Schistosoma Mansoni Adult Worms Research Articles

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 μM) and S. mansoni (IC50=64.25 μM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

In vitro Assessment of Antischistosomal Effect of the Marine Hyrtios sp. Sponge Extract against Schistosoma mansoni Adult Worms

In vitro Assessment of Antischistosomal Effect of the Marine Hyrtios sp. Sponge Extract against Schistosoma mansoni Adult Worms

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.

Enhancing the antischistosomal activity of carvacryl acetate using nanoemulsion.

Aim: To formulate a carvacryl acetate nanoemulsion (CANE) and test its antischistosomal activity. Materials & methods: CANE was prepared and tested in vitro on Schistosoma mansoni adult worms and both human and animal cell lines. Next, CANE was administered orally to mice infected with either a prepatent infection or a patent infection of S. mansoni. Results: CANE was stable during 90 days of analysis. CANE showed in vitro anthelmintic activity, and no cytotoxic effects were observed. In vivo, CANE was more effective than the free compounds in reducing worm burden and egg production. Treatment with CANE was more effective for prepatent infections than praziquantel. Conclusion: CANE improves antiparasitic properties and may be a promising delivery system for schistosomiasis treatment.

Synthesis, in vitro schistosomicidal activity and ultrastructural alterations caused by thiosemicarbazones and thiazolidinones against juvenile and adult Schistosoma mansoni worms (Sambon, 1907)

Schistosomiasis is a neglected disease that affects about 258 million people worldwide. Caused by Schistosoma mansoni, helminth which, in Brazil, it is present on 19 states and capital. Praziquantel (PZQ) treatment presents low efficacy and adverse effects in parasites juvenile stages. Thiosemicarbazones and thiazolidinones are rising as potent chemical groups that have biological activity wide spectrum, and with radical modifications, they may become more effective and selective. Aiming to evaluate the action of these molecules against S. mansoni, JF series thiosemicarbazones and thiazolidinones (LqIT/UFPE) were synthesized: JF30, JF31, JF33, JF34, JF35, JF36, JF38, JF39, JF42 and JF43. Several parameters were evaluated, such as: their cytotoxicity in VERO cells, in vitro schistosomicidal activity for juvenile and adult worms and their action on worms through ultrastructural changes. Cytotoxicity indices ranged from 272 µM to 725 µM. When evaluating mortality rate, adult and juvenile worms showed 100 % mortality rate within 24 h and 48 h, respectively, when exposed to the compounds JF31 and JF43 at a dose of 200 µM. Also, motility, mortality and oviposition parameters were evaluated: JF31 and JF43 presented a score of 0 in 24 h, meaning total absence of movement, whereas no eggs and soft tissue damage were observed under optical microscopy. Through scanning electron microscopy, integumentary alterations caused by the compounds JF31 and JF43 were observed, such as: exposure of the musculature, formation of integumentary bubbles, integuments with abnormal morphology and destruction of tubercles and spikes. The results shoerd that the compound JF31 was 2.39 times more selective for adult worms and JF43 was 3.74 times more selective for juvenile worms. Thus, the compounds JF43 and JF31 are the most promising for presenting schistosomicidal activity of S. mansoni.

Lippia alba and Lippia gracilis essential oils affect the viability and oviposition of Schistosoma mansoni

Schistosomiasis is a neglected tropical disease that affects millions of people around the world. Currently, the only drug available for the treatment of this disease is praziquantel, which has low efficacy against immature helminth stages and there are reports of drug resistance. In this study, the chemical composition and the in vitro effect of essential oils (EOs) and major compounds from Lippia gracilis and Lippia alba against schistosomula and adult Schistosoma mansoni worms were evaluated. Adult S. mansoni worms cultured for 8h in the presence of L. gracilis EO (50 and 100 µg/mL) or for 2h with its major compound, carvacrol (100 µg/mL), had a 100% reduction in viability. After interaction with L. alba EO (100µg/mL), there was a reduction of approximately 60% in the viability of adult worms after 24 hours of exposure; citral (50 and 100 µg/mL), its major compound, reduced the viability after 24 hours by more than 75%. Treatment of schistosomula with 100 µg/mL of L. gracilis or L. alba EOs for 6h led to a reduction in parasite viability of 80% and 16% respectively. Both EOs and their major compounds significantly reduced the oviposition of adult worms exposed to a non-lethal concentration (5 µg/mL). In addition, morphological changes such as the destruction of the tegument and disorganization of the reproductive system of male and female worms were visualized. Both EOs showed low cytotoxicity at a concentration of 50 µg/mL. The results encourage further investigation of these plants as a potential source of bioactive compounds against S. mansoni.

Evaluation of Antischistosomal Activities of Crude Aqueous Extracts of Artemisia annua, Nigella sativa, and Allium sativum against Schistosoma mansoni in Hamsters.

Schistosomiasis is a neglected disease, as the World Health Organization classified it in the second category after malaria. World Health Organization approved praziquantel (PZQ) as the only chemotherapy to treat schistosomiasis. Over the years, some problems have arisen with PZQ, as it showed poor efficacy in the early stages of infection as well as the emergence of some resistance to it. In searching for new alternative drugs to treat schistosomiasis, the researchers intensified their efforts to find a new drug. The present study focuses on evaluating the effect of three plant extracts Artemisia annua, Nigella sativa, and Allium sativum at different doses of 31.25, 62.5, 125, 250, and, 500 μg/ml; in vitro study was accomplished on the Schistosoma mansoni adult worms. The results declared that the concentration of 500, 250, and 125 of Artemisia annua was more effective on adult worms, and the same concentrations of Nigella sativa and Allium sativum gave less effect on the adult worms than the previous plant. In vivo study was accomplished on the hamster's tissue after exposing it to doses of the plants' extracts with different concentrations; it showed the presence of calcifications and damage to the worm eggs in the liver and spleen, as well as reducing the size of granulomas. After conducting many confirmatory studies Artemisia annua extract can be used as an effective and safe treatment for Schistosoma disease.

In Vitro Schistosomicidal Activities of the Leaf Extracts from Casearia sylvestris Varieties.

Schistosomiasis, a tropical disease caused by flatworms, may affect the liver, spleen, bladder, and intestine. Casearia sylvestris Swartz, a medicinal plant, displays antiprotozoal, antimicrobial, antifungal, and antiulcer activities. We have evaluated the in vitro schistosomicidal activity of two C. sylvestris varieties against Schistosoma mansoni adult worms at concentrations between 12.5 and 200 μg/mL. At 100 and 200 μg/mL, the ethanolic C. sylvestris var. sylvestris leaf extract enriched in casearin-like diterpenes eliminated 100 % of the parasites after incubation for 72 h and 48 h, respectively, whilst the same extract at 200 μg/mL eliminated 96 %, 100 %, and 100 % of the parasites after incubation for 24, 48, and 72 h, respectively. On the other hand, the hydroalcoholic C. sylvestris var. lingua leaf extract at 200 μg/mL eliminated 60.4 and 66.7 % of the parasites after incubation for 48 and 72 h, respectively. The presence of casearin-like diterpenes and glycosylated flavonoids was confirmed based on chromatographic techniques and mass spectrometry data.

Schistosoma mansoni Adult Worm Protective and Diagnostic Proteins in n-Butanol Extracts Revealed by Proteomic Analysis.

The S. mansoni adult worm n-butanol extract (Sm-AWBE) has been previously shown to contain specific S. mansoni antigens that have been used for immunodiagnosis of schistosomiasis in solid phase alkaline phosphatase immunoassay (APIA) and western blot (WB) analyses. Sm-AWBE was also used in immunoprotection studies against a fatal live-cercariae challenge in experimental mouse vaccination (~43% protection). The Sm-AWBE fraction was prepared by mixing adult worm membranous suspensions with aqueous-saturated n-butanol, centrifuging and recovering n-butanol-resistant proteins in the aqueous phase. Here we report a preliminary identification of Sm-AWBE protein components as revealed from a qualitative proteomic study after processing Sm-AWBE by 1D-gel electrophoresis, in-gel and in-solution tryptic digestions, and mass spectrometry analyses. We identified 33 proteins in Sm-AWBE, all previously known S. mansoni proteins and antigens; among them, immunomodulatory proteins and proteins mostly involved in host–parasite interactions. About 81.8% of the identified Sm-AWBE proteins are antigenic. STRING analysis showed a set of Sm-AWBE proteins configuring a small network of interactive proteins and a group of proteins without interactions. Functional groups of proteins included muscle contraction, antioxidant, GPI-anchored phosphoesterases, regulatory 14-3-3, various enzymes and stress proteins. The results widen the possibilities to design novel antigen combinations for better diagnostic and immunoprotective strategies for schistosomiasis control.

Licarin A, a neolignan isolated from Nectandra oppositifolia Nees & Mart. (Lauraceae), exhibited moderate preclinical efficacy against Schistosoma mansoni infection.

Schistosomiasis is a widespread human parasitic disease currently affecting over 200 million people, particularly in poor communities. Chemotherapy for schistosomiasis relies exclusively on praziquantel (PZQ). Previous studies have shown that licarin A (LIC-A), a dihydrobenzofuran neolignan, exhibited in vitro antiparasitic activity against Schistosoma mansoni adult worms. This study aimed to investigate the potential of LIC-A, isolated as main metabolite from leaves of Nectandra oppositifolia Nees & Mart. (Lauraceae), as an antischistosomal agent orally active in schistosomiasis animal model. PZQ was used as a reference compound. As result, LIC-A showed, at a single dose of 400 mg/kg, to be able to partially cure infected mice (worm burden reductions of ~50%). Parasite eggs, that are responsible for a variety of pathologies and transmission of schistosomiasis, were also moderately inhibited by LIC-A (egg burden reductions of ~50%-60%). Furthermore, it was observed that LIC-A achieved a slight reduction of hepatomegaly and splenomegaly. Collectively, although LIC-A was partially active when administered orally, these results give support for the antiparasitic potential LIC-A as lead compound for novel antischistosomal agent.

Effects of multiple doses of simvastatin and artesunate monotherapy on SCHISTOSOMA MANSONI adult worms during infection in hyperlidemic mice

A single dose of simvastatin and of artesunate monotherapy cause damage to the reproductive system of schistosomes as well as severe tegumental damage in male worms recovered from mice fed high-fat chow. This study aims to investigate whether treatment with multipledose regimes may offer more antischistosomal activity advantages than single daily dosing in mice fed high-fat chow. For this purpose, nine weeks post-infection, Swiss Webster mice were gavaged with simvastatin (200 mg/kg) or artesunate (300 mg/kg) for five consecutive days and euthanized two weeks post-treatment. Adult worms were analyzed using brightfieldmicroscopy, confocal microscopy and scanning electron microscopy, presenting damages caused by simvastatin and artesunate to the reproductive system of males and females as well as tegument alterations, including peeling, sloughing areas, loss of tubercles, tegumental bubbles and tegument rupture exposing subtegumental tissue. The overall findings in this study revealed the potential antischistosomal activity of simvastatin and artesunate against Schistosoma mansoni adult worms, in addition to showing that multiple doses of either monotherapy caused severe damage to the tegument.KEY WORDS: Schistosoma mansoni; hyperlipidemia; simvastatin; artesunate; microscopy.

In vitro Antischistosomal Activity of Clerodendrum umbellatum Poir (Labiateae) Leaves Aqueous Extract and Derived Fractions against Schistosoma mansoni Adult Worms

Aims: Treatment against schistosomiasis relies on praziquantel. Its treatment failure and the possible development of resistant schistosomes strains have been reported in the literature. Clerodendrum umbellatum leaves are used in Africa for the treatment of intestinal helminthiasis. The aim of this study was to evaluate the in vitro activity of C. umbellatum leaves aqueous extract and derived fractions on Schistosoma mansoni adult worms.
 Methodology: Five male and five female Schistosoma mansoni adult worms were incubated in each well for 48 h in a GMEM culture medium with C. umbellatum aqueous extract (125 to 4000 µg/mL) or its n-hexane, ethyl acetate and methanol fractions or the aqueous residue (62.5 to 2000 µg/mL). The main parameters assessed were the worm’s mortality and the reduction of motor activity. Phytochemical screening of all our tested substances was also performed. The cytotoxicity assay using mouse melanoma liver cells line was performed on the aqueous extract and on the most active fraction.
 Results: Our study shown that C. umbellatum leaves aqueous extract and its derived fractions promoted worm mortality. The aqueous extract disclosed a LC50 of 805.21 µg/mL while the LC50 of the methanol fraction was 343.10 µg/mL. With this lowest LC50, the methanol fraction from C. umbellatum aqueous extract was therefore the most active. Moreover, it showed low level of toxicity on hepatocytes. Incubation of worms with C. umbellatum aqueous extract and fractions also resulted in a significant reduction of the motor activity of survival worms with a 39.54 to 100% reduction after 48h. The phytochemical screening of C. umbellatum aqueous extract and fractions revealed the presence of alkaloids, phenols, flavonoids, tannins, saponins and terpenoids.
 Conclusion: The present study demonstrated the in vitro activity of C. umbellatum aqueous extract and derived fractions on S. mansoni adult worms and could then justify its empirical use to combat schistosomiasis.

Antischistosomal, antionchocercal and antitrypanosomal potentials of some Ghanaian traditional medicines and their constituents.

Ghana is endemic for some neglected tropical diseases (NTDs) including schistosomiasis, onchocerciasis and lymphatic filariasis. The major intervention for these diseases is mass drug administration of a few repeatedly recycled drugs which is a cause for major concern due to reduced efficacy of the drugs and the emergence of drug resistance. Evidently, new treatments are needed urgently. Medicinal plants, on the other hand, have a reputable history as important sources of potent therapeutic agents in the treatment of various diseases among African populations, Ghana inclusively, and provide very useful starting points for the discovery of much-needed new or alternative drugs. In this study, extracts of fifteen traditional medicines used for treating various NTDs in local communities were screened in vitro for efficacy against schistosomiasis, onchocerciasis and African trypanosomiasis. Two extracts, NTD-B4-DCM and NTD-B7-DCM, prepared from traditional medicines used to treat schistosomiasis, displayed the highest activity (IC50 = 30.5 μg/mL and 30.8 μg/mL, respectively) against Schistosoma mansoni adult worms. NTD-B2-DCM, also obtained from an antischistosomal remedy, was the most active against female and male adult Onchocera ochengi worms (IC50 = 76.2 μg/mL and 76.7 μg/mL, respectively). Antitrypanosomal assay of the extracts against Trypanosoma brucei brucei gave the most promising results (IC50 = 5.63 μg/mL to 18.71 μg/mL). Incidentally, NTD-B4-DCM and NTD-B2-DCM, also exhibited the greatest antitrypanosomal activities (IC50 = 5.63 μg/mL and 7.12 μg/mL, respectively). Following the favourable outcome of the antitrypanosomal screening, this assay was selected for bioactivity-guided fractionation. NTD-B4-DCM, the most active extract, was fractionated and subsequent isolation of bioactive constituents led to an eupatoriochromene-rich oil (42.6%) which was 1.3-fold (IC50 <0.0977 μg/mL) more active than the standard antitrypanosomal drug, diminazene aceturate (IC50 = 0.13 μg/mL). These findings justify the use of traditional medicines and demonstrate their prospects towards NTDs drug discovery.

Spironolactone: A promising anti-schistosomal drug as revealed by scanning electron microscopy of adult worms

Background: Schistosomiasis mansoni is still a widespread parasitic infection especially among poor developing countries. Depending on praziquantel (PZQ) as a single medication for treatment and control, causes the emergence of isolates resistant to this drug. Continuous efforts are needed for the introduction of new effective therapies. Some diuretics including spironolactone, showed promising anti-parasitic effects. Objectives: In this study, spironolactone, a potassium-sparing diuretic, was evaluated regarding its in vitro lethal effect on Schistosomamansoni (S. mansoni) adult worms using scanning electron microscopy (SEM). Material and Methods: A total of 144 worms; 72 males and 72 females were exposed to a concentration of 10 μg/ml of spironolactone for 5 days at 37±0.5°C in 5% CO2 incubator. A pure medium and a medium containing 0.5% of dimethyl sulfoxide (DMSO) (vehicle) were used as negative controls, while PZQ at 10 μg/ml was used as a reference drug. The compound was then retested using the same technique by successive descending dilutions of the solution. Mortality rate of 50% (lethal concentration) (LC50) and 100% (lethal concentration) (LC100) were calculated after 72 h and 5 days exposure. Results: Our results highlighted the potent anti-schistosome effect of spironolactone as it showed 100% mortality of worms at 6.4 μg/ml and 5 μg/ml after 72 h and 5 days exposure, respectively. While 50% mortality of worms was obtained at 4.5 μg/ml and 3 μg/ml after 72 h and 5 days exposure, respectively. Moreover, SEM of male and female S. mansoni worms exposed to spironolactone in vitro, showed disintegration and sloughing of the tubercles on the dorsal surface of males, erosion of the tegument with exposure and appearance of the sub-tegumental tissue in males and females. Conclusion: Being a safe, oral, inexpensive, and well tolerated drug, spironolactone is capable of being a potent future anti-schistosome drug.

In vitro effects of febrifugine on Schistosoma mansoni adult worms

BackgroundReports on the antischistosomal effect of several antimalarial drugs such as artesunate, mefloquine, and amodiaquine suggest that febrifugine, which exerts an antimalarial effect, can also be expected to possess antischistosomal potential. The present study investigates the antischistosomal effects of febrifugine.MethodsIn experiment 1, Schistosoma mansoni adult worm pairs were incubated in a medium alone as a control or supplemented with febrifugine at 0.05, 0.1, 0.2, and 0.5 μg/ml for 14 days. The morphology of the worms and the egg production of the female worms were observed simultaneously. In experiment 2, the incubation was conducted as in experiment 1, except that the febrifugine concentrations were reduced to 0.005, 0.01, and 0.02 μg/ml. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml febrifugine or none as a control for 5 days and stained with neutral red dye.ResultsFebrifugine significantly reduced the survival of S. mansoni male and female worms at concentrations of 0.02–0.5 μg/ml following incubation for 14 days and remarkably inhibited the daily egg output of the female worms. The non-treated male and female worms remained morphologically normal within the period of 14 days, whereas male and female worms treated with febrifugine at different concentrations gradually twisted and subsequently died. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml febrifugine or none as a control for 5 days and stained with neutral red dye. Non-treated male worms were morphologically normal and stained dark red with neutral red, while febrifugine-treated male worms appeared similar to those in the control group and were stained at a slightly lower level of dark red than the non-treated male worms. Non-treated female worms were morphologically normal, and their intestinal tract and vitellaria were stained deep red and dark red, respectively. In contrast, febrifugine-treated female worms were morphologically damaged, and their intestinal tract and vitellaria remained mostly unstained and stained dark red, respectively.ConclusionFebrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug.

Schiff bases of 4-Phenyl-2-Aminothiazoles as hits to new antischistosomals: Synthesis, in vitro, in vivo and in silico studies

The treatment of schistosomiasis is based on a single drug, the praziquantel (PZQ), an oral bioavailable and efficient agent which causes minimal side effects. The main concern about this approach, however, is that relying on only one drug to treat a helminthic disease is a dangerous strategy since history shows that pathogens easily evolve to resistant forms. Actually, reports about experimental strains exhibiting low sensibility to PZQ can be found in literature. The search for new antischistosomals, consequently, is urgent. Here we report the synthesis of seventeen Schiff bases of 4-(4-Substituted phenyl)-N-(4-substituted benzylidene)thiazole-2-amines which were tested in vitro and in vivo against Schistosoma mansoni adult worms. Moreover, in silico studies to propose potential macromolecular targets and to predict the oral bioavailability were also performed. The analog GPQF-108 exhibited the best in vitro performance (IC50: 29.4 µM, SI:6.1) associated with promising in vivo activity, with a significant decrease in the adult life forms and oviposition. Oral bioavailability could be impaired by the predicted low water solubility of GPQF-108, although it also exhibited good membrane permeability. The water solubility, however, could be improved by decreasing the particles size. Serine/Threonine- and Tyrosine Kinases, Carbonic Anhydrase, Tyrosine Phosphatase and Arginase were predicted as potential macromolecular targets through which the GPQF-108 could be acting against the helminth. This class of compounds exhibited an interesting initial therapeutic profile with the advantage of being chemically diverse from the PZQ and be easily synthesized from commercial reagents which could lead to low-cost drugs. These aspects make this class of compounds interesting hits to be explored against schistosomiasis.

One‐step formation of polyurea gel as a multifunctional approach for biological and environmental applications

AbstractThis work presents a facile one‐pot fabrication of polyurea (PU) organogels based on polyetheramine (PEO, Jeffamine ED‐2003) and a crosslinker hexamethylene diisocyanate trimer (HDI) which were subsequently used as a drug carrier to incorporate a curcumin hydrophobic molecule in aqueous conditions and for removal of an anionic pollutant in water. PU can be obtained in different shapes with easy control of film thickness with high transparency, flexibility and homogeneous dispersion of curcumin in the matrix. Due to the hydrophilic nature of PEO a high swelling degree was demonstrated by the PU gel. The phase separated domains and the temperature's influence on the system's structural order/disorder were examined by small‐angle X‐ray scattering, showing a more PU ordered system (interface between hard and soft segments) after decreasing the temperature to −90 °C. The presence of curcumin in the structure of PU was confirmed by Fourier transform infrared, photoluminescence and release studies. A highly efficient removal of Congo red dye from aqueous solution using PU as adsorbent was observed. Moreover, the effect of unloaded and curcumin‐loaded PU gels was evaluated on Schistosoma mansoni adult worms. Detailed in vitro cell viability experiments showed the biocompatibility of loaded and unloaded PU gels. The easy processability of the multifunctional PU shows that it has promising applications as transdermal and soft tissue implantable delivery devices for a large number of poorly water‐soluble drugs and as an efficient adsorbent for removal of organic dyes; it can also be used in the future in dermatological treatments against malignant melanoma. © 2020 Society of Chemical Industry

Proteomic analysis of two populations of Schistosoma mansoni-derived extracellular vesicles: 15k pellet and 120k pellet vesicles

Helminth parasites secrete extracellular vesicles (EVs) into their environment that have potential roles in host-parasite communication, and thus represent potentially useful targets for novel control strategies. Here, we carried out a comprehensive proteomic analysis of two different populations of EVs – 15k pellet and 120k pellet EVs – from Schistosoma mansoni adult worms. We characterised the proteins present in the membranes of the EVs (including external trypsin-liberated peptides, integral membrane proteins (IMPs) and peripheral membrane proteins (PMPs)), as well as cargo proteins, using LC–MS/MS. A total of 286 and 716 proteins were identified in 15k and 120k pellets, respectively. Some of the most abundant proteins identified from both 15k and 120k pellets include known vaccine candidates such as Sm-TSP-2, saponin B domain-containing proteins, calpain glutathione-S-transferase, Sm29 and cathepsin domain-containing proteins. Other abundant proteins that have not been tested as vaccines include DM9 domain-containing protein, 13 kDa tegumental antigen and histone H4-like protein. Sm23, a member of the tetraspanin family with known vaccine efficacy, was identified in the cargo and IMP compartments of only 15k pellet vesicles. Moreover, a collection of proteins with known or potential relevance in host-parasite communication including proteases, antioxidants and EV biogenesis/trafficking of both vesicle types were identified. Our results provide the first report of a comprehensive compartmental proteomic analysis of adult S. mansoni-derived EVs. Future research should investigate recombinant forms of these proteins as vaccine and serodiagnostic antigens as well as the roles of EV proteins in host-parasite communication.

In vitro efficacy of new synthetic benzimidazole-related compounds against Schistosoma mansoni adult worms

Objective: To evaluate the in vitro antischistosomal activity of two new synthetic benzimidazole-related compounds: NBTP-OH and NBTP-F.Methods: Schistosoma adult worms were recovered from mice infected with Schistosoma mansoni cercaria, washed and then incubated in the culture media with different concentrations of compounds NBTP-OH and NBTP-F up to 72 h. Scanning electron microscopy was conducted to report morphological changes. Results: Incubation of adult Schistosoma mansoni with 10 μg/mL of NBTP-OH for 48 h killed 81.25% of worms. The calculated LC50 and LC90 72 h post-incubation were 6.8 μg/mL and 9.8 μg/ mL, respectively. Exposure of worms to 10 μg/mL of NBTP-F killed 89.5% of worms after 48 h, mostly males (83.3%), the LC50 and LC90 after 72 h of incubation were 4.8 μg/mL and 6.9 μg/mL, respectively. Worms incubated for 72 h with these compounds revealed swelling and deformity of oral sucker, disorganization and erosion of the tegument when examined with scanning electron microscopy.Conclusions: NBTP-OH and NBTP-F possess in vitro antischistosomal activities; however, in vivo studies should be conducted to examine their antischistosomal effects.

Long-term ethanol intake causes morphological changes in Schistosoma mansoni adult worms in mice

Schistosoma mansoni adult worms are extensively challenged by reactive oxygen species from intrinsic sources. However, the effects of extrinsic sources such as ethanol have not been looked at in schistosomes. We examined adult worms recovered from ethanol-consuming mice by light (LM), confocal (CM) and scanning electron microscopy (SEM) to address this question. Schistosomiasis-infected mice were orally gavaged with 18% (v/v) ethanol from 35 to 63 days post-infection, when they were euthanized. CM examination revealed reduced germ cells density (−36%, p = 0.0001) and sperm density (−58%, p = 0.0001) in testicular lobes, and immature cells in seminal vesicle compared to unexposed control worms. Female worms showed reduced density of vitellin glands (−71%, p = 0.0001), maturation of oocytes (−7%, p = 0.0071) and reduced spermatozoa density (−23%, p = 0.0002) within the seminal receptacle. SEM revealed remarkable damages in male's tegument, including tubercles flattening, tegumental peeling and erosive lesions. Given that lipids are present in reproductive system and tegument, our results suggest that phenotypic changes are due to ethanol-induced lipid peroxidation. To the best of our knowledge, this is the first report revealing the biological action of ethanol intake on adult schistosomes in vivo.