Schistosomiasis Research Articles

T cell subsets, regulatory T, regulatory B cells and proinflammatory cytokine profile in Schistosoma haematobium associated bladder cancer: First report from Upper Egypt

The function of different populations of the immune system in bladder cancer (BCa) is well established. However, the cohesive role of the immune cell profile of schistosomal BCa at systemic and tissue levels is still lacking, especially in endemic countries. The balance hypothesized between protumorigenic and antitumor molecules determines the prognosis of tumor progression. This study aimed to investigate the frequency of T cell subsets at both blood and tumor tissue, regulatory T(Treg), regulatory B cells (Breg) and proinflammatory cytokines in S. haematobium-related BCa patients in Egypt. The frequency of T cell subsets at both blood and tumor tissue, regulatory T(Treg), regulatory B cells (Breg) were studied by flow cytometry and proinflammatory cytokines by ELISA in S. haematobium-related BCa patients in Egypt. The results indicated a significant increase in the activity of T-cell populations, particularly CD3+, CD4+, and regulatory T cells (Tregs), and a decrease in cytotoxic CD8+ T cells in the patient group. An increased proportion of CD19+CD24+CD38+ Bregs and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) was also observed. However, T-cell subpopulations in the tumor microenvironment showed a significant reduction in cancer patients compared to controls. Moreover, positive correlations were observed between the frequencies of Bregs and Tregs, suggesting the promotion of cancer progression besides their relation to the intensity of schistosomal infection. Trapped Schistosoma haematobium eggs in bladder tissue might lead to persistent inflammation that contributes to immunomodulation and promotes tumor progression, as evidenced by the increase in peripheral T helper, Tregs, Bregs and serum tumor-promoting cytokines. Considering the role and integrated functions of specific immune responses in BCa could help future diagnostic and therapeutic implications.

A 14-year follow-up of ultrasound-detected urinary tract pathology associated with urogenital schistosomiasis in women living in the Msambweni region of coastal Kenya.

Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied. Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000. Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality. Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.

The abundance and morphology of human large intestinal goblet and tuft cells during chronic schistosomiasis.

Schistosomiasis affects nearly 240 million people in predominately low- and middle-income countries and ranks second in the number of cases and socio-economic burden among all parasitic diseases. Despite the enormous burden posed by schistosomes, our understanding of how schistosomiasis impacts infected human tissues remains limited. Intestinal schistosomiasis in animal models leads to goblet cell hyperplasia, likely increasing mucus production and reflecting an intestinal type 2 immune response. However, it is unknown whether these same changes occur in schistosome-infected humans. Using immunofluorescence and light microscopy, we compared the abundance and morphology of goblet cells in patients diagnosed with schistosomiasis to uninfected controls. The mucin-containing vesicles in goblet cells from schistosome-infected patients were significantly larger (hypertrophic) than uninfected individuals, although goblet cell hyperplasia was absent in chronic human schistosomiasis. In addition, we examined tuft cells in the large intestinal epithelium of control and schistosome-infected patients. Tuft cell numbers expand during helminth infection in mice, but these cells have not been characterized in human parasite infections. We found no evidence of tuft cell hyperplasia during human schistosome infection. Thus, our study provides novel insight into schistosome-associated changes to the intestinal epithelium in humans, suggesting an increase in mucus production by large intestinal goblet cells but relatively minor effects on tuft cell numbers.

A Critical Review on Human Malaria and Schistosomiasis Vaccines: Current State, Recent Advancements, and Developments.

Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a variety of host, parasitic, and environmental variables. Chronic schistosomiasis causes malnutrition and cognitive impairments in children, while malaria can cause fatal acute infections. There are effective drugs available to treat malaria and schistosomiasis. However, the occurrence of allelic polymorphisms and the rapid selection of parasites with genetic mutations can confer reduced susceptibility and lead to the emergence of drug resistance. Moreover, the successful elimination and complete management of these parasites are difficult due to the lack of effective vaccines against Plasmodium and Schistosoma infections. Therefore, it is important to highlight all current vaccine candidates undergoing clinical trials, such as pre-erythrocytic and erythrocytic stage malaria, as well as a next-generation RTS,S-like vaccine, the R21/Matrix-M vaccine, that conferred 77% protection against clinical malaria in a Phase 2b trial. Moreover, this review also discusses the progress and development of schistosomiasis vaccines. Furthermore, significant information is provided through this review on the effectiveness and progress of schistosomiasis vaccines currently under clinical trials, such as Sh28GST, Sm-14, and Sm-p80. Overall, this review provides insights into recent progress in malarial and schistosomiasis vaccines and their developmental approaches.

Anti-schistosomal immunity to core xylose/fucose in N-glycans.

Schistosomiasis is a globally prevalent, debilitating disease that is poorly controlled by chemotherapy and for which no vaccine exists. While partial resistance in people may develop over time with repeated infections and treatments, some animals, including the brown rat (Rattus norvegicus), are only semi-permissive and have natural protection. To understand the basis of this protection, we explored the nature of the immune response in the brown rat to infection by Schistosoma mansoni. Infection leads to production of IgG to parasite glycoproteins with complex-type N-glycans that contain a non-mammalian-type modification by core α2-Xylose and core α3-Fucose (core Xyl/Fuc). These epitopes are expressed on the surfaces of schistosomula and adult worms. Importantly, IgG to these epitopes can kill schistosomula by a complement-dependent process in vitro. Additionally, sera from both infected rhesus monkey and infected brown rat were capable of killing schistosomula in a manner inhibited by glycopeptides containing core Xyl/Fuc. These results demonstrate that protective antibodies to schistosome infections in brown rats and rhesus monkeys include IgG responses to the core Xyl/Fuc epitopes in surface-expressed N-glycans, and raise the potential of novel glyco-based vaccines that might be developed to combat this disease.

CD193 (CCR3) expression by B cells correlates with reduced IgE production in paediatric schistosomiasis.

We demonstrate that CD193, the eotaxin receptor, is highly expressed on circulating B cells in paediatric schistosomiasis mansoni. CD193 plays a role in directing granulocytes into sites of allergic-like inflammation in the mucosa, but little is known about its functional significance on human B cells. We sought to characterize CD193 expression and its relationship with S. mansoni infection. We found that CD193+ B cells increased with the intensity of schistosome infection. In addition, a significant negative association was observed between CD193 expression by B cells and IgE production. Decreased IgE levels are generally associated with susceptibility to re-infection. B cell stimulation with eotaxin-1 increased CD193 levels whereas IL-4 led to a reduction. This was supported by plasma levels of eotaxin-1 correlating with CD193 levels on B cells and other cells. In contrast, CD193 expression was induced on naive B cells with a combination of IL-10 and schistosome antigens. Whereas T cells had a modest increase in CD193 expression, only B cell CD193 appeared functionally chemotactic to eotaxin-1. Thus, CD193+ B cells, which co-express CXCR5, may be enroute to sites with allergic-like inflammation, such as gastrointestinal follicles, or even to Th2 granulomas, which develop around parasite eggs. Overall, our results suggest that schistosome infection may promote CD193 expression and suppress IgE via IL-10 and other undefined mechanisms related to B cell trafficking. This study adds to our understanding of why young children may have poor immunity. Nonetheless, praziquantel treatment was shown to reduce percentages of circulating CD193+ B cells lending hope for future vaccine efforts.

Incorporating the diagnosis and management of female genital schistosomiasis in primary healthcare in Liberia: a mixed methods pilot study.

Liberia's national neglected tropical disease (NTD) master plan 2016-2020 adopted the need for integrated approaches to tackle the threat of specific NTDs including schistosomiasis. Female genital schistosomiasis (FGS) affects up to 75% of women and girls living in schistosomiasis-endemic areas. Liberia's Bong and Nimba counties are endemic for schistosomiasis. The communities affected are poor and dependent on primary healthcare services. Incorporating the diagnosis and treatment of FGS within primary healthcare is a critical step in the control and elimination of schistosomiasis in Liberia. The Calling Time for Neglected Tropical Diseases (COUNTDOWN) research programme partnership included the Liberia Ministry of Health NTD programme. Together, partners designed this study to co-develop, pilot and evaluate a primary healthcare package for clinical diagnosis and management of FGS in Liberia. Mixed methods were applied to assess the intervention outcomes and process. Quantitative descriptive analysis of routine health facility (secondary) data was used to characterise women and girls diagnosed and treated for FGS. Qualitative rapid analysis of meeting reports and training observations, thematic framework analysis of in-depth interviews with women and girls and key-informant interviews with health system actors were used to establish the success and sustainability of intervention components. In 6 months, 258 women and girls were diagnosed and treated for FGS within routine service delivery across six primary health facilities. Diagnosis and treatment were completed by health facility staff who had been trained in the FGS intervention developed within this study. Some women diagnosed and treated had symptom relief or were optimistic about the intervention due to improved diagnostic and treatment communication by health workers. Health workers and stakeholders were satisfied with the care package and attributed intervention success to the all-inclusive approach to intervention design and development; cascaded training of all cadres of the health system; and the locally driven intervention rollout, which promoted local ownership and uptake of intervention components. This study demonstrates the possibility of using a clinical care package to diagnose women and girls suspected of FGS, including the provision of treatment using praziquantel when it is made available at primary healthcare facilities.

Mixed-methods evaluation of integrating female genital schistosomiasis management within primary healthcare: a pilot intervention in Ogun State, Nigeria.

Detection and management of female genital schistosomiasis (FGS) within primary healthcare is crucial for achieving schistosomiasis elimination, however, current technical strategies are not feasible in many settings. In Nigeria, there are currently no established standard operating procedures to support front-line health workers. This article presents an evaluation of piloting an FGS care package in two LGAs of Ogun State, Nigeria. We used quantitative and qualitative analysis, including 46 interviews with patients, health workers and the quality improvement team; observations of training, learning sessions and supervision across 23 heath facilities; and records of patients detected and managed. Of 79 women and girls who were screened, 66 were treated and followed up. Health workers assimilated knowledge of FGS and effectively diagnosed and managed patients, demonstrating the feasibility of using symptomatic screening and treatment tools to diagnose and care for women or girls with suspected FGS. Challenges included establishing a referral pathway to tertiary care for patients with complications, insecurity, gender norms that limited uptake and sensitization, the limited capacity of the workforce, conflicting priorities and praziquantel acquisition. Simple tools can be used in primary healthcare settings to detect and manage women and girls with FGS. Contextual challenges must be addressed. Sustainability will require political and financial commitments.

A quality improvement approach in co-developing a primary healthcare package for raising awareness and managing female genital schistosomiasis in Nigeria and Liberia.

Girls and women living in endemic areas for urogenital schistosomiasis may have lifelong vulnerability to female genital schistosomiasis (FGS). For >2decades, the importance of FGS has been increasing in sub-Saharan Africa, but without established policies for case detection and treatment. This research aimed to understand the level of FGS knowledge of frontline health workers and health professionals working in endemic areas and to identify health system needs for the effective management of FGS cases and prevention of further complications due to ongoing infections. Workshops were conducted with health workers and stakeholders using participatory methods. These workshops were part of a quality improvement approach to develop the intervention. Health workers' and system stakeholders' knowledge regarding FGS was low. Participants identified key steps to be taken to improve the diagnosis and treatment of FGS in schistosomiasis-endemic settings, which focused mainly on awareness creation, supply of praziquantel, development of FGS syndromic management and mass administration of praziquantel to all eligible ages. The FGS intervention component varies across countries and depends on the health system structure, existing facilities, services provided and the cadre of personnel available. Our study found that co-developing a new service for FGS that responds to contextual variations is feasible, promotes ownership and embeds learning across health sectors, including healthcare providers, NTD policymakers and implementers, health professionals and community health workers.

A genome sequence for Biomphalaria pfeifferi, the major vector snail for the human-infecting parasite Schistosoma mansoni.

Biomphalaria pfeifferi is the world's most widely distributed and commonly implicated vector snail species for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. In efforts to control S. mansoni transmission, chemotherapy alone has proven insufficient. New approaches to snail control offer a way forward, and possible genetic manipulations of snail vectors will require new tools. Towards this end, we here offer a diverse set of genomic resources for the important African schistosome vector, B. pfeifferi. Based largely on PacBio High-Fidelity long reads, we report a genome assembly size of 772 Mb for B. pfeifferi (Kenya), smaller in size than known genomes of other planorbid schistosome vectors. In a total of 505 scaffolds (N50 = 3.2Mb), 430 were assigned to 18 large linkage groups inferred to represent the 18 known chromosomes, based on whole genome comparisons with Biomphalaria glabrata. The annotated B. pfeifferi genome reveals a divergence time of 3.01 million years with B. glabrata, a South American species believed to be similar to the progenitors of B. pfeifferi which undertook a trans-Atlantic colonization < five million years ago. The genome for this preferentially self-crossing species is less heterozygous than related species known to be preferential out-crossers; its smaller genome relative to congeners may similarly reflect its preference for selfing. Expansions of gene families with immune relevance are noted, including the FReD gene family which is far more similar in its composition to B. glabrata than to Bulinus truncatus, a vector for Schistosoma haematobium. Provision of this annotated genome will help better understand the dependencies of trematodes on snails, enable broader comparative insights regarding factors contributing to susceptibility/ resistance of snails to schistosome infections, and provide an invaluable resource with respect to identifying and manipulating snail genes as potential targets for more specific snail control programs.

Subclinical vascular damage in Schistosoma spp. endemic regions.

Background: Cardiovascular abnormalities have been described in patients with schistosomiasis. Their true prevalence and clinical features in endemic settings are unknown. Patients and methods: The study aimed to assess the prevalence of subclinical cardiovascular damage in a population endemic to schistosomiasis. A cross-sectional study was conducted using colour-ultrasound assessment of abdominal and carotid arteries among adults aged >18 years living in Kome Island, Tanzania. Carotid intimal medial thickness, carotid plaque, mean abdominal aortic diameter, and presence of aneurysms were assessed. Anamnestic data on previous Schistosoma infection was collected; the actual prevalence of Schistosoma mansoni and Schistosoma haematobium was also assessed through stool and urine investigations. Results: A total of 264 participants (166 female, 98 male) were enrolled (mean age of 50±15.5 years). The history of previous schistosomiasis was 27.3%, and actual positivity for Schistosoma mansoni was 5.9%. The Latero-lateral Abdominal Aortic Diameter was significantly increased among participants with a previous history of schistosomiasis (16.7±2.8 mm vs. 17.6±3mm; p=0.02), with an aOR of 1.15 [CI 1.04-1.28]; p=0.007]. Conclusions: The significant difference in the Latero-lateral Abdominal Aortic Diameter in participants with previous Schistosomiasis history schistosomiasis, suggests the need for further investigations on aortic damage in endemic populations, independently from the positive laboratory investigations.

Differential Analysis of Key Proteins Related to Fibrosis and Inflammation in Soluble Egg Antigen of Schistosoma mansoni at Different Infection Times.

Schistosomiasis is a major global health problem. Schistosomes secrete antigens into the host tissue that bind to chemokines or inhibit immune cell receptors, regulating the immune responses to allow schistosome development. However, the detailed mechanism of chronic schistosome infection-induced liver fibrosis, including the relationship between secreted soluble egg antigen (SEA) and hepatic stellate cell (HSC) activation, is still unknown. We used mass spectrometry to identify the SEA protein sequences from different infection weeks. In the 10th and 12th infection weeks, we focused on the SEA components and screened out the special protein components, particularly fibrosis- and inflammation-related protein sequences. Our results have identified heat shock proteins, phosphorylation-associated enzymes, or kinases, such as Sm16, GSTA3, GPCRs, EF1-α, MMP7, and other proteins linked to schistosome-induced liver fibrosis. After sorting, we found many special proteins related to fibrosis and inflammation, but studies proving their association with schistosomiasis infection are limited. Follow-up studies on MICOS, MATE1, 14-3-3 epsilon, and CDCP1 are needed. We treated the LX-2 cells with the SEA from the 8th, 10th, and 12th infection weeks to test HSC activation. In a trans-well cell model in which PBMCs and HSCs were co-cultured, the SEA could significantly induce TGF-β secretion, especially from the 12th week of infection. Our data also showed that TGF-β secreted by PBMC after the SEA treatment activates LX-2 and upregulates hepatic fibrotic markers α-SMA and collagen 1. Based on these results, the CUB domain-containing protein 1 (CDCP1) screened at the 12th infection week could be investigated further. This study clarifies the trend of immune mechanism variation in the different stages of schistosome infection. However, how egg-induced immune response transformation causes liver tissue fibrosis needs to be studied further.

Status Quo and Future Perspectives of Molecular and Genomic Studies on the Genus Biomphalaria-The Intermediate Snail Host of Schistosoma mansoni.

Schistosomiasis, or also generally known as bilharzia or snail fever, is a parasitic disease that is caused by trematode flatworms of the genus Schistosoma. It is considered by the World Health Organisation as the second most prevalent parasitic disease after malaria and affects more than 230 million people in over 70 countries. People are infected via a variety of activities ranging from agricultural, domestic, occupational to recreational activities, where the freshwater snails Biomphalaria release Schistosoma cercariae larvae that penetrate the skin of humans when exposed in water. Understanding the biology of the intermediate host snail Biomphalaria is thus important to reveal the potential spread of schistosomiasis. In this article, we present an overview of the latest molecular studies focused on the snail Biomphalaria, including its ecology, evolution, and immune response; and propose using genomics as a foundation to further understand and control this disease vector and thus the transmission of schistosomiasis.

Diagnostic performances of Schistosoma haematobium and Schistosoma mansoni recombinant proteins, peptides and chimeric proteins antibody based tests. Systematic scoping review.

Traditional diagnostic tests for schistosome infections are suboptimal, particularly when the parasite burden is low. In the present review we sought to identify recombinant proteins, peptides, and chimeric proteins with potential to be used as sensitive and specific diagnostic tools for schistosomiasis. The review was guided by PRISMA-ScR guidelines, Arksey and O'Malley's framework, and guidelines from the Joanna Briggs Institute. Five databases were searched: Cochrane library, PubMed, EMBASE, PsycInfo and CINAHL, alongside preprints. Identified literature were assessed by two reviewers for inclusion. A narrative summary was used to interpret the tabulated results. Diagnostic performances were reported as specificities, sensitivities, and AUC. The AUC for S. haematobium recombinant antigens ranged from 0.65 to 0.98, and 0.69 to 0.96 for urine IgG ELISA. S. mansoni recombinant antigens had sensitivities ranging from 65.3% to 100% and specificities ranging from 57.4% to 100%. Except for 4 peptides which had poor diagnostic performances, most peptides had sensitivities ranging from 67.71% to 96.15% and specificities ranging from 69.23% to 100%. S. mansoni chimeric protein was reported to have a sensitivity of 86.8% and a specificity of 94.2%. The tetraspanin CD63 antigen had the best diagnostic performance for S. haematobium. The tetraspanin CD63 antigen Serum IgG POC-ICTs had a sensitivity of 89% and a specificity of 100%. Peptide Smp_150390.1 (216-230) serum based IgG ELISA had the best diagnostic performance for S. mansoni with a sensitivity of 96.15% and a specificity of 100%. Peptides were reported to demonstrate good to excellent diagnostic performances. S. mansoni multi-peptide chimeric protein further improved the diagnostic accuracy of synthetic peptides. Together with the advantages associated with urine sampling technique, we recommend development of multi-peptide chimeric proteins urine based point of care tools.

Biomphalaria pfeifferi (Gastropoda: Planorbidae) in Lake Malawi and Upper Shire River, Mangochi District, Malawi: Distribution, Genetic Diversity and Pre-Patent Schistosome Infections.

In November 2017, Biomphalaria pfeifferi, the key intermediate host for Schistosoma mansoni in Africa, was first reported in Lake Malawi, Mangochi District. Two subsequent malacological surveys in 2018 and 2019 confirmed its lacustrine presence, as well as its presence along the Upper Shire River. These surveys provided sufficient specimens for analyses of the genetic structure and a transmission assessment for intestinal schistosomiasis. A total of 76 collected snails were characterized by a DNA sequence analysis of a 650 bp fragment of the mitochondrial cytochrome oxidase subunit 1 (cox1); by size fractionation of six fluorescently labelled microsatellite loci (Bgμl16, Bgμl, Bpf8, rg6, U-7, and rg9);by denaturing PAGE; and by detection of pre-patent Schistosoma infection by real-time PCR with a TaqMan® probe. Five closely related cox1 haplotypes were identified, all present within a single location, with only one haplotype common across all the other locations sampled. No allelic size variation was detected with the microsatellites and all loci were monomorphic. Overall, the pre-patent prevalence of Schistosoma spp. was 31%, with infected snails found at several sampling locations. In this part of Lake Malawi, Bi. pfeifferi exhibits low genetic diversity and is clearly being exposed to the miracidia of S. mansoni, which is likely facilitating the autochthonous transmission of this parasite.

Profiling the knowledge of female medical/para-medical students, and expertise of health care professionals on female genital schistosomiasis in Anambra, South Eastern Nigeria.

Female genital schistosomiasis (FGS) is a largely neglected tropical disease (NTD), with little or no attention in the primary health care unit. Towards building momentum to address this challenge, we investigated the perception of medical and para-medical students about FGS, as well as the expertise of health care professionals in Anambra State, Nigeria. We conducted a cross-sectional survey among 587 female medical and para-medical university students (MPMS), and 65 health care professionals (HCPs) saddled with the responsibility of delivering care for schistosomiasis-affected persons. Pretested questionnaires were administered to document the awareness and knowledge about the disease. In addition, the expertise of HCPs vis-à-vis suspicion of FGS and management of FGS patients during routine health care service were documented. Data were subjected to descriptive, chi-square tests and regression analysis in R software. Over half of the students recruited; 54.2% for schistosomiasis and 58.1% for FGS, were not aware of the disease. Knowledge about schistosomiasis was associated with student's year of study, with those in 2nd (OR: 1.66, 95% CI: 1.0, 2.7), 4th (OR: 1.97, 95% CI: 1.2, 3.2), and 6th (OR: 5.05, 95% CI: 1.2, 34.2) year having higher likelihoods of been more informed about schistosomiasis. For HCPs, we observed a contrastingly high knowledge about schistosomiasis (96.9%), but low knowledge about FGS (61.9%). Knowledge for both schistosomiasis and FGS was not associated with year of practice and expertise (95% OR included 1, p > 0.05). A considerable proportion (>40%) of the HCPs never suspected schistosomiasis during routine clinical diagnosis of patients who presented probable FGS symptoms (p < 0.05). Similarly, only 20% were certain about the use of praziquantel for treating FGS, and about 35% were uncertain of the eligibility criteria and dosage regimens. Commodities for managing FGS were also largely unavailable in about 39% of the health facilities where the HCPs operate. Awareness and knowledge about FGS among MPMS and HCPs were poor in Anambra, Nigeria. It is therefore important to invest in innovative methods of building capacity of MPMS and HCPs, with complementary provision of necessary diagnostics to perform colposcopy, as well as competence to diagnose pathognomonic lesions using diagnostic atlas or Artificial Intelligence (AI).

Bulinus snails in the Lake Victoria Basin in Kenya: Systematics and their role as hosts for schistosomes.

The planorbid gastropod genus Bulinus consists of 38 species that vary in their ability to vector Schistosoma haematobium (the causative agent of human urogenital schistosomiasis), other Schistosoma species, and non-schistosome trematodes. Relying on sequence-based identifications of bulinids (partial cox1 and 16S) and Schistosoma (cox1 and ITS), we examined Bulinus species in the Lake Victoria Basin in Kenya for naturally acquired infections with Schistosoma species. We collected 6,133 bulinids from 11 sites between 2014-2021, 226 (3.7%) of which harbored Schistosoma infections. We found 4 Bulinus taxa from Lake Victoria (B. truncatus, B. tropicus, B. ugandae, and B. cf. transversalis), and an additional 4 from other habitats (B. globosus, B. productus, B. forskalii, and B. scalaris). S. haematobium infections were found in B. globosus and B. productus (with infections in the former predominating) whereas S. bovis infections were identified in B. globosus, B. productus, B. forskalii, and B. ugandae. No nuclear/mitochondrial discordance potentially indicative of S. haematobium/S. bovis hybridization was detected. We highlight the presence of Bulinus ugandae as a distinct lake-dwelling taxon closely related to B. globosus yet, unlike all other members of the B. africanus species group, is likely not a vector for S. haematobium, though it does exhibit susceptibility to S. bovis. Other lake-dwelling bulinids also lacked S. haematobium infections, supporting the possibility that they all lack compatibility with local S. haematobium, thereby preventing widespread transmission of urogenital schistosomiasis in the lake's waters. We support B. productus as a distinct species from B. nasutus, B. scalaris as distinct from B. forskalii, and add further evidence for a B. globosus species complex with three lineages represented in Kenya alone. This study serves as an essential prelude for investigating why these patterns in compatibility exist and whether the underlying biological mechanisms may be exploited for the purpose of limiting schistosome transmission.

Urogenital schistosomiasis (UGS) and female genital schistosomiasis (FGS) in Cameroon: an observational assessment of key reproductive health determinants of girls and women in the Matta Health Area

Objectives and settingAcross sub-Saharan Africa, urogenital schistosomiasis (UGS), in particular female genital schistosomiasis (FGS), is a significant waterborne parasitic disease, with its direct burden on the sexual and reproductive health...

First bovine vaccine to prevent human schistosomiasis - a cluster randomised Phase 3 clinical trial

ObjectiveSchistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, and SjCTPI bovine vaccination on the rate of human infection. MethodsA 5-year phase IIIa cluster randomized control trial was conducted among 18 schistosomiasis-endemic villages comprising 18,221 residents in Northern Samar, The Philippines. ResultsOverall, bovine vaccination resulted in a statistically significant decrease in human infection (relative risk [RR] = 0.75; 95% confidence interval [CI] = 0.69 to 0.82) across all trial follow-ups. The best outcome of the trial was when bovine vaccination was combined with snail mollusciciding. This combination resulted in a 31% reduction (RR = 0.69; 95% CI = 0.61 to 0.78) in human infection. ConclusionThis is the first trial to demonstrate the effectiveness of a bovine vaccine for schistosomiasis in reducing human schistosome infection. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001048178).

Metabolomics for biomarker discovery in schistosomiasis: A systematic scoping review

BackgroundMetabolomic based approaches are essential tools in the discovery of unique biomarkers for infectious diseases via high-throughput global assessment of metabolites and metabolite pathway dysregulation. This in-turn allows the development of diagnostic tools and provision of therapeutics. In this review, we aimed to give an overview of metabolite biomarkers and metabolic pathway alterations during Schistosoma haematobium and Schistosoma mansoni infections.MethodsWe conducted the review by systematically searching electronic databases and grey literature to identify relevant metabolomics studies on schistosomiasis. Arksey and O’Malley methodology for conducting systematic scoping reviews was applied. A narrative summary of results was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping review guidelines.ResultsTwelve articles included in the review identified 127 metabolites, whose concentrations were considerably altered during S. mansoni and S. haematobium infections. The metabolites were assigned to metabolic pathways involved in energy (34.6%), gut microbial (11.0%), amino acid (25.2%), nucleic acids (6.3%), immune proteins (8.7%) hormones (2.4%) and structural proteins/lipids (11.8%). Energy related metabolic pathways were the most affected during schistosome infections with metabolites such as succinate, citrate, aconitate and fumarate of the tricarbocylic acid cycle being significantly altered in organ, serum and plasma samples. Amino acid metabolism was also impacted during schistosome infections as phenylacetylglycine, alanine, taurine, 2-oxoisocaproate and 2-oxoisovalerate emerged as potent biomarkers. Elevated structural proteins such as actin, collagen and keratin concentrations were identified as biomarkers of liver fibrosis, a common pathological feature in chronic schistosomiasis infections. Hippurate was a major metabolite biomarker in the gut microbial related pathway.ConclusionsThe analysis of the literature revealed that energy related metabolic pathways are considerably altered during S. mansoni and S. haematobium infections. Therefore, their metabolites may provide biomarkers for diagnosis and prognosis in addition to providing therapeutics for parasitic infections. This scoping review has identified a need to replicate more schistosomiasis metabolomic studies in humans to complement animal-model based studies.