Potential i-Nos/Arg-1 Switch with NLRP3 and Parasitic Load Down Regulation in Experimental Schistosoma mansoni Infection via Chloroquine Repurposing.

In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double-bladed sword in schistosomiasis (anti-inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i-Nos/Arg-1 expression, splenomegaly, hepatic insult and NLRP3-immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel-induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i-Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i-Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage-1 polarisation. On the flip side, the chloroquine-induced low Arg-1 seemed to abate immune tolerance and probably macrophage-2 polarisation. Collectively, chloroquine synergised the praziquantel-schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.

Biological, biochemical and genotoxicological alterations of Benzylamine on Biomphalaria alexandrina snails and its Schistosoma mansoni larvicidal potential.

Biomphalaria spp. snails are freshwater gastropods that responsible for Schistosoma mansoni transmission. Schistosomiasis is a chronic illness that occurred in underdeveloped regions with poor sanitation. The aim of the present study is to evaluate the molluscicidal activity of benzylamine against B. alexandrina snails and it larvicidal effects on the free larval stages of S. mansoni. Results showed that benzylamine has molluscicidal activity against adult B. alexandrina snails after 24 h of exposure with median lethal concentration (LC50) 85.7 mg/L. The present results indicated the exposure of B. alexandrina snails to LC10 or LC25 of benzylamine resulted in significant decreases in the survival, fecundity (eggs/snail/week) and reproductive rates, acetylcholinesterase, albumin, protein, uric acid and creatinine concentrations, levels of Testosterone (T) and 17ß Estradiol (E), while alkaline phosphatase levels were significantly increased in comparison with control ones. The present results showed that the sub lethal concentration LC50 (85.7 mg/L) of benzylamine has miracidial and cercaricidal activities, where the Lethal Time (LT50) for miracidiae was 17.08 min while for cercariae was 30.6 min. Also, results showed that were decreased significantly after exposure to sub lethal concentrations compared with control. The present results showed that the expression level of NADH dehydrogenase subunit 1 (ND1) genes and cytochrome oxidase subunit I (COI) in B. alexandrina snails exposed to LC10 or LC25 concentrations benzylamine were significantly decreased compared to the control groups. Therefore, benzylamine could be used as effective molluscicide to control schistosomiasis.

In Situ Preparation of Dehydrodieugenol-Loaded Silver Nanoparticles and their Antischistosomal Activity.

Schistosomiasis is a major neglected disease that imposes a substantial worldwide health burden, affecting approximately 250 million people globally. As praziquantel is the only available drug to treat schistosomiasis, there is a critical need to identify new anthelmintic compounds, particularly from natural sources. To enhance the activity of different natural products, one potential avenue involves its combination with silver nanoparticles (AgNP). Based on this approach, a one-step green method for the in situ preparation of dehydrodieugenol (DHDG) by oxidation coupling reaction using silver and natural eugenol is presented. AgNP formation was confirmed by UV-Vis spectroscopy due to the appearance of the surface plasmon resonance (SPR) band at 430 nm which is characteristic of silver nanoparticles. The nanoparticles were spherical with sizes in the range of 40 to 50 nm. Bioassays demonstrated that the silver nanoparticles loaded with DHDG exhibited significant anthelmintic activity against Schistosoma mansoni adult worms without toxicity to mammalian cells and an in vivo animal model (Caenorhabditis elegans), contributing to the development of new prototypes based on natural products for the treatment of schistosomiasis.

Preparation of polyclonal anti-Schistosoma mansoni cysteine protease antibodies for early diagnosis.

In many parts of the tropics, schistosomiasis is a major parasitic disease second only to malaria as a cause of morbidity and mortality. Diagnostic approaches include microscopic sampling of excreta such as the Kato-Katz method, radiography, and serology. Due to their vital role in many stages of the parasitic life cycle, proteases have been under investigation as targets of immunological or chemotherapeutic anti-Schistosoma agents. Five major classes of protease have been identified on the basis of the peptide hydrolysis mechanism: serine, cysteine, aspartic, threonine, and metalloproteases. Proteases of all five catalytic classes have been identified from S. mansoni through proteomic or genetic analysis. The study aimed to produce polyclonal antibodies (pAbs) against schistosomal cysteine proteases (CP) to be used in the diagnosis of schistosomiasis. This study was conducted on S. mansoni-infected patients from highly endemic areas and from outpatients' clinic and hospitals and other patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids). In this study, the produced polyclonal antibodies against S. mansoni cysteine protease antigens were labeled with horseradish peroxidase (HRP) conjugate and used to detect CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA. The study involved 200 S. mansoni-infected patients (diagnosed by finding characteristic eggs in the collected stool samples), 100 patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids), and 100 individuals who served as parasite-free healthy negative control. The prepared pAb succeeded in detecting CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA with a sensitivity of 98.5% and 98.0% respectively. A positive correlation was observed between S. mansoni egg counts and both stool and serum antigen concentrations. Purified 27.5 kDa CP could be introduced as a suitable candidate antigen for early immunodiagnosis using sandwich ELISA for antigen detection. KEY POINTS: • Detection of cysteine protease antigens can replace parasitological examination. • Sandwich ELISA has a higher sensitivity than microscopic examination of eggs. • Identification of antigens is important for the goal of obtaining diagnostic tools.

In vitro and In silico assessment of antischistosomal activities of ethanolic extract of Cornulacamonacantha.

Schistosomiasis is the second most prevailing parasitic disease worldwide. Although praziquantel is considered an effective drug in the treatment against schistosomiasis to some extent, there is an emerging drug resistance that widely recorded. Therefore, there is an urgent need to develop effective and safe anti-schistosomal drugs. In this study, Cornulaca monacantha (C. monacantha), a sub-saharan plant, was extracted using aqueous ethanol and characterized by High-Performance Liquid Chromatography (HPLC). Major constituents of the extract are belonging to flavonoids, tannins and phenolic glycosides. Worms' viability and surface morphology of Schistosoma mansoni (S. mansoni) adult worms treated with the extract were assessed using in vitro viability assay, Scanning Electron Microscopy (SEM), and histological examination. The extract (80-350 µg/ml) reduced viability percentage of worms by 40-60% and caused degeneration of both oral and ventral suckers, tegumental, sub-tegumental and muscular damage. Molecular docking approach was utilized to assess the binding affinities of the extracted compounds with S. mansoni alpha-carbonic anhydrase (SmCA), an essential tegument protein. Pharmacokinetic analysis using SwissADME showed that 7 compounds have high drug similarity. This study confirms the in vitro schistomicidal activity of C. monacantha extract against S. mansoni adult worms and suggests potential SmCA inhibition.

Design, Synthesis and Evaluation of Praziquantel Analogues and New Molecular Hybrids as Potential Antimalarial and Anti-Schistosomal Agents.

Malaria and schistosomiasis are two of the neglected tropical diseases that persistently wreak havoc worldwide. Although many antimalarial drugs such as chloroquine are readily available, the emergence of drug resistance necessitates the development of new therapies to combat this disease. Conversely, Praziquantel (PZQ) remains the sole effective drug against schistosomiasis, but its extensive use raises concerns about the potential for drug resistance to develop. In this project, the concept of molecular hybridization was used as a strategy to design the synthesis of new molecular hybrids with potential antimalarial and antischistosomal activity. A total of seventeen molecular hybrids and two PZQ analogues were prepared by coupling 6-alkylpraziquanamines with cinnamic acids and cyclohexane carboxylic acid, respectively. The synthesised compounds were evaluated for their antimalarial and antischistosomal activity; while all of the above compounds were inactive against Plasmodium falciparum (IC50 > 6 µM), many were active against schistosomiasis with four particular compounds exhibiting up to 100% activity against newly transformed schistosomula and adult worms at 50 µM. Compared to PZQ, the reference drug, the activity of which is 91.7% at 1 µM, one particular molecular hybrid, compound 32, which bears a para-isopropyl group on the cinnamic acid moiety, exhibited a notable activity at 10 µM (78.2% activity). This compound has emerged as the front runner candidate that might, after further optimization, hold promise as a potential lead compound in the fight against schistosomiasis.

Schistosoma mansoni miracidia: revisiting motility and survival parameters for improved computational modelling.

Schistosoma mansoni is the main causative agent of intestinal schistosomiasis which affects millions of people worldwide. At the larval stage, miracidia are released into bodies of water where they utilize their motility to successfully infect their intermediate host, snails. Here, we revisit the motility and survival of S. mansoni miracidia throughout its life span. Briefly, miracidia motility was monitored at 30-min and 60-min intervals under the presence/absence of natural/artificial light. Based on a subjective evaluation of activity, body shape and transparency, 6 categories of miracidia activity were established from its fully active stage to its immobile larva stage. The estimated life span of miracidia was 5.8 and 3.5 h in the experiments with 60-min and 30-min observation intervals, respectively. Death was defined by an absence of cilia and body movement. When mobility was used as a proxy for infectivity, infective miracidia were detected at 2.5 and 4.5 h, respectively. The present miracidia motility and survival re-evaluation supports parameters optimization for computational modelling of schistosomiasis transmission dynamics. Target control interventions, especially at late stages next to transmission interruption, may greatly benefit from improved modelling studies.

Excretion patterns of Schistosoma mansoni antigens CCA and CAA by adult male and female worms, using a mouse model and ex vivo parasite cultures.

Assays which enable the detection of schistosome gut-associated circulating anodic (CAA) and cathodic (CCA) antigen in serum or urine are increasingly used as a diagnostic tool for schistosome infection. However, little is known about the production and clearance of these circulating antigens in relation to the sex and reproductive maturity of the parasite. Here we describe CAA and CCA excretion patterns by exploring a mouse model after exposure to 36 male-only, female-only and mixed (male/female) Schistosoma mansoni cercariae. We found that serum and urine CAA levels, analysed at 3 weeks intervals, peaked at 6 weeks post-infection. Worms recovered after perfusion at 14 weeks were cultured ex vivo. Male parasites excreted more circulating antigens than females, in the mouse model as well as ex vivo. In mixed infections (supporting egg production), serum CAA levels correlated to the number of recovered worms, whereas faecal egg counts or Schistosoma DNA in stool did not. No viable eggs and no inflammation were seen in the livers from mice infected with female worms only. Ex vivo, CAA levels were higher than CCA levels. Our study confirms that CAA levels reflect worm burden and allows detection of low-level single-sex infections.

In vitro and in vivo impacts of nifedipine and diltiazem on praziquantel chemotherapy in murine Schistosoma mansoni.

AIM: This study was planned to evaluate the in vitro and in vivo antischistosomal effects of the widely used antihypertensive drugs, nifedipine (NIF) and diltiazem (DTZ), and their combinations with praziquantel (PZQ) on early and late Schistosoma (S.) mansoni infections 21- and 45- days old stages. METHODS: In the In vitro study, Calcium channel blockers (CCBs), NIF and DTZ were added to schistosomula and adult worm cultures in different concentrations 10, 20 and 30 mg/ml. The mortality percentage was calculated 1, 12 and 24 h after incubation. In vivo, NIF and DTZ either alone or combined with PZQ were used to treat male albino mice. The parasitological and total immunoglobulin (Ig) G and IgM anti-soluble egg antigen (SEA) were assessed to demonstrate the disease severity. RESULTS: In the In vitro study, 10 mg/ml NIF induced 100% mortality percentage of both schistosomula and adult worms after 24 h incubation, while DTZ induced similar mortality percentage at 30 mg/ml concentration. In vivo results showed that early or late combination of 30 mg/kg of NIF, but not DTZ, significantly (P <0.05) enhanced the reductive efficacy of PZQ based on the parasitological data. The maximal reduction (P <0.05) of anti-SEA IgM and IgG levels was developed during NIF-PZQ administration 21- (1.12 ± 0.06 and 1.09 ± 0.04, respectively) or 45- (1.00 ± 0.03 and 0.8 ± 0.06, respectively) days post infection (PI), compared to either PZQ or NIF individual treatments. The decreased concentration of anti-SEA antibodies was correlated with the diminished granulomatous diameter and disease severity. CONCLUSION: Nifedipine improved PZQ chemotherapy targeting either early or late S. mansoni infection in mice compared to the PZQ mono-therapy. Administering NIF can be considered as a promising drug candidate for schistosomiasis chemotherapy.

Measuring the Manipulation of T Helper Immune Responses by Schistosoma mansoni.

Schistosoma mansoni uses different mechanisms to escape its host's immunity. Understanding the ability of memory T cells to withstand this pathogen's manipulation is important for the development of effective vaccines against this immunomodulatory pathogen. In this study, ovalbumin (OVA) transgenic S. mansoni is used as a tool to investigate whether fully differentiated Th1, Th2 and Th17 cells are able to withstand pathogen manipulation. Naïve T cells from OT-II T cell receptor transgenic mice with a specificity for OVA were differentiated into Th1, Th2, and Th17 polarised memory cells in vitro. These cells were adoptively transferred into recipient mice to investigate whether these polarised immune memory T cells are resilient in the face of pathogen-mediated manipulation. After transferring memory cells, mice were challenged with OVA-transduced S. mansoni eggs as well as wild-type controls. The in vitro differentiated Th1, Th2 and Th17 memory cells continued to produce the same cytokines when challenged by OVA-expressing S. mansoni eggs as to these they produced when transferred in vivo, suggesting that the Th phenotypes of the memory T cells remains unaltered in the face of stimulation by S. mansoni. The ability of memory T cells to remain resilient to manipulation by the parasite suggests that vaccines might be able to produce immune memory responses able to withstand S. mansoni immune manipulation and hence protect the host from infection.

In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models.

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs' suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.

Association of TNF (rs1800629) promoter polymorphism and schistosomiasis with sub-microscopic asymptomatic Plasmodium falciparum infections in a schistosomiasis-endemic area in Zimbabwe.

OBJECTIVES: Infection with Plasmodium falciparum parasites may result in a wide spectrum of symptoms ranging from asymptomatic to mild or severe. A number of factors are associated with this heterogeneous response to P. falciparum infection. In the present study, associations of sub-microscopic asymptomatic P. falciparum with Schistosoma species and TNF (rs1800629) polymorphism were investigated. METHODS: 361 clinically healthy primary school children were microscopically screened for S. haematobium, S. mansoni and P. falciparum. Sub-microscopic asymptomatic P. falciparum infections were determined by PCR. Genotypic profiles were identified using ARMS-PCR. Logistic regression was used to assess the association of sub-microscopic asymptomatic P. falciparum with Schistosoma species and TNF (rs1800629) polymorphism. RESULTS: 17.2% of the children were infected with S. mansoni, and 27.4% were infected with S. haematobium. Microscopic examination of thick smears detected only one child infected with P. falciparum. Based on PCR results, 46.1% were infected with sub-microscopic asymptomatic P. falciparum. Children carrying heterozygous AG (OR: 16.964, 95% CI: 0.496-586.547) and homozygous GG (OR: 2.280, 95% CI: 0.111-46.796) genotypes of rs1800629 were associated with an increased likelihood of sub-microscopic asymptomatic P. falciparum infections compared with those carrying homozygous AA genotype. Children without S. haematobium infections (OR: 1.051, 95% CI: 0.146-8.985) and S. mansoni (OR: 2.658, 95% CI: 0.498-14.184) also had an increased likelihood (risk) of being infected with sub-microscopic asymptomatic P. falciparum compared with the Schistosoma-infected groups. However, all the associations observed were not statistical significant. CONCLUSION: No associations were observed between rs1800629 and schistosomiasis with sub-microscopic asymptomatic P. falciparum infections. This study also reports a high prevalence of sub-microscopic asymptomatic P. falciparum infection concomitant with low malaria transmission.

OBJECTIFS: L'infection par les parasites P. falciparum peut entraîner un large éventail de présentations allant d'asymptomatiques à bénignes ou sévères. Un certain nombre de facteurs sont associés à cette réaction hétérogène à l'infection à P. falciparum. Dans la présente étude, les associations entre la présentation asymptomatique sous-microscopique de P. falciparum avec les espèces de Schistosoma et le polymorphisme du TNF (rs1800629) ont été investiguées. MÉTHODES: 364 écoliers du primaire en bonne santé clinique ont subi microscopique pour S. haematobium, S. mansoni et P. falciparum. Les infections asymptomatiques sous-microscopiques à P. falciparum ont été déterminées par PCR. Les profils génotypiques ont été identifiés en utilisant ARMS-PCR. La régression logistique a été utilisée pour évaluer l'association entre la présentation asymptomatique sous-microscopique de P. falciparum avec les espèces de Schistosoma et le polymorphisme du TNF (rs1800629). RÉSULTATS: Parmi les enfants, 17,2% étaient infectés par S. mansoni et 27,4% étaient infectés par S. haematobium. L'examen microscopique de frottis épais n'a détecté qu'un seul enfant infecté par P. falciparum. D'après les résultats de la PCR, 46,1% étaient infectés par P. falciparum asymptomatique sous-microscopique. Les enfants porteurs des génotypes hétérozygotes AG (OR: 16,964 ; IC95%: 0,496-586,547) et homozygotes GG (OR: 2,280 ; IC95%: 0,111-46,796) de rs1800629 étaient associés à une probabilité accrue d'infections asymptomatiques sous-microscopiques à P. falciparum par rapport à ceux porteurs du génotype homozygote AA. Les enfants sans infection à S. haematobium (OR: 1,051 ; IC95%: 0,146-8,985) et S. mansoni (OR: 2,658 ; IC95%: 0,498 à 14,184) présentaient également une probabilité (risque) accrue d'être infectés par P. falciparum asymptomatique sous-microscopique par rapport à ceux infectés par Schistosoma. Cependant, toutes les associations observées n'étaient pas statistiquement significatives. CONCLUSION: Aucune association n'a été observée entre le rs1800629 et la schistosomiase avec des infections asymptomatiques sous-microscopiques à P. falciparum. Cette étude rapporte une prévalence élevée d' infection asymptomatique sous-microscopique à P. falciparum concomitante à une faible transmission du paludisme.

Comparison among FLOTAC, Kato-Katz and formalin ether concentration techniques for diagnosis of intestinal parasitic infections in school children in an Egyptian rural setting.

The study aimed to compare the diagnostic performance of the Kato-Katz, formalin ether concentration method (FECM) and FLOTAC using Sheather's sugar solution (FS1), saturated sodium chloride (FS2) and zinc sulfate (FS7) for the diagnosis of intestinal parasites among school children, focusing on Schistosoma mansoni. Ninety fecal samples were examined using the above mentioned techniques. The overall infection rate was 87.7%. Concerning protozoa, FLOTAC (FS1 and FS2) and FECM detected nearly equal infection rates (43.3% and 44.4%, respectively) with very good agreement. Kato-Katz diagnosed the highest helminthic infection rate (57.8%) followed by FLOTAC FS7 (44.4%) and FECM showed the lowest helminthic infection rate (27.7%). As for S. mansoni, Kato-Katz showed an infection rate of 38.8% vs FLOTAC (22.2%) and FECM (11.1%). The three techniques detected the same infection rate (11.1%) with egg counts more than 72 eggs/gram of feces. The FLOTAC sensitivity and accuracy for the diagnosis of protozoa were 97% and 99%, respectively. Regarding helminths diagnosis, FLOTAC technique showed higher sensitivity (77%) and accuracy (87%) compared to FECM (48% sensitivity and 70% accuracy). Therefore, FLOTAC can be used synchronously or in replacement to other diagnostic techniques. This can strategically impact future control programmes of intestinal parasitic infections in limited resources settings.

Prophylactic versus therapeutic role of the transplanted CD34+ Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.

Schistosoma mansoni infection and risk factors among the fishermen of Lake Hawassa, southern Ethiopia.

Schistosomiasis is a neglected tropical parasitic disease caused by different species of genus Schistosoma. Schistosoma mansoni causes a severe intestinal parasitic infection of high public and medical importance in Ethiopia. This study aimed to determine the prevalence of, and risk factors for, S. mansoni infection among the fishermen of Lake Hawassa, southern Ethiopia, using a cross-sectional study design. A total of 243 fishermen were selected from the Hawassa Town Fishermen Association's list in 2013. Data on socio-demographic characteristics and risk factors were collected from the fishermen using semi-structured questionnaires. Stool samples were collected and processed using the Kato-Katz thick smear technique. The overall prevalence of S. mansoni among the fishermen was 29.21% and the mean intensity of infection was 158.88 eggs per gram (EPG). The overall prevalence of intestinal helminths, including S. mansoni, was 69.54%. Similar prevalences of S. mansoni were recorded in age groups 15-19, 20-24 and 25-29 years: 31.82%, 31.75% and 31.94%, respectively. Fishermen who swam a minimum of once a week in Lake Hawassa were 2.92 times (95% CI: 1.554, 5.502) more likely to have acquired S. mansoni infection than those who swam in the lake less than once a week. The results indicate moderate endemicity of S. mansoni infection among the fishermen of Lake Hawassa. These fishermen could be a potentially high-risk group for S. mansoni infection and might be responsible for the transmission of infection to other segments of the community visiting the lake for recreation. Moreover, a high prevalence of soil-transmitted helminths (STHs) was recorded among the fishermen. Integrated prevention and control strategies for schistosomiasis and STHs by different sectors are needed to tackle this problem.

Knowledge, attitudes and practices on Schistosomiasis in sub-Saharan Africa: a systematic review.

BACKGROUND: Schistosomiasis remains a global health problem with an estimated 250 million people in 78 countries infected, of whom 85% live in Sub-Saharan Africa. Preventive chemotherapy remains the key public health strategy to combat schistosomiasis worldwide. Recently the WHO emphasized on the use of integrative approaches in the control and elimination of schistosomiasis. However, a detailed understanding of sociocultural factors that may influence the uptake of the intended health activities and services is vital. Thus, our study sought to understand the knowledge, attitudes, perceptions, beliefs and practices about schistosomiasis in various communities in Sub-Saharan Africa. METHODS: A systematic search of literature for the period 2006-2016 was done on Medline, PubMed, CINAHL, Psych info and Google Scholar using the following key words "Schistosomiasis, S. mansoni, S. haematobium, knowledge, attitudes, perceptions, beliefs and practices in Sub-Saharan Africa" in combination with Bolean operators (OR, AND). In this context, we reviewed studies conducted among school children, community members and caregivers of preschool children. Thematic analysis was utilised for the overall synthesis of the selected studies. This was done after reading the articles in depth. Themes were identified and examined for similarities, differences and contradictions. RESULTS: Gaps in schistosomiasis related knowledge and sociocultural barriers towards the uptake of preventive and treatment services among communities in Sub-Saharan Africa were identified. In addition to limited knowledge and negative attitudes, risky water related practices among community members, school children and caregivers of preschool children were identified as key factors promoting transmission of the disease. CONCLUSION: The study concluded that a comprehensive health education programme using contextual and standardised training tools may improve peoples' knowledge, attitudes and practices in relation to schistosomiasis prevention and control. Findings also highlight the significance of including caregivers in the planning and implementation schistosomiasis control programs targeting pre-school children.

Schistosomal-derived lysophosphatidylcholine triggers M2 polarization of macrophages through PPARγ dependent mechanisms.

Mansonic schistosomiasis is a disease caused by the trematode Schistosoma mansoni, endemic to tropical countries. S. mansoni infection induces the formation of granulomas and potent polarization of Th2-type immune response. There is great interest in understanding the mechanisms used by this parasite that causes a modulation of the immune system. Recent studies from our group demonstrated that lipids of S. mansoni, including lysophosphatidylcholine (LPC) have immunomodulatory activity. In the present study, our aim was to investigate the role of lipids derived from S. mansoni in the activation and polarization of macrophages and to characterize the mechanisms involved in this process. Peritoneal macrophages obtained from wild type C57BL/6mice or bone marrow derived macrophages were stimulated in vitro with lipids extracted from adult worms of S. mansoni. We demonstrated that total schistosomal-derived lipids as well as purified LPC induced alternatively activated macrophages/M2 profile observed by increased expression of arginase-1, mannose receptor, Chi3l3, TGFß and production of IL-10 and PGE2 24h after stimulation. The involvement of the nuclear receptor PPARγ in macrophage response against LPC was investigated. Through Western blot and immunofluorescence confocal microscopy we demonstrated that schistosomal-derived LPC induces increased expression of PPARγ in macrophages. The LPC-induced increased expression of arginase-1 were significantly inhibited by the PPAR-γ antagonist GW9662. Together, these results demonstrate an immunomodulatory role of schistosomal-derived LPC in activating macrophages to a profile of the type M2 through PPARγ-dependent mechanisms, indicating a novel pathway for macrophage polarization triggered by parasite-derived LPC with potential implications to disease pathogenesis.

Co-infection of Schistosoma mansoni/hepatitis C virus and their associated factors among adult individuals living in fishing villages, north-western Tanzania.

BACKGROUND: Schistosoma mansoni and Hepatitis C virus (HCV) are co-existence in sub-Saharan Africa and co-infection is common among humans population. The immunological responses characterized with Th2-immune responses for S. mansoni and Th1-immune responses for HCV are responsible for development hepatic morbidities in infected individuals. However, the co-occurrences of S. mansoni and HCV infection, their related ultrasound detectable morbidities and associated risk factors at community levels have not been examined in fishing communities, north-western Tanzania. In this context, the present study covers that gap. METHODS: A cross-sectional study was conducted among 1924 asymptomatic individuals aged 15-55 years in four fishing villages (Igombe, Igalagala, Sangabuye and Kayenze) of Northwestern Tanzania. A single stool sample was collected from each study participants and examined for S. mansoni eggs using Kato Katz technique. Hepatitis C surface antigen (HCVsAg) was determined from a finger prick blood sample using a rapid test. RESULTS: Overall, 51.8% (997/1924; 95%CI: 49.6-54.1) of the study participants were infected with S. mansoni and had a mean intensity of 223.7epg (95%; 202.4-247.1). Of the study participants, 90 (4.7%) were infected with hepatitis C virus (HCV). Overall, 2. 4% (47/1924) of the study participants were co-infected with S. mansoni and hepatitis C virus. Among the co-infected individuals, 42.6%, 70.2% and 19.1% had splenomegaly, hepatomegaly and periportal fibrosis (PPF). Factors associated with S. mansoni/HCV co-infection were being aged 26-35 years (aRR = 2.67, 95%CI: 1.03-6.93, P < 0.04), 46-55 years (aRR = 2.89, 95%CI: 1.10-7.57, P < 0.03) and having marked hepatomegaly (aRR = 2.32, 95%CI: 1.09-4.9, P < 0.03). CONCLUSION: In this setting, S. mansoni and Hepatitis C are co-endemic and a proportion of individuals were co-infected. Hepatosplenic morbidities characterized with hepatomegaly, splenomegaly, hepatosplenomegaly and PPF were observed in co-infected individuals. These results highlight the need for integrated interventions measures against parasitic and viral diseases.

Molecular characterization of transport lectin vesicular integral membrane protein 36 kDa (VIP36) in the life cycle of Schistosoma mansoni.

VIP36 is a protein described as an L-type lectin in animals, responsible for the intracellular transport of glycoproteins within the secretory pathway, and also localized on the plasma membrane. Schistosoma mansoni has a complex system of vesicles and protein transport machinery to the cell surface. The excreted/secreted products of the larvae and eggs are known to be exposed to the host immune system. Hence, characterizing the role and action of SmVIP36 in the S. mansoni life cycle is important for a better understanding of the parasite-host relationship. To this purpose, we firstly performed in silico analysis. Analysis of SmVIP36 in silico revealed that it contains a lectin leg-like domain with a jellyroll fold as seen by its putative 3D tertiary structure. Additionally, it was also observed that its CRD contains calcium ion-binding amino acids, suggesting that the binding of SmVIP36 to glycoproteins is calcium-dependent. Finally, we observed that the SmVIP36 predicted amino acid sequence relative to its orthologs was conserved. However, phylogenetic analysis revealed that SmVIP36 follows species evolution, forming a further cluster with its definitive host Homo sapiens. Moreover, q-PCR analysis in the S. mansoni life cycle points to a significant increase in gene expression in the eggs, schistosomulae, and female adult stages. Similarly, protein expression increased in eggs, cercariae, schistosomulae, and adult worm stages. These results suggest that SmVIP36 might participate in the complex secretory activity within the egg envelope and tegument proteins, both important for the stages of the parasite that interact with the host.

Schistosoma mansoni α1,3-fucosyltransferase-F generates the Lewis X antigen.

Genetic evidence suggests that the Schistosoma mansoni genome contains six genes that encode α1,3-fucosyltransferases (smFuTs). To date, the activities and specificities of these putative fucosyltransferases are unknown. As Schistosoma express a variety of fucosylated glycans, including the Lewis X antigen Galß1-4(Fucα1-3)GlcNAcß-R, it is likely that this family of genes encode enzymes that are partly responsible for the generation of those structures. Here, we report the molecular cloning of fucosyltransferase-F (smFuT-F) from S. mansoni, as a soluble, green fluorescent protein fusion protein and its acceptor specificity. The gene smFuT-F was expressed in HEK freestyle cells, purified by affinity chromatography, and analyzed toward a broad panel of glycan acceptors. The enzyme product of smFuT-F effectively utilizes a type II chain acceptor Galß1-4GlcNAc-R, but notably not the LDN sequence GalNAcß1-4GlcNAc-R, to generate Lewis X type-glycans, and smFuT-F transcripts are present in all intramammalian life stages.