Schistosome Life Cycle Research Articles

Review on Schistosomiasis: Epidemiology and Clinical Manifestation up to Date

Schistosomiasis is a parasite disease that affects both humans and animals and is brought on by the blood flukes of the genus Schistosoma. It is one of the world’s most enduring neglected tropical diseases. Sub-Saharians make up more than 90% of them, and a significant portion of Ethiopians are afflicted and at risk. It spread across the entire nation and was correlated with the rapid development of water resources and population growth. The two species of freshwater snails, Biomphalaria pfeifferi and Biomphalaria sudanica, are responsible for the parasite’s transmission in Ethiopia. Compared to the three primary schistosomes that infect people, Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Schistosoma intercalatum, and Schistosoma mekongi have less of an epidemiological impact. Geographically, S. haematobium and S. mansoni are more common in Africa than other species. Epidemiological coverage is also influenced by seasonal distributions throughout the postrainy season, as well as the cold and dry seasons. The organs and systems implicated in its pathogenic dissemination include the intestines, urogenital systems, the pulmonary system, the liver, spleen, and the brain. Ecological change and sociocultural influences are risk factors for water contamination. Regarding clinical symptoms, the penetration of cercariae into the dermis, cercarial dermatitis, acute schistosomiasis, and the chronic stage of infection are significant. Mammals and snails serve as the two hosts for the schistosome life cycle. It can be diagnosed through clinical exams and laboratory techniques. Praziquantel can be used to treat this condition, and it can be prevented by taking precautions during ecological shifts that may result in epidemics. Other measures to take include providing clean water, maintaining good hygiene, controlling mosquitoes, and spreading health awareness.

Schistosoma mansoni Fibroblast Growth Factor Receptor A Orchestrates Multiple Functions in Schistosome Biology and in the Host-Parasite Interplay.

Stem cells play significant roles in driving the complex life cycle of Schistosoma mansoni. Fibroblast growth factor (FGF) receptor A (SmFGFRA) is essential for maintaining the integrity of schistosome stem cells. Using immunolocalization, we demonstrated that SmFGFRA was distributed abundantly in germinal/stem cells of different S. mansoni life stages including eggs, miracidia, cercariae, schistosomula and adult worms. Indeed, SmFGFRA was also localized amply in embryonic cells and in the perinuclear region of immature eggs; von Lichtenberg’s layer and the neural mass of mature eggs; the ciliated surface and neural mass of miracidia; the tegument cytosol of cercariae, schistosomula and adult worms; and was present in abundance in the testis and vitellaria of adult worms of S. mansoni. The distribution pattern of SmFGFRA illustrates the importance of this molecule in maintaining stem cells, development of the nervous and reproductive system of schistosomes, and in the host-parasite interplay. We showed SmFGFRA can bind human FGFs, activating the mitogen activated protein kinase (MAPK) pathway of adult worms in vitro. Inhibition of FGF signaling by the specific tyrosine kinase inhibitor BIBF 1120 significantly reduced egg hatching ability and affected the behavior of miracidia hatched from the treated eggs, emphasizing the importance of FGF signaling in driving the life cycle of S. mansoni. Our findings provide increased understanding of the complex schistosome life cycle and host-parasite interactions, indicating components of the FGF signaling pathway may represent promising targets for developing new interventions against schistosomiasis.

Analysis of rhodopsin G protein-coupled receptor orthologs reveals semiochemical peptides for parasite (Schistosoma mansoni) and host (Biomphalaria glabrata) interplay

Schistosomiasis is a medically significant disease caused by helminth parasites of the genus Schistosoma. The schistosome life cycle requires chemically mediated interactions with an intermediate (aquatic snail) and definitive (human) host. Blocking parasite development within the snail stage requires improved understanding of the interactions between the snail host and the Schistosoma water-borne free-living form (miracidium). Innovations in snail genomics and aquatic chemical communication provide an ideal opportunity to explore snail-parasite coevolution at the molecular level. Rhodopsin G protein-coupled receptors (GPCRs) are of particular interest in studying how trematode parasites navigate towards their snail hosts. The potential role of GPCRs in parasites makes them candidate targets for new antihelminthics that disrupt the intermediate host life-cycle stages, thus preventing subsequent human infections. A genomic-bioinformatic approach was used to identify GPCR orthologs between the snail Biomphalaria glabrata and miracidia of its obligate parasite Schistosoma mansoni. We show that 8 S. mansoni rhodopsin GPCRs expressed within the miracidial stage share overall amino acid similarity with 8 different B. glabrata rhodopsin GPCRs, particularly within transmembrane domains, suggesting conserved structural features. These GPCRs include an orphan peptide receptor as well as several with strong sequence homologies with rhabdomeric opsin receptors, a serotonin receptor, a sulfakinin (SK) receptor, an allatostatin-A (buccalin) receptor and an FMRFamide receptor. Buccalin and FMRFa peptides were identified in water conditioned by B. glabrata, and we show synthetic buccalin and FMRFa can stimulate significant rates of change of direction and turn-back responses in S. mansoni miracidia. Ortholog GPCRs were identified in S. mansoni miracidia and B. glabrata. These GPCRs may detect similar ligands, including snail-derived odorants that could facilitate miracidial host finding. These results lay the foundation for future research elucidating the mechanisms by which GPCRs mediate host finding which can lead to the potential development of novel anti-schistosome interventions.

Innovations and Advances in Schistosome Stem Cell Research.

Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle involving alternating infection of freshwater snail intermediate and definitive mammalian hosts. To survive and flourish in these diverse environments, schistosomes transition through a number of distinct life-cycle stages as a result of which they change their body plan in order to quickly adapt to each new environment. Current research suggests that stem cells, present in adults and larvae, are key in aiding schistosomes to facilitate these changes. Given the recent advances in our understanding of schistosome stem cell biology, we review the key roles that two major classes of cells play in the different life cycle stages during intramolluscan and intramammalian development; these include the germinal cells of sporocysts involved in asexual reproduction in molluscan hosts and the neoblasts of adult worms involved in sexual reproduction in human and other mammalian hosts. These studies shed considerable new light in revealing the stem cell heterogeneity driving the propagation of the schistosome life cycle. We also consider the possibility and value of establishing stem cell lines in schistosomes to advance schistosomiasis research. The availability of such self-renewable resources will provide new platforms to study stem cell behavior and regulation, and to address fundamental aspects of schistosome biology, reproductive development and survival. In turn, such studies will create new avenues to unravel individual gene function and to optimize genome-editing processes in blood flukes, which may lead to the design of novel intervention strategies for schistosomiasis.

Human water contact patterns in active schistosomiasis endemic areas.

One major risk factor common to individuals in schistosomiasis endemic areas is water contact patterns. Effort to determine the dynamics in water contact patterns in different regions needs utmost attention in order to suggest a better control strategy for schistosome infection. Quantitative observations on human water contact activities were recorded in Yewa North Local Government Area of Ogun State for a period of two years. Frequency and duration of observed water contact activities were recorded. Males had the highest water contact during the rainy season with 51.1% compared to females with 48.9%. Females had the highest water contact with 51.0% while males had 49.0% during the dry season. The age group 10-19 years had the highest water contact with 27.1%, this was followed by 20-29 years and 30-39 years age groups with 23.6% and 22.1%, respectively, during the rainy season. Our results showed that water contact activities differ with respect to different communities, sex and age groups. Previous high prevalence of schistosome infection in the study areas could be attributed to high water contact activities. Therefore, provision of adequate pipe-borne water, good sanitation and improved knowledge on schistosome life cycle among the community members will reduce the high rate of human water contacts.

Analyses of the expression, immunohistochemical properties and serodiagnostic potential of Schistosoma japonicum peroxiredoxin-4

BackgroundSchistosoma japonicum, which inhabits the mesenteric vein of the mammalian hosts for about 20 to 30 years, is subjected to the oxidative stresses from the host defense mechanism during their intra-mammalian stages. To counteract this host immune attack, the parasite utilizes their antioxidant system for survival inside the host. Peroxiredoxins (Prxs), thiol-specific antioxidant proteins, play an essential role for protecting the parasite against oxidative stress by reducing hydrogen peroxide to water. Only three types of 2-Cys Prxs have been previously characterized in S. japonicum whereas a fourth Prx has been identified for Schistosoma mansoni as Prx-4. A sequence coding homologous to this gene in the S. japonicum database was identified, characterized and expressed as recombinant SjPrx-4 protein (rSjPrx-4). Furthermore, rSjPrx-4 was evaluated in this study for its diagnostic potentials in detecting S. japonicum infection in humans.ResultsThe gene found in the parasite genome contained 2 active-site cysteines with conserved sequences in the predicted amino acid (AA) sequence and showed 75% identity with that of the previously characterized Prx (TPx-1) of S. japonicum. The gene was expressed in different stages of schistosome life-cycle with highest transcription level in the adult male. The gene was cloned into a plasmid vector and then transfected into Escherichia coli for expression of rSjPrx-4. Anti-rSjPrx-4 mouse sera recognized native SjPrx-4 in egg and adult worm lysate by western blotting. The result of a mixed function oxidation assay in which rSjPrx-4 prevented the nicking of DNA from hydroxyl radicals confirmed its antioxidant activity. Subsequently, immunolocalization analysis showed the localization of SjPrx-4 inside the egg, on the tegument and in the parenchyma of the adult worm. Enzyme-linked immunosorbent assay results showed that rSjPrx-4 has 83.3% sensitivity and 87.8% specificity. Its diagnostic potential was further evaluated in combination with recombinant SjTPx-1 protein, yielding an improved sensitivity and specificity of 90% and 92.7%, respectively.ConclusionsThese results suggest that SjPrx-4 plays a role as an antioxidant dealing with oxidative stresses of S. japonicum, and its diagnostic potential improved by coupling it with SjTPx-1 is a proof for developing a serological test with better diagnostic performance for human schistosomiasis.

Effects of agrochemical pollution on schistosomiasis transmission: a systematic review and modelling analysis

BackgroundAgrochemical pollution of surface waters is a growing global environmental challenge, especially in areas where agriculture is rapidly expanding and intensifying. Agrochemicals might affect schistosomiasis transmission through direct and indirect effects on Schistosoma parasites, their intermediate snail hosts, snail predators, and snail algal resources. We aimed to review and summarise the effects of these agrochemicals on schistosomiasis transmission dynamics.MethodsWe did a systematic review of agrochemical effects on the lifecycle of Schistosoma spp and fitted dose-response models to data regarding the association between components of the lifecycle and agrochemical concentrations. We incorporated these dose-response functions and environmentally relevant concentrations of agrochemicals into a mathematical model to estimate agrochemical effects on schistosomiasis transmission. Dose-response functions were used to estimate individual agrochemical effects on estimates of the agrochemically influenced basic reproduction number, R0, for Schistosoma haematobium. We incorporated time series of environmentally relevant agrochemical concentrations into the model and simulated mass drug administration control efforts in the presence of agrochemicals.FindingsWe derived 120 dose-response functions describing the effects of agrochemicals on schistosome lifecycle components. The median estimate of the basic reproduction number under agrochemical-free conditions, was 1·65 (IQR 1·47–1·79). Agrochemical effects on estimates of R0 for S haematobium ranged from a median three-times increase (R0 5·05, IQR 4·06–5·97) to transmission elimination (R0 0). Simulations of transmission dynamics subject to interacting annual mass drug administration and agrochemical pollution yielded a median estimate of 64·82 disability-adjusted life-years (DALYs) lost per 100,000 people per year (IQR 62·52–67·68) attributable to atrazine use. In areas where aquatic arthropod predators of intermediate host snails suppress transmission, the insecticides chlorpyrifos (6·82 DALYs lost per 100,000 people per year, IQR 4·13–8·69) and profenofos (103·06 DALYs lost per 100,000 people per year, IQR 89·63–104·90) might also increase the disability burden through their toxic effects on arthropods.InterpretationExpected environmental concentrations of agrochemicals alter schistosomiasis transmission through direct and indirect effects on intermediate host and parasite densities. As industrial agricultural practices expand in areas where schistosomiasis is endemic, strategies to prevent increases in transmission due to agrochemical pollution should be developed and pursued.

(+)-(R)- and (−)-(S)-Perhexiline maleate: Enantioselective synthesis and functional studies on Schistosoma mansoni larval and adult stages

Schistosomiasis is a neglected tropical disease mainly affecting the poorest tropical and subtropical areas of the world with the impressive number of roughly 200 million infections per year. Schistosomes are blood trematode flukes of the genus Schistosoma causing symptoms in humans and animals. Organ morbidity is caused by the accumulation of parasite eggs and subsequent development of fibrosis. If left untreated, schistosomiasis can result in substantial morbidity and even mortality. Praziquantel (PZQ) is the most effective and widely used compound for the treatment of the disease, in prevention and control programs in the last 30 years. Unfortunately, it has no effect on juvenile immature schistosomes and cannot prevent reinfection or interfere with the schistosome life cycle; moreover drug-resistance represents a serious threat. The search for an alternative or complementary treatment is urgent and drug repurposing could accelerate a solution. The anti-anginal drug perhexiline maleate (PHX) has been previously shown to be effective on larval, juvenile, and adult stages of S. mansoni and to impact egg production in vitro. Since PHX is a racemic mixture of R-(+)- and S-(−)-enantiomers, we designed and realized a stereoselective synthesis of both PHX enantiomers and developed an analytical procedure for the direct quantification of the enantiomeric excess also suitable for semipreparative separation of PHX enantiomers. We next investigated the impact of each enantiomer on viability of newly transformed schistosomula (NTS) and worm pairs of S. mansoni as well as on egg production and vitellarium morphology by in vitro studies. Our results indicate that the R-(+)-PHX is mainly driving the anti-schistosomal activity but that also the S-(−)-PHX possesses a significant activity towards S. mansoni in vitro.

The repositioning of epigenetic probes/inhibitors identifies new anti-schistosomal lead compounds and chemotherapeutic targets.

Praziquantel represents the frontline chemotherapy used to treat schistosomiasis, a neglected tropical disease (NTD) caused by infection with macro-parasitic blood fluke schistosomes. While this drug is safe, its inability to kill all schistosome lifecycle stages within the human host often requires repeat treatments. This limitation, amongst others, has led to the search for novel anti-schistosome replacement or combinatorial chemotherapies. Here, we describe a repositioning strategy to assess the anthelmintic activity of epigenetic probes/inhibitors obtained from the Structural Genomics Consortium. Thirty-seven epigenetic probes/inhibitors targeting histone readers, writers and erasers were initially screened against Schistosoma mansoni schistosomula using the high-throughput Roboworm platform. At 10 μM, 14 of these 37 compounds (38%) negatively affected schistosomula motility and phenotype after 72 hours of continuous co-incubation. Subsequent dose-response titrations against schistosomula and adult worms revealed epigenetic probes targeting one reader (NVS-CECR2-1), one writer (LLY-507 and BAY-598) and one eraser (GSK-J4) to be particularly active. As LLY-507/BAY-598 (SMYD2 histone methyltransferase inhibitors) and GSK-J4 (a JMJD3 histone demethylase inhibitor) regulate an epigenetic process (protein methylation) known to be critical for schistosome development, further characterisation of these compounds/putative targets was performed. RNA interference (RNAi) of one putative LLY-507/BAY-598 S. mansoni target (Smp_000700) in adult worms replicated the compound-mediated motility and egg production defects. Furthermore, H3K36me2, a known product catalysed by SMYD2 activity, was also reduced by LLY-507 (25%), BAY-598 (23%) and siSmp_000700 (15%) treatment of adult worms. Oviposition and packaging of vitelline cells into in vitro laid eggs was also significantly affected by GSK-J4 (putative cell permeable prodrug inhibitor of Smp_034000), but not by the related structural analogue GSK-J1 (cell impermeable inhibitor). Collectively, these results provide further support for the development of next-generation drugs targeting schistosome epigenetic pathway components. In particular, the progression of histone methylation/demethylation modulators presents a tractable strategy for anti-schistosomal control.

Identification of a new panel of reference genes to study pairing-dependent gene expression in Schistosoma mansoni

Facilitated by the Schistosoma mansoni genome project, multiple transcriptomic studies were performed over the last decade to elucidate gene expression patterns among different developmental stages of the complex schistosome life cycle. While these analyses enable the identification of candidate genes with key functions in schistosome biology, a diverse molecular tool set is needed that allows comprehensive functional characterization at the single gene level. This includes the availability of reliable reference genes to confirm changes in the transcription of genes of interest over different biological samples and experimental conditions. In particular, the investigation of one key aspect of schistosome biology, the pairing-dependent gene expression in females and males, requires knowledge on reference genes that are expressed independently of both pairing and of in vitro culture effects. Therefore, the present study focused on the identification of quantitative reverse transcription (qRT)-PCR reference genes suitable for the investigation of pairing-dependent gene expression in the S. mansoni male. The “pipeline” we present here is based on qRT-PCR analyses of high biological replication combined with three different statistical analysis tools, BestKeeper, geNorm, and NormFinder. Our approach resulted in a statistically robust ranking of 15 selected reference genes with respect to their transcription stability between pairing-unexperienced and -experienced males. We further tested the top seven candidate genes for their transcription stability during invitro culture of adult S. mansoni. Of these, the two most suitable reference genes were used to investigate the influence of the pairing contact on the transcription of genes of interest, comprising a tyrosine decarboxylase gene Smtdc1, an ebony ortholog Smebony, and the follistatin ortholog Smfst in S. mansoni males. Performing pairing, separation and re-pairing experiments with adult S. mansoni in vitro, our results indicate for the first time that pairing can act as a molecular on/off-switch of specific genes to strictly control their expression in schistosome males.

Effects of Agrochemical Pollution on Schistosomiasis Transmission: A Systematic Review and Modeling Analysis

Background: Agrochemical pollution of surface waters is a growing global environmental challenge, especially in areas where agriculture is rapidly expanding and intensifying. Recent work suggests that agrochemicals may affect schistosomiasis transmission through direct and indirect effects on Schistosoma parasites, their intermediate snail hosts, snail predators, and snail algal resources. Methods: We conducted a systematic review of agrochemical effects on the lifecycle of Schistosoma spp. and fitted dose-response models to data relating components of the lifecycle and agrochemical concentrations. We incorporated these dose-response functions and environmentally-relevant concentrations of agrochemicals into a mathematical model to estimate agrochemical effects on schistosomiasis transmission. Findings: We derived 120 dose-response functions describing effects of agrochemicals on schistosome lifecycle components. Agrochemical effects on estimates of the basic reproduction number, R0, for S. haematobium ranged from an increase of 306% (IQR: 246% – 362%) to transmission elimination (R0 -> 0). Simulations of transmission dynamics subject to interacting annual mass drug administration and agrochemical pollution yield a median estimate of 64·82 (IQR: 62·52 – 67·68) DALYs lost per 100,000 people per year attributable to atrazine use. In areas where aquatic arthropod predators of intermediate host snails suppress transmission, the insecticides chlorpyrifos and profenofos may also increase disability (6·82 [4·13 – 8·69] and 103·06 [89·63 – 104·90] DALYs lost per 100,000 people per year, respectively) through their toxic effects to arthropods. Interpretation: Expected environmental concentrations of agrochemicals alter schistosomiasis transmission through direct and indirect effects on intermediate host and parasite densities. As industrial agricultural practices expand in areas where schistosomiasis is endemic, strategies to limit increases in transmission due to agrochemical pollution should be developed and pursued. Funding Statement: Funding from the National Institutes of Health [1R01TW010286 and R01AI125842], the National Science Foundation Water, Sustainability and Climate program [1360330 and 1646708] and DS421 training program [1450053], and by the University of California Multicampus Research Programs and Initiatives [award MRP-17-446315]. Declaration of Interests: The authors report no competing interests.

Gene Expression in Developmental Stages of Schistosoma japonicum Provides Further Insight into the Importance of the Schistosome Insulin-Like Peptide.

We showed previously that the Schistosoma japonicum insulin-like peptide (SjILP) binds the worm insulin receptors, thereby, activating the parasite’s insulin pathway and emphasizing its important role in regulating uptake of glucose, a nutrient essential for parasite survival. Here we show that SjILP is differentially expressed in the schistosome life cycle and is especially highly transcribed in eggs, miracidia, and adult female worms. RNA inference was employed to knockdown SjILP in adults in vitro, with suppression confirmed by significantly reduced protein production, declined adenosine diphosphate levels, and reduction in glucose consumption. Immunolocalization showed that SjILP is located to lateral gland cells of mature intra-ovular miracidia in the schistosome egg, and is distributed on the ciliated epithelium and internal cell masses of newly transformed miracidia. In schistosomula, SjILP is present on the tegument in two antero-lateral points, indicating highly polarized expression during cercarial transformation. Analysis of serum from S. japonicum-infected mice by ELISA using a recombinant form of SjILP as an antigen revealed IgG immunoreactivity to this molecule at 7 weeks post-infection indicating it is likely secreted from mature eggs into the host circulation. These findings provide further insights on ILP function in schistosomes and its essential roles in parasite survival and growth in different development stages.

Artemether and Praziquantel: Origin, Mode of Action, Impact, and Suggested Application for Effective Control of Human Schistosomiasis.

The stumbling block for the continued, single-drug use of praziquantel (PZQ) against schistosomiasis is less justified by the risk of drug resistance than by the fact that this drug is inactive against juvenile parasites, which will mature and start egg production after chemotherapy. Artemisinin derivatives, currently used against malaria in the form of artemisinin-based combination therapy (ACT), provide an opportunity as these drugs are not only active against malaria plasmodia, but surprisingly also against juvenile schistosomes. An artemisinin/PZQ combination would be complementary, and potentially additive, as it would kill two schistosome life cycle stages and thus confer a transmission-blocking modality to current chemotherapy. We focus here on single versus combined regimens in endemic settings. Although the risk of artemisinin resistance, already emerging with respect to malaria therapy in Southeast Asia, prevents use in countries where ACT is needed for malaria care, an artemisinin-enforced praziquantel treatment (APT) should be acceptable in regions of North Africa (including Egypt), the Middle East, China, and Brazil that are not endemic for malaria. Thanks to recent progress with respect to high-resolution diagnostics, based on circulating schistosome antigens in humans and molecular approaches for snail surveys, it should be possible to keep areas scheduled for schistosomiasis elimination under surveillance, bringing rapid response to bear on problems arising. The next steps would be to investigate where and for how long APT should be applied to make a lasting impact. A large-scale field trial in an area with modest transmission should tell how apt this approach is.

Stem cell heterogeneity drives the parasitic life cycle of Schistosoma mansoni

Schistosomes are parasitic flatworms infecting hundreds of millions of people. These parasites alternate between asexual reproduction in molluscan hosts and sexual reproduction in mammalian hosts; short-lived, water-borne stages infect each host. Thriving in such disparate environments requires remarkable developmental plasticity, manifested by five body plans deployed throughout the parasite's life cycle. Stem cells in Schistosoma mansoni provide a potential source for such plasticity; however, the relationship between stem cells from different life-cycle stages remains unclear, as does the origin of the germline, required for sexual reproduction. Here, we show that subsets of larvally derived stem cells are likely sources of adult stem cells and the germline. We also identify a novel gene that serves as the earliest marker for the schistosome germline, which emerges inside the mammalian host and is ultimately responsible for disease pathology. This work reveals the stem cell heterogeneity driving the propagation of the schistosome life cycle.

Mobile Diagnostics Based on Motion? A Close Look at Motility Patterns in the Schistosome Life Cycle.

Imaging at high resolution and subsequent image analysis with modified mobile phones have the potential to solve problems related to microscopy-based diagnostics of parasitic infections in many endemic regions. Diagnostics using the computing power of “smartphones” is not restricted by limited expertise or limitations set by visual perception of a microscopist. Thus diagnostics currently almost exclusively dependent on recognition of morphological features of pathogenic organisms could be based on additional properties, such as motility characteristics recognizable by computer vision. Of special interest are infectious larval stages and “micro swimmers” of e.g., the schistosome life cycle, which infect the intermediate and definitive hosts, respectively. The ciliated miracidium, emerges from the excreted egg upon its contact with water. This means that for diagnostics, recognition of a swimming miracidium is equivalent to recognition of an egg. The motility pattern of miracidia could be defined by computer vision and used as a diagnostic criterion. To develop motility pattern-based diagnostics of schistosomiasis using simple imaging devices, we analyzed Paramecium as a model for the schistosome miracidium. As a model for invasive nematodes, such as strongyloids and filaria, we examined a different type of motility in the apathogenic nematode Turbatrix, the “vinegar eel.” The results of motion time and frequency analysis suggest that target motility may be expressed as specific spectrograms serving as “diagnostic fingerprints.”

Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases.

It is long known that some parasite infections are able to modulate specific pathways of host's metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases.

Infection with schistosome parasites in snails leads to increased predation by prawns: implications for human schistosomiasis control

Schistosomiasis - a parasitic disease that affects over 200 million people across the globe - is primarily transmitted between human definitive hosts and snail intermediate hosts. To reduce schistosomiasis transmission, some have advocated disrupting the schistosome life cycle through biological control of snails, achieved by boosting the abundance of snails' natural predators. But little is known about the effect of parasitic infection on predator-prey interactions, especially in the case of schistosomiasis. Here, we present the results of laboratory experiments performed on Bulinus truncatus and Biomphalaria glabrata snails to investigate: (i) rates of predation on schistosome-infected versus uninfected snails by a sympatric native river prawn, Macrobrachium vollenhovenii, and (ii) differences in snail behavior (including movement, refuge-seeking and anti-predator behavior) between infected and uninfected snails. In predation trials, prawns showed a preference for consuming snails infected with schistosome larvae. In behavioral trials, infected snails moved less quickly and less often than uninfected snails, and were less likely to avoid predation by exiting the water or hiding under substrate. Although the mechanism by which the parasite alters snail behavior remains unknown, these results provide insight into the effects of parasitic infection on predator-prey dynamics and suggest that boosting natural rates of predation on snails may be a useful strategy for reducing transmission in schistosomiasis hotspots.

Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs*[S

Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1–4(Fucα1–3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1–4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1–3(Galβ1–6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated stretches enriched in mature eggs and miracidia. This global analysis of the developing schistosome's glycome provides new insights into how stage-specifically expressed glycans may contribute to different aspects of schistosome-host interactions.

The temporal patterns of disease severity and prevalence in schistosomiasis.

Schistosomiasis is one of the most widespread public health problems in the world. In this work, we introduce an eco-epidemiological model for its transmission and dynamics with the purpose of explaining both intra- and inter-annual fluctuations of disease severity and prevalence. The model takes the form of a system of nonlinear differential equations that incorporate biological complexity associated with schistosome's life cycle, including a prepatent period in snails (i.e., the time between initial infection and onset of infectiousness). Nonlinear analysis is used to explore the parametric conditions that produce different temporal patterns (stationary, endemic, periodic, and chaotic). For the time-invariant model, we identify a transcritical and a Hopf bifurcation in the space of the human and snail infection parameters. The first corresponds to the occurrence of an endemic equilibrium, while the latter marks the transition to interannual periodic oscillations. We then investigate a more realistic time-varying model in which fertility of the intermediate host population is assumed to seasonally vary. We show that seasonality can give rise to a cascade of period-doubling bifurcations leading to chaos for larger, though realistic, values of the amplitude of the seasonal variation of fertility.

Novel Upconversion Fluorescent Probe for Schistosoma japonicum Cercariae Imaging

Schistosomiasis has influence on people’s security and daily life significantly, while cercarial stage of the schistosome life-cycle is the only infectious period. To detect cercarial efficiently, we synthesized rare-earth upconversion nanophosphors UCs-Ni loaded with niclosamide. The fluorescenceof UCs-Ni was demonstrated by the fluorescence emission spectra. The cell imaging test illustrated that UCs-Ni was biocompatible, cell-permeable and suitable for cercariae imaging. When it has been utilized for cercariae imaging, we found that the UCs-Ni could penetrate into cercariae.