Mansoni Infection Research Articles

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.

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.

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.

Early symptom-associated inflammatory responses shift to type 2 responses in controlled human schistosome infection.

Schistosomiasis is an infection caused by contact with Schistosoma-contaminated water and affects more than 230 million people worldwide with varying morbidity. The roles of T helper 2 (TH2) cells and regulatory immune responses in chronic infection are well documented, but less is known about human immune responses during acute infection. Here, we comprehensively map immune responses during controlled human Schistosoma mansoni infection using male or female cercariae. Immune responses to male or female parasite single-sex infection were comparable. An early TH1-biased inflammatory response was observed at week 4 after infection, which was particularly apparent in individuals experiencing symptoms of acute schistosomiasis. By week 8 after infection, inflammatory responses were followed by an expansion of TH2 and regulatory cell subsets. This study demonstrates the shift from TH1 to both TH2 and regulatory responses, typical of chronic schistosomiasis, in the absence of egg production and provides immunological insight into the clinical manifestations of acute schistosomiasis.

Immunological and Haematological Relevance of Helminths and Mycobacterium tuberculosis Complex Coinfection among Newly Diagnosed Pulmonary Tuberculosis Patients from Bobo-Dioulasso, Burkina Faso.

The effect of helminthiasis on host immunity is a neglected area of research, particularly in tuberculosis (TB) infection. This study aimed to evaluate the effect of helminthiasis on immunological and haematological parameters in newly diagnosed TB patients in Bobo-Dioulasso. After all biological analyses, we formed three subpopulations: group 1 (n = 82), as control, were participants without helminthic or Mycobacterium tuberculosis complex infection (Mtb-/Helm-), group 2 (n = 73) were TB patients without helminthic infection (Mtb+/Helm-), and group 3 (n = 22) were TB patients with helminthic infection (Mtb+/Helm+). The proportion of helminth coinfection was 23.16% (22/95) in TB patients, and Schistosoma mansoni infection was found in 77.3% (17/22) cases of helminthiasis observed in this study. A low CD4 T cell count and a low CD4:CD8 ratio were significantly associated with concomitant infection with helminths and the Mtb complex (Mtb+/Helm+) compared to the other groups (p < 0.05). However, there was no statistically significant difference in the CD8 median among the three participating groups (p > 0.05). Lymphopenia, monocytosis, thrombocytosis, and hypochromic microcytic anaemia were the haematological defects observed in the Mtb+/Helm+ and Mtb+/Helm- patients. Exploring these types of immune-haematological biomarkers would be a valuable aid in diagnosing and a better follow-up and monitoring of the tuberculosis-helminthiasis coinfection.

Schistosomiasis in areas of low endemicity: an overly neglected disease. The example of Schistosoma monsoni in BrazilEsquistossomose em áreas de baixa endemicidade, uma doença muito negligenciada. O exemplo de Schistosoma mansoni no Brasil

Human schistosomiasis is a parasitic disease caused by an infection with trematodes of the genus Schistosoma. The disease mainly affects impoverished populations. Around 800 million people are exposed to the infection, which is a public health problem in the tropical and subtropical regions of Africa, Asia, the Caribbean and South America. In Brazil, Schistosoma mansoni is the only species that causes schistosomiasis and the disease is widely distributed. Conventional diagnosis of the disease is carried out by detecting eggs using parasitological methods, such as the Kato-Katz test. Schistosomiasis has been reported in all regions of Brazil and is characterized as endemic in seven states in the Northeast Region and two states in the Southeast Region. In 2015, 78,7% of all cases reported in Brazil occurred in the Northeast Region. It is estimated that 1,5 million people is infected with this disease in Brazil and more than 25 millions live in areas with a high risk of transmission. Despite the reduction in mortality and morbidity, schistosomiasis was responsible for 8,756 deaths between 2000 and 2011 and 2,517 deaths between 2015 and 2019 in Brazil and it remains an important public health problem. In the state of Rio de Janeiro, some areas have low endemicity or isolated foci of Schistosoma mansoni and the majority of infected individuals have mild infections. The last survey of the disease in the state of Rio de Janeiro was carried out between 2010 and 2015 in students aged 7 to 17.Schistosomiasis was reported in 10 of the 21 municipalities studied. Of the 5,111 school children screened for S. mansoni infection, 46 (1,65%) were tested positive. Studies carried out in areas of low endemicity in Rio de Janeiro showed that among the 205 patients infected by S. mansoni in Sumidouro, around 84% were aged 14 or over and all, except one individual, had the intestinal form (91,2%) or hepato-intestinal (8,3%) of schistosomiasis. Another study carried out in Sumidouro showed that with tests based on patent Schistosoma egg infection determined by the Kato-Katz test, active infections were diagnosed in eight (8/108) individuals. The intensity of infection expressed by parasite loads ranged from 6 to 72 eggs per gram of feces/individual. The results showed DNA amplification in 32 of the 100 individuals tested by real-time PCR. All individuals with patent ovo infection showed positive DNA amplification. These studies showed that if we only analyzed school-age children using the Kato-Katz test, the majority of the infected population would never be diagnosed with S. mansoni infection. In situations of low endemicity, with low intensities of infection, with low severity in the population and in the most affected age groups, schistosomiasis requires a more sensitive diagnostic approach (e.g. screening by PCR rather than Kato test), otherwise many infected individuals will remain invisible to the healthcare system.

Gut microbiota and immune profiling of microbiota-humanised versus wildtype mouse models of hepatointestinal schistosomiasis

Mounting evidence of the occurrence of direct and indirect interactions between the human blood fluke, Schistosoma mansoni, and the gut microbiota of rodent models raises questions on the potential role(s) of the latter in the pathophysiology of hepatointestinal schistosomiasis. However, substantial differences in both the composition and function between the gut microbiota of laboratory rodents and that of humans hinders an in-depth understanding of the significance of such interactions for human schistosomiasis. Taking advantage of the availability of a human microbiota-associated mouse model (HMA), we have previously highlighted differences in infection-associated changes in gut microbiota composition between HMA and wildtype (WT) mice. To further explore the dynamics of schistosome-microbiota relationships in HMA mice, in this study we (i) characterize qualitative and quantitative changes in gut microbiota composition of a distinct line of HMA mice (D2 HMA) infected with S. mansoni prior to and following the onset of parasite egg production; (ii) profile local and systemic immune responses against the parasite in HMA as well as WT mice and (iii) assess levels of faecal inflammatory markers and occult blood as indirect measures of gut tissue damage. We show that patent S. mansoni infection is associated with reduced bacterial alpha diversity in the gut of D2 HMA mice, alongside expansion of hydrogen sulphide-producing bacteria. Similar systemic humoral responses against S. mansoni in WT and D2 HMA mice, as well as levels of faecal lipocalin and markers of alternatively activated macrophages, suggest that these are independent of baseline gut microbiota composition. Qualitative comparative analyses between faecal microbial profiles of S. mansoni-infected WT and distinct lines of HMA mice reveal that, while infection-induced alterations of the gut microbiota composition are highly dependent on the baseline flora, bile acid composition and metabolism may represent key elements of schistosome-microbiota interactions through the gut-liver axis.

Rapid appraisal of liver diseases using transient elastography, abdominal ultrasound, and microbiology in Côte d'Ivoire: A single-center study.

Liver diseases of infectious and non-infectious etiology cause considerable morbidity and mortality, particularly in low- and middle-income countries (LMICs). However, data on the prevalence of liver diseases and underlying risk factors in LMICs are scarce. The objective of this study was to elucidate the occurrence of infectious diseases among individuals with chronic liver damage in a rural setting of Côte d'Ivoire. In 2021, we screened 696 individuals from four villages in the southern part of Côte d'Ivoire for hepatic fibrosis and steatosis, employing transient elastography (TE) and controlled attenuation parameter (CAP). We classified CAP ≥248 dB/m as steatosis, TE ≥7.2 kPa as fibrosis, and did subgroup analysis for participants with TE ranging from 7.2 kPa to 9.1 kPa. Clinical and microbiologic characteristics were compared to an age- and sex-matched control group (TE <6.0 kPa; n = 109). Stool samples were subjected to duplicate Kato-Katz thick smears for diagnosis of Schistosoma mansoni. Venous blood samples were examined for hepatitis B and hepatitis C virus. Additionally, an abdominal ultrasound examination was performed. Among 684 individuals with valid TE measurements, TE screening identified hepatic pathologies in 149 participants (17% with fibrosis and 6% with steatosis). 419 participants were included for further analyses, of which 261 had complete microbiologic analyses available. The prevalence of S. mansoni, hepatitis B, and hepatitis C were 30%, 14%, and 7%, respectively. Logistic regression analysis revealed higher odds for having TE results between 7.2 kPa and 9.1 kPa in individuals with S. mansoni infection (odds ratio [OR] = 3.02, 95% confidence interval [CI] = 1.58-5.76, P = 0.001), while HCV infection (OR = 5.02, 95% CI = 1.72-14.69, P = 0.003) and steatosis (OR = 4.62, 95% CI = 1.60-13.35, P = 0.005) were found to be risk factors for TE ≥9.2 kPa. Besides viral hepatitis, S. mansoni also warrants consideration as a pathogen causing liver fibrosis in Côte d'Ivoire. In-depth diagnostic work-up among individuals with abnormal TE findings might be a cost-effective public health strategy.

Factors associated with hookworm and Schistosoma mansoni infections among school-aged children in Mayuge district, Uganda

BackgroundHookworm infection and schistosomiasis are two of sub-Saharan Africa's most common neglected tropical diseases. An annual mass drug administration (MDA) program against schistosomiasis and soil-transmitted helminths (STHs), including hookworm, has been implemented in Mayuge district, Uganda, since 2003 to date. However, hookworm and schistosomiasis remain prevalent in Mayuge district. Understanding the factors that predispose children to these infections in the context of MDA could inform interventions to reduce prevalence in Uganda and similar settings.MethodThis cross-sectional study took place in 33 randomly selected primary schools in the Mayuge district from January to February 2022. Children in primary classes 4 or 5, in the selected schools provided single stool samples and completed questionnaires. Stool specimens were examined using the Kato-Katz method to determine the prevalence of hookworm and schistosomiasis. We performed univariable and multivariable logistic regression to assess the associations of each infection with potential risk factors.ResultA total of 1,617 students (mean age 12.1 years, 50.1% male) were enrolled. The prevalence of hookworm infection and schistosomiasis was 21.8% (95% confidence interval (CI): 19.8–23.9%) and 18.7% (95% CI: 16.8–20.7%), respectively. In multivariable analysis, longer water fetching time (over 30 min versus less than 30 min) and working daily in the soil were associated with increased odds of hookworm infection (adjusted odds ratio (AOR): 1.49, 95% CI: 1.13–1.96 and 1.37, 95% CI: 1.03–1.82, respectively). Higher odds of schistosomiasis were linked to proximity to water bodies within a one-hour walking distance (AOR: 1.84, 95% CI: 1.35–2.50), and not always washing hands before eating (AOR: 2.00, 95% CI: 1.50–2.67). Swimming, bathing, or washing in water bodies twice a week, compared to never, also increased schistosomiasis odds (AOR: 2.91, 95% CI: 1.66–5.13).ConclusionConsistent with the mechanisms of acquisition, hookworm infection increased with exposure to soil, and schistosomiasis increased with exposure to unclean water. Our findings highlight the importance of Water, Sanitation, and Hygiene programs and strategies aimed at reducing exposure within the framework of Neglected Tropical Disease elimination programs.