An assessment of a GMP schistosomiasis vaccine (SchistoShield®).

Introduction: Schistosomiasis is a neglected tropical disease that puts over 200 million people at risk, and prevention options are sparse with no approved vaccine. Our vaccine candidate, SchistoShield®, is based on an approximately 87 kDa large subunit of calcium activated neutral protease - termed Sm-p80 - combined with a potent TLR4 agonist-based adjuvant. SchistoShield® has been shown to prevent disease throughout the parasitic life cycle - including egg, juvenile, and adult worm stages - in numerous animal models up to and including baboons. SchistoShield® has been shown safe in both preclinical toxicology studies in rabbits and in a Phase 1 clinical trial in the USA. A Phase 1b trial was initiated in 2023 in endemic regions of Africa, and to date no serious safety signals have been reported. Methods: In preparation for large-scale Phase 2 clinical trials and eventual vaccine deployment, the Sm-p80 antigen production process has been transferred to a manufacturing organization, Quratis Corporation in South Korea, which specializes in preparation of vaccines for large-scale European and African trials. The process of scaling from our current production level of ~2000 vaccine doses, to a process that will generate more than 100 million doses has required multiple improvement steps in the process including fermentation, downstream purification of the protein antigen, lyophilization, and fill and finish. Results: In this study, we detail the large-scale production process of the SchistoShield® protein product by Quratis. In addition, an effort was made to analyze and compare the Quratis-made lot of Sm-p80, referred to as QTP-105, to the cGMP lot of Sm-p80 which is in use in human trials in the USA and Africa, referred to as Sm-p80 DP (made in USA). We show that QTP-105 demonstrates excellent potency, purity, identity, and endotoxin levels compared to our Phase 1 Sm-p80 DP and is suitable for use in Phase 2 studies and beyond.

Elimination of schistosomiasis mekongi in reach for Lao PDR: The last patient with severe disease?

Schistosomiasis mekongi is endemic in a restricted area in Northern Cambodia and the Southern Lao People's Democratic Republic. Severe hepatobiliary morbidity is associated with chronic untreated S. mekongi infection. Since the 1980s extensive control efforts have been employed in endemic areas, resulting in substantial reduction of infection rates and disease burden. We report on a patient with a fatal course of clinically-assessed chronic schistosomiasis. This report underscores that patients with severe chronic Mekong schistosomiasis may still exist and may need treatment support.

Potential associations between Schistosoma mansoni infection and physico-chemical characteristics and water-related human activities in Côte d'Ivoire: a cross-sectional study.

BACKGROUND: Schistosomiasis remains a public health problem, particularly in sub-Saharan Africa. The disease is intimately connected to poverty and environmental factors. Our research was readily embedded into a multi-country schistosomiasis oversampling study. The aim of the study presented here was to determine the prevalence of Schistosoma mansoni and to investigate the role of water body characteristics and water-related human activities in disease transmission. METHODS: In August and September 2022, a cross-sectional study was conducted in the western part of Côte d'Ivoire. Stool and urine samples were collected from 1602 and 1729 children aged 5-14 years, respectively, in 65 villages in the health districts of Biankouma, Ouaninou and Touba. Additionally, data were collected from direct observation of water-related activities at water bodies and interviews conducted with community leaders and health workers. The prevalence and risk factors for Schistosoma infection were assessed using generalised estimating equation models. RESULTS: The prevalence ofS. mansoni and S. haematobium were 27.4% (95% confidence interval [CI] 21.5-34.3%) and 0.1% (95% CI 0.03-0.5%), respectively. Low prevalence of soil-transmitted helminths was observed with 2.4%, 0.4% and 0.2% for hookworm, Trichuris trichiura and Ascaris lumbricoides, respectively. At the health district level, we found S. mansoni prevalence of 34.4% (95% CI 25.0-45.3%), 34.3% (95% CI 24.0-46.2%) and 16.3% (95% CI 9.5-26.6%) for Biankouma, Ouaninou and Touba, respectively. Female and male participants were at a similar risk of infection (29.0% vs. 26.0%, odds ratio [OR]: 1.18, 95% CI 0.92-1.50). Children aged 9-14 years showed a higher prevalence than their younger counterparts aged 5-8 years (34.5% vs. 22.7%, OR: 1.80, 95% CI 1.42-2.27). High infection prevalence was observed in villages where children were washing clothes and dishes at open surface water sites and pursued recreational activities (e.g. swimming and playing in the water). The temperature, total dissolved solids and pH of water samples showed no significant association with S. mansoni infection at the village unit. CONCLUSIONS: Human water-related activities such as washing clothes and playing in the water are risk factors for S. mansoni transmission. Hence, preventive chemotherapy should be combined with information, education and communication to avoid or reduce the frequency of water exposure in children as part of a comprehensive package of interventions towards elimination of schistosomiasis as a public health problem.

Female genital schistosomiasis (FGS) in returned travellers - A review of reported cases.

INTRODUCTION: Female genital schistosomiasis (FGS) is the manifestation of schistosomiasis in the lower and the upper reproductive organs. In endemic areas FGS is frequent with a tremendous impact on reproductive health. Anecdotal observations indicate that FGS also occurs in travellers who became infected when exposing themselves in natural water bodies in endemic areas. The objective of this study is to summarize existing knowledge on FGS in travellers with a focus on FGS-associated morbidity, diagnosis, and treatment. MATERIAL AND METHODS: The PubMed database was searched for reports on FGS in travellers from 1980 to 2023. Case reports of FGS in travellers were identified and reviewed. RESULTS: Thirty-eight case reports were identified. The most common manifestation of FGS were lesions at the vulva (n = 16), the cervix (n = 11), the ovaries and Fallopian tubes (n = 6), the vagina (n = 3) and the endometrium (n = 2). With a few exceptions the diagnosis was spurious. 15 patients with vulval schistosomiasis were treated with the anti-helminthic drug praziquantel (i.e. 40 mg/kg) in 1-3 doses. In all but one patient the lesions disappeared three to six months after treatment. CONCLUSIONS: This study shows that FGS in travellers exhibits the same disease manifestations as in FGS patients living in endemic areas. However, correct diagnosis was established after months to years delaying treatment and cure. This precludes the inclusion of FGS in diagnostic guidelines for female travellers returning from endemic areas for schistosomiasis.

Therapeutic and vaccinomic potential of moonlighting proteins for the discovery and design of drugs and vaccines against schistosomiasis.

Despite significant and coordinated efforts to combat schistosomiasis, such as providing clean water, sanitation, hygiene, and snail control, these strategies still fall short, as regions previously thought to be disease-free have shown active schistosomiasis transmission. Therefore, it is necessary to implement integrated control methods, emphasizing vaccine development for sustainable control of schistosomiasis. Vaccination has significantly contributed to global healthcare and has been the most economically friendly method for avoiding pathogenic infections. Over the years, different vaccine candidates for schistosomiasis have been investigated with varying degrees of success in clinical trials with many not proceeding past the early clinical phase. Recently, proteins have been mentioned as targets for drug discovery and vaccine development, especially those with multiple functions in schistosomes. Moonlighting proteins are a class of proteins that can perform several functions besides their known functions. This multifunctional property is believed to have been expressed through evolution, where the polypeptide chain gained the ability to perform other tasks without undergoing any structural changes. Since proteins have gained more traction as drug targets, multifunctional proteins have thus become attractive for discovering and developing novel drugs since the drug can target more than one function. Moonlighting proteins are promising drug and vaccine candidates for diseases such as schistosomiasis, since they aid in disease promotion in the human host. This manuscript elucidates vital moonlighting proteins used by schistosomes to drive their life cycle and to ensure their survival in the human host, which can be used to develop anti-schistosomal therapeutics and vaccinomics.

Eosinophil and B cell dynamics in the milky spots from Schistosoma mansoni-infected mice - Comparison with spleen and bone marrow, and extramedullary eosinopoiesis.

The milky spots are structures found in the omentum of humans and other vertebrates, representing a fraction of the lymphomyeloid tissue associated with the celom. They majorly consist of B lymphocytes, T lymphocytes, and macrophages. Also found in smaller quantities are mesothelial, stromal, dendritic, and rare mast cells. In an experimental model of Schistosoma mansoni infection, there is significant activation of the omentum and milky spots, which exhibit numerous eosinophils. Despite being described for many years, the complete profile of cells found in milky spots and their functions remains largely unexplored. Here, we evaluate the leukocyte populations of the milky spots in homeostasis and a murine model of Schistosoma mansoni infection. The histopathological characterizations, phenotypic profile analysis, and characterization of the eosinophilic potential of progenitors and precursors comparing the milky spots with the spleen and bone marrow showed significant activation of milky spots in infected mice, with changes in the profile over the analyzed times, showing signs of migration and activation of eosinophils, with local eosinopoiesis and maintenance of the eosinophilic population. In naive mice, B1a and B1b cells comprise only a small fraction of B lymphocytes. However, B1b cells expand significantly during infection, peaking at 60 DPI before stabilizing by 90 DPI. B1a cells also increase initially but decrease over time. The behavior of milky spots differs from other primary and secondary lymphoid organs, acting as a central lymphoid organ in cavity immunity.

Awareness of Primary Care Providers on Genital Schistosomiasis Infection in Northern Nigeria.

BACKGROUND: Genital schistosomiasis (GS) is a debilitating neglected tropical disease caused by Schistosoma haematobium. Despite its significant impact on reproductive health, awareness and knowledge of GS among healthcare providers, especially in Sub-Saharan Africa, remain inadequate, leading to underdiagnosis and mistreatment. METHODS: This study conducted a cross-sectional online survey to assess the awareness and knowledge of GS among 139 primary healthcare providers in Northern Nigeria. A semi-structured self-administered questionnaire was utilized, covering various aspects of GS including its aetiopathogenesis, clinical features, complications, diagnosis, and prevention/treatment. Respondents were scored based on their answers, with an overall score of ≥35 considered indicative of good awareness. RESULTS: Most respondents were aged 31-50 years (41.0%), male (59.7%), married (84.9%), and working in the public sector (97.8%). Mean scores indicated varying levels of awareness across different aspects of GS, with higher awareness regarding aetiopathogenesis (13.99 ±3.275) and prevention/treatment (11.27±1.592). However, awareness of complications remained comparatively lower. Overall, 43.9% of respondents demonstrated good awareness of GS. Regional disparities in awareness were observed, with the North-western region exhibiting the highest awareness (52.6%) followed by the Northeast (40.6%) and Northcentral regions (36.0%). CONCLUSION: The study underscores the urgent need for targeted educational interventions to enhance healthcare providers' knowledge of GS, particularly in regions with lower awareness levels. Improving awareness and knowledge among primary healthcare providers can facilitate early detection, appropriate management, and prevention strategies, thus alleviating the burden of GS on affected communities in Northern Nigeria and beyond.

CONTEXTE: La schistosomiase génitale (SG) est une maladie tropicale négligée et débilitante causée par Schistosoma haematobium. Malgré son impact significatif sur la santé reproductive, la connaissance et la sensibilisation à la SG parmi les prestataires de soins de santé, en particulier en Afrique subsaharienne, restent insuffisantes, conduisant à un sous-diagnostic et à des traitements inappropriés. MÉTHODES: Cette étude a mené une enquête transversale en ligne pour évaluer la connaissance et la sensibilisation à la SG parmi 139 prestataires de soins de santé primaires dans le nord du Nigéria. Un questionnaire semi-structuré auto-administré a été utilisé, couvrant divers aspects de la SG, notamment son étiopathogénie, ses caractéristiques cliniques, ses complications, son diagnostic, ainsi que sa prévention et son traitement. Les répondants ont été notés en fonction de leurs réponses, un score global de ≥ 35 étant considéré comme indicatif d'une bonne connaissance. RÉSULTATS: La plupart des répondants avaient entre 31 et 50 ans (41,0%), étaient des hommes (59,7 %), mariés (84,9 %) et travaillaient dans le secteur public (97,8 %). Les scores moyens indiquaient des niveaux variables de sensibilisation aux différents aspects de la SG, avec une meilleure connaissance de l'étiopathogénie (13,99 ± 3,275) et de la prévention/traitement (11,27 ± 1,592). Cependant, la sensibilisation aux complications restait comparativement plus faible. Globalement, 43,9 % des répondants ont montré une bonne connaissance de la SG. Des disparités régionales dans la sensibilisation ont été observées, la région du nord-ouest affichant la plus grande sensibilisation (52,6 %), suivie des régions du nord-est (40,6 %) et du centre-nord (36,0 %). CONCLUSION: L'étude souligne la nécessité urgente d'interventions éducatives ciblées pour améliorer les connaissances des prestataires de soins de santé sur la SG, en particulier dans les régions où les niveaux de sensibilisation sont plus faibles. Améliorer la sensibilisation et les connaissances des prestataires de soins de santé primaires peut faciliter la détection précoce, la gestion appropriée et les stratégies de prévention, atténuant ainsi le fardeau de la SG sur les communautés touchées dans le nord du Nigéria et au-delà. MOTS-CLÉS: Sensibilisation, Prestataires de soins primaires, Schistosomiase génitale, Nord du Nigéria.

Schistosoma japonicum infection-mediated downregulation of lncRNA Malat1 contributes to schistosomiasis hepatic fibrosis by the Malat1/miR-96/Smad7 pathway.

BACKGROUND: Schistosoma japonicum infection causes hepatic fibrosis, a primary cause of morbidity and mortality associated with the disease, and effective treatments are still lacking. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenic process of various tissue fibroses. However, the role of lncRNAs in schistosomiasis hepatic fibrosis (HF) is poorly understood. Understanding the role of lncRNAs in schistosomiasis HF will enhance knowledge of disease processes and aid in the discovery of therapeutic targets and diagnostic biomarkers. METHODS: Differentially expressed lncRNA profiles in primary hepatic stellate cells (HSCs) of mice infected with S. japonicum were identified using high-throughput lncRNA sequencing. Primary HSCs were isolated from infected mice using collagenase digestion and density-gradient centrifugation, cultured in DMEM with 10% fetal bovine serum. Dual-luciferase reporter assays, nuclear cytoplasm fractionation and RIP assays were employed to assess the relationship between Malat1 and miRNA-96. Malat1 lentivirus and ASO-Malat1 were constructed for forced expression and downregulated expression of Malat1. The Malat1-KO mouse was constructed by CRISPR/Cas9 technology. Pathological features of the liver were evaluated by hematoxylin-eosin (HE), Masson's trichrome staining and immunohistochemistry (IHC). The expression levels of fibrosis-related genes were determined by quantitative real-time PCR (qRT-PCR) and Western blot. RESULTS: A total of 1561 differentially expressed lncRNAs were identified between infected and uninfected primary HSCs. Among the top altered lncRNAs, the downregulated Malat1 was observed in infected HSCs and verified by qPCR. Treatment of infected mice with praziquantel (PZQ) significantly increased the Malat1 expression. Elevated Malat1 expression in infected primary HSC reduced the expressions of profibrogenic genes, whereas Malat1 knockdown had the opposite effect. Moreover, Malat1 was found to interact with miR-96, a profibrotic miRNA, by targeting Smad7. Forced Malat1 expression reduced miR-96 levels in infected primary HSCs, attenuating fibrogenesis and showing negative correlation between Malat1 expression and the expression levels of miR-96 and profibrogenic genes α-SMA and Col1α1. Notably, in Malat1-KO mice, knockout of Malat1 aggravates schistosomiasis HF, while restored Malat1 expression in the infected HSCs reduced the expression of profibrogenic genes. CONCLUSIONS: We demonstrate that lncRNA is involved in regulation of schistosomiasis HF. Elevated lncRNA Malat1 expression in infected HSCs reduces fibrosis via the Malat1/miR-96/Smad7 pathway, thus providing a novel therapeutic target for schistosomiasis HF. Furthermore, Malat1 expression is sensitive to PZQ treatment, thus offering a potential biomarker for assessing the response to chemotherapy.

Depression in the schistosomiasis japonica population based on the PHQ-9 scale: a cross-sectional survey from Jiangxi Province, China.

Depression is the second leading-cause of disability in China. Although studies have shown that more than 80% of patients with advanced schistosomiasis (AS) suffer from anxiety and depression, these study groups are all hospitalized patients with AS and do not represent the extent of the disease in the whole group. To our knowledge, there are no studies assessing the severity of depression in patients with other forms of schistosomiasis japonicum. Therefore, it is necessary to evaluate the occurrence and potential risk factors of depression in the schistosomiasis endemic population. This cross-sectional study was conducted in Jiangxi Province, where schistosomiasis is relatively common in China, as the investigation site. The Patient Health Questionnaire-9 (PHQ-9) scale was selected to assess the depressive symptoms in the study population. At the same time, basic personal information of the research subjects and relevant socio-economics and schistosomiasis endemic area indicators were collected. The survey results show that AS has the highest incidence of depression (34.35%), while non-advanced schistosomiasis (N-AS) and control group (CG) have 22.35% and 22.24% respectively; the incidence of depression in AS is significantly higher than in N-AS and CG, while there is no statistical significance in the comparison between N-AS and CG; the incidence of mild depressive symptoms accounts for 61.08%-75.54% of the total incidence of depression in different groups; multivariate analysis shows that the occurrence of moderate/severe depressive symptoms in the AS group was significantly related to above 60 years old, male, the combination of other serious diseases, personal financial difficulties, and marshland and lake endemic areas. In the N-AS group, the occurrence of moderate/severe depressive symptoms was significantly related to the combination of other serious diseases, personal financial difficulties, significant correlation between marshland and lake endemic areas and the level of control of schistosomiasis epidemics. In conclusion, depression is still relatively common among patients with schistosomiasis patients, especially those with AS. It is recommended that the government and relevant departments consider mental health care when developing prevention and control work in schistosomiasis-endemic areas, in order to effectively protect the physical and mental health of schistosomiasis patients and residents in endemic areas.

Current status of schistosomiasis in school-aged children in Mwanga district, Tanzania: impact of two decades of annual Mass Drug Administration programme.

Schistosomiasis is a neglected tropical disease with significant health implications, particularly among children. A cross-sectional study was conducted among school-aged children (SAC) in Mwanga district, Tanzania, a region known to be co-endemic for S. haematobium and S. mansoni infection and where annual mass drug administration (MDA) has been conducted for 20 years. In total, 576 SAC from 5 schools provided a urine sample for the detection of Schistosoma circulating anodic antigen using the upconverting particle-based lateral flow (UCP-LF CAA) test. Additionally, the potential of the point-of-care circulating cathodic antigen (POC-CCA) and microhaematuria dipstick test as field-applicable diagnostic alternatives for schistosomiasis were assessed and the prevalence outcome compared to UCP-LF CAA. Risk factors associated with schistosomiasis was assessed based on UCP-LF CAA. The UCP-LF CAA test revealed an overall schistosomiasis prevalence of 20.3%, compared to 65.3% based on a combination of POC-CCA and microhaematuria dipstick. No agreement was observed between the combined POC tests and UCP-LF CAA. Factors associated with schistosomiasis included age (5­10 years), involvement in fishing, farming, swimming activities and attending 2 of the 5 primary schools. Our findings suggest a significant progress in infection control in Mwanga district due to annual MDA, although not enough to interrupt transmission. Accurate diagnostics play a crucial role in monitoring intervention measures to effectively combat schistosomiasis.

Structure-Based Discovery of Phytocompounds from Azadirachta indica as Potential Inhibitors of Thioredoxin Glutathione Reductase in Schistosoma mansoni.

Schistosomiasis, a parasitic disease caused by Schistosoma species such as S. haematobium, S. mansoni, and S. japonicum, poses a significant global health burden. The thioredoxin glutathione reductase (TGR) enzyme, crucial for maintaining the parasite's redox balance and preventing oxidative stress, has been identified as a promising target for anti-schistosomal drug development. This study aims to identify potential TGR inhibitors from Azadirachta indica phytochemicals using molecular modeling approaches. We screened 60 compounds derived from A. indica bark and leaves through molecular docking to assess their binding affinity, followed by the evaluation of binding-free energies for the most promising candidates. Drug-likeness and pharmacokinetic properties were assessed, and molecular dynamics simulations were conducted to explore the conformational stability of the protein-ligand complexes. Our findings revealed that several A. indica compounds exhibited significantly lower docking scores (up to -9.669 kcal/mol) compared to the standard drug praziquantel (-4.349 kcal/mol). Notably, Isorhamnetin, Isomargolonone, Nimbaflavone, Quercetin, and Nimbionol demonstrated strong interactions with TGR, although Isorhamnetin showed potential mutagenicity. Further binding free energy calculations and molecular dynamics simulations confirmed the stability of Isomargolonone, Nimbionol, and Quercetin as potential TGR inhibitors. In conclusion, these findings suggest that Isomargolonone, Nimbionol, and Quercetin warrant further experimental validation as promising candidates for anti-schistosomal therapy.

Home-Made Lateral Flow Test Strip Versus POC-CCA Assay for Detection of Active Schistosomiasis in Egypt.

BACKGROUND: For years, the Kato-Katz (KK) technique has been considered the gold standard for diagnosing schistosomiasis. The aim of this study was to compare the effectiveness of our previously developed gold nanoparticle-based lateral flow test strip (AuNPs-LFTS) for diagnosing active Schistosoma mansoni with that of the commercially available point-of-care Circulating Cathodic Antigen detection (POC-CCA) kit. METHODS: In this study, we collected sixty positive and twenty negative urine samples from patients in endemic hot spots in the Nile Delta, as well as from patients visiting the internal medicine clinic at Theodor Bilharz Research Institute (TBRI). We produced monoclonal antibodies (MAbs) against S. mansoni soluble egg antigen (SEA) from cloned hybridoma cells (4D/1D). These MAbs were conjugated with gold and mesoporous silica nanoparticles, and used to develop the LFTS. RESULTS: The LFTS demonstrated a limit of detection (LoD) of 3 ng/ml. The sensitivity and specificity of the developed LFTS were found to be 96.7% and 95%, respectively, compared to 85% and 90% for the POC-CCA detection kit. The cases were divided into groups based on egg count in the stool, categorized as light, moderate, and heavy infections. The sensitivity of the LFTS in the group with light infection was higher than that of the POC-CCA. When using the KK technique (eggs per gram of stool sample [EPG]) as the reference test, the kappa value for the nano-based strips was 0.902, compared to 0.672 for the CCA strips, indicating an almost perfect agreement between KK and our developed LFTS. CONCLUSION: These results confirm the reliability and effectiveness of the LFTS compared to commercially available kits for rapid, sensitive, and early diagnosis of schistosomiasis. However, it is recommended to conduct further assessments of the developed strip on a larger scale with a broader range of cases before considering its introduction to local or international markets.

Prevalence of human Schistosoma mansoni infection in endemic regions (2010-2024): a systematic review and meta-analysis.

Background: Schistosoma mansoni infection poses a substantial public health challenge globally, and the World Health Organization (WHO) aims for the elimination of schistosomiasis by 2030. This study aimed to assess the current prevalence of human S. mansoni infection in endemic regions worldwide between 2010 and 2024. Methods: We conducted a comprehensive search in PubMed/Medline and Scopus databases as well as other public sources from 1 January 2010 to 15 July 2024. Population-based studies reporting the prevalence of S. mansoni infection were eligible. We undertook a random-effects meta-analysis to estimate pooled prevalences with 95% confidence intervals (CIs) in WHO-defined regions and assessed potential risk factors associated with S. mansoni infection. The protocol for this study was registered on PROSPERO (CRD42023438455). Findings: We identified a total of 542 eligible studies involving 1,163,866 individuals who had been tested for S. mansoni infection in 38 countries. The overall, pooled global prevalence of S. mansoni infection in endemic region was 14.8% (95% CI, 13.5%-16.1%). The pooled prevalences (95% CI) in specific regions were: 15.3% (13.9-16.8%) in sub-Saharan Africa, 12.4% (8.9-16.4%) in South America and 9.5% (5.4-14.6%) in the Eastern Mediterranean region. There was a 52.6% decrease in prevalence of S. mansoni infection and a 37% decrease in high-intensity infection for studies conducted between 2010 and 2014 compared to those conducted between 2020 and 2023. The present analysis revealed that factors including male gender, bathing or swimming in natural water bodies, crossing rivers or lakes, and engaging in water irrigation activities such as fishing, working in rice paddies or maintaining irrigation canals were significantly associated with S. mansoni infection. Interpretation: The findings of this investigation revealed that, despite a decline in prevalence and high-intensity infection, 7-12% of people in endemic regions, notably in sub-Saharan Africa, remained affected by schistosomiasis mansoni between 2020 and 2024. This study provides data of relevance to policymakers to support efforts to eliminate this disease. Funding: This study received no funding.

Revisiting immunity vs. exposure in schistosomiasis: A mathematical modeling study of delayed concomitant immunity.

The relative contributions of exposure vs. acquired immunity to the epidemiology of human schistosomiasis has been long debated. While there is considerable evidence that humans acquire partial immunity to infection, age- and sex-related contact patterns with water bodies contaminated with infectious cercarial schistosome larvae also contribute to typical epidemiological profiles of infection. Here, we develop a novel schistosome transmission model that incorporates both partially protective "delayed concomitant" acquired immunity-stimulated by dying worms-and host age- and sex-dependent patterns of exposure. We use a contemporary Bayesian approach to fit the model to historical individual data on exposure to infectious cercaria, eggs per gram of feces, and immunoglobulin E antibodies specific to Schistosoma mansoni Tegumental-Allergen-Like protein 1 collected from a highly endemic community in Uganda, estimating the relative contributions of exposure and acquired immunity. We find that model variants incorporating or omitting delayed concomitant immunity describe equally well the age- and sex-specific immunoepidemiological patterns observed before intervention and 18 months after treatment. Over longer time horizons, we find that acquired immunity creates subtle differences in immunoepidemiological profiles during routine mass drug administration that may confer resilience against elimination. We discuss our findings in the broader context of the immunoepidemiology of schistosomiasis.

Combination Therapy and Phytochemical-Loaded Nanosytems for the Treatment of Neglected Tropical Diseases.

Background: Neglected tropical diseases (NTDs), including leishmaniasis, trypanosomiasis, and schistosomiasis, impose a significant public health burden, especially in developing countries. Despite control efforts, treatment remains challenging due to drug resistance and lack of effective therapies. Objective: This study aimed to synthesize the current research on the combination therapy and phytochemical-loaded nanosystems, which have emerged as promising strategies to enhance treatment efficacy and safety. Methods/Results: In the present review, we conducted a systematic search of the literature and identified several phytochemicals that have been employed in this way, with the notable efficacy of reducing the parasite load in the liver and spleen in cases of visceral leishmaniasis, as well as lesion size in cutaneous leishmaniasis. Furthermore, they have a synergistic effect against Trypanosoma brucei rhodesiense rhodesain; reduce inflammation, parasitic load in the myocardium, cardiac hypertrophy, and IL-15 production in Chagas disease; and affect both mature and immature stages of Schistosoma mansoni, resulting in improved outcomes compared to the administration of phytochemicals alone or with conventional drugs. Moreover, the majority of the combinations studied demonstrated enhanced solubility, efficacy, and selectivity, as well as increased immune response and reduced cytotoxicity. Conclusions: These formulations appear to offer significant therapeutic benefits, although further research is required to validate their clinical efficacy in humans and their potential to improve treatment outcomes in affected populations.

A Recent Advance in the Diagnosis, Treatment, and Vaccine Development for Human Schistosomiasis.

Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species (S. mansoni, S. japonicum, and S. haematobium) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials.

Schistosoma antigens: A future clinical magic bullet for autoimmune diseases?

Autoimmune diseases are characterized by dysregulated immunity against self-antigens. Current treatment of autoimmune diseases largely relies on suppressing host immunity to prevent excessive inflammation. Other immunotherapy options, such as cytokine or cell-targeted therapies, have also been used. However, most patients do not benefit from these therapies as recurrence of the disease usually occurs. Therefore, more effort is needed to find alternative immune therapeutics. Schistosoma infection has been a significant public health problem in most developing countries. Schistosoma parasites produce eggs that continuously secrete soluble egg antigen (SEA), which is a known modulator of host immune responses by enhancing Th2 immunity and alleviating outcomes of Th1 and Th17 responses. Recently, SEA has shown promise in treating autoimmune disorders due to their substantial immune-regulatory effects. Despite this interest, how these antigens modulate human immunity demonstrates only limited pieces of evidence, and whether there is potential for Schistosoma antigens in other diseases in the future remains an unsolved question. This review discusses how SEA modulates human immune responses and its potential for development as a novel immunotherapeutic for autoimmune diseases. We also discuss the immune modulatory effects of other non-SEA schistosome antigens at different stages of the parasite's life cycle.

Title: Les antigènes de Schistosoma : une solution clinique miracle pour les maladies auto-immunes? Abstract: Les maladies auto-immunes sont caractérisées par une immunité dysrégulée contre les auto-antigènes. Le traitement actuel des maladies auto-immunes repose en grande partie sur la suppression de l'immunité de l'hôte pour prévenir une inflammation excessive. D'autres options d'immunothérapie, telles que les thérapies à base de cytokines ou à cellules ciblées, ont également été utilisées. Cependant, la plupart des patients ne bénéficient pas de ces thérapies car la maladie récidive généralement. Par conséquent, des efforts supplémentaires doivent être faits pour trouver des thérapies immunitaires alternatives. L'infection à Schistosoma est un problème de santé publique important dans la plupart des pays en développement. Les parasites Schistosoma produisent des œufs qui sécrètent en continu des antigènes solubles d'œufs (ASO), qui sont connus comme des modulateurs des réponses immunitaires de l'hôte en renforçant l'immunité Th2 et en atténuant les résultats des réponses Th1 et Th17. Récemment, les ASO se sont révélés prometteurs dans le traitement des troubles auto-immuns en raison de leurs effets immuno-régulateurs substantiels. Malgré cet intérêt, la façon dont ces antigènes modulent l'immunité humaine ne montre que des éléments de preuve limités, et la question de savoir si les antigènes de Schistosoma pourraient être utiles dans d'autres maladies à l'avenir reste sans réponse. Cette revue examine la manière dont les ASO modulent les réponses immunitaires humaines et leur potentiel pour le développement de nouveaux traitements immunothérapeutiques contre les maladies auto-immunes. Nous discutons également des effets immunomodulateurs d'autres antigènes de schistosomes non-ASO à différents stades du cycle de vie du parasite.

Evaluation of the epidemiological situation of intestinal schistosomiasis using the POC-CCA parasite antigen test and the Kato-Katz egg count test in school-age children in endemic villages in western Côte d'Ivoire.

Schistosomiasis is an endemic disease in Côte d'Ivoire. We compared the conventional Kato Katz (KK) test and a more sensitive but rarely used method, the point-of-care circulating cathodic antigen (POC-CCA), in order to contribute to the development of a more appropriate strategy for the control and elimination of intestinal schistosomiasis in western Côte d'Ivoire. A cross-sectional epidemiological survey was conducted in eight elementary schools in the Guémon and Cavally regions from February to December 2020. Selected schoolchildren provided stool and urine samples to detect the presence of Schistosoma mansoni eggs and parasite antigen using the KK and POC-CCA tests, respectively. A total of 554 schoolchildren were included in the study. The overall prevalence of intestinal schistosomiasis was 10% and 67% for KK and POC-CCA, respectively. The POC-CCA detected an infection rate of 100%, while the KK yielded a rate of 42%. In schools, prevalence ranged from 27 to 100% with POC-CCA and from 0 to 42% with KK. Swimming, fishing, washing clothes, and dishwashing were significantly associated with the onset of infection and high intensities. The epidemiological risk factors for intestinal schistosomiasis updated here using KK and POC-CCA diagnostic methods showed that prevalence was much higher than previously estimated using the KK. The POC-CCA is more sensitive and ways should be considered to improve its specificity in order to improve the diagnosis.

Title: Évaluation de la situation épidémiologique de la schistosomiase intestinale à l'aide du test antigénique parasitaire POC-CCA et du test de numération des œufs Kato-Katz chez les enfants d'âge scolaire de villages endémiques de l'ouest de la Côte d'Ivoire. Abstract: La schistosomiase est une maladie endémique en Côte d'Ivoire. Nous avons comparé le test conventionnel Kato Katz (KK) et une méthode plus sensible mais rarement utilisée, l'antigène cathodique circulant au point d'intervention (POC-CCA), afin de contribuer au développement d'une stratégie plus appropriée pour le contrôle et l'élimination de la schistosomiase intestinale dans l'ouest de la Côte d'Ivoire. Une enquête épidémiologique transversale a été menée dans huit écoles élémentaires des régions de Guémon et Cavally de février à décembre 2020. Des écoliers sélectionnés ont fourni des échantillons de selles et d'urine pour détecter la présence d'œufs de Schistosoma mansoni et d'antigène parasitaire à l'aide respectivement des tests KK et POC-CCA. Au total, 554 écoliers ont été inclus dans cette étude. La prévalence globale de la schistosomiase intestinale était respectivement de 10% et 67% pour KK et POC-CCA. Le POC-CCA a détecté un taux d'infection de 100%, tandis que le KK a donné un taux de 42%. Dans les écoles, la prévalence variait de 27 à 100% avec POC-CCA et de 0 à 42% avec KK. La natation, la pêche, la lessive et la vaisselle étaient associées de manière significative à l'apparition de l'infection et à des intensités élevées. La mise à jour ici des facteurs de risque épidémiologiques de la schistosomiase intestinale à l'aide des méthodes de diagnostic KK et POC-CCA a montré que la prévalence était beaucoup plus élevée que celle estimée précédemment à l'aide du KK. Le POC-CCA est plus sensible et des moyens devraient être envisagés pour améliorer sa spécificité afin de rendre un meilleur diagnostic.

Safety and efficacy of praziquantel in pregnant women infected with Schistosoma haematobium in Lambaréné, Gabon - Clinical results from the randomized, single-blinded, controlled freeBILy-Gabon trial.

OBJECTIVES: Despite evidence of praziquantel's (PZQ) safety for treating schistosomiasis in pregnancy, many countries withhold treatment. Only two randomized controlled trials have investigated PZQ in pregnancy, none involving Schistosoma haematobium. METHODS: Pregnant women during the second trimester in Lambaréné (Gabon) were screened for S. haematobium infection using urine microscopy and circulating anodic antigen detection. Participants positive for either test were randomized (3:1) to single-dose PZQ 40 mg/kg during pregnancy versus no treatment during pregnancy. Investigators were blinded for allocation. Primary outcomes were reduction of egg (egg reduction rate [ERR]) and antigen production (infection reduction rate [IRR]) while explorative outcomes included assessment of cure rate, adverse events, maternal hemoglobin levels, maternal anemia prevalence at delivery, pregnancy outcomes, and newborn anthropometric parameters. RESULTS: Of 761 women screened 165 were eligible and randomized (intervention n = 124, control n = 41). Of them, 124 completed the study (n = 90 and n = 34, respectively). Treatment led to a significantly higher ERR (95.0% [91-97%] vs 27.0% [-42-63%]) and IRR (95% [91-97%] vs 56% [14-78%]). Common adverse events were dizziness, nausea, and vomiting. Maternal anemia at delivery was significantly lower in the intervention group (odds ratio: 0.40 [0.16;0.96], P = 0.04). No increased risk for adverse pregnancy outcomes was observed. CONCLUSIONS: This first randomized controlled trial investigating PZQ in pregnant women with S. haematobium found PZQ to be safe, effective, and reducing maternal anemia. We recommend treating confirmed infections to prevent morbidity in pregnant women.

Schistosomiasis-Microbiota Interactions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Schistosomiasis, a tropical disease affecting humans and animals, affected 251.4 million people in 2021. Schistosoma mansoni, S. haematobium, S. intercalatum, and S. japonicum are primary human schistosomes, causing tissue damage, granulomas, ulceration, hemorrhage, and opportunistic pathogen entry. The gut and urinary tract microbiota significantly impact a host's susceptibility to schistosomiasis, disrupting microbial balance; however, this relationship is not well understood. This systematic review and meta-analysis explores the intricate relationship between schistosomiasis and the host's microbiota, providing crucial insights into disease pathogenesis and management. METHODS: This systematic review used PRISMA guidelines to identify peer-reviewed articles on schistosomiasis and its interactions with the host microbiome, using multiple databases and Google Scholar, providing a robust dataset for analysis. The study utilized Meta-Mar v3.5.1; descriptive tests, random-effects models, and subgroups were analyzed for the interaction between Schistosomiasis and the microbiome. Forest plots, Cochran's Q test, and Higgins' inconsistency statistic (I2) were used to assess heterogeneity. RESULTS: The human Schistosoma species were observed to be associated with various bacterial species isolated from blood, stool, urine, sputum, skin, and vaginal or cervical samples. A meta-analysis of the interaction between schistosomiasis and the host microbiome, based on 31 studies, showed 29,784 observations and 5871 events. The pooled estimates indicated a significant association between schistosomiasis and changes in the microbiome of infected individuals. There was considerable heterogeneity with variance effect sizes (p < 0.0001). Subgroup analysis of Schistosoma species demonstrated that S. haematobium was the most significant contributor to the overall heterogeneity, accounting for 62.1% (p < 0.01). S. mansoni contributed 13.0% (p = 0.02), and the coinfection of S. haematobium and S. mansoni accounted for 16.8% of the heterogeneity (p < 0.01), contributing to the variability seen in the pooled analysis. Similarly, praziquantel treatment (RR = 1.68, 95% CI: 1.07-2.64) showed high heterogeneity (Chi2 = 71.42, df = 11, p < 0.01) and also indicated that Schistosoma infections in males (RR = 1.46, 95% CI: 0.00 to 551.30) and females (RR = 2.09, 95% CI: 0.24 to 18.31) have a higher risk of altering the host microbiome. CONCLUSIONS: Schistosomiasis significantly disrupts the host microbiota across various bodily sites, leading to increased susceptibility to different bacterial taxa such as E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Staphylococcus, Streptococcus, and Mycobacterium species (M. tuberculosis and M. leprae). This disruption enables these bacteria to produce toxic metabolites, which in turn cause inflammation and facilitate the progression of disease. The impact of schistosomiasis on the vaginal microbiome underscores the necessity for gender-specific approaches to treatment and prevention. Effective management of female genital schistosomiasis (FGS) requires addressing both the parasitic infection and the resulting microbiome imbalances. Additionally, praziquantel-treated individuals have different microbiome compositions compared to individuals with no praziquantel treatment. This suggests that combining praziquantel treatment with probiotics could potentially decrease the disease severity caused by an altered microbiome.