Local cytokine modulation and parasite visceralization during murine coinfection with Leishmania amazonensis and Schistosoma mansoni.

Various forms of voluntary migration have been and remain among the leading causes of the worldwide dispersal of parasites. Although helminthic infections are common in Africa, they are rare in Israel, making diagnosis challenging for many clinicians. We present 22 years of experience diagnosing under-recognized, long-lasting helminthic infections in migrants from African countries: Strongyloides stercoralis (up to 24 years), Schistosoma mansoni (up to 15 years), and hookworm (up to 12 years).

Schistosomiasis is a neglected tropical disease caused by human-infective schistosomes (Trematoda: Schistosoma). Intestinal schistosomiasis in sub-Saharan Africa and the Neotropics is caused primarily by Schistosoma mansoni and is transmitted by several Biomphalaria planorbid snail species. Adult male and female parasites in the definitive mammalian host pair and reside in the mesenteric vasculature; females lay eggs that traverse the intestinal wall to be excreted, but a significant proportion become trapped in host tissues, especially the liver, eliciting granulomatous immune responses that underlie most disease pathology. Schistosoma mansoni is the primary lab model for research, and, due to the abundance and ease of harvesting, liver-derived eggs are almost exclusively used to maintain the life cycle and to study miracidia and subsequent larval stages. However, recent evidence shows that eggs from the liver or intestine have key morphometric, transcriptomic, and antigenic differences, which can profoundly affect experimental outcomes. To determine whether these differences extend to the miracidia stage, we compared miracidia hatched from mouse liver and intestine-derived eggs, sequencing their transcriptomes and assessing their unstimulated behaviors over time in an arena allowing for high-resolution tracking of miracidia behavior at a large spatiotemporal scale. We found that while transcriptomic profiles of miracidia are distinguishable based on egg tissue origin, only a small subset of genes is differentially expressed. Further, the basic, unstimulated behavior of miracidia that developed in different niches of the definitive host was significantly different. These different behavioral programs may reflect intrinsic developmental programming or differential viability and hardiness related to tissue origin. These findings underscore the importance of egg source in experimental design and interpretation, with significant implications for the maintenance of laboratory life cycles and the use of miracidia in schistosomiasis research.

Schistosoma mansoni is a major cause of schistosomiasis, a neglected tropical disease that induces granulomatous inflammation, fibrosis, and liver damage. Fucoidan (FUC), a sulfated polysaccharide from brown seaweed, was evaluated for its anti-helminthic, anti-inflammatory, and antifibrotic effects against immature stages of S. mansoni in mice. Forty-eight CD-1 Swiss male albino mice were infected and allocated into six groups: infected untreated control, praziquantel-treated, and FUC-treated groups at 7, 21, 35, and 42 days post-infection. Treatment with FUC at 7, 21, and 35 dpi significantly reduced worm burden, granuloma size, fibrosis, and the expression of TNF-α, IL-1β, and iNOS in liver tissue. The strongest antipathological effects were observed with early-to-mid treatment, particularly FUC7, FUC21, and FUC35. In contrast, FUC42 showed weaker benefit, indicating that efficacy is timing-dependent. These findings suggest that FUC may be a promising candidate for early intervention in S. mansoni infection.

Schistosomiasis control relies on the continued effectiveness of praziquantel (PZQ), yet individual and spatial heterogeneity in PZQ efficacy in the context of repeated mass drug administration (MDA) remains poorly understood. This study aimed to identify individual and spatial determinants of PZQ efficacy against Schistosoma mansoni in rural Uganda. We studied 3870 participants aged 5-90 years from 52 villages in Pakwach, Buliisa, and Mayuge districts in Uganda. Participants were recruited to the SchistoTrack cohort in January-February of 2022 and 2023. Participants received PZQ and were followed up four to five weeks later to assess cure using Kato-Katz (KK) microscopy and point-of-care circulating cathodic antigen (POC-CCA) tests. Logistic regression models were used to identify predictors of cure, defined as a 100% egg reduction rate (ERR). We explored a comprehensive set of 18 sociodemographic, biomedical, water, sanitation, and hygiene, and spatial factors. Subgroup analyses were conducted for adults (aged 18-90) versus children (aged 5-17). Spatial autocorrelation in the outcome and model residuals was assessed using join count statistics and Moran's I. Of 3870 clinical participants, 3704 (95.7%) received PZQ, and 3395 of these had complete clinical data. Among the 3395 treated participants, 1406 (41.4%) were infected with S. mansoni at baseline. The overall cure rate (ERR of 100%) was 76.3%, ranging from 68.9% to 85.4% across districts. Higher odds of cure were associated with older age (OR 1.34) and lower baseline infection intensity (moderate/heavy vs light OR 0.39-0.61). Greater height was associated with lower odds of cure (OR 0.99), which was driven by adults. Compared with Mayuge district, participants in Western districts had lower odds of cure (OR 0.48-0.53). In children, greater distance to water sites with snail presence was linked to higher odds of cure (OR 1.05 per 100m). Results were similar when using POC-CCA outcomes. Spatial clustering of treatment outcomes was observed by district, but no residual spatial autocorrelation remained after accounting for district effects. Incorporating spatial analyses, refining dose assessment, and strengthening post-MDA monitoring may help maintain PZQ effectiveness and support sustainable schistosomiasis control efforts.

BackgroundIntestinal parasitic infections affect more than 1·5 billion people globally, leading to severe health consequences such as malnutrition, anemia, diarrhea, and impaired cognitive development.Methodology/Principal findingsSamples were collected from 3,872 individuals (all ages and both sexes) across 31 rural communities in Madagascar between 2013 and 2017, representing diverse ecological and socioeconomic regions. Intestinal parasite prevalence was assessed by fecal microscopy. Bayesian multilevel logistic regression models were used to estimate overall and regional prevalences while accounting for demographic and spatial variability.Parasite prevalence varied widely across Madagascar, with the highest rates observed for Ascaris lumbricoides (22·0%) and Trichuris trichiura (15·3%), followed by Hymenolepis nana (up to 10·5%), hookworm (up to 8·1%), Strongyloides (0·5%), and Schistosoma mansoni (0·5%). Infection burden was greatest in the northeast and southeast—especially among school-aged children aged 5–19. Sex differences were minor, except for higher hookworm prevalence in males.Conclusions/SignificanceThis study provides the most comprehensive assessment to date of intestinal parasite prevalence across Madagascar, revealing that A. lumbricoides and T. trichiura infections were highly endemic in the humid eastern regions, while H. nana was most common in dry regions. The findings highlight substantial geographic heterogeneity and underscore the need for regionally targeted, multi-sectoral interventions, including improved sanitation and deworming.

Schistosomiasis remains a significant public health challenge, especially in Sub-Saharan Africa (SSA). While individual species prevalence is well documented, the global burden of concurrent co-infection remains poorly quantified, despite its significant clinical and therapeutic implications. This study determined the prevalence of Schistosoma haemtobium (Sh) and Schistosoma mansoni (Sm) co-infection in SSA and its variation with age and geographical location. Following PRISMA guidelines, a systematic search of PubMed, African Journal Online, EMBASE and Google Scholar for studies published between 1980 and 2025 reporting Sh and Sm co-infection was conducted. A random-effects model was used to estimate pooled prevalence, with subgroup analyses conducted by geographical region and age. The study protocol was registered with PROSPERO (CRD420251176915). Twenty-six studies involving 33,121 participants across 11 African countries were included. The overall pooled prevalence of Schistosoma co-infection was 19.1% [95% CI; 12.3%-27.0%, I2= 99.6%, n = 26 studies p < 0.001]. The Western Africa region had the highest pooled prevalence of 26.9% [CI; 14.6%-41.4%, I2 = 99.6%, n = 19 studies, p < 0.001] while the Eastern Africa had the lowest prevalence of 4.8% [CI; 1.7%-9.2%, I2 = 97.2%, n = 5 studies. p < 0.001]. There was a significant difference in the pooled prevalence of Schistosoma co-infection across the various African sub-regions (p < 0.001). There was no significant difference in the pooled prevalence of co-infection across the various age groups (p = 0.47). The prevalence of Schistosoma co-infection is substantial in SSA, particularly within the West African subregion. However, the high heterogeneity observed in this study necessitates a cautious interpretation of the data. Not applicable.

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.

ABSTRACTSchistosomiasis is a neglected disease caused by parasites of the genus Schistosoma that poses serious public health problems. The liver is one of the organs seriously affected by the disease as it lodges Schistosoma eggs. We show results by nonlinear imaging techniques, Second Harmonic Generation and Two‐Photon Excitation Fluorescence, to characterize mice tissues infected with Schistosoma mansoni in an experimental model. We followed the evolution of the disease in liver tissue sections through three stages: 30, 60, and 120 days post‐infection—the pre‐patent, acute, and early chronic phases, respectively. The presence of the Schistosoma eggs causes an increase in the collagen content and also changes in its architecture. The results allow us to clearly evaluate the disease progress helping to improve the understanding of liver fibrosis.Second Harmonic Generation and Two‐Photon Excitation Fluorescence microscopy allows to characterize mice tissues infected with Schistosoma mansoni in an experimental model.

Ethyl acetate extract from Dinizia excelsa Ducke wood: A potential phytotherapeutic agent with antioxidant, cytotoxic and hemolytic (in normal cells), immunomodulatory, antimicrobial, antiparasitic and antitumor activities.

Schistosomiasis, a parasitic disease transmitted by freshwater snails, affects over 251.4 million people globally, with sub-Saharan Africa bearing 95% of the disease burden. This study evaluates the phytochemical composition, characterizes the bioactive secondary metabolites, antioxidant, anti-inflammatory, and the cercaricidal properties, as well as the biosafety of the methanolic and hexane extracts of Chromolaena odorata. Phytochemical screening of C. odorata extracts identified tannins, flavonoids, and saponins in the methanolic extract and steroids and alkaloids in the hexane extract. LC-MS and HPLC-UVESI-TOF-MS analyses confirmed the presence of polyphenols (flavonoids) and aromatic dicarboxylic acid compounds. Antioxidant analysis revealed strong free radical scavenging potential of the plant extracts. Both extracts demonstrated potent cercaricidal activity against Schistosoma mansoni, with LC50 values as low as 0.2012 and 0.2410 μg/mL, respectively. The anti-inflammatory effects were determined via inhibition of heat-induced albumin denaturation, with plant extracts able to inhibit protein denaturation, particularly the methanolic extract that shows a percentage of inhibition of 73.56% at the highest concentration tested. Cytotoxicity assays on LLCMK2 cells showed low toxicity of the extracts. These findings suggest that crude C. odorata extracts possess antischistosomal, antioxidant, and anti-inflammatory properties, supporting their potential integration into primary healthcare strategies for schistosomiasis control.

Preliminary in vitro evaluation of the immunomodulatory, schistosomicidal, antibacterial, antifungal, and antitumor activities of naphthyl-thiazole compounds.

Thiamine (Vitamin B1) metabolism in schistosomes.

Current understanding of gut microbiota alterations during helminthiasis is largely derived from experimental models, often focusing on a narrow range of metrics. This study investigates the structural and functional shifts in the gut microbiome associated withSchistosoma mansoniinfection in a paediatric cohort. We conducted a cross-sectional study of preschool-aged children (12–47 months) comparingS. mansoni-infected individuals (56) to uninfected controls (57). Microbial DNA was extracted from stool samples and sequenced via the Illumina MiSeq v3 platform targeting the V4-16S rRNA region. Diversity was assessed through alpha (Chao1, Simpson, Shannon) and beta (UniFrac and Bray-Curtis distance) metrics. Functional potential was predicted using PICRUSt2 mapped against the KEGG database. The infected group (median age 36 months) exhibited significantly higher alpha diversity and species richness compared to uninfected peers (median age 26 months). Beta diversity analysis confirmed distinct microbial clustering between the two groups (p-value = 0.001). Notably,S. mansoniinfection was characterized by the proliferation of pro-inflammatory taxa and a concomitant depletion of short-chain fatty acid (SCFA) producers. Functional modeling indicated a significant downregulation of metabolic pathways involved in energy metabolism and SCFA biosynthesis.S. mansoniinfection is associated with profound structural and functional dysbiosis in preschool-aged children. The depletion of SCFA producers and altered metabolic pathways suggest that infection may impair host nutritional status and influence the parasite’s lifecycle, necessitating further longitudinal investigation.

Schistosomiasis, caused by worms of the genus Schistosoma, especially S. mansoni, remains a major global health challenge, with over 200 million people infected annually. Notably, sterile immunity does not naturally develop, and drug selection pressure has intensified due to the extensive use of praziquantel (PZQ) in endemic areas for nearly four decades, in addition to the emergence of resistance and lack of sterile immunity. This study investigated the effects of nanoparticle-loaded with natural plant extracts-Ficus carica (Fig) and Olea europaea (Olive)-administered in vivo at all S. mansoni developmental stages: cercariae (G4), schistosomulae (G5), immature worms (G6), and mature worms (G7). The primary objectives were to determine which stage was most susceptible to be eliminated in infected C57BL/6 mice. Fig and Olive were used in this study based on the oath in the wholly Quran. The results demonstrated a progressive improvement from G4 (Lowest) through G7 (Best) in immunological parameters, oxidative stress markers, inflammatory and apoptotic profiles, comet assay results, and liver function tests.

De-novo discovery of posttranslational histone modifications in Schistosoma mansoni stages.

Schistosomiasis remains as a parasitic disease with major morbidity, ongoing transmission, and economic burden, particularly in tropical regions. Praziquantel is the first-line treatment but has limited efficacy against juvenile stages of the parasite. In this context, this study assessed the repurposing potential of anthelmintics against Schistosoma mansoni, focusing on the schistosomicidal activity of nitazoxanide (NTZ), levamisole (LVZ), and thiabendazole (TBZ). In vitro, NTZ exhibited a significant schistosomicidal activity, emerging as a repurposing candidate. In contrast, LVZ and TBZ showed no significant schistosomicidal activity. NTZ was active from 40µg/mL, affecting schistosomula and adult worms in a dose-dependent manner. Ultrastructural analysis revealed wrinkling of the oral and ventral suckers and tegumental alterations in male worms, including shortening of ridges near the tubercles and the presence of multiple small protrusions. In vivo, NTZ showed partial efficacy, with 57.14% reduction in adult worm recovery, whereas PZQ achieved complete elimination. Infected animals presented a mean of 541.86 ± 273.13 viable eggs/cm2, while treatment with nitazoxanide (205mg/kg) or praziquantel (400mg/kg) reduced these values to 247.98 ± 109.68 and 144.92 ± 133.46 eggs/cm2, respectively. Combined administration of NTZ and PZQ resulted in the greatest reduction in viable egg counts, with a mean of 96.75 ± 49.55 eggs/cm2. Although praziquantel resistance has been reported, in this study it fully eliminated adult worms, while nitazoxanide showed lower but relevant activity against both schistosomula and adult stages. These findings confirm the efficacy of praziquantel against adult worms and highlight therapeutic potential of nitazoxanide, underscoring the need for further bioavailability studies.

Schistosomiasis remains difficult to control due to persistent transmission via freshwater snails and reliance on praziquantel (PZQ) as the primary treatment. Novel adjunctive strategies targeting multiple stages of the parasite life cycle are needed. This study investigated the surfactant protein D (SP-D) mimetic CGSPS18 as a potential complementary agent against Schistosoma mansoni. The efficacy of CGSPS18 was evaluated using complementary murine, snail, and in vitro models. In mice, therapeutic PZQ monotherapy was compared with prophylactic and therapeutic combination regimens of CGSPS18 and PZQ, assessing worm burden, oogram patterns, and tissue egg counts. In vitro assays tested the larvicidal activity of CGSPS18 against miracidia and cercariae. In Biomphalaria alexandrina, prophylactic and therapeutic exposure to a sublethal concentration of CGSPS18 was evaluated by survival rate, infection rate, hemocyte parameters, phagocytic activity, and histopathological changes. CGSPS18 demonstrated rapid, concentration-dependent larvicidal activity, achieving 100% mortality of miracidia and cercariae at 50-100 ppm within 10 minutes. In snails, post-infection treatment improved 8-week survival (40.0% vs. 30.0% in infected controls) and significantly reduced infection rates (60.0% vs. 89.67%), alongside alterations in hemocyte profiles, enhanced phagocytic activity, and sporocyst morphological changes. In mice, both therapeutic PZQ monotherapy and therapeutic CGSPS18 + PZQ achieved complete adult worm clearance, with no significant difference between groups. The prophylactic regimen showed only partial efficacy. CGSPS18 exhibits promising laboratory larvicidal activity and beneficial effects in the snail host model. However, in the murine model, co-administration with PZQ did not enhance therapeutic outcomes compared to PZQ alone, although it did not compromise its efficacy. These findings support further mechanistic, safety, and dose-optimization studies rather than definitive claims of synergy or immediate field applicability.Schistosomiasis remains difficult to control because transmission through freshwater snails sustains reinfection, while treatment still relies heavily on praziquantel (PZQ). This study evaluated the surfactant protein D (SP-D) mimetic CGSPS18 in complementary murine, snail, and in vitro models of Schistosoma mansoni. In mice, therapeutic PZQ monotherapy was compared with prophylactic and therapeutic combination regimens containing CGSPS18 by assessing worm burden, oogram patterns, and tissue egg counts. In vitro, CGSPS18 was tested against miracidia and cercariae. In Biomphalaria alexandrina, prophylactic and therapeutic exposure to a sublethal concentration of CGSPS18 was evaluated by survival, infection rate, hemocyte parameters, phagocytic activity, and histopathology. CGSPS18 showed rapid concentration-dependent larvicidal activity, producing 100% mortality of miracidia and cercariae at 50-100 ppm within 10 min. In snails, post-infection treatment improved 8-week survival (40.0% vs. 30.0% in infected controls) and reduced the infection rate (60.0% vs. 89.67%), with associated changes in hemocyte profiles, phagocytic activity, and sporocyst morphology. In mice, therapeutic PZQ alone and therapeutic CGSPS18 + PZQ both achieved complete adult worm clearance, with no significant difference between them, whereas the prophylactic regimen was only partially effective. Overall, CGSPS18 showed promising laboratory larvicidal activity and favorable effects in the snail model. In the murine model, co-administration with PZQ did not outperform PZQ monotherapy but also did not compromise PZQ efficacy. These findings support further mechanistic, safety, and dose-optimization studies rather than definitive claims of synergy or field applicability.

Background/Objectives: Intestinal schistosomiasis caused by Schistosoma mansoni is often underestimated in low-transmission settings due to the limited sensitivity of traditional stool microscopy. More sensitive approaches, including antigen detection and molecular diagnostics, are required to detect infections where egg excretion is low or intermittent. This study aimed to determine the prevalence of S. mansoni infection among school-going children in Nelson Mandela Bay (NMB) using a multi-modal diagnostic approach. Methods: This cross-sectional study included 759 schoolchildren aged 5–14 years from 15 primary schools in NMB. Stool samples were analyzed using the Kato–Katz technique to detect S. mansoni eggs, while urine samples were tested using the point-of-care circulating cathodic antigen (POC-CCA) assay for antigen detection. A subset of stool samples from POC-CCA-positive participants (n = 28) was further analyzed using conventional PCR (cPCR), targeting the S. mansoni cox1 gene, for molecular confirmation. Only a single stool specimen was collected per participant. Results: Among the 759 participants (58% male, 42% female), no egg-positive cases were detected. However, POC-CCA testing identified S. mansoni antigen in 3.2% of participants. Of the 28 POC-CCA-positive samples analyzed by cPCR, 9 (32.1%) were PCR-positive, representing molecular confirmation within the antigen-positive subset rather than overall prevalence. Conclusions: Traditional microscopy underestimated S. mansoni prevalence in this low-prevalence setting. Antigen detection combined with molecular diagnostics improved case identification and highlighted ongoing transmission. These findings support the integration of sensitive diagnostic tools into schistosomiasis surveillance and control strategies in South Africa.

Praziquantel (PZQ) is the mainstay treatment for schistosomiasis, but its efficacy against juvenile schistosomes is limited, which can lead to treatment failure and reinfection. Artemisinin derivatives (ARTs) exhibit potent activity against juvenile worms, offering a complementary mechanism. However, the potential risk of accelerating artemisinin resistance, particularly in schistosomiasis-malaria co-endemic regions, warrants consideration when evaluating ART-based regimens. To find a more optimal regimen for the treatment of schistosomiasis, this meta-analysis evaluated the effectiveness of ARTs and PZQ in combination or as a single agent for the treatment of schistosomiasis. To evaluate the efficacy and safety of PZQ combined with ARTs compared with praziquantel alone for the treatment of schistosomiasis through a meta-analysis of randomized controlled trials. Randomized controlled trials (RCTs) of artemisinin derivatives in combination with praziquantel in the treatment of schistosomiasis were selected from computerized searches of PubMed, Embase, Cochrane Library, and Web of Science, up to November 2025. The inclusion criteria were randomized controlled trials involving participants diagnosed with Schistosoma mansoni, S. haematobium, or S. japonicum, who were treated with PZQ combined with ARTs or PZQ alone, and reporting on efficacy and safety outcomes. The primary outcome indicator was cure rate (CR), and secondary outcome indicators were egg count reduction rate and number of adverse events. The meta-analysis was performed using a random-effects model. Subgroup analyses were conducted to explore the impact of different types of schistosomes. A total of eight studies, involving 1595 patients with schistosomiasis, explored the cure rate of PZQ combined with ARTs and PZQ alone. The pooled result showed that PZQ combined with ARTs had a significantly higher cure rate than PZQ alone (RR 1.12; 95% CI 1.01-1.24; P = 0.02). The corresponding subgroup analysis results showed that the CR of patients with S. mansoni treated with PZQ combined with ARTs was still higher than that of patients treated with PZQ alone (RR 1.16; 95% CI 1.01-1.34; P = 0.03). However, there was no statistically significant difference between PZQ combined with ARTs and PZQ for S. haematobium (RR 1.11; 95% CI 0.99-1.23; P = 0.06) or S. japonicum (RR 1.02; 95% CI 0.95-1.09; P = 0.60) in subgroup analyses. In addition, our study also found that there was no significant difference in egg count reduction between the PZQ-ARTs and PZQ-alone groups, either for S. mansoni (MD -4.54, 95% CI -17.67 to 8.58; P = 0.50) or for S. haematobium (MD -13.74; 95% CI -55.64 to 28.15; P = 0.52). Furthermore, the combination therapy was associated with a higher incidence of adverse events compared with PZQ alone (RR 1.41; 95% CI 1.01 to 1.96; P = 0.04). The combination of PZQ and ARTs can significantly improve the CR for S. mansoni, but not for other schistosome species, at the cost of a higher incidence of adverse events, which were however manageable.