Low doses and short duration of prednisolone administration in guinea pigs experimentally infected with Schistosoma haematobium: Histopathology of liver and lungs.

In our previous study, administration of 5 mg prednisolone for five days pre-Schistosoma haematobium infection in guinea pigs increased susceptibility and produced pathological reactions in the liver and bladder. Since corticosteroids can suppress granuloma formation, maturation, and size, this study sought to investigate if prednisolone given at low doses and short duration can produce granulomatous lesions in the tissues of guinea pigs experimentally infected with S. haematobium. Guinea pigs were shared into six groups: group I and II were the immunosuppressed-infected guinea pigs (I0.5 and I1.5- 20 animals each), group III was the unimmunosuppressed-infected guinea pigs (UI- 20 animals), and group IV, V and VI were the immunosuppressed-uninfected and normal guinea pigs (D0.5, D1.5, and normal- 10 animals each). Prednisolone was given in doses of 0.5 mg/kg and 1.5 mg/kg to the different groups, a day before infection and on day 5 post-infection. The infected groups were subcutaneously injected with 250-300 S. haematobium cercariae. Screening for S. haematobium eggs in urine and fecal samples of animals, and quantitative analysis for leukocyte and red blood cell (RBC) counts in urine samples of guinea pigs began nine weeks post-infection (WPI). Guinea pigs were killed, perfused, worms recovered and sections of the liver, lungs, and bladder excised for histopathological examination at 6, 8, 11, 14 and 16 WPI. S. haematobium eggs were only seen in urine samples of I1.5 at 15 and 16WPI. Although the parasite eggs were seen in fecal samples of all infected guinea pigs from 9WPI, those of UI were sparse and took longer time to hatch. High leukocyte counts were seen in all immunosuppressed groups at 6WPI, which returned to normal levels in D1.5 and D0.5 at 16WPI. At 16WPI, significant numbers of leukocyte and RBC counts were seen in urine samples of I1.5. The immunosuppressed-infected groups had significant numbers of mature and total worm loads than UI group (p > 0.05). However, the worm burden of I1.5 was higher than I0.5 at 14WPI and 16WPI. Non-granulomatous lesions were only recorded in the liver sections of the immunosuppressed-infected animals and in lung sections of UI and I1.5 guinea pigs. Liver lesions seen were hepatocyte degeneration; necrosis; Kupffer cell involvements as hyperplasia, phagocytosis, proliferation; hyperaemia and haemorrhage, and mononuclear leukocyte infiltration. Lung lesions seen in I1.5 at 11-16WPI were hemosiderin depositions and hyperaemia, emphysema and atelectasis, and mononuclear leukocyte infiltrations while in UI, emphysema and mononuclear leukocyte infiltration were seen only at 16WPI. In the immunosuppressed-infected groups, composite liver lesion scores showed that peak lesion severity was at 8WPI and 11WPI in I1.5 and I0.5, respectively. However, there was no significant difference (p = 0.105) in composite liver lesion scores of I1.5 and I0.5. Lung lesion score of UI at 16WPI was significantly higher (p > 0.05) than that of I1.5. Findings from this study show that even at low doses and short duration of administration, corticosteroids can only increase susceptibility of guinea pigs but cannot improve its suitability as experimental models of S. haematobium infection.

Urogenital schistosomiasis infection prevalence targets to determine elimination as a public health problem based on microhematuria prevalence in school-age children.

BACKGROUND: Recent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a "background" level of morbidity. METHODOLOGY: Data obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%. PRINCIPAL FINDINGS: An infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels. CONCLUSIONS/SIGNIFICANCE: A target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria.

Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoni.

BACKGROUND: World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children. METHODOLOGY: A total of 22,488 children aged 6-15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003-2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data. PRINCIPAL FINDINGS: S. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed. CONCLUSIONS/SIGNIFICANCE: Current status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual's intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.

Interleukin-4 Signaling Plays a Major Role in Urogenital Schistosomiasis-Associated Bladder Pathogenesis.

Interleukin-4 (IL-4) is crucial in many helminth infections, but its role in urogenital schistosomiasis, infection with Schistosoma haematobium worms, remains poorly understood due to a historical lack of animal models. The bladder pathology of urogenital schistosomiasis is caused by immune responses to eggs deposited in the bladder wall. A range of pathology occurs, including urothelial hyperplasia and cancer, but associated mechanisms and links to IL-4 are largely unknown. We modeled urogenital schistosomiasis by injecting the bladder walls of IL-4 receptor-alpha knockout (Il4ra-/- ) and wild-type mice with S. haematobium eggs. Readouts included bladder histology and ex vivo assessments of urothelial proliferation, cell cycle, and ploidy status. We also quantified the effects of exogenous IL-4 on urothelial cell proliferation in vitro, including cell cycle status and phosphorylation patterns of major downstream regulators in the IL-4 signaling pathway. There was a significant decrease in the intensity of granulomatous responses to bladder-wall-injected S. haematobium eggs in Il4ra-/- versus wild-type mice. S. haematobium egg injection triggered significant urothelial proliferation, including evidence of urothelial hyper-diploidy and cell cycle skewing in wild-type but not Il4ra-/- mice. Urothelial exposure to IL-4 in vitro led to cell cycle polarization and increased phosphorylation of AKT. Our results show that IL-4 signaling is required for key pathogenic features of urogenital schistosomiasis and that particular aspects of this signaling pathway may exert these effects directly on the urothelium. These findings point to potential mechanisms by which urogenital schistosomiasis promotes bladder carcinogenesis.

Schistosoma haematobium infection morbidity, praziquantel effectiveness and reinfection rate among children and young adults in Gabon.

BACKGROUND: Sub-Saharan Africa carries most of the global burden of schistosomiasis. To optimize disease control and reduce morbidity, precise data are needed for control measures adapted to the local epidemiological situation. The objective of this study is to provide baseline information on schistosomiasis dynamics, including praziquantel (PZQ) treatment outcome in children and young adults living in the vicinity of Lambaréné, Gabon. METHODS: Eligible volunteers were included into a prospective longitudinal study. Urine filtration technique was used to detect eggs in urine for schistosomiasis diagnosis. Subjects were treated with 60 mg of PZQ once per month for three consecutive months, and the outcome was assessed by cure rate (CR) and egg reduction rate (ERR). RESULTS: A total of 328 volunteers were enrolled in the study with a mean (± SD) age of 12.2 ± 4.7 years-old. The female-to-male ratio was 0.99. Out of 258 participants in total, 45% had schistosomiasis during the survey and 43% presented with heavy infections. The incidences of haematuria and schistosomiasis were 0.11 and 0.17 person-years, respectively. After the first and third dose of PZQ, overall ERR of 93% and 95% were found, respectively; while the CR were 78% and 88%, respectively. Both ERR (100 vs 88%) and CR (90 vs 68%) were higher among females than males after the first dose. The CR increased for both groups after the third dose to 95% and 80%, respectively. After the first PZQ dose, ERR was higher for heavy compared to light infections (94 vs 89%), while the CR was higher for light than for heavy infections (87 vs 59%). After the third PZQ dose, ERR increased only for light infections to 99%, while CR increased to 98% and 75% for light and for heavy infections, respectively. The reinfection rate assessed at a mean of 44.6 weeks post-treatment was 25%. CONCLUSIONS: The prevalence of schistosomiasis is moderate in communities living in the vicinity of Lambaréné, where a subpopulation with a high risk of reinfection bears most of the burden of the disease. To improve schistosomiasis control in this scenario, we suggest education of these high-risk groups to seek themselves a one-year PZQ treatment. Trial registration clinicaltrials.gov Identifier NCT02769103. Registered 11 May 2016, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02769013.

Differential responses of epithelial cells from urinary and biliary tract to eggs of Schistosoma haematobium and S. mansoni.

Chronic urogenital schistosomiasis can lead to squamous cell carcinoma of the bladder. The International Agency for Research on Cancer classifies the infection with S. haematobium as a group 1 carcinogen, a definitive cause of cancer. By contrast, hepatointestinal schistosomiasis due to the chronic infection with S. mansoni or S. japonicum associated with liver periportal fibrosis, does not apparently lead to malignancy. The effects of culturing human epithelial cells, HCV29, established from normal urothelium, and H69, established from cholangiocytes, in the presence of S. haematobium or S. mansoni eggs were investigated. Cell growth of cells co-cultured with schistosome eggs was monitored in real time, and gene expression analysis of oncogenesis, epithelial to mesenchymal transition and apoptosis pathways was undertaken. Schistosome eggs promoted proliferation of the urothelial cells but inhibited growth of cholangiocytes. In addition, the tumor suppressor P53 pathway was significantly downregulated when exposed to schistosome eggs, and downregulation of estrogen receptor was predicted in urothelial cells exposed only to S. haematobium eggs. Overall, cell proliferative responses were influenced by both the tissue origin of the epithelial cells and the schistosome species.

Esquistosomiasis vesical urinaria: caso anatomoclínico diagnosticado en Chile / Urinary bladder schistosomiasis: a case report diagnosed in Chile

Resumen La esquistomiasis urinaria es producida por Schistosoma haematobium. Es una enfermedad endémica en muchas regiones del mundo, no existente en Chile. Se presenta el caso de un hombre joven que viajó a Malawi, en África meridional, y que a su regreso al país, años después, presentó un síndrome miccional con hematuria macroscópica. La biopsia de vejiga mostró una cistitis granulomatosa y eosinofílica con huevos de Schistosoma haematobium.

Urinary schistosomiasis is produced by Schistosoma haematobium. It is an endemic disease in many regions of the world, non-existent in Chile. We report a case of a young man who traveled to Malawi, in southern Africa, and who returned to Chile. Few years later, he presented a urinary syndrome with macroscopic hematuria. The bladder biopsy showed a granulomatous and eosinophilic cystitis with eggs of Schistosoma haematobium.

Schistosoma haematobium causing pulmonary schistosomiasis in a returning traveller.

Schistosomiasis is infrequently seen in the UK, but remains an important cause of haematuria in endemic areas. It may also be complicated by systemic illness, and can affect multiple organs, including the bladder, liver and lungs. We discuss a case of haematuria associated with lower abdominal discomfort and dry cough/wheeze in a returning traveller diagnosed as pulmonary and urinary schistosomiasis, caused by Schistosomahaematobium This case was particularly notable for the radiological findings seen on CT scan of the chest (figure 2A,B), as well as the characteristic sago nodules discovered within the bladder. It is also unusual to see pulmonary schistosomiasis associated with S. haematobium, an organism more typically characterised by bladder involvement. It is important to consider schistosomiasis and its complications, while rare in the western world, it remains an important differential diagnosis in at-risk groups with considerable morbidity if untreated.

Urogenital schistosomiasis is associated with signatures of microbiome dysbiosis in Nigerian adolescents.

Urogenital schistosomiasis is a neglected tropical disease caused by the parasite Schistosoma haematobium, which resides in the vasculature surrounding the urogenital system. Previous work has suggested that helminthic infections can affect the intestinal microbiome, and we hypothesized that S. haematobium infection could result in an alteration of immune system-microbiota homeostasis and impact the composition of the gut microbiota. To address this question, we compared the fecal microbiomes of infected and uninfected schoolchildren from the Argungu Local Government Area of Kebbi State, Nigeria, detecting significant differences in community composition between the two groups. Most remarkably, we observed a decreased abundance of Firmicutes and increased abundance of Proteobacteria - a shift in community structure which has been previously associated with dysbiosis. More specifically, we detected a number of changes in lower taxa reminiscent of inflammation-associated dysbiosis, including decreases in Clostridiales and increases in Moraxellaceae, Veillonellaceae, Pasteurellaceae, and Desulfovibrionaceae. Functional potential analysis also revealed an enrichment in orthologs of urease, which has been linked to dysbiosis and inflammation. Overall, our analysis indicates that S. haematobium infection is associated with perturbations in the gut microbiota and may point to microbiome disruption as an additional consequence of schistosome infection.

Gene Expression Differences in Host Response to Schistosoma haematobium Infection.

Schistosome worms infect over 200 million people worldwide. They live in the host's bloodstream and alter host immunity. Epidemiological data suggest that males and females have different responses to schistosome infection, but the effect of sex on systemic response is undetermined. Our objective was to characterize differences in peripheral blood transcriptional profiles in people with or without active Schistosoma haematobium infection and to determine whether this signature differs between males and females. mRNA was isolated using poly(A) selection and sequenced on an Illumina Hi-Seq4000 platform. Transcripts were aligned to the human hg19 reference genome and counted with the HTSeq package. Genes were compared for differential expression using DESeq2. Ingenuity Pathway Analysis (IPA) was used to identify gene networks altered in the presence of S. haematobium We enrolled 33 participants from villages in rural Tanzania where S. haematobium is endemic. After correction for multiple comparisons, we observed 383 differentially expressed genes between those with or without S. haematobium infection when sex was included as a covariate. Heat-mapping of the genes with >1.5-fold differences in gene expression revealed clustering by S. haematobium infection status. The top networks included development, cell death and survival, cell signaling, and immunologic disease pathways. We observed a distinct whole blood transcriptional profile, as well as differences in men and women, with S. haematobium infection. Additional studies are needed to determine the clinical effects of these divergent responses. Attention to sex-based differences should be included in studies of human schistosome infection.

Schistosoma haematobium cercarial infection alters subsequent systemic immune responses to eggs but has minimal impact on immune responses to egg injection of the bladder.

AIMS: Mouse bladder wall injection with Schistosoma haematobium eggs has been used to overcome limitations in animal models of urogenital schistosomiasis. However, the effect of the absence of cercarial infection on immune responses to eggs in this model is unknown. We hypothesized that cercarial infection would alter local bladder and systemic immune responses to eggs in this model. METHODS AND RESULTS: Mice were infected or not infected with S haematobium cercariae, and then, their bladder walls injected with S haematobium eggs or vehicle 5 weeks following cercarial infection. Three weeks later, mice were bled, sacrificed, perfused and their bladders harvested. Parasitological parameters and gross bladder pathology were not changed in egg-injected bladders by cercarial exposure. Figure S1 shows no changes in either granulomas or fibrosis. The only bladder cytokine upregulated in egg-injected bladders by cercarial exposure (vs no exposure) was leptin. Cercarial exposure, compared to no exposure, resulted in increased serum, IL-1α, IL-13 and TGF-ß in bladder egg-injected mice. CONCLUSION: Cercarial exposure altered systemic responses of several cytokines in bladder egg-injected mice, but surprisingly, only modified leptin expression in bladder tissue. This suggests that depending on the specific application, cercarial exposure may not be strictly necessary to model local immune responses in the bladder wall egg injection mouse model of urogenital schistosomiasis.

Ultrasound Evolution of Pediatric Urinary Schistosomiasis after Treatment with Praziquantel in a Highly Endemic Area.

Urinary schistosomiasis causes damage to the urological system. Ultrasound is a method that detects the burden of secondary disease, individually and in epidemiological studies. In this study, the Schistosoma haematobium-associated urinary tract pathology is analyzed before and after treatment in a short period of time. Seventy children who had previously participated in an epidemiological study on schistosomiasis in the city of Cubal, Angola, and had also performed urinary ultrasound between August 2013 and February 2014 were cited 6-8 months later to assess the possible reinfection and repeat new urinary ultrasound, analyzing changes at the level of urinary pathology. The presence of hematuria and proteinuria was also analyzed. Of the 70 children analyzed, 29 (41.4%) were girls, with an average age of 10.4 years (standard deviation 2.3). Fifty-three (75.7%) had an improvement in their bladder and/or kidney scores, whereas 12 (17.1%) had no change and five (7.1%) had progression of the disease. None of the parameters analyzed completely disappeared. After one single course of treatment with praziquantel, all the analyzed parameters showed regression. Improvement was greater in the urinary bladder than in the upper urinary tract, though these lesions also reversed; the reversion of all parameters was greater among children older than 10 years old than the younger ones. Proteinuria was the parameter with a smaller reduction. Ultrasound should be a usual tool for diagnosis and follow-up in urinary schistosomiasis, particularly in children; more accurate recommendations about follow-up in the case of children whose lesions do not reverse should be established.

Schistosomiasis (Bilharziasis) ova: An incidental finding in testicular tissue of an obstructive azoospermic man.

Congenital bilateral absence of vas deferens (CBAVD) results in obstructive azoospermia in which testicular function, such as spermatogenesis, is preserved. Bilateral testicular biopsy is not only diagnostic but also therapeutic as retrieved spermatozoa are usually cryopreserved for assisted reproduction. In this case report, CBAVD was confirmed in a 24-year-old azoospermic man on the basis of persistent azoospermia associated with low semen volume, absent fructose and normal hormonal levels, ultrasonographically (absent seminal vesicles) and histologically (intact spermatogenesis). Interestingly and incidentally, only the right testicular biopsy showed ova of two parasitic species of Schistosoma, namely Schistosoma haematobium which infests the genitourinary tract and Schistosoma mansoni which infests the gastrointestinal tract. Both species are rare causes of azoospermia, and the case should be further managed as CBAVD in which the left testicle is considered the preferred site of sperm retrieval for assisted reproduction.

Efficacy and safety of ascending doses of praziquantel against Schistosoma haematobium infection in preschool-aged and school-aged children: a single-blind randomised controlled trial.

BACKGROUND: Despite decades of experience with praziquantel treatment in school-aged children (SAC) and adults, we still face considerable knowledge gaps relevant to the successful treatment of preschool-aged children (PSAC). This study aimed to assess the efficacy and safety of escalating praziquantel dosages in PSAC infected with Schistosoma haematobium. METHODS: We conducted a randomised, dose-finding trial in PSAC (2-5 years) and as comparator a cohort of SAC (6-15 years) infected with S. haematobium in Côte d'Ivoire. A total of 186 PSAC and 195 SAC were randomly assigned to 20, 40 or 60 mg/kg praziquantel or placebo. The nature of the dose-response relationship in terms of cure rate (CR) was the primary objective. Egg reduction rate (ERR) and tolerability were secondary outcomes. CRs and ERRs were assessed using triplicate urine filtration over 3 consecutive days. Available-case analysis was performed including all participants with primary endpoint data. RESULTS: A total of 170 PSAC and 174 SAC received treatment. Almost 90% of PSAC and three quarters of SAC were lightly infected with S. haematobium. Follow-up data were available for 157 PSAC and 166 SAC. In PSAC, CRs of praziquantel were 85.7% (30/35), 78.0% (32/41) and 68.3% (28/41) at 20, 40 and 60 mg/kg and 47.5% (19/40) for placebo. In SAC, CRs were 10.8% for placebo (4/37), 55.6% for 20 mg/kg (25/45), 68.3% for 40 mg/kg (28/41) and 60.5% for 60 mg/kg (26/43). ERRs based on geometric means ranged between 96.5% (60 mg/kg) and 98.3% (20 mg/kg) in PSAC and between 97.6% (20 mg/kg and 60 mg/kg) and 98.6% (40 mg/kg) in SAC. Adverse events were mild and transient. CONCLUSIONS: Praziquantel revealed dose-independent efficacy against light infections of S. haematobium. Over the dose range tested, praziquantel displayed a ceiling effect with the highest response for 20 mg/kg in PSAC. In SAC maximum efficacy was obtained with 40 mg/kg praziquantel. Further investigations are required in children with moderate to heavy infections. TRIAL REGISTRATION: This trial is registered with International Standard Randomised Controlled Trial Number ISRCTN15280205 .

Arsenicosis in bladder pathology and schistosomiasis in Eggua, Nigeria.

Background: Chronic schistosomiasis and arsenic exposure through drinking water are some of the risk factors for bladder cancer. To determine the association of schistosomiasis and arsenicosis with bladder pathologies, 122 individuals from Eggua in southwest Nigeria were recruited for this study. Methods: Prevalence of schistosomiasis was determined by urine microscopy and PCR. Total urinary arsenic concentration and arsenic levels in three different water sources in the community were assessed by flame atomic absorption spectrometry. Bladder pathologies were investigated by ultrasonography. The data collected were evaluated with chi-square (χ2) and ANOVA tests to examine the relationships among demographic factors, infection, bladder pathologies and urinary arsenic concentrations. Results: The prevalence and mean intensity of schistosomiasis were 21.3% and 20.7 eggs/10 mL urine, respectively. Arsenic concentration in two of the water sources, River Yewa (0.46 mg/L) and borehole (0.52 mg/L), were above the WHO standard (0.01 mg/L); and the mean concentration in urine samples, 1.17 mg/L, was also above the WHO standard (0.2 mg/L). There was no evidence of an association between bladder pathology and arsenicosis, or between schistosomiasis associated-bladder pathology and arsenicosis (p=0.66). Conclusions: Arsenicosis is a public health concern in the study population. At the moment no clear roles are envisaged for it in the development of bladder pathologies or urinary schistosomiasis-associated bladder pathologies in Eggua.

Metabolite profiling for biomarkers in Schistosoma haematobium infection and associated bladder pathologies.

BACKGROUND: Metabolic fingerprinting analysis can offer insights into underlying reactions in a biological system; hence it is crucial to the understanding of disease pathogenesis and could provide useful tools for discovering biomarkers. We sought to examine the urine and plasma metabolome in individuals affected by urogenital schistosomiasis and its associated-bladder pathologies. METHODOLOGY: Blood and midstream urine were obtained from volunteers who matched our inclusion criteria among residents from Eggua, southwestern Nigeria. Samples were screened by urinalysis, microscopy, PCR and ultrasonography, and categorised as advanced (urogenital schistosomiasis associated-bladder pathologies), infection-only (urogenital schistosomiasis alone) and controls (no infection and no pathology). Metabolites were extracted and data acquired with ultra high-performance liquid chromatography coupled with Thermo Q-Exactive orbitrap HRMS. Data was analysed with MetaboAnalyst, Workflow4Metabolomics, HMDB, LipidMaps and other bioinformatics tools, with univariate and multivariate statistics for metabolite selection. PRINCIPAL FINDINGS: There were low levels of host sex steroids, and high levels of several benzenoids, catechols and lipids (including ganglioside, phosphatidylcholine and phosphatidylethanolamine), in infection-only and advanced cases (FDR<0.05, VIP>2, delta>2.0). Metabolites involved in biochemical pathways related to chorismate production were abundant in controls, while those related to choline and sphingolipid metabolism were upregulated in advanced cases (FDR<0.05). Some of these human host and Schistosoma haematobium molecules, including catechol estrogens, were good markers to distinguish infection-only and advanced cases. CONCLUSIONS: Altered glycerophospholipid and sphingolipid metabolism could be key factors promoting the development of bladder pathologies and tumours during urogenital schistosomiasis.