Search Results (497)

In the context of the current low endemicity of schistosomiasis in China, Schistosoma japonicum (S. japonicum) infections increasingly have been reported in field-captured rodents, highlighting the need for rapid and scalable tools to support surveillance during the elimination stage. This study developed and evaluated a quantitative polymerase chain reaction (qPCR) assay targeting a highly repetitive S. japonicum sequence for detecting infection in liver tissues. Analytical performance was assessed using adult-worm genomic DNA, DNA from non-target pathogens, egg-spiked mouse liver samples, experimentally infected BALB/c mice, and liver samples from field-captured rodents collected in Dongzhi and Duchang counties. The optimized assay generated a single melting peak at 79 ± 0.5 °C, used Ct < 33 as the positivity cutoff, and showed no apparent cross-reactivity with the non-target pathogens tested. Using serially diluted adult-worm genomic DNA, the assay consistently detected S. japonicum DNA at concentrations as low as 1 pg/μL. In the egg-spiked liver model, as few as two eggs were detected in 200 mg of liver tissue. In the experimentally infected model, all infected mice tested positive, whereas all non-infected controls tested negative, indicating complete agreement between the qPCR results and the experimentally defined infection status. In the field evaluation, qPCR yielded a higher positivity rate than parasitological examination in Dongzhi County (66.81% vs. 51.72%) and identified six positive samples in Duchang County, where all samples were negative by parasitological examination. These findings indicate that the qPCR assay can facilitate sensitive and high-throughput detection of S. japonicum infection in field-captured rodents and may provide a useful complementary tool for surveillance during schistosomiasis elimination. Full article

Background: Dysregulated immune cells contribute to Schistosoma japonicum-induced liver injury. However, the underlying mechanisms remain poorly understood. This study aimed to identify feature genes and immune infiltration patterns linked to chronic schistosomiasis-associated liver injury. Methods: Differential gene expression analysis was conducted using dataset GSE61376 from the Gene Expression Omnibus (GEO) database. Functional enrichment of differentially expressed genes (DEGs) was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to construct further characterization of molecular networks. LASSO regression and random forest algorithms were combined to screen hub genes, whose diagnostic efficacy was assessed by ROC analysis. CIBERSORT estimated immune cell infiltration, and GSEA explored pathways associated with hub genes. Results: A total of 412 DEGs were identified between chronic schistosomiasis and control groups. The green module from WGCNA exhibited significant correlation with chronic schistosomiasis (r = −0.85, p < 0.05). ANKMY2 and FCER1A were identified as hub genes with AUC values of 0.875 (95% CI, 0.500–1.000) and 0.792 (95% CI, 0.458–1.000). GSEA revealed associations with cytokine–receptor interaction and other signaling pathways. A total of 11 differentially distributed immune cell subsets were observed, and hub genes were correlated with multiple immune cell populations. Conclusions: ANKMY2 and FCER1A participate in liver injury of chronic schistosomiasis by regulating the hepatic immunopathological microenvironment. These two genes may serve as promising targets for immunotherapy against S. japonicum-induced liver injury. Full article

Background: Adult Schistosoma mansoni parasites inhabit the hepatic portal system of the vertebrate host, their deposited eggs causing granulomatous pathology in both the intestines and liver. In the intestines, egg secretions drive inflammatory processes involved in extravasation to the gut lumen. Methods: Here, we investigate parasite-host interactions in a mouse model during the acute phase of a patent infection at 5 and 7 weeks, using parallel histological and proteomic analysis of paraffin-embedded ileal tissues. Results: Histology at week 7 showed infected animals had more inflammation and longer villi than at week 5, as well as more Goblet cells reflecting enhanced mucus production. LC-MS/MS analysis of deparaffinized ileal sections, subjected to in-solution tryptic digestion, revealed a total of 1615 protein groups. Differentially abundant proteins were found early at week 5, coinciding with the onset of egg deposition. A contrasting scenario, dominated by upregulation of protein components from the innate and adaptive immune systems, was seen at week 7; at this point, egg migration and excretion are underway. Among the proteins were mast cell proteases, fibrinogens, arginase-1, and molecules associated with extracellular matrix remodeling. Conclusions: Our findings reflect intestinal proteome changes likely participating in S. mansoni egg passage from the vascular bed to the intestinal lumen. Full article

Although praziquantel (PZQ) is the main antischistosomal drug currently in use, concerns remain regarding incomplete reversal of schistosomiasis-induced pathology and the emergence of drug resistance. This study evaluates the combined effect of PZQ with safranal, a bioactive saffron constituent, on Schistosoma mansoni-induced pathology in mice. Male CD1 Swiss albino mice were exposed to 60 S. mansoni cercariae and, at week 9 post-infection, were treated with PZQ (500 mg/kg orally for two consecutive days), safranal (50 mg/kg/day), or both, for three weeks. The animals were sacrificed at week 11 post-infection. Worm and egg burdens, liver histopathology, fibrotic markers, oxidative stress, and inflammatory cytokines were assessed. Combined PZQ + safranal therapy significantly reduced adult worm counts and hepatic and intestinal egg loads compared to PZQ alone. All treatments decreased liver index (hepatomegaly), with the combination treatment providing the best intervention. Histological analyses revealed significantly reduced granuloma size and hepatic necrosis post-treatment, particularly in the combination group. The levels of proinflammatory cytokines (TNF-α, IL-1β) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were significantly lowered in treated mice, most notably with the combination treatment. Oxidative stress was also markedly attenuated, and infected mice exhibited elevated malondialdehyde and depleted antioxidant enzymes (SOD, CAT, GSH). Interestingly, PZQ and/or safranal restored antioxidant status and reduced lipid peroxidation, with the combination being most effective. Furthermore, collagen deposition and expression of hepatic fibrotic markers α-smooth muscle actin (α-SMA), TGF-β1, and matrix metalloproteinase-9 were most effectively suppressed by combined therapy. To conclude, safranal enhances PZQ’s antischistosomal efficacy and confers additive protection against Schistosoma-induced liver fibrosis. Full article

Background/Objectives: Schistosomiasis, a parasitic disease caused by Schistosoma worms with freshwater snails as intermediate hosts, affects over 250 million people. The current control relies solely on praziquantel, which raises concerns on drug resistance and highlights the need for new therapeutic alternatives. Our bioprospection studies have focused on marine macroalgae as an unexplored source of antischistosomal metabolites with promising results. Guided by WHO recommendations to target both the parasite and its transmission vectors, this study aimed to investigate Ochtodes secundiramea to: (i) isolate active metabolites; (ii) evaluate the isolated compounds against adult worms and oviposition to identify leads for drug development; and (iii) perform an independent screening of their effects against the environmental transmission stages on cercariae and B. glabrata embryos. Methods: A dichloromethane extract of O. secundiramea was submitted to an NMR–biomonitored guided fractionation against Schistosoma mansoni adult worms. Active fractions were further purified through HPLC and characterized by ¹H and ¹³C NMR spectroscopy to identify the isolated compounds. Results: Three halogenated monoterpenes were isolated: ochtodene 1 (4-bromo-1,6,8-trichloro-2,3-ochtodene), ochtodene 2 (2-chloro-1,6,8-tribromo-3,8-ochtodene), and the novel natural product ochtodene 3 [2,6-dibromo-4-(2-chloroethylidene)-1,1dimethylcyclohexane]. Ochtodene 1 was the primary active metabolite against Schistosoma mansoni adult worms, with IC₅₀/96 h values of 47.2 and 46.1 µM for male and female worms respectively, and totally suppressed egg laying with 60 µM, while showing no toxicity toward human fibroblasts. Notably, all metabolites, including the novel ochtodene 3, caused 100% mortality in cercariae and embryos at low concentrations. Conclusions: The discovery of the novel ochtodene 3 and the identification of distinct leads for host treatment and transmission elimination position O. secundiramea as a promising source for integrated schistosomiasis control. Full article

Schistosomiasis remains a major public health concern in Nigeria. We molecularly characterized Schistosoma eggs obtained from human urine to identify species and assess the presence of hybrid schistosomes in Abuja, Nigeria. Urine samples were collected from 1887 participants aged five years and above. Samples were examined for Schistosoma eggs using light microscopy. A total of 507 (26.9%) were positive for any form of Schistosoma while 91 (4.8%) had atypical Schistosoma eggs. DNA extracted from pooled ova was analyzed using metagenomic sequencing, read mapping, phylogenetic analysis, and BLASTn confirmation. Molecular analyses identified genetic signatures associated with both S. haematobium and S. bovis within pooled human urine samples, indicating the co-circulation of multiple schistosome species in the study area. Phylogenetic analyses based on trans-ITS and mitochondrial COX1 markers supported the presence of distinct nuclear and mitochondrial schistosome lineages. However, because sequencing was performed on pooled egg samples, the findings cannot distinguish between true recombinants and mixed infections involving co-circulating parental species. These findings highlight the potential complexity of schistosome transmission dynamics in endemic communities and underscore the need for enhanced molecular surveillance, especially single-parasite genomic approaches, and integrated One Health investigations to better understand schistosome transmission and its implications for control and elimination efforts in Nigeria. Full article

Schistosomiasis is an important snail-borne neglected tropical disease, and detecting infected snails is a priority for its control and elimination. However, conventional parasitological methods, such as crushed snails and cercarial shedding, have limited sensitivity. In this study, we developed a novel loop-mediated isothermal amplification (LAMP) assay (smND1-LAMP) targeting the mitochondrial NADH dehydrogenase subunit 1 (ND1) gene of Schistosoma mansoni. The assay was optimized at 65 °C for 1 h and demonstrated a detection limit of one copy of the pUC57/smND1 recombinant plasmid. Its diagnostic performance was evaluated using laboratory-infected Biomphalaria snails and field-collected samples from Zimbabwe and Burkina Faso, and compared with microscopy, conventional PCR and SYBR Green real-time PCR (SGPCR). In laboratory experiments, smND1-LAMP achieved 100% specificity and 75% sensitivity, outperforming microscopy and showing a similar performance to SGPCR. In field surveys, smND1-LAMP detected a higher positive rate (25.9%) than conventional PCR (22.2%) in Burkina Faso, while microscopy failed to identify any positive snails. Both molecular methods identified infections that were missed by parasitological techniques. These findings demonstrate that smND1-LAMP assay is a sensitive, specific, and field-applicable tool for detecting S. mansoni infection in snails. It provides an effective alternative for routine surveillance and early warning of changing schistosomiasis endemicity. Full article

Background: International travel and global mobility have led to an increasing number of pediatric patients presenting with infections acquired outside Europe. However, epidemiological data on imported infectious diseases in children remain fragmented, with substantial heterogeneity across studies. This systematic review aimed to synthesize current evidence on the spectrum, distribution, and epidemiological characteristics of imported infections in children and adolescents returning to Europe. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420251245531). PubMed, Scopus, and the Cochrane Library were searched for studies published between 2010 and December 2025. Studies reporting laboratory-confirmed or clinically diagnosed imported infections in pediatric populations (0–18 years) returning to Europe were included. Data were extracted and synthesized descriptively, with separate analyses for malaria-specific, non-malarial, and syndromic cohorts. Results: A total of 31 studies was included. Malaria was the most consistently reported infection, predominantly caused by Plasmodium falciparum and most frequently reported in association with travel to sub-Saharan Africa, which accounted for the largest proportion of reported exposures in clinical cohorts. Visiting friends and relatives (VFR) was the dominant travel category, representing between 45.8% and 87.4% of cases in disaggregated malaria cohorts and a substantial proportion across non-malarial studies. Non-malarial infections—including gastrointestinal, bacterial, parasitic, and viral diseases—represented a substantial proportion of cases in mixed and post-travel cohorts, with gastrointestinal illness frequently constituting the leading diagnosis. Considerable heterogeneity was observed across studies in terms of design, diagnostic approaches, and reporting practices, precluding formal meta-analysis. Conclusions: Imported infections in pediatric travelers encompass a broad and heterogeneous spectrum extending beyond malaria alone. Diagnostic approaches should integrate travel history, geographic exposure, and clinical presentation. Standardized pediatric-specific surveillance and harmonized reporting are needed to improve comparability and support more accurate epidemiological assessment. Full article

Schistosomiasis remains the second leading cause of death among parasitic diseases globally, contributing substantially to chronic morbidity and disability. South Africa (SA) is endemic for schistosomiasis, with ongoing efforts to expand mass drug administration. In the absence of true prevalence data, this study retrospectively analysed public sector laboratory-confirmed schistosomiasis cases from 2019 to 2024. Over this period, 73,680 cases were microscopically diagnosed, with Schistosoma haematobium accounting for 99.9% of infections. The test positivity rate of 20 per 100,000 population is lower than previously reported, with the burden concentrated among boys aged 5–19 years, particularly in the KwaZulu-Natal, Limpopo, and Mpumalanga provinces. These findings highlight a persistent burden within defined demographic groups and geographic areas, while also suggesting possible early signs of improvement that are potentially linked to public health interventions. The results provide valuable evidence to inform the scale-up of national schistosomiasis control programmes and the prioritisation of interventions towards the most affected populations. Full article

Background: Schistosomiasis remains a major neglected tropical disease, with praziquantel (PZQ) as the only widely used treatment, despite its limitations. Parthenolide (PTL), a sesquiterpene lactone, exhibits potent in vitro antischistosomal activity; however, its poor aqueous solubility, low oral bioavailability, and chemical instability may limit its in vivo efficacy. Objective: This study investigated whether nanoencapsulation in nanostructured lipid carriers (NLC) could enable the in vivo antischistosomal activity of PTL. Methods: PTL was isolated from Tanacetum parthenium and incorporated into NLC using hot emulsification followed by ultrasonication. The resulting formulation (NLC-PTL) was physicochemically characterized, and its in vivo antischistosomal efficacy was evaluated in a murine model of Schistosoma mansoni infection. Results: NLC-PTL exhibited nanoscale size, low polydispersity, high encapsulation efficiency, and sustained drug release. In vivo, free PTL showed no significant effect on worm burden, whereas NLC-PTL achieved a marked reduction (77.9%) in adult worms and significantly decreased egg output compared to controls (p < 0.001). Blank NLC had no antiparasitic effect. Conclusions: Nanoencapsulation was associated with in vivo antischistosomal activity of PTL compared to the free compound. These findings suggest that formulation strategies may influence the in vivo performance of lipophilic natural products in schistosomiasis. Full article

Emerging tolerance of Schistosoma mansoni to praziquantel, the only drug available for schistosomiasis treatment, highlights the need for new therapeutic targets. Snake venoms contain pharmacologically active proteins and peptides that can decrease the viability of S. mansoni worms in vitro. Long non-coding RNAs (lncRNAs) play important roles in S. mansoni and are promising new therapeutic targets. However, new candidates still need to be identified, as only four S. mansoni lncRNAs have been functionally characterized to date. Therefore, we investigated lncRNA expression changes in S. mansoni following incubation with Bothrops venoms. Adult worms were incubated with eight venoms at a sublethal dose, and phenotypic parameters were evaluated. RNA-Seq was conducted on worms incubated with Bothrops jararacussu or Bothrops moojeni venoms, followed by Weighted Gene Co-expression Network Analysis for each sex. B. moojeni venom reduced all phenotypic measurements, while B. jararacussu reduced oviposition. Both venoms altered global gene expression, including lncRNAs. Females showed two lncRNA hub genes in two venom-associated co-expression modules, while males showed 61 lncRNA hub genes in nine venom-associated modules. RT-qPCR validated six out of seven selected hub lncRNAs in male worms. These results reveal the involvement of lncRNAs in S. mansoni gene expression modulation induced by Bothrops venoms and point to lncRNAs that should be prioritized in future functional studies, such as SmLINC121220-IBu, SmLINC152105-IBu and SmLNCA123831-IBu. Full article

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, requiring a mean pulmonary artery pressure greater than 20 mmHg at rest, a pulmonary arterial wedge pressure of 15 mmHg or below, and a pulmonary vascular resistance exceeding 2 Wood units. PAH is an autosomal dominant disorder with markedly incomplete penetrance of approximately 20–30%, indicating that germline mutations alone are insufficient to cause disease. Disease manifestation requires additional “second hits”, including chronic hypoxia, systemic inflammation, hemodynamic stress, hormonal influences, and common genetic modifiers such as single-nucleotide polymorphisms (SNPs). This genetic and environmental complexity underpins the broad clinical heterogeneity observed across PAH subtypes, which include idiopathic PAH, heritable PAH, and disease associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and drug or toxin exposure. This review provides a comprehensive and critical appraisal of the molecular-genetic architecture of PAH. Thirty genes have now been implicated in disease pathogenesis, spanning seven functional categories: receptors of the TGF-β/BMP signaling family (BMPR2, ACVRL1, ENG, BMPR1B); circulating BMP ligands (GDF2, BMP10); transcription factors (TBX4, SOX17, KLF4, FOXF1, SMAD1, SMAD4, SMAD9); membrane and polyamine transporters (ATP13A3, AQP1); potassium channel regulators (KCNA5, KCNK3, ABCC8); metabolic and mitochondrial genes (EIF2AK4, NFU1, GGCX); signaling receptors and structural proteins (NOTCH3, KDR, CAV1, PLEKHH2); vasoactive and extracellular matrix regulators (KLK1, CBLN2, CD248); and epigenetic regulators (TET2, TOPBP1). Among these, BMPR2 is the dominant contributor, accounting for 53–86% of heritable PAH and 14–35% of idiopathic cases. The remaining genes each account for fewer than 5% of cases individually, collectively reflecting a broad landscape of rare and ultra-rare genetic contributions. For each gene, we critically evaluate the strength of genetic evidence, pathogenic mechanisms, degree of mechanistic resolution, and clinical relevance. We further discuss the contribution of emerging technologies, including whole-genome sequencing, single-cell and spatial transcriptomics, multi-omics integration, iPSC-derived vascular models, and artificial intelligence, to expanding the PAH genetic architecture beyond single-gene discovery. A key theme across this landscape is convergence: despite mechanistic diversity at the gene level, most PAH-associated variants ultimately impair endothelial quiescence, promote smooth muscle proliferation, and drive apoptosis resistance through disruption of BMP signaling amplitude, transcriptional stability, ion channel homeostasis, metabolic integrity, or epigenetic regulation. This convergence supports both a unified therapeutic rationale and a precision medicine framework for genotype-stratified intervention in PAH. Full article

Although schistosome eggs are widely recognized as the principal drivers of hepatic granulomatous inflammation and fibrosis, the independent effects of adult worms may be masked by strong egg antigen-mediated responses. This study aimed to investigate whether adult Schistosoma japonicum worms alter the miRNA expression profile of hepatic stellate cells and to explore the potential relevance of these changes to liver fibrosis and hepatocellular carcinoma-related processes. A non-contact Transwell co-culture system was established using paired Schistosoma japonicum worms or male worms and hepatic stellate cells. Male worms were additionally included to further assess worm-derived effects independent of egg production–related influences. Untreated hepatic stellate cells served as controls. Total RNA was extracted for miRNA sequencing, and differentially expressed miRNAs were identified. Target gene prediction, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and validation using The Cancer Genome Atlas database were subsequently performed. Both paired worms and male worms significantly altered the miRNA expression profile of hepatic stellate cells. Several differentially expressed miRNAs were identified, among which hsa-miR-103a-3p showed relatively stable changes. Pathway enrichment analysis suggested that the potential target genes of hsa-miR-103a-3p were mainly enriched in AMP-activated protein kinase, mechanistic target of rapamycin, tumor necrosis factor, insulin signaling, and cellular senescence pathways. Further analysis using The Cancer Genome Atlas database showed that hsa-miR-103a-3p had diagnostic value in hepatocellular carcinoma and was associated with alpha-fetoprotein level, albumin level, Ishak fibrosis score, pathological stage, histological type, and tumor status. These findings suggest that adult S. japonicum worms may alter the miRNA expression profile of hepatic stellate cells, and that hsa-miR-103a-3p may be associated with fibrogenic responses and may have potential relevance to hepatocellular carcinoma-related processes. However, this inference is based on correlative TCGA data and does not imply a causal role in schistosomiasis-associated hepatocarcinogenesis. Full article

Schistosomiasis remains one of the most significant neglected tropical diseases (NTDs) worldwide, sustained by the complex biology of Schistosoma species and the host’s immunopathological responses to tissue-trapped eggs. Despite decades of reliance on praziquantel (PZQ) as the sole chemotherapeutic option, major limitations persist, including its lack of activity against juvenile worms, incomplete protection against reinfection, and concerns regarding emerging tolerance. These challenges, together with persistent hotspots of transmission and uneven global progress toward disease elimination, underscore the urgent need for alternative or complementary therapies. Plant-derived terpenes have emerged as promising antischistosomal candidates due to their structural diversity, broad-spectrum bioactivity, and favourable safety profiles. Evidence from in vitro and in vivo studies demonstrates that monoterpenes, sesquiterpenes, diterpenes, triterpenes, and triterpenoid saponins exert multimodal effects on Schistosoma, including tegumental disruption, interference with metabolic and redox pathways, inhibition of oviposition, and modulation of host immune and fibrotic responses. Advances in mechanistic studies, supported by omics and computational approaches, further highlight their potential as leads for drug development. Additionally, nano-enabled delivery systems offer strategies to overcome pharmacokinetic limitations and enhance therapeutic performance. This review integrates current knowledge on schistosome biology, treatment challenges, and the growing evidence supporting terpenoids as viable components of a diversified antischistosomal therapeutic arsenal. Full article

Schistosomiasis, caused by Schistosoma species, is notoriously difficult to accurately diagnose with conventional methods. In this study, we present an innovative biosensor that integrates CRISPR–Cas12a technology with nucleic acid aptamers for the highly sensitive detection of Schistosoma japonicum eggs. The biosensor leverages a Y-shaped DNA structure (Y-DNA) that incorporates an aptamer specific to S. japonicum eggs, along with an activator DNA and a segment for immobilization on magnetic nanomaterials. Upon target recognition, the Y-DNA releases the activator, which triggers the collateral cleavage activity of Cas12a, enabling the direct detection of eggs. This system demonstrates remarkable sensitivity, being capable of detecting individual eggs in infected rabbit serum and feces. Moreover, it effectively distinguishes the eggs of S. japonicum from those of other parasitic species. The simplicity, high sensitivity, and rapid detection of our biosensor offer significant potential for improving the diagnosis of schistosomiasis, providing a novel, reliable tool for early detection in clinical settings. Full article