Mansoni Infection Research Articles

Current water contact and Schistosoma mansoni infection have distinct determinants: a data-driven population-based study in rural Uganda

Water contact is a key element of the system of human-environment interactions that determine individual exposure to schistosome parasites and, in turn, community transmission. Yet, there is a limited understanding of the complexity of water contact. We characterised patterns and determinants of water contact within the large-scale SchistoTrack study on 2867 individuals aged 5-90 years in Eastern and Western Uganda, employing Bayesian variable selection and advanced statistical modelling. We found a 15-year gap between the population-level peak in water contact (age 30) and infection (age 15) with practically no correlation (ρ = 0.03) between individual-level water contact and infection. Adults had higher water contact than children, and 80% of individuals with water contact lived within 0.43 km of water bodies. Domestic water contact was most common for children and women, while occupational water contact was most common for men. Water contact was positively associated with older age, fishing or fish mongering occupations, the number of water sites, and type (beach/pond/swamp), and lower village-level infection prevalence. Only older age and fishing were positively, though inconsistently, associated with infection status/intensity. By providing profiles of at-risk groups, and suitable water contact metrics, our research opens avenues for spatially-targeted interventions and exposure monitoring in endemic countries.

Mapping schistosomiasis risk landscapes and implications for disease control: A case study for low endemic areas in the Middle Paranapanema river basin, São Paulo, Brazil.

Schistosomiasis, a chronic parasitic disease, remains a public health issue in tropical and subtropical regions, especially in low and moderate-income countries lacking assured access to safe water and proper sanitation. A national prevalence survey carried out by the Brazilian Ministry of Health from 2011 to 2015 found a decrease in human infection rates to 1%, with 19 out of 26 states still classified as endemic areas. There is a risk of schistosomiasis reemerging as a public health concern in low-endemic regions. This study proposes an integrated landscape-based approach to aid surveillance and control strategies for schistosomiasis in low-endemic areas. In the Middle Paranapanema river basin, specific landscapes linked to schistosomiasis were identified using a comprehensive methodology. This approach merged remote sensing, environmental, socioeconomic, epidemiological, and malacological data. A team of experts identified ten distinct landscape categories associated with varying levels of schistosomiasis transmission potential. These categories were used to train a supervised classification machine learning algorithm, resulting in a 92.5% overall accuracy and a 6.5% classification error. Evaluation revealed that 74.6% of collected snails from water collections in five key municipalities within the basin belonged to landscape types with higher potential for S. mansoni infection. Landscape connectivity metrics were also analysed. This study highlights the role of integrated landscape-based analyses in informing strategies for eliminating schistosomiasis. The methodology has produced new schistosomiasis risk maps covering the entire basin. The region's low endemicity can be partly explained by the limited connectivity among grouped landscape-units more prone to triggering schistosomiasis transmission. Nevertheless, changes in social, economic, and environmental landscapes, especially those linked to the rising pace of incomplete urbanization processes in the region, have the potential to increase risk of schistosomiasis transmission. This study will help target interventions to bring the region closer to schistosomiasis elimination.

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

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 and2024. 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). 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. 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. This study received no funding.

The effect of intensive praziquantel administration on vaccine-specific responses among schoolchildren in Ugandan schistosomiasis-endemic islands (POPVAC A): an open-label, randomised controlled trial

Vaccine responses differ between populations and are often impaired in rural and low-income settings. The reasons for this are not fully understood, but observational data suggest that the immunomodulating effects of parasitic helminths might contribute. We hypothesised that Schistosoma mansoni infection suppresses responses to unrelated vaccines, and that suppression could be reversed-at least in part-by intensive praziquantel administration. We conducted an open-label, randomised controlled trial of intensive versus standard intervention against S mansoni among schoolchildren aged 9-17 years from eight primary schools in Koome islands, Uganda. Children were randomly allocated to either an intensive group or a standard group with a computer-generated 1:1 randomisation using permuted blocks sizes 4, 6, 8, and 10. Participants in the intensive group received three praziquantel doses (approximately 40 mg/kg) 2 weeks apart before first vaccination at week 0, and every 3 months thereafter. Participants in the standard group were given one dose of approximately 40 mg/kg praziquantel after the week 8 primary endpoint. Participants in both groups received the BCG vaccine (Serum Institute of India, Pune, India) at week 0; the yellow fever (Sanofi Pasteur, Lyon, France), oral typhoid (PaxVax, London, UK), and first human papillomavirus (HPV) vaccination (Merck, Rahway, NJ, USA) at week 4; and the HPV booster and tetanus-diphtheria vaccine (Serum Institute of India) at week 28. The primary outcome was vaccine response at week 8 (except for tetanus and diphtheria, which was assessed at week 52). The primary analysis population was participants who were infected with S mansoni at baseline, determined retrospectively using either plasma circulating anodic antigen (CAA) or stool PCR. The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN60517191) and is complete. Between July 9 and Aug 14, 2019, we enrolled 478 participants, with 239 children per group. 276 (58%) participants were male and 202 (42%) participants were female. Among participants who were positive for S mansoni at baseline (171 [72%] in the intensive group and 164 [69%] in the standard group) intensive praziquantel administration significantly reduced pre-vaccination infection intensity (to median 30 CAA pg/mL [IQR 7-223] vs 1317 [243-8562], p<0·001) compared with standard treatment. Intensive praziquantel administration also reduced week 8 HPV-16-specific IgG response (geometric mean ratio 0·71 [95% CI 0·54-0·94], p=0·017), but had no effect on other primary outcomes. Among all participants (regardless of S mansoni status at baseline) intensive praziquantel administration significantly improved week 8 BCG-specific IFNγ ELISpot response (1·20 [1·01-1·43], p=0·038). Recognised adverse effects of praziquantel were reported more frequently in the intensive group. There were no recorded serious adverse events in either group. We show evidence suggesting that praziquantel administration improves the BCG-specific cellular response, but not humoral responses to other vaccines. Despite observational evidence that helminths impair vaccine response, these results show minimal immediate benefits of reducing helminth burden. The effect of longer-term helminth control should be investigated. UK Medical Research Council. For the Luganda translation of the abstract see Supplementary Materials section.

Multiple lung nodules revealing chronic pulmonary schistosomiasis.

We described the case of a Guinea-Conakry patient presented with a pulmonary Schistosoma mansoni infection. Hypereosinophilia, positive serology and multiple lung nodules led us to suspect the diagnosis. However, parasitic examination of stool and urine were negative. The diagnosis was obtained thanks to specific serum PCR.

Protective effect of Schistosoma mansoni infection and/or soluble egg antigen on allergic reaction in male mice

BackgroundInnovative treatments are being examined to develop more effective and innocuous protective medications for allergic conditions. In recent times, helminth-based immunotherapy is gaining attention as a potential therapeutic approach that could establish a pathway for controlling anaphylaxis. To the extent of our knowledge, there are no previous studies that examine the protective effect of both Schistosoma mansoni (S. mansoni) and its soluble egg antigen (SEA) together against anaphylaxis. Therefore, the purpose of the current study was to examine and compare the impact of SEA immunization and/or S. mansoni infection on Ovalbumin (OVA)-induced systemic anaphylaxes in mice model.ResultsThe outcome results revealed that S. mansoni infection and SEA immunization were able to improve body weight, reduce the mortality rate, increase plasma IgE and IgG4 levels and decrease histamine levels in broncho-alveolar lavage fluid (BALF). Additionally, they elevated interleukin-(IL)-4, IL-10, interferon-gamma (IFN-γ) and transforming growth factor-beta (ΤGF-β) levels in BALF. They also restored the stabilization of peritoneal mast cells (MCs) membrane in inverted light microscopy results accompanied by amelioration of the lung and liver histology.ConclusionsThe present study provided indication for the prophylactic effects of S. mansoni infection and SEA immunization against OVA-induced systemic anaphylaxes in mice model. Also, it focuses on the possible therapeutic mechanisms of helminth-derived products administration that might be related to upregulation of immune regulatory mechanisms. As a result, S. mansoni-derived products may be used as preventative supplemented treatments to inhibit the development of anaphylaxis which provides us with a new vision for developing pioneering therapy.

High prevalence of intestinal schistosomiasis in school-age children in the villages adjacent to Lake Chamo in the southern Rift Valley of Ethiopia.

The prevalence of intestinal schistosomiasis remains a challenge despite government efforts to eliminate the disease. This study aims to assess the prevalence of intestinal schistosomiasis in school-age children living in the villages surrounding Lake Chamo in southern Rift Valley of Ethiopia. A cross-sectional study was conducted from January to July 2023 in Shele Mela Kebele in Gamo Zone, South Ethiopia. Stool samples were collected from 597 school-age children. A singe Kato-Katz for helminths and formalin-ether concentration technique for protozoan parasites were used to process the samples. The intensity of Schistosoma mansoni infection among school-age children was determined by counting the number of eggs per gram of stool. Of the 597 children screened, 52.3% (95% CI: 48.4.4-56.4) were positive for Schistosoma mansoni. These findings showed that 55% of the infections were light, 30.3% were moderate, and 14.7% were heavy. The mean egg count of S. mansoni parasites was 182.1 eggs per gram. The prevalence of other intestinal parasites (Hymenolopis nana, Ascaris lumbricoides, Hookworm, Taenia species, Giardia lamblia and Entamoeba histolytica) was found to be 7.7% (46/597). The overall prevalence of S. mansoni co-infection with other intestinal parasites was 5.0% (30/597). Specifically, the co-infection rates were 1.5% for A. lumbricoides, 1.3% for H. nana, 1.0% for Taenia species, 0.2% for Hookworm, 0.2% for E. histolytica, and 0.2% for G. lamblia. The study showed a high rate of S. mansoni infection among school-age children. This calls for immediate action, such as school-based deworming, to protect these children from the disease and reduce the burden. Further research is needed to understand the transmission of the infection by the intermediate host.

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 (5–10 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.

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

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. 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 5-14years, 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. 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 9-14years showed a higher prevalence than their younger counterparts aged 5-8years (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. 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.

Molecular epidemiology and population genetics of Schistosoma mansoni infecting school-aged children situated along the southern shoreline of Lake Malawi, Malawi.

In areas of low disease endemicity, highly sensitive diagnostic tools to identify, diagnose, and monitor intestinal schistosomiasis transmission are needed to reliably measure the burden and risk of infection. Here, we used highly sensitive molecular diagnostic methods to investigate Schistosoma mansoni prevalence and transmission along the southern shoreline of Lake Malawi, five years post-disease outbreak. Faecal and urine samples were provided by school-aged children situated along the southern shoreline of Lake Malawi. Kato-Katz faecal-egg microscopy and point-of-care circulating cathodic antigen (POC-CCA) rapid diagnostic tests were then performed to diagnose infection with S. mansoni. Urine-egg microscopy was also used to diagnose infection with Schistosoma haematobium. In addition, Schistosoma miracidia were isolated from faecal material using a standard miracidium hatching technique. A two-step real-time PCR approach was then used to diagnose infection with S. mansoni using DNA isolated from faecal samples. Furthermore, isolated miracidia were genotyped to species level through PCR and Sanger sequencing. Phylogenetic analyses were then carried out to identify which previously defined S. mansoni cox1 lineage group S. mansoni miracidia were most closely related to. The measured prevalence of S. mansoni infection varied considerably depending on which diagnostic assay was used. When compared to real-time PCR, faecal-egg microscopy had a sensitivity of 9% and a specificity of 100%. When POC-CCA 'trace' results were considered positive, POC-CCA had a sensitivity of 73% and a specificity of 81% when compared to real-time PCR. However, when considered negative, POC-CCA sensitivity was reduced to 56%, whereas specificity was increased to 90%. In addition, a high degree of S. haematobium DNA was detected in DNA isolated from faecal samples and motile S. haematobium miracidia were recovered from faecal samples. Schistosoma mansoni miracidia were closely related to two independent cox1 lineage groups, suggesting multiple recent introduction and colonisation events originating from surrounding east African countries. Intestinal schistosomiasis is now highly prevalent along the southern shoreline of Lake Malawi just five years post-disease outbreak. In addition, a high prevalence of urogenital schistosomiasis persists. The revision of ongoing schistosomiasis control programmes in this area is therefore recommended. Our study also highlights the need for reliable diagnostic assays capable of distinguishing between Schistosoma species in multispecies co-endemic areas.

Control and elimination of Schistosoma mansoni infection in adult individuals on Ukerewe island, northwestern Tanzania: baseline results before implementation of intervention measures

BackgroundCommunities living along the shoreline and on the islands of Lake Victoria in northwestern Tanzania remain endemic for schistosomiasis and suffer from the life-threatening morbidities associated with the disease. Nevertheless, the control measures particularly the mass drug administration do not cover the adult population. The current project on Ukerewe island aims to close this gap by involving adult community members in the control program. Here we report the baseline results of S. mansoni infection and associated hepatosplenic morbidities and factors before implementing the project activities.MethodsA cross-sectional analytical study was conducted with 4,043 participants aged ≥ 18 years living in 20 villages on Ukerewe island, northwestern Tanzania. Individual stool and urine samples were collected and examined using the Kato-Katz (KK) technique and point-of-care circulating cathodic antigen testing(POC-CCA) to identify S. mansoni eggs and antigens, respectively. All study participants underwent ultrasound evaluation of S. mansoni hepatosplenic morbidities using the Niamey protocol. Rapid diagnostic tests were used to diagnose HIV infection, hepatitis C and chronic hepatitis B. A questionnaire was used to collect demographic data and reported clinical symptoms of study participants.ResultsA total of 4,043 participants took part in the study, of which 49.7% (n = 2,009) and 50.3% (n = 2,035) were male and female, respectively. The overall prevalence of S. mansoni infection was 30.4% (95%CI:29.0-31.9%) and 84.7% (95%CI:83.3–85.9%), respectively, based on the KK technique and the POC-CCA test. The geometrical mean eggs per gram of faeces (GMepg) was 105.3 (95%CI:98.7-112.3% GMepg) with 53.9%, 32.4% and 13.7% of the participants having mild, had moderate and severe intensity of infection. The prevalence of hepatitis C, HIV, and hepatitis B was 0.4%, 2.2% and 4.7%, with 0.2%, 2.2% and 5.4% of the infected individuals coexisting with S. mansoni infection. The prevalence of splenomegaly, periportal fibrosis, hepatomegaly, and portal vein dilatation was 40.5%(95%CI: 38.8–42.1%), 48.1%(95%CI:64.4–49.7%), 66.2%(95%CI:4.6–67.7%) and 67.7%(95%CI:66.2–69.2%), with their prevalence varying depending on the demographic information and infection status of the participants. Other detectable ultrasound-related morbidities included ascites (1.7%), collateral veins (18.3%) and gall bladder wall thickness (40.4%). Age groups, gender, reported clinical characteristics, reported non-use of the drug praziquantel, liver imaging pattern, and place of residence remained independently associated with hepatosplenic morbidities.ConclusionThe current study setting is endemic for S. mansoni infection and the population has a high prevalence of the disease associated hepatosplenic morbidities characterized by hepatomegaly, splenomegaly, ascites, gall bladder wall thickening, periportal fibrosis and portal vein dilatation. Several demographic, clinical and epidemiological circumstances remained independently associated with S. mansoni infection and associated morbidities. These findings call for integrative intervention efforts, starting with whole community MDA that includes all out of schools community members.

Epidemiology of periportal fibrosis and relevance of current Schistosoma mansoni infection within the context of repeated mass drug administration in rural Uganda: a population-based, cross-sectional study

WHO guidelines for schistosomiasis-related morbidity control and elimination rely on current infection as a proxy indicator for morbidity. We evaluated these guidelines within the context of repeated mass drug administration and periportal fibrosis attributable to chronic intestinal schistosomiasis. We examined 1442households randomly sampled from 38villages in Buliisa, Pakwach, and Mayuge districts of Uganda within the SchistoTrack cohort. Periportal fibrosis was diagnosed in 2834individuals aged 5-90years using ultrasound and image patterns C-F from the Niamey protocol. Schistosoma mansoni status and intensity were diagnosed by Kato-Katz microscopy and point-of-care circulating cathodic antigen tests. Schistosome infection, co-infections, and comorbidities were examined as exposures for periportal fibrosis. Multivariable logistic regressions were run with SEs clustered by household. Between Jan 6and Feb 3, 2022, 342 (12·1%) of 2834 participants were diagnosed with periportal fibrosis. ByKato-Katz microscopy, 1229 (43·4%) of 2834participants were infected. 1863 (65·7%) of 2834participants had trace positive point-of-care circulating cathodic antigen tests, which was higher than prevalence by Kato-Katz microscopy, and 1158 (40·9%) of 2834participants had trace negative point-of-care circulating cathodic antigen tests. Individual schistosome status, intensity, and prevalence of heavy intensity infections of less than 1% and less than 5% were not correlated with periportal fibrosis likelihood or village prevalence. Periportal fibrosis likelihood linearly increased with age from age 5 years to age 25years, non-linearly increased from age 26 years to age 45years, attenuated or remained unchanged from age 46 years to age 60years, and steadily decreased past 60years of age. History of liver diseases, HIV, and ultrasound-detected chronic hepatitis or early cirrhosis-like disease were associated with more than two-times increased periportal fibrosis likelihood. WHO guidelines reliant on current schistosome status and intensity are uninformative for identifying probable cases or communities with periportal fibrosis. History of HIV and underlying chronic hepatitis or early cirrhosis-like disease are risk factors that could be investigated for periportal fibrosis surveillance and management. NDPH Pump Priming Fund, Wellcome Trust, John Fell Fund, Robertson Foundation, and UK Research and Innovation Engineering and Physical Sciences Research Council.

Oral Administration of Kaempferol Isolated from Baccharis Mattogrosensis Enables In Vivo Activity Against Schistosoma Mansoni.

Baccharis mattogrosensis is a species from Asteraceae which has been used in Brazilian folk medicine to treatment of several illnesses, including those caused by parasites. In the present work, the MeOH extract of aerial parts of B. mattogrosensis was subjected to chromatographic fractionation to afford three flavonoids: apigenin (1), quercetin (2), and kaempferol (3) as well as a mixture three chlorogenic acids: 3,4-O-dicaffeoylquinic (4), 3,5-O-dicaffeoylquinic (5), and 4,5-O-dicaffeoylquinic (6) acids. When tested in vitro, kaempferol (3) exhibited activity against Schistosoma mansoni with EC50=81.86 μM, whereas compounds 1, 2, 4-6 showed to be inactives. Considering this result, the effects of kaempferol (3) against S. mansoni infection using an experimental approach (in vivo assay) was tested at first time. Using a single oral dose (400 mg/kg) of kaempferol (3) to S. mansoni-infected mice reduced the worm burden by 25.5 %. Similarly, the number of eggs, which are responsible for a variety of pathologies and transmission of schistosomiasis, was decreased by 28.8 % in treated mice. Collectively, although kaempferol (3) is partially active when administered orally in a mouse model of schistosomiasis, our results suggest that this compound could be, in future studies, administered in different forms, such as nanoformulation.

Intestinal Protozoa and Schistosoma Mansoni (Sambon 1907) Infections Among Some Pupils in Akko Local Government Area of Gombe State, Nigeria

The prevalence of intestinal protozoa and Schistosoma mansoni infections among primary school pupils in Akko Local Government Area of Gombe State, Nigeria was investigated. Stool samples were collected from 450 pupils aged 5–13 years in the three (3) districts of Akko Local Government Area. A structured questionnaire was used to collect relevant demographic and risk factor data associated with intestinal protozoa and S. mansoni infections. The stool samples were processed using the formol-ether concentration technique and microscopically examined for protozoan cysts and S. mansoni eggs; 12.4 % of the stool samples were positive for cysts and eggs. The prevalence of intestinal protozoa were: Entamoeba histolytica (4.9 %), Entamoeba coli (3.8 %) and Balantidium coli (2 %); Schistosoma mansoni eggs had a prevalence of 1.6 %. The prevalence of infection with protozoa and S. mansoni infections in individual schools was not uniform despite the similarity in the local topography and weather conditions. Source of drinking water and type of toilet used significantly associated with infection by intestinal protozoa and S. mansoni (Odd’s Ratio value for Pit-latrine was 18.959). The prevalence of intestinal protozoa and Schistosoma mansoni infections among the primary school pupils was associated with poor personal hygiene habits at home and in school, and improper disposal of human and animal waste as implied by the responses to the questionnaire. It is therefore recommended that a concerted health education effort is necessary in order to curb the infections within the schools and the communities.

Development of a Lipid-encapsulated TGFβRI-siRNA Drug for Liver Fibrosis Induced by Schistosoma mansoni.

Schistosoma mansoni infection leads to chronic schistosomiasis and severe hepatic fibrosis. We designed a liver-targeted lipid nanoparticle (LNP) carrying siRNA against type I TGF-β receptor (TGFβRI) mRNA to treat schistosomiasis-induced liver fibrosis in BALB/c mice. Knockdown of TGFβRI by LNP-siTGFβRI reduced LX-2 cell activation in vitro and alleviated liver fibrosis in S. mansoni-infected mice. αSMA and Col1a1 fibrotic markers in the liver tissues of infected mice were significantly suppressed in the treatment groups. In the serum of the LNP-siTGFβRI-treated groups, cytokines IFNγ, IL-1α, IL-6, IL-12, RANTES (CCL5), and TNFα increased, while GM-CSF, IL-2, IL-4, IL-10, IL-13, and KC (CXCL1) decreased compared to the control. Cell proportions were significantly altered in S. mansoni-infected mice, with increased CD56d NK cells and decreased CD19+ B cells and CD4+ T cells compared to naïve mice. Following LNP-siTGFβRI treatment, CD56d NK cells were downregulated, while B and memory Th cell populations were upregulated. The density of fibrotic regions significantly decreased with LNP-siTGFβRI treatment in a dose-dependent manner, and no systemic toxicity was observed in the major organs. This targeted siRNA delivery strategy effectively reduced granulomatous lesions in schistosomiasis-induced liver fibrosis without detectable side effects.

Endogenous PGD2 acting on DP2 receptor counter regulates Schistosoma mansoni infection-driven hepatic granulomatous fibrosis.

Identifying new molecular therapies targeted at the severe hepatic fibrosis associated with the granulomatous immune response to Schistosoma mansoni infection is essential to reduce fibrosis-related morbidity/mortality in schistosomiasis. In vitro cell activation studies suggested the lipid molecule prostaglandin D2 (PGD2) as a potential pro-fibrotic candidate in schistosomal context, although corroboratory in vivo evidence is still lacking. Here, to investigate the role of PGD2 and its cognate receptor DP2 in vivo, impairment of PGD2 synthesis by HQL-79 (an inhibitor of the H-PGD synthase) or DP2 receptor inhibition by CAY10471 (a selective DP2 antagonist) were used against the fibrotic response of hepatic eosinophilic granulomas of S. mansoni infection in mice. Although studies have postulated PGD2 as a fibrogenic molecule, HQL-79 and CAY10471 amplified, rather than attenuated, the fibrotic response within schistosome hepatic granulomas. Both pharmacological strategies increased hepatic deposition of collagen fibers - an unexpected outcome accompanied by further elevation of hepatic levels of the pro-fibrotic cytokines TGF-β and IL-13 in infected animals. In contrast, infection-induced enhanced LTC4 synthesis in the schistosomal liver was reduced after HQL-79 and CAY10471 treatments, and therefore, inversely correlated with collagen production in granulomatous livers. Like PGD2-directed maneuvers, antagonism of cysteinyl leukotriene receptors CysLT1 by MK571 also promoted enhancement of TGF-β and IL-13, indicating a key down-regulatory role for endogenous LTC4 in schistosomiasis-induced liver fibrosis. An ample body of data supports the role of S. mansoni-driven DP2-mediated activation of eosinophils as the source of LTC4 during infection, including: (i) HQL-79 and CAY10471 impaired systemic eosinophilia, drastically decreasing eosinophils within peritoneum and hepatic granulomas of infected animals in parallel to a reduction in cysteinyl leukotrienes levels; (ii) peritoneal eosinophils were identified as the only cells producing LTC4 in PGD2-mediated S. mansoni-induced infection; (iii) the magnitude of hepatic granulomatous eosinophilia positively correlates with S. mansoni-elicited hepatic content of cysteinyl leukotrienes, and (iv) isolated eosinophils from S. mansoni-induced hepatic granuloma synthesize LTC4 in vitro in a PGD2/DP2 dependent manner. So, our findings uncover that granulomatous stellate cells-derived PGD2 by activating DP2 receptors on eosinophils does stimulate production of anti-fibrogenic cysLTs, which endogenously down-regulates the hepatic fibrogenic process of S. mansoni granulomatous reaction - an in vivo protective function which demands caution in the future therapeutic attempts in targeting PGD2/DP2 in schistosomiasis.

Schistosoma mansoni infection and hepatocellular carcinoma: a comorbidity study.

The implication of human Schistosoma mansoni (S. mansoni) infection in concomitance with other risk factors such as hepatitis C virus (HCV) and hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC) is still under controversy. This work aimed. to evaluate the role of S. mansoni infection in association with hepatitis B virus (HBV), hepatitis C virus (HCV) and other risk factors in the development and/or progress of HCC. The present study was carried out on 90 HCC patients recruited from Kafr El-Sheikh Liver Disease Research Institute. After obtaining their informed consents, socio-demographic and clinical data were collected and patients were examined for S. mansoni by Kato-Katz and indirect hemagglutination (IHA) techniques. Alpha-fetoprotein (AFP) level was determined. The Child-Pugh scoring system and Barcelona Clinic Liver Cancer (BCLC) staging system were used to evaluate the pathological features of the studied patients. All participants were negative for active S. mansoni by Kato-Katz. Based on IHA, the participants were categorized into two groups: group I: sixty-two patients negative for S. mansoni and group II: twenty-eight schistosomiasis positive. The patients' age ranged between 40->60, HCC was more prevalent in the age range of > 50-60 years in both groups. Males were more than females and rural participants were more than urban patients in both groups. Most of the patients (88.9%) had HCV while 7.8% had HBV. A higher proportion of HCC patients showed concomitant HCV and S. mansoni (92.6%) than the S. mansoni negative group. The frequency of upper gastrointestinal bleeding (GIB) was four-fold higher among HCC patients positive for schistosomiasis compared to negative schistosomiasis cases (64% vs. 16%). Alpha-fetoprotein (AFP) level was higher in group II than that in group I with no significant difference. Statistical analysis showed no difference between the two studied groups regarding Child scores. On the contrary, BCLC class D was significantly higher among HCC positive schistosomiasis cases compared to the negative group. Concomitant S. mansoni with HCV and HBV potentiate HCC progression.

ARGONAUTE2 Localizes to Sites of Sporocysts in the Schistosome-Infected Snail, Biomphalaria glabrata.

MicroRNAs (miRNAs) are a class of small regulatory RNA that are generated via core protein machinery. The miRNAs direct gene-silencing mechanisms to mediate an essential role in gene expression regulation. In mollusks, miRNAs have been demonstrated to be required to regulate gene expression in various biological processes, including normal development, immune responses, reproduction, and stress adaptation. In this study, we aimed to establishment the requirement of the miRNA pathway as part of the molecular response of exposure of Biomphalaria glabrata (snail host) to Schistosoma mansoni (trematode parasite). Initially, the core pieces of miRNA pathway protein machinery, i.e., Drosha, DGCR8, Exportin-5, Ran, and Dicer, together with the central RNA-induced silencing complex (RISC) effector protein Argonaute2 (Ago2) were elucidated from the B. glabrata genome. Following exposure of B. glabrata to S. mansoni miracidia, we identified significant expression up-regulation of all identified pieces of miRNA pathway protein machinery, except for Exportin-5, at 16 h post exposure. For Ago2, we went on to show that the Bgl-Ago2 protein was localized to regions surrounding the sporocysts in the digestive gland of infected snails 20 days post parasite exposure. In addition to documenting elevated miRNA pathway protein machinery expression at the early post-exposure time point, a total of 13 known B. glabrata miRNAs were significantly differentially expressed. Of these thirteen B. glabrata miRNAs responsive to S. mansoni miracidia exposure, five were significantly reduced in their abundance, and correspondingly, these five miRNAs were determined to putatively target six genes with significantly elevated expression and that have been previously associated with immune responses in other animal species, including humans. In conclusion, this study demonstrates the central importance of a functional miRNA pathway in snails, which potentially forms a critical component of the immune response of snails to parasite exposure. Further, the data reported in this study provide additional evidence of the complexity of the molecular response of B. glabrata to S. mansoni infection: a molecular response that could be targeted in the future to overcome parasite infection and, in turn, human schistosomiasis.

Longevity of Schistosoma mansoni circulating cathodic antigens in filter paper dried urine spots

ObjectivesThis study aims to determine the temporal stability of Schistosoma mansoni circulating cathodic antigens (CCA) in filter paper-based dried urine spot (FP-DUS) samples under varying temperatures condition. MethodsUrine from 20 children confirmed to have S. mansoni infection using Kato-Katz (at least 1 egg per gram of stool) and Schisto POC-CCA (2+ and 3+) methods were stored in form of FP-DUS and urine at room temperature (RT), 4 °C and −20 °C. Standard urine and FP-DUS Schisto POC-CCA methods were employed to detect CCA in urine and FP-DUS samples respectively, at weeks 4, 8 and 12. The results were reported as negative or positive (trace, 1+. 2+, and 3+). ResultsIn FP-DUS samples, POC-CCA scores initially increase after 4–8 weeks, but then showed a decrease in intensity while still remaining positive, independent of temperature condition. From week 4 to week 12, at least 80 % of urine samples had POC-CCA score of 3+, independent of temperature condition. However, 2 urine samples at RT tested negative at weeks 8 and 12. ConclusionsDespite the decrease in the intensity of test line in many samples, S. mansoni CCA remains stable and detectable in urine samples stored in FP-DUS.

Effectiveness of Three Sampling Approaches for Optimizing Mapping and Preventive Chemotherapy against Schistosoma mansoni in the Western Part of Côte d'Ivoire.

The elimination of schistosomiasis as a public health problem by 2030 is one of the main goals put forth in the World Health Organization's roadmap for neglected tropical diseases. This study aimed to compare different sampling approaches to guide mapping and preventive chemotherapy. A cross-sectional parasitological survey was conducted from August to September 2022 in the health districts of Biankouma, Ouaninou, and Touba in the western part of Côte d'Ivoire. The prevalence and intensity of Schistosoma mansoni infection were assessed in children aged 5-14 years using three sampling approaches. The first approach involved a random selection of 50% of the villages in the health districts. The second approach involved a random selection of half of the villages selected in approach 1, thus constituting 25% of the villages in the health district. The third approach consisted of randomly selecting 15 villages from villages selected by approach 2 in each health district. The overall prevalence of S. mansoni was 23.5% (95% confidence interval (CI): 19.9-27.6%), 21.6% (95% CI: 17.1-26.8%), and 18.3% (95% CI: 11.9-27.1%) with the first, second, and third approach, respectively. The respective geometric mean S. mansoni infection intensity was 117.9 eggs per gram of stool (EPG) (95% CI: 109.3-127.3 EPG), 104.6 EPG (95% CI: 93.8-116.6 EPG), and 94.6 EPG (95% CI 79.5-112.7 EPG). We conclude that, although randomly sampling up to 50% of villages in a health district provides more precise population-based prevalence and intensity measures of S. mansoni, randomly selecting only 15 villages in a district characterized by low heterogeneity provides reasonable estimates and is less costly.