Schistosome Eggs Research Articles

Sex as a biological variable in HIV-1 and schistosome co-infection.

The sex of people living with HIV-1 infection, schistosome infection, or both, is a fundamental determinant of their clinical outcomes and of how these two infections interact in the host. Data from longitudinal and cross-sectional human studies and animal models indicate that males with HIV-1 and schistosome co-infection excrete fewer schistosome eggs and might have higher HIV-1 RNA viral loads and greater liver damage. Females with schistosome infection appear to have higher risk of HIV-1 acquisition than females without, particularly in Schistosoma haematobium infection, and a greater risk of death in HIV-1 and schistosome co-infection. Greater transmission of HIV-1 to partners has been shown in both sexes in those with schistosome infection. Biological sex is a consequential factor affecting pathophysiological and clinical responses in HIV-1 and schistosome co-infection. Designing future analyses to incorporate sex is vital to optimise research and care for people living with HIV-1, schistosomes, and HIV-1 and schistosome co-infection.

An assessment of gynecological manifestations in women with female genital schistosomiasis with reference to Schistosoma biomarkers, sexually transmitted infections and bacterial vaginosis

BackgroundAlthough a variety of different gynecological manifestations have been reported in women with female genital schistosomiasis (FGS), causality remains to be established. This study aimed to evaluate the gynecological manifestations in women with FGS in accordance with the status of Schistosoma biomarkers, sexually transmitted infections (STIs), and bacterial vaginosis (BV).MethodsThe study was conducted in an endemic Schistosoma haematobium (Sh) area in northern Madagascar in conjunction with a randomized controlled trial investigating the effects and safety of a praziquantel repeated-dosing regimen for women with FGS-associated cervical lesions. Urogenital complaints, pelvic exam abnormalities, and cervical lesion types were assessed in relation to cervicovaginal Schistosoma DNA, circulating anodic antigen (CAA) in serum, and urinary Sh egg count, in addition to STIs and BV.ResultsAmong the included 116 women with a median of 26 years (range 15 to 35), the distribution of Schistosoma DNA and CAA outcomes, specified as either positive (+) or negative (-), were as follows: +/+ (18.1%), +/- (0%), -/+ (58.6%), and -/- (23.3%). Of the three Schistosoma biomarkers, only Schistosoma DNA and the urogenital complaint of blood in the urine were significantly associated. None of the biomarkers were significantly associated with pelvic exam abnormalities or cervical lesions. Sixty women (52.6%) were diagnosed with STIs and/or BV. A positive status was not significantly associated with any of the gynecological manifestations, except BV and homogeneous yellow sandy patches.ConclusionIt remains uncertain whether biomarkers such as cervicovaginal Schistosoma DNA, serum CAA, and Schistosoma eggs in urine adequately cover the full spectrum of gynecological manifestations reported in women with FGS, including urogenital complaints, pelvic exam abnormalities, and cervical lesions. Moreover, it seems difficult to determine the origin of the different manifestations due to the common co-existence of STIs and/or BV as potential confounders.

S. mansoni -derived omega-1 prevents OVA-specific allergic airway inflammation via hampering of cDC2 migration.

Chronic infection with Schistosoma mansoni parasites is associated with reduced allergic sensitization in humans, while schistosome eggs protects against allergic airway inflammation (AAI) in mice. One of the main secretory/excretory molecules from schistosome eggs is the glycosylated T2-RNAse Omega-1 (ω1). We hypothesized that ω1 induces protection against AAI during infection. Peritoneal administration of ω1 prior to sensitization with Ovalbumin (OVA) reduced airway eosinophilia and pathology, and OVA-specific Th2 responses upon challenge, independent from changes in regulatory T cells. ω1 was taken up by monocyte-derived dendritic cells, mannose receptor (CD206)-positive conventional type 2 dendritic cells (CD206+ cDC2), and by recruited peritoneal macrophages. Additionally, ω1 impaired CCR7, F-actin, and costimulatory molecule expression on myeloid cells and cDC2 migration in and ex vivo, as evidenced by reduced OVA+ CD206+ cDC2 in the draining mediastinal lymph nodes (medLn) and retainment in the peritoneal cavity, while antigen processing and presentation in cDC2 were not affected by ω1 treatment. Importantly, RNAse mutant ω1 was unable to reduce AAI or affect DC migration, indicating that ω1 effects are dependent on its RNAse activity. Altogether, ω1 hampers migration of OVA+ cDC2 to the draining medLn in mice, elucidating how ω1 prevents allergic airway inflammation in the OVA/alum mouse model.

Intrapulmonary T Cells Are Sufficient for Schistosoma-Induced Pulmonary Hypertension.

Schistosomiasis is a parasitic infection that can cause pulmonary hypertension (PH). Th2 CD4 T cells are necessary for experimental Schistosoma-PH. However, if T cells migrate to the lung to initiate, the localized inflammation that drives vascular remodeling and PH is unknown. Mice were sensitized to Schistosoma mansoni eggs intraperitoneally and then challenged using tail vein injection. FTY720 was administered, which blocks lymphocyte egress from lymph nodes. T cells were quantified using flow cytometry, PH severity via heart catheterization, and cytokine concentration through ELISA. FTY720 decreased T cells in the peripheral blood, and increased T cells in the mediastinal lymph nodes. However, FTY720 treatment resulted in no change in PH or type 2 inflammation severity in mice sensitized and challenged with S. mansoni eggs, and the number of memory and effector CD4 T cells in the lung parenchyma was also unchanged. Notably, intraperitoneal Schistosoma egg sensitization alone resulted in a significant increase in intravascular lymphocytes and T cells, including memory T cells, although there was no significant change in parenchymal cell density, IL-4 or IL-13 expression, or PH. Blocking T cell migration did not suppress PH following Schistosoma egg challenge. Memory CD4 T cells, located in the lung intravascular space following egg sensitization, appear sufficient to cause type 2 inflammation and PH.

The impact of ICOSL/ICOS pathway-regulated long non-coding RNAs on liver fibrosis in mice infected with Schistosoma japonicum

BackgroundThe primary pathogenic mechanism of schistosomiasis-associated liver fibrosis involves the deposition of schistosome eggs, leading to the formation of liver egg granulomas and subsequent liver fibrosis. Hepatic stellate cells are abnormally activated, resulting in excessive collagen deposition and fibrosis development. While specific long non-coding RNAs (lncRNAs) have been associated with fibrotic processes, their roles in schistosomiasis-associated liver fibrosis remain unclear.MethodsOur previous research indicated that downregulating the ICOSL/ICOS could partially alleviate liver fibrosis. In this study, we established a schistosomiasis infection model in C57BL/6 and ICOSL knockout (KO) mice, and the liver pathology changes were observed at various weeks postinfection (wpi) using hematoxylin and eosin and Masson’s trichrome staining. Within the first 4 wpi, no significant liver abnormalities were observed. However, mice exhibited evident egg granulomas and fibrosis in their livers at 7 wpi. Notably, ICOSL-KO mice had significantly smaller pathological variations compared with simultaneously infected C57BL/6 mice. To investigate the impact of lncRNAs on schistosomiasis-associated liver fibrosis, quantitative real-time polymerase chain reaction (RT-qPCR) was used to monitor the dynamic changes of lncRNAs in hepatic stellate cells of infected mice.ResultsThe results demonstrated that lncRNA-H19, -MALAT1, -PVT1, -P21 and -GAS5 all participated in liver fibrosis formation after schistosome infection. In addition, ICOSL-KO mice exhibited significantly inhibited expression of lncRNA-H19, -MALAT1 and -PVT1 after 7 wpi. In contrast, they showed enhanced expression of lncRNA-P21 and -GAS5 compared with C57BL/6 mice, influencing liver fibrosis development. Furthermore, small interfering RNA transfection (siRNA) in JS-1 cells in vitro confirmed that lncRNA-H19, -MALAT1, and -PVT1 promoted liver fibrosis, whereas lncRNA-P21 and -GAS5 had the opposite effect on key fibrotic molecules, including α- smooth muscle actin and collagen I expression.ConclusionsThis study uncovers that ICOSL/ICOS may play a role in activating hepatic stellate cells and promoting liver fibrosis in mice infected with Schistosoma japonicum by dynamically regulating the expression of specific lncRNAs. These findings offer potential therapeutic targets for schistosomiasis-associated liver fibrosis.Graphical

Schistosomiasis diagnosis: Challenges and opportunities for elimination.

The roadmap adopted by the World Health Organization (WHO) for eliminating neglected tropical diseases aims to eliminate schistosomiasis, as a public health concern, by 2030. While progress has been made towards reducing schistosomiasis morbidity control in several sub-Saharan African countries, there is still more that needs to be done. Proper surveillance using accurate diagnostics with acceptable sensitivity and specificity is essential for evaluating the success of all efforts against schistosomiasis. Microscopy, despite its low sensitivity, remains the gold standard approach for diagnosing the disease. Although many efforts have been made to develop new diagnostics based on circulating parasite proteins, genetic markers, schistosome egg morphology, and their paramagnetic properties, none has been robust enough to replace microscopy. This review highlights common diagnostic approaches for detecting schistosomiasis in field and clinical settings, major challenges, and provides new and novel opportunities and diagnosis pathways that will be critical in supporting elimination of schistosomiasis. We searched for relevant and reliable published literature from PubMed, Scopus, google scholar, and Web of science. The search strategies were primarily determined by subtopic, and hence the following words were used (schistosom*, diagnosis, Kato-Katz, antibody test, circulating antigen, POC-CCA, UCP-LF-CAA, molecular diagnostics, nucleic acid amplification test, microfluidics, lab-on a disk, lab-on chip, recombinase polymerase amplification (RPA), LAMP, portable sequencer, nanobody test, identical multi-repeat sequences, diagnostic TPPs, REASSURED, extraction free), and Boolean operators AND and/OR were used to refine the searching capacity. Due to the global public health nature of schistosomiasis, we also searched for reliable documents, reports, and research papers published by international health organizations, World Health Organization (WHO), and Center for Disease control and Elimination.

Imported schistosomiasis in travelers: Experience from a referral tropical medicine unit in Barcelona, Spain

BackgroundAcute schistosomiasis occurs most often in travelers to endemic regions. The aim of the study is to describe the epidemiological, clinical and parasitological characteristics of patients with schistosomiasis acquired during an international travel. MethodsObservational retrospective study including all travel-related schistosomiasis cases seen at the International Health Unit Vall d’Hebron-Drassanes (Barcelona, Spain) from 2009 to 2022. Diagnosis of schistosomiasis was defined by the presence of Schistosoma eggs in stools or urine or the positivity of a serological test. We collected demographic, epidemiological, clinical, parasitological, and therapeutic information. Results917 cases of schistosomiasis were diagnosed, from whom 96 (10.5 %) were travel-related. Mean age of the patients was 34.9 years, and 53.1 % were women. Median duration of the travel was 72 days, and geographical areas where travelers had contact with fresh water were Africa (82.3 %), Asia (12.5 %), and South America (5.2 %). Twenty (20.8 %) patients reported having had some clinical symptom, being gastrointestinal symptoms the most frequent. Two patients developed the classical Katayama syndrome. In eleven (11.5 %) cases eggs were observed in urine or feces samples, and 85 (88.5 %) cases were diagnosed by a positive serology. Ninety-one (94.8 %) patients received treatment with praziquantel with different therapeutic schemes. The two patients with Katayama syndrome received concomitant treatment with corticosteroids. ConclusionsSchistosomiasis in travelers represented 10 % of the overall schistosomiasis cases in our center. Increasing the awareness in the pre-travel advice and implementing specific screening in those travelers at risk (long travelers, contact with fresh water) could reduce the incidence and associated morbidity in this group.

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.

Human Placental Schistosomiasis-A Systematic Review of the Literature.

Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause placental schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any systematic review on PS. We conducted a systematic literature search on PubMed, EMBASE, and Medline and included all publications that reported microscopically confirmed cases of PS, as well as the relevant secondary literature found in the citations of the primarily included publications. Out of 113 abstracts screened we found a total of 8 publications describing PS with a total of 92 cases describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association with adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only <1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. PS is a highly unattended and underdiagnosed condition in endemic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation.

Human Passage of Schistosoma incognitum, Tamil Nadu, India, and Review of Autochthonous Schistosomiasis, South Asia.

A fecal survey in Tamil Nadu, India, revealed 2 persons passed schistosome eggs, later identified as Schistosoma incognitum, a parasite of pigs, dogs, and rats. We investigated those cases and reviewed autochthonous schistosomiasis cases from India and Nepal. Whether the 2 new cases represent true infection or spurious passage is undetermined.

Comparison of tissue biomarkers between non-schistosoma and schistosoma-associated urothelial carcinoma

BackgroundHigh-grade urothelial carcinoma either non-Schistosoma (NS-UBC) or Schistosoma (S-UBC)-associated is the tenth cause of death worldwide and represents a serious therapeutic problem. AimEvaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker. Material and methodsSixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers’ expression in S-UBC. ResultsThe area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1. ConclusionDue to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit.

Trematode infection in ruminants and diversity of snail hosts across three agro-ecological zones in Ethiopia

The occurrence of trematodes among ruminants and their snail vectors is a major concern across various agro-ecological regions of Ethiopia. Trematodes pose significant threats to animals, causing considerable economic losses and impacting public health. In this study, we have investigated 784 ruminant fecal samples, and 520 abattoir samples, alongside the collection and identification of snail vectors from various agro-ecological regions. Fecal examinations revealed Fasciola, Paramphistomum and Schistosoma species infected 20.5% (95% CI: 17.6, 23.8), 11.7% (95% CI: 9.6, 14.2), and 6.3% (95% CI: 4.1, 9.1) of the animals, respectively. The overall prevalence of trematodes among ruminants was 28.8% (95% CI: 25.7, 32.1%), with 6.0% (95% CI: 4.3, 7.7) showing mixed infections. Fasciola was more prevalent in Asela (26%) compared to Batu (19%) and Hawassa (11.5%), while a higher proportion of animals in Batu were infected with Paramphistomum. Schistosoma eggs were detected only in Batu (12.5%), but not in other areas. Sheep and cattle exhibited higher infection rates with Fasciola, Paramphistoma, and Schistosoma compared to goats. Significant associations were observed between trematode infections and risk factors including agro-ecology, animal species, body condition score, and deworming practices. About 20.8% and 22.7% of the slaughtered animals harbored Fasciola and Paramphistomum flukes, respectively, with a higher prevalence in Asela and Hawassa abattoirs compared to Batu abattoir. Additionally, a total of 278 snails were collected from the study areas and identified as lymnae natalensis, lymnae trancatula, Biomphalaria pffiferi, Biomphlaria sudanica, and Bulinus globosus. In conclusion, the study highlights the widespread occurrence of trematode infections, emphasizing the need for feasible control measures to mitigate their economic and public health impacts.

Prevalence of diverse colorectal polyps and risk factors for colorectal carcinoma in situ and neoplastic polyps

BackgroundMost colorectal cancers originate from precancerous polyps. This study aimed to determine the prevalence of colorectal polyps with diverse pathological morphologies and to explore the risk factors for colorectal carcinoma in situ (CCS) and neoplastic polyps.MethodsInpatients admitted from January 2018 to May 2023 were screened through the hospital information system. Polyps were classified according to pathological morphology. The prevalence of polyps was described by frequency and 95% confidence interval. Univariate and multivariate logistic regression analyses were used to explore the risk factors for CCS and neoplastic polyps.ResultsIn total, 2329 individuals with 3550 polyps were recruited. Among all patients, 76.99% had neoplastic polyps and 44.31% had advanced adenomas. Tubular adenoma had the highest prevalence at 60.15%, and the prevalence of CCS was 3.86%. Patients with a colorectal polyp diameter ≥ 1.0 cm or number ≥ 3 were 8.07 times or 1.98 times more likely to develop CCS than were those with a diameter < 1.0 cm or number < 3, respectively (OR 8.07, 95%CI 4.48–14.55, p < 0.0001; and OR 1.98, 95%CI 1.27–3.09, p = 0.002). The risk of CCS with schistosome egg deposition was also significantly increased (OR 2.70, 95%CI 1.05–6.98). The higher the levels of carbohydrate antigen (CA) 724 (OR 1.01, 95%CI 1.00–1.02) and CA211 (OR 1.16, 95%CI 1.03–1.32) in patients with colorectal polyps were, the greater the risk of CCS. When colorectal neoplastic polyps were analyzed, we discovered that for each 1-year increase in age, the risk of neoplastic polyps increased by 3% (OR 1.03, 95%CI 1.02–1.04), p < 0.0001. Patients with a polyp diameter ≥ 1.0 cm had a 2.11-fold greater risk of neoplastic polyps compared to diameter < 1.0 cm patients (OR 3.11, 95%CI 2.48–3.92), p < 0.0001. In addition, multiple polyps and CA199 levels are risk factors for neoplastic polyps.ConclusionMore than 3/4 of colorectal polyp patients have neoplastic polyps. Patients are more inclined to develop CCS and neoplastic polyps if they have large polyps (> 1.0 cm) or multifocal polyps. The levels of the tumor markers CA724 and CA211 show some potential usefulness for predicting CCS and may be exploited for early identification of high-risk populations.

Sja-let-7 suppresses the development of liver fibrosis via Schistosoma japonicum extracellular vesicles.

Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic "partner" in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-β/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-β/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.

Prevalence of Bovine Schistosomiasis and Associated Risk Factors in and Around Haramaya, Oromia Region, East Ethiopia.

Schistosomiasis is caused by the Schistosoma genus and is transmitted through intermediate hosts, such as snails. A cross-sectional investigation was conducted within and surrounding Haramaya town between December 2022 and May 2023 to estimate the prevalence of schistosomiasis in cattle and associated risk factors. The degree of prevalence was estimated using surveys carried out in slaughterhouses and coprological laboratories. For statistical estimation, chi-square tests and logistic regression were utilized. A total of 390 samples were obtained through simple random sampling. In the survey that was undertaken on abattoirs, a total of 384 samples were chosen through the utilization of a systematic random sampling approach. The recovery of Schistosoma eggs from fecal specimens was achieved by sedimentation. The overall rates of schistosomiasis in cattle were estimated to be 21.28% and 18.23% through coprological and postmortem examinations, respectively. The analysis conducted through multivariable logistic regression indicated that management system, body condition, and age were significant risk factors. Cattle under extensive management (OR = 5.9, 95% CI = 2-17) and those in the young age category (OR = 2.7, 95% CI = 1.0-7.00) were more susceptible to acquiring schistosomiasis than cattle under intensive management and those in the adult age category, respectively. According to the odds ratio, there was a positive association between the incidence rate of schistosomiasis in cattle and poor body condition (OR: 3.048, 95% CI = 1.07-8.68; P = 0.00). Schistosomiasis infection was 3.048 times more likely to manifest in animals in poor physical condition. This affliction has had a profound impact on the livestock industry, as substantiated by the elevated prevalence of schistosomiasis in cattle within the studied region. Consequently, an integrated approach to prevention and control that targets the parasite is needed.

Harnessing Schistosoma-associated metabolite changes in the human host to identify biomarkers of infection and morbidity: Where are we and what should we do next?

Schistosomiasis is the second most widespread parasitic disease affecting humans. A key component of today's infection control measures is the diagnosis and monitoring of infection, informing individual- and community-level treatment. However, newly acquired infections and/or low parasite burden are still difficult to diagnose reliably. Furthermore, even though the pathological consequence of schistosome egg sequestration in host tissues is well described, the evidence linking egg burden to morbidity is increasingly challenged, making it inadequate for pathology monitoring. In the last decades, omics-based instruments and methods have been developed, adjusted, and applied in parasitic research. In particular, the profiling of the most reliable determinants of phenotypes, metabolites by metabolomics, emerged as a powerful boost in the understanding of basic interactions within the human host during infection. As such, the fine detection of host metabolites produced upon exposure to parasites such as Schistosoma spp. and the ensuing progression of the disease are believed to enable the identification of Schistosoma spp. potential biomarkers of infection and associated pathology. However, attempts to provide such a comprehensive understanding of the alterations of the human metabolome during schistosomiasis are rare, limited in their design when performed, and mostly inconclusive. In this review, we aimed to briefly summarize the most robust advances in knowledge on the changes in host metabolic profile during Schistosoma infections and provide recommendations for approaches to optimize the identification of metabolomic signatures of human schistosomiasis.

An improved medium for in vitro studies of female reproduction and oviposition in Schistosoma japonicum

BackgroundSchistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum.MethodsWe optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4′,6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male β-alanyl-tryptamine (BATT) was conducted using liquid chromatography–mass spectrometry (LC–MS).ResultsBoth m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone β-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum’s reproductive and oviposition processes.ConclusionsWe developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production.Graphical

Accurate Diagnosis of Schistosoma mansoni and S. haematobium from Filtered Urine Samples Collected in Tanzania, Africa.

Schistosomiasis is a bloodborne, and waterborne parasitic disease caused by the human Schistosoma species, namely Schistosoma mansoni and S. haematobium. The parasite requires an intermediate snail host, where they grow and develop, along with a human host (definitive). Schistosoma egg detection in feces (S. mansoni) and urine (S. haematobium) are the WHO-recommended confirmatory diagnostic tests. The goal of our research was to determine the efficacy of detecting single or dual Schistosome species from filtered human urine samples collected in Tanzania by amplifying species-specific cell-free repeat DNA fragments via polymerase chain reaction (PCR) and gel electrophoresis. In total, 104 filtered human urine samples were evaluated and collected from individuals residing in the village of Kayenze, Tanzania. All samples were detected with 100% accuracy and no cross-amplification was present. For a single infection of S. mansoni, 22 (21%) of the samples were positive, while 15 (14%) of the samples were negative via PCR. Moreover, for a single infection of S. haematobium, 7 (7%) of the samples were positive, while 15 (14%) of the samples were negative. Dual infections were found in a higher percentage, with 60 (58%) of the samples being positive. Thus, we have justified that PCR is more sensitive and specific by amplifying species-specific cell-free repeat DNA fragments from the same urine sample than WHO-recommended methods of processing stool and urine.

Antimalarial artesunate–mefloquine versus praziquantel in African children with schistosomiasis: an open-label, randomized controlled trial

Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of the antimalarial combination artesunate–mefloquine for the treatment of schistosomiasis in a proof-of-concept, pragmatic, open-label, randomized controlled trial in primary schools of six villages endemic for schistosomiasis in northern Senegal. Children (6–14 years) were eligible if Schistosoma eggs were detected by microscopy in urine and/or stool. In total, 726 children were randomized 1:1 to praziquantel (standard care: 40 mg kg−1 single dose; n = 364) or to artesunate–mefloquine (antimalarial dosage: artesunate 4 mg kg−1 and mefloquine 8 mg kg−1 daily for three consecutive days; n = 362). Eight children not meeting the inclusion criteria were excluded from efficacy analysis. Median age of the remaining 718 participants was 9 years; 399 (55.6%) were male, and 319 (44.4%) female; 99.3% were infected with Schistosoma haematobium and 15.2% with S. mansoni. Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate–mefloquine versus praziquantel at 4 weeks after treatment. Cure rate was 59.6% (208/349) in the artesunate–mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%). All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate–mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel (P < 0.001). Artesunate–mefloquine at antimalarial dosage was moderately safe and noninferior to standard-care praziquantel for the treatment of schistosomiasis, predominantly due to S. haematobium. Multicentric trials in different populations and epidemiological settings are needed to confirm these findings. ClinicalTrials.gov identifier: NCT03893097.

Hypothesis Explaining Development of Squamous Cell Carcinoma During Infection with Schistosoma Haematobium

Schistosome worms are blood-dwelling flukes that cause chronic infection in more than 200 million people and are thought to be responsible for 500,000 deaths annually. During infection with Schistosoma haematobium, eggs are deposited in the mucosa and submucosa of the bladder and lower ureters. Squamous cell carcinoma (SCC) of the bladder is a long-term sequela of chronic infection. The mechanisms underlying the association between S. haematobium and SCC of the bladder are largely unknown, with all reports to date exclusively demonstrating epidemiological evidence linking S. haematobium infection with SCC of the bladder. Scientists hypothesised that the parasite antigens might induce alterations in epithelial cells towards cancer. Scientists used Chinese Hamster Ovary (CHO) cells and treated the cells in culture with S. haematobium total antigen (Sh). Results showed increased proliferation, increased S-phase and decreased apoptosis, as well as down-regulation of tumor suppressor p27 and up-regulation of anti-apoptotic molecule Bcl-2 (Botelho et al., 2009). Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions (Dematei et al., 2017). S. haematobium is classified as a Group 1 carcinogen by the World Health Organization’s International Agency for Research on Cancer (Hodderet al., 2000). Another factor that may play a major role in bladder carcinogenesis in schistosomiasis patients is the presence of continuous physical irritation and inflammation produced by Schistosoma eggs in the bladder mucosa. The adult S. haematobium worms inhabit the veins of the perivesical plexus, where the female lays eggs. Some eggs pass through the bladder mucosa and are excreted in the urine. Other eggs are trapped in the tissue. A chronic inflammatory reaction is initiated, with the invasion of histiocytes and other inflammatory cells into the bladder, the formation of granulomas and eventually fibrosis. In addition, the eruption of the eggs through the mucosa stimulates reparative urothelial hyperplasia and cell turnover (Rosin et al., 1994). In our article we try to explain possible mechanism of conversion normal cells into tumor cells from the position of karyogamic theory.