Search Results (191)

Schistosoma mansoni infection is associated with hepatic inflammation and fibrosis, but its systemic metabolic effects remain poorly understood. This study aimed to investigate changes in the serum lipidomic profile associated with S. mansoni infection and parasite load in individuals from an endemic area. This cross-sectional analysis was nested within a longitudinal cohort study conducted in northeastern Brazil. Parasitological diagnosis and quantification were performed using the Kato–Katz technique. A total of 45 individuals were selected and divided into three groups: high parasite load (HL), low parasite load (LL), and uninfected controls (NegE). Serum samples were analyzed using mass-spectrometry-based lipidomics. The most abundant lipid subclasses across all groups were phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines (PE). However, individuals in the HL group exhibited distinct lipidomic profiles, with increased levels of specific phosphatidylinositols (PI) and reduced levels of certain TAG species compared to the NegE group. These changes may reflect host–parasite interactions and immune–metabolic alterations driven by intense infection. Our findings suggest that S. mansoni infection, particularly at higher parasite burdens, can influence the host’s serum lipid profile and may contribute to metabolic disturbances in endemic populations. Full article

Neglected diseases significantly impact the world, and there is a lack of effective treatments, requiring therapeutic alternatives. Thus, the study of the phytochemical and schistosomicidal activity evaluation of Copaifera oblongifolia leaves’ crude extract was conducted. The quercitrin (1) and afzelin (2) were isolated from the crude extract. In the in vitro schistosomicidal activity test, the isolated compounds demonstrated promising results, with 75% mortality at a concentration of 12.5 µM after 72 h. Molecular docking calculations indicated that compounds 1 and 2 could potentially interact with the amino acids of the FAD binding site in the TGR enzyme, a crucial enzyme for the survival of Schistosoma mansoni. These interactions could have binding energies comparable to praziquantel, a preferred drug for treating schistosomiasis. Therefore, in silico and in vitro investigations are crucial for developing new studies that can reveal the antiparasitic potential of compounds of plant origin. Full article

Background: Dyslipidemia and schistosomiasis are major public health challenges, particularly in endemic regions where their coexistence may influence host metabolism and immune responses. This study aimed to evaluate visceral adipose tissue (AT) remodeling in a murine model of acute Schistosoma mansoni infection combined with diet-induced dyslipidemia. Methodology: Female Swiss Webster mice were fed either a standard or high-fat diet (HFD) for 29 weeks and infected with S. mansoni at week 20. Nine weeks after infection, biochemical, morphometric, histopathological, and immunological analyses were performed. Results: The HFD promoted weight gain and dyslipidemia, while S. mansoni infection alone did not alter lipid profiles but partially mitigated the metabolic effects of the HFD. Morphometric analysis revealed adipocyte hypertrophy and reduced cell number in HFD-fed animals. In HFD-fed infected mice, infection partially reversed hypertrophy, suggesting a modulatory effect on AT remodeling. Histopathological examinations showed that while a HFD induced mild inflammation, infection led to intense leukocyte infiltration, hyperemia, and plasma cell degeneration. Peritoneal lavage confirmed a proinflammatory immune profile. Conclusions: These findings indicate that the interaction between a HFD and S. mansoni infection exacerbates adipose tissue inflammation and metabolic alterations, highlighting the complex interplay between parasitic infection, diet, and immune-metabolic regulation. Full article

Schistosomiasis mansoni is a neglected tropical disease caused by the parasite Schistosoma mansoni, affecting approximately 200 million people annually. Currently, treatment relies primarily on a single drug, praziquantel (PZQ), which shows limited efficacy against the parasite’s immature forms. As a result, Thioredoxin Glutathione Reductase from S. mansoni (SmTGR) has emerged as a promising target for novel drug development. This study presents the development of integrated in silico methods to identify alkaloids from medicinal plants with potential activity against S. mansoni. Fourteen alkaloids were identified, with predicted activity ranging from 61.3 to 85.2%. Among these, lindoldhamine and daibucarboline A demonstrated, for the first time, potential SmTGR inhibition, with probabilities of 85.2% and 75.8%, respectively. These findings highlight the potential of these alkaloids as promising candidates for the development of new therapies against schistosomiasis. Full article

Schistosomiasis is a parasitic disease caused by helminth parasites of the genus Schistosoma, affecting >200 million people worldwide. Current schistosomiasis treatment relies on a single drug, praziquantel, highlighting the urgent need for new therapies. We have identified a non-neuronal tegumental acetylcholinesterase from Schistosoma mansoni (SmTAChE) as a rational and molecularly defined drug target. Molecular modeling reveals significant structural differences between SmTAChE and human AChE, suggesting the potential for identifying parasite-specific inhibitors. Here, we screened recombinant SmTAChE (rSmTAChE) against two chemical libraries: the Broad Institute Drug Repurposing Hub (5440 compounds) and the Diversity-Oriented Synthesis (DOS)-A library (3840 compounds). High-throughput screening identified 116 hits from the Repurposing Hub (2.13% hit rate) and 44 from the DOS-A (1.14% hit rate) library that inhibited rSmTAChE ≥60% at 20 µM. Dose–response assays using both rSmTAChE and recombinant human AChE (rHsAChE) revealed 19 Repurposing Hub compounds (IC₅₀: 0.4–24 µM) and four DOS-A scaffolds (IC₅₀: 13–29 µM), with higher selectivity for rSmTAChE. Selective inhibitors such as cepharanthine, primaquine, mesalazine, and embelin emerged as promising candidates for further evaluation in schistosomiasis treatment. These 23 newly identified selective hits provide a foundation for the further development of novel anti-schistosome therapies. Full article

Recent work has identified biomphalysin (BM) protein from the snail Biomphalaria glabrata as a cytolytic toxin against the Schistosoma mansoni parasite. Ex vivo interactome studies further evidenced BM’s ability to bind bacterial outer membrane proteins, but its specific antibacterial mechanisms and selectivity remain unclear. Accordingly, this study aims to elucidate the interaction between BM and two model bacteria with distinct cell surface architectures: Escherichia coli (Gram−) and Micrococcus luteus (Gram+). Employing a multiscale approach, we used in vivo single-molecule force spectroscopy (SMFS) to probe molecular interactions at the single cell level. Combined with cell aggregation assays, immunoblotting and Atomic Force Microscopy (AFM) imaging, SMFS results evidenced a selective interaction of BM from snail plasma with M. luteus but not E. coli. Exposure of M. luteus to BM compromised cell surface integrity and induced cell aggregation. These effects correlated with a patch-like distribution of BM on M. luteus reminiscent of pore-forming toxins, as revealed by the anti-BM antibody-functionalized AFM tip. Overall, this work highlights the utility of SMFS in dissecting host–pathogen molecular dialogs. It reveals BM’s selective action against M. luteus, potentially via surface clustering, and it shows spatially heterogeneous responses to the toxin within and between individual cells. Full article

Schistosomes are intravascular parasitic worms that cause the debilitating tropical disease schistosomiasis, affecting >200 million people worldwide. How the worms survive within the body of immunocompetent hosts for many years is unclear. Here, using chromatography and mass spectrometry, we report on the ex vivo ability of adult Schistosoma mansoni worms to modulate the levels of 27 small molecule (often immunomodulatory) metabokines in murine plasma. Schistosomes significantly alter the relative amounts of most (16) of these molecules. Three (inosine, genistein, and glucose) are significantly decreased in the presence of the parasites. While levels of several immunomodulatory metabolites from the kynurenine pathway (kynurenine, kynurenic acid, and xanthurenic acid) remain unchanged, levels of anthranilate (an endogenous regulator of innate immunity) are significantly increased. Of particular interest are increases in levels of metabolites that are known to skew immune responses in a manner that is seen following natural schistosome infection, such as by promoting Th2 immunity (succinate), Treg generation (lactate) and M2 macrophage polarization (lactate and succinate). In addition, significant increases are also observed for 2-hydroxyglutarate, adenine, hypoxanthine, xanthine, myoinositol, betaine and N-acetylglucosamine. Each of these compounds can have immunosuppressive effects that could impact host immunological status and contribute to schistosome survival. Full article

Biomphalaria pfeifferi is a key intermediate host for Schistosoma mansoni transmission in Sudan. In total, 27 complete mitochondrial genomes from seven B. pfeifferi populations in Gezira State, Sudan, were sequenced for the first time to investigate their population structure and phylogenetic relationships. This involved comparing the nucleotide composition, codon usage, rRNAs, and tRNAs of the East Gezira (EG), South Gezira (SG), Hasahisa (HA), Greater Wad Medani (GW), Managil (MA), and North Umelgura (NU1, NU3) populations. All 27 mitogenomes (13,688–13,696 bp) contained 37 genes with conserved AT/GC content (76.7/23.4%). Phylogenetic analysis revealed that although samples clustered within the same clade, B. pfeifferi from EG, SG, NU1, and NU3 grouped closely with B. pfeifferi from Kenya, whereas HA and GW samples formed distinct ancestral lineages. The MA population exhibited unique genetic characteristics, supported by phylogenetic trees and nucleotide/amino acid identity, suggesting the potential presence of a distinct B. pfeifferi subspecies that warrants further investigation. All protein-coding genes evolved under negative selection, with the amino acids of nad1 and nad6 being highly conserved, while nad3 exhibited some variation. Further research on the mitogenomic diversity of B. pfeifferi and other Biomphalaria species in Sudan and across Africa is needed in order to better understand the population structure and evolutionary history of Biomphalaria. Full article

Introduction: One of the global strategies for the elimination of schistosomiasis is by Mass Drug Administration (MDA) of a single oral dose of praziquantel (40 mg/kg) without a prior individual diagnosis, with a target of >75% treatment coverage among school-aged children. This study was conducted to determine the endemicity of schistosomiasis among school-aged children and adults in Abuja, Nigeria. Methods: A total of 1370 participants were recruited, which consisted of 667 (48.67%) males and 703 (51.31%) females. Urine and stool specimens were collected from each participant and analyzed using standard procedures. Results: The overall prevalence of schistosomiasis was 27.5% in this study with Abuja Municipal having the highest prevalence of 49%, while the least (6.1%) was reported in Bwari LAC. The prevalence of schistosomiasis significantly differs (p < 0.05) between the area councils. The location of communities significantly affected the prevalence of schistosomiasis in Abaji, AMAC, and Gwagwalada LACs (p < 0.005). The Schistosoma recovered in this study were S. haematobium and S. mansoni. The prevalence of schistosomiasis increased from the baseline of 21.1% to 49% in Gwagwalada LAC. Gender significantly affected the prevalence of schistosomiasis as more males were infected (33.1%) than their female counterparts (22.2%) (p < 0.05). The prevalence of schistosomiasis was 31% and 23.9% among SAC and adults, respectively. The participants’ activities in the river significantly affected the prevalence of schistosomiasis in this study (p < 0.05). Conclusions: The clamour for urgent government and non-government intervention through alternate sources of water like boreholes or pipe-borne water, as well as implementing a behavioural change campaign across the communities to prevent the recurrence, are advocated. Full article

Objective: Schistosoma mansoni (S. mansoni) infection is endemic in Ugandan fishing communities. We investigated its potential impact on Hepatitis B (Hep B) vaccine responses and its role in mediating the association between the gut microbiome and long-term effectiveness of the vaccine. Methods: Participants were tested for S. mansoni infections at baseline and received the Hep B vaccine at baseline, month 1, and month 6. Those with infections were treated. Stool samples were collected at baseline and analyzed using 16S rRNA sequencing. The Wilcoxon rank-sum test was used to compare alpha diversity between groups. A linear regression model was applied to estimate the association between one-year Hep B vaccine responses and the baseline gut microbiome by infection status, adjusting for age and sex. Results: A total of 107 participants were included (44 from the fishing community and 63 from the Kampala community). There was no significant difference in microbiome composition by location or infection status at baseline or discharge. In the linear regression analysis, S. mansoni infection (β = 1.24, p = 0.025) and a higher alpha diversity (β = 0.001, p = 0.07) were associated with higher Hep B vaccine responses, while older age was associated with a lower Hep B vaccine response (β = −0.06, p = 0.0013). Conclusions: S. mansoni infection status before vaccination may modify the association between the gut microbiome and Hep B vaccine response. Potential interventions could focus on infection control as well as improving microbiome richness before implementing vaccine programs in fishing communities. Full article

Identification of individuals of Biomphalaria is a challenging task, since morphological aspects alone are not sufficient to distinguish between species, which share many similar characteristics. However, the accurate identification of species of Biomphalaria is crucial for monitoring of schistosomiasis, since these species are intermediate hosts of the parasite Schistosoma mansoni, which causes the disease, which is prevalent in the north region of Brazil. In this context, the objective of this study was to identify specimens of Biomphalaria that occur in Mapiri Lake, in the lower Amazon region, in Santarém, Pará, Brazil. An integrated approach was used for identification of specimens of Biomphalaria, which included embryological and morphological analyses (comparison of diagnostic characteristics between species of the genus), as well as molecular assays using the Sanger sequencing method with dideoxy chain termination, as a method to reinforce the precision of species identification. The results establish the first record of B. amazonica in the state of Pará. This species has a development cycle consistent with that observed for other species of the genus Biomphalaria but possesses morphological characteristics that make accurate identification at the species level difficult, which reinforces the need for the molecular analyses. The first record of B. amazonica in the state of Pará in this study enlarges the distribution area of this species in Brazil, which demonstrates the importance of research focused on the identification of species of Amazonian mollusks as an auxiliary tool that can be used to combat schistosomiasis. Full article

Background: Schistosomiasis (SCH) and soil transmitted helminthiasis (STH) have been targeted for elimination as a public health problem (EPHP) within the World Health Organization (WHO)’s Roadmap for Neglected Tropical Diseases (NTDs) 2021–2030. One of the global strategies for the control and elimination of these diseases is the mass administration of praziquantel and albendazole/mebendazole without prior individual diagnosis. To measure the progress towards the 2030 target, we conducted an assessment to determine the impact of the 3–5 rounds of annual mass drug administration among school age children in Ekiti State. Such scientific insights into the impact of these treatments will facilitate improved planning and targeting of resources towards reaching the last mile. Methodology: This assessment was conducted in 16 local government areas (LGAs) of Ekiti State between October and November 2023. Samples were collected from pupils in 166 primary and junior secondary schools across 166 wards of the State. Urine and stool samples were collected from 7670 pupils of ages 5 to 14 years, following standard laboratory procedures. Urine membrane filtration techniques were used for urine preparation while the Kato–Katz technique was used for stool preparation. A novel AiDx digital microscope was used to examine the presence of any ova in the prepared specimen. Parasite ova in urine were reported as the number of ova/10 mL of urine, and were categorized as light infection (˂50 ova/10 mL of urine) or heavy infection (>50 ova/10 mL of urine) while ova of parasites in stool samples were reported as eggs per gram of stool (EPG) and categorized into light, moderate and heavy infection. Results: Overall, 0.76% (0.56–0.95) at 95% CI of the 7670 respondents were infected with Schistosomia haematobium. No Schistosoma mansoni infection was recorded in the study. Similarly, 3.9% (3.43–4.29) at 95% CI were infected with STHs. The overall prevalence of schistosomiasis had significantly reduced from 8.2% in 2008 to 0.8%, while the overall prevalence of STHs significantly reduced from 30.9% to 3.9% with Ascaris lumbricoides being the dominant species of STH. In the 16 LGAs assessed, Ekiti West had the highest S. haematobium prevalence of 4.26%. Ise/Orun and Oye ranked second and third with a prevalence of 3.48% and 2.40% respectively, while all other LGAs had <1% prevalence. The prevalence of STHs was highest in Ekiti-West with a prevalence of 10.45% while Emure and Ikole Local Governments had the lowest prevalence of 0.31% and 0.38%, respectively. There was no significant difference in the prevalence of schistosomiasis between male (0.76%) and female (0.75%) as p ≥ 0.05. Similarly, the difference in prevalence for STH among males (3.95%) was not significantly different from their female counterparts (3.77%), p ≥ 0.05. Conclusions: Based on the WHO guidelines, this study demonstrated that only three LGAs require continued MDA every 2/3 years, seven require only surveillance while six are now non-endemic for schistosomiasis. Similarly, two of the LGAs require one round of MDA yearly, eight LGAs need one round of MDA every two to three years and six LGAs are now below the treatment threshold and no longer require treatment for STH. Full article

Introduction: Freshwater snails, particularly snails from the genus Biomphalaria, play a key role in the transmission of schistosomiasis, a parasitic disease prevalent in tropical regions. Schistosomiasis poses a significant public health challenge in these regions, leading to chronic illness, reduced productivity, and impaired childhood development, particularly in communities with limited access to healthcare and sanitation. Understanding the seasonal and spatial variations in snail populations and infection rates is crucial for controlling schistosomiasis, especially in areas like Southwest Ethiopia, where the disease burden is high. Methods: This study was conducted in Mizan Aman, Southwest Ethiopia, across two seasons, dry and wet. A total of 1150 snail samples were collected from 20 freshwater sites, and their species, abundance, and infection status were assessed. Environmental parameters, including temperature, pH, salinity, and conductivity, were measured to analyze their impact on snail populations. Results: Four snail species were identified, Biomphalaria pfeifferi, Biomphalaria sudanica, Lymnaea natalensis, and Bulinus globosus, with B. pfeifferi and B. sudanica being the most prevalent. Snail abundance varied by site and season, with 598 in the dry season and 552 in the wet season. Snail abundance and species composition showed significant spatial variation, with higher counts in sites like Sasin and Agu 1, while some sites had no snails. Biomphalaria snails, particularly B. pfeifferi, are the principal intermediate host for Schistosoma mansoni. The overall prevalence of Biomphalaria snails exceeded 85% in both seasons, and their average infection rate in Mizan Aman was 13.5%. This infection rate showed a strong correlation (r = 0.733, p < 0.001) with the incidence of schistosomiasis cases in the community. Seasonal variation in environmental factors, such as temperature and pH, had no significant effect on snail abundance; however, water salinity showed to be correlated with snail abundance during the dry season. Furthermore, community-led vegetation clearance at selected sites significantly reduced snail abundance. Conclusions: This study highlights the seasonal and spatial dynamics of freshwater snails, particularly Biomphalaria species, in relation to schistosomiasis transmission in Mizan Aman, Southwest Ethiopia. The findings confirm that B. pfeifferi species is the predominant intermediate host for schistosoma in this region and that schistosomiasis infection rates among snails significantly correlate with human cases in the community. While environmental factors such as temperature and pH showed no significant influence on snail abundance, water salinity had an impact during the dry season. Additionally, community-led vegetation clearance was an effective intervention in reducing snail populations. These results emphasize the need for targeted, site-specific control measures integrating ecological and community-based interventions to sustainably reduce schistosomiasis transmission. Full article

Background/objectives: Schistosomiasis is caused by flatworms of the genus Schistosoma, for which mollusks of the genus Biomphalaria are intermediate hosts. Niclosamide (NCL) is a molluscicide recommended by the World Health Organization (WHO) for control of Biomphalaria. Although effective, it is expensive and environmentally toxic, which raises concerns regarding its widespread use. As a result, we explored new synthetic substances as alternative strategies for controlling Biomphalaria glabrata. We evaluated the molluscicidal activity of 2-(1H-py-razol-1-yl)-1,3,4-thiadiazole and 2-(4,5-dihydro-1H-pyrazol-1-yl)-1,3,4-thiadiazole derivatives against B. glabrata snails and embryos, as well as Schistosoma cercariae (infective larvae). Methods: Adult and young snails were added to 24-well plates containing 20 synthetic compounds from the PDAN series for initial screening over 96 h at a concentration of 100 ppm. Water and NCL (2 ppm) were used as the negative and positive controls, respectively. Active compounds in the adult B. glabrata assay were selected for the tests vs. embryos and cercariae. Results: In the initial screen, only PDAN 52 (63 ± 4%) and 79 (12 ± 3%) showed molluscicidal activity at a concentration of 100 ppm up to 48 h. Consequently, we selected only PDAN 52. The LC₅₀ value found in the tests on embryos after 24 h of treatment was 20 ± 2 ppm and, after 48 h, it was 4 ± 0.5 ppm. Against cercariae, we measured an LC₅₀ value of 68 ± 5 ppm after 4 h of treatment. PDAN 52 did not induce marked toxicity against a second mollusk, Physella acuta, after 48 h of exposure. Conclusions: We highlight the promising molluscicidal activity of PDAN 52 against different developmental stages of the mollusk, B. glabrata, as well the infective larvae of Schistosoma mansoni. Full article

Background/Objectives: Following previous successful Phase I clinical trials conducted in men and women in a non-endemic area for schistosomiasis in Brazil, the Sm14 vaccine was evaluated in an endemic region in Senegal. We report successful clinical trials in adults (Phase IIa) and school children (Phase IIb), respectively, of a Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) vaccine + a glucopyranosyl lipid A (GLA-SE) adjuvant. Methods: Participants were evaluated based on clinical assessments, laboratory tests (including hematologic and biochemical analyses of renal and hepatic functions), and immunological parameters (humoral and cellular responses) up to 12 months after the first vaccination dose in the Phase IIa trial and after 120 days in the Phase IIb trial. Results: The results showed strong immunogenic responses and good tolerance in both adults and children, with no major adverse effects. Importantly, significant increases in Sm14-specific total IgG (IgG1 and IgG3) were observed as early as 30 days after the first vaccination, with high titres remaining at least 120 days afterwards. Sm14-specific total IgG serum levels were also significantly enhanced in adults and in both infected and non-infected, vaccinated children and elicited robust cytokine responses with increased TNFα, IFN-γ, and IL-2 profiles. Conclusions: Overall, the Sm14+GLA-SE vaccine is safe and highly immunogenic, with a clearly protective potential against schistosomiasis, supporting progression to the next Phase III clinical trials. Full article