42.0% (353/840) and 58.0% (487/840) of miracidia revealed Schistosoma bovis and S. haematobium Cox1 profiles, respectively; 95.7 (885/925) and 4.3% (40/925) revealed S. haematobium and S. haematobium/S. curassoni profiles for ITS/18S genes, respectively. There was a significant difference in the Cox1 and ITS2/18S profile distribution according to the village (P < 0.0001). Overall, 45.6% (360/789) were hybrids, of which 72.0% (322/447) were from Diakalèl. Three hybrids' profiles (Sb/Sc_ShxSc with 2.3%; Sb/Sc_ShxSh with 40.5%; Sh_ShxSc with 2.8%) and one pure profile (Sh_ShxSh with 54.4%) were identified.
CONCLUSION
Our findings show, for the first time to our knowledge, high prevalence of hybrid schistosomes in Mali. More studies are needed on population genetics of schistosomes at the human and animal interface to evaluate the parasite's gene flow and its consequences on epidemiology of the disease as well as the transmission to humans.
Topics: Child; Animals; Humans; Schistosoma haematobium; Parasites; Disease Hotspot; Genetic Profile; Schistosoma; Schistosomiasis; Schistosomiasis haematobia
PubMed: 37542265
DOI: 10.1186/s13071-023-05860-8 -
PLoS Neglected Tropical Diseases Dec 2021Schistosomes cause schistosomiasis, the world's second most important parasitic disease after malaria in terms of public health and social-economic impacts. A peculiar...
Schistosomes cause schistosomiasis, the world's second most important parasitic disease after malaria in terms of public health and social-economic impacts. A peculiar feature of these dioecious parasites is their ability to produce viable and fertile hybrid offspring. Originally only present in the tropics, schistosomiasis is now also endemic in southern Europe. Based on the analysis of two genetic markers the European schistosomes had previously been identified as hybrids between the livestock- and the human-infective species Schistosoma bovis and Schistosoma haematobium, respectively. Here, using PacBio long-read sequencing technology we performed genome assembly improvement and annotation of S. bovis, one of the parental species for which no satisfactory genome assembly was available. We then describe the whole genome introgression levels of the hybrid schistosomes, their morphometric parameters (eggs and adult worms) and their compatibility with two European snail strains used as vectors (Bulinus truncatus and Planorbarius metidjensis). Schistosome-snail compatibility is a key parameter for the parasites life cycle progression, and thus the capability of the parasite to establish in a given area. Our results show that this Schistosoma hybrid is strongly introgressed genetically, composed of 77% S. haematobium and 23% S. bovis origin. This genomic admixture suggests an ancient hybridization event and subsequent backcrosses with the human-specific species, S. haematobium, before its introduction in Corsica. We also show that egg morphology (commonly used as a species diagnostic) does not allow for accurate hybrid identification while genetic tests do.
Topics: Animals; Body Size; Bulinus; Chimera; Disease Vectors; Europe; Female; Genome, Helminth; Humans; Hybridization, Genetic; Male; Schistosoma; Schistosoma haematobium; Schistosomiasis; Snails
PubMed: 34941866
DOI: 10.1371/journal.pntd.0010062 -
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