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Scientific Reports Mar 2023Schistosomiasis is a major neglected tropical disease targeted for elimination as a public health issue by 2030, however there is an urgent need for more sensitive and...
Schistosomiasis is a major neglected tropical disease targeted for elimination as a public health issue by 2030, however there is an urgent need for more sensitive and specific diagnostic tests suitable to resource-limited settings. Here we developed CATSH, a CRISPR-assisted diagnostic test for Schistosoma haematobium, utilising recombinase polymerase amplification, Cas12a-targeted cleavage and portable real-time fluorescence detection. CATSH showed high analytical sensitivity, consistent detection of a single parasitic egg and specificity for urogenital Schistosoma species. Thanks to a novel CRISPR-compatible sample preparation developed using simulated urine samples containing parasitic eggs, CATSH had a sample-to-result within 2 h. The components of CATSH can be lyophilised, reducing cold chain dependence and widening access to lower and middle-income countries. This work presents a new application of CRISPR diagnostics for highly sensitive and specific detection of parasitic pathogens in remote areas and could have a significant impact on the elimination of neglected tropical diseases.
Topics: Animals; Schistosoma haematobium; Schistosomiasis haematobia; Sensitivity and Specificity; Neglected Diseases; Eggs
PubMed: 36973334
DOI: 10.1038/s41598-023-31238-y -
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 -
The Journal of Infectious Diseases Mar 2015Approximately 200,000,000 people have schistosomiasis (schistosome infection). Among the schistosomes, Schistosoma haematobium is responsible for the most infections,... (Review)
Review
Approximately 200,000,000 people have schistosomiasis (schistosome infection). Among the schistosomes, Schistosoma haematobium is responsible for the most infections, which are present in 110 million people globally, mostly in sub-Saharan Africa. This pathogen causes an astonishing breadth of sequelae: hematuria, anemia, dysuria, stunting, uremia, bladder cancer, urosepsis, and human immunodeficiency virus coinfection. Refined estimates of the impact of schistosomiasis on quality of life suggest that it rivals malaria. Despite S. haematobium's importance, relevant research has lagged. Here, we review advances that will deepen knowledge of S. haematobium. Three sets of breakthroughs will accelerate discoveries in the pathogenesis of urogenital schistosomiasis (UGS): (1) comparative genomics, (2) the development of functional genomic tools, and (3) the use of animal models to explore S. haematobium-host interactions. Comparative genomics for S. haematobium is feasible, given the sequencing of multiple schistosome genomes. Features of the S. haematobium genome that are conserved among platyhelminth species and others that are unique to S. haematobium may provide novel diagnostic and drug targets for UGS. Although there are technical hurdles, the integrated use of these approaches can elucidate host-pathogen interactions during this infection and can inform the development of techniques for investigating schistosomes in their human and snail hosts and the development of therapeutics and vaccines for the control of UGS.
Topics: Animals; Disease Models, Animal; Genes, Helminth; Genomics; Humans; Molecular Sequence Annotation; Schistosoma haematobium; Schistosomiasis haematobia
PubMed: 25240172
DOI: 10.1093/infdis/jiu527 -
PLoS Neglected Tropical Diseases Jan 2022Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with...
Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S. haematobium (Sh-TSP-2, Sh-TSP-4, Sh-TSP-5, Sh-TSP-6, Sh-TSP-18 and Sh-TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh-TSP-2, and Sh-TSP-18 were identified on the tegument, whereas Sh-TSP-4, Sh-TSP-5, Sh-TSP-6 and Sh-TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh-TSPs was assessed using the urine of individuals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh-TSPs were the targets of urine IgG responses in all cohorts, including individuals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S. haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanins.
Topics: Animals; Antibodies, Helminth; Antigens, Helminth; Enzyme-Linked Immunosorbent Assay; Helminth Proteins; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Neoplasms; Ovum; Schistosoma haematobium; Schistosomiasis haematobia; Tetraspanins; Urinary Bladder; Urine
PubMed: 35073344
DOI: 10.1371/journal.pntd.0010151 -
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 -
PloS One 2022Despite twelve rounds of school-based preventive chemotherapy for schistosomiasis in endemic areas of Tanzania such as Mtama district, Lindi: the burden of Schistosoma...
BACKGROUND
Despite twelve rounds of school-based preventive chemotherapy for schistosomiasis in endemic areas of Tanzania such as Mtama district, Lindi: the burden of Schistosoma haematobium infection has remained highly conceivable due to re-infections. The factors associated with continuity of S.haematobium transmission in Mtama district, Lindi have not been fully established. This study investigated the burden and factors contributing to the ongoing transmission of S.haematobium infection in the endemic district of Mtama, Lindi.
METHODS
A quantitative cross-sectional survey was carried out among 649 school-age children in the Mtama district to determine the burden and factors associated with continuity of S.haematobium infection transmission. A single urine specimen was obtained from each pupil and tested for macro- and microhaematuria, presence of S.haematobium ova, as well intensity of infection; this was complemented with a survey of Bulinus spp snail intermediate hosts and their infectivity. A structured questionnaire was employed to gather information on individual and environmental risk factors for S.haematobium transmission. Summary statistics were computed for individual variables; while a univariate and multivariate logistic regression analysis was performed to assess the association between risk factors with S.haematobium infection.
RESULTS
Prevalence of S.haematobium infection by macro- and microhaematuria was 13.1% and 46.2% respectively. The prevalence of S.haematobium ova was 52.7%; intensity of infection was light in 53.1%, and heavy in 46.9%. Snail intermediate hosts were Bulinus globosus and B.nasutus, whose infectivity was 2.2% and 1.3%, respectively. Among the assessed risk factors, long residency (10-13 years) in the area was a significant risk factor for the continuity of S.haematobium transmission (AOR: 21.79, 95% CI: 1.37-346.4).
CONCLUSIONS
The observed 52.7% prevalence of S.haematobium infection represents unacceptably high prevalence after 12 rounds of preventive chemotherapy. Therefore, an urgent need for the implementation of integrated multiple control interventions in the Mtama district; is considered to be imperative.
Topics: Adolescent; Animals; Child; Cross-Sectional Studies; Disease Vectors; Endemic Diseases; Female; Humans; Logistic Models; Male; Prevalence; Risk Factors; Schistosoma haematobium; Schistosomiasis haematobia; School Health Services; Schools; Snails; Tanzania
PubMed: 35167622
DOI: 10.1371/journal.pone.0263929 -
PLoS Neglected Tropical Diseases Oct 2021Infectious disease risk is driven by three interrelated components: exposure, hazard, and vulnerability. For schistosomiasis, exposure occurs through contact with water,...
BACKGROUND
Infectious disease risk is driven by three interrelated components: exposure, hazard, and vulnerability. For schistosomiasis, exposure occurs through contact with water, which is often tied to daily activities. Water contact, however, does not imply risk unless the environmental hazard of snails and parasites is also present in the water. By increasing reliance on hazardous activities and environments, socio-economic vulnerability can hinder reductions in exposure to a hazard. We aimed to quantify the contributions of exposure, hazard, and vulnerability to the presence and intensity of Schistosoma haematobium re-infection.
METHODOLOGY/PRINCIPAL FINDINGS
In 13 villages along the Senegal River, we collected parasitological data from 821 school-aged children, survey data from 411 households where those children resided, and ecological data from all 24 village water access sites. We fit mixed-effects logistic and negative binomial regressions with indices of exposure, hazard, and vulnerability as explanatory variables of Schistosoma haematobium presence and intensity, respectively, controlling for demographic variables. Using multi-model inference to calculate the relative importance of each component of risk, we found that hazard (Ʃwi = 0.95) was the most important component of S. haematobium presence, followed by vulnerability (Ʃwi = 0.91). Exposure (Ʃwi = 1.00) was the most important component of S. haematobium intensity, followed by hazard (Ʃwi = 0.77). Model averaging quantified associations between each infection outcome and indices of exposure, hazard, and vulnerability, revealing a positive association between hazard and infection presence (OR = 1.49, 95% CI 1.12, 1.97), and a positive association between exposure and infection intensity (RR 2.59-3.86, depending on the category; all 95% CIs above 1).
CONCLUSIONS/SIGNIFICANCE
Our findings underscore the linkages between social (exposure and vulnerability) and environmental (hazard) processes in the acquisition and accumulation of S. haematobium infection. This approach highlights the importance of implementing both social and environmental interventions to complement mass drug administration.
Topics: Adolescent; Animals; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Reinfection; Rural Population; Schistosoma haematobium; Schistosomiasis haematobia; Senegal; Social Vulnerability; Vulnerable Populations; Water
PubMed: 34610025
DOI: 10.1371/journal.pntd.0009806 -
Parasite (Paris, France) 2022While population genetics of Schistosoma haematobium have been investigated in West Africa, only scant data are available from Côte d'Ivoire. The purpose of this study...
While population genetics of Schistosoma haematobium have been investigated in West Africa, only scant data are available from Côte d'Ivoire. The purpose of this study was to analyze both genetic variability and genetic structure among S. haematobium populations and to quantify the frequency of S. haematobium × S. bovis hybrids in school-aged children in different parts of Côte d'Ivoire. Urine samples were subjected to a filtration method and examined microscopically for Schistosoma eggs in four sites in the western and southern parts of Côte d'Ivoire. A total of 2692 miracidia were collected individually and stored on Whatman FTA cards. Of these, 2561 miracidia were successfully genotyped for species and hybrid identification using rapid diagnostic multiplex mitochondrial cox1 PCR and PCR Restriction Fragment Length Polymorphism (PCR-RFLP) analysis of the nuclear ITS2 region. From 2164 miracidia, 1966 (90.9%) were successfully genotyped using at least 10 nuclear microsatellite loci to investigate genetic diversity and population structure. Significant differences were found between sites in all genetic diversity indices and genotypic differentiation was observed between the site in the West and the three sites in the East. Analysis at the infrapopulation level revealed clustering of parasite genotypes within individual children, particularly in Duekoué (West) and Sikensi (East). Of the six possible cox1-ITS2 genetic profiles obtained from miracidia, S. bovis cox1 × S. haematobium ITS2 (42.0%) was the most commonly observed in the populations. We identified only 15 miracidia (0.7%) with an S. bovis cox1 × S. bovis ITS2 genotype. Our study provides new insights into the population genetics of S. haematobium and S. haematobium × S. bovis hybrids in humans in Côte d'Ivoire and we advocate for researching hybrid schistosomes in animals such as rodents and cattle in Côte d'Ivoire.
Topics: Animals; Cattle; Child; Cote d'Ivoire; Genetic Structures; Humans; Parasites; Polymorphism, Restriction Fragment Length; Schistosoma haematobium
PubMed: 35522066
DOI: 10.1051/parasite/2022023 -
Parasitology Mar 2020Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been...
Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been reported in West Africa, no data about Schistosoma hybrids in humans are available from Côte d'Ivoire. This study aimed to identify and quantify S. haematobium-bovis hybrids among schoolchildren in four localities of Côte d'Ivoire. Urine samples were collected and examined by filtration to detect Schistosoma eggs. Eggs were hatched and 503 miracidia were individually collected and stored on Whatman® FTA cards for molecular analysis. Individual miracidia were molecularly characterized by analysis of mitochondrial cox1 and nuclear internal transcribed spacer 2 (ITS 2) DNA regions. A mitochondrial cox1-based diagnostic polymerase chain reaction was performed on 459 miracidia, with 239 (52.1%) exhibiting the typical band for S. haematobium and 220 (47.9%) the S. bovis band. The cox1 and ITS 2 amplicons were Sanger sequenced from 40 randomly selected miracidia to confirm species and hybrids status. Among the 33 cox1 sequences analysed, we identified 15 S. haematobium sequences (45.5%) belonging to seven haplotypes and 18 S. bovis sequences (54.5%) belonging to 12 haplotypes. Of 40 ITS 2 sequences analysed, 31 (77.5%) were assigned to pure S. haematobium, four (10.0%) to pure S. bovis and five (12.5%) to S. haematobium-bovis hybrids. Our findings suggest that S. haematobium-bovis hybrids are common in Côte d'Ivoire. Hence, intense prospection of domestic and wild animals is warranted to determine whether zoonotic transmission occurs.
Topics: Adolescent; Animals; Child; Child, Preschool; Cote d'Ivoire; DNA, Helminth; DNA, Intergenic; Electron Transport Complex IV; Helminth Proteins; Humans; Hybridization, Genetic; Mitochondrial Proteins; Prevalence; Schistosoma; Schistosoma haematobium; Schistosomiasis
PubMed: 31727202
DOI: 10.1017/S0031182019001549 -
PLoS Pathogens Feb 2022Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million...
Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover 'new' genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation within S. haematobium among some geographical locations in Africa revealed unique genomic 'signatures' that matched species other than S. haematobium, indicating the occurrence of introgression events. The present reference genome (designated Shae.V3) and the findings from this study solidly underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved and sustained control of urogenital schistosomiasis.
Topics: Animals; Chromosomes; Genes, Protozoan; Genetic Variation; Genome; Genome, Protozoan; Genome-Wide Association Study; Schistosoma haematobium; Schistosomiasis haematobia; Sequence Analysis, DNA; Transcriptome
PubMed: 35167626
DOI: 10.1371/journal.ppat.1010288