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Sample records for mansoni ressonancia magnetica

  1. Immunopathology of Schistosoma mansoni infection.

    PubMed Central

    Boros, D L

    1989-01-01

    Schistosomiasis mansoni is a chronic helminthic disease that affects about 100 million people in the tropics. The worms have a life span of 5 to 10 years, and they live in the mesenteric veins of the host. Lightly infected individuals are asymptomatic or manifest mild intestinal symptoms. Heavily infected individuals often develop severe morbidity with hepatosplenomegaly, sometimes with a fatal outcome. Morbidity is attributed to the strong humoral and T-cell-mediated host immune responses developed to a variety of parasite antigens and expressed as tissue inflammations. The immunopathology includes dermatitis, immune complex-mediated kidney disease, and, chiefly, T-cell-mediated granuloma formation and fibrosis around disseminated parasite eggs. This review describes the mechanisms of induction and expression of immunopathology in infected persons and experimental animals. Immunoregulatory mechanisms that modulate the enhanced immune responses and may ameliorate excessive morbidity are discussed. PMID:2504481

  2. Ectopic Schistosoma mansoni Eggs Inside a Lipoma.

    PubMed

    Sabino, Kelly Renata; Nunes, Maurício Buzelin; Petroianu, Andy

    2016-01-01

    Ectopic schistosomiasis is uncommon and tends to occur when the parasite's eggs or adult forms are located far from their normal site. This report presents the first described case of ectopic Schistosoma mansoni eggs inside a subcutaneous lipoma far from the tissues of this worm's life cycle and with no connection to either portal veins or any other vascular system. These eggs were found inside giant cells surrounded by inflammatory cells. In conclusion, in humans, ectopic S. mansoni eggs can be found far from the tissues of the described life cycle of this worm, with no connection to portal veins or other blood vessels used for their migration. PMID:26598562

  3. Proteomic Analysis of Schistosoma mansoni Egg Secretions

    PubMed Central

    Cass, Cynthia L.; Johnson, Jeffrey R.; Califf, Lindsay L.; Xu, Tao; Hernandez, Hector J.; Stadecker, Miguel J.; Yates, John R.; Williams, David L.

    2007-01-01

    Schistosomiasis remains a largely neglected, global health problem. The morbid pathology of the disease stems from the host's inflammatory response to parasite eggs trapped in host tissues. Long term host/parasite survival is dependent upon the successful modulation of the acute pathological response, which is induced by egg antigens. In this study, using Multidimensional Protein Identification Technology, we identified the Schistosoma mansoni egg secretome consisting of 188 proteins. Notably we identified proteins involved in redox balance, molecular chaperoning and protein folding, development and signaling, scavenging and metabolic pathways, immune response modulation, and 32 novel, previously uncharacterized schistosome proteins. We localized a subset of previously-characterized schistosome proteins identified in egg secretions in this study, to the surface of live S. mansoni eggs using the circumoval precipitin reaction. The identification of proteins actively secreted by live schistosome eggs provides important new information for understanding immune modulation and the pathology of schistosomiasis. PMID:17644200

  4. Schistosoma mansoni: cercarial responses to irradiance changes

    SciTech Connect

    Saladin, K.S.

    1982-02-01

    Cercariae of Schistosoma mansoni alternate between active swimming and passive drifting. They began swimming in response to either an increase or decrease in irradiance experienced during the passive phase. The number of cercariae reacting to a shadow was proportional to the magnitude of the stimulus. The shadow response may be mediated by the cercaria's ciliary receptors. About half as many cercariae reacted to an irradiance increase as to an equivalent decrease. This report is the first quantitative study of photosensory stimulus-response relationships in schistosome cercariae.

  5. Praziquantel inhibits Schistosoma mansoni attachment in vitro.

    PubMed

    da-Silva, S P; Noel, F

    1990-01-01

    Male adult Schistosoma mansoni worms were placed in a glass dish containing Tyrode solution and observed for 15 min after addition of praziquantel (0.01 to 1 microM). Praziquantel promoted a concentration- and time-dependent inhibition of sucker-mediated attachment of the worm. Attachment inhibition was correlated with shortening of the parasite. We propose that the rapid and total inhibition of worm attachment observed in vitro with 1 microM praziquantel indicates that therapeutic concentrations of this drug should promote a rapid hepatic shift, in vivo, which may facilitate host tissue reaction. PMID:2101049

  6. A next-generation proteome array for Schistosoma mansoni.

    PubMed

    de Assis, Rafael Ramiro; Ludolf, Fernanda; Nakajima, Rie; Jasinskas, Al; Oliveira, Guilherme C; Felgner, Philip L; Gaze, Soraya T; Loukas, Alex; LoVerde, Philip T; Bethony, Jeffrey M; Correa-Oliveira, Rodrigo; Calzavara-Silva, Carlos E

    2016-06-01

    A proteome microarray consisting of 992 Schistosoma mansoni proteins was produced and screened with sera to determine antibody signatures indicative of the clinical stages of schistosomiasis and the identification of subunit vaccine candidates. Herein, we describe the methods used to derive the gene list for this array (representing approximately 10% of the predicted S. mansoni proteome). We also probed a pilot version of the microarray with sera from individuals either acutely or chronically infected with S. mansoni from endemic areas in Brazil and sera from individuals resident outside the endemic area (USA) to determine if the array is functional and informative. PMID:27131510

  7. Schistosoma mansoni and Biomphalaria: past history and future trends.

    PubMed

    Morgan, J A; Dejong, R J; Snyder, S D; Mkoji, G M; Loker, E S

    2001-01-01

    Schistosoma mansoni is one of the most abundant infectious agents of humankind. Its widespread distribution is permitted by the broad geographic range of susceptible species of the freshwater snail genus Biomphalaria that serve as obligatory hosts for its larval stages. Molecular phylogenetic studies suggest that Schistosoma originated in Asia, and that a pulmonate-transmitted progenitor colonized Africa and gave rise to both terminal-spined and lateral-spined egg species groups, the latter containing S. mansoni. Schistosoma mansoni likely appeared only after the trans-Atlantic dispersal of Biomphalaria from the Neotropics to Africa, an event that, based on the present African fossil record, occurred only 2-5 million years ago. This parasite became abundant in tropical Africa and then entered the New World with the slave trade. It prospered in the Neotropics because a remarkably susceptible and productive host, B. glabrata, was widely distributed there. Indeed, a snail similar to B. glabrata may have given rise to the African species of Biomphalaria. Schistosoma mansoni has since spread into other Neotropical Biomphalaria species and mammalian hosts. The distribution of S. mansoni is in a state of flux. In Egypt, S. mansoni has nearly completely replaced S. haematobium in the Nile Delta, and has spread to other regions of the country. A susceptible host snail, B. straminea, has been introduced into Asia and there is evidence of S. mansoni transmission in Nepal. Dam and barrage construction has lead to an epidemic of S. mansoni in Senegal, and the parasite continues its spread in Brazil. Because of competition with introduced aquatic species and environmental changes, B. glabrata and consequently S. mansoni have become less abundant on the Caribbean islands. Control of S. mansoni using praziquantel and oxamniquine has reduced global prevalence but control is difficult to sustain, and S. mansoni can develop tolerance/resistance to praziquantel, raising concerns about

  8. Proteomic Analysis of the Schistosoma mansoni Miracidium

    PubMed Central

    Wang, Tianfang; Zhao, Min; Rotgans, Bronwyn A.; Strong, April; Liang, Di; Ni, Guoying; Limpanont, Yanin; Ramasoota, Pongrama; McManus, Donald P.; Cummins, Scott F.

    2016-01-01

    Despite extensive control efforts, schistosomiasis continues to be a major public health problem in developing nations in the tropics and sub-tropics. The miracidium, along with the cercaria, both of which are water-borne and free-living, are the only two stages in the life-cycle of Schistosoma mansoni which are involved in host invasion. Miracidia penetrate intermediate host snails and develop into sporocysts, which lead to cercariae that can infect humans. Infection of the snail host by the miracidium represents an ideal point at which to interrupt the parasite’s life-cycle. This research focuses on an analysis of the miracidium proteome, including those proteins that are secreted. We have identified a repertoire of proteins in the S. mansoni miracidium at 2 hours post-hatch, including proteases, venom allergen-like proteins, receptors and HSP70, which might play roles in snail-parasite interplay. Proteins involved in energy production and conservation were prevalent, as were proteins predicted to be associated with defence. This study also provides a strong foundation for further understanding the roles that neurohormones play in host-seeking by schistosomes, with the potential for development of novel anthelmintics that interfere with its various life-cycle stages. PMID:26799066

  9. Proteomic Analysis of the Schistosoma mansoni Miracidium.

    PubMed

    Wang, Tianfang; Zhao, Min; Rotgans, Bronwyn A; Strong, April; Liang, Di; Ni, Guoying; Limpanont, Yanin; Ramasoota, Pongrama; McManus, Donald P; Cummins, Scott F

    2016-01-01

    Despite extensive control efforts, schistosomiasis continues to be a major public health problem in developing nations in the tropics and sub-tropics. The miracidium, along with the cercaria, both of which are water-borne and free-living, are the only two stages in the life-cycle of Schistosoma mansoni which are involved in host invasion. Miracidia penetrate intermediate host snails and develop into sporocysts, which lead to cercariae that can infect humans. Infection of the snail host by the miracidium represents an ideal point at which to interrupt the parasite's life-cycle. This research focuses on an analysis of the miracidium proteome, including those proteins that are secreted. We have identified a repertoire of proteins in the S. mansoni miracidium at 2 hours post-hatch, including proteases, venom allergen-like proteins, receptors and HSP70, which might play roles in snail-parasite interplay. Proteins involved in energy production and conservation were prevalent, as were proteins predicted to be associated with defence. This study also provides a strong foundation for further understanding the roles that neurohormones play in host-seeking by schistosomes, with the potential for development of novel anthelmintics that interfere with its various life-cycle stages. PMID:26799066

  10. Activity of epiisopiloturine against Schistosoma mansoni.

    PubMed

    Veras, L M; Guimaraes, M A; Campelo, Y D; Vieira, M M; Nascimento, C; Lima, D F; Vasconcelos, L; Nakano, E; Kuckelhaus, S S; Batista, M C; Leite, J R; Moraes, J

    2012-01-01

    Schistosomiasis, caused by blood flukes of the genus Schistosoma, still imposes a considerable public health burden on large parts of the world. The control of this disease depends almost exclusively on the drug praziquantel, and there are no alternative drugs in sight. Natural compounds have recently attracted significant attention due to their relevance to parasitic infection and potential development into new therapeutic agents. Epiisopiloturine is an imidazole alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native plant from Brazil. Here, we report the in vitro effect of this drug on the survival time of Schistosoma mansoni of different ages, such as 3 h old and 1, 3, 5, and 7 days old schistosomula, 49-day-old adults, and on egg output by adult worms. Epiisopiloturine at a concentration of 300 μg/mL caused the death of all schistosomula within 120 h. Extensive tegumental alterations and death were observed when adult schistosomes had been exposed to 150 μg/mL of the epiisopiloturine. At the highest sub-lethal dose of alkaloid (100 μg/mL), a 100% reduction in egg laying of paired adult worms was observed. Additionally, epiisopiloturine showed selective antischistosomal activity and exhibited no cytotoxicity to mammalian cells. This report provides the first evidence that epiisopiloturine is able to kill S. mansoni of different ages and inhibit worm egg laying. PMID:22420337

  11. A chemokinetic response in Schistosoma mansoni cercariae.

    PubMed

    Shiff, C J; Graczyk, T K

    1994-12-01

    Schistosoma mansoni cercariae have been shown to aggregate in the presence of glass slides treated with clear nail varnish and linoleic acid. In choice chambers cercariae move toward the stimulant, but this behavior is not seen when linoleic acid is omitted. After 30-45 min, the cercariae were concentrated near the end of the choice-chamber containing the linoleic acid slide. When the cercariae were added in the center of the choice chamber, they formed a diffuse cloud that dispersed slowly in both directions in the absence of linoleic acid. Cercariae aggregating in the vicinity of a stimulant surface are not immediately stimulated to commence penetration; this appears to be time and dose related. PMID:7799158

  12. Schistosoma mansoni Annexin 2: molecular characterization and immunolocalization.

    PubMed

    Tararam, Cibele Aparecida; Farias, Leonardo Paiva; Wilson, R Alan; Leite, Luciana Cezar de Cerqueira

    2010-10-01

    We here describe the cloning and characterization of the Schistosoma mansoni Annexin 2, previously identified in the tegument by proteomic studies, and as an up-regulated gene in schistosomulum stage by microarray data. In silico analysis predicts a conserved core containing four repeat domains of Annexin (ANX) and a variable N-terminal region similar to that described for mammalian isoforms. Real-time RT-PCR and Western blot analysis determined that S. mansoni Annexin 2 is significantly up-regulated in the transition from free-living cercaria to schistosomulum and adult worm parasitic stages. Immunolocalization experiments and tegument membrane preparations confirmed Annexin 2 as a protein mainly localized in the tegument of schistosomula and adult worms. Furthermore, it binds to the tegument surface membranes in a calcium-dependent manner. These results suggest that S. mansoni Annexin 2 is closely associated to the tegument arrangement, being a potential target for immune intervention. PMID:20417203

  13. Structural bioinformatics study of PNP from Schistosoma mansoni.

    PubMed

    da Silveira, Nelson José Freitas; Uchôa, Hugo Brandão; Canduri, Fernanda; Pereira, José Henrique; Camera, João Carlos; Basso, Luiz Augusto; Palma, Mário Sergio; Santos, Diógenes Santiago; de Azevedo, Walter Filgueira

    2004-09-10

    The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs. PMID:15313179

  14. THE SUSCEPTIBILITY OF RECENT ISOLATES OF Schistosoma mansoni TO PRAZIQUANTEL

    PubMed Central

    MENDONÇA, Adriana Maria B.; FEITOSA, Ana Paula S.; VERAS, Dyana L.; MATOS-ROCHA, Thiago J.; CAVALCANTI, Marília G. dos Santos; BARBOSA, Constança Clara G. S.; BRAYNER, Fábio A.; ALVES, Luiz C.

    2016-01-01

    Introduction: Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma and its control is dependent on a single drug, praziquantel (PZQ), but concerns over PZQ resistance have renewed interest in evaluating the in vitro susceptibility of recent isolates of Schistosoma mansoni to PZQ in comparison with well-established strains in the laboratory. Material and methods: The in vitro activity of PZQ (6.5-0.003 µg/mL) was evaluated in terms of mortality, reduced motor activity and ultrastructural alterations against S. mansoni. Results: After 3 h of incubation, PZQ, at 6.5 µg/mL, caused 100% mortality of all adult worms in the three types of recent isolates, while PZQ was inactive at concentrations of 0.08-0.003 µg/mL after 3 h of incubation. The results show that the SLM and Sotave isolates basically presented the same pattern of susceptibility, differing only in the concentration of 6.5 µg/mL, where deaths occurred from the range of 1.5 h in Sotave and just in the 3 h range of SLM. Additionally, this article presents ultrastructural evidence of rapid severe PZQ-induced surface membrane damage in S. mansoni after treatment with the drug, such as disintegration, sloughing, and erosion of the surface. Conclusion: According to these results, PZQ is very effective to induce tegument destruction of recent isolates of S. mansoni. PMID:26910445

  15. Possible eggshell protein gene from Schistosoma mansoni.

    PubMed

    Johnson, K S; Taylor, D W; Cordingley, J S

    1987-01-01

    We have identified and sequenced a cDNA clone of a mRNA found only in mature female schistosomes. This mRNA is not detectably synthesized by female worms from single sex infections (unisexual females), by males or by the developing miracidia in the eggs. The clone hybridises to a highly abundant polyadenylated mRNA of approximately 1500 nucleotides. The nucleotide sequence of the clone predicts a polypeptide comprising two repetitive regions. A pentapeptide repeat with the consensus sequence Gly-Tyr-Asp-Lys-Tyr, and a region rich in histidine residues. Hybrid selected mRNA translated in vitro with [3H]tyrosine as labelled amino acid yields a polypeptide of 48 kDa (p48) that corresponds to the major [3H]tyrosine labelled translation product of female worm total mRNA. p48 does not label with [35S]methionine and is absent from the translation products of male and unisexual female mRNAs. The amino acid sequence of p48 has significant homologies to silk moth chorion proteins and we suggest that it is one of the major components of the schistosome eggshell probably accounting for the high level of [3H]tyrosine incorporation into the vitellaria of Schistosoma mansoni. The tyrosine content of the polypeptide suggests that it may play a role in phenol oxidase mediated cross-linking of the schistosome eggshell and in support of this we find that mushroom phenol oxidase will cause the specific cross-linking of p48 in in vitro translation products. PMID:3100949

  16. Whole genome resequencing of the human parasite Schistosoma mansoni reveals population history and effects of selection

    PubMed Central

    Crellen, Thomas; Allan, Fiona; David, Sophia; Durrant, Caroline; Huckvale, Thomas; Holroyd, Nancy; Emery, Aidan M.; Rollinson, David; Aanensen, David M.; Berriman, Matthew; Webster, Joanne P.; Cotton, James A.

    2016-01-01

    Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5–147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20–90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16–19th Century Atlantic Slave Trade. PMID:26879532

  17. Whole genome resequencing of the human parasite Schistosoma mansoni reveals population history and effects of selection.

    PubMed

    Crellen, Thomas; Allan, Fiona; David, Sophia; Durrant, Caroline; Huckvale, Thomas; Holroyd, Nancy; Emery, Aidan M; Rollinson, David; Aanensen, David M; Berriman, Matthew; Webster, Joanne P; Cotton, James A

    2016-01-01

    Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5-147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20-90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16-19th Century Atlantic Slave Trade. PMID:26879532

  18. Effect of Maternal Schistosoma mansoni Infection and Praziquantel Treatment During Pregnancy on Schistosoma mansoni Infection and Immune Responsiveness among Offspring at Age Five Years

    PubMed Central

    Tweyongyere, Robert; Naniima, Peter; Mawa, Patrice A.; Jones, Frances M.; Webb, Emily L.; Cose, Stephen; Dunne, David W.; Elliott, Alison M.

    2013-01-01

    Introduction Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. Methods In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. Results Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. Conclusion We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood

  19. Human schistosomiasis: Schistosoma mansoni antigen detection in renal glomeruli.

    PubMed

    Hoshino-Shimizu, S; De Brito, T; Kanamura, H Y; Canto, A L; Silva, A O; Campos, A R; Penna, D O; Da Silva, L C

    1976-01-01

    Twelve kidney, five biopsy and seven necropsy specimens, all from schistosomiasis mansoni patients were studied by light and immunoflurescent microscopy in an attempt to detect antigen in the glomerular walls. Deposits of IgM, IgG,I gA, IgE, complement C3 and fibrinogen were observered in most cases. Antigen was successfully detected in two cases(one biopsy and one necropsy specimen), both exhibiting proliferative glomerulonephritis. The only clinical manifestation was a slight proteinuria. IgG antibodies eluted from the sutopsy kidney homogenates showed specific binding mostly to Schistosoma mansoni gut, thus spggesting that the fixed antibodies (eluates) are, at least partially, consituted by antibodies similar to the anti-circulating antigen. These data reinfroce the hypothesis that renal injury in schistosomiasis is mediated through an immune complex disease. PMID:65811

  20. Murine immunization by cesium-137 irradiation attenuated Schistosoma mansoni cercariae

    SciTech Connect

    Stek, M. Jr.; Minard, P.; Cruess, D.F.

    1984-06-01

    Cesium-137, becoming a more readily available ionizing gamma radiation source for laboratory use, was shown to effectively attenuate Schistosoma mansoni cercariae for vaccine production. In parallel comparison studies with the murine model, cesium-137 attenuated cercariae consistently afforded better protection than did the cobalt-60 prepared vaccine. Dose-response data indicated that the optimal total irradiation with cesium-137 was between 45 and 50 Krad.

  1. Immunization of Baboons with Schistosoma mansoni Cercariae attenuated by gamma irradiation

    SciTech Connect

    Stek, M.; Minard, P.; Dean, D.A.; Hall, J.E.

    1981-06-01

    Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70 percent) and egg excretion rates (82 percent). These results support immunization as a potential method for schistosomiasis control.

  2. Immunization of baboons with Schistosoma mansoni cercariae attenuated by gamma irradiation

    SciTech Connect

    Stek, M. Jr.; Minard, P.; Dean, D.A.; Hall, J.E.

    1981-06-26

    Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70%) and egg excretion rates (82%). These results support immunization as a potential method for schistosomiasis control.

  3. Papain-Based Vaccination Modulates Schistosoma mansoni Infection-Induced Cytokine Signals.

    PubMed

    Abdel Aziz, N; Tallima, H; Hafez, E A; El Ridi, R

    2016-02-01

    We have previously shown that immunization of outbred rodents with cysteine peptidases-based vaccine elicited type 2-biased immune responses associated with consistent and reproducible protection against challenge Schistosoma mansoni. We herein start to elucidate the molecular basis of C57BL/6 mouse resistance to S. mansoni following treatment with the cysteine peptidase, papain. We evaluated the early cytokine signals delivered by epidermal, dermal, and draining lymph node cells of naïve, and S. mansoni -infected mice treated 1 day earlier with 0 or 50 μg papain, or immunized twice with papain only (10 μg/mouse), papain-free recombinant S. mansoni glyceraldehyde 3-phosphate dehydrogenase and 2-Cys peroxiredoxin peptide (10 and 15 μg/mouse, respectively = antigen Mix), or papain-adjuvanted antigen Mix. Schistosoma mansoni infection induced epidermal and lymph node cells to release type 1, type 2 and type 17 cytokines, known to counteract each other. Expectedly, humoral immune responses were negligible until patency. Papain pretreatment or papain-based vaccination diminished or shut off S. mansoni infection early induction of type 1, type 17 and type 2 cytokines except for thymic stromal lymphopoietin and programmed the immune system towards a polarized type 2 immune milieu, associated with highly significant (P < 0.005 - <0.0001) resistance to S. mansoni infection. PMID:26603950

  4. Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules.

    PubMed

    Hirst, Natasha L; Lawton, Scott P; Walker, Anthony J

    2016-06-01

    Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A regulates multiple processes in eukaryotes by phosphorylating diverse cellular substrates, including metabolic and signalling enzymes, ion channels and transcription factors. Here we provide insight into protein kinase A signalling in cercariae and 24h in vitro cultured somules of the blood parasite, Schistosoma mansoni, which causes human intestinal schistosomiasis. Functional mapping of activated protein kinase A using anti-phospho protein kinase A antibodies and confocal laser scanning microscopy revealed activated protein kinase A in the central and peripheral nervous system, oral-tip sensory papillae, oesophagus and excretory system of intact cercariae. Cultured 24h somules, which biologically represent the skin-resident stage of the parasite, exhibited similar activation patterns in oesophageal and nerve tissues but also displayed striking activation at the tegument and activation in a region resembling the germinal 'stem' cell cluster. The adenylyl cyclase activator, forskolin, stimulated somule protein kinase A activation and produced a hyperkinesia phenotype. The biogenic amines, serotonin and dopamine known to be present in skin also induced protein kinase A activation in somules, whereas neuropeptide Y or [Leu(31),Pro(34)]-neuropeptide Y attenuated protein kinase A activation. However, neuropeptide Y did not block the forskolin-induced somule hyperkinesia. Bioinformatic investigation of potential protein associations revealed 193 medium confidence and 59 high confidence protein kinase A interacting partners in S. mansoni, many of which possess putative protein kinase A phosphorylation sites. These data provide valuable insight into the intricacies of protein kinase A signalling in S. mansoni and a framework for further physiological investigations into the roles of protein kinase A in schistosomes, particularly in the context of interactions between the parasite and the host. PMID:26777870

  5. Role of Host Granulomatous Response in Murine Schistosomiasis Mansoni

    PubMed Central

    Olds, G. Richard; Mahmoud, Adel A. F.

    1980-01-01

    Eosinophils form 50% of cells in the host granulomatous response to Schistosoma mansoni eggs, but their functional role in these granulomas and their relation to egg destruction is unknown. We have studied the course of S. mansoni infection in mice treated with normal rabbit serum (NRS) or depleted of their eosinophils by monospecific anti-eosinophil serum (AES). At 6-wk of infection (after 2 wk of egg deposition) the AES-treated animals were similar to NRS-treated controls with the exception that hepatic granulomas in the AES-treated animals were 50% smaller and devoid of eosinophils. At 8 wk of infection, AES-treated mice had significantly higher mortality, spleen weight, portal pressure, and 80% more eggs retained in their livers. These data suggest that eosinophil depletion delayed egg destruction. We subsequently studied destruction of eggs injected into the pulmonary microvasculature of sensitized mice. 2,000 S. mansoni eggs were intravenously injected into the tail veins of mice treated with NRS, anti-neutrophil serum, AES or ATG (anti-thymocyte globulin); at time intervals the remaining eggs were recovered from the lungs by tissue digestion. Egg recovery from NRS- or anti-neutrophil serum-treated mice began to decrease by day 16 and the percent recovery of eggs at day 24 was 55 and 52%, respectively. In contrast, animals treated with AES had smaller lung granulomas that were devoid of eosinophils and a marked delay of egg destruction was seen. It took until day 44 for 50% of the eggs to be destroyed. In ATG-treated animals smaller granulomas were seen that had diminished lymphocytes and also 75% less eosinophils. ATG treatment apparently slowed egg destruction but was not statistically significant. Our data define the role of the eosinophils in destruction of schistosome eggs in vivo and delineates the protective function of these cells within the host granulomatous response. PMID:7440710

  6. Impact of Schistosoma mansoni on Malaria Transmission in Sub-Saharan Africa

    PubMed Central

    Ndeffo Mbah, Martial L.; Skrip, Laura; Greenhalgh, Scott; Hotez, Peter; Galvani, Alison P.

    2014-01-01

    Background Sub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children. Methodology We developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities. Principal Findings Our results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities. Conclusions/Significance Schistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also

  7. Identification of new markers for the Schistosoma mansoni vitelline lineage.

    PubMed

    Wang, Jipeng; Collins, James J

    2016-06-01

    Schistosomes cause significant morbidity and mortality in millions of the world's poorest people. While parasite egg-induced inflammation is the primary driver of host pathology, relatively little is known at the molecular level about the organ systems that participate in schistosome egg production (i.e., testes, ovaries and vitellaria). Here we use transcriptional profiling and in situ hybridization to characterise the vitellarium of Schistosoma mansoni. We uncovered several previously uncharacterised vitellaria-specific factors and defined molecular markers for various stages in the vitellocyte differentiation process. These data provide the framework for future in-depth molecular studies exploring the biology of this important parasite organ. PMID:27056273

  8. COMPARATIVE STUDY ON IMMUNOBLOT VERSUS PCR IN DIAGNOSIS OF SCHISTOSOMIASIS MANSONI IN EXPERIMENTAL INFECTED MICE.

    PubMed

    Ismail, Mousa A M; Mousa, Wahed Mohammed Ali; Abu-Sarea, Enas Yahia; Basyouni, Maha M A; Mohammed, Samah Sayed

    2016-04-01

    This study compared PCR and Western blot techniques in diagnosis of schistosomiasis mansoni. Forty Swiss albino mice were used, thirty two mice were infected with cercariae of S. mansoni and eight mice were kept uninfected which were used as a control. Blood was obtained from four infected mice weekly beginning from the 1st week to the 8th week post infection. The study found that PCR was positive from the first week post infection, while Western blot technique was positive from the second week post infection. Thus, PCR diagnosed schistosomiasis mansoni earlier than Western blot technique, but both were able to diagnose. PMID:27363045

  9. [Schistosomiasis mansoni in the southwest of the State of Minas Gerais (Brazil)].

    PubMed

    Carvalho, O dos S; Massara, C L; Rocha, R S; Katz, N

    1989-08-01

    A new focus of schistosomiasis mansoni at Passos, a town in the Southwest of the State of Minas Gerais (Brazil), region until now considered free of the disease is reported. Malacological surveys showed Biophalaria glabrata naturally infected with Schistosoma mansoni in a country club near Passos. All B. straminea captured at the pisciculture station of the Furnas hydroelectric dam were negative. Six out of seven individuals living in the country club were found to be infected with S. mansoni, including four children who had never been out of Passos. The epidemiological importance of these findings is discussed. PMID:2517153

  10. Oral immunization of mice against Schistosoma mansoni using drinking water from trays containing Biomphalaria alexandrina infected with Schistosoma mansoni.

    PubMed

    Noureldin, M S

    1999-01-01

    Water collected from trays containing Biomphalaria alexandrina infected with Schistosoma mansoni at the time of cercariae shedding (SmISW) and trays containing clean, non-infected, B. alexandrina (NISW) and underground water (UW), were filtered used as a drinking water for 3 groups of albino mice males. After two months, blood samples were collected from the 3 groups and serum was tested for anti-cercarial IgG, then mice were infected with 150 S. mansoni cercariae. Eight weeks after infection, mice were perfused and adult S. mansoni worms were counted. Anti-cercarial IgG was positive in 23 (82.1%) out of the 28 samples collected from mice drinking SmISW and only in 2 (9.5%) out of the 21 samples collected from mice drinking NISW, while all samples collected from mice drinking UW were negative for anti-cercarial IgG (X2=45.897; P<0.001). Worm load was significantly lower in the group of mice drinking SmISW than mice drinking NISW (P=0.032) and mice drinking UW (P=0.02). In mice drinking SmISW, adult worm count showed significant negative correlation with anti-cercarial IgG concentration (Kendall's taub =-0.325 and P=0.018). The results indicate that antigens present in drinking water stimulate a level of immunity against schistosomiasis, (inhabitants of endemic areas) resulting in a lower intensity and severity of infection. Also, it may reduce the specificity of serological tests used for diagnosis of Schistosoma infection, based on antibody determination. PMID:12561896

  11. Serological Screening of the Schistosoma mansoni Adult Worm Proteome

    PubMed Central

    Ludolf, Fernanda; Patrocínio, Paola R.; Corrêa-Oliveira, Rodrigo; Gazzinelli, Andréa; Falcone, Franco H.; Teixeira-Ferreira, André; Perales, Jonas; Oliveira, Guilherme C.; Silva-Pereira, Rosiane A.

    2014-01-01

    Background New interventions tools are a priority for schistosomiasis control and elimination, as the disease is still highly prevalent. The identification of proteins associated with active infection and protective immune response may constitute the basis for the development of a successful vaccine and could also indicate new diagnostic candidates. In this context, post-genomic technologies have been progressing, resulting in a more rational discovery of new biomarkers of resistance and antigens for diagnosis. Methodology/Principal Findings Two-dimensional electrophoresed Schistosoma mansoni adult worm protein extracts were probed with pooled sera of infected and non-infected (naturally resistant) individuals from a S. mansoni endemic area. A total of 47 different immunoreactive proteins were identified by mass spectrometry. Although the different pooled sera shared most of the immunoreactive protein spots, nine protein spots reacted exclusively with the serum pool of infected individuals, which correspond to annexin, major egg antigen, troponin T, filamin, disulphide-isomerase ER-60 precursor, actin and reticulocalbin. One protein spot, corresponding to eukaryotic translation elongation factor, reacted exclusively with the pooled sera of non-infected individuals living in the endemic area. Western blotting of two selected recombinant proteins, major egg antigen and hemoglobinase, showed a similar recognition pattern of that of the native protein. Concluding/Significance Using a serological proteome analysis, a group of antigens related to the different infection status of the endemic area residents was identified and may be related to susceptibility or resistance to infection. PMID:24651847

  12. Thoracoscopic examination of empyema in a patient with sparganosis mansoni.

    PubMed

    Takeda, Keita; Suzuki, Junko; Nagai, Hideaki; Watanabe, Kaoru; Yokoyama, Akira; Ando, Takahiro; Suzuki, Jun; Ohshima, Nobuharu; Masuda, Kimihiko; Tamura, Atsuhisa; Akagawa, Shinobu; Kitani, Masashi; Hebisawa, Akira; Matsui, Hirotoshi; Kobayashi, Nobuyuki; Maruyama, Haruhiko; Ohta, Ken

    2016-02-01

    A 27-year-old man was admitted to our hospital with right pleural effusion. He had suffered from right chest and back pain and a high fever for one week prior to the admission. He had been treated with clarithromycin without improvement. Since thoracoscopy under local anesthesia revealed purulent effusion, synechiae and fibrous septa in the thoracic cavity, synechiotomy was performed and we started antibiotic treatment with the diagnosis of acute bacterial empyema. At the same time, we also suspected parasitic infection because of massive eosinophilic infiltration in pleural effusion and his dietary history of eating raw frogs. During the course of the disease, he had an infiltration in the right lower lobe and pneumothorax. Finally, we diagnosed him with sparganosis mansoni because his serum as well as pleural effusion was positive for the binding to sparganosis mansoni plerocercoid antigen, without any positive findings in bacteriology. His pleural effusion and lung infiltration were resolved after the administration of a high-dose praziquantel. We report this rare parasitic empyema with findings by thoracoscopic examination. PMID:26603428

  13. Immunization of mice with ultraviolet-irradiated Schistosoma mansoni cercariae: a re-evaluation

    SciTech Connect

    Dean, D.A.; Murrell, K.D.; Xu, S.; Mangold, B.L.

    1983-07-01

    Mice immunized by percutaneous exposure to ultraviolet-irradiated Schistosoma mansoni cercariae developed levels of resistance to subsequent S. mansoni infection comparable to those induced by gamma-irradiated cercariae (50-70% reduction in adult worm burden). Cercariae treated with ultraviolet doses ranging from one to three times the minimum dose required to prevent long-term survival induced the highest levels of resistance.

  14. Immunization of mice with ultraviolet-irradiated Schistosoma mansoni cercariae: a re-evaluation.

    PubMed

    Dean, D A; Murrell, K D; Xu, S T; Mangold, B L

    1983-07-01

    Mice immunized by percutaneous exposure to ultraviolet-irradiated Schistosoma mansoni cercariae developed levels of resistance to subsequent S. mansoni infection comparable to those induced by gamma-irradiated cercariae (50-70% reduction in adult worm burden). Cercariae treated with ultraviolet doses ranging from one to three times the minimum dose required to prevent long-term survival induced the highest levels of resistance. PMID:6881427

  15. Potential Use of Biomphalaria alexandrina Snail Antigens for Serodiagnosis of Schistosomiasis Mansoni by Immunoblot Analysis

    PubMed Central

    Basyoni, Maha MA; EL-Wahab, Azza Abd

    2013-01-01

    Background The aim of this study was to evaluate the possible use of Biomphalaria alexandrina snail antigens in diagnosis of schistosomiasis mansoni using enzyme linked immunolectrotransfere blot (EITB). Methods S. mansoni adult worm crude antigens (AWA), feet and visceral humps of B. alexandrina and Bulinus truncatus were used. Hyperimmune mice sera (HIS) versus each antigen were prepared for diagnosis of S. mansoni using western blot (WB). Results Snail foot antigens were more specific in antibodies detection than visceral hump antigens. Three of five polypeptides of B. alexandrina foot antigen identified by S. mansoni HIS showed specific positive reactivity. These polypeptides were at MW of 31/32 and 43 kDa. While, only one of the six polypeptides of B. alexandrina hepatopancrease antigen identified by S. mansoni HIS, at a MW of 43 kDa was specific. Similarly, 2 polypeptides at MW of 44 and 55 kDa were specific in detection of anti- S. haematobium antibodies. However, the antigenically active polypeptide of B. truncatus hepatopancrease antigen had no specific reactivity towards anti-S. haematobium antibodies. Conclusion B. alexandrina foot antigens were the most specific of the tested snail antigens in diagnosis of schistosomiasis mansoni. PMID:23682262

  16. Use of Geospatial Modeling to Predict Schistosoma mansoni Prevalence in Nyanza Province, Kenya

    PubMed Central

    Woodhall, Dana M.; Wiegand, Ryan E.; Wellman, Michael; Matey, Elizabeth; Abudho, Bernard; Karanja, Diana M. S.; Mwinzi, Pauline M. N.; Montgomery, Susan P.; Secor, W. Evan

    2013-01-01

    Background Schistosomiasis, a parasitic disease that affects over 200 million people, can lead to significant morbidity and mortality; distribution of single dose preventative chemotherapy significantly reduces disease burden. Implementation of control programs is dictated by disease prevalence rates, which are determined by costly and labor intensive screening of stool samples. Because ecological and human factors are known to contribute to the focal distribution of schistosomiasis, we sought to determine if specific environmental and geographic factors could be used to accurately predict Schistosoma mansoni prevalence in Nyanza Province, Kenya. Methodology/Principal Findings A spatial mixed model was fit to assess associations with S. mansoni prevalence in schools. Data on S. mansoni prevalence and GPS location of the school were obtained from 457 primary schools. Environmental and geographic data layers were obtained from publicly available sources. Spatial models were constructed using ArcGIS 10 and R 2.13.0. Lower S.mansoni prevalence was associated with further distance (km) to Lake Victoria, higher day land surface temperature (LST), and higher monthly rainfall totals. Altitude, night LST, human influence index, normalized difference vegetation index, soil pH, soil texture, soil bulk density, soil water capacity, population, and land use variables were not significantly associated with S. mansoni prevalence. Conclusions Our model suggests that there are specific environmental and geographic factors that influence S. mansoni prevalence rates in Nyanza Province, Kenya. Validation and use of schistosomiasis prevalence maps will allow control programs to plan and prioritize efficient control campaigns to decrease schistosomiasis burden. PMID:23977096

  17. Diagnosis of Schistosoma mansoni without the Stool: Comparison of Three Diagnostic Tests to Detect Schiostosoma mansoni Infection from Filtered Urine in Zambia

    PubMed Central

    Lodh, Nilanjan; Mwansa, James C. L.; Mutengo, Mable M.; Shiff, Clive J.

    2013-01-01

    Diagnosis for intestinal Schistosoma mansoni lacks sensitivity and is arduous to conduct. The standard diagnostic tests, Kato-Katz (KK) and circulating cathodic antigen (CCA) both lack sensitivity and with KK, require obtaining, transporting, and examining fresh stool. We compared diagnostic efficacy of KK, CCA, and polymerase chain reaction (PCR) to detect S. mansoni infection (species-specific DNA) from 89 filtered urine samples collected in Zambia. The PCR was the strongest indicator of positive cases with sensitivity and specificity of 100% in comparison to CCA (67% and 60%) and KK (50% and 100%). High positive and negative predictive values (100%) were also indicative of robustness of PCR. The same pattern was observed when stratified for sex and age group-specific analysis. Diagnosis of S. mansoni from filtered urine samples by PCR is an effective means to detect low intensity infection and would enhance the effectiveness of surveillance and control programs of schistosomiasis. PMID:23716406

  18. Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets

    PubMed Central

    Lancelot, Julien; Caby, Stéphanie; Dubois-Abdesselem, Florence; Vanderstraete, Mathieu; Trolet, Jacques; Oliveira, Guilherme; Bracher, Franz; Jung, Manfred; Pierce, Raymond J.

    2013-01-01

    Background The chemotherapy of schistosomiasis currently depends on the use of a single drug, praziquantel. In order to develop novel chemotherapeutic agents we are investigating enzymes involved in the epigenetic modification of chromatin. Sirtuins are NAD+ dependent lysine deacetylases that are involved in a wide variety of cellular processes including histone deacetylation, and have been demonstrated to be therapeutic targets in various pathologies, including cancer. Methodology, Principal Findings In order to determine whether Schistosoma mansoni sirtuins are potential therapeutic targets we first identified and characterized their protein sequences. Five sirtuins (SmSirt) are encoded in the S. mansoni genome and phylogenetic analysis showed that they are orthologues of mammalian Sirt1, Sirt2, Sirt5, Sirt6 and Sirt7. Both SmSirt1 and SmSirt7 have large insertion in the catalytic domain compared to their mammalian orthologues. SmSirt5 is the only mitochondrial sirtuin encoded in the parasite genome (orthologues of Sirt3 and Sirt4 are absent) and transcripts corresponding to at least five splicing isoforms were identified. All five sirtuins are expressed throughout the parasite life-cycle, but with distinct patterns of expression. Sirtuin inhibitors were used to treat both schistosomula and adult worms maintained in culture. Three inhibitors in particular, Sirtinol, Salermide and MS3 induced apoptosis and death of schistosomula, the separation of adult worm pairs, and a reduction in egg laying. Moreover, Salermide treatment led to a marked disruption of the morphology of ovaries and testes. Transcriptional knockdown of SmSirt1 by RNA interference in adult worms led to morphological changes in the ovaries characterized by a marked increase in mature oocytes, reiterating the effects of sirtuin inhibitors and suggesting that SmSirt1 is their principal target. Conclusion, Significance Our data demonstrate the potential of schistosome sirtuins as therapeutic targets

  19. Characterization of the phytochelatin synthase of Schistosoma mansoni.

    PubMed

    Ray, Debalina; Williams, David L

    2011-05-01

    Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends exclusively on the use of praziquantel. Millions of people are treated annually with praziquantel and drug resistant parasites are likely to evolve. In order to identify novel drug targets the Schistosoma mansoni sequence databases were queried for proteins involved in glutathione metabolism. One potential target identified was phytochelatin synthase (PCS). Phytochelatins are oligopeptides synthesized enzymatically from glutathione by PCS that sequester toxic heavy metals in many organisms. However, humans do not have a PCS gene and do not synthesize phytochelatins. In this study we have characterized the PCS of S. mansoni (SmPCS). The conserved catalytic triad of cysteine-histidine-aspartate found in PCS proteins and cysteine proteases is also found in SmPCS, as are several cysteine residues thought to be involved in heavy metal binding and enzyme activation. The SmPCS open reading frame is considerably extended at both the N- and C-termini compared to PCS from other organisms. Multiple PCS transcripts are produced from the single encoded gene by alternative splicing, resulting in both mitochondrial and cytoplasmic protein variants. Expression of SmPCS in yeast increased cadmium tolerance from less than 50 µM to more than 1,000 µM. We confirmed the function of SmPCS by identifying PCs in yeast cell extracts using HPLC-mass spectrometry. SmPCS was found to be expressed in all mammalian stages of worm development investigated. Increases in SmPCS expression were seen in ex vivo worms cultured in the presence of iron, copper, cadmium, or zinc. Collectively, these results indicate that SmPCS plays an important role in schistosome response to heavy metals and that PCS is a potential drug target for schistosomiasis treatment. This is the first characterization of a PCS from a parasitic organism. PMID:21629724

  20. Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni

    PubMed Central

    Leite, Luiz Arthur Calheiros; Pimenta Filho, Adenor Almeida; Ferreira, Rita de Cássia dos Santos; da Fonseca, Caíque Silveira Martins; dos Santos, Bianka Santana; Montenegro, Silvia Maria Lucena; Lopes, Edmundo Pessoa de Almeida; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lucia de Menezes

    2015-01-01

    Background Schistosomiasis mansoni is a chronic liver disease, in which some patients (5–10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients. Methodology/Principal Findings Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1. Conclusion/Significance This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status. PMID:26267788

  1. Frequency and mitotic heritability of epimutations in Schistosoma mansoni.

    PubMed

    Roquis, David; Rognon, Anne; Chaparro, Cristian; Boissier, Jerome; Arancibia, Nathalie; Cosseau, Celine; Parrinello, Hugues; Grunau, Christoph

    2016-04-01

    Schistosoma mansoni is a parasitic platyhelminth responsible for intestinal bilharzia. It has a complex life cycle, infecting a freshwater snail of the Biomphalaria genus, and then a mammalian host. Schistosoma mansoni adapts rapidly to new (allopatric) strains of its intermediate host. To study the importance of epimutations in this process, we infected sympatric and allopatric mollusc strains with parasite clones. ChIP-Seq was carried out on four histone modifications (H3K4me3, H3K27me3, H3K27ac and H4K20me1) in parallel with genomewide DNA resequencing (i) on parasite larvae shed by the infected snails and (ii) on adult worms that had developed from the larvae. No change in single nucleotide polymorphisms and no mobilization of transposable elements were observed, but 58-105 copy number variations (CNVs) within the parasite clones in different molluscs were detected. We also observed that the allopatric environment induces three types of chromatin structure changes: (i) host-induced changes on larvae epigenomes in 51 regions of the genome that are independent of the parasites' genetic background, (ii) spontaneous changes (not related to experimental condition or genotype of the parasite) at 64 locations and (iii) 64 chromatin structure differences dependent on the parasite genotype. Up to 45% of the spontaneous, but none of the host-induced chromatin structure changes were transmitted to adults. In our model, the environment induces epigenetic changes at specific loci but only spontaneous epimutations are mitotically heritable and have therefore the potential to contribute to transgenerational inheritance. We also show that CNVs are the only source of genetic variation and occur at the same order of magnitude as epimutations. PMID:26826554

  2. Characterization of the Phytochelatin Synthase of Schistosoma mansoni

    PubMed Central

    Ray, Debalina; Williams, David L.

    2011-01-01

    Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends exclusively on the use of praziquantel. Millions of people are treated annually with praziquantel and drug resistant parasites are likely to evolve. In order to identify novel drug targets the Schistosoma mansoni sequence databases were queried for proteins involved in glutathione metabolism. One potential target identified was phytochelatin synthase (PCS). Phytochelatins are oligopeptides synthesized enzymatically from glutathione by PCS that sequester toxic heavy metals in many organisms. However, humans do not have a PCS gene and do not synthesize phytochelatins. In this study we have characterized the PCS of S. mansoni (SmPCS). The conserved catalytic triad of cysteine-histidine-aspartate found in PCS proteins and cysteine proteases is also found in SmPCS, as are several cysteine residues thought to be involved in heavy metal binding and enzyme activation. The SmPCS open reading frame is considerably extended at both the N- and C-termini compared to PCS from other organisms. Multiple PCS transcripts are produced from the single encoded gene by alternative splicing, resulting in both mitochondrial and cytoplasmic protein variants. Expression of SmPCS in yeast increased cadmium tolerance from less than 50 µM to more than 1,000 µM. We confirmed the function of SmPCS by identifying PCs in yeast cell extracts using HPLC-mass spectrometry. SmPCS was found to be expressed in all mammalian stages of worm development investigated. Increases in SmPCS expression were seen in ex vivo worms cultured in the presence of iron, copper, cadmium, or zinc. Collectively, these results indicate that SmPCS plays an important role in schistosome response to heavy metals and that PCS is a potential drug target for schistosomiasis treatment. This is the first characterization of a PCS from a parasitic organism. PMID:21629724

  3. Influence of Schistosoma mansoni and Hookworm Infection Intensities on Anaemia in Ugandan Villages

    PubMed Central

    Chami, Goylette F.; Fenwick, Alan; Bulte, Erwin; Kontoleon, Andreas A.; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

    2015-01-01

    Background The association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women. Methods We sampled 1,832 individuals aged 5–90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated. Findings Household and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001). Conclusion Community-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes. PMID:26513151

  4. Impact of gold nanoparticles on brain of mice infected with Schistosoma mansoni.

    PubMed

    Dkhil, Mohamed A; Bauomy, Amira A; Diab, Marwa S M; Wahab, Rizwan; Delic, Denis; Al-Quraishy, Saleh

    2015-10-01

    Schistosomiasis is a condition characterized by high rates of morbidity and cognitive impairment. It afflicts many people in tropical and sub-tropical countries. Our study aimed to investigate the protective role of gold nanoparticles (GNPs) on the brain of mice infected with Schistosoma mansoni. Characterizations of GNPs were determined by using high-resolution transmission electron microscopy. Three doses of GNPs (0.25, 0.5, and 1.0 mg/kg body weight) were used to treat animals after S. mansoni infection. The infection induced impairments in histological picture as a result of schistosome infection resulting in a disturbance in the content of the brain neurotransmitters, norepinephrine (NE), and dopamine (DA). Also, the infection induced significant reduction in glutathione level; oppositely, the levels of nitric oxide and malondialdehyde were increased significantly. In addition, S. mansoni was able to disregulate the infected mice brain Cacnb4, Cabp4, Vdac3, Glrb, and Adam23 messenger RNA (mRNA). On the other hand, treatment of mice with GNPs could alleviate the histological impairments, the changes in the content of NE and DA, and the brain oxidative damage. Also, GNPs could regulate the gene expression due to S. mansoni infection. Generally, GNPs could decrease the neurooxidative stress and regulated the gene expression in the brain of infected mice. Consequently, our results revealed an anti-neuroschistosomal effect of GNPs in mice infected with S. mansoni. PMID:26122996

  5. Increase of malaria attacks among children presenting concomitant infection by Schistosoma mansoni in Senegal

    PubMed Central

    Sokhna, Cheikh; Le Hesran, Jean-Yves; Mbaye, Pape A; Akiana, Jean; Camara, Pape; Diop, Mamadou; Ly, Abdoulaye; Druilhe, Pierre

    2004-01-01

    Helminthic infections concomitant with malaria are common in inter-tropical areas. A recent study showed that mice co-infected with Schistosoma mansoni and Plasmodium chabaudi develop higher P. chabaudi parasitaemia and had a higher mortality rate. This important observation deserved to be further investigated among human populations. Malaria attacks were recorded in 512 children aged 6–15 years living in Richard Toll (Northern Senegal) among whom 336 were infected by S. mansoni, and 175 were not. The incidence rate of malaria attacks was significantly higher among S. mansoni-infected individuals, particularly those carrying the highest worm loads, as compared to uninfected subjects (26.6% versus 16,4 %). In contrast, the rate of malaria attacks was lower, without reaching significance, in medium grade S. mansoni infections. Thus, infection by S. mansoni affects susceptibility to malaria, but this can vary according to the intensity of parasite load. The immunological mechanisms underlying this dual effect need to be further explored. PMID:15544703

  6. Schistosoma mansoni shares a protective carbohydrate epitope with keyhole limpet hemocyanin

    PubMed Central

    1987-01-01

    The glycanic epitope of the 38,000 Mr Schistosoma mansoni schistosomula major immunogen defined by the IPLSm1 protective mAb was identified in the hemocyanin of the marine mollusc Megathura crenulata, better known as KLH. This antigenic community was exploited to investigate further the biological properties of this epitope. KLH was shown to strongly inhibit the binding of IPLSm1 mAb to its 38,000 Mr target antigen. Immunization of naive LOU rats with KLH elicited the production of anti- S. mansoni antibodies capable of immunoprecipitating the 38,000 Mr schistosomulum antigen. Antibodies to KLH mediated a marked eosinophil- dependent cytotoxicity and passively transferred immunity towards S. mansoni infection. Finally, rats immunized with KLH were significantly protected against a challenge with S. mansoni cercariae. The deglycosylation of KLH completely abolishes its immunological and functional KLH properties, indicating the participation of an oligosaccharidic epitope of the native KLH that is also recognized by the sera of S. mansoni-infected patients. These observations provide new opportunities of access to the well-defined structure of a glycanic epitope potentially available for the immunoprophylaxis and seroepidemiology of schistosomiasis, and a new approach to the isotypic response towards a well-chemically defined epitope. PMID:2434601

  7. Comparison of cysteine peptidase activities in Trichobilharzia regenti and Schistosoma mansoni cercariae.

    PubMed

    Kasný, M; Mikes, L; Dalton, J P; Mountford, A P; Horák, P

    2007-10-01

    Cercariae of the bird schistosome Trichobilharzia regenti and of the human schistosome Schistosoma mansoni employ proteases to invade the skin of their definitive hosts. To investigate whether a similar proteolytic mechanism is used by both species, cercarial extracts of T. regenti and S. mansoni were biochemically characterized, with the primary focus on cysteine peptidases. A similar pattern of cysteine peptidase activities was detected by zymography of cercarial extracts and their chromatographic fractions from T. regenti and S. mansoni. The greatest peptidase activity was recorded in both species against the fluorogenic peptide substrate Z-Phe-Arg-AMC, commonly used to detect cathepsins B and L, and was markedly inhibited (> 96%) by Z-Phe-Ala-CHN2 at pH 4.5. Cysteine peptidases of 33 kDa and 33-34 kDa were identified in extracts of T. regenti and S. mansoni cercariae employing a biotinylated Clan CA cysteine peptidase-specific inhibitor (DCG-04). Finally, cercarial extracts from both T. regenti and S. mansoni were able to degrade native substrates present in skin (collagen II and IV, keratin) at physiological pH suggesting that cysteine peptidases are important in the pentration of host skin. PMID:17517170

  8. Brain magnetic resonance imaging findings in young patients with hepatosplenic schistosomiasis mansoni without overt symptoms.

    PubMed

    Manzella, Adonis; Borba-Filho, Paulo; Brandt, Carlos T; Oliveira, Keyla

    2012-06-01

    The purpose of this study was to describe the brain magnetic resonance imaging (MRI) findings in young patients with hepatosplenic schistosomiasis mansoni without overt neurologic manifestations. This study included 34 young persons (age range = 9-25 years) with hepatosplenic schistosomiasis mansoni who had been previously treated. Patients were scanned on a 1.5-T system that included multiplanar pre-contrast and post-contrast sequences, and reports were completed by two radiologists after a consensus review. Twenty (58.8%) patients had MRI signal changes that were believed to be related to schistosomiasis mansoni. Twelve of the 20 patients had small focal hyperintensities on T2WI in the cerebral white matter, and eight patients had symmetric hyperintense basal ganglia on T1WI. There was a high frequency of brain MRI signal abnormalities in this series. Although not specific, these findings may be related to schistosomiasis. PMID:22665605

  9. From Incidentaloma to Suspicion of Malignancy: The Diverse Clinical Presentation of Gonadal Schistosomiasis mansoni

    PubMed Central

    Almeida, Laiana do Carmo; de Oliveira, Marbele Guimarães; Castro Pereira, Fábio Meira; de Bessa Júnior, José

    2013-01-01

    Schistosomiasis is the second most widespread parasitic disease in the world, second only to malaria. The usual places the Schistosoma mansoni can be found in are the rectal and sigmoidal venules, as well as other segments of the large intestine of men. It may also be present in other ectopic topographies. Gonadal schistosomiasis is an unusual presentation of Schistosomiasis mansoni and its different clinical signs and symptoms disrupt correct diagnosis and culminate in surgical treatment that is, in most cases, unnecessary. In this study, we report four cases of gonadal Schistosomiasis mansoni, two in the ovary and two in the testicles. These cases were clinically investigated as a bacterial infection, a benign neoplasm, and a suspected cancer, whilst one of them was an incidentaloma. PMID:24392230

  10. Emergence of cercariae of Echinostoma caproni and Schistosoma mansoni from Biomphalaria glabrata under different laboratory conditions.

    PubMed

    Fried, B; LaTerra, R; Kim, Y

    2002-12-01

    Release of Echinostoma caproni cercariae and Schistosoma mansoni from experimentally infected Biomphalaria glabrata snails maintained under different laboratory conditions was studied. Infected snails were isolated individually for 1 h in Stender dishes containing 5 ml of artificial spring water and the number of cercariae released during this time was recorded. Of numerous conditions tested, the addition of lettuce, the use of water conditioned by B. glabrata snails and a temperature of 35 degrees C significantly increased the release of E. caproni cercariae. A significant increase in cercarial release of S. mansoni was seen only in cultures fed lettuce. A temperature of 12 degrees C caused a significant decrease in cercarial release of both E. caproni and S. mansoni. Increased snail activity associated with feeding behaviour was probably responsible for the enhanced cercarial sheds observed in this study. PMID:12498644

  11. Schistosoma mansoni larvicidal activity of murine bronchoalveolar lavage cells.

    PubMed

    Lewis, F A; White-Ziegler, C A; Ball, J E; Niemann, G M

    1990-12-01

    We have investigated the ability of cells obtained from both normal and immune mice by bronchoalveolar lavage (BACs) to kill Schistosoma mansoni larvae in vitro. In cultures with mechanically derived schistosomules, high levels of larvicidal activity were displayed by BACs from both normal and irradiated cercaria-immunized C57BL/6 mice. Based on effector-to-target-cell ratios, BAC-mediated killing was two- to threefold more efficient than killing mediated by macrophage-rich cell populations obtained from the peritoneal cavity. BACs from normal A/J mice were essentially as larvicidal as normal C57BL/6 cells. However, BACs from a strain of mouse (P/J) with a known macrophage defect possessed negligible larvicidal activity. Macrophages made up 85 to 95% of BACs from all three strains tested. In contrast to cells of the IC-21 macrophage cell line, B6 BACs did not show enhanced killing activity when preincubated with lymphokine-containing supernatants. Lung schistosomules harvested 10 days after cercarial penetration were refractory to BAC-mediated killing. PMID:2254018

  12. Schistosoma mansoni larvicidal activity of murine bronchoalveolar lavage cells.

    PubMed Central

    Lewis, F A; White-Ziegler, C A; Ball, J E; Niemann, G M

    1990-01-01

    We have investigated the ability of cells obtained from both normal and immune mice by bronchoalveolar lavage (BACs) to kill Schistosoma mansoni larvae in vitro. In cultures with mechanically derived schistosomules, high levels of larvicidal activity were displayed by BACs from both normal and irradiated cercaria-immunized C57BL/6 mice. Based on effector-to-target-cell ratios, BAC-mediated killing was two- to threefold more efficient than killing mediated by macrophage-rich cell populations obtained from the peritoneal cavity. BACs from normal A/J mice were essentially as larvicidal as normal C57BL/6 cells. However, BACs from a strain of mouse (P/J) with a known macrophage defect possessed negligible larvicidal activity. Macrophages made up 85 to 95% of BACs from all three strains tested. In contrast to cells of the IC-21 macrophage cell line, B6 BACs did not show enhanced killing activity when preincubated with lymphokine-containing supernatants. Lung schistosomules harvested 10 days after cercarial penetration were refractory to BAC-mediated killing. PMID:2254018

  13. Protein acetylation sites mediated by Schistosoma mansoni GCN5

    SciTech Connect

    Moraes Maciel, Renata de; Furtado Madeiro da Costa, Rodrigo; Meirelles Bastosde Oliveira, Francisco; Rumjanek, Franklin David; Fantappie, Marcelo Rosado

    2008-05-23

    The transcriptional co-activator GCN5, a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcription activation. As in other eukaryotes, the DNA from the parasite Schistosome mansoni is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Using a series of synthetic peptides we determined that Lys-14 of histone H3 was acetylated by the recombinant SmGCN5-HAT domain. SmGCN5 was also able to acetylate schistosome non-histone proteins, such as the nuclear receptors SmRXR1 and SmNR1, and the co-activator SmNCoA-62. Electron microscopy revealed the presence of SmGCN5 protein in the nuclei of vitelline cells. Within the nucleus, SmGCN5 was found to be located in interchromatin granule clusters (IGCs), which are transcriptionally active structures. The data suggest that SmGCN5 is involved in transcription activation.

  14. Levels of Schistosoma mansoni Circulating Antigen in Chronic Hepatitis C Patients with Different Stages of Liver Fibrosis.

    PubMed

    Attallah, Abdelfattah M; El-Far, Mohamed; Omran, Mohamed M; Farid, Khaled; Attallah, Ahmed A; Abd-Elaziz, Dalal; El-Bendary, Mohamed S; El-Dosoky, Ibrahim; Ismail, Hisham

    2016-01-01

    The goal of this study was to determine the levels of S. mansoni antigen in different liver fibrosis stages with chronic hepatitis C (CHC) Egyptian patients. A total of 174 CHC patients showing HCV-NS4 antigen and HCV- RNA in their sera were included. S. mansoni antigen was detected in serum using Western blot and ELISA. The levels of interferon-γ (IFN- γ) were determined using ELISA. The 50 kDa S. mansoni antigen discriminated patients infected with S. mansoni from healthy individuals with 0.93 area under curve (AUC), 92% sensitivity, and 97% specificity. The level of S. mansoni antigen (μg/ml) was significantly (P < 0.0001) increased with the progression of liver fibrosis stages (26.9 ± 17.5 in F1, 42.1 ± 25.2 in F2, 49.8 ± 30.3 in F3 and 62.2 ± 26.3 μg/mL in F4 liver cirrhosis), 26.9 ± 17.59 in significant fibrosis (F2-F4); 51.2 ± 27.9 in advanced fibrosis (F3-F4). A significant correlation (r = 0.506; P < 0.0001) was shown between the levels of the S. mansoni antigen and the HCV-NS4 antigen. In conclusion, the presence of S. mansoni antigen in different liver fibrosis stages of CHC patients confirming that concomitant schistosome infection aggravates liver disease. PMID:26745203

  15. Experimental evaluation of Candonocypris novaezelandiae (Crustacea: Ostracoda) in the biocontrol of Schistosomiasis mansoni transmission

    PubMed Central

    Yousif, Fouad; Hafez, Sherif; El Bardicy, Samia; Tadros, Menerva; Taleb, Hoda Abu

    2013-01-01

    Objective To test Candonocypris novaezelandiae (Baird) (C. novaezelandiae), sub-class Ostracoda, obtained from the Nile, Egypt for its predatory activity on snail, Biomphalaria alexandrina (B. alexandrina), intermediate host of Schistosoma mansoni (S. mansoni) and on the free-living larval stages of this parasite (miracidia and cercariae). Methods The predatory activity of C. novaezelandiae was determined on B. alexandrina snail (several densities of eggs, newly hatched and juveniles). This activity was also determined on S. mansoni miracidia and cercariae using different volumes of water and different numbers of larvae. C. novaezelandiae was also tested for its effect on infection of snails and on the cercarial production. Results C. novaezelandiae was found to feed on the eggs, newly hatched and juvenile snails, but with significant reduction in the consumption in the presence of other diet like the blue green algae (Nostoc muscorum). This ostracod also showed considerable predatory activity on the free-living larval stages of S. mansoni which was affected by certain environmental factors such as volume of water, density of C. novaezelandiae and number of larvae of the parasite. Conclusions The presence of this ostracod in the aquatic habitat led to significant reduction of snail population, infection rate of snails with schistosme miracidia as well as of cercarial production from the infected snails. This may suggest that introducing C. novaezelandiae into the habitat at schistosome risky sites could suppress the transmission of the disease. PMID:23620849

  16. Effect of bee venom or proplis on molecular and parasitological aspects of Schistosoma mansoni infected mice.

    PubMed

    Mohamed, Azza H; Hassab El-Nabi, Sobhy E; Bayomi, Asmaa E; Abdelaal, Ahmed A

    2016-06-01

    The present study was performed to elucidate the efficacy of Apis mellifera L bee venom (BV) or proplis (200 mg/kg orally for three consecutive days) on Schistosoma mansoni infected mice. The results recorded reduction in the total worm burden, numbers of immature eggs and the ova count in hepatic tissue in BV (sting or injection) or proplis treated groups as compared to the infected group. Histological examination illustrated a significant increase (P ≤ 0.05) in the diameter of hepatic granuloma in BV treated groups (272.78 and 266.9, respectively) and a significant decrease in proplis treated mice (229.35) compared with the infected group (260.67). Electrophoretic pattern of RNA showed a decrease in mean of maximal optical density in liver and intestine of S. mansoni infected mice treated with bee venom (sting or injection) as compared with infected group. Flow cytometry analyses of RNA or apoptotic percentage of worms recovered from BV sting (19 and 49 % respectively); BV injected (20.5 and 51.17 %, respectively) and proplis (35 and 23.93 %, respectively) groups were compared with S. mansoni infected group (37.87 and 39.21 %, respectively). It can be concluded that administration of bee venom or proplis are effective in case of S. mansoni infection. Although bee venom cause increase of granuloma diameter and this might be due to venom concentration and further studies are required to avoid such harmful effect. PMID:27413311

  17. Immunological characterization of a chimeric form of Schistosoma mansoni aquaporin in the murine model.

    PubMed

    Figueiredo, Barbara Castro Pimentel; De Assis, Natan Raimundo Gonçalves; De Morais, Suellen Batistoni; Martins, Vicente Paulo; Ricci, Natasha Delaqua; Bicalho, Rodrigo Marques; Pinheiro, Carina Da Silva; Oliveira, Sergio Costa

    2014-09-01

    Aquaporin (SmAQP) is the most abundant transmembrane protein in the tegument of Schistosoma mansoni. This protein is expressed in all developmental stages and seems to be essential in parasite survival since it plays a crucial role in osmoregulation, nutrient transport and drug uptake. In this study, we utilized the murine model to evaluate whether this protein was able to induce protection against challenge infection with S. mansoni cercariae. A chimeric (c) SmAQP was formulated with Freund's adjuvant for vaccination trial and evaluation of the host's immune response was performed. Our results demonstrated that immunization with cSmAQP induced the production of high levels of specific anti-cSmAQP IgG antibodies and a Th1/Th17 type of immune response characterized by IFN-γ, TNF-α and IL-17 cytokines. However, vaccination of mice with cSmAQP failed to reduce S. mansoni worm burden and liver pathology. Finally, we were unable to detect humoral immune response anti-cSmAQP in the sera of S. mansoni-infected human patients. Our results lead us to believe that SmAQP, as formulated in this study, may not be a good target in the search for an anti-schistosomiasis vaccine. PMID:24786243

  18. Anthelmintic effects of the essential oil of fennel (Foeniculum vulgare Mill., Apiaceae) against Schistosoma mansoni.

    PubMed

    Wakabayashi, Kamila A L; de Melo, Nathalya I; Aguiar, Daniela P; de Oliveira, Pollyanna F; Groppo, Milton; da Silva Filho, Ademar A; Rodrigues, Vanderlei; Cunha, Wilson R; Tavares, Denise C; Magalhães, Lizandra G; Crotti, Antônio E M

    2015-07-01

    Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 μg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity. PMID:26172330

  19. BLOCKADE OF PGE2, PGD2 RECEPTORS CONFERS PROTECTION AGAINST PREPATENT SCHISTOSOMIASIS MANSONI IN MICE.

    PubMed

    Abdel-Ghany, Rasha; Rabia, Ibrahim; El-Ahwany, Eman; Saber, Sameh; Gamal, Rasha; Nagy, Faten; Mahmoud, Olaa; Hamad, Rabab Salem; Barakat, Walled

    2015-12-01

    Schistosomiasis is a chronic disease with considerable social impact. Despite the availability of affordable chemotherapy, drug treatment has not significantly reduced the overall number of disease cases. Among other mechanisms, the parasite produces PGE2 and PGD2 to evade host immune defenses. To investigate the role of PGE2 and PGD2 in schistosomiasis, we evaluated the effects of L-161,982, Ah6809 (PGE2 receptor antagonists alone of combined with each other) and MK-0524 (PGD2 receptor antagonist) during prepatent Schistosoma mansoni infection. Drugs were administered intraperitoneally an hour before and 24 hours after infection of C57BL/6 mice with 100 Schistosoma mansoni cercariae. L-161,982, Ah6809, their combination and MK-0524 caused partial protection against pre-patent S. mansoni infection which was mediated by biasing the immune response towards Th1 phenotype. These results showed that blockade of PGE2 and PGD2 receptors confers partial protection against pre-patent S. mansoni infection in mice and that they may be useful as adjunctive therapy to current anti-schistosomal drugs or vaccines. PMID:26939228

  20. Immunoproteomic Analysis of the Excretory-Secretory Proteins from Spirometra mansoni Sparganum

    PubMed Central

    HU, Dan Dan; CUI, Jing; WANG, Li; LIU, Li Na; WEI, Tong; WANG, Zhong Quan

    2013-01-01

    Background Sparganosis is caused by the invasion of Spirometra sparganum into various tissues/organs. Subcutaneous sparganosis can be diagnosed by biopsy, while visceral/cerebral sparganosis is not easy to be diagnosed. The diagnosis depends largely on the detection of specific anti-sparganum antibodies. The specificity of the ELISA could be increased by using S. mansoni sparganum excretory–secretory (ES) antigens, but it also had the cross-reactions with sera of patients with cysticercosis or paragonimiasis. The aim of this study was to identify early specific diagnostic antigens in S. mansoni sparganum ES proteins. Methods The sparganum ES proteins were analyzed by two-dimensional electrophoresis (2-DE) and Western blot probed with early sera from infected mice at 14 days post-infection. The immunoreactive protein spots were characterized by MALDI-TOF/ TOF-MS. Results A total of approximately 149 proteins spots were detected with isoelectric point (pI) varying from 3 to 7.5 and molecular weight from 20 to 115 kDa and seven protein spots with molecular weight of 23-31 kDa were recognized by the infection sera. Three of seven spots were successfully identified and characterized as the same S. mansoni protein (cysteine protease), and the proteins of other 4 spots were not included in the databases. Conclusion The cysteine protease from S. mansoni ES proteins recognized by early infection sera might be the early diagnostic antigens for sparganosis. PMID:24454434

  1. The hepatoprotective activity of blue green algae in Schistosoma mansoni infected mice.

    PubMed

    Mohamed, Azza H; Osman, Gamalat Y; Salem, Tarek A; Elmalawany, Alshimaa M

    2014-10-01

    This study aims to evaluate the immunomodulatory effects of a natural product, blue green algae (BGA) (100 mg/kg BW), alone or combined with praziquantel PZQ (250 mg/kg BW) on granulomatous inflammation, liver histopathology, some biochemical and immunological parameters in mice infected with Schistosoma mansoni. Results showed that the diameter and number of egg granuloma were significantly reduced after treatment of S. mansoni-infected mice with BGA, PZQ and their combination. The histopathological alterations observed in the liver of S. mansoni-infected mice were remarkably inhibited after BGA treatments. BGA decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as well as the level of total protein (TP) while the level of albumin was increased. Treatment of infected mice with BGA, PZQ as well as their combination led to significant elevation in the activities of hepatic antioxidant enzymes glutathione peroxidase (GPX) and glutathione-S-transferase (GST) as compared with control group. Combination of BGA and PZQ resulted in significant reduction in the level of intercellular adhesion molecules-1 (ICAM-1), vascular adhesion molecules-1 (VCAM-1) and tumor necrosis factor-alpha (TNF-α) when compared to those of the S. mansoni-infected group. Overall, BGA significantly inhibited the liver damage accompanied with schistosomiasis, exhibited a potent antioxidant and immunoprotective activities. This study suggests that BGA can be considered as promising for development a complementary and/or alternative medicine against schistosomiasis. PMID:25016189

  2. Activity of Praziquantel Enantiomers and Main Metabolites against Schistosoma mansoni

    PubMed Central

    Meister, Isabel; Ingram-Sieber, Katrin; Cowan, Noemi; Todd, Matthew; Robertson, Murray N.; Meli, Claudia; Patra, Malay; Gasser, Gilles

    2014-01-01

    A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R- and S-cis- and R- and S-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans- and R-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adult S. mansoni were determined in vitro. S-trans- and S-cis-4′-hydroxypraziquantel were not active at 100 μg/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ. PMID:24982093

  3. Human immune responses to Schistosoma mansoni vaccine candidate antigens.

    PubMed

    Ribeiro de Jesus, A; Araújo, I; Bacellar, O; Magalhães, A; Pearce, E; Harn, D; Strand, M; Carvalho, E M

    2000-05-01

    To determine the naturally occurring immunological responses to the Schistosoma mansoni antigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including "resistant" subjects (n = 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP- and paramyosin-specific IgG1 and IgG4 (P < 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P < 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-gamma levels in PBMC supernatants stimulated with paramyosin (P < 0.05) and IrV-5 (P < 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3- and MAP-4-stimulated PBMC supernatants (P < 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio = 11.2 [95% confidence interval, 2.7 to 45.8]). PMID:10768975

  4. Adult somatic stem cells in the human parasite, Schistosoma mansoni

    PubMed Central

    Collins, James J.; Wang, Bo; Lambrus, Bramwell G.; Tharp, Marla; Iyer, Harini; Newmark, Phillip A.

    2013-01-01

    Summary Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide1. The etiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades2, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms3,4 (e.g., planarians), and neoblast-like cells have been described in some parasitic tapeworms5, little is known about whether similar cell types exist in any trematode species. Here, we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources6,7 and RNAseq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor ortholog. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations suggest that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes likely contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites. PMID:23426263

  5. Characterization of the Ras homologue of Schistosoma mansoni.

    PubMed

    Osman, A; Niles, E G; LoVerde, P T

    1999-05-15

    Ras is a member of a super-family of guanine-binding or G-proteins. Ras functions as a molecular switch in the transduction of signals generated by the activation of a variety of cell surface receptors and relays the signals to downstream effectors. Little is known about signal transduction in schistosomes. In order for Schistosoma mansoni to survive different immune responses triggered by the host as well as to migrate from the site of penetration at the skin to the final destination in portal circulation, they must receive signals from the host environment and respond to them in a way that allows their survival. We have isolated the schistosome Ras cDNA by using sequence information of the schistosome Ras homologue submitted to the Genbank database. Analysis of the encoded peptide revealed 81% identity and 92% similarity with K-Ras from various species. Ras is a single copy gene as determined by quantitative hybridization experiments. The cDNA was cloned into pGEX-4T and the expressed peptide was used to generate specific antibody reagents. Affinity purified antibodies identified a 23 kDa native protein that localizes to the subtegument. Ras is not associated with the tegument. Ras is expressed in all the developmental stages of the parasite. However, Ras is over-expressed in female worms compared to males. Schistosome Ras was also shown to be post-translationally modified by addition of farnesyl isoprenoid moiety to the cysteine residue in the C-terminal box. Using a schistosome extract in vitro SmRas farnesylation was inhibited by the farnesyl transferase inhibitor, FTI-277, at concentrations comparable to those required to inhibit K-Ras processing. These initial studies on signal transduction in schistosomes should provide a solid basis for improving our understanding of schistosome-host interactions. PMID:10376991

  6. Tandem repeat recombinant proteins as potential antigens for the sero-diagnosis of Schistosoma mansoni infection.

    PubMed

    Kalenda, Yombo Dan Justin; Kato, Kentaro; Goto, Yasuyuki; Fujii, Yoshito; Hamano, Shinjiro

    2015-12-01

    The diagnosis of schistosome infection, followed by effective treatment and/or mass drug administration, is crucial to reduce the disease burden. Suitable diagnostic tests and field-applicable tools are required to sustain schistosomiasis control programs. We therefore assessed the potential of tandem repeat (TR) proteins for sero-diagnosis of Schistosoma mansoni infection using an experimental mouse model. TR genes in the genome of S. mansoni were searched in silico and 7 candidates, named SmTR1, 3, 8, 9, 10, 11 and 15, were selected. Total RNA was extracted from S. mansoni adult worms and eggs. Target TR genes were amplified, cloned, and the proteins were expressed in Escherichia coli competent cells. Female BALB/c mice were infected with 100 S. mansoni cercariae and sera were collected each week post-infection for 18 weeks. The levels of IgG antibodies to SmTR antigens were compared to those to soluble egg antigen (SEA) and to soluble worm antigen preparation (SWAP). Sera of infected mice reacted to all the antigens whereas those of naïve mice did not. IgG responses to SmTR1, 3, 9 and 10 were detected at the early stage of infection. Interestingly, antibodies reacting to SmTR3, 9, 10 and 15 dramatically decreased 4 weeks after treatment with praziquantel, while those against SEA and SWAP remained elevated. Our study suggests that TR proteins, especially SmTR10, may be suitable antigens for sero-diagnosis of infection by S. mansoni and are potential markers for monitoring and surveillance of schistosomiasis, including re-infection after treatment with praziquantel. PMID:26148816

  7. Reconstructing Colonization Dynamics of the Human Parasite Schistosoma mansoni following Anthropogenic Environmental Changes in Northwest Senegal

    PubMed Central

    Van den Broeck, Frederik; Maes, Gregory E.; Larmuseau, Maarten H. D.; Rollinson, David; Sy, Ibrahima; Faye, Djibril; Volckaert, Filip A. M.; Polman, Katja; Huyse, Tine

    2015-01-01

    Background Anthropogenic environmental changes may lead to ecosystem destabilization and the unintentional colonization of new habitats by parasite populations. A remarkable example is the outbreak of intestinal schistosomiasis in Northwest Senegal following the construction of two dams in the ‘80s. While many studies have investigated the epidemiological, immunological and geographical patterns of Schistosoma mansoni infections in this region, little is known about its colonization history. Methodology/Principal Findings Parasites were collected at several time points after the disease outbreak and genotyped using a 420 bp fragment of the mitochondrial cytochrome c oxidase subunit 1 gene (cox1) and nine nuclear DNA microsatellite markers. Phylogeographic and population genetic analyses revealed the presence of (i) many genetically different haplotypes at the non-recombining mitochondrial marker and (ii) one homogenous S. mansoni genetic group at the recombining microsatellite markers. These results suggest that the S. mansoni population in Northwest Senegal was triggered by intraspecific hybridization (i.e. admixture) between parasites that were introduced from different regions. This would comply with the extensive immigration of infected seasonal agricultural workers from neighboring regions in Senegal, Mauritania and Mali. The spatial and temporal stability of the established S. mansoni population suggests a swift local adaptation of the parasite to the local intermediate snail host Biomphalaria pfeifferi at the onset of the epidemic. Conclusions/Significance Our results show that S. mansoni parasites are very successful in colonizing new areas without significant loss of genetic diversity. Maintaining high levels of diversity guarantees the adaptive potential of these parasites to cope with selective pressures such as drug treatment, which might complicate efforts to control the disease. PMID:26275049

  8. Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial.

    PubMed Central

    Ferrari, M. L. A.; Coelho, P. M. Z.; Antunes, C. M. F.; Tavares, C. A. P.; da Cunha, A. S.

    2003-01-01

    OBJECTIVE: To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection. METHODS: In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The chi2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments. FINDINGS: The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%. CONCLUSIONS: Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides. PMID:12764515

  9. Soil-Transmitted Helminths and Schistosoma mansoni Infections in Ethiopian Orthodox Church Students around Lake Tana, Northwest Ethiopia

    PubMed Central

    Afework Bitew, Aschalew; Abera, Bayeh; Seyoum, Walle; Endale, Befekadu; Kiber, Tibebu; Goshu, Girma; Admass, Addiss

    2016-01-01

    Background Soil-transmitted helminths (STH) and Schistosoma mansoni infections are the major neglected tropical diseases that result in serious consequences on health, education and nutrition in children in developing countries. The Ethiopian Orthodox church students, who are called Yekolotemari in Amharic, live in areas with poor sanitation and hygiene. Moreover, they are not included in the national STH control programs. Thus, STH and S. mansoni infections prevalence is unknown. Methods A cross-sectional study was conducted on 384 students in June 2014 to determine STH and S. mansoni infections prevalence. Moreover, the knowledge of students about STH and S. mansoni was assessed. Data on knowledge and clinical symptoms were collected using structured questionnaires via face to face interview. Stool specimens were examined by formol-ether concentration method. Results The overall prevalence of intestinal helminths infections was 85.9% (95% confidence interval (CI): 82.1–89%). STHs infections prevalence was 65.6% (95% CI: 60.7–70.2%). The prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura were 31.8% (95% CI: 27.3–36.6%), 29.4% (25–31%) and 3.1% (1.8–5.4%), respectively. On the other hand, S. mansoni prevalence was 14.3% (95% CI: 11.1–18.1%). Majority of students infected with S. mansoni had bloody stool with crud odds-ratio of 2.9 (95% CI: 1.5–5.5). Knowledge assessment showed that 50 (13%) and 18 (4.9%) of the respondents knew about transmission of STH and S. mansoni, respectively. Conclusions The prevalence of STH and S. mansoni infections were high thus de-worming program should include the students of Ethiopian Orthodox churches. Furthermore, provision and use of sanitary facilities, health education for students to create awareness of parasitic infections and improved personal hygiene should be in place. PMID:27203749

  10. Cercarial transformation and in vitro cultivation of Schistosoma mansoni schistosomules.

    PubMed

    Milligan, John N; Jolly, Emmitt R

    2011-01-01

    Schistosome parasites are the causative agents of schistosomiasis, a chronically debilitating disease that affects over 200 million people globally and ranks second to malaria among parasitic diseases in terms of public health and socio-economic impact (1-4). Schistosome parasites are trematode worms with a complex life cycle interchanging between a parasitic life in molluscan and mammalian hosts with intervening free-swimming stages. Briefly, free-swimming cercariae infect a mammalian host by penetrating the skin with the aid of secreted proteases, during which time the cercariae lose their tails, transforming into schistosomules. The schistosomules must now evade the host immune system, develop a gut for digestion of red blood cells, and migrate though the lungs and portal circulation en route to their final destination in the hepatic portal system and eventually the mesenteric veins (for S. mansoni) where male and female worms pair and mate, producing hundreds of eggs daily. Some of the eggs are excreted from the body into fresh water, where the eggs hatch into free-swimming miracidia (5-10). The miracidia infect specific snail species and transform into mother and daughter sporocysts, which in turn, produce infective cercariae, completing the life cycle. Unfortunately, the entire schistosome life cycle cannot be cultured in vitro, but infective cercariae can be transformed into schistosomules, and the schistosomules can be cultured for weeks for the analysis of schistosome development in vitro or microarray analysis. In this protocol, we provide a visual description of cercarial transformation and in vitro culturing of schistosomules. We shed infectious cercariae from the snail host Biomphalaria glabrata and manually transform them into schistosomules by detaching their tails using an emulsifying double-ended needle. The in vitro cercarial transformation and schistosomules culture techniques described avoid the use of a mammalian host, which simplifies

  11. Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review

    PubMed Central

    Toda, Karla Sawada; Kikuchi, Luciana; Chagas, Aline Lopes; Tanigawa, Ryan Yukimatsu; Paranaguá-Vezozzo, Denise Cerqueira; Pfiffer, Túlio; Rocha, Manoel de Souza; Alves, Venâncio Avancini Ferreira; Carrilho, Flair José

    2015-01-01

    Background and Aims: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrum of pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. Methods: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of São Paulo School of Medicine and Hospital das Clínicas, Brazil. Results: Seven cases were included. The mean age of patients was 62.1±10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related to portal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. Conclusions: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the

  12. Epidemiological study on Schistosoma mansoni infection in Sanja area, Amhara region, Ethiopia

    PubMed Central

    2014-01-01

    Background The epidemiology of schistosomiasis is well documented and its geographic distribution has been mapped and there is an ongoing mapping in Ethiopia. Nevertheless, new transmission foci have been discovered in different parts of the country. The objective of this study was to assess the establishment of transmission and determine the prevalence of Schistosoma mansoni infection in school children from Sanja Town, northwest Ethiopia. Methods A cross-sectional parasitological survey involving 384 school children in two primary schools of Sanja Town was conducted between February and April 2013. Stool specimens were collected and microscopically examined using Kato-Katz and Sodium acetate-acetic acid-formalin (SAF) concentration methods. Malacological survey was also carried out to identify snail intermediate hosts and larval infection rate in the snail. The snails collected were checked for trematode infection by shedding. Observation was also made on water contact habits of the study population. Results The prevalence of Schistosoma mansoni infection using Kato-Katz method was high among male (79.5%) children in Sanja Primary school while it was high among female (75%) children in Ewket Amba Primary school. The prevalence of Schistosoma mansoni infection among Sanja Primary school children in the age groups 5–9 and 10–14 years were 84.6% and 75.2%, respectively while in Ewket Amba Primary school, the prevalence was 66% and 77.9% in the age groups 5–9 and 10–14 years respectively. The prevalence of schistosome infection in Biomphalaria pfeifferi was 16.9% and 0.027% during February and April, respectively. S. mansoni infection was successfully established in laboratory mice and adult worms were harvested after six weeks of laboratory maintenance. Observations made on water contact activities showed swimming, bathing and washing in the river and the stream as the high risk activities for Schistosoma mansoni infection. Conclusion The study has shown

  13. The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

    SciTech Connect

    Aitken, R.; Wilson, R.A. )

    1989-12-01

    The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.

  14. Identification of genes encoding Schistosoma mansoni antigens using an antigenic sequence tag strategy.

    PubMed

    Zouain, C S; Azevedo, V A; Franco, G R; Pena, S D; Goes, A M

    1998-12-01

    Another approach for the identification of genes that code for antigenic products is described using an antigenic sequence tag (AST) strategy. A Schistosoma mansoni adult worm cDNA library was screened with affinity chromatography-purified immunoglobulins from infected human sera and a mild oxidation treatment with sodium periodate. From 1 or both ends of 30 cDNA clones, 30 ASTs were obtained. Of these, 22 were previously known Sm antigens. One clone had matches with entries for other organisms in the databases and 6 had homology with Sm-expressed sequence tags (EST) entries. These clones, together with another 1 that had no significant database matches, were considered new antigenic genes in S. mansoni. The strategy proved to be efficient for the identification of genes that could be used for immunological studies and evaluation as vaccine candidates. PMID:9920341

  15. Immunostimulatory effects of extract of Pulicaria crispa before and after Schistosoma mansoni infection.

    PubMed

    Maghraby, Amany S; Shalaby, Nagwa; Abd-Alla, Howida I; Ahmed, Samia A; Khaled, Hussein M; Bahgat, Mahmoud M

    2010-01-01

    The immunostimulatory effects of methanolic extract from Pulicaria crispa were investigated in mice before and after infection with Schistosoma mansoni. Mice were subjected for daily intra-peritoneal injection by the extract (33 ng/mouse) for 10 successive days followed by infecting every mouse with 100 S. mansoni cercariae. Treatment with the extract induced significant increase (p < 0.05) in sera-IL-2 before and after infection. Upon using soluble worm antigen preparation or cancer bladder homogenates as antigens in ELISA, the detected levels of IgG were significantly (p < 0.05) higher in sera from treated-infected mice than untreated P. crispa infected mice. Using crude Escherichia coli lysate as an antigen in ELISA, it was detected a significant (p < 0.05) increase in IgG levels in sera from the extract-treated mice before and after infection. PMID:20210082

  16. Schistosomicidal activity and docking of Schistosoma mansoni ATPDase 1 with licoflavone B isolated from Glycyrrhiza inflata (Fabaceae).

    PubMed

    Aleixo de Carvalho, Lara Soares; Geraldo, Reinaldo Barros; de Moraes, Josué; Silva Pinto, Pedro Luiz; de Faria Pinto, Priscila; Pereira, Olavo dos Santos; Da Silva Filho, Ademar A

    2015-12-01

    Schistosomiasis is one of the world's major public health problems, and its treatment is widely dependent on praziquantel (PZQ), the only available drug. Schistosoma mansoni ATP diphosphohydrolases are ecto-enzymes localized on the external tegumental surface of S. mansoni and considered an important target for action of new drugs. In this work, the in vitro schistosomicidal activity of the crude extract of Glycyrrhiza inflata roots (GI) and its isolated compounds echinatin, licoflavone A and licoflavone B were evaluated against S. mansoni adult worms. Results showed that GI (200 μg/mL) was active against adult schistosomes, causing 100% mortality after 24 h of incubation. Chromatographic fractionation of GI led to isolation of echinatin, licoflavone A and licoflavone B. Licoflavone B (25-100 μM) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms, without affecting mammalian Vero cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after incubation with licoflavone B. Licoflavone B also showed high S. mansoni ATPase (IC50 of 23.78 μM) and ADPase (IC50 of 31.50 μM) inhibitory activities. Docking studies predicted different interactions between licoflavone B and S. mansoni ATPDase 1, corroborating with the in vitro inhibitory activity. This report demonstrated the first evidence for the schistosomicidal activity of licoflavone B and suggests that its mechanism of action involve the inhibition of S. mansoni ATP diphosphohydrolases. PMID:26454044

  17. Detection of Schistosoma mansoni and Schistosoma haematobium by Real-Time PCR with High Resolution Melting Analysis

    PubMed Central

    Sady, Hany; Al-Mekhlafi, Hesham M.; Ngui, Romano; Atroosh, Wahib M.; Al-Delaimy, Ahmed K.; Nasr, Nabil A.; Dawaki, Salwa; Abdulsalam, Awatif M.; Ithoi, Init; Lim, Yvonne A. L.; Chua, Kek Heng; Surin, Johari

    2015-01-01

    The present study describes a real-time PCR approach with high resolution melting-curve (HRM) assay developed for the detection and differentiation of Schistosoma mansoni and S. haematobium in fecal and urine samples collected from rural Yemen. The samples were screened by microscopy and PCR for the Schistosoma species infection. A pair of degenerate primers were designed targeting partial regions in the cytochrome oxidase subunit I (cox1) gene of S. mansoni and S. haematobium using real-time PCR-HRM assay. The overall prevalence of schistosomiasis was 31.8%; 23.8% of the participants were infected with S. haematobium and 9.3% were infected with S. mansoni. With regards to the intensity of infections, 22.1% and 77.9% of S. haematobium infections were of heavy and light intensities, respectively. Likewise, 8.1%, 40.5% and 51.4% of S. mansoni infections were of heavy, moderate and light intensities, respectively. The melting points were distinctive for S. mansoni and S. haematobium, categorized by peaks of 76.49 ± 0.25 °C and 75.43 ± 0.26 °C, respectively. HRM analysis showed high detection capability through the amplification of Schistosoma DNA with as low as 0.0001 ng/µL. Significant negative correlations were reported between the real-time PCR-HRM cycle threshold (Ct) values and microscopic egg counts for both S. mansoni in stool and S. haematobium in urine (p < 0.01). In conclusion, this closed-tube HRM protocol provides a potentially powerful screening molecular tool for the detection of S. mansoni and S. haematobium. It is a simple, rapid, accurate, and cost-effective method. Hence, this method is a good alternative approach to probe-based PCR assays. PMID:26193254

  18. Detection of Schistosoma mansoni and Schistosoma haematobium by Real-Time PCR with High Resolution Melting Analysis.

    PubMed

    Sady, Hany; Al-Mekhlafi, Hesham M; Ngui, Romano; Atroosh, Wahib M; Al-Delaimy, Ahmed K; Nasr, Nabil A; Dawaki, Salwa; Abdulsalam, Awatif M; Ithoi, Init; Lim, Yvonne A L; Chua, Kek Heng; Surin, Johari

    2015-01-01

    The present study describes a real-time PCR approach with high resolution melting-curve (HRM) assay developed for the detection and differentiation of Schistosoma mansoni and S. haematobium in fecal and urine samples collected from rural Yemen. The samples were screened by microscopy and PCR for the Schistosoma species infection. A pair of degenerate primers were designed targeting partial regions in the cytochrome oxidase subunit I (cox1) gene of S. mansoni and S. haematobium using real-time PCR-HRM assay. The overall prevalence of schistosomiasis was 31.8%; 23.8% of the participants were infected with S. haematobium and 9.3% were infected with S. mansoni. With regards to the intensity of infections, 22.1% and 77.9% of S. haematobium infections were of heavy and light intensities, respectively. Likewise, 8.1%, 40.5% and 51.4% of S. mansoni infections were of heavy, moderate and light intensities, respectively. The melting points were distinctive for S. mansoni and S. haematobium, categorized by peaks of 76.49 ± 0.25 °C and 75.43 ± 0.26 °C, respectively. HRM analysis showed high detection capability through the amplification of Schistosoma DNA with as low as 0.0001 ng/µL. Significant negative correlations were reported between the real-time PCR-HRM cycle threshold (Ct) values and microscopic egg counts for both S. mansoni in stool and S. haematobium in urine (p < 0.01). In conclusion, this closed-tube HRM protocol provides a potentially powerful screening molecular tool for the detection of S. mansoni and S. haematobium. It is a simple, rapid, accurate, and cost-effective method. Hence, this method is a good alternative approach to probe-based PCR assays. PMID:26193254

  19. The 26S proteasome in Schistosoma mansoni: bioinformatics analysis, developmental expression, and RNA interference (RNAi) studies.

    PubMed

    Nabhan, Joseph F; El-Shehabi, Fouad; Patocka, Nicholas; Ribeiro, Paula

    2007-11-01

    The 26S proteasome is a proteolytic complex responsible for the degradation of the vast majority of eukaryotic proteins. Regulated proteolysis by the proteasome is thought to influence cell cycle progression, transcriptional control, and other critical cellular processes. Here, we used a bioinformatics approach to identify the proteasomal constituents of the parasitic trematode Schistosoma mansoni. A detailed search of the S. mansoni genome database identified a total of 31 putative proteasomal subunits, including 17 subunits of the regulatory (19S) complex and 14 predicted catalytic (20S) subunits. A quantitative real-time RT-PCR analysis of subunit expression levels revealed that the S. mansoni proteasome components are differentially expressed among cercaria, schistosomula, and adult worms. In particular, the data suggest that the proteasome may be downregulated during the early stages of schistosomula development and is subsequently upregulated as the parasite matures to the adult stage. To test for biological relevance, we developed a transfection-based RNA interference method to knockdown the expression of the proteasome subunit, SmRPN11/POH1. Transfection of in vitro transformed S. mansoni schistosomula with specific short-interfering RNAs (siRNAs) diminished SmRPN11/POH1 expression nearly 80%, as determined by quantitative RT-PCR analysis, and also decreased parasite viability 78%, whereas no significant effect could be seen after treatment with the same amount of an irrelevant siRNA. These results indicate that the subunit SmRPN11/POH1 is an essential gene in schistosomes and further suggest an important role for the proteasome in parasite development and survival. PMID:17892869

  20. Molecular characterization of serine protease inhibitor isoform 3, SmSPI, from Schistosoma mansoni.

    PubMed

    Pakchotanon, Pattarakul; Molee, Patamaporn; Nuamtanong, Supaporn; Limpanont, Yanin; Chusongsang, Phiraphol; Limsomboon, Jareemate; Chusongsang, Yupa; Maneewatchararangsri, Santi; Chaisri, Urai; Adisakwattana, Poom

    2016-08-01

    Serine protease inhibitors, known as serpins, are pleiotropic regulators of endogenous and exogenous proteases, and molecule transporters. They have been documented in animals, plants, fungi, bacteria, and viruses; here, we characterize a serpin from the trematode platyhelminth Schistosoma mansoni. At least eight serpins have been found in the genome of S. mansoni, but only two have characterized molecular properties and functions. Here, the function of S. mansoni serpin isoform 3 (SmSPI) was analyzed, using both computational and molecular biological approaches. Phylogenetic analysis showed that SmSPI was closely related to Schistosoma haematobium serpin and Schistosoma japonicum serpin B10. Structure determined in silico confirmed that SmSPI belonged to the serpin superfamily, containing nine α-helices, three β-sheets, and a reactive central loop. SmSPI was highly expressed in schistosomules, predominantly in the head gland, and in adult male and female with intensive accumulation on the spines, which suggests that it may have a role in facilitating intradermal and intravenous survival. Recombinant SmSPI was overexpressed in Escherichia coli; the recombinant protein was of the same size (46 kDa) as the native protein. Immunological analysis suggested that mice infected with S. mansoni responded to rSmSPI at 8 weeks postinfection (wpi) but not earlier. The inhibitory activity of rSmSPI was specific to chymotrypsin but not trypsin, neutrophil elastase, and porcine pancreatic elastase. Elucidating the biological and physiological functions of SmSPI as well as other serpins will lead to further understanding of host-parasite interaction machinery that may provide novel strategies to prevent and control schistosomiasis in the future. PMID:27083187

  1. [Developmental bilharziasis caused by Schistosoma mansoni discovered 37 years after infestation].

    PubMed

    Chabasse, D; Bertrand, G; Leroux, J P; Gauthey, N; Hocquet, P

    1985-01-01

    The authors report a case of Mansoni Schistosomiasis whose course in always running thirty-seven years after the first and alone infestation in a fifty-six old man who come back from Madagascar in February 1948 and lives in France since this period eggs of schistosomiasis were living in a biopsy of rectal and sigmoid mucosea. Problem of adult worms longevity and clinical importance of such prolonged inapparent schistosomiasis are discussed. PMID:3936631

  2. Clinico-epidemiological study of Schistosomiasis mansoni in Waja-Timuga, District of Alamata, northern Ethiopia

    PubMed Central

    2014-01-01

    Background Intestinal schistosomiasis, caused by digenetic trematodes of the genus Schistosoma, is the most prevalent water related disease that causes considerable morbidity and mortality. Although prevalence of Schistosoma mansoni infection has been reported for the present study area, earlier studies have not estimated intensity of infections in relation to periportal fibrosis, which would have been crucial for epidemiological and clinical evaluations. Hence, a community based cross sectional study was conducted from December 2011 to March 2012 to assess prevalence of infection and schistosomal periportal fibrosis in Waja-Timuga, northern Ethiopia. Methods In a cross sectional study involving 371 randomly selected individuals, fresh stool samples were collected and processed by the Kato-Katz method and examined microscopically. Ultrasonography was used to determine status of schistosomal periportal fibrosis and to detect hepatomegaly and/or splenomegaly. Serum was collected for assay of hepatic activity. Statistical analysis was performed using STATA 11 statistical soft ware. P-value <0.05 was reported as statistically significant. Results The prevalence of S.mansoni infection was 73.9%, while the prevalence of schistosomal periportal fibrosis was 12.3% and mean intensity of infection was 234 eggs per gram of stool. Peak prevalence and intensity of S.mansoni infection was documented in the age range of 10–20 years. Among the study individuals, hepatomegaly was recorded in 3.7% and splenomegaly was recorded in 7.4% of the study individuals. Similarly, among the study individuals who had definite periportal fibrosis, 5.9% had elevated liver enzyme levels. Conclusion The high prevalence of Schistosoma mansoni infection and schistosomal periportal fibrosis observed in the study area calls for a periodic deworming program to reduce disease, morbidity and transmission. Preventive chemotherapy complemented with other control measures is highly required for

  3. Kinetics of interleukin-6 production after experimental infection of mice with Schistosoma mansoni.

    PubMed Central

    Khalil, R M; Hültner, L; Mailhammer, R; Luz, A; Moeller, J; Mohamed, A A; Omran, S; Dörmer, P

    1996-01-01

    It has been reported that interleukin-6 (IL-6) is expressed in cells of acute inflammatory granulomas experimentally induced in mice by eggs of Schistosoma mansoni. Moreover, in vitro IL-6 was shown to enhance the cytotoxic activity of human platelets against larvae of S. mansoni. To elucidate further a proposed biological significance of this cytokine during the course of schistosomiasis, we studied the kinetics of IL-6 production and concomitantly performed a histopathological analysis of the livers in BALB/c mice subcutaneously infected with S. mansoni cercariae. Over a period of 24 weeks postinfection (p.i.) we monitored serum IL-6 levels, IL-6 production in vitro by pokeweed mitogen (PWM)-stimulated spleen cells as well as IL-6 mRNA expression in livers, spleens and kidneys. We found significantly elevated IL-6 levels in PWM-stimulated spleen cell-conditioned media (SCM) at weeks 6 to 20 p.i., peaking at week 10 p.i. In contrast, serum IL-6 concentrations started to rise not before week 8 but remained significantly elevated above normal control values until week 24 p.i. The time pattern of enhanced IL-6 mRNA expression detected in spleens and livers, but not in kidneys, as well as the rises of IL-6 in SCM and with a delay of 2 weeks in serum samples correlated with the onset of the egg-induced inflammatory reactions as well as the incidence and the number of the granulomas observed histopathologically in the livers of infected mice. Our data emphasize both a local and a systemic role of IL-6 in the host immune response following infection of mice with S. mansoni. Images Figure 3 PMID:8943723

  4. Activities of N,N′-Diarylurea MMV665852 Analogs against Schistosoma mansoni

    PubMed Central

    Cowan, Noemi; Dätwyler, Philipp; Ernst, Beat; Wang, Chunkai; Vennerstrom, Jonathan L.; Spangenberg, Thomas

    2015-01-01

    There is an unmet need to discover and develop novel antischistosomal drugs. As exemplified by MMV665852, N,N′-diarylureas have recently emerged as a promising antischistosomal chemotype. In this study, we evaluated the structure-activity relationships of 46 commercially available analogs of MMV665852 on newly transformed schistosomula (NTS) and adult Schistosoma mansoni worms in vitro. Active compounds were evaluated with a cytotoxicity assay, in silico calculations, metabolic stability studies, and an in vivo assay with mice harboring adult S. mansoni worms. Of the 46 compounds tested at 33.3 μM, 13 and 14 compounds killed NTS and adult worms, respectively, within 72 h. Nine compounds had 90% inhibitory concentrations (IC90s) of ≤10 μM against adult worms, with selectivity indexes of ≥2.8. Their physicochemical properties and permeation through an artificial membrane indicated good to moderate intestinal absorption. Their metabolic stabilities ranged from low to high. Despite satisfactory in vitro results and in silico predictions, only one compound resulted in a statistically significant worm burden reduction (66%) after administration of a single oral dose of 400 mg/kg of body weight to S. mansoni-infected mice. Worm burden reductions of 0 to 43% were observed for the remaining eight compounds tested. In conclusion, several analogs of the N,N′-diarylurea MMV665852 had high efficacy against S. mansoni in vitro and favorable physicochemical properties for permeation through the intestinal wall. To counteract the low efficacy observed in the mouse model, further investigations should focus on identifying compounds with improved solubility and pharmacokinetic properties. PMID:25583726

  5. Eosinophils as effector cells in the destruction of Schistosoma mansoni eggs in granulomas.

    PubMed

    Hsü, S Y; Hsü, H F; Mitros, F A; Helms, C M; Solomon, R I

    1980-04-01

    Histopathological sections of wedge-biopsied liver and surgically removed gallbladder of a schistosomiasis mansoni patient were studied for the eosinophil-mediated destruction of eggs in granulomas. Apparent degranulation of eosinophils on the eggs in the granulomas and concomittant deterioration of miracidia were observed. It was construed that granule-associated enzymes may be released upon the degranulation of eosinophils, pass through the micropores of the egg shell and cause death of the miracidium inside the egg. PMID:7436603

  6. Structural and morphological characterization of hemozoin produced by Schistosoma mansoni and Rhodnius prolixus.

    PubMed

    Oliveira, Marcus F; Kycia, Stefan W; Gomez, Ariel; Kosar, Aaron J; Bohle, D Scott; Hempelmann, Ernst; Menezes, Diego; Vannier-Santos, Marcos André; Oliveira, Pedro L; Ferreira, Sérgio T

    2005-11-01

    Hemozoin (Hz) is a heme crystal produced upon the digestion of hemoglobin (Hb) by blood-feeding organisms as a main mechanism of heme disposal. The structure of Hz consists of heme dimers bound by reciprocal iron-carboxylate interactions and stabilized by hydrogen bonds. We have recently described heme crystals in the blood fluke, Schistosoma mansoni, and in the kissing bug, Rhodnius prolixus. Here, we characterized the structures and morphologies of the heme crystals from those two organisms and compared them to synthetic beta-hematin (betaH). Synchrotron radiation X-ray powder diffraction showed that all heme crystals share the same unit cell and structure. The heme crystals isolated from S. mansoni and R. prolixus consisted of very regular units assembled in multicrystalline spherical structures exhibiting remarkably distinct surface morphologies compared to betaH. In both organisms, Hz formation occurs inside lipid droplet-like particles or in close association to phospholipid membranes. These results show, for the first time, the structural and morphological characterization of natural Hz samples obtained from these two blood-feeding organisms. Moreover, Hz formation occurring in close association to a hydrophobic environment seems to be a common trend for these organisms and may be crucial to produce very regular shaped phases, allowing the formation of multicrystalline assemblies in the guts of S. mansoni and R. prolixus. PMID:16229843

  7. Towards an Understanding of the Function of the Phytochelatin Synthase of Schistosoma mansoni

    PubMed Central

    Rigouin, Coraline; Nylin, Elyse; Cogswell, Alexis A.; Schaumlöffel, Dirk; Dobritzsch, Dirk; Williams, David L.

    2013-01-01

    Phytochelatin synthase (PCS) is a protease-like enzyme that catalyzes the production of metal chelating peptides, the phytochelatins, from glutathione (GSH). In plants, algae, and fungi phytochelatin production is important for metal tolerance and detoxification. PCS proteins also function in xenobiotic metabolism by processing GSH S-conjugates. The aim of the present study is to elucidate the role of PCS in the parasitic worm Schistosoma mansoni. Recombinant S. mansoni PCS proteins expressed in bacteria could both synthesize phytochelatins and hydrolyze various GSH S-conjugates. We found that both the N-truncated protein and the N- and C-terminal truncated form of the enzyme (corresponding to only the catalytic domain) work through a thiol-dependant and, notably, metal-independent mechanism for both transpeptidase (phytochelatin synthesis) and peptidase (hydrolysis of GSH S-conjugates) activities. PCS transcript abundance was increased by metals and xenobiotics in cultured adult worms. In addition, these treatments were found to increase transcript abundance of other enzymes involved in GSH metabolism. Highest levels of PCS transcripts were identified in the esophageal gland of adult worms. Taken together, these results suggest that S. mansoni PCS participates in both metal homoeostasis and xenobiotic metabolism rather than metal detoxification as previously suggested and that the enzyme may be part of a global stress response in the worm. Because humans do not have PCS, this enzyme is of particular interest as a drug target for schistosomiasis. PMID:23383357

  8. Comparison of Schistosoma mansoni Soluble Cercarial Antigens and Soluble Egg Antigens for Serodiagnosing Schistosome Infections

    PubMed Central

    Doenhoff, Mike; Aitken, Cara; Bailey, Wendi; Ji, Minjun; Dawson, Emily; Gilis, Henk; Spence, Grant; Alexander, Claire; van Gool, Tom

    2012-01-01

    A Schistosoma mansoni cercarial antigen preparation (cercarial transformation fluid – SmCTF) was evaluated for detection of anti-schistosome antibodies in human sera in 4 collaborating laboratories. The performance of SmCTF was compared with that of S. mansoni egg antigens (SmSEA) in an indirect enzyme-immunoassay (ELISA) antigen assay, the latter being used routinely in 3 of the 4 participating laboratories to diagnose S. mansoni and S. haematobium infections. In the fourth laboratory the performance of SmCTF was compared with that of S. japonicum egg antigens (SjSEA) in ELISA for detection of anti-S. japonicum antibodies. In all 4 laboratories the results given by SmCTF in ELISA were very similar to those given by the antigen preparation routinely used in the respective laboratory to detect anti-schistosome antibodies in human infection sera. In so far as the ELISA results from SmCTF are thus so little different from those given by schistosome egg antigens and also cheaper to produce, the former is a potentially useful new diagnostic aid for schistosomiasis. PMID:23029577

  9. Anti-Inflammatory Properties of Menthol and Menthone in Schistosoma mansoni Infection

    PubMed Central

    Zaia, Mauricio G.; Cagnazzo, Túlio di Orlando; Feitosa, Karina A.; Soares, Edson G.; Faccioli, Lúcia H.; Allegretti, Silmara M.; Afonso, Ana; Anibal, Fernanda de Freitas

    2016-01-01

    Schistosomiasis is a parasitic disease caused by several species of trematode worms and it is believed that more than 261 million people are affected worldwide. New drug development has become essential because there is a risk of the parasite becoming resistant to Praziquantel, the only drug available for this infection. This study evaluated parasitological, immunological and histological parameters in mice infected with Schistosoma mansoni and treated with an herbal commercial medicine. This drug consists of menthol (30–55%) and menthone (14–32%). A 60 day treatment regimen with the herbal medicine decreased the number of S. mansoni eggs in the feces, liver, and intestine and reduced the number of hepatic granulomas. We observed a reduction of 84% in blood eosinophilia and a decrease in the IL-4 and IL-10 blood levels after treatment. Therefore, we propose that schistosomiasis treatment with this herbal medicine for 60 days has an immunomodulatory and anti-inflammatory action in this animal model for schistosomiasis thus contributing to the decrease in physio pathological effects caused by S. mansoni infection. PMID:27378927

  10. Activation-induced apoptosis in peripheral blood mononuclear cells during hepatosplenic Schistosoma mansoni infections.

    PubMed

    Ghoneim, H M; Demian, S R; Heshmat, M G; Ismail, N S; El-Sayed, Laila H

    2008-01-01

    It is well established that programmed cell death (apoptosis) is an important regulator of host responses during infection with a variety of intra- and extra-cellular pathogens. The present work aimed at assessment of in vitro spontaneous and phytohemagglutinin (PHA)-induced apoptosis in mononuclear cells isolated from patients with hepatosplenic form of S. mansoni infections. Cell death data were correlated to the degree of lymphoproliferative responses to PHA as well as to the serum anti-schistosomal antibody titers. A markedly significant increase in PHA-induced apoptosis in lymphocytes isolated from S. mansoni-infected patients was seen when compared to the corresponding healthy controls. However, a slight difference was recorded between the two studied groups regarding the spontaneous apoptosis. This was accompanied with a significant impairment of in vitro PHA-induced lymphoproliferation of T cells from S. mansoni patients. Data of the present study supports the hypothesis that activation-induced cell death (AICD) is a potentially contributing factor in T helper (Th) cell regulation during chronic stages of schistosomiasis, which represents a critically determinant factor in the host-parasite interaction and might influence the destiny of parasitic infections either towards establishment of chronic infection or towards host death. PMID:20306689

  11. Anti-Inflammatory Properties of Menthol and Menthone in Schistosoma mansoni Infection.

    PubMed

    Zaia, Mauricio G; Cagnazzo, Túlio di Orlando; Feitosa, Karina A; Soares, Edson G; Faccioli, Lúcia H; Allegretti, Silmara M; Afonso, Ana; Anibal, Fernanda de Freitas

    2016-01-01

    Schistosomiasis is a parasitic disease caused by several species of trematode worms and it is believed that more than 261 million people are affected worldwide. New drug development has become essential because there is a risk of the parasite becoming resistant to Praziquantel, the only drug available for this infection. This study evaluated parasitological, immunological and histological parameters in mice infected with Schistosoma mansoni and treated with an herbal commercial medicine. This drug consists of menthol (30-55%) and menthone (14-32%). A 60 day treatment regimen with the herbal medicine decreased the number of S. mansoni eggs in the feces, liver, and intestine and reduced the number of hepatic granulomas. We observed a reduction of 84% in blood eosinophilia and a decrease in the IL-4 and IL-10 blood levels after treatment. Therefore, we propose that schistosomiasis treatment with this herbal medicine for 60 days has an immunomodulatory and anti-inflammatory action in this animal model for schistosomiasis thus contributing to the decrease in physio pathological effects caused by S. mansoni infection. PMID:27378927

  12. In silico analysis and developmental expression of ubiquitin-conjugating enzymes in Schistosoma mansoni.

    PubMed

    Costa, Marcela P; Oliveira, Victor F; Pereira, Roberta V; de Abreu, Fabiano C P; Jannotti-Passos, Liana K; Borges, William C; Guerra-Sá, Renata

    2015-05-01

    Ubiquitin-conjugating enzymes (Ub-E2) perform the second step of ubiquitination and, consequently, are essential for regulating proteolysis and for modulating protein function, interactions and trafficking. Previously, our group demonstrated the crucial role of ubiquitination and the Ub-proteasome pathway during the Schistosoma mansoni life cycle. In the present investigation, we used a homology-based genome-wide bioinformatics approach to identify and molecularly characterise the Ub-E2 enzymes in S. mansoni. The putative functions were further investigated through molecular phylogenetic and expression profile analyses using cercariae, adult worms, eggs and mechanically transformed schistosomula (MTS) cultured in vitro for 3.5 h or 1 or 3 days. We identified, via in silico analysis, 17 Ub-E2 enzymes with conserved structural characteristics: the beta-sheet and the helix-2 form a central core bordered by helix-1 at one side and helix-3 and helix-4 at the other. The observed quantitative differences in the steady-state transcript levels between the cercariae and adult worms may contribute to the differential protein ubiquitination observed during the parasite's life cycle. This study is the first to identify and characterise the E2 ubiquitin conjugation family in S. mansoni and provides fundamental information regarding their molecular phylogenetics and developmental expression during intra-mammalian stages. PMID:25663106

  13. Prevalence of hepatitis B surface antigenemia among patients with schistosoma mansoni.

    PubMed

    Al-Freihi, H M

    1993-03-01

    This case-control study was designed to determine the prevalence of persistent hepatitis B surface antigenemia (HBsAG) among patients with schistosoma mansoni and to rationalize their vaccination against hepatitis B virus (HBV) infection. Seventy consecutive patients with a confirmed diagnosis of schistosoma mansoni were matched for age, sex, nationality, and residence (for Saudis only) with 70 healthy controls. Despite identical mean ages, sex, and nationality distribution, 18 schistosomiasis patients (26%) had positive HBsAg as compared with only three of the controls (4%). The odd ratio for HBsAg antigenemia among patients as compared to controls was 7.73 (95% confidence interval (CI) = 2-35.01, P = 0.0004. Neither sex nor nationality had any influence on the positive rate for HBsAg found in schistosomiasis patients. Patients with schistosomiasis and a concomitant positive HBsAg had significantly more derangement of their hepatic enzymes (14 out of 18; 78%) as compared with those without this viral serological marker (22 out of 52; 42%) (odd ratio - 4.77; 95% CI=1.22-20.11; P = 0.009). I have concluded that patients with schistosoma mansoni are exposed to a higher risk of acquiring HBV infection and that concomitant schistosomiasis and HBV infection has a deleterious effect on hepatic enzymes as well as other liver functions. Prospective evaluation of the preventive role of HBV vaccine among these patients is warranted. PMID:17588014

  14. Worm development in hamsters infected with unisex and cross-mated Schistosoma mansoni and Schistosoma haematobium.

    PubMed

    Khalil, S B; Mansour, N S

    1995-02-01

    Schistosoma mansoni and Schistosoma haematobium coexist in Egypt and in other areas in Africa, and people frequently are infected with parasites of both species. The effects of the interactions between worms of both sexes of the 2 species on development and egg laying were evaluated in vivo by infecting hamsters with cercariae from Biomphalaria alexandrina and Bulinus truncatus snails infected with single miracidia. In hamsters with unisex infections, male worms of both species were small. Schistosoma mansoni females were stunted and partially mature but did not contain eggs. Schistosoma haematobium females, though stunted, sometimes contained and laid small eggs, which were deposited in the liver, but few of which contained motile embryos. This suggests that unisexual infection with S. haematobium female worms produces a risk for liver damage due to egg deposition in tissues. Both S. mansoni and S. haematobium females that mated with males of the heterologous species were significantly larger than females from unisexual infections; they were sexually mature and possessed eggs in the uterus. The eggs in the liver homogenates of cross-specific infected hamsters contained fully developed miracidia that hatched in filtered pond water. PMID:7876983

  15. Involvement of the Cytokine MIF in the Snail Host Immune Response to the Parasite Schistosoma mansoni

    PubMed Central

    Baeza Garcia, Alvaro; Pierce, Raymond J.; Gourbal, Benjamin; Werkmeister, Elisabeth; Colinet, Dominique; Reichhart, Jean-Marc; Dissous, Colette; Coustau, Christine

    2010-01-01

    We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions. PMID:20886098

  16. ULTRASTRUCTURAL CHANGES IN Schistosoma mansoni MALE WORMS AFTER in vitro INCUBATION WITH THE ESSENTIAL OIL OF Mentha x villosa Huds

    PubMed Central

    MATOS-ROCHA, Thiago José; CAVALCANTI, Marília Gabriela dos Santos; VERAS, Dyana Leal; FEITOSA, Ana Paula Sampaio; GONÇALVES, Gabriel Gazzoni Araújo; PORTELA-JUNIOR, Nairomberg Cavalcanti; LÚCIO, Ana Silvia Suassuna Carneiro; da SILVA, Anekécia Lauro; PADILHA, Rafael José Ribeiro; MARQUES, Márcia Ortiz Mayo; BARBOSA-FILHO, José Maria; ALVES, Luiz Carlos; BRAYNER, Fábio André

    2016-01-01

    Introduction: The essential oil Mentha x villosa (MVEO) has a wide range of actions, including antibacterial, antifungal, antiprotozoal and schistosomicidal actions. The present study aimed to investigate the ultrastructural changes of MVEO on the tegument of adult Schistosoma mansoni. Materials and Methods: Different concentrations of MVEO were tested on S. mansoni adult worms in vitro. Ultrastructural changes on the tegument of these adult worms were evaluated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: The MVEO caused the death of all worms at 500 μg mL-1 after 24 h. After 24h of 500 μg mL-1 MVEO treatment, bubble lesions were observed over the entire body of worms and they presented loss of tubercles in some regions of the ventral portion. In the evaluation by TEM, S. mansoni adult worms treated with MVEO, 500 μg mL-1, presented changes in the tegument and vacuoles in the syncytial matrix region. Glycogen granules close to the muscle fibers were visible. Conclusion: The ability of MVEO to cause extensive ultrastructural damage to S. mansoni adult worms correlates with its schistosomicidal effects and confirms earlier findings with S. mansoni. PMID:26910448

  17. Prevalence of Schistosoma mansoni Infection in Four Health Areas of Kisantu Health Zone, Democratic Republic of the Congo

    PubMed Central

    Mbanzulu Makola, K.

    2016-01-01

    Background. Schistosomiasis is a public health problem in Democratic Republic of the Congo but estimates of its prevalence vary widely. The aim of this study was to determine prevalence of Schistosoma mansoni infection and associated risk factors among children in 4 health areas of Kisantu health zone. Methods. A cross-sectional study was carried out in 4 health areas of Kisantu health zone. 388 children randomly selected were screened for S. mansoni using Kato Katz technique and the sociodemographic data was collected. Data were entered and encoded using software EpiData version 3.1. Analysis was performed using SPSS version 21 software. Results. The prevalence of S. mansoni was 26.5% (103); almost two-thirds (63) (61.2%) had light infection intensity. A significant association was found between S. mansoni infection and age (p = 0.005), educational level (p = 0.001), and practices of swimming/bathing (p < 0.001) and using water from river/lake/stream for domestic use (p < 0.001). Kipasa health area had high prevalence of schistosomiasis (64.6%) (64/99; 95% CI 54.4–74.0) compared to other health areas. Conclusion. Schistosoma mansoni infection still remains a public health problem in these areas. There is a need to promote health education and promote behavioral changes in children towards schistosomiasis. PMID:27579346

  18. Prevalence of Schistosoma mansoni Infection in Four Health Areas of Kisantu Health Zone, Democratic Republic of the Congo.

    PubMed

    Khonde Kumbu, R; Mbanzulu Makola, K; Bin, Lu

    2016-01-01

    Background. Schistosomiasis is a public health problem in Democratic Republic of the Congo but estimates of its prevalence vary widely. The aim of this study was to determine prevalence of Schistosoma mansoni infection and associated risk factors among children in 4 health areas of Kisantu health zone. Methods. A cross-sectional study was carried out in 4 health areas of Kisantu health zone. 388 children randomly selected were screened for S. mansoni using Kato Katz technique and the sociodemographic data was collected. Data were entered and encoded using software EpiData version 3.1. Analysis was performed using SPSS version 21 software. Results. The prevalence of S. mansoni was 26.5% (103); almost two-thirds (63) (61.2%) had light infection intensity. A significant association was found between S. mansoni infection and age (p = 0.005), educational level (p = 0.001), and practices of swimming/bathing (p < 0.001) and using water from river/lake/stream for domestic use (p < 0.001). Kipasa health area had high prevalence of schistosomiasis (64.6%) (64/99; 95% CI 54.4-74.0) compared to other health areas. Conclusion. Schistosoma mansoni infection still remains a public health problem in these areas. There is a need to promote health education and promote behavioral changes in children towards schistosomiasis. PMID:27579346

  19. AN INITIAL INDICATION OF PREDISPOSING RISK OF SCHISTOSOMA MANSONI INFECTION FOR HEPATOCELLULAR CARCINOMA.

    PubMed

    Sabry, Abd El Hamid A; El-Aal, Amany A Abd; Mahmoud, Naglaa Saad; Nabil, Yossra; Aziz, Inas Z Abdel

    2015-08-01

    Estimated 500,000 - 1 million cases of hepatocellular carcinoma (HCC) are reported to occur yearly worldwide, with a mean annual incidence of around 3 - 4% of global population. HCC is rapidly fatal in most patients; that makes its incidence and mortality rates almost equal. In the last 5-10 years there were many alarming reports of sharply increased incidence of HCC. In Egypt, HCC reported to account for about 4.7% of chronic liver disease (CLD) patients, which has tremendous impact on socio-economic development in the country. Available data suggests indirect evidence of an association between Schistosoma mansoni and hepatocellular carcinoma, possibly through potentiation of hepatitis infections. The present study was conducted case control analysis of 60 HCC patients. Chronic schistosomiasis cases were confirmed by finding Anti-Schistosoma mansoni antibodies IgG by ELISA. Hepatitis C viral infection was proved by detection of viral load by quantitative Real time PCR. Among the study group 56.6% (34/60) were dweller in rural in Al-Fayoum governorate. Within hepatocellular carcinoma cases 26.7% (16/60) and 33.3% (20/60) suffered mono chronic schistosomiasis and mono hepatitis C (HCV) infections respectively, with no statistically significant differences (p=0.37), indicating comparable risk value of both infections in predisposing directly to HCC. Additionally; frequency of HCC patients with assumed potentiated HCV infection by chronic Schistosoma mansoni 6.7% (4/60) were statistically significant (p<0.05) less among total HCC patients included in this study, when compared to HCC patients preceded by either pure chronic schistosomiasis 26.7% (16/60) or pure HCV infection 33.3% (20/60). Our present study is one of few, addressing the possibility of direct relation between S. mansoni & hepatic carcinoma, concluding an initial indication of equal risk value of both human chronic S. mansoni infection and hepatitis C viral infections in precipitating hepatocellular

  20. Green tea (Camellia sinesis) ameliorates female Schistosoma mansoni-induced changes in the liver of Balb/C mice

    PubMed Central

    Bin Dajem, Saad M.; Shati, Ali A.; Adly, Mohamed A.; Ahmed, Osama M.; Ibrahim, Essam H.; Mostafa, Osama M.S.

    2011-01-01

    This study was designed to assess the effect of green tea, an aqueous extract of Camellia sinensis, on the oxidative stress, antioxidant defense system and liver pathology of Schistosoma mansoni-infected mice. Green tea at concentration of 3% (w/v) was given orally to treated mice as sole source of drinking water from the end of the 4th week to the end of 10th week post-infection; untreated mice were allowed to drink normal water. The data of the studied S. mansoni-infected mice exhibited a suppression of hepatic total antioxidant capacity, superoxide dismutase (SOD), catalase (CAT) activity and glutathione content. The liver lipid peroxidation was deleteriously elevated in S. mansoni-infected mice. The hepatic total protein content, AST and ALT activities were profoundly decreased in the S. mansoni-infected mice. Most hepatocytes were damaged and showed abnormal microscopic appearance with aggressive necrosis. Both total protein and glycogen levels have been greatly reduced as indicated by histochemical examination. The treatment of S. mansoni-infected mice with green tea succeeded to suppress oxidative stress by decreasing the lipid peroxides but failed to significantly enhance the antioxidant defense system and deteriorated changes owing to liver damage and necrosis. In consistence with biochemical data, histopathological and histochemical data indicated that treatment of S. mansoni-infected mice with green tea could ameliorate hepatocytes thus reduce cellular necrosis and partially restore both total protein and glycogen levels. Thus, the study concluded that the green tea suppresses the oxidative stress through its constituent with free radicals scavenging properties rather than through the endogenous antioxidant defense system. PMID:23961148

  1. Rapid screening for Schistosoma mansoni in western Côte d'Ivoire using a simple school questionnaire.

    PubMed Central

    Utzinger, J.; N'Goran, E. K.; Ossey, Y. A.; Booth, M.; Traoré, M.; Lohourignon, K. L.; Allangba, A.; Ahiba, L. A.; Tanner, M.; Lengeler, C.

    2000-01-01

    The distribution of schistosomiasis is focal, so if the resources available for control are to be used most effectively, they need to be directed towards the individuals and/or communities at highest risk of morbidity from schistosomiasis. Rapid and inexpensive ways of doing this are needed, such as simple school questionnaires. The present study used such questionnaires in an area of western Côte d'Ivoire where Schistosoma mansoni is endemic; correctly completed questionnaires were returned from 121 out of 134 schools (90.3%), with 12,227 children interviewed individually. The presence of S. mansoni was verified by microscopic examination in 60 randomly selected schools, where 5047 schoolchildren provided two consecutive stool samples for Kato-Katz thick smears. For all samples it was found that 54.4% of individuals were infected with S. mansoni. Moreover, individuals infected with S. mansoni reported "bloody diarrhoea", "blood in stools" and "schistosomiasis" significantly more often than uninfected children. At the school level, Spearman rank correlation analysis showed that the prevalence of S. mansoni significantly correlated with the prevalence of reported bloody diarrhoea (P = 0.002), reported blood in stools (P = 0.014) and reported schistosomiasis (P = 0.011). Reported bloody diarrhoea and reported blood in stools had the best diagnostic performance (sensitivity: 88.2%, specificity: 57.7%, positive predictive value: 73.2%, negative predictive value: 78.9%). The study, which is probably the largest of its kind ever undertaken in Africa, revealed a moderate diagnostic performance of questionnaires for identifying individuals and/or communities at high risk from S. mansoni. PMID:10812739

  2. Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk.

    PubMed

    Obuku, Andrew Ekii; Asiki, Gershim; Abaasa, Andrew; Ssonko, Isaac; Harari, Alexandre; van Dam, Govert J; Corstjens, Paul L; Joloba, Moses; Ding, Song; Mpendo, Juliet; Nielsen, Leslie; Kamali, Anatoli; Elliott, Alison M; Pantaleo, Giuseppe; Kaleebu, Pontiano; Pala, Pietro

    2016-07-01

    In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV-specific responses by intracellular cytokine staining for IFN-γ, IL-2, and TNF-α. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM- individuals. In addition, the TNF-α response to the imidazoquinoline compound CL097 and β-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-γ+IL-2-TNF-α- CD8 T cells and IFN-γ+IL-2-TNF-α+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals. PMID:26864743

  3. Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk

    PubMed Central

    Asiki, Gershim; Abaasa, Andrew; Ssonko, Isaac; Harari, Alexandre; van Dam, Govert J.; Corstjens, Paul L.; Joloba, Moses; Ding, Song; Mpendo, Juliet; Nielsen, Leslie; Kamali, Anatoli; Elliott, Alison M.; Pantaleo, Giuseppe; Kaleebu, Pontiano; Pala, Pietro

    2016-01-01

    Abstract In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV-specific responses by intracellular cytokine staining for IFN-γ, IL-2, and TNF-α. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM− individuals. In addition, the TNF-α response to the imidazoquinoline compound CL097 and β-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-γ+IL-2–TNF-α− CD8 T cells and IFN-γ+IL-2–TNF-α+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals. PMID:26864743

  4. Developmental expression analysis and immunolocalization of a biogenic amine receptor in Schistosoma mansoni

    PubMed Central

    El-Shehabi, Fouad; Vermeire, Jon J.; Yoshino, Timothy P.; Ribeiro, Paula

    2013-01-01

    A Schistosoma mansoni G-protein coupled receptor (SmGPCR) was previously cloned and shown to be activated by the biogenic amine, histamine. Here we report a first investigation of the receptor’s subunit organization, tissue distribution and expression levels in different stages of the parasite. A polyclonal antibody was produced in rabbits against the recombinant third intracellular loop (il3) of SmGPCR. Western blot studies of the native receptor and recombinant protein expressed in HEK293 cells showed that SmGPCR exists both as a monomer (65 kDa) and an apparent dimer of ≈130 kDa These species were verified by immunoprecipitation of SmGPCR from S. mansoni extracts, using antibody that was covalently attached to agarose beads. Further investigation determined that the SmGPCR dimer was resistant to treatment with various detergents, 4 M urea and 0.1 M DTT but could be made to dissociate at acidic pH, suggesting the dimer is non-covalent in nature. Confocal immunofluorescence studies revealed significant SmGPCR immunoreactivity in sporocysts, schistosomula and adult worms but not miracidia. SmGPCR was found to be most widely expressed in the schistosomula, particularly the tegument, the subtegumental musculature and the acetabulum. In the adult stage we detected SmGPCR immunofluorescence mainly in the tubercles of male worms and, to a lesser extent, the body wall musculature. Localization in sporocysts was mainly confined to the tegument and cells within parenchymal matrices. A realtime quantitative reverse-transcription PCR analysis revealed that SmGPCR is upregulated at the mRNA level in the parasitic stages compared to the free-living miracidium and cercariae, and it is particularly elevated during early sporocyst and schistosomula development. The results identify SmGPCR as an important parasite receptor with potential functions in muscle and the tegument of S. mansoni. PMID:19545530

  5. Developmental expression analysis and immunolocalization of a biogenic amine receptor in Schistosoma mansoni.

    PubMed

    El-Shehabi, Fouad; Vermeire, Jon J; Yoshino, Timothy P; Ribeiro, Paula

    2009-05-01

    A Schistosoma mansoni G-protein coupled receptor (SmGPCR) was previously cloned and shown to be activated by the biogenic amine, histamine. Here we report a first investigation of the receptor's subunit organization, tissue distribution and expression levels in different stages of the parasite. A polyclonal antibody was produced in rabbits against the recombinant third intracellular loop (il3) of SmGPCR. Western blot studies of the native receptor and recombinant protein expressed in HEK293 cells showed that SmGPCR exists both as a monomer (65 kDa) and an apparent dimer of approximately 130 kDa These species were verified by immunoprecipitation of SmGPCR from S. mansoni extracts, using antibody that was covalently attached to agarose beads. Further investigation determined that the SmGPCR dimer was resistant to treatment with various detergents, 4 M urea and 0.1 M DTT but could be made to dissociate at acidic pH, suggesting the dimer is non-covalent in nature. Confocal immunofluorescence studies revealed significant SmGPCR immunoreactivity in sporocysts, schistosomula and adult worms but not miracidia. SmGPCR was found to be most widely expressed in the schistosomula, particularly the tegument, the subtegumental musculature and the acetabulum. In the adult stage we detected SmGPCR immunofluorescence mainly in the tubercles of male worms and, to a lesser extent, the body wall musculature. Localization in sporocysts was mainly confined to the tegument and cells within parenchymal matrices. A real-time quantitative reverse-transcription PCR analysis revealed that SmGPCR is upregulated at the mRNA level in the parasitic stages compared to the free-living miracidium and cercariae, and it is particularly elevated during early sporocyst and schistosomula development. The results identify SmGPCR as an important parasite receptor with potential functions in muscle and the tegument of S. mansoni. PMID:19545530

  6. The Role of Efflux Pumps in Schistosoma mansoni Praziquantel Resistant Phenotype

    PubMed Central

    Armada, Ana; Belo, Silvana; Carrilho, Emanuel; Viveiros, Miguel; Afonso, Ana

    2015-01-01

    Background Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Praziquantel (PZQ) is the drug of choice to treat this disease due to its high cure rates and no significant side effects. However, in the last years increasingly cases of tolerance to PZQ have been reported, which has caused growing concerns regarding the emergency of resistance to this drug. Methodology/Principal Findings Here we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. It has been reported that drug resistance in helminths might involve efflux pumps such as members of ATP-binding cassette transport proteins, including P-glycoprotein and multidrug resistance-associated protein families. Here we evaluate the role of efflux pumps in Schistosoma mansoni resistance to PZQ, by comparing the efflux pumps activity in susceptible and resistant strains. The evaluation of the efflux activity was performed by an ethidium bromide accumulation assay in presence and absence of Verapamil. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR. Conclusions/Significance This work strongly suggests the involvement of Pgp-like transporters SMDR2 in Praziquantel drug resistance in S. mansoni. Low doses of Verapamil successfully reverted drug resistance. Our results might give an indication that a combination therapy with PZQ and natural or synthetic Pgp modulators can be an effective strategy for the treatment of confirmed cases of resistance to PZQ in S. mansoni. PMID:26445012

  7. Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi.

    PubMed

    Nyakundi, Ruth K; Nyamongo, Onkoba; Maamun, Jeneby; Akinyi, Mercy; Mulei, Isaac; Farah, Idle O; Blankenship, D'Arbra; Grimberg, Brian; Hau, Jann; Malhotra, Indu; Ozwara, Hastings; King, Christopher L; Kariuki, Thomas M

    2016-05-01

    Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n = 8 each) and a schistosomiasis control group (n = 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n = 8) were intravenously inoculated with 10(5) Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P = 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P = 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. PMID:26883586

  8. Schistosoma mansoni: effects of in vitro serotonin (5-HT) on aerobic and anaerobic carbohydrate metabolism.

    PubMed

    Rahman, M S; Mettrick, D F; Podesta, R B

    1985-08-01

    The effect of Serotonin on carbohydrate metabolism, excreted end products, and adenine nucleotide pools in Schistosoma mansoni was determined following 60 min in vitro incubations under air (= 21% O2) and anaerobic (95% N2:5% CO2) conditions. In the presence of 0.25 mM Serotonin, glucose uptake increased by 82-84% and lactate excretion increased by 77-78%; levels of excreted lactate were significantly higher under aerobic than under anaerobic conditions. The tissue pools of glucose, hexosephosphates, fructose 1,6-bisphosphate, pyruvate, and lactate were significantly increased under anaerobic conditions compared to air incubation; the presence of Serotonin decreased tissue glucose pools and increased the size of the pyruvate and lactate tissue pools. The glycolytic carbon pool was significantly greater under anaerobic than under aerobic conditions, irrespective of Serotonin. Serotonin increased adenosine 5'-diphosphate and adenosine 5'-monophosphate levels under aerobic conditions; neither Serotonin nor gas phase significantly affected total adenine nucleotide levels or the adenylate energy charge. Serotonin increased energy requirements by S. mansoni due to increased muscle contractions; demand was met by enhanced rates of carbohydrate metabolism. Irrespective of gas phase, 74-78% of available carbohydrate was converted to lactate. In the presence of Serotonin, conversion of glucose to lactate was reduced to 63-67%. In view of the requirements by S. mansoni for an abundant supply of glycoprotein and glycolipid precursors for surface membrane renewal, it is suggested that carbohydrate (glucose and glycogen) that was not converted to lactate may have been incorporated into biosynthetic processes leading to membrane synthesis. PMID:4018216

  9. Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study

    PubMed Central

    Eissa, Maha M.; El-Moslemany, Riham M.; Ramadan, Alyaa A.; Amer, Eglal I.; El-Azzouni, Mervat Z.; El-Khordagui, Labiba K.

    2015-01-01

    Miltefosine (MFS) is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD). This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs) as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%), good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs, allowing targeting

  10. RNA interference targeting leucine aminopeptidase blocks hatching of Schistosoma mansoni eggs

    PubMed Central

    Rinaldi, Gabriel; Morales, Maria E.; Alrefaei, Yousef N.; Cancela, Martín; Castillo, Estela; Dalton, John P.; Tort, José F.; Brindley, Paul J.

    2009-01-01

    Schistosoma mansoni leucine aminopeptidase (LAP) is thought to play a central role in hatching of the miracidium from the schistosome egg. We identified two discrete LAPs genes in the Schistosoma mansoni genome, and their orthologs in S. japonicum. The similarities in sequence and exon/intron structure of the two genes, LAP1 and LAP2, suggest that they arose by gene duplication and that this occurred before separation of the mansoni and japonicum lineages. The SmLAP 1 and 2 genes have different expression patterns in diverse stages of the cycle; whereas both are equally expressed in the blood dwelling stages (schistosomules and adult), SmLAP 2 expression was higher in free living larval (miracidia) and in parasitic intra-snail (sporocysts) stages. We investigated the role of each enzyme in hatching of schistosome eggs and the early stages of schistosome development by RNA interference (RNAi). Using RNAi, we observed marked and specific reduction of mRNAs, along with a loss of exopeptidase activity in soluble parasite extracts against the diagnostic substrate L-leucine-7-amido-4-methylcoumarin hydroxide. Strikingly, knockdown of either SmLAP1 or SmLAP2, or both together, was accompanied by ≥ 80% inhibition of hatching of schistosome eggs showing that both enzymes are important to the escape of miracidia from the egg. The methods employed here refine the utility of RNAi for functional genomics studies in helminth parasites and confirm these can be used to identify potential drug targets, in this case schistosome aminopeptidases. PMID:19463860

  11. Thyroid hormone receptor orthologues from invertebrate species with emphasis on Schistosoma mansoni

    PubMed Central

    Wu, Wenjie; Niles, Edward G; LoVerde, Philip T

    2007-01-01

    Background: Thyroid hormone receptors (TRs) function as molecular switches in response to thyroid hormone to regulate gene transcription. TRs were previously believed to be present only in chordates. Results: We isolated two TR genes from the Schistosoma mansoni and identified TR orthologues from other invertebrates: the platyhelminths, S. japonium and Schmidtea mediterranea, the mollusc, Lottia gigantean and the arthropod Daphnia pulex. Phylogenetic analysis of the DNA binding domain and/or ligand binding domain shows that invertebrate and vertebrate TRs cluster together, TRs from the vertebrates and from the jawless vertebrate (lamprey) clustered within separate subgroups, Platyhelminth TRs cluster outside of the vertebrate TR subgroups and that the schistosome TRs and S. mediterranea TRs clustered within separate subgroups. Alignment of the C-terminus of the A/B domain revealed a conserved TR-specific motif, termed TR 'N-terminus signature sequence', with a consensus sequence of (G/P)YIPSY(M/L)XXXGPE(D/E)X. Heterodimer formation between S. mansoni TRs and SmRXR1 suggests that the invertebrate TR protein gained the ability to form a heterodimer with RXR. ESMA analysis showed that SmTRα could bind to a conserved DNA core motif as a monomer or homodimer. Conclusion: Vertebrate TR genes originated from a common ancestor of the Bilateria. TR genes underwent duplication independently in the Protostomia and Deuterostomia. The duplication of TRs in deuterostomes occurred after the split of jawless and jawed vertebrates. In protostomes, TR genes underwent duplication in Platyhelminths, occurring independently in trematode and turbellarian lineages. Using S. mansoni TRs as an example, invertebrate TRs exhibited the ability to form a dimer with RXR prior to the emergence of the vertebrate TRs and were able to bind to vertebrate TR core DNA elements as a monomer or homodimer. PMID:17727708

  12. The tegumental surface membranes of Schistosoma mansoni are enriched in parasite-specific phospholipid species.

    PubMed

    Retra, Kim; deWalick, Saskia; Schmitz, Marion; Yazdanbakhsh, Maria; Tielens, Aloysius G M; Brouwers, Jos F H M; van Hellemond, Jaap J

    2015-08-01

    The complex surface structure of adult Schistosoma mansoni, the tegument, is essential for survival of the parasite. This tegument is syncytial and is covered by two closely-apposed lipid bilayers that form the interactive surface with the host. In order to identify parasite-specific phospholipids present in the tegument, the species compositions of the major glycerophospholipid classes, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol, including lysophospholipid species, were analysed in adult S. mansoni worms, isolated tegumental membranes and hamster blood cells. It was shown that there are large differences in species composition in all four phospholipid classes between the membranes of S. mansoni and those of the host blood cells. The species compositions of phosphatidylserine and phosphatidylcholine were strikingly different in the tegument compared with the whole worm. The tegumental membranes are especially enriched in lysophospholipids, predominantly eicosenoic acid (20:1)-containing lyso-phosphatidylserine and lyso-phosphatidylethanolamine species. Furthermore, the tegument was strongly enriched in phosphatidylcholine that contained 5-octadecenoic acid, an unusual fatty acid that is not present in the host. As we have shown previously that lysophospholipids from schistosomes affect the parasite-host interaction, excretion of these tegument-specific phospholipid species was examined in vitro and in vivo. Our experiments demonstrated that these lysophospholipids are not significantly secreted during in vitro incubations and are not detectable in peripheral blood of infected hosts. However, these analyses demonstrated a substantial decrease in PI content of blood plasma from schistosome-infected hamsters, which might indicate that schistosomes influence exosome formation by the host. PMID:25975668

  13. Diagnostic and prognostic value of cell free circulating Schistosoma mansoni DNA: an experimental study.

    PubMed

    Eraky, Maysa Ahmad; Aly, Nagwa Shaban Mohamed

    2016-09-01

    Searching for a more sensitive and accurate marker for schistosomiasis diagnosis and treatment follow up is a potential necessity. Hereby, we evaluated usefulness of circulating free DNA as a marker for schistosomiasis diagnosis, assessing drug efficacy and monitoring the control interventions impact using SYBR green real-time PCR. A batch of mice were infected by 90 ± 10 Schistosoma mansoni cercariae. Starting from the 2nd day post infection (p.i.), groups of 2 or 3 mice were sacrificed every 3 days until 30 days p.i. The remaining animals were treated by a single dose of 400 mg/kg mefloquine and sacrificed in group at 5, 10, 21 days post treatment (35, 40, 51 days p.i.). Using SYBR green real time qPCR, pooled sera DNA were extracted and amplified. The results showed that, circulating free S. mansoni DNA was detected from the 2nd day post infection (p.i.) onwards with gradual decrease in the cycle threshold value Ct which indicates the gradual elevation of the DNA level (Log quantity was 2.6-3.1 IU/ml), As the infection progressed, DNA quantity was increased(Log quantity was 6.29 IU/ml). Initial increase of circulating free DNA was observed 10 days post treatment (40 days p.i.) (Log quantity was 7.38 IU/ml). That was followed by a progressive decrease in DNA level by the end of 21st day, post treatment (51 p.i.) (Log quantity 4.35 IU/ml). In conclusion, circulating free S. mansoni DNA is a reliable marker in the diagnosis of schistosomiasis and for assessing drug efficacy and monitoring the impact of control interventions. PMID:27605830

  14. Identification of Candidate Serum Biomarkers for Schistosoma mansoni Infected Mice Using Multiple Proteomic Platforms

    PubMed Central

    Kardoush, Manal I.

    2016-01-01

    Background Schistosomiasis is an important helminth infection of humans. There are few reliable diagnostic biomarkers for early infection, for recurrent infection or to document successful treatment. In this study, we compared serum protein profiles in uninfected and infected mice to identify disease stage-specific biomarkers. Methods Serum collected from CD1 mice infected with 50–200 Schistosoma mansoni cercariae were analyzed before infection and at 3, 6 and 12 weeks post-infection using three mass spectrometric (MS) platforms. Results Using SELDI-TOF MS, 66 discriminating m/z peaks were detected between S. mansoni infected mice and healthy controls. Used in various combinations, these peaks could 1) reliably diagnose early-stage disease, 2) distinguish between acute and chronic infection and 3) diagnose S. mansoni infection regardless the parasite burden. The most important contributors to these diagnostic algorithms were peaks at 3.7, 13 and 46 kDa. Employing sample fractionation and differential gel electrophoresis, we analyzed gel slices either by MALDI-TOF MS or Velos Orbitrap MS. The former yielded eight differentially-expressed host proteins in the serum at different disease stages including transferrin and alpha 1- antitrypsin. The latter suggested the presence of a surprising number of parasite-origin proteins in the serum during both the acute (n = 200) and chronic (n = 105) stages. The Orbitrap platform also identified many differentially-expressed host-origin serum proteins during the acute and chronic stages (296 and 220 respectively). The presence of one of the schistosome proteins, glutathione S transferase (GST: 25 KDa), was confirmed by Western Blot. This study provides proof-of-principle for an approach that can yield a large number of novel candidate biomarkers for Schistosoma infection. PMID:27138990

  15. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms

    PubMed Central

    Anderson, Leticia; Venancio, Thiago M.; Nakaya, Helder I.; Miyasato, Patrícia A.; Rofatto, Henrique K.; Zerlotini, Adhemar; Nakano, Eliana; Oliveira, Guilherme; Verjovski-Almeida, Sergio

    2015-01-01

    Background Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis. Methodology We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay. Principal Findings We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females), indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect. Conclusions Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with

  16. Molecular approach for detecting early prepatent Schistosoma mansoni infection in Biomphalaria alexandrina snail host.

    PubMed

    Farghaly, Adel; Saleh, Ayman A; Mahdy, Soad; Abd El-Khalik, Dalia; Abd El-Aal, Naglaa F; Abdel-Rahman, Sara A; Salama, Marwa A

    2016-09-01

    The present study aimed to evaluate a polymerase chain reaction (PCR) assay used for detection of Schistosoma mansoni infection in Biomphalaria alexandrina snails in early prepatent period and to compare between it and the ordinary detection methods (shedding and crushing). Biomphalaria alexandrina snails are best known for their role as intermediate hosts of S. mansoni. DNA was extracted from infected snails in addition to non-infected "negative control" (to optimized the efficiency of PCR reaction) and subjected to PCR using primers specific to a partial sequence of S. mansoni fructose-1,6-bus phosphate aldolase (SMALDO). SMALDO gene was detected in the infected laboratory snails with 70, 85, and 100 % positivity at the 1st, 3rd, and 7th day of infection, respectively. In contrast, the ordinary method was not sensitive enough in detection of early prepatent infection even after 7 days of infection which showed only 25 % positivity. By comparing the sensitivity of the three methods, it was found that the average sensitivity of shedding method compared to PCR was 23.8 % and the average sensitivity of crushing method compared to PCR was 46.4 % while the sensitivity of PCR was 100 %. We conclude that PCR is superior to the conventional methods and can detect positive cases that were negative when examined by shedding or crushing methods. This can help in detection of the areas and times of high transmission which in turn will be very beneficial in planning of the exact timing of the proper control strategy. PMID:27605788

  17. A Loop-Mediated Isothermal Amplification (LAMP) Assay for Early Detection of Schistosoma mansoni in Stool Samples: A Diagnostic Approach in a Murine Model

    PubMed Central

    Fernández-Soto, Pedro; Gandasegui Arahuetes, Javier; Sánchez Hernández, Alicia; López Abán, Julio; Vicente Santiago, Belén; Muro, Antonio

    2014-01-01

    Background Human schistosomiasis, mainly due to Schistosoma mansoni species, is one of the most prevalent parasitic diseases worldwide. To overcome the drawbacks of classical parasitological and serological methods in detecting S. mansoni infections, especially in acute stage of the disease, development of cost-effective, simple and rapid molecular methods is still needed for the diagnosis of schistosomiasis. A promising approach is the loop-mediated isothermal amplification (LAMP) technology. Compared to PCR-based assays, LAMP has the advantages of reaction simplicity, rapidity, specificity, cost-effectiveness and higher amplification efficiency. Additionally, as results can be inspected by the naked eye, the technique has great potential for use in low-income countries. Methodology/Principal findings A sequence corresponding to a mitochondrial S. mansoni minisatellite DNA region was selected as a target for designing a LAMP-based method to detect S. mansoni DNA in stool samples. We used a S. mansoni murine model to obtain well defined stool and sera samples from infected mice with S. mansoni cercariae. Samples were taken weekly from week 0 to 8 post-infection and the Kato-Katz and ELISA techniques were used for monitoring the infection. Primer set designed were tested using a commercial reaction mixture for LAMP assay and an in house mixture to compare results. Specificity of LAMP was tested using 16 DNA samples from different parasites, including several Schistosoma species, and no cross-reactions were found. The detection limit of our LAMP assay (SmMIT-LAMP) was 1 fg of S. mansoni DNA. When testing stool samples from infected mice the SmMIT-LAMP detected S. mansoni DNA as soon as 1 week post-infection. Conclusions/Significance We have developed, for the first time, a cost-effective, easy to perform, specific and sensitive LAMP assay for early detection of S. mansoni in stool samples. The method is potentially and readily adaptable for field diagnosis and

  18. Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase

    PubMed Central

    Awama, Ayman M.; Paracuellos, Patricia; Laurent, Sabine; Dissous, Colette; Marcillat, Olivier; Gouet, Patrice

    2008-01-01

    The 716-amino-acid guanidino kinase from the parasitic flatworm Schistosoma mansoni results from the fusion of two guanidino kinase subunits. Crystals of this 80 kDa protein have been obtained in the monoclinic space group P21, with unit-cell parameters a = 52.7, b = 122.1, c = 63.2 Å, β = 108.5°. Synchrotron data were collected to 2.8 Å resolution on ESRF beamline ID29. The structure was solved by the molecular-replacement method, using the 357-amino-acid structure of the arginine kinase from Trypanosoma cruzi as the search model. PMID:18765922

  19. Individual household water supplies as a control measure against Schistosoma mansoni

    PubMed Central

    Unrau, G. O.

    1975-01-01

    As part of a programme to evaluate single control measures for reducing the transmission of Schistosoma mansoni, household water supplies were installed in 5 rural settlements in the Riche Fond Valley of St Lucia. About 2 000 persons who previously were dependent on rivers and streams are now receiving safe water at their homes. The systems provide useful design data on individual water requirements in rural areas. This experience suggests that future rural water systems can be designed more economically and efficiently by using consumption rates that are closer to the actual requirements and by eliminating water wastage at the taps. PMID:1082378

  20. Cholinergic components of nervous system of Schistosoma mansoni and S. haematobium (Digenea: Schistosomatidae).

    PubMed

    Reda, Enayat S; El-Shabasy, Eman A; Said, Ashraf E; Mansour, Mohamed F A; Saleh, Mai A

    2016-08-01

    A comparison has been made for the first time between the cholinergic components of the nervous system of important human digeneans namely Schistosoma mansoni and Schistosoma haematobium from infected hamster (Cricentus auratus) in Egypt. In each parasite, the central nervous system consists of two cerebral ganglia and three pairs of nerve cords (ventral, lateral, and dorsal) linked together by some transverse connectives and numerous ring commissures. Peripheral cholinergic innervation was detected in oral and ventral suckers and in some parts of female reproductive system in both species, but there were some differences. The possible functions of some of these nervous components are discussed. PMID:27130318

  1. Immunizing potential of ultraviolet-attenuated cercariae of Schistosoma mansoni in rodent hosts.

    PubMed

    Kamiya, H; Ozaki, T; Nakayama, H; Inaba, T

    1993-01-01

    Schistosoma mansoni cercariae attenuated with ultraviolet (UV) irradiation (254 nm) at a dose of 18 mJ/cm2 induced partial resistance against a homologous challenge in male ICR mice and male Hartley guinea pigs. The reduction in the adult worm burden was 51% and 37% +/- 13%, respectively. On the other hand, male and female Mongolian gerbils (Meriones unguiculatus) vaccinated with UV-attenuated cercariae exhibited marginal resistance (13% +/- 9% and 22% +/- 10%, respectively). This raises the possibility that gerbils might have an unknown immune-characteristic nature. The usefulness of UV-attenuated cercariae is discussed with respect to the control of the disease. PMID:8327451

  2. Digenetic larvae in Schistosome snails from El Fayoum, Egypt with detection of Schistosoma mansoni in the snail by PCR.

    PubMed

    Aboelhadid, Shawky M; Thabet, Marwa; El-Basel, Dayhoum; Taha, Ragaa

    2016-09-01

    The present study aims to detect the digenetic larvae infections in Bulinus truncatus and Biomphalaria alexandrina snails and also PCR detection of Schistosoma mansoni infection. The snails were collected from different branches of Yousef canal and their derivatives in El Fayoum Governorate. The snails were investigated for infection through induction of cercarial shedding by exposure to light and crushing of the snails. The shed cercariae were S. mansoni, Pharyngeate longifurcate type I and Pharyngeate longifurcate type II from B. alexandrina, while that found in B. truncatus were Schitosoma haematobium and Xiphidiocercaria species cercariae. The seasonal prevalence of infection was discussed. Polymerase chain reaction was used for the detection of S. mansoni in the DNA from field collected infected and non infected snails. The results of PCR showed that the pool of B. alexandrina snails which shed S. mansoni cercariae in the laboratory, gave positive reaction in the samples. Pooled samples of field collected B. alexandrina that showed negative microscopic shedding of cercariae gave negative and positive PCR in a consecutive manner. Accordingly, a latent infection in the snail (negative microscopic) could be detected by using PCR. PMID:27605774

  3. Involvement of IL-18 in the Expansion of Unique Hepatic T Cells with Unconventional Cytokine Profiles during Schistosoma mansoni Infection

    PubMed Central

    Adachi, Keishi; Nakamura, Risa; Osada, Yoshio; Senba, Masachika; Tamada, Koji; Hamano, Shinjiro

    2014-01-01

    Infection with schistosomes invokes severe fibrotic granulomatous responses in the liver of the host. Schistosoma mansoni infection induces dramatic fluctuations in Th1 or Th2 cytokine responses systemically; Th1 reactions are provoked in the early phase, whilst Th2 responses become dominant after oviposition begins. In the liver, various unique immune cells distinct from those of conventional immune competent organs or tissues exist, resulting in a unique immunological environment. Recently, we demonstrated that S. mansoni infection induces unique CD4+ T cell populations exhibiting unconventional cytokine profiles in the liver of mice during the period between Th1- and Th2-phases, which we term the transition phase. They produce both IFN-γ and IL-4 or both IFN-γ and IL-13 simultaneously. Moreover, T cells secreting triple cytokines IFN-γ, IL-13 and IL-4 were also induced. We term these cells Multiple Cytokine Producing Hepatic T cells (MCPHT cells). During the transition phase, when MCPHT cells increase, IL-18 secretion was up-regulated in the liver and sera. In S. mansoni-infected IL-18-deficient mice, expansion of MCPHT cells was curtailed. Thus our data suggest that IL-18 produced during S. mansoni infection play a role in the expansion of MCPHT cells. PMID:24824897

  4. Efficacy and Safety of Arachidonic Acid for Treatment of School-Age Children in Schistosoma mansoni High-Endemicity Regions

    PubMed Central

    Barakat, Rashida; Abou El-Ela, Nadia E.; Sharaf, Soraya; El Sagheer, Ola; Selim, Sahar; Tallima, Hatem; Bruins, Maaike J.; Hadley, Kevin B.; El Ridi, Rashika

    2015-01-01

    Arachidonic acid (ARA), an omega-6 fatty acid, is a potent schistosomicide that displayed significant and safe therapeutic effects in Schistosoma mansoni-infected schoolchildren in S. mansoni low-prevalence regions. We here report on ARA efficacy and safety in treatment of schoolchildren in S. mansoni high-endemicity areas of Kafr El Sheikh, Egypt. The study was registered with ClinicalTrials.gov (NCT02144389). In total, 268 schoolchildren with light, moderate, or heavy S. mansoni infection were assigned to three study arms of 87, 91, and 90 children and received a single dose of 40 mg/kg praziquantel (PZQ), ARA (10 mg/kg per day for 15 days), or PZQ combined with ARA, respectively. The children were examined before and after treatment for stool parasite egg counts and blood biochemical, hematological, and immunological parameters. ARA, like PZQ, induced moderate cure rates (50% and 60%, respectively) in schoolchildren with light infection and modest cure rates (21% and 20%, respectively) in schoolchildren with high infection. PZQ and ARA combined elicited 83% and 78% cure rates in children with light and heavy infection, respectively. Biochemical and immunological profiles were either unchanged or ameliorated after ARA therapy. Combination of PZQ and ARA might be useful for treatment of children with schistosomiasis in high-endemicity regions. PMID:25624403

  5. Risk Factors and Spatial Distribution of Schistosoma mansoni Infection among Primary School Children in Mbita District, Western Kenya

    PubMed Central

    Nagi, Sachiyo; Chadeka, Evans A.; Sunahara, Toshihiko; Mutungi, Faith; Justin, Yombo K. Dan; Kaneko, Satoshi; Ichinose, Yoshio; Matsumoto, Sohkichi; Njenga, Sammy M.; Hashizume, Masahiro; Shimada, Masaaki; Hamano, Shinjiro

    2014-01-01

    Background An increasing risk of Schistosoma mansoni infection has been observed around Lake Victoria, western Kenya since the 1970s. Understanding local transmission dynamics of schistosomiasis is crucial in curtailing increased risk of infection. Methodology/Principal Findings We carried out a cross sectional study on a population of 310 children from eight primary schools. Overall, a total of 238 (76.8%) children were infected with S. mansoni, while seven (2.3%) had S. haematobium. The prevalence of hookworm, Trichuris trichiura and Ascaris lumbricoides were 6.1%, 5.2% and 2.3%, respectively. Plasmodium falciparum was the only malaria parasite detected (12.0%). High local population density within a 1 km radius around houses was identified as a major independent risk factor of S. mansoni infection. A spatial cluster of high infection risk was detected around the Mbita causeway following adjustment for population density and other potential risk factors. Conclusions/Significance Population density was shown to be a major factor fuelling schistosome infection while individual socio-economic factors appeared not to affect the infection risk. The high-risk cluster around the Mbita causeway may be explained by the construction of an artificial pathway that may cause increased numbers of S. mansoni host snails through obstruction of the waterway. This construction may have, therefore, a significant negative impact on the health of the local population, especially school-aged children who frequently come in contact with lake water. PMID:25058653

  6. Ultrastructural studies of the killing of schistosomula of Schistosoma mansoni by activated macrophages in vitro.

    PubMed

    McLaren, D J; James, S L

    1985-05-01

    Immunologically activated murine macrophages have been shown elsewhere to kill skin stage schistosomula of Schistosoma mansoni in vitro, in a manner analogous to the extracellular killing of tumour cell targets. In this study, the kinetics of the interaction between activated macrophages and larval targets and the resultant ultrastructural changes in parasite morphology that culminated in death have been analysed in detail. Unlike granulocyte-mediated schistosomular killing, macrophage-mediated cytotoxicity did not appear to be directed against the surface tissues of the parasite. Macrophages adhered only transiently following initiation of the cultures, yet changes in the subtegumental mitochondria and muscle cells of the larva were detected within the first hour of incubation. Progressive internal disorganisation followed rapidly, but the tegument and tegumental outer membrane remained intact, to form a 'shell' that maintained the general shape of the parasite. Such changes were recognised irrespective of whether the effector cell population comprised peritoneal macrophages activated by lymphokine treatment in vitro, or by infection with Mycobacterium bovis (strain BCG), or S. mansoni in vivo. That macrophages rather than contaminating granulocytes or lymphocytes, had mediated the observed damage was demonstrated by the use of a lymphokine treated macrophage cell line, IC-21. The observation that macrophage cytotoxicity is directed against internal organelles rather than the tegumental outer membrane of this multicellular target, may help to elucidate the general mechanism of extracellular killing by these cells. PMID:3892433

  7. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

    1987-11-01

    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

  8. Regional and splenic lymphocyte proliferative responses of mice exposed to normal or irradiated Schistosoma mansoni cercariae

    SciTech Connect

    Lewis, F.A.; Wilson, E.M.

    1982-05-01

    Developing larvae of Schistosoma mansoni migrate through various tissues en route to the liver and mesenteric veins of their definitive host. Regional (lymph node) and systemic (spleen) blastogenic responses to cercarial, adult and egg antigens were measured in CBA/J mice at various times after exposure to normal or irradiated S. mansoni cercariae. Among the separate lymph node groups studied were those draining the tail, thoracic region, intestines, head and neck, and the pelvis. Blastogenic responses were assayed by a micromethod requiring 10(5) cells in 20 microliter volumes per culture. Up to 5 weeks post-cercarial exposure the pattern of responses in lymphoid tissues of infected mice coincided with the migratory route of the parasites. Following oviposition, cellular reactivity was pronounced in all lymph node groups. The reactivity of mice exposed to irradiated cercariae followed a pattern suggestive of a sustained antigenic stimulus only in the nodes draining the tail and lungs. Splenic (systemic) reactivity was roughly comparable between the two exposure groups. These data show the independence and vast differences in the host regional responses following normal or irradiated cercarial exposure.

  9. Efficacy of Niclosamide as a potential topical antipenetrant (TAP) against cercariae of Schistosoma mansoni in monkeys.

    PubMed

    Bruce, J I; Miller, R; Lightner, L; Yoganathan, S

    1992-01-01

    A 1% (W/V) formulation of Niclosamide (2', 5-Dichloro-4-nitrosalicylanilide) (TAP) was tested on Cebus apella monkeys as a topical prophylactic against schistosomiasis mansoni. Two experiments were conducted using the same formulation. In the first experiment, the TAP provided complete protection against schistosomiasis for 3 days. Of the 4 monkeys treated with TAP 7 days before exposure to Schistosoma mansoni cercariae, 2 were completely protected. The remaining 2 monkeys of the 7 day treatment group had a 78% or greater reduction in adult worm burdens when compared to the placebo treated monkeys. The second experiment was designed to determine the time between day 3 and 7 when the TAP no longer provided complete protection. However, all of the TAP treated monkeys in this experiment were completely protected, even the monkeys treated 7 days earlier. In both experiments, all monkeys used as infection controls and those receiving only the placebo became infected and showed typical experimental schistosomiasis. These results demonstrate that the TAP could provide fast acting, short-term protection to people who must enter cercariae infested water. PMID:1343909

  10. QSAR-Driven Discovery of Novel Chemical Scaffolds Active against Schistosoma mansoni.

    PubMed

    Melo-Filho, Cleber C; Dantas, Rafael F; Braga, Rodolpho C; Neves, Bruno J; Senger, Mario R; Valente, Walter C G; Rezende-Neto, João M; Chaves, Willian T; Muratov, Eugene N; Paveley, Ross A; Furnham, Nicholas; Kamentsky, Lee; Carpenter, Anne E; Silva-Junior, Floriano P; Andrade, Carolina H

    2016-07-25

    Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol-3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents. PMID:27253773

  11. Impact of experimental duel infections with Schistosoma mansoni and Echinoccocus granulosus on hepatic histopathology.

    PubMed

    Elwakil, Hala S; Ali, Nehad M; Talaat, Roba M; Osman, Wesam M

    2007-12-01

    Experimental duel infection with S. mansoni and E. granulosus was induced in mice to determine their effect on serum nitric oxide (NO) level and accordingly on the sequences of histopathological lesions affecting the liver. The results showed that serum NO level was significantly increased (p<0.05) in mice infected with both parasites (GI) in comparison to either S. mansoni (GIV) or E. granulosus (GV). The NO elevation on hepatic pathological lesions of both diseases showed a marked reduction of granuloma size with absence of concentric fibrosis in GI as early as 4 weeks of concomitant infection as compared to GIV. In spite of the significant increase of NO level when E. granulosus infection induced in late stages of schistosomisais (GsII & III), yet granuloma size was not suppressed. Also, there was absence or death of hydatid cyst in mice (GI) compared to E. granulosus (GV). So, the duel infection with the two parasites affected serum NO level and hepatic histopathology, by ameliorative or deteriorative effects, according to duration of infection with either. PMID:18431992

  12. Evolution of sex chromosomes ZW of Schistosoma mansoni inferred from chromosome paint and BAC mapping analyses.

    PubMed

    Hirai, Hirohisa; Hirai, Yuriko; LoVerde, Philip T

    2012-12-01

    Chromosomes of schistosome parasites among digenetic flukes have a unique evolution because they exhibit the sex chromosomes ZW, which are not found in the other groups of flukes that are hermaphrodites. We conducted molecular cytogenetic analyses for investigating the sex chromosome evolution using chromosome paint analysis and BAC clones mapping. To carry this out, we developed a technique for making paint probes of genomic DNA from a single scraped chromosome segment using a chromosome microdissection system, and a FISH mapping technique for BAC clones. Paint probes clearly identified each of the 8 pairs of chromosomes by a different fluorochrome color. Combination analysis of chromosome paint analysis with Z/W probes and chromosome mapping with 93 BAC clones revealed that the W chromosome of Schistosoma mansoni has evolved by at least four inversion events and heterochromatinization. Nine of 93 BAC clones hybridized with both the Z and W chromosomes, but the locations were different between Z and W chromosomes. The homologous regions were estimated to have moved from the original Z chromosome to the differentiated W chromosome by three inversions events that occurred before W heterohcromatinization. An inversion that was observed in the heterochromatic region of the W chromosome likely occurred after W heterochromatinization. These inversions and heterochromatinization are hypothesized to be the key factors that promoted the evolution of the W chromosome of S. mansoni. PMID:22831897

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

    PubMed

    Mickum, Megan L; Rojsajjakul, Teerapat; Yu, Ying; Cummings, Richard D

    2016-03-01

    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 Galβ1-4(Fucα1-3)GlcNAcβ-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 Galβ1-4GlcNAc-R, but notably not the LDN sequence GalNAcβ1-4GlcNAc-R, to generate Lewis X type-glycans, and smFuT-F transcripts are present in all intramammalian life stages. PMID:26582608

  14. Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite.

    PubMed

    Mafud, Ana C; Silva, Marcos P N; Monteiro, Daniela C; Oliveira, Maria F; Resende, João G; Coelho, Mayara L; de Sousa, Damião P; Mendonça, Ronaldo Z; Pinto, Pedro L S; Freitas, Rivelilson M; Mascarenhas, Yvonne P; de Moraes, Josué

    2016-01-25

    The use of natural products has a long tradition in medicine, and they have proven to be an important source of lead compounds in the development of new drugs. Among the natural compounds, terpenoids present broad-spectrum activity against infective agents such as viruses, bacteria, fungi, protozoan and helminth parasites. In this study, we report a biological screening of 38 chemically characterized terpenes from different classes, which have a hydroxyl group connected by hydrophobic chain or an acceptor site, against the blood fluke Schistosoma mansoni, the parasite responsible for schistosomiasis mansoni. In vitro bioassays revealed that 3,7-dimethyl-1-octanol (dihydrocitronellol) (10) was the most active terpene (IC50 values of 13-52 μM) and, thus, we investigated its antischistosomal activity in greater detail. Confocal laser scanning microscopy revealed that compound 10 induced severe tegumental damage in adult schistosomes and a correlation between viability and tegumental changes was observed. Furthermore, we compared all the inactive compounds with dihydrocitronellol structurally by using shape and charge modeling. Lipophilicity (miLogP) and other molecular properties (e.g. molecular polar surface area, molecular electrostatic potential) were also calculated. From the 38 terpenes studied, compound 10 is the one with the greatest flexibility, with a sufficient apolar region by which it may interact in a hydrophobic active site. In conclusion, the integration of biological and chemical analysis indicates the potential of the terpene dihydrocitronellol as an antiparasitic agent. PMID:26697994

  15. Detection of Schistosoma mansoni circulating cathodic antigen for evaluation of resistance induced by irradiated cercariae.

    PubMed

    Barsoum, I S; Bogitsh, B J; Colley, D G

    1992-08-01

    The appearance of serum levels of circulating cathodic antigen (CCA) detectable by a monoclonal antibody (mAb) (5H11) antigen-capture sandwich enzyme-linked immunosorbent assay (ELISA) system was evaluated during acute Schistosoma mansoni infections in female CF1 mice exposed to either 100 or 25 cercariae. Measurable CCA levels occurred in these groups at 5 and 7 wk after infection, respectively. The kinetics of appearance of CCA were thus related to the intensity of infection. The level of resistance developed by female C57BL/6 mice upon immunization with irradiated cercariae, as expressed by both worm burden and CCA levels after cercarial challenge was evaluated. Immunization conferred 44% protection against the challenge infection, and the level of CCA detected in the sera of the control group was significantly (P less than 0.02) higher than that found in the sera of the immunized group, 6 wk after challenge. These results demonstrate that CCA detection by the 5H11 mAb antigen-capture sandwich ELISA can reflect vaccine-induced resistance against S. mansoni. Localization studies showed that 5H11 reacts with a CCA epitope in the adult worm gut and to a lesser extent with the male tegument. Adaptations of this and other antigen detection systems may prove useful in monitoring the efficacy of developmental vaccines, an ability that may be essential for the extension of such studies to humans. PMID:1635027

  16. Evaluation of protective immunity of 28KD-GST as a vaccine against experimental Schistosoma mansoni.

    PubMed

    Hassan, Mohsen M; Moustafa, Nahed E; El-Motayam, Mona H; El-Settawy, Magda A; Taha, Afaf A

    2009-08-01

    Schistosoma mansoni GST was purified from adult worm homogenates by affinity chromatography. SDS-PAGE analysis of the purified antigen revealed that SmGST has molecular weight around 28 KD was used as a vaccine in a dose of 25 and 35 microg. Eleven groups of BALB/c mice of 10 mice each were vaccinated by GST. Complete Freund's adjuvant (CFA) and BCG vaccine were used as adjuvant. Booster doses were given after 2 & 4 weeks. Two weeks after the last dose of vaccine, mice were challenged by S. mansoni cercariae. Blood samples were taken 7 weeks post infection for detection of IgGl, IgE and circulating antigens. Then mice were sacrificed for histopathological study of the liver. Highly significant (p > 0.001) increase in the mean optical density of IgGl & IgE in groups vaccinated by 35 microg GST and CFA was demonstrated. On the other hand, highly significant (P < 0.001) decrease in circulating antigen, grnuloma number and size in the same group. PMID:19795747

  17. Cellular and humoral immune responses to recombinant Smp17.7 Schistosoma mansoni antigen.

    PubMed

    Al-Sherbiny, Maged M; Galal, Iman F; Karim, Amr M; Ashour, Ameen A; Saad, Abdel-Hakim M

    2003-12-01

    To determine the immunological responses to S. mansoni antigen rSmp17.7, a total of 184 subjects, 174 patients from a schistosomiasis endemic area, and 10 controls were used. Proliferation, cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells and specific IgG1, IgG3, IgG4, IgA, IgM & IgE levels were assessed. The highest stimulation index to rSmp17.7 was detected in S. mansoni patients. The evaluation of the cytokine profile [IL-2, IL-4 & IFN-gamma] in response to this antigen showed a significant increase as demonstrated by ELISA. Specifically, IFN-gamma and IL-2 were significantly detected by flow cytometry. IgG1 and IgM were the only Igs which showed a significant increase. These results highlight the importance of rSmp17.7 as a candidate vaccine for schistosomiasis. The results pave the way to understand the mechanism of schistosome-vaccine efficacy. PMID:14708863

  18. Schistosoma mansoni: autoantibodies and polyclonal B cell activation in infected mice.

    PubMed Central

    Fischer, E; Camus, D; Santoro, F; Capron, A

    1981-01-01

    The appearance of autoantibodies was investigated during the course of Schistosoma mansoni infection in C57Bl/6 mice. Anti-liver autoantibodies or lymphocyte-reactive alloantibodies were detected respectively without cell-mediated immunity against liver antigen or lymphocytotoxic activity. Anti-liver, anti-DNA, anti-Ig and anti-lymphocyte antibodies were shown 6-7 weeks after the beginning of the infection concomitantly with the increase of immunoglobulin levels and circulating immune complexes. At this period, the antibody response to polyvinylpyrrolidone (PVP) was increased and the injection of spleen cells from day-45-infected mice to uninfected recipients increased the anti-PVP antibody response. Conversely, the injection of spleen cells from uninfected to infected mice did not modify the anti-PVP Ab response. After 6 weeks of infection, the basal thymidine incorporation of spleen cells was increased contrasting with the marked inhibition of spleen cell response to PHA. The present data are consistent with the induction of a polyclonal non-specific B cell activation by S. mansoni. PMID:6978217

  19. Discovery of new inhibitors of Schistosoma mansoni PNP by pharmacophore-based virtual screening.

    PubMed

    Postigo, Matheus P; Guido, Rafael V C; Oliva, Glaucius; Castilho, Marcelo S; da R Pitta, Ivan; de Albuquerque, Julianna F C; Andricopulo, Adriano D

    2010-09-27

    Schistosomiasis is considered the second most important tropical parasitic disease, with severe socioeconomic consequences for millions of people worldwide. Schistosoma mansoni , one of the causative agents of human schistosomiasis, is unable to synthesize purine nucleotides de novo, which makes the enzymes of the purine salvage pathway important targets for antischistosomal drug development. In the present work, we describe the development of a pharmacophore model for ligands of S. mansoni purine nucleoside phosphorylase (SmPNP) as well as a pharmacophore-based virtual screening approach, which resulted in the identification of three thioxothiazolidinones (1-3) with substantial in vitro inhibitory activity against SmPNP. Synthesis, biochemical evaluation, and structure-activity relationship investigations led to the successful development of a small set of thioxothiazolidinone derivatives harboring a novel chemical scaffold as new competitive inhibitors of SmPNP at the low-micromolar range. Seven compounds were identified with IC(50) values below 100 μM. The most potent inhibitors 7, 10, and 17 with IC(50) of 2, 18, and 38 μM, respectively, could represent new potential lead compounds for further development of the therapy of schistosomiasis. PMID:20695479

  20. Immunolocalization of Schistosoma mansoni and Schistosoma haematobium antigens reacting with their Egyptian snail vectors.

    PubMed

    El-Dafrawy, Shadia M; Mohamed, Amira H; Hammam, Olfat A; Rabia, Ibrahim

    2007-12-01

    The reaction of the haemolymph and the tissue of infected intermediate hosts, Biomphalaria alexandrina and Bulinus truncatus to Schistosoma mansoni and S. haematobium antigens were investigated using the indirect immunoperoxidase technique. A new technique, Agarose cell block was used in collection of haemolymph which helped in collecting plenty of well formed cells in comparison to the ordinary one using the cytospin. Collected haemolymph and prepared tissues of uninfected and infected B. alexandria and B. truncatus were fixed and then reacted with anti-S. mansoni and anti-S. haematobium IgG polyclonal antibodies. The haemolymph and tissue of infected B. alexandrina and B. truncatus gave a positive peroxidase reaction represented by a brown colour. In haemolymph, the positive peroxidase reaction was detected mainly in the cytoplasm of the amoebocytes. In the tissue, it was detected in epithelial cells lining the tubules, male cells in the lumen of the tubules and in female oogonia cells along the periphery of the tubules. The similarity in the strength and distribution of positive reaction in B. alexandrina and B. truncates was observed as compared to control. Thus, the immunoperoxidase technique proved to be an effective indicator for the schistosome-antigen in the snails. PMID:18383803

  1. Preliminary trials with praziquantel in human infections due to Schistosoma mansoni

    PubMed Central

    Katz, N.; Rocha, R.S.; Chaves, A.

    1979-01-01

    As part of a programme of multicentre trials of the tolerance and therapeutic effect of praziquantel, clinical trials were carried out in Brazil in patients with active Schistosoma mansoni infections, each of whom had a minimum geometric mean egg output of 100 eggs per gram of faeces calculated from multiple pretreatment stool examinations. The first stage was a double-blind assessment of tolerance and efficacy of oral doses of 1 × 20, 2 × 20, or 3 × 20 mg of praziquantel per kg of body weight. Subsequently, single-blind trials explored the effects of 3 × 20 mg/kg at 4-hourly intervals, and a single dose of 50 mg/kg. Side effects increased in frequency as dosage increased. Nausea, epigastric pain, headache, dizziness, and drowsiness were all noted but their severity was mild or moderate and they disappeared in 48 hours. In general, monitoring laboratory tests showed little change. Following a stringent parasitological follow-up, 96% of 28 patients followed at 1 year after treatment with either 3 × 20 mg/kg or 1 × 50 mg/kg were cured. Praziquantel seems to be a very promising drug against S. mansoni and further clinical trials should be strongly encouraged. PMID:396054

  2. Differential gene expression in haemocytes of the snail Biomphalaria glabrata: effects of Schistosoma mansoni infection.

    PubMed

    Miller, A N; Raghavan, N; FitzGerald, P C; Lewis, F A; Knight, M

    2001-05-15

    Parasite encapsulation and destruction in Biomphalaria glabrata has been shown to involve the cellular component of the snail's internal defence system, the haemocytes. To identify genes involved in the immunobiology of these cells, we used the method of differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) to investigate differential gene regulation in haemocytes isolated from Schistosoma mansoni exposed and unexposed snails. RNA isolated from circulating haemocytes from resistant snails (BS-90 stock), previously exposed to S. mansoni, was analysed using 12 different arbitrary primers in conjunction with an anchored Oligo d(T(11)CG) primer. Transcription profiles between haemocytes of parasite exposed and unexposed snails were compared and a total of 87 differentially regulated bands were identified and isolated. Of these, 65 bands were cloned and used as probes in Southern blots to show the presence of corresponding sequences in the snail genome. RT-PCR was performed to verify the regulation of these transcripts. DNA sequence analysis showed that the majority of the cloned sequences were novel, although a few showed a high degree of sequence similarity to other sequences in the DNA and protein databases. One of these included a differentially expressed transcript that showed a significant degree of sequence identity to E. coli transposase Tn5, an enzyme whose activity is normally associated with generating mobility and instability in the genome. PMID:11336750

  3. Polymerase Chain Reaction: A Better Method for Diagnosing Chronic Schistosoma mansoni Infections

    PubMed Central

    Abdel-Hafeez, Ekhlas Hamed; Mohamed, Rabie M.; Belal, Usama S.; Abdel-Raheem, Ehab M.; Naoi, Koji; Norose, Kazumi

    2015-01-01

    For more effective diagnosis of the acute and chronic stages of Schistosoma mansoni infection in humans, the polymerase chain reaction (PCR) technique was compared with the Kato-Katz method. A total of 150 stool samples were collected from inpatient and outpatient clinics at the Department of Tropical Medicine, Minia University Hospital, Egypt. Three groups of patients, 50 with acute intestinal schistosomiasis, 70 with chronic intestinal schistosomiasis and 30 normal healthy controls were studied. Stool samples were analyzed by PCR and the Kato-Katz method. The mean number of eggs per gram of feces was 4.6 when estimated by the Kato-Katz method in positive stool samples from acute schistosomiasis cases but only 1.7 in chronic cases. In acute intestinal schistosomiasis, 15 and 45 out of 50 cases were positive by Kato-Katz and PCR, respectively. In the chronic intestinal schistosomiasis cases, 6 and 68 out of 70 cases were positive by the Kato-Katz and PCR methods, respectively. We conclude that PCR appears to be an effective diagnostic technique for S. mansoni infection, especially where a low worm burden exists, such as in chronic cases. PMID:26865821

  4. Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and Secretion

    PubMed Central

    Truscott, Martha; Evans, D. Andrew; Gunn, Matt

    2013-01-01

    The trematode Schistosoma mansoni is one of the etiological agents of schistosomiasis, a key neglected tropical disease responsible for an estimated annual loss of 70 million disability-adjusted life years. Hematophagy represents the primary nutrient acquisition pathway of this parasite, but digestion of hemoglobin also liberates toxic heme. Schistosomes detoxify heme via crystallization into hemozoin, which is subsequently regurgitated into the host's circulation. Here we demonstrate that during experimental schistosomiasis, hemozoin accumulating in the mouse liver is taken up by phagocytes at a time coincident with the development of the egg-induced T-helper 2 (Th2) granulomatous immune response. Furthermore, the uptake of hemozoin also coincides with the hepatic expression of markers of alternative macrophage activation. Alternatively activated macrophages are a key effector cell population associated with protection against schistosomiasis, making hemozoin well placed to play an important immunomodulatory role in this disease. To systematically explore this hypothesis, S. mansoni hemozoin was purified and added to in vitro bone marrow-derived macrophage cultures concurrently exposed to cytokines chosen to reflect the shifting state of macrophage activation in vivo. Macrophages undergoing interleukin-4 (IL-4)-induced alternative activation in the presence of hemozoin developed a phenotype specifically lacking in Retnla, a characteristic alternatively activated macrophage product associated with regulation of Th2 inflammatory responses. As such, in addition to its important detoxification role during hematophagy, we propose that schistosome hemozoin also provides a potent immunomodulatory function in the coevolved network of host-parasite relationships during schistosomiasis. PMID:23090958

  5. The distinct C-terminal acidic domains of HMGB proteins are functionally relevant in Schistosoma mansoni.

    PubMed

    de Abreu da Silva, Isabel Caetano; Carneiro, Vitor Coutinho; Vicentino, Amanda Roberta Revoredo; Aguilera, Estefania Anahi; Mohana-Borges, Ronaldo; Thiengo, Silvana; Fernandez, Monica Ammon; Fantappié, Marcelo Rosado

    2016-04-01

    The Schistosoma mansoni High Mobility Group Box (HMGB) proteins SmHMGB1, SmHMGB2 and SmHMGB3 share highly conserved HMG box DNA binding domains but have significantly different C-terminal acidic tails. Here, we used three full-length and tailless forms of the S. mansoni HMGB proteins to examine the functional roles of their acidic tails. DNA binding assays revealed that the different lengths of the acidic tails among the three SmHMGB proteins significantly and distinctively influenced their DNA transactions. Spectroscopic analyses indicated that the longest acidic tail of SmHMGB3 contributes to the structural stabilisation of this protein. Using immunohistochemical analysis, we showed distinct patterns of SmHMGB1, SmHMGB2 and SmHMGB3 expression in different tissues of adult worms. RNA interference approaches indicated a role for SmHMGB2 and SmHMGB3 in the reproductive system of female worms, whereas for SmHMGB1 no clear phenotype was observed. Schistosome HMGB proteins can be phosphorylated, acetylated and methylated. Importantly, the acetylation and methylation of schistosome HMGBs were greatly enhanced upon removal of the acidic tail. These data support the notion that the C-terminal acidic tails dictate the differences in the structure, expression and function of schistosome HMGB proteins. PMID:26820302

  6. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy.

    PubMed

    Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lúcia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Corrêa-Oliveira, Rodrigo; Teixeira-Carvalho, Andréa

    2013-01-01

    Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. PMID:23401741

  7. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    PubMed Central

    Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lúcia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Corrêa-Oliveira, Rodrigo; Teixeira-Carvalho, Andréa

    2013-01-01

    Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. PMID:23401741

  8. Histamine signalling in Schistosoma mansoni: immunolocalisation and characterisation of a new histamine-responsive receptor (SmGPR-2).

    PubMed

    El-Shehabi, Fouad; Ribeiro, Paula

    2010-10-01

    In parasitic platyhelminthes, including Schistosoma mansoni, biogenic amines play several important roles in the control of motility, metabolism and reproduction. A bioinformatics analysis of the S. mansoni genome identified approximately 16 full-length G protein-coupled receptors (GPCRs) that share significant homology with aminergic receptors from other species. Six of these sequences are structurally related to SmGPR-1 (formerly SmGPCR), a previously described histamine receptor of S. mansoni, and constitute a new clade of amine-like GPCRs. Here we report the cloning of a second member of this clade, named SmGPR-2. The full-length receptor cDNA was expressed in Saccharomyces cerevisiae and shown to be activated by histamine and 1-methylhistamine, whereas other common biogenic amines had no significant effect. Antagonist assays showed that SmGPR-2 was inhibited by classical biogenic amine antagonists but the pharmacological profile was unlike those of known mammalian histamine receptors. Confocal immunolocalisation studies revealed that SmGPR-2 was expressed in the nervous system and was particularly enriched in the subtegumental neuronal plexus of adult S. mansoni and larvae. The ligand, histamine, was found to be widely distributed, mainly in the peripheral nervous system including the subtegumental plexus where the receptor is also expressed. Finally, SmGPR-2 was shown to be developmentally regulated at the RNA level. Quantitative PCR studies showed it was up-regulated in the parasitic stages compared with cercaria and expressed at the highest level in young schistosomula. The widespread distribution of histamine and the presence of at least two receptors in S. mansoni suggest that this transmitter is an important neuroactive substance in schistosomes. PMID:20430030

  9. Metabolic profiling of a Schistosoma mansoni infection in mouse tissues using magic angle spinning-nuclear magnetic resonance spectroscopy.

    PubMed

    Li, Jia V; Holmes, Elaine; Saric, Jasmina; Keiser, Jennifer; Dirnhofer, Stephan; Utzinger, Jürg; Wang, Yulan

    2009-04-01

    In order to enhance our understanding of physiological and pathological consequences of a patent Schistosoma mansoni infection in the mouse, we examined the metabolic responses of different tissue samples recovered from the host animal using a metabolic profiling strategy. Ten female NMRI mice were infected with approximately 80 S. mansoni cercariae each, and 10 uninfected age- and sex-matched animals served as controls. At day 74 post infection (p.i.), mice were killed and jejunum, ileum, colon, liver, spleen and kidney samples were removed. We employed (1)H magic angle spinning-nuclear magnetic resonance spectroscopy to generate tissue-specific metabolic profiles. The spectral data were analyzed using multivariate modelling methods including an orthogonal signal corrected-projection to latent structure analysis and hierarchical principal component analysis to assess the differences and/or similarities in metabolic responses between infected and non-infected control mice. Most tissues obtained from S. mansoni-infected mice were characterized by high levels of amino acids, such as leucine, isoleucine, lysine, glutamine and asparagine. High levels of membrane phospholipid metabolites, including glycerophosphoryl choline and phosphoryl choline were found in the ileum, colon, liver and spleen of infected mice. Additionally, low levels of energy-related metabolites, including lipids, glucose and glycogen were observed in ileum, spleen and liver samples of infected mice. Energy-related metabolites in the jejunum, liver and renal medulla were found to be positively correlated with S. mansoni worm burden upon dissection. These findings show that a patent S. mansoni infection causes clear disruption of metabolism in a range of tissues at a molecular level, which can be interpreted in relation to the previously reported signature in a biofluid (i.e. urine), giving further evidence of the global effect of the infection. PMID:19068218

  10. Miltefosine lipid nanocapsules: Intersection of drug repurposing and nanotechnology for single dose oral treatment of pre-patent schistosomiasis mansoni.

    PubMed

    El-Moslemany, Riham M; Eissa, Maha M; Ramadan, Alyaa A; El-Khordagui, Labiba K; El-Azzouni, Mervat Z

    2016-07-01

    A dual drug repurposing/nanotechnological approach was used to develop an alternative oral treatment for schistosomiasis mansoni using miltefosine (MFS), an anticancer alkylphosphocholine, and lipid nanocapsules (LNCs) as oral nanovectors. We demonstrated earlier that MFS possesses significant activity against different developmental stages of Schistosoma mansoni in the mouse model using 5 successive 20mg/kg/day oral doses. Moreover, an effective single dose (20mg/kg) oral treatment against the adult stage of S. mansoni in mice was developed using LNCs, particularly modified with CTAB, a positive charge imparting agent (MFS-LNC-CTAB(+)), or oleic acid as membrane permeabilizer (MFS-LNC-OA). Efficacy enhancement involved, at least in part, targeting of the worm tegument with MFS-LNCs as a new therapeutic entity. As the tegument surface charge and composition may differ in pre-patent stages of the parasite, it was of importance in the present study to assess the efficacy of a single oral dose of the two MFS-LNC formulations against invasive and immature stages for potential advantage relative to praziquantel. Results indicated potent schistosomicidal effects against both invasive and immature stages of S. mansoni in infected mice, efficacy being both formulation and developmental stage dependent. This was indicated by the significant reduction in the total worm burden of the invasive stage by 91.6% and 76.8% and the immature stage by 82.7% and 96.7% for MFS-LNC-CTAB+ and MFS-LNC-OA, respectively. Histopathological findings indicated amelioration of hepatic pathology with regression of the granulomatous inflammatory reaction and reduction in granulomas number and size, verifying marked improvement in architecture of hepatic lobules. From a clinical perspective, MFS-LNCs offer potential as an alternative single oral dose nanomedicine with a wide therapeutic profile for the mass chemotherapy of schistosomiasis mansoni. PMID:27039667

  11. Acetylcholinesterase of Schistosoma mansoni--functional correlates. Contributed in honor of Professor Hans Neurath's 90th birthday.

    PubMed

    Arnon, R; Silman, I; Tarrab-Hazdai, R

    1999-12-01

    Acetylcholinesterase (AChE) is an enzyme broadly distributed in many species, including parasites. It occurs in multiple molecular forms that differ in their quaternary structure and mode of anchoring to the cell surface. This review summarizes biochemical and immunological investigations carried out in our laboratories on AChE of the helmint, Schistosoma mansoni. AChE appears in S. mansoni in two principal molecular forms, both globular, with sedimentation coefficients of approximately 6.5 and 8 S. On the basis of their substrate specificity and sensitivity to inhibitors, both are "true" acetylcholinesterases. Approximately half of the AChE activity of S. mansoni is located on the outer surface of the parasite, attached to the tegumental membrane via a covalently attached glycosylphosphatidylinositol anchor. The remainder is located within the parasite, mainly associated with muscle tissue. Whereas the internal enzyme is most likely involved in termination of neurotransmission at cholinergic synapses, the role of the surface enzyme remains to be established; there are, however, indications that it is involved in signal transduction. The two forms of AChE differ in their heparin-binding properties, only the internal 8 S form of the AChE being retained on a heparin column. The two forms differ also in their immunological specificity, since they are selectively recognized by different monoclonal antibodies. Polyclonal antibodies raised against S. mansoni AChE purified by affinity chromatography are specific for the parasite AChE, reacting with both molecular forms, but do not recognize AChE from other species. They interact with the surface-localized enzyme on the intact organism, and produce almost total complement-dependent killing of the parasite. S. mansoni AChE is thus demonstrated to be a functional protein, involved in multifaceted activities, which can serve as a suitable candidate for diagnostic purposes, vaccine development, and drug design. PMID:10631970

  12. A Very High Infection Intensity of Schistosoma mansoni in a Ugandan Lake Victoria Fishing Community Is Required for Association with Highly Prevalent Organ Related Morbidity

    PubMed Central

    Tukahebwa, Edridah M.; Magnussen, Pascal; Madsen, Henry; Kabatereine, Narcis B.; Nuwaha, Fred; Wilson, Shona; Vennervald, Birgitte J.

    2013-01-01

    Background In schistosomiasis control programmes using mass chemotherapy, epidemiological and morbidity aspects of the disease need to be studied so as to monitor the impact of treatment, and make recommendations accordingly. These aspects were examined in the community of Musoli village along Lake Victoria in Mayuge district, highly endemic for Schistosoma mansoni infection. Methodology and Principal Findings A cross sectional descriptive study was undertaken in a randomly selected sample of 217 females and 229 males, with a mean age of 26 years (SD ±16, range 7–76 years). The prevalence of S. mansoni was 88.6% (95% CI: 85.6–91.5). The geometric mean intensity (GMI) of S. mansoni was 236.2 (95% CI: 198.5–460.9) eggs per gram (epg) faeces. Males had significantly higher GMI (370.2 epg) than females (132.6 epg) and age was also significantly associated with intensity of infection. Levels of water contact activities significantly influenced intensity of infection and the highest intensity of infection was found among people involved in fishing. However, organomegaly was not significantly associated with S. mansoni except for very heavy infection (>2000 epg). Liver image patterns C and D indicative of fibrosis were found in only 2.2% and 0.2%, respectively. S. mansoni intensity of infection was associated with portal vein dilation and abnormal spleen length. Anaemia was observed in 36.4% of the participants but it was not associated with S. mansoni infection intensity. Considering growth in children as one of the morbidity indicators of schistosomiasis, intensity of S. mansoni was significantly associated with stunting. Conclusion Although organ-related morbidity, with the exception of periportal fibrosis, and S. mansoni infections were highly prevalent, the two were only associated for individuals with very high infection intensities. These results contrast starkly with reports from Ugandan Lake Albert fishing communities in which periportal fibrosis is more

  13. Schistosoma mansoni Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation

    PubMed Central

    2016-01-01

    Background Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host. Methodology and Principal Findings The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs. Conclusion Taken together, these findings

  14. Environmental, genetic and immunological factors in human resistance to Schistosoma mansoni.

    PubMed

    Dessein, A J; Couissinier, P; Demeure, C; Rihet, P; Kohlstaedt, S; Carneiro-Carvalho, D; Ouattara, M; Goudot-Crozel, V; Dessein, H; Bourgois, A

    1992-08-01

    The design of programs for the control of endemies requires the knowledge of the principal factors that determine parasite transmission and infection levels in exposed populations. In the studies summarized in this article, the role of environmental and host specific factors in the infection by S. mansoni have been evaluated. It is shown that a limited number of factors actually influences infection intensity: water contacts, age, and sex were shown to account for 20 to 25% of infection variance, while 35 to 40% of it was accounted for by the effect of a major codominant gene. A remarkable fact is the important weighting (around 55% of the variance) of factors (the major gene and age) that influence human capacities of resistance. This observation strongly supports control measures aimed at increasing human resistance, such as vaccination. The effect of age on the development of resistance has now been observed in several studies on S. mansoni or S. haematobium. It is, therefore, a constant finding in schistosomiasis infections that resistance develops extremely slowly requiring a long period of exposure to the parasite and repeated infections. These studies provide strong incentives to increase efforts in the evaluation of the immune response of subjects living in endemic areas. Such evaluations are necessary to define vaccine and vaccination programs, and they are also urgently needed to evaluate the effects of chemotherapy on the development of immunity in children and adolescents, as well as on the persistence of protective immunity in adults. Immunological studies begin to provide a clearer picture of the role of acquired immunity in human protection against S. mansoni. It is increasingly clear that the slow development of resistance in children, as well as its alteration in certain age groups, are related to the maturation of parasite specific immunity and its alteration by specific immune factors. Thus, the development of resistance is associated with the

  15. Biological, biochemical and histopathological features related to parasitic castration of Biomphalaria glabrata infected by Schistosoma mansoni.

    PubMed

    Faro, Marta Julia; Perazzini, Mariana; Corrêa, Lygia dos Reis; Mello-Silva, Clélia Christina; Pinheiro, Jairo; Mota, Ester Maria; de Souza, Samaly; de Andrade, Zilton; Júnior, Arnaldo Maldonado

    2013-06-01

    Parasitic castration in the snail-trematode relationship can be understood as any change in the reproductive function of the snail that is due to interference by the developing larvae inside the snail that leads to the reduction or complete disruption of egg-laying activity. This study was designed to observe the parasitic castration of Biomphalaria glabrata infected with Schistosoma mansoni during both the pre-patent and patent periods. The effect of infection on snail fecundity and fertility, growth rate and survival was studied during the 62 days following miracidia exposure. An integrated approach was employed that used biochemical and histological tools over the same period. To study the effect of infection on reproduction, we individually exposed 30 snails to 5 miracidia each and tracked their fertility and fecundity. For our histopathological studies, 50 snails were exposed to 20 miracidia each, and for our histochemical studies, 50 snails were exposed to 5 miracidia each. An equal number of uninfected snails were used as a control for each group. The B. glabrata exposed to the BH strain of S. mansoni showed 50% positivity for cercarial shedding. Both the experimental and control groups showed 100% survival. The pre-patent period lasted until 39 days after exposure to miracidia. Exposed snails that showed cercarial shedding exhibited higher growth rates than either exposed snails that did not demonstrate cercarial shedding or uninfected controls. Exposed snails without cercarial shedding and uninfected controls showed no differences in the reproductive parameters evaluated during the patent period; snails experiencing cercarial shedding showed a reduction in fecundity and fertility. These snails began to lay eggs only after the 50th day post miracidia exposure. The haemolymph glucose levels showed an oscillating pattern that decreased during periods of greater mobilisation of energy by the larvae and was accompanied by a depletion of glycogen in the

  16. Venus Kinase Receptors Control Reproduction in the Platyhelminth Parasite Schistosoma mansoni

    PubMed Central

    Cailliau, Katia; Morel, Marion; Hahnel, Steffen; Leutner, Silke; Beckmann, Svenja; Grevelding, Christoph G.; Dissous, Colette

    2014-01-01

    The Venus Kinase Receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G Protein Coupled Receptors. This receptor tyrosine kinase (RTK) was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a large variety of invertebrates. A single vkr gene is found in most genomes, except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a unique family of RTKs present only in invertebrates and their biological functions are still to be discovered. In this work, we show that SmVKRs are expressed in the reproductive organs of S. mansoni, particularly in the ovaries of female worms. By transcriptional analyses evidence was obtained that both SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr expression by RNA interference induced spectacular morphological changes in female worms with a strong disorganization of the ovary, which was dominated by the presence of primary oocytes, and a defect of egg formation. Following expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be activated by distinct ligands which are L-Arginine and calcium ions, respectively. Signalling analysis in Xenopus oocytes revealed the capacity of SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c-Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results of yeast two-hybrid experiments identifying several components of the JNK pathway as specific interacting partners of SmVKR1. In conclusion, these results demonstrate the functions of SmVKR in gametogenesis, and particularly in oogenesis and egg formation. By eliciting signalling pathways potentially involved in oocyte proliferation, growth and migration

  17. A Novel Toll-Like Receptor (TLR) Influences Compatibility between the Gastropod Biomphalaria glabrata, and the Digenean Trematode Schistosoma mansoni

    PubMed Central

    Pila, Emmanuel A.; Tarrabain, Mahmoud; Kabore, Alethe L.; Hanington, Patrick C.

    2016-01-01

    Schistosomiasis, a devastating disease caused by parasitic flatworms of the genus Schistosoma, affects over 260 million people worldwide especially in tropical and sub-tropical regions. Schistosomes must undergo their larval development within specific species of snail intermediate hosts, a trait that is shared among almost all digenean trematodes. This unique and long-standing host-parasite relationship presents an opportunity to study both the importance of conserved immunological features in novel immunological roles, as well as new immunological adaptations that have arisen to combat a very specific type of immunological challenge. While it is well supported that the snail immune response is important for protecting against schistosome infection, very few specific snail immune factors have been identified and even fewer have been functionally characterized. Here, we provide the first functional report of a snail Toll-like receptor, which we demonstrate as playing an important role in the cellular immune response of the snail Biomphalaria glabrata following challenge with Schistosoma mansoni. This TLR (BgTLR) was identified as part of a peptide screen of snail immune cell surface proteins that differed in abundance between B. glabrata snails that differ in their compatibility phenotype to challenge by S. mansoni. The S. mansoni-resistant strain of B. glabrata (BS-90) displayed higher levels of BgTLR compared to the susceptible (M-line) strain. Transcript expression of BgTLR was found to be very responsive in BS-90 snails when challenged with S. mansoni, increasing 27 fold relative to β-actin (non-immune control gene); whereas expression in susceptible M-line snails was not significantly increased. Knockdown of BgTLR in BS-90 snails via targeted siRNA oligonucleotides was confirmed using a specific anti-BgTLR antibody and resulted in a significant alteration of the resistant phenotype, yielding patent infections in 43% of the normally resistant snails, which

  18. A Novel Toll-Like Receptor (TLR) Influences Compatibility between the Gastropod Biomphalaria glabrata, and the Digenean Trematode Schistosoma mansoni.

    PubMed

    Pila, Emmanuel A; Tarrabain, Mahmoud; Kabore, Alethe L; Hanington, Patrick C

    2016-03-01

    Schistosomiasis, a devastating disease caused by parasitic flatworms of the genus Schistosoma, affects over 260 million people worldwide especially in tropical and sub-tropical regions. Schistosomes must undergo their larval development within specific species of snail intermediate hosts, a trait that is shared among almost all digenean trematodes. This unique and long-standing host-parasite relationship presents an opportunity to study both the importance of conserved immunological features in novel immunological roles, as well as new immunological adaptations that have arisen to combat a very specific type of immunological challenge. While it is well supported that the snail immune response is important for protecting against schistosome infection, very few specific snail immune factors have been identified and even fewer have been functionally characterized. Here, we provide the first functional report of a snail Toll-like receptor, which we demonstrate as playing an important role in the cellular immune response of the snail Biomphalaria glabrata following challenge with Schistosoma mansoni. This TLR (BgTLR) was identified as part of a peptide screen of snail immune cell surface proteins that differed in abundance between B. glabrata snails that differ in their compatibility phenotype to challenge by S. mansoni. The S. mansoni-resistant strain of B. glabrata (BS-90) displayed higher levels of BgTLR compared to the susceptible (M-line) strain. Transcript expression of BgTLR was found to be very responsive in BS-90 snails when challenged with S. mansoni, increasing 27 fold relative to β-actin (non-immune control gene); whereas expression in susceptible M-line snails was not significantly increased. Knockdown of BgTLR in BS-90 snails via targeted siRNA oligonucleotides was confirmed using a specific anti-BgTLR antibody and resulted in a significant alteration of the resistant phenotype, yielding patent infections in 43% of the normally resistant snails, which

  19. Characterization of the O- and N-linked oligosaccharides in glycoproteins synthesized by Schistosoma mansoni

    SciTech Connect

    Nyame, A.K.

    1987-01-01

    The structures of the O- and N-linked oligosaccharides in glycoproteins synthesized by larval and adult schistosomes of Schistosoma mansoni have been investigated. Mechanically transformed schistosomula or adult schistosomes were incubated in media containing either (/sup 3/H)mannose, (/sup 3/H)glucosamine or (/sup 3/H)galactose for 48 and 24 hr, respectively, to radiolabel metabolically the oligosaccharide moieties of newly synthesized glycoproteins. Analyses of the radiolabeled glycoproteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS/PAGE) and fluorography demonstrated that numerous glycoproteins from 48-hr old schistosomula and adult schistosomes were labeled by both the (/sup 3/H)mannose and (/sup 3/H)glucosamine precursors. The (/sup 3/H)galactose precursor was incorporated into numerous glycoproteins in adult schistosomes; however, few, if any, glycoproteins in schistosomula were labeled by this radioactive sugar precursor.

  20. Attrition of schistosomes in an irradiation-attenuated cercarial immunization model of Schistosoma mansoni

    SciTech Connect

    Stek, M. Jr.; Dean, D.A.; Clark, S.S.

    1981-09-01

    The attrition of Schistosoma mansoni challenge worms was studied in irradiation-attenuated cercaria-immunized mice as a function of site and time. The peak recovery of schistosomula from the lungs of immunized mice was delayed 2 days in comparison with non-immunized controls. The difference between the peak recoveries of control and immunized mice accounted for about half of the final attrition observed at the 7-week adult worm stge. Hepatic-mesenteric vein worm recoveries obtained 10 to 42 days after challenge were reduced in most cases at least as much as the 49-day counts. Somewhat higher reductions were observed at 14 to 28 days than at 49 days, confirming the evidence of delayed migration obtained at the lung phase. These findings, coupled with histologic observations, indicate that at least half of the worm elimination attributable to immunization occurs 8 or more days after the challenge infection.

  1. Challenges in predicting the effects of climate change on Schistosoma mansoni and Schistosoma haematobium transmission potential.

    PubMed

    McCreesh, Nicky; Booth, Mark

    2013-11-01

    Climate change will inevitably influence both the distribution of Schistosoma mansoni and Schistosoma haematobium and the incidence of schistosomiasis in areas where it is currently endemic, and impact on the feasibility of schistosomiasis control and elimination goals. There are several limitations of current models of climate and schistosome transmission, and substantial gaps in empirical data that impair model development. In this review we consider how temperature, precipitation, heat waves, drought, and flooding could impact on snail and schistosome population dynamics. We discuss how widely used degree day models of schistosome development may not be accurate at lower temperatures, and highlight the need for further research to improve our understanding of the relationship between air and water temperature and schistosome and snail development. PMID:24064438

  2. Garlic attenuates histological and histochemical alterations in livers of Schistosoma mansoni infected mice.

    PubMed

    Mahmoud, Y I; Riad, N H; Taha, H

    2016-08-01

    Interest in screening for new anti-schistosomal agents is growing because of increased concerns about resistance to and safety of praziquantel. We investigated the anti-schistosomal action of prophylactic and therapeutic doses of garlic on the histological and histochemical alterations caused by Schistosoma mansoni infection. Livers of infected mice were characterized by granulomas, periportal inflammation and fibrosis, hepatocyte vacuolation, fatty degeneration and necrosis, and hypertrophy and pigmentation of Kupffer cells. Significant depletion of carbohydrates and increased lipid vacuoles also were observed. All garlic regimens caused suppression of granuloma formation and amelioration of histological and histochemical changes; the continuous treatment protocol produced the best results. Garlic appears to be a safe and economical anti-schistosomal adjuvant for attenuating the pathogenicity of schistosomiasis. PMID:27045197

  3. Do intestinal parasites interfere with the seroepidemiologic surveillance of Schistosoma mansoni infection?

    PubMed Central

    Alarcón de Noya, B.; Colmenares, C.; Losada, S.; Fermin, Z.; Masroua, G.; Ruiz, L.; Soto, L.; Noya, O.

    1996-01-01

    In view of the known cross-reactivity of sera from patients with intestinal parasites to some Schistosoma mansoni antigens, field work was conducted in an area of Venezuela non-endemic for schistosomiasis using the routine immunoenzymatic assay (ELISA) with soluble egg antigen (SEA). False positive reactions represented 15.3% of the total population as determined by SEA-ELISA. SEA-immunoblotting of the false positive sera indicated that protein fractions of 91 and 80 kDa appear to be responsible for cross-reactivity. Sera from hookworm infected individuals produced a higher frequency and intensity of cross-reaction than other sera. SEA-fractions of 105, 54, 46, 42, 32, 25 and 15 kDa were the most specific. Images Fig. 2 PMID:8666077

  4. Synthesis of angiotensins by cultured granuloma macrophages in murine schistosomiasis mansoni

    SciTech Connect

    Weinstock, J.V.; Blum, A.M.

    1986-03-01

    Components of the angiotensin system are present in granulomas of murine schistosomiasis mansoni. Angiotensins may have immunoregulatory function. Granuloma macrophages cultured for up to 3 days generated substantial angiotensin I (AI) and angiotensin II (AII) which appeared in the culture supernatants. Macrophage monolayers were incubated with (/sup 3/H) amino acids, and culture supernatants were extracted with acetone and analyzed by HPLC. Radiolabeled products eluded at times corresponding to those of authentic angiotensins. Immunoadsorption of angiotensins with angiotensin antisera removed reputed radiolabeled angiotensins from the supernatants. Treatment of the elution fraction corresponding to that of authentic AI with angiotensin converting enzyme resulted in the generation of radiolabeled polypeptides which co-eluted with authentic AII and His-Leu. Similar experiments conducted with nonadherent granuloma cells devoid of macrophages failed to demonstrate angiotensin production. These results suggest that granuloma macrophages can synthesize angiotensin.

  5. Schistosoma mansoni: migration potential of normal and radiation attenuated parasites in naive guinea pigs

    SciTech Connect

    Kamiya, H.; McLaren, D.J.

    1987-02-01

    Compressed tissue autoradiography using (75Se)selenomethionine labelled parasites has been used to investigate the migration potential of normal and radiation attenuated cercariae of Schistosoma mansoni in naive guinea pigs. By Day 14 after infection. 44% of normal parasites were detected as reduced silver foci in the liver; this value corresponded well with the number of liver parasites recovered by retrograde perfusion of the hepatic portal system on Day 42 (42% of the challenge). In contrast, cercariae subjected to 50 krad of gamma irradiation failed to migrate out of the skin. The migration capacity of 20 krad irradiated parasites was less severely affected in that about half of the challenge parasites reached the lungs, but virtually none moved to the liver. These data are discussed in relation to the kinetics of immunity induced in guinea pigs by infection or vaccination with normal or radiation attenuated parasites.

  6. Effect of artemether on cytokine profile and egg induced pathology in murine schistosomiasis mansoni

    PubMed Central

    Madbouly, Neveen A.; Shalash, Ibraheem R.; El Deeb, Somaya O.; El Amir, Azza M.

    2014-01-01

    Artemether (ART), the methylated derivative of artemisinin, is an efficacious antimalarial drug that also displays antischistosomal properties. This study was designed to evaluate the immunomodulatory action of a single intramuscular dose (50 mg/kg body weight) of ART in comparison with PZQ treatment (42 days PI). ART administration was 7, 14, 21 and 45 days PI. ART effect was studied parasitologically, histopathologically and immunologically. It was found that maximum effect was reached when ART treatment interfered with 14 or 21 days old schistosomula. ART treatment 14 or 21 days PI was associated with shift from Th2 to Th1 predominancy (decrease in IL-4 and upgrading of serum IFN-γ levels). In conclusion, ART is a promising drug in control of schistosomiasis mansoni due to its reductive effect on worm burden and its role in improvement of hepatic granulomatous lesions. PMID:26644922

  7. Autoantibodies to intermediate filaments in sera of patients with Schistosoma mansoni infection.

    PubMed Central

    Boehme, M W; Kataaha, P K; Holborow, E J

    1989-01-01

    Autoantibodies to the intermediate filament proteins vimentin and keratin were studied in sera of 50 Caribbean patients with Schistosoma mansoni infection and 50 control subjects. Autoantibodies were detected by indirect immunofluorescence on HEp-2 cells pretreated with colchicine. The incidence of anti-vimentin antibodies in patients' sera was 94% for IgM, 12% for IgG, and 4% for IgA; in the control subjects incidence was 52%, 0%, and 4%, respectively. Anti-keratin antibodies were found in 82%, 4%, and 4% of patients' sera and 42%, 0%, and 2% in controls, respectively. The difference between the geometric means of titres for patients (1:150) and controls (1:26) was highly significant (P less than 0.001). The possible role and genesis of autoantibodies to intermediate filaments is discussed. PMID:2476270

  8. Structural basis for selective inhibition of purine nucleoside phosphorylase from Schistosoma mansoni: kinetic and structural studies.

    PubMed

    Castilho, Marcelo S; Postigo, Matheus P; Pereira, Humberto M; Oliva, Glaucius; Andricopulo, Adriano D

    2010-02-15

    Selectivity plays a crucial role in the design of enzyme inhibitors as novel antiparasitic agents, particularly in cases where the target enzyme is also present in the human host. Purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive target for the discovery of potential antischistosomal agents. In the present work, kinetic studies were carried out in order to determine the inhibitory potency, mode of action and enzyme selectivity of a series of inhibitors of SmPNP. In addition, crystallographic studies provided important structural insights for rational inhibitor design, revealing consistent structural differences in the binding mode of the inhibitors in the active sites of the SmPNP and human PNP (HsPNP) structures. The molecular information gathered in this work should be useful for future medicinal chemistry efforts in the design of new inhibitors of SmPNP having increased affinity and selectivity. PMID:20129792

  9. Direct filtration for recovery of Schistosoma mansoni cercariae in the field

    PubMed Central

    Sandt, Donald G.

    1973-01-01

    The recovery of schistosome cercariae from natural waters has been limited by variations in turbidity and in the accuracy of recovery with different techniques. A modification of the Rowan vacuum paper filtration method employing a battery-operated pumping system, a glass—silicone plate filter, and a specially designed filter holder is described and evaluated. Field tests on St Lucia indicate a mean filtration volume of 12.2 litres per filter at a mean turbidity of 20.3 Jackson turbidity units. Overall, 86% of the volumes filtered per filter were in excess of 6 litres. Particle size, rather than turbidity, was found to be the main factor influencing filter blockage, reading time, and accuracy. Recoveries of 0.01 cercaria (Schistosoma mansoni) per litre sampled were obtained, but the practical limit of the method is considered to be closer to 0.1 cercaria per litre sampled. PMID:4541145

  10. S. mansoni Bolsters Anti-Viral Immunity in the Murine Respiratory Tract

    PubMed Central

    Scheer, Sebastian; Krempl, Christine; Kallfass, Carsten; Frey, Stefanie; Jakob, Thilo; Mouahid, Gabriel; Moné, Hélène; Schmitt-Gräff, Annette; Staeheli, Peter; Lamers, Marinus C.

    2014-01-01

    The human intestinal parasite Schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia. According to the current literature, the parasite induces vigorous immune responses that are controlled by Th2 helper cells at the expense of Th1 helper cells. The latter cell type is, however, indispensable for anti-viral immune responses. Remarkably, there is no reliable literature among 230 million patients worldwide describing defective anti-viral immune responses in the upper respiratory tract, for instance against influenza A virus or against respiratory syncitial virus (RSV). We therefore re-examined the immune response to a human isolate of S. mansoni and challenged mice in the chronic phase of schistosomiasis with influenza A virus, or with pneumonia virus of mice (PVM), a mouse virus to model RSV infections. We found that mice with chronic schistosomiasis had significant, systemic immune responses induced by Th1, Th2, and Th17 helper cells. High serum levels of TNF-α, IFN-γ, IL-5, IL-13, IL-2, IL-17, and GM-CSF were found after mating and oviposition. The lungs of diseased mice showed low-grade inflammation, with goblet cell hyperplasia and excessive mucus secretion, which was alleviated by treatment with an anti-TNF-α agent (Etanercept). Mice with chronic schistosomiasis were to a relative, but significant extent protected from a secondary viral respiratory challenge. The protection correlated with the onset of oviposition and TNF-α-mediated goblet cell hyperplasia and mucus secretion, suggesting that these mechanisms are involved in enhanced immune protection to respiratory viruses during chronic murine schistosomiasis. Indeed, also in a model of allergic airway inflammation mice were protected from a viral respiratory challenge with PVM. PMID:25398130

  11. Cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin.

    PubMed

    El-Sayed, Nagwa Mostafa; Fathy, Ghada Mahmoud; Abdel-Rahman, Sara Abdel-Rahman; El-Shafei, Mahmoud Abdel-Atei

    2016-09-01

    The purpose of this study was to determine cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin. The study was conducted upon 100 mice that were divided into five groups; 20 each: uninfected control group, Schistosoma mansoni infected untreated mice (infected control), infected mice treated with praziquantel (PZQ), infected mice treated with silymarin and infected mice treated with both praziquantel and silymarin. 10 mice from each group were sacrificed at 10th and 18th weeks post infection respectively. Histopathological investigations were performed. Liver sections were stained with hematoxylin-eosin and Masson's trichrome stain to evaluate changes of granuloma sizes and numbers. Serum levels of the cytokines (TNF-α, IFN-γ, IL-4 and TGF-β1) were assessed in the sera of all groups by immunoassay. The measured levels of cytokines (IFN-γ, IL-4, TNF-α, TGF-β1) were found to be significantly increased in infected mice compared to normal control. At the same time, treated groups with silymarin alone or combined with PZQ showed significant decrease in IL-4, TNF-α and TGF-β1 levels compared to infected control. On the other hand, there was a significant increase in IFN-γ level observed in all treated groups compared to infected control. In addition, the histopathological examination of the liver in the group treated with PZQ showed a reduction in the number of livers eggs granuloma at all periods of sacrification compared with the infected untreated group. However, there was more decrease in granulomas diameter in both silymarin treated group or combined with PZQ at all periods of sacrification when compared to infected untreated group. In conclusion; treatment with silymarin combined with PZQ in murine schistosomiasis could reduce hepatic fibrosis by their action on the production of pro-inflammatory cytokines. PMID:27605811

  12. A catecholamine transporter from the human parasite Schistosoma mansoni with low affinity for psychostimulants

    PubMed Central

    Larsen, Mads B.; Fontana, Andréia C. K.; Magalhães, Lizandra G.; Rodrigues, Vanderlei; Mortensen, Ole V.

    2011-01-01

    The trematode Schistosoma mansoni is the primary cause of schistosomiasis, a devastating neglected tropical disease that affects 200 million individuals. Identifying novel therapeutic targets for the treatment of schistosomiasis is therefore of great public interest. The catecholamines norepinephrine (NE) and dopamine (DA) are essential for the survival of the parasite as they cause muscular relaxation and a lengthening in the parasite and thereby control movement. Here we characterize a novel dopamine/norepinephrine transporter (SmDAT) gene transcript, from Schistosoma mansoni. The SmDAT is expressed in the adult form and in the sporocyst form (infected snails) of the parasite, and also in the egg and miracidium stage. It is absent in the cercaria stage but curiously a transcript missing the exon encoding transmembrane domain 8 was identified in this stage. Heterologous expression of the cDNA in mammalian cells resulted in saturable, dopamine transport activity with an apparent affinity for dopamine comparable to that of the human dopamine transporter. Efflux experiments reveal notably higher substrate selectivity compared with its mammalian counterparts as amphetamine is a much less potent efflux elicitor against SmDAT compared to the human DAT. Pharmacological characterization of the SmDAT revealed that most human DAT inhibitors including psychostimulants such as cocaine were significantly less potent in inhibiting SmDAT. Like DATs from other simpler organisms the pharmacology for SmDAT was more similar to the human norepinephrine transporter. We were not able to identify other dopamine transporting carriers within the completed parasite genome and we hypothesize that the SmDAT is the only catecholamine transporter in the parasite and could be responsible for not only clearing DA but also NE. PMID:21251927

  13. In Vitro and In Vivo Activities of Arachidonic Acid against Schistosoma mansoni and Schistosoma haematobium▿

    PubMed Central

    El Ridi, Rashika; Aboueldahab, Marwa; Tallima, Hatem; Salah, Mohamed; Mahana, Noha; Fawzi, Samia; Mohamed, Shadia H.; Fahmy, Omar M.

    2010-01-01

    The development of arachidonic acid (ARA) for treatment of schistosomiasis is an entirely novel approach based on a breakthrough discovery in schistosome biology revealing that activation of parasite tegument-bound neutral sphingomyelinase (nSMase) by unsaturated fatty acids, such as ARA, induces exposure of parasite surface membrane antigens to antibody binding and eventual attrition of developing schistosomula and adult worms. Here, we demonstrate that 5 mM ARA leads to irreversible killing of ex vivo 1-, 3-, 4-, 5-, and 6-week-old Schistosoma mansoni and 9-, 10-, and 12-week-old Schistosoma haematobium worms within 3 to 4 h, depending on the parasite age, even when the worms were maintained in up to 50% fetal calf serum. ARA-mediated worm attrition was prevented by nSMase inhibitors, such as CaCl2 and GW4869. Scanning and transmission electron microscopy revealed that ARA-mediated worm killing was associated with spine destruction, membrane blebbing, and disorganization of the apical membrane structure. ARA-mediated S. mansoni and S. haematobium worm attrition was reproduced in vivo in a series of 6 independent experiments using BALB/c or C57BL/6 mice, indicating that ARA in a pure form (Sigma) or included in infant formula (Nestle) consistently led to 40 to 80% decrease in the total worm burden. Arachidonic acid is already marketed for human use in the United States and Canada for proper development of newborns and muscle growth of athletes; thus, ARA has potential as a safe and cost-effective addition to antischistosomal therapy. PMID:20479203

  14. Human TNF-α induces differential protein phosphorylation in Schistosoma mansoni adult male worms.

    PubMed

    Oliveira, Katia C; Carvalho, Mariana L P; Bonatto, José Matheus C; Schechtman, Debora; Verjovski-Almeida, Sergio

    2016-02-01

    Schistosoma mansoni and its vertebrate host have a complex and intimate connection in which several molecular stimuli are exchanged and affect both organisms. Human tumor necrosis factor alpha (hTNF-α), a pro-inflammatory cytokine, is known to induce large-scale gene expression changes in the parasite and to affect several parasite biological processes such as metabolism, egg laying, and worm development. Until now, the molecular mechanisms for TNF-α activity in worms are not completely understood. Here, we aimed at exploring the effect of hTNF-α on S. mansoni protein phosphorylation by 2D gel electrophoresis followed by a quantitative analysis of phosphoprotein staining and protein identification by mass spectrometry. We analyzed three biological replicates of adult male worms exposed to hTNF-α and successfully identified 32 protein spots with a statistically significant increase in phosphorylation upon in vitro exposure to hTNF-α. Among the differentially phosphorylated proteins, we found proteins involved in metabolism, such as glycolysis, galactose metabolism, urea cycle, and aldehyde metabolism, as well as proteins related to muscle contraction and to cytoskeleton remodeling. The most differentially phosphorylated protein (30-fold increase in phosphorylation) was 14-3-3, whose function is known to be modulated by phosphorylation, belonging to a signal transduction protein family that regulates a variety of processes in all eukaryotic cells. Further, 75% of the identified proteins are known in mammals to be related to TNF-α signaling, thus suggesting that TNF-α response may be conserved in the parasite. We propose that this work opens new perspectives to be explored in the study of the molecular crosstalk between host and pathogen. PMID:26547565

  15. Small gene family encoding an eggshell (chorion) protein of the human parasite Schistosoma mansoni

    SciTech Connect

    Bobek, L.A.; Rekosh, D.M.; Lo Verde, P.T.

    1988-08-01

    The authors isolated six independent genomic clones encoding schistosome chorion or eggshell proteins from a Schistosoma mansoni genomic library. A linkage map of five of the clones spanning 35 kilobase pairs (kbp) of the S. mansoni genome was constructed. The region contained two eggshell protein genes closely linked, separated by 7.5 kbp of intergenic DNA. The two genes of the cluster were arranged in the same orientation, that is, they were transcribed from the same strand. The sixth clone probably represents a third copy of the eggshell gene that is not contained within the 35-kbp region. The 5- end of the mRNA transcribed from these genes was defined by primer extension directly off the RNA. The ATCAT cap site sequence was homologous to a silkmoth chorion PuTCATT cap site sequence, where Pu indicates any purine. DNA sequence analysis showed that there were no introns in these genes. The DNA sequences of the three genes were very homologous to each other and to a cDNA clone, pSMf61-46, differing only in three or four nucleotices. A multiple TATA box was located at positions -23 to -31, and a CAAAT sequence was located at -52 upstream of the eggshell transcription unit. Comparison of sequences in regions further upstream with silkmoth and Drosophila sequences revealed very short elements that were shared. One such element, TCACGT, recently shown to be an essential cis-regulatory element for silkmoth chorion gene promoter function, was found at a similar position in all three organisms.

  16. Human Schistosomiasis mansoni associated with hepatocellular carcinoma in Egypt: current perspective.

    PubMed

    El-Tonsy, Manar Mahmoud; Hussein, Hesham Mohammed; Helal, Thanaa El-Sayed; Tawfik, Rania Ayman; Koriem, Khalid Mohamed; Hussein, Hend Mohamed

    2016-09-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It was reported to account for about 4.7 % of chronic liver disease in Egyptian patients. The present study aimed at studying the different factors that may be implicated in the relationship of schistosomiasis mansoni with HCC in Egypt. A total of 75 Egyptian patients with primary liver tumours (HCC) were enrolled in this study. They were subjected to full history taking and indirect hemagglutination assay (IHA) for the diagnosis of schistosomiasis. According to the results, the patients were categorized into two groups: Group I: 29 patients with negative IHA for schistosomiasis and hepatitis C virus (HCV) positive with no history or laboratory evidence of previous or current Schistosoma mansoni infection. Group II: 46 patients with positive IHA for schistosomiasis and HCV positive. The significant higher proportion of HCC patients in the present study had concomitant HCV and schistosomiasis (61.3 %) compared to HCC patients with HCV alone (38.7 %) suggesting that the co-infection had increased the incidence of HCC among these patients. Analysis of the age distribution among HCC patients revealed that patients in Group II were younger in age at time of diagnosis of HCC with mean age 57.1 years, as compared to patients in Group I with mean age 64.3 years with a highly significant statistical difference between the 2 groups. HCC in Group II was more common in rural residents while it was more common in urban areas in Group I with a significant statistical difference between the 2 groups. Analysis of the sex distribution among the studied groups showed that HCC was more common in males than females in both groups. As regards the aggression of HCC, it was more commonly multifocal and larger in size in patients with concomitant infection than in patients with HCV alone. PMID:27605822

  17. Detection of Schistosoma mansoni Antibodies in a Low-Endemicity Area Using Indirect Immunofluorescence and Circumoval Precipitin Test

    PubMed Central

    Carvalho do Espírito-Santo, Maria Cristina; Pinto, Pedro Luiz; Gargioni, Cybele; Viviana Alvarado-Mora, Monica; Pagliusi Castilho, Vera Lúcia; Pinho, João Ranato Rebello; de Albuquerque Luna, Expedito José; Borges Gryschek, Ronaldo Cesar

    2014-01-01

    Parasitological diagnostic methods for schistosomiasis lack sensitivity, especially in regions of low endemicity. The objective of this study was to determine the prevalence of Schistosoma mansoni infections by antibody detection using the indirect immunofluorescence assay (IFA-IgM) and circumoval precipitin test (COPT). Serum samples of 572 individuals were randomly selected. The IFA-IgM and COPT were used to detect anti-S. mansoni antibodies. Of the patients studied, 15.9% (N = 91) were IFA-IgM positive and 5.1% (N = 29) had COPT reactions (P < 0.001 by McNemar's test). Immunodiagnostic techniques showed higher infection prevalence than had been previously estimated. This study suggests that combined use of these diagnostic tools could be useful for the diagnosis of schistosomiasis in epidemiological studies in areas of low endemicity. PMID:24639303

  18. Diagnostic significance of Schistosoma mansoni proteins Sm31 and Sm32 in human schistosomiasis in an endemic area in Egypt.

    PubMed

    El-Sayed, L H; Ghoneim, H; Demian, S R; El-Sayed, M H; Tawfik, N M; Sakr, I; Abou-Basha, L M; Renganathan, E; Klinkert, M Q; Abou-Rawash, N

    1998-09-01

    We performed a series of ELISAs to evaluate the diagnostic significance of two Schistosoma mansoni proteins, Sm31 (cysteine proteinase, cathepsin B) and Sm32 (asparaginyl endopeptidase). Our study populations were chosen from two villages in an endemic area close to Alexandria. Using fusion proteins MS2-Sm31 and MS2-Sm32 as antigens, 70% and 78.9%, respectively, of patient sera from 134 parasitologically confirmed cases reacted positively. The percentage of seropositivity increased to 84.5% when parasite-derived proteins Sm31 and Sm32 were used. The serum levels of antibodies to these two proteins in recombinant or native forms do not correlate with intensity of infection and hence are detected even when egg counts are low, which makes proteins Sm31 and Sm32 useful antigens in the identification of S. mansoni infected cases, particularly in endemic areas in Egypt. PMID:9754667

  19. New Praziquantel Derivatives Containing NO-donor Furoxans and Related Furazans as Active Agents against Schistosoma mansoni

    PubMed Central

    Guglielmo, Stefano; Cortese, Daniela; Vottero, Francesca; Rolando, Barbara; Kommer, Valerie P.; Williams, David L.; Fruttero, Roberta; Gasco, Alberto

    2014-01-01

    A series of NO-donor praziquantel hybrid compounds was obtained by combining praziquantel (PZQ) and furoxan moieties in a single entity. NO-donor properties of the furoxan derivatives were evaluated by detecting nitrite after incubation of the products in 7.4 pH buffered solution in the presence of L-cysteine. Structurally-related furazans, devoid of NO release capacity, were also synthesized for control purposes. All products were studied for their ability to inhibit recombinant Schistosoma mansoni thioredoxin glutathione reductase (TGR). Mobility and death of adult Schistosoma mansoni worms cultured in the presence of the products were evaluated versus PZQ. Analysis of the results showed that some products were endowed with both PZQ and NO-dependent antiparasitic properties. Compounds 6, 7, 18, and 24 emerged as the most interesting balanced hybrids, worthy of additional study on PZQ-resistant parasites. PMID:25016371

  20. Bone marrow-derived cells migrate to the liver and contribute to the generation of different cell types in chronic Schistosoma mansoni infection.

    PubMed

    Azevedo, Carine Machado; Solano de Freitas Souza, Bruno; Andrade de Oliveira, Sheilla; Paredes, Bruno Diaz; Barreto, Elton Sá; Neto, Hélio Almeida; Ribeiro dos Santos, Ricardo; Pereira Soares, Milena Botelho

    2015-12-01

    The main pathogenic event caused by Schistosoma mansoni infection is characterized by a granulomatous inflammatory reaction around parasite eggs and fibrosis in the liver. We have previously shown that transplantation of bone marrow cells (BMC) promotes a reduction in liver fibrosis in chronically S. mansoni-infected mice. Here we investigated the presence and phenotype of bone marrow-derived cells in livers of S. mansoni-infected mice. During the chronic phase of infection, C57BL/6 mice had an increased number of circulating mesenchymal stem cells and endothelial progenitor cells in the peripheral blood when compared to uninfected controls. In order to investigate the fate of BMC in the liver, we generated bone marrow chimeric mice by transplanting BMC from transgenic green fluorescent protein (GFP) mice into lethally irradiated wild-type C57BL/6 mice. S. mansoni-infected chimeric mice did not demonstrate increased mortality and developed similar liver histopathological features, when compared to wild-type S. mansoni-infected mice. GFP(+) bone marrow-derived cells were found in the liver parenchyma, particularly in periportal regions. CD45(+)GFP(+) cells were found in the granulomas. Flow cytometry analysis of digested liver tissue characterized GFP(+) cells as lymphocytes, myeloid cells and stem cells. GFP(+) cells were also found in areas of collagen deposition, although rare GFP(+) cells expressed the myofibroblast cell marker α-SMA. Additionally GFP(+) endothelial cells (co-stained with von Willebrand factor) were frequently observed, while BMC-derived hepatocytes (GFP(+) albumin(+) cells) were sparsely found in the liver of chimeric mice chronically infected with S. mansoni. In conclusion, BMC are recruited to the liver during chronic experimental infection with S. mansoni and contribute to the generation of different cell types involved, not only in disease pathogenesis, but possibly in liver regeneration and repair. PMID:26297681

  1. New Insights into the Molecular Epidemiology and Population Genetics of Schistosoma mansoni in Ugandan Pre-school Children and Mothers

    PubMed Central

    Betson, Martha; Sousa-Figueiredo, Jose C.; Kabatereine, Narcis B.; Stothard, J. Russell

    2013-01-01

    Significant numbers of pre-school children are infected with Schistosoma mansoni in sub-Saharan Africa and are likely to play a role in parasite transmission. However, they are currently excluded from control programmes. Molecular phylogenetic studies have provided insights into the evolutionary origins and transmission dynamics of S. mansoni, but there has been no research into schistosome molecular epidemiology in pre-school children. Here, we investigated the genetic diversity and population structure of S. mansoni in pre-school children and mothers living in lakeshore communities in Uganda and monitored for changes over time after praziquantel treatment. Parasites were sampled from children (<6 years) and mothers enrolled in the longitudinal Schistosomiasis Mothers and Infants Study at baseline and at 6-, 12- and 18-month follow-up surveys. 1347 parasites from 35 mothers and 45 children were genotyped by direct sequencing of the cytochrome c oxidase (cox1) gene. The cox1 region was highly diverse with over 230 unique sequences identified. Parasite populations were genetically differentiated between lakes and non-synonymous mutations were more diverse at Lake Victoria than Lake Albert. Surprisingly, parasite populations sampled from children showed a similar genetic diversity to those sampled from mothers, pointing towards a non-linear relationship between duration of exposure and accumulation of parasite diversity. The genetic diversity six months after praziquantel treatment was similar to pre-treatment diversity. Our results confirm the substantial genetic diversity of S. mansoni in East Africa and provide significant insights into transmission dynamics within young children and mothers, important information for schistosomiasis control programmes. PMID:24349589

  2. Saci-1, -2, and -3 and Perere, Four Novel Retrotransposons with High Transcriptional Activities from the Human Parasite Schistosoma mansoni

    PubMed Central

    DeMarco, Ricardo; Kowaltowski, Andre T.; Machado, Abimael A.; Soares, M. Bento; Gargioni, Cybele; Kawano, Toshie; Rodrigues, Vanderlei; Madeira, Alda M. B. N.; Wilson, R. Alan; Menck, Carlos F. M.; Setubal, João C.; Dias-Neto, Emmanuel; Leite, Luciana C. C.; Verjovski-Almeida, Sergio

    2004-01-01

    Using the data set of 180,000 expressed sequence tags (ESTs) of the blood fluke Schistosoma mansoni generated recently by our group, we identified three novel long-terminal-repeat (LTR)- and one novel non-LTR-expressed retrotransposon, named Saci-1, -2, and -3 and Perere, respectively. Full-length sequences were reconstructed from ESTs and have deduced open reading frames (ORFs) with several uncorrupted features, characterizing them as possible active retrotransposons of different known transposon families. Alignment of reconstructed sequences to available preliminary genome sequence data confirmed the overall structure of the transposons. The frequency of sequenced transposon transcripts in cercariae was 14% of all transcripts from that stage, twofold higher than that in schistosomula and three- to fourfold higher than that in adults, eggs, miracidia, and germ balls. We show by Southern blot analysis, by EST annotation and tallying, and by counting transposon tags from a Social Analysis of Gene Expression library, that the four novel retrotransposons exhibit a 10- to 30-fold lower copy number in the genome and a 4- to 200-fold-higher transcriptional rate per copy than the four previously described S. mansoni retrotransposons. Such differences lead us to hypothesize that there are two different populations of retrotransposons in S. mansoni genome, occupying different niches in its ecology. Examples of retrotransposon fragment inserts were found into the 5′ and 3′ untranslated regions of four different S. mansoni target gene transcripts. The data presented here suggest a role for these elements in the dynamics of this complex human parasite genome. PMID:14990715

  3. Regular treatments of praziquantel do not impact on the genetic make-up of Schistosoma mansoni in Northern Senegal.

    PubMed

    Huyse, T; Van den Broeck, F; Jombart, T; Webster, B L; Diaw, O; Volckaert, F A M; Balloux, F; Rollinson, D; Polman, K

    2013-08-01

    The Senegal River Basin (SRB) experienced a major epidemic of intestinal schistosomiasis in the early nineties, after the construction of a dam for irrigation purposes. Exceptionally low cure rates following praziquantel (PZQ) treatment at the onset of the epidemic raised concerns about PZQ resistant strains of Schistosoma mansoni, although they could also be attributed to the intense transmission at that time. A field study in the same region more than 15 years later found cure rates for S. mansoni still to be low, whereas Schistosomahaematobium responded well to treatment. We collected S. mansoni miracidia from children at base-line prior to treatment, six months after two PZQ treatments and two years after the start of the study when they had received a total of five PZQ treatments. In total, 434 miracidia from 12 children were successfully genotyped with at least six out of nine DNA microsatellite loci. We found no significant differences in the genetic diversity of, and genetic differentiation between parasite populations before and after repeated treatment, suggesting that PZQ treatment does not have an impact on the neutral evolution of the parasite. This is in stark contrast with a similar study in Tanzania where a significant decrease in genetic diversity was observed in S. mansoni miracidia after a single round of PZQ treatment. We argue that PZQ resistance might play a role in our study area, although rapid re-infection cannot be excluded. It is important to monitor this situation carefully and conduct larger field studies with short-term follow-up after treatment. Since PZQ is the only general schistosomicide available, the possibility of PZQ resistance is of great concern both for disease control and for curative use in clinical practice. PMID:23684792

  4. Schistosoma mansoni Infection Impairs Antimalaria Treatment and Immune Responses of Rhesus Macaques Infected with Mosquito-Borne Plasmodium coatneyi

    PubMed Central

    Semenya, Amma A.; Sullivan, JoAnn S.; Barnwell, John W.

    2012-01-01

    Malaria and schistosomiasis are the world's two most important parasitic infections in terms of distribution, morbidity, and mortality. In areas where Plasmodium and Schistosoma species are both endemic, coinfections are commonplace. Mouse models demonstrate that schistosomiasis worsens a malaria infection; however, just as mice and humans differ greatly, the murine-infecting Plasmodium species differ as much from those that infect humans. Research into human coinfections (Schistosoma haematobium-Plasmodium falciparum versus Schistosoma mansoni-P. falciparum) has produced conflicting results. The rhesus macaque model provides a helpful tool for understanding the role of S. mansoni on malaria parasitemia and antimalarial immune responses using Plasmodium coatneyi, a malaria species that closely resembles P. falciparum infection in humans. Eight rhesus macaques were exposed to S. mansoni cercariae. Eight weeks later, these animals plus 8 additional macaques were exposed to malaria either through bites of infected mosquitos or intravenous inoculation. When malaria infection was initiated from mosquito bites, coinfected animals displayed increased malaria parasitemia, decreased hematocrit levels, and suppressed malaria-specific antibody responses compared to those of malaria infection alone. However, macaques infected by intravenous inoculation with erythrocytic-stage parasites did not display these same differences in parasitemia, hematocrit, or antibody responses between the two groups. Use of the macaque model provides information that begins to unravel differences in pathological and immunological outcomes observed between humans with P. falciparum that are coinfected with S. mansoni or S. haematobium. Our results suggest that migration of malaria parasites through livers harboring schistosome eggs may alter host immune responses and infection outcomes. PMID:22907811

  5. Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation.

    PubMed

    Cardoso, L S; Oliveira, S C; Góes, A M; Oliveira, R R; Pacífico, L G; Marinho, F V; Fonseca, C T; Cardoso, F C; Carvalho, E M; Araujo, M I

    2010-05-01

    Schistosoma mansoni infection has been associated with protection against allergies. The mechanisms underlying this association may involve regulatory cells and cytokines. We evaluated the immune response induced by the S. mansoni antigens Sm22.6, PIII and Sm29 in a murine model of ovalbumin (OVA)-induced airway inflammation. BALB/c mice were sensitized with subcutaneously injected OVA-alum and challenged with aerolized OVA. Mice were given three doses of the different S. mansoni antigens. Lung histopathology, cellularity of bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in lung were evaluated. Immunoglobulin (Ig)E levels in serum and cytokines in BAL were also measured. Additionally, we evaluated the frequency of CD4+forkhead box P3 (FoxP3)+ T cells in cultures stimulated with OVA and the expression of interleukin (IL)-10 by these cells. The number of total cells and eosinophils in BAL and the levels of OVA-specific IgE were reduced in the immunized mice. Also, the levels of IL-4 and IL-5 in the BAL of mice immunized with PIII and Sm22.6 were decreased, while the levels of IL-10 were higher in mice immunized with Sm22.6 compared to the non-immunized mice. The frequency of CD4+FoxP3+ T cells was higher in the groups of mice who received Sm22.6, Sm29 and PIII, being the expression of IL-10 by these cells only higher in mice immunized with Sm22.6. We concluded that the S. mansoni antigens used in this study are able to down-modulate allergic inflammatory mediators in a murine model of airway inflammation and that the CD4+FoxP3+ T cells, even in the absence of IL-10 expression, might play an important role in this process. PMID:20132231

  6. Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation

    PubMed Central

    Cardoso, L S; Oliveira, S C; Góes, A M; Oliveira, R R; Pacífico, L G; Marinho, F V; Fonseca, C T; Cardoso, F C; Carvalho, E M; Araujo, M I

    2010-01-01

    Schistosoma mansoni infection has been associated with protection against allergies. The mechanisms underlying this association may involve regulatory cells and cytokines. We evaluated the immune response induced by the S. mansoni antigens Sm22·6, PIII and Sm29 in a murine model of ovalbumin (OVA)-induced airway inflammation. BALB/c mice were sensitized with subcutaneously injected OVA-alum and challenged with aerolized OVA. Mice were given three doses of the different S. mansoni antigens. Lung histopathology, cellularity of bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in lung were evaluated. Immunoglobulin (Ig)E levels in serum and cytokines in BAL were also measured. Additionally, we evaluated the frequency of CD4+forkhead box P3 (FoxP3)+ T cells in cultures stimulated with OVA and the expression of interleukin (IL)-10 by these cells. The number of total cells and eosinophils in BAL and the levels of OVA-specific IgE were reduced in the immunized mice. Also, the levels of IL-4 and IL-5 in the BAL of mice immunized with PIII and Sm22·6 were decreased, while the levels of IL-10 were higher in mice immunized with Sm22·6 compared to the non-immunized mice. The frequency of CD4+FoxP3+ T cells was higher in the groups of mice who received Sm22·6, Sm29 and PIII, being the expression of IL-10 by these cells only higher in mice immunized with Sm22·6. We concluded that the S. mansoni antigens used in this study are able to down-modulate allergic inflammatory mediators in a murine model of airway inflammation and that the CD4+FoxP3+ T cells, even in the absence of IL-10 expression, might play an important role in this process. PMID:20132231

  7. Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib.

    PubMed

    Beckmann, Svenja; Long, Thavy; Scheld, Christina; Geyer, Rudolf; Caffrey, Conor R; Grevelding, Christoph G

    2014-12-01

    In the search for new drugs and drug targets to treat the flatworm disease schistosomiasis, protein kinases (PKs) have come under particular scrutiny because of their essential roles in developmental and physiological processes in schistosome parasites. In this context the application of the anti-cancer Abl tyrosine kinase (TK) inhibitor Imatinib (Gleevec/Glivec; STI-571) to adult Schistosoma mansoni in vitro has indicated negative effects on diverse physiological processes including survival. Motivated by these in vitro findings, we performed in vivo experiments in rodent models of S. mansoni infection. Unexpectedly, Imatinib had no effect on worm burden or egg-production. We found that the blood components serum albumin (SA) and alpha-1 acid glycoprotein (AGP or orosomucoid) negated Imatinib's deleterious effects on adult S. mansoni and schistosomula (post-infective larvae) in vitro. This negative effect was partially reversed by erythromycin. AGP synthesis can increase as a consequence of inflammatory processes or infection; in addition upon infection AGP levels are 6-8 times higher in mice compared to humans. Therefore, mice and probably other rodents are poor infection models for measuring the effects of Imatinib in vivo. Accordingly, we suggest the routine evaluation of the ability of AGP and SA to block in vitro anti-schistosomal effects of small molecules like Imatinib prior to laborious and expensive animal experiments. PMID:25516839

  8. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Wilson, R.A.

    1988-05-15

    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

  9. Characterization of antigens from Schistosoma mansoni and construction of a cDNA library for the study of schistosomiasis

    SciTech Connect

    Bugra, K.

    1986-01-01

    To examine the antigens of adult Schistosoma mansoni, /sup 35/S-methionine-labelled, detergent-extracted proteins were immunoprecipitated and analyzed on SDS-PAGE. Human infection serum immunoprecipitated 14 polypeptides with M/sub r/'s of 120, 105, 88, 86, 66, 64, 54, 48, 42, 38, 35, 32, 29, and 20 Kd. Upon digestion with endoglycosidase F polypeptides with M/sub r/'s of 120, 105, 54, 48, and 29 appeared to have carbohydrate moieties. Extracts of female and male S. mansoni were analyzed by immunoprecipitation and immunoblotting. Two polypeptides with M/sub r/'s of 86 Kd and 54 Kd were detected only in extracts of males. Polyadenylated RNA was extracted from S. mansoni and translated in rabbit reticulocyte lysates. Among the in vitro translation products, polypeptides with 120, 94, 64, 43, 37, 35, 30, 26 and 22 Kd apparent molecular weights were immunoprecipitated by human infection serum. When the translation products of female worms and male worms were compared, the polypeptides with M/sub r/'s of 94 and 64 Kd were only observed in males.

  10. Protein Kinase C and Extracellular Signal-Regulated Kinase Regulate Movement, Attachment, Pairing and Egg Release in Schistosoma mansoni

    PubMed Central

    Ressurreição, Margarida; De Saram, Paulu; Kirk, Ruth S.; Rollinson, David; Emery, Aidan M.; Page, Nigel M.; Davies, Angela J.; Walker, Anthony J.

    2014-01-01

    Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using ‘smart’ antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance. PMID:24921927

  11. Efficacy and Safety of Arachidonic Acid for Treatment of Schistosoma mansoni-Infected Children in Menoufiya, Egypt

    PubMed Central

    Selim, Sahar; El Sagheer, Ola; El Amir, Azza; Barakat, Rashida; Hadley, Kevin; Bruins, Maaike J.; El Ridi, Rashika

    2014-01-01

    Arachidonic acid (ARA), an omega-6 fatty acid, kills juvenile and adult schistosomes in vitro and displays highly significant and safe therapeutic effects in mice and hamsters infected with Schistosoma mansoni or S. haematobium. This study aims to examine the efficacy and safety of ARA in treatment of school-age children infected with S. mansoni. In total, 66 S. mansoni-infected schoolchildren (20–23 children/study arm) received a single dose of 40 mg/kg praziquantel (PZQ), ARA (10 mg/kg per day for 15 days), or PZQ combined with ARA. The children were examined before and after treatment for worm egg counts in stool and blood biochemical and immunological parameters. ARA proved to be as efficacious as PZQ in treatment of schoolchildren with low infection intensity (78% and 85% cure rates, respectively). For moderate-intensity infection, the ARA and PZQ combination led to 100% cure rate. Biochemical, hematological, and immunological parameters were either unchanged or ameliorated after ARA therapy. PMID:25246692

  12. Fasciola gigantica Fatty Acid Binding Protein (FABP) as a Prophylactic Agent against Schistosoma mansoni Infection in CD1 Mice

    PubMed Central

    Diab, M.; El-Amir, A. M.; Hendawy, M.; Kadry, S.

    2012-01-01

    Although schistosomicidal drugs and other control measures exist, the advent of an efficacious vaccine remains the most potentially powerful means for controlling this disease. In this study, native fatty acid binding protein (FABP) from Fasciola gigantica was purified from the adult worm's crude extract by saturation with ammonium sulphate followed by separation on DEAE-Sephadex A-50 anion exchange chromatography and gel filtration using Sephacryl HR-100, respectively. CD1 mice were immunized with the purified, native F. gigantica FABP in Freund's adjuvant and challenged subcutaneously with 120 Schistosoma mansoni cercariae. Immunization of CD1 mice with F. gigantica FABP has induced heterologous protection against S. mansoni, evidenced by the significant reduction in mean worm burden (72.3%), liver and intestinal egg counts (81.3% and 80.8%, respectively), and hepatic granuloma counts (42%). Also, it elicited mixed IgG1/IgG2b immune responses with predominant IgG1 isotype, suggesting that native F. gigantica FABP is mediated by a mixed Th1/Th2 response. However, it failed to induce any significant differences in the oogram pattern or in the mean granuloma diameter. This indicated that native F. gigantica FABP could be a promising vaccine candidate against S. mansoni infection. PMID:22451732

  13. Synthesis and activity of new triphenylphosphonium derivatives of betulin and betulinic acid against Schistosoma mansoni in vitro and in vivo.

    PubMed

    Spivak, Anna Yu; Keiser, Jennifer; Vargas, Mireille; Gubaidullin, Rinat R; Nedopekina, Darya A; Shakurova, Elvira R; Khalitova, Rezeda R; Odinokov, Victor N

    2014-11-01

    We studied the antischistosomal activity of betulin, betulinic acid and its 9 triphenylphosphonium derivatives characterized by a covalently linkage of the hydrophobic fragment of triterpenoid at C(2)- or C(30)-position with the triphenylphosphonium moiety via a hydrocarbon bridge. The triphenylphosphonium salts showed in vitro antischistosomal activity against newly transformed schistosomula (NTS) and adult worms of Schistosoma mansoni at low micromolar concentrations. In contrast betulin and betulinic acid were inactive against NTS and adult S. mansoni. Of the 9 triphenylphosphonium derivatives tested, the allyl salts 10 (IC50 of 0.76 μg/mL) and 11 (IC50 of 0.64 μg/mL) demonstrated the highest antischistosomal activity against adult S. mansoni. Low worm burden reductions of 22% were observed in vivo for these two compounds. In conclusion, triphenylphosphonium derivatives were obtained from available natural betulin by simple transformations, rendering it practical and useful for large scale application. However, further structural modifications are necessary to translate the promising antischistosomal in vitro activities into in vivo. PMID:25245671

  14. Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib

    PubMed Central

    Beckmann, Svenja; Long, Thavy; Scheld, Christina; Geyer, Rudolf; Caffrey, Conor R.; Grevelding, Christoph G.

    2014-01-01

    In the search for new drugs and drug targets to treat the flatworm disease schistosomiasis, protein kinases (PKs) have come under particular scrutiny because of their essential roles in developmental and physiological processes in schistosome parasites. In this context the application of the anti-cancer Abl tyrosine kinase (TK) inhibitor Imatinib (Gleevec/Glivec; STI-571) to adult Schistosoma mansoni in vitro has indicated negative effects on diverse physiological processes including survival. Motivated by these in vitro findings, we performed in vivo experiments in rodent models of S. mansoni infection. Unexpectedly, Imatinib had no effect on worm burden or egg-production. We found that the blood components serum albumin (SA) and alpha-1 acid glycoprotein (AGP or orosomucoid) negated Imatinib’s deleterious effects on adult S. mansoni and schistosomula (post-infective larvae) in vitro. This negative effect was partially reversed by erythromycin. AGP synthesis can increase as a consequence of inflammatory processes or infection; in addition upon infection AGP levels are 6–8 times higher in mice compared to humans. Therefore, mice and probably other rodents are poor infection models for measuring the effects of Imatinib in vivo. Accordingly, we suggest the routine evaluation of the ability of AGP and SA to block in vitro anti-schistosomal effects of small molecules like Imatinib prior to laborious and expensive animal experiments. PMID:25516839

  15. Myrrh and artesunate modulate some Th1 and Th2 cytokines secretion in Schistosoma mansoni infected mice

    PubMed Central

    Abdelaziz, Mohamed M.

    2016-01-01

    The effects of artesunate and myrrh on S. mansoni infection and the levels of some Th1 and Th2 cytokines were evaluated in the present study. Six weeks after infection, a group of mice was treated with 4 mg/kg of artesunate and other group was treated with 10 mg/kg of myrrh for 3 successive days. Worm burden was reduced with a percentage of 53.7% and 58.78% after treatment with myrrh and artesunate respectively as well as the levels of IgG antibodies were significantly reduced compared with infected group. No obvious changes were observed in the level of interferon γ after treatment. After treatment with artesunate, interleukin 2 (IL-2) level was significantly decreased, while no significant difference was observed in myrrh-treated group compared with the infected group. On the other hand, the level of IL-10 was not significantly decreased after treatment with artesunate, but it was significantly increased after treatment with myrrh. However, IL-12 levels were significantly decreased after treatment with artesunate. The results demonstrated that, artesunate or myrrh treatment could give a level of protection against S. mansoni infection and modulate the levels of some Th1 and Th2 cytokines in mice infected with S. mansoni. PMID:27536198

  16. Wharton’s jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis

    PubMed Central

    Hammam, Olfat A.; Elkhafif, Nagwa; Attia, Yasmeen M.; Mansour, Mohamed T.; Elmazar, Mohamed M.; Abdelsalam, Rania M.; Kenawy, Sanaa A.; El-Khatib, Aiman S.

    2016-01-01

    Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8th week post infection) and late (16th week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10th month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone. PMID:26876222

  17. Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis.

    PubMed

    Hammam, Olfat A; Elkhafif, Nagwa; Attia, Yasmeen M; Mansour, Mohamed T; Elmazar, Mohamed M; Abdelsalam, Rania M; Kenawy, Sanaa A; El-Khatib, Aiman S

    2016-01-01

    Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8(th) week post infection) and late (16(th) week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10(th) month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone. PMID:26876222

  18. Evidence that cytokine-mediated immune interactions induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris

    PubMed Central

    1995-01-01

    In murine models of Schistosoma mansoni infection, egg production is associated with a switch from T helper cell (Th)1- to Th2-type responses to both schistosome-specific and unrelated antigens. Polyparasitism is common in human populations within S. mansoni endemic areas. We have, therefore, examined whether coinfection with S. mansoni could affect the outcome of a second parasitic infection, through Th2 cytokine-dependent modifications to the host immune response. We find that when mice susceptible to infection with the gut nematode Trichuris muris are coinfected with S. mansoni, they acquire the capacity to resolve T. muris infection, thus demonstrating a resistant phenotype. This ability to expel T. muris is associated with the production of Th2- associated cytokines, and corresponding antibody isotypes, in response to S. mansoni egg antigens. The Th2 response shows that there is no compartmentalization between spleen and mesenteric lymph nodes, and that the expulsion of T. muris is not caused by any changes in the host intestine associated with excretion of schistosome eggs. This influence of schistosome infections may be important, not only for the outcome of infections with unrelated pathogens in endemic areas, but also for the efficacy of vaccines in such areas. PMID:7836929

  19. Cloning and sequence analysis of the Schistosoma mansoni membrane glycoprotein antigen gene GP22.

    PubMed

    el-Sherbeini, M; Ramadan, N; Bostian, K A; Knopf, P M

    1991-11-01

    A family of Schistosoma mansoni proteins (18-22 kDa, pI 5.3-5.8) are biosynthesized in juvenile worms and immunoprecipitated by antibodies uniquely present in protective Fischer rat antiserum. A cDNA clone, lambda gt11-40, expressing epitopes common to this protein family was used to obtain a genomic DNA clone, by hybridization with a lambda gt11-40 oligonucleotide probe. In the 1.37 kb of genomic DNA sequenced, an open reading frame of 182 amino acids was identified on the strand corresponding to lambda gt11-40 coding sequences, and those of identical independently isolated cDNA clones defining a 25-kDa surface membrane glycoprotein. The new S. mansoni gene is termed GP22. There are two candidate promoters, confirmed by primer extension studies with worm RNA. Promoter 1 (P1) is preceded by a G + C-rich region and potential CAAT sequences, and is to the 5'-side of P2. Transcription from P1 is initiated at 2 different sites, apparently producing mRNAs with different translation start sites (ATG). Decoding these mRNAs yields protein products of 182 (P1), 175 (P1), 140 (P2) and 136 (P2) amino acids. The polypeptides share the following features: a hydrophobic segment near the carboxy terminus sufficient to span a lipid bilayer, with a consensus sequence for thio-esterification by a fatty acid; an external domain containing 2 potential N-linked glycosylation sites; and a candidate leucine-zipper motif, suggesting the protein may exist as a dimer on the worm surface. While sharing these common features in their carboxy terminal regions, the three proteins differ in the length and properties of their amino termini. The 140-amino acid protein has a short hydrophobic amino terminus, while the 175- and 182-amino acid proteins have more extensive hydrophobic sequences, each preceded by a hydrophilic amino terminal sequence. The heterogeneity observed in 2-dimensional gels of the antigen may be explained in part by the size and charge differences among the proteins deduced

  20. Functional Characterization of a Novel Family of Acetylcholine-Gated Chloride Channels in Schistosoma mansoni

    PubMed Central

    MacDonald, Kevin; Buxton, Samuel; Kimber, Michael J.; Day, Tim A.; Robertson, Alan P.; Ribeiro, Paula

    2014-01-01

    Acetylcholine is the canonical excitatory neurotransmitter of the mammalian neuromuscular system. However, in the trematode parasite Schistosoma mansoni, cholinergic stimulation leads to muscle relaxation and a flaccid paralysis, suggesting an inhibitory mode of action. Information about the pharmacological mechanism of this inhibition is lacking. Here, we used a combination of techniques to assess the role of cholinergic receptors in schistosome motor function. The neuromuscular effects of acetylcholine are typically mediated by gated cation channels of the nicotinic receptor (nAChR) family. Bioinformatics analyses identified numerous nAChR subunits in the S. mansoni genome but, interestingly, nearly half of these subunits carried a motif normally associated with chloride-selectivity. These putative schistosome acetylcholine-gated chloride channels (SmACCs) are evolutionarily divergent from those of nematodes and form a unique clade within the larger family of nAChRs. Pharmacological and RNA interference (RNAi) behavioral screens were used to assess the role of the SmACCs in larval motor function. Treatment with antagonists produced the same effect as RNAi suppression of SmACCs; both led to a hypermotile phenotype consistent with abrogation of an inhibitory neuromuscular mediator. Antibodies were then generated against two of the SmACCs for use in immunolocalization studies. SmACC-1 and SmACC-2 localize to regions of the peripheral nervous system that innervate the body wall muscles, yet neither appears to be expressed directly on the musculature. One gene, SmACC-1, was expressed in HEK-293 cells and characterized using an iodide flux assay. The results indicate that SmACC-1 formed a functional homomeric chloride channel and was activated selectively by a panel of cholinergic agonists. The results described in this study identify a novel clade of nicotinic chloride channels that act as inhibitory modulators of schistosome neuromuscular function. Additionally, the

  1. Microarray analysis of gene expression induced by sexual contact in Schistosoma mansoni

    PubMed Central

    Waisberg, Michael; Lobo, Francisco P; Cerqueira, Gustavo C; Passos, Liana KJ; Carvalho, Omar S; Franco, Glória R; El-Sayed, Najib M

    2007-01-01

    Background The parasitic trematode Schistosoma mansoni is one of the major causative agents of Schistosomiasis, a disease that affects approximately 200 million people, mostly in developing countries. Since much of the pathology is associated with eggs laid by the female worm, understanding the mechanisms involved in oogenesis and sexual maturation is an important step towards the discovery of new targets for effective drug therapy. It is known that the adult female worm only develops fully in the presence of a male worm and that the rates of oviposition and maturation of eggs are significantly increased by mating. In order to study gene transcripts associated with sexual maturation and oviposition, we compared the gene expression profiles of sexually mature and immature parasites using DNA microarrays. Results For each experiment, three amplified RNA microarray hybridizations and their dye swaps were analyzed. Our results show that 265 transcripts are differentially expressed in adult females and 53 in adult males when mature and immature worms are compared. Of the genes differentially expressed, 55% are expressed at higher levels in paired females while the remaining 45% are more expressed in unpaired ones and 56.6% are expressed at higher levels in paired male worms while the remaining 43.4% are more expressed in immature parasites. Real-time RT-PCR analysis validated the microarray results. Several new maturation associated transcripts were identified. Genes that were up-regulated in single-sex females were mostly related to energy generation (i.e. carbohydrate and protein metabolism, generation of precursor metabolites and energy, cellular catabolism, and organelle organization and biogenesis) while genes that were down-regulated related to RNA metabolism, reactive oxygen species metabolism, electron transport, organelle organization and biogenesis and protein biosynthesis. Conclusion Our results confirm previous observations related to gene expression induced

  2. RNA Interference in Schistosoma mansoni Schistosomula: Selectivity, Sensitivity and Operation for Larger-Scale Screening

    PubMed Central

    Horn, Martin; Braschi, Simon; Sojka, Daniel; Ruelas, Debbie S.; Suzuki, Brian; Lim, Kee-Chong; Hopkins, Stephanie D.; McKerrow, James H.; Caffrey, Conor R.

    2010-01-01

    Background The possible emergence of resistance to the only available drug for schistosomiasis spurs drug discovery that has been recently incentivized by the availability of improved transcriptome and genome sequence information. Transient RNAi has emerged as a straightforward and important technique to interrogate that information through decreased or loss of gene function and identify potential drug targets. To date, RNAi studies in schistosome stages infecting humans have focused on single (or up to 3) genes of interest. Therefore, in the context of standardizing larger RNAi screens, data are limited on the extent of possible off-targeting effects, gene-to-gene variability in RNAi efficiency and the operational capabilities and limits of RNAi. Methodology/Principal Findings We investigated in vitro the sensitivity and selectivity of RNAi using double-stranded (ds)RNA (approximately 500 bp) designed to target 11 Schistosoma mansoni genes that are expressed in different tissues; the gut, tegument and otherwise. Among the genes investigated were 5 that had been previously predicted to be essential for parasite survival. We employed mechanically transformed schistosomula that are relevant to parasitism in humans, amenable to screen automation and easier to obtain in greater numbers than adult parasites. The operational parameters investigated included defined culture media for optimal parasite maintenance, transfection strategy, time- and dose- dependency of RNAi, and dosing limits. Of 7 defined culture media tested, Basch Medium 169 was optimal for parasite maintenance. RNAi was best achieved by co-incubating parasites and dsRNA (standardized to 30 µg/ml for 6 days); electroporation provided no added benefit. RNAi, including interference of more than one transcript, was selective to the gene target(s) within the pools of transcripts representative of each tissue. Concentrations of dsRNA above 90 µg/ml were directly toxic. RNAi efficiency was transcript

  3. Inhibition of Schistosoma mansoni ether-a-go-go related gene-encoded potassium channels leads to hypermotility and impaired egg production.

    PubMed

    Parker-Manuel, S J; Hahnel, S; Grevelding, C G

    2015-11-01

    The purpose of this work was to investigate the effect of ether-a-go-go related gene (ERG) potassium channel inhibition on Schistosoma mansoni. Use of dofetilide to block the schistosome ERGs resulted in a striking 'corkscrew' effect. The worms were unable to control their motility; they were hypermotile. The treated worms produced abnormal eggs, some of which consisted of little more than a spine. One of the S. mansoni ERGs (SmERGs), Smp_161140, was chosen for further study by RNAi. The transcript was knocked down to 50% compared to the controls. These RNAi-treated worms demonstrated seizure-like movements. In S. mansoni, as in other organisms, ERG channels seem to play a role in regulating muscle excitability. This work shows that egg production can be greatly reduced by effectively targeting muscle coordination in these important parasites. PMID:26188142

  4. Clinical-epidemiologic study of schistosomiasis mansoni in Ponte do Pasmado, a village in the municipality of Itinga, state of Minas Gerais, Brazil, 1992.

    PubMed

    Rodrigues, R N; Murta, C; Teixeira Júnior, M A; Cury, G C; Rocha, M O

    1995-01-01

    A clinical-epidemiologic study of schistosomiasis mansoni was conducted in the population of Ponte do Pasmado, a village in the municipality of Itinga, state of Minas Gerais, Brazil. Faecal parasitology by the Kato-Katz method and clinical examination were performed in 93.8% and 82.8% of the local population, respectively. A socioeconomic survey was also made and the signs and symptoms presented by the patients were recorded, as well as their contacts with natural waters. The rate of Schistosoma mansoni infection was 50.3%; the peak of infection occurred during the second decade of life; there was a predominance of low egg counts in faeces (85.89% of positive patients eliminated less than 500 eggs per gram of faeces); the splenomegaly rate was 1.23%. When the risk factors for S. mansoni infection were studied, significant risks were detected in activities such as fetching water, washing dishes, bathing, and crossing streams. PMID:7569646

  5. Serodiagnosis of Schistosoma mansoni infections in an endemic area of Burkina Faso: performance of several immunological tests with different parasite antigens.

    PubMed

    Sorgho, Hermann; Bahgat, Mahmoud; Poda, Jean-Noel; Song, Wenjian; Kirsten, Christa; Doenhoff, Michael J; Zongo, Issaka; Ouédraogo, Jean-Bosco; Ruppel, Andreas

    2005-02-01

    The performance of indirect haemagglutination assays (IHA), enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescent antibody tests (IFAT) were compared with 450 sera from a Schistosoma mansoni-endemic area in Burkina Faso. All participants in this survey provided at least one sample each of stool, urine and serum. From those with an egg-negative Kato-Katz thick smear, a second stool sample was examined. IHA was based on either extracts of adult S. mansoni worms (SmIHA) or S. japonicum egg antigen (SjIHA). For ELISA, three antigen preparations were used, namely: (i) soluble S. mansoni adult worm antigens (SWAP); (ii) soluble S. mansoni egg antigens (SEA); and (iii) a cationic exchange fraction of S. mansoni eggs (CEF6). IFAT was performed with S. mansoni male worm sections. Among the egg-excretors, the sensitivity of ELISA was high and egg antigens performed slightly better (SEA, 96%; CEF6, 97%) than worm antigen (94%). Sensitivity of IHA was satisfactory with homologous (Sm, >85%), but not heterologous (Sj, 56%) parasite antigen. In IFAT, the parenchyma-associated fluorescence showed high sensitivity (95%), but gut-associated fluorescence, which is known to be a sensitive diagnostic marker for schistosome-infected European travelers, was observed only in 76% of a sub-sample of 100 of the endemic sera. Among sera from egg-negative individuals, many gave positive reactions in several or all of the tests employed. These reactions (formally "false positive") are considered to represent true infections, since chemotherapy had not yet been delivered to this population. For the purpose of further surveys in Burkina Faso or other resource-poor settings, we suggest IHA as an accurate diagnostic test and propose to further improve its performance by including egg rather than worm antigens. PMID:15652331

  6. Larval excretory-secretory products from the parasite Schistosoma mansoni modulate HSP70 protein expression in defence cells of its snail host, Biomphalaria glabrata

    PubMed Central

    Zahoor, Zahida; Davies, Angela J.; Kirk, Ruth S.; Rollinson, David

    2010-01-01

    Synthesis of heat shock proteins (HSPs) following cellular stress is a response shared by many organisms. Amongst the HSP family, the ∼70 kDa HSPs are the most evolutionarily conserved with intracellular chaperone and extracellular immunoregulatory functions. This study focused on the effects of larval excretory-secretory products (ESPs) from the parasite Schistosoma mansoni on HSP70 protein expression levels in haemocytes (defence cells) from its snail intermediate host Biomphalaria glabrata. S. mansoni larval stage ESPs are known to interfere with haemocyte physiology and behaviour. Haemocytes from two different B. glabrata strains, one which is susceptible to S. mansoni infection and one which is resistant, both showed reduced HSP70 protein levels following 1 h challenge with S. mansoni ESPs when compared to unchallenged controls; however, the reduction observed in the resistant strain was less marked. The decline in intracellular HSP70 protein persisted for at least 5 h in resistant snail haemocytes only. Furthermore, in schistosome-susceptible snails infected by S. mansoni for 35 days, haemocytes possessed approximately 70% less HSP70. The proteasome inhibitor, MG132, partially restored HSP70 protein levels in ESP-challenged haemocytes, demonstrating that the decrease in HSP70 was in part due to intracellular degradation. The extracellular signal-regulated kinase (ERK) signalling pathway appears to regulate HSP70 protein expression in these cells, as the mitogen-activated protein-ERK kinase 1/2 (MEK1/2) inhibitor, U0126, significantly reduced HSP70 protein levels. Disruption of intracellular HSP70 protein expression in B. glabrata haemocytes by S. mansoni ESPs may be a strategy employed by the parasite to manipulate the immune response of the intermediate snail host. PMID:20182834

  7. Sustaining Control of Schistosomiasis Mansoni in Western Côte d’Ivoire: Results from a SCORE Study, One Year after Initial Praziquantel Administration

    PubMed Central

    Assaré, Rufin K.; Tian-Bi, Yves-Nathan T.; Yao, Patrick K.; N’Guessan, Nicaise A.; Ouattara, Mamadou; Yapi, Ahoua; Coulibaly, Jean T.; Meïté, Aboulaye; Hürlimann, Eveline; Knopp, Stefanie; Utzinger, Jürg; N’Goran, Eliézer K.

    2016-01-01

    Background The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has launched several large-scale trials to determine the best strategies for gaining and sustaining control of schistosomiasis and transitioning toward elimination. In Côte d’Ivoire, a 5-year cluster-randomized trial is being implemented in 75 schools to sustain the control of schistosomiasis mansoni. We report Schistosoma mansoni infection levels in children one year after the initial school-based treatment (SBT) with praziquantel and compare with baseline results to determine the effect of the intervention. Methodology The baseline cross-sectional survey was conducted in late 2011/early 2012 and the first follow-up in May 2013. Three consecutive stool samples were collected from 9- to 12-year-old children in 75 schools at baseline and 50 schools at follow-up. Stool samples were subjected to duplicate Kato-Katz thick smears. Directly observed treatment (DOT) coverage of the SBT was assessed and the prevalence and intensity of S. mansoni infection compared between baseline and follow-up. Principal Findings The S. mansoni prevalence in the 75 schools surveyed at baseline was 22.1% (95% confidence interval (CI): 19.5–24.4%). The DOT coverage was 84.2%. In the 50 schools surveyed at baseline and one year after treatment, the overall prevalence of S. mansoni infection decreased significantly from 19.7% (95% CI: 18.5–20.8%) to 12.8% (95% CI: 11.9–13.8%), while the arithmetic mean S. mansoni eggs per gram of stool (EPG) among infected children slightly increased from 92.2 EPG (95% CI: 79.2–105.3 EPG) to 109.3 EPG (95% CI: 82.7–135.9 EPG). In two of the 50 schools, the prevalence increased significantly, despite a DOT coverage of >75%. Conclusions/Significance One year after the initial SBT, the S. mansoni prevalence had decreased. Despite this positive trend, an increase was observed in some schools. Moreover, the infection intensity among S. mansoni-infected children

  8. Determination and quantification of Schistosoma mansoni cercarial emergence from Biomphalaria glabrata snails.

    PubMed

    Tucker, Matthew S; Lewis, Fred A; Driver, James D; Granath, Willard O

    2014-12-01

    Living and fixed samples of Schistosoma mansoni -infected Biomphalaria glabrata snails were used to determine the relative contributions of different snail tissues to cercarial emergence (shedding). Three methods of observations were employed: (1) direct microscopical observations of shedding snails; (2) microscopic analysis of 5 μm serial sections (H&E stained) of actively shedding snails; and (3) scanning electron microscopic (SEM) observations of snails that were fixed while actively shedding. For this investigation, there were advantages and disadvantages to using each method. We confirmed the results of others that there were 3 tissues of the snail that contributed most prominently to cercarial release (mantle collar, pseudobranch, and headfoot). Based on histological analysis of cercarial accumulations in presumed shedding sites in these 3 tissues, 57% of the cercariae could be seen in the mantle collar, 30.6% in the pseudobranch, and 12.5% in the headfoot. Other anterior structures were involved to a much lesser extent. SEM observations clearly showed cercariae emerging either body first, tail first, or likely emerging en masse from blebs, especially from the mantle collar. These studies provide a more quantitative appraisal of the role the different anterior snail tissues play in cercarial emergence. PMID:25019357

  9. Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae

    SciTech Connect

    Dalton, J.P.; Strand, M.; Mangold, B.L.; Dean, D.A.

    1986-06-15

    The humoral immune response of mice patently infected with Schistosoma mansoni and of mice vaccinated with radiation-attenuated cercariae were compared by radioimmunoassays and one-and two-dimensional polyacrylamide gel analyses of radioimmunoprecipitates. The binding observed with antibodies of mice vaccinated twice with radiation-attenuated cercariae over a period of 7 to 11 wk was less than 50% of the binding observed with antibodies of mice patently infected for 20 wk, but three to four times greater than that obtained with antibodies of mice infected for 6 wk, irrespective of whether the test extracts were derived from schistosomula or adult worms. Sera of vaccinated mice precipitated a restricted number of predominantly high m.w. glycoproteins of both schistosomula and adult worms metabolically labeled with sulfur-35 methionine. Each of the glycoproteins of 36 hr in vitro-cultured schistosomula that was precipitated by the sera of vaccinated mice was also precipitated by the sera of infected mice. Although radiation-attenuated larvae do not reach the adult stage, mice vaccinated with these still elicit a strong immune response against egg glycoproteins. These results show that the antibody response in mice vaccinated with radiation-attenuated larvae differs qualitatively and quantitatively from that of infected mice.

  10. Simvastatin and artesunate impact the structural organization of adult Schistosoma mansoni in hypercholesterolemic mice.

    PubMed

    Alencar, Alba Cristina Miranda de Barros; Santos, Thais da Silva; Neves, Renata Heisler; Lopes Torres, Eduardo José; Nogueira-Neto, José Firmino; Machado-Silva, José Roberto

    2016-08-01

    Experimental data have shown that simvastatin and artesunate possess activity against Schistosoma mansoni worms in mice fed standard chow. However, little is known regarding the roles of these drugs in mice fed high-fat chow. We have extended past studies by measuring the effects of these drugs on the structural organization of adult schistosomes in hypercholesterolemic mice. For this purpose, mice were gavaged with either simvastatin or artesunate at nine weeks post-infection and were euthanized by cervical dislocation at two weeks post-treatment. Adult worms were then collected and examined by conventional light microscopy, morphometry and confocal laser scanning microscopy. Plasma total cholesterol and worm reduction rates were significantly increased in mice fed high-fat chow compared with their respective control groups. Simvastatin and artesunate caused changes in the tegument, tubercles, and reproductive system (testicular lobes, vitelline glands and ovarian cells), particularly when administered to mice fed high-fat chow. In particular, the tegument and tubercles were significantly thinner in artesunate-treated worms in mice fed high-fat chow compared with mice fed standard chow. This study thus demonstrated that simvastatin and artesunate have several novel effects on the structural organization of adult worms. Together, these results show, for the first time, that simvastatin and artesunate display antischistosomal activity in hypercholesterolemic mice. PMID:27228897

  11. Autotransplantation of hepatic granulomas into the skin of mice with Schistosoma mansoni infection

    SciTech Connect

    Nishimura, M.; Epstein, W.L.; Fukuyama, K.

    1982-09-01

    Hepatic egg granulomas of mice infected with Schistosoma mansoni were transplanted into the skin of the same animal and changes occurring to macrophages, eosinophils, and mast cells over time were studied by light and electron microscopy and by autoradiographic techniques. Disappearance of cellular components about the egg granulomas occurred within 1 week; the entire implant became encapsulated by inflammatory cells and stroma. By 3 weeks mononuclear cells and macrophages reorganized the granulomas around the eggs and neutrophils disappeared. Activated macrophages contained both secretory rough endoplasmic reticulum and lysosomal-dense bodies. Granuloma size increased up to 5 weeks after implantation and mast cells and eosinophils tended to migrate into the granulomas. The mast cell index always remained lower than in the original hepatic granulomas, while eosinophils were seen in large numbers. During 3 to 8 weeks after implantation mononuclear cells undergoing DNA synthesis in the granulomas ranged from 2.9-4.8%. Some 3-week-old autotransplants were injected with /sup 3/H-thymidine and biopsied from 1 to 21 days later. Labeled mononuclear cells peaked in the granulomas by 10 days (24%) and the numbers fell off sharply after that. These findings indicate that autologously implanted schistosome egg granulomas can be maintained successfully in the skin for prolonged periods with marked ingress of macrophages and eosinophils. The autoradiographic data suggest the lesions are high turnover granulomas.

  12. Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae

    SciTech Connect

    Dalton, J.P.; Strand, M.; Mangold, B.L.; Dean, D.A.

    1986-01-01

    The humoral immune responses of mice patently infected with Schistosoma mansoni and of mice vaccinated with radiation-attenuated cercariae were compared by radioimmunoassays and one-and two-dimensional polyacrylamide gel analyses of radioimmunoprecipitates. Sera of vaccinated mice precipitated a restricted number of predominantly high m.w. glycoproteins of both schistosomula and adult worms metabolically labeled with (/sup 35/S) methinonine. Each of the glycoproteins of 36 hr in vitro-cultured schistosomula that was precipitated by the sera of vaccinated mice was also precipitated by sera of infected mice. In contrast, sera of vaccinated mice uniquely precipitated a 38,000 m.w. glycoprotein of schistosomula cultured for 5 days and a 94,000 m.w. glycoprotein of adult male worms. Although radiation-attenuated larvae do not reach the adult stage, mice vaccinated with these still elicit a strong immune response against egg glycoproteins. In particular, an egg glycoprotein of 85,000 to 70,000 and isoelectric point of 4.8 showed an enhanced reactivity with sera of vaccinated mice in comparison with infected mice. These results show that the antibody response in mice vaccinated with radiation-attenuated larvae differs qualitatively and quantitatively from that of infected mice.

  13. Prophylactic effect of artemether on human schistosomiasis mansoni among Egyptian children: A randomized controlled trial.

    PubMed

    Elmorshedy, Hala; Tanner, Marcel; Bergquist, Robert N; Sharaf, Soraya; Barakat, Rashida

    2016-06-01

    A double-blind, randomized controlled trial was conducted in an endemic focus for Schistosoma mansoni in Kafr El-Sheikh Governorate, Northern Nile Delta, Egypt, to evaluate the prophylactic effect of artemether (ART) given in conjunction with praziquantel (PZQ). The study encompassed 913 primary school children randomly assigned to two treatment groups PZQ/ART and PZQ/ART-placebo. At baseline, both groups received 40 mg/kg body weight of PZQ twice four weeks apart, after which one group received 6 mg/kg body weight of ART every 3 weeks in 5 cycles during the transmission season and the other group received ART-placebo. At the end of the study, prevalence of infection among the PZQ/ART was approximately half that of the PZQ/ART-placebo group, i.e. 6.7% versus 11.6%, and incidence of new infections for the PZQ/ART was 2.7% versus 6.5% for the PZQ/ART-placebo. In conclusion, PZQ/ART combined therapy might be considered as an adjunct measure against human schistosomiasis, by specifically reducing transmission and therefore contribute to disease elimination. PMID:26921676

  14. Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray.

    PubMed

    Mickum, Megan L; Prasanphanich, Nina Salinger; Song, Xuezheng; Dorabawila, Nelum; Mandalasi, Msano; Lasanajak, Yi; Luyai, Anthony; Secor, W Evan; Wilkins, Patricia P; Van Die, Irma; Smith, David F; Nyame, A Kwame; Cummings, Richard D; Rivera-Marrero, Carlos A

    2016-05-01

    Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses, we used a shotgun glycomics approach in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, and humans and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which also were analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fucα3GalNAcβ4(Fucα3)GlcNAc-R], which is also recognized by the IgG monoclonal antibody F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts, and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants, including core β-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis. PMID:26883596

  15. An Isochore-Like Structure in the Genome of the Flatworm Schistosoma mansoni

    PubMed Central

    Lamolle, Guillermo; Protasio, Anna V.; Iriarte, Andrés; Jara, Eugenio; Simón, Diego; Musto, Héctor

    2016-01-01

    Eukaryotic genomes are compositionally heterogeneous, that is, composed by regions that differ in guanine–cytosine (GC) content (isochores). The most well documented case is that of vertebrates (mainly mammals) although it has been also noted among unicellular eukaryotes and invertebrates. In the human genome, regarded as a typical mammal, this heterogeneity is associated with several features. Specifically, genes located in GC-richest regions are the GC3-richest, display CpG islands and have shorter introns. Furthermore, these genes are more heavily expressed and tend to be located at the extremes of the chromosomes. Although the compositional heterogeneity seems to be widespread among eukaryotes, the associated properties noted in the human genome and other mammals have not been investigated in depth in other taxa. Here we provide evidence that the genome of the parasitic flatworm Schistosoma mansoni is compositionally heterogeneous and exhibits an isochore-like structure, displaying some features associated, until now, only with the human and other vertebrate genomes, with the exception of gene concentration. PMID:27435793

  16. Choline incorporation by Schistosoma mansoni: distribution of choline metabolites during development and after sexual differentiation

    SciTech Connect

    Ancelin, M.L.; Torpier, G.; Vial, H.J.; Capron, A.

    1987-06-01

    Choline metabolism was investigated in Schistosoma mansoni during the main phases of its development, namely, schistosomula, 11- and 15-day-old worms, and adults. At the physiological choline concentration used in the assay (20 microM), betaine was, along with phosphatidylcholine, one of the most abundant choline metabolites, revealing considerable choline oxidation activity. Very little radioactivity was associated with CDP-choline, whereas a sustained incorporation into phosphocholine occurred. These results provide good evidence that CTP:phosphocholine cytidylyltransferase plays a regulatory role in the de novo pathway of phosphatidylcholine biosynthesis. During development, the incorporation of choline into its various metabolites was maximal in 11-day-old worms. At this stage, the oxidative pathway predominated over the Kennedy pathway, whereas at all other stages the de novo phosphatidylcholine biosynthesis was predominant. Furthermore, choline incorporation into betaine was much more important in the adult female worm than in the male, indicating a major difference in choline incorporation and distribution between the 2 sexes of the adult worms.

  17. The prolonged use of niclosamide as a molluscicide for the control of Schistosoma mansoni.

    PubMed

    Coura-Filho, P; Mendes, N M; de Souza, C P; Pereira, J P

    1992-01-01

    Applications of niclosamide at three-monthly intervals were undertaken for 14 years in foci of Biomphalaria glabrata in the water sources of Peri-Peri (Capim Branco, MG). All the residents of the area were submitted to an annual fecal examination (Kato/Katz) and those individuals eliminating Schistosoma mansoni eggs were treated with oxamniquine. A malacological survey was undertaken at three-monthly intervals by means of ten scoops with a perforated ladle each ten metres along the two banks of the ditches and streams of the region. Where snails were found, molluscicide was applied by means of dripping or aspersion using a 3 ppm aqueous suspension of niclosamide. Initially, a mean of 14.3% of snails in the region were found to be eliminating cercariae. Following the first four applications of molluscicide, this was reduced to 0.0% and maintained at about 1.5% throughout the program. Thus, there was a continued possibility of schistosomiasis transmission in the area and it was observed that the population of snails reestablished itself within three months of molluscicide application. The results obtained in this study do not encourage the continual use of niclosamide as the only method of control of schistosomiasis. PMID:1342106

  18. [Bilharziasis caused by Schistosoma mansoni in a traveler returning from Guinea: failure of serodiagnostic testing].

    PubMed

    Raccurt, C P; El Samad, Y; Chouaki, T; Borel, A; Agnamey, P; Totet, A; Schmit, J L

    2007-04-01

    The purpose of this report is to describe a case of febrile hypereosinophilic syndrome in a traveler three weeks after returning from a sightseeing trip to Guinea. Laboratory testing demonstrated an inflammatory response syndrome and hepatic cytolysis. Parasite serology led to suspicion of toxocariasis that was treated using albendazole. Follow-up tests at two months showed the presence of Schistosoma mansoni eggs in stools despite negative standard serodiagnostic testing (hemagglutination). Secondarily Western blot testing of serum samples at one, two and 14 months after returning from Guinea continued to show only protein bands specific to toxocariasis with no bands specific to bilhariziasis. These findings provide further evidence of the limitations of serological testing for detection of bilharziasis in travelers and the difficulty of diagnosis. Guinea is a high-risk tourist destination. Intestinal and urinary bilharziasis are endemic over three-fourths of country. Travelers planning even short stays in areas where bilharziasis is endemic should be advised on preventive measures. PMID:17691438

  19. Sensory Protein Kinase Signaling in Schistosoma mansoni Cercariae: Host Location and Invasion

    PubMed Central

    Ressurreição, Margarida; Kirk, Ruth S.; Rollinson, David; Emery, Aidan M.; Page, Nigel M.; Walker, Anthony J.

    2015-01-01

    Schistosoma mansoni cercariae display specific behavioral responses to abiotic/biotic stimuli enabling them to locate and infect the definitive human host. Here we report the effect of such stimulants on signaling pathways of cercariae in relation to host finding and invasion. Cercariae exposed to various light/temperature regimens displayed modulated protein kinase C (PKC), extracellular signal–regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) activities, with distinct responses at 37°C and intense light/dark, when compared to 24°C under normal light. Kinase activities were localized to regions including the oral sensory papillae, acetabular ducts, tegument, acetabular glands, and nervous system. Furthermore, linoleic acid modulated PKC and ERK activities concurrent with the temporal release of acetabular gland components. Attenuation of PKC, ERK, and p38 MAPK activities significantly reduced gland component release, particularly in response to linoleic acid, demonstrating the importance of these signaling pathways to host penetration mechanisms. PMID:26401028

  20. Schistosoma mansoni: molecular characterization of Alkaline Phosphatase and expression patterns across life cycle stages.

    PubMed

    Araujo-Montoya, B O; Rofatto, H K; Tararam, C A; Farias, L P; Oliveira, K C; Verjovski-Almeida, S; Wilson, R A; Leite, L C C

    2011-11-01

    Here we describe the cloning and characterization of the Schistosoma mansoni Alkaline Phosphatase (SmAP), previously identified in the tegument of adult worms. SmAP encodes a complete sequence composed of 536 amino acids containing an N-terminal signal peptide, five N-glycosylation sites, and a GPI anchor signal, similar to that described for mammalian orthologs. Real-time RT-PCR and Western blot experiments suggest a rapid translation as soon as cercariae are transformed into schistosomula. Immunolocalization analysis shows that the protein is widely distributed in the worm tissues, with increased concentration in the vitelline glands of female parasites. Furthermore, the surface localization of this enzyme was quantitatively supported by its enzymatic activity in live ex vivo or cultured parasites throughout the life cycle stages. The fact that cercariae accumulate large amounts of SmAP mRNA, which rapidly translates into protein upon schistosomula transformation, indicates it may have an important role in host invasion. PMID:21784070

  1. Schistosoma mansoni-Related Hepatosplenic Morbidity in Adult Population on Kome Island, Sengerema District, Tanzania

    PubMed Central

    Kaatano, Godfrey M.; Min, Duk-Young; Siza, Julius E.; Yong, Tai-Soon; Chai, Jong-Yil; Ko, Yunsuk; Chang, Su-Young; Changalucha, John M.; Eom, Keeseon S.; Rim, Han-Jong

    2015-01-01

    Schistosomiasis is one of the important neglected tropical diseases (NTDs) in Tanzania, particularly in Lake Victoria zone. This baseline survey was a part of the main study of integrated control of schistosomiasis and soil-transmitted helminths (STHs) aimed at describing morbidity patterns due to intestinal schistosomiasis among adults living on Kome Island, Sengerema District, Tanzania. Total 388 adults from Kome Islands (about 50 people from each village) aged between 12 and 85 years, were examined by abdominal ultrasound according to the Niamey protocol. Liver image patterns (LIPs) A and B were considered normal, and C-F as distinct periportal fibrosis (PPF). The overall prevalence of PPF was 42.2%; much higher in males than in females (47.0% in male vs 34.4% in females, P=0.007). Abnormal increase of segmental branch wall thickness (SBWT) and dilated portal vein diameter (PVD) were also more common in males than in females. Hepatosplenomegaly was frequently encountered; 68.1% had left liver lobe hepatomegaly and 55.2% had splenomegaly. Schistosoma mansoni-related morbidity is quite high among adults in this community justifying the implementation of integrated control strategies through mass drug administration, improved water supply (pumped wells), and health education that had already started in the study area. PMID:26537033

  2. An Isochore-Like Structure in the Genome of the Flatworm Schistosoma mansoni.

    PubMed

    Lamolle, Guillermo; Protasio, Anna V; Iriarte, Andrés; Jara, Eugenio; Simón, Diego; Musto, Héctor

    2016-01-01

    Eukaryotic genomes are compositionally heterogeneous, that is, composed by regions that differ in guanine-cytosine (GC) content (isochores). The most well documented case is that of vertebrates (mainly mammals) although it has been also noted among unicellular eukaryotes and invertebrates. In the human genome, regarded as a typical mammal, this heterogeneity is associated with several features. Specifically, genes located in GC-richest regions are the GC3-richest, display CpG islands and have shorter introns. Furthermore, these genes are more heavily expressed and tend to be located at the extremes of the chromosomes. Although the compositional heterogeneity seems to be widespread among eukaryotes, the associated properties noted in the human genome and other mammals have not been investigated in depth in other taxa Here we provide evidence that the genome of the parasitic flatworm Schistosoma mansoni is compositionally heterogeneous and exhibits an isochore-like structure, displaying some features associated, until now, only with the human and other vertebrate genomes, with the exception of gene concentration. PMID:27435793

  3. Schistosoma mansoni: interactive effects of irradiation and cryopreservation on parasite maturation and immunization of mice

    SciTech Connect

    James, E.R.; Dobinson, A.R.

    1984-06-01

    Mechanically transformed schistosomula of Schistosoma mansoni were irradiated with levels of 60Co irradiation between 2.5 and 54 krad, cryopreserved by the two-step addition of ethanediol and rapid cooling technique, and were injected intramuscularly into groups of mice which were perfused 40 days later. The schistosomula were either irradiated and then cryopreserved (IC) or cryopreserved and then irradiated in the frozen state (CI). Development into adult worms was prevented with 4 krad for IC schistosomula, but for CI schistosomula a small number of worms (1.6%) was recovered using 8.8 krad. A dose of 4 krad was sufficient to prevent development of unfrozen controls (I), but for schistosomula irradiated while exposed to ethanediol (EI), a dose of 7 krad was required. Using the different protocols, the peak levels of protection against a challenge infection were achieved with 9 (IC) and 16 krad (CI), compared to 20 krad for unfrozen schistosomula (I) reported previously. The highest level of protection (65%) was achieved with CI schistosomula. Possible interactions between the radioprotective and damaging effects of cryopreservation are discussed.

  4. The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation

    SciTech Connect

    Coutinho Carneiro, Vitor; Moraes Maciel, Renata de; Caetano de Abreu da Silva, Isabel; Furtado Madeira da Costa, Rodrigo; Neto Paiva, Claudia; Torres Bozza, Marcelo; Rosado Fantappie, Marcelo

    2009-12-25

    Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1{Delta}C) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1{Delta}C were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1 was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed.

  5. Schistosoma mansoni polypeptides immunogenic in mice vaccinated with radiation-attenuated cercariae

    SciTech Connect

    Dalton, J.P.; Strand, M.

    1987-10-01

    We compared the humoral immune response of mice protected against Schistosoma mansoni by vaccination with radiation-attenuated cercariae to that of patently infected mice, and we identified antigens that elicit a greater, or unique, immune response in the vaccinated mice. These comparisons were based upon radioimmunoprecipitations and immunodepletion of (/sup 35/S)methionine-labeled schistosomular and adult worm polypeptides, followed by one- and two-dimensional polyacrylamide gel analyses. The humoral responses of patently infected mice and of mice vaccinated once were remarkably similar and were directed against schistosome glycoproteins ranging in molecular size from greater than 300 to less than 10 kDa. Exposing mice to a second vaccination resulted in a marked change in the immune response, to one predominantly directed toward high molecular size glycoproteins. Sequential immunodepletion techniques identified five schistosomular and seven adult worm antigens that showed a greater or unique immunogenicity in vaccinated mice as compared with patently infected mice. These adult worm antigens were purified by preparative sequential immunoaffinity chromatography and used to prepare a polyclonal antiserum, anti-irradiated vaccine. This antiserum bound to the surface of live newly transformed and lung-stage schistosomula, as assessed by immunofluorescence assays, and was reactive with a number of /sup 125/I-labeled schistosomular surface polypeptides, including a doublet of 150 kDa that was also recognized by sera of vaccinated mice but not by sera of patently infected mice.

  6. Therapeutic effect of mefloquine on Schistosoma mansoni in experimental infection in mice.

    PubMed

    Abou-Shady, Omaima Mohammed; Mohammed, Soheir Sayed; Attia, Samar Sayed; Yusuf, Hebat-Allah Salah; Helmy, Dina Omar

    2016-06-01

    Schistosomiasis is one of the most prevalent parasitic infections worldwide. Praziquantel is the drug of choice for treatment of schistosomiasis for its high efficacy. The present work was carried out on 160 mice to evaluate the therapeutic effect of mefloquine on experimental schistosomiasis mansoni. Mice were classified into 3 groups; group I (20 infected non-treated mice), group II included 60 infected mice which were further divided into group IIm (20 mice treated with 400 mg/kg mefloquine), group IIp (20 mice treated with 1,000 mg/kg/2 days praziquantel) and group IIpm (20 mice treated with 200 mg/kg mefloquine and 500 mg/kg praziquantel), group III included 80 non-infected mice subdivided into group IIIn (20 non-treated mice), group IIIm (20 mice treated with 400 mg/kg mefloquine), group IIIp (20 mice treated with 1,000 mg/kg/2 days praziquantel), group IIIpm (20 mice treated with 200 mg mefloquine and 500 mg praziquantel). Mefloquine significantly reduced worm burden, tissue egg load, number of liver granulomas and increased the percent of dead ova within granulomas. Combination of mefloquine and praziquantel gave better curative effects than praziquantel or mefloquine given alone. PMID:27413290

  7. Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules

    SciTech Connect

    Lewis, F.A.; Stirewalt, M.A.; Leef, J.L.

    1984-06-01

    Protection against a Schistosoma mansoni cercarial challenge was evaluated in mice immunized with a vaccine composed of 10-krad-irradiated, cryopreserved schistosomules. The level of resistance induced in C57B1/6 or NMRI (CV) mice increased with the number of schistosomules injected. Up to 83% reduction in challenge worm burden was achieved when 5000 schistosomules were injected per mouse. Intramuscular injection of the vaccine was superior to subcutaneous. Multiple immunizations, up to 3 at 4-week intervals, did not increase the resistance induced by a single immunization. A high level of protection developed in as little as 2 weeks and was maintained through at least 12 weeks postimmunization. The vaccine irradiated with 10 krad from either a 60-cobalt or 137-cesium source induced equivalent levels of resistance, and no differences were found in the immunogenicity of vaccines comprised of organisms irradiated as cercariae or as 1- to 3-hr-old schistosomules. These findings are basic to the development of a cryopreserved, live vaccine against schistosomiasis of humans or domestic animals.

  8. Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni

    PubMed Central

    Panic, Gordana; Vargas, Mireille; Scandale, Ivan; Keiser, Jennifer

    2015-01-01

    Background As plans to expand mass drug treatment campaigns to fight schistosomiasis form, worries about reliance on praziquantel as the sole available treatment motivate the investigation for novel antischistosomal compounds. Drug repurposing might be an inexpensive and effective source of novel antischistosomal leads. Methodology 1600 FDA approved compounds were first assayed against Schistosoma mansoni schistosomula at a concentration of 10 µM. Active compounds identified from this screen were advanced to the adult worm screen at 33.33 µM, followed by hit characterization. Leads with complementary pharmacokinetic and toxicity profiles were then selected for in vivo studies. Principal Findings The in vitro screen identified 121 and 36 compounds active against the schistosomula and adult stage, respectively. Further, in vitro characterization and comparison with already available pharmacokinetic and toxicity data identified 11 in vivo candidates. Doramectin (10 mg/kg) and clofazimine (400 mg/kg) were found to be active in vivo with worm burden reductions of 60.1% and 82.7%, respectively. Conclusions/Significance The work presented here expands the knowledge of antischistosomal properties of already approved compounds and underscores variations observed between target-based and phenotypic approaches and among laboratories. The two in vivo-active drugs identified in this study, doramectin and clofazimine are widely available and present as novel drug classes as starting points for further investigation. PMID:26230921

  9. FASCIOLA HEPATICA AND SCHISTOSOMA MANSONI: IDENTIFICATION OF COMMON PROTEINS BY COMPARATIVE PROTEOMIC ANALYSIS

    PubMed Central

    Boukli, Nawal M.; Delgado, Bonnibel; Ricaurte, Martha; Espino, Ana M.

    2013-01-01

    It is not unusual to find common molecules among parasites of different species, genera, or phyla. When those molecules are antigenic, they may be used for developing drugs or vaccines that simultaneously target different species or genera of parasite. In the present study, we used a proteomic-based approach to identify proteins that are common to adult Fasciola hepatica and Schistosoma mansoni. Whole-worm extracts from each parasite were separated by 2-dimensional electrophoresis (2-DE), and digital images of both proteomes were superimposed using imaging software to identify proteins with identical isoelectric points and molecular weights. Protein identities were determined by mass spectrometry. Imaging and immunoblot analyses identified 28 immunoreactive proteins that are common to both parasites. Among these molecules are antioxidant proteins (thioredoxin and glutathione-S-transferase), glycolytic enzymes (glyceraldehyde 6-phosphate dehydrogenase and enolase), proteolytic enzymes (cathepsin-L and -D), inhibitors (Kunitz-type, Stefin-1), proteins with chaperone activity (heat shock protein 70 and fatty acid–binding protein), and structural proteins (calcium-binding protein, actin, and myosin). Some of the identified proteins could be used to develop drugs and vaccines against fascioliasis and schistosomiasis. PMID:21506812

  10. Metabolic fingerprinting of Schistosoma mansoni infection in mice urine with capillary electrophoresis.

    PubMed

    García-Pérez, Isabel; Whitfield, Philip; Bartlett, Ann; Angulo, Santiago; Legido-Quigley, Cristina; Hanna-Brown, Melissa; Barbas, Coral

    2008-08-01

    Schistosoma mansoni infection in mice has been fingerprinted using CE to study the capabilities of this technique as a diagnostic tool for this parasitic disease. Two modes of separation were used in generating the electrophoretic data, with each untreated urine sample the following methods were applied: (i) a fused-silica capillary, operating with an applied potential of 18 kV, in micellar EKC (MEKC) and (ii) a polyacrylamide-coated capillary, operating with an applied potential of -20 kV under zonal CZE conditions. By combining normal and reverse polarities in the data treatment we have extracted more information from the samples, which is a better approach for CE metabolomics. The traditional problems associated with variability in electrophoretic peak migration times for analytes were countered by using a dynamic programming algorithm for the electropherograms alignment. Principal component analyses of these aligned electropherograms and partial least square discriminant analysis (PLS-DA) data are shown to provide a valuable means of rapid and sample classification. This approach may become an important tool for the identification of biomarkers, diagnosis and disease surveillance. PMID:18633941

  11. Sensory Protein Kinase Signaling in Schistosoma mansoni Cercariae: Host Location and Invasion.

    PubMed

    Ressurreição, Margarida; Kirk, Ruth S; Rollinson, David; Emery, Aidan M; Page, Nigel M; Walker, Anthony J

    2015-12-01

    Schistosoma mansoni cercariae display specific behavioral responses to abiotic/biotic stimuli enabling them to locate and infect the definitive human host. Here we report the effect of such stimulants on signaling pathways of cercariae in relation to host finding and invasion. Cercariae exposed to various light/temperature regimens displayed modulated protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) activities, with distinct responses at 37 °C and intense light/dark, when compared to 24 °C under normal light. Kinase activities were localized to regions including the oral sensory papillae, acetabular ducts, tegument, acetabular glands, and nervous system. Furthermore, linoleic acid modulated PKC and ERK activities concurrent with the temporal release of acetabular gland components. Attenuation of PKC, ERK, and p38 MAPK activities significantly reduced gland component release, particularly in response to linoleic acid, demonstrating the importance of these signaling pathways to host penetration mechanisms. PMID:26401028

  12. Genetic structure of Schistosoma mansoni in western Kenya: the effects of geography and host sharing

    PubMed Central

    Steinauer, M. L.; Hanelt, B.; Agola, L. E.; Mkoji, G. M.; Loker, E. S.

    2010-01-01

    We examined the spatial structure of Schistosoma mansoni, a parasite of humans, from natural infections at two levels: across the Lake Victoria basin of Kenya and among snail hosts. Using 20 microsatellite markers we examined geographic patterns of relatedness and population structure of cercariae and found weak, but significant structure detected by some, but not all analyses. We hypothesize structure created by aggregations of clonal individuals or adherence of hosts to local transmission sites is eroded by high amounts of gene flow in the region. This finding also supports previous hypotheses concerning the evolution of drug resistance in the region. Intrasnail dynamics were investigated in the context of aggregation and kin selection theory to determine how relatedness and also sex influence host sharing and host exploitation. Cercarial production did not differ significantly between snails with one or two genotypes suggesting that mixed infections resulted in decreased individual fitness and provides a framework for reproductive competition. Coinfection patterns in snails were independent of parasite relatedness indicating that schistosomes were not aggregated according to their relatedness and that kin selection was not influencing host sharing. Additionally, host exploitation in coinfections (measured by cercarial production) was not negatively correlated with relatedness, as predicted by classical models due to increased competition and thus exploitation when parasites are unrelated. Because of the low levels of relatedness within the population, schistosomes may rarely encounter close relatives and kin selection mechanisms that influence the distribution of individuals within snails or the virulence mode of the parasites may simply have not evolved. PMID:19464296

  13. Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles.

    PubMed

    Dvořák, Jan; Fajtová, Pavla; Ulrychová, Lenka; Leontovyč, Adrian; Rojo-Arreola, Liliana; Suzuki, Brian M; Horn, Martin; Mareš, Michael; Craik, Charles S; Caffrey, Conor R; O'Donoghue, Anthony J

    2016-03-01

    Schistosomiasis is one of a number of chronic helminth diseases of poverty that severely impact personal and societal well-being and productivity. Peptidases (proteases) are vital to successful parasitism, and can modulate host physiology and immunology. Interference of peptidase action by specific drugs or vaccines can be therapeutically beneficial. To date, research on peptidases in the schistosome parasite has focused on either the functional characterization of individual peptidases or their annotation as part of global genome or transcriptome studies. We were interested in functionally characterizing the complexity of peptidase activity operating at the host-parasite interface, therefore the excretory-secretory products of key developmental stages of Schistosoma mansoni that parasitize the human were examined. Using class specific peptidase inhibitors in combination with a multiplex substrate profiling assay, a number of unique activities derived from endo- and exo-peptidases were revealed in the excretory-secretory products of schistosomula (larval migratory worms), adults and eggs. The data highlight the complexity of the functional degradome for each developmental stage of this parasite and facilitate further enquiry to establish peptidase identity, physiological and immunological function, and utility as drug or vaccine candidates. PMID:26409899

  14. Purine nucleoside phosphorylase from Schistosoma mansoni in complex with ribose-1-phosphate

    PubMed Central

    D’Muniz Pereira, Humberto; Oliva, Glaucius; Garratt, Richard Charles

    2011-01-01

    Schistosomes are blood flukes which cause schistosomiasis, a disease affecting approximately 200 million people worldwide. Along with several other important human parasites including trypanosomes and Plasmodium, schistosomes lack the de novo pathway for purine synthesis and depend exclusively on the salvage pathway for their purine requirements, making the latter an attractive target for drug development. Part of the pathway involves the conversion of inosine (or guanosine) into hypoxanthine (or guanine) together with ribose-1-phosphate (R1P) or vice versa. This inter-conversion is undertaken by the enzyme purine nucleoside phosphorylase (PNP) which has been used as the basis for the development of novel anti-malarials, conceptually validating this approach. It has been suggested that, during the reverse reaction, R1P binding to the enzyme would occur only as a consequence of conformational changes induced by hypoxanthine, thus making a binary PNP–R1P complex unlikely. Contradictory to this statement, a crystal structure of just such a binary complex involving the Schistosoma mansoni enzyme has been successfully obtained. The ligand shows an intricate hydrogen-bonding network in the phosphate and ribose binding sites and adds a further chapter to our knowledge which could be of value in the future development of selective inhibitors. PMID:21169694

  15. Immobilized purine nucleoside phosphorylase from Schistosoma mansoni for specific inhibition studies.

    PubMed

    de Moraes, Marcela Cristina; Cardoso, Carmen L; Cass, Quezia B

    2013-05-01

    The parasite Schistosoma mansoni (Sm) depends exclusively on the salvage pathway for its purine requirements. The enzyme purine nucleoside phosphorylase (PNP) is, therefore, a promising target for development of antischistosomal agents and an assay for screening of inhibitors. To enable this, immobilized SmPNP reactors were produced. By quantification of hypoxanthine by liquid chromatography, kinetic constants (K M) for the substrate inosine were determined for the free and immobilized enzyme as 110 ± 6.90 μmol L (-1) and 164 ± 13.4 μmol L (-1), respectively, indicating that immobilization did not affect enzyme activity. Furthermore, the enzyme retained 25 % of its activity after four months. Non-Michaelis kinetics for the phosphate substrate, and capacity for Pi-independent hydrolysis were also demonstrated, despite the low rate of enzymatic catalysis. Use of an SmPNP immobilized enzyme reactor (IMER) for inhibitor-screening assays was demonstrated with a small library of 9-deazaguanine analogues. The method had high selectivity and specificity compared with screening by use of the free enzyme by the Kalckar method, and furnished results without the need for verification of the absence of false positives. PMID:23535739

  16. Newly Established Monoclonal Antibody Diagnostic Assays for Schistosoma mansoni Direct Detection in Areas of Low Endemicity

    PubMed Central

    Grenfell, Rafaella Fortini Queiroz; Coelho, Paulo Marcos Zech; Taboada, Diana; de Mattos, Ana Carolina Alves; Davis, Ruth; Harn, Donald A.

    2014-01-01

    Background Current available methods for diagnosis of schistosomiasis mansoni lack sufficient sensitivity, which results in underreporting of infectious in areas of low endemicity. Methodology/Principal Findings We developed three novel diagnostic methodologies for the direct detection of schistosome infection in serum samples. These three new methods were evaluated with positive patients from a low endemicity area in southeast Brazil. The basis of the assay was the production of monoclonal antibodies against the protein backbone of heavily glycosylated Circulating Cathodic Antigen (CCA). The antibodies were also selected for having no specificity to repeating poly-Lewis x units. Assays based on the detection CCA-protein should not encounter a limitation in sensitivity due to a biological background of this particular epitope. Three diagnostic methodologies were developed and validated, (i) Immunomagnetic Separation based on improved incubation steps of non-diluted serum, (ii) Direct Enzyme-linked Immunosorbent Assay and (iii) Fluorescent Microscopy Analysis as a qualitative assay. The two quantitative assays presented high sensitivity (94% and 92%, respectively) and specificity (100%), equivalent to the analysis of 3 stool samples and 16 slides by Kato-Katz, showing promising results on the determination of cure. Conclusions/Significance The Immunomagnetic Separation technique showed excellent correlation with parasite burden by Cohen coefficient. The qualitative method detected 47 positive individuals out of 50 with the analysis of 3 slides. This easy-to-do method was capable of discriminating positive from negative cases, even for patients with low parasite burden. PMID:24498191

  17. Cost analysis of tests for the detection of Schistosoma mansoni infection in children in western Kenya.

    PubMed

    Worrell, Caitlin M; Bartoces, Monina; Karanja, Diana M S; Ochola, Elizabeth A; Matete, Daniel O; Mwinzi, Pauline N M; Montgomery, Susan P; Secor, W Evan

    2015-06-01

    Financial resources tend to be limited in schistosomiasis endemic areas, forcing program managers to balance financial and scientific considerations when selecting detection assays. Therefore, we compared the costs of using single stool Kato-Katz, triplicate stool Kato-Katz, and point-of-contact circulating cathodic antigen (POC-CCA) assays for the detection of Schistosoma mansoni infection. Economic and financial costs were estimated from the viewpoint of a schistosomiasis control program using the ingredients approach. Costs related to specimen collection, sample processing and analysis, and treatment delivery were considered. Analysis inputs and assumptions were tested using one-way and two-way sensitivity analysis. The total per-person cost of performing the single Kato-Katz, triplicate Kato-Katz, and POC-CCA was US$6.89, US$17.54, and US$7.26, respectively. Major cost drivers included labor, transportation, and supplies. In addition, we provide a costing tool to guide program managers in evaluating detection costs in specific settings, as costs may vary temporally and spatially. PMID:25870422

  18. Schistosoma mansoni-Related Hepatosplenic Morbidity in Adult Population on Kome Island, Sengerema District, Tanzania.

    PubMed

    Kaatano, Godfrey M; Min, Duk-Young; Siza, Julius E; Yong, Tai-Soon; Chai, Jong-Yil; Ko, Yunsuk; Chang, Su-Young; Changalucha, John M; Eom, Keeseon S; Rim, Han-Jong

    2015-10-01

    Schistosomiasis is one of the important neglected tropical diseases (NTDs) in Tanzania, particularly in Lake Victoria zone. This baseline survey was a part of the main study of integrated control of schistosomiasis and soil-transmitted helminths (STHs) aimed at describing morbidity patterns due to intestinal schistosomiasis among adults living on Kome Island, Sengerema District, Tanzania. Total 388 adults from Kome Islands (about 50 people from each village) aged between 12 and 85 years, were examined by abdominal ultrasound according to the Niamey protocol. Liver image patterns (LIPs) A and B were considered normal, and C-F as distinct periportal fibrosis (PPF). The overall prevalence of PPF was 42.2%; much higher in males than in females (47.0% in male vs 34.4% in females, P=0.007). Abnormal increase of segmental branch wall thickness (SBWT) and dilated portal vein diameter (PVD) were also more common in males than in females. Hepatosplenomegaly was frequently encountered; 68.1% had left liver lobe hepatomegaly and 55.2% had splenomegaly. Schistosoma mansoni-related morbidity is quite high among adults in this community justifying the implementation of integrated control strategies through mass drug administration, improved water supply (pumped wells), and health education that had already started in the study area. PMID:26537033

  19. Schistosoma mansoni infection along the coast of Lake Victoria in Mwanza region, Tanzania.

    PubMed

    Olsen, Annette; Kinung'hi, Safari; Magnussen, Pascal

    2015-06-01

    Prevalence and intensity of Schistosoma mansoni infection according to age, sex, and occupation were investigated in 100 first-year students (aged 7-8 years), 100 schoolchildren (aged 9-12 years), and 50 adults (aged 20-55 years) from 149 villages. The schoolchildren provided three stool specimens while the rest provided only one specimen. A total of 31,865 individuals provided at least one specimen with an overall prevalence of 38.5% and geometric mean intensity of positives of 107.0 eggs per gram of feces. With the exception of first-year students, males had higher prevalence than females (P < 0.0005). Schoolchildren had higher prevalence than first-year students that again had higher prevalence than adults. There was no sex difference in intensities among the children, but adult males had higher intensities than adult females. Intensity among the children was higher than that of the adults (P < 0.0005). Prevalence was significantly higher in those having fishing as their main occupation. Three stools samples were obtained from 13,119 schoolchildren, resulting in a prevalence of 38.1% if only one sample was included, 47.5% including two samples, and 52.6% if all three samples were included. PMID:25825388

  20. Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis

    PubMed Central

    2015-01-01

    The X-ray crystal structure of arginase from Schistosoma mansoni (SmARG) and the structures of its complexes with several amino acid inhibitors have been determined at atomic resolution. SmARG is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea, and this enzyme is upregulated in all forms of the parasite that interact with the human host. Current hypotheses suggest that parasitic arginases could play a role in host immune evasion by depleting pools of substrate l-arginine that would otherwise be utilized for NO biosynthesis and NO-dependent processes in the immune response. Although the amino acid sequence of SmARG is only 42% identical with that of human arginase I, residues important for substrate binding and catalysis are strictly conserved. In general, classical amino acid inhibitors such as 2(S)-amino-6-boronohexanoic acid (ABH) tend to bind more weakly to SmARG than to human arginase I despite identical inhibitor binding modes in each enzyme active site. The identification of a patch on the enzyme surface capable of accommodating the additional Cα substitutent of an α,α-disubstituted amino acid inhibitor suggests that such inhibitors could exhibit higher affinity and biological activity. The structures of SmARG complexed with two different α,α-disubstituted derivatives of ABH are presented and provide a proof of concept for this approach in the enhancement of enzyme–inhibitor affinity. PMID:25007099

  1. Induction of cellular and humoral immunological responsiveness to a soluble cercarial antigen preparation from Schistosoma mansoni.

    PubMed Central

    Katz, S P; Colley, D G

    1976-01-01

    The development of immunological responsiveness to a soluble cercarial antigenic preparation (CAP) from Schistosoma mansoni was analyzed in inbred CBA/J mice infected with cercariae, one or multiple times, or sensitized using CAP. Repeated exposure to 75 cercariae at three weekly intervals (3X-75) or subcutaneous administration of 20 mug of CAP (CAP/complete Freund adjuvant [CFA]) stimulated the development of specific anti-CAP lymph node cell blastogenesis. The degree of responsiveness was dependent upon the concentration of CAP in the culture system and was optimal in the dose range of 20 to 30 mug of protein of CAP per culture. Animals exposed once to 75 or 225 cercariae or to two sequential weekly infections with 75 cercariae exhibited a minimal response to CAP in comparison to the responsiveness of 3X-75 or CAP/CFA lymph node cells. Assessment of anti-CAP agglutinating antibody by application of a microtiter passive hemagglutination technique revealed that both 3X-75 and CAP/CFA animals possessed low titers of activity. In addition, both 3X-75 and CAP/CFA sera contained reagin-like antibodies to CAP as detected by the heterologous (rat), 72-h latent period, passive cutaneous anaphylaxis technique. PMID:971960

  2. Daily emergence of Schistosoma mansoni and S. haematobium cercariae from naturally infected snails under field conditions.

    PubMed

    Wolmarans, C T; de Kock, K N; Strauss, H D; Bornman, M

    2002-09-01

    The daily emergence of Schistosoma mansoni and S. haematobium cercariae was investigated under field conditions. Intermediate host snails of both schistosome species were collected during the rainy season, cold dry season and warm dry season and kept separately in test tubes in habitat water. Shed cercariae were collected from each of the test tubes at two hourly intervals, transferred to Petri dishes and counted. Mice were exposed to these cercariae to establish the identity of the schistosome parasites. Peak shedding for both species was observed at 1100 h during the rainy and warm dry seasons and at 0900 h during the cold dry season. Shedding before 0900 h was found only for S. haematobium in the rainy season while shedding after 1700 h occurred only during this season at both species. Shedding observed during 1900 h observation period was in the low category for both species. No shedding was observed during the 2100 h observation period for any of the species and the investigation was discontinued after this period. Only S. haematobium ova were found in the exposed mice. PMID:12363382

  3. Development and behavior of cultured Schistosoma mansoni fed on human erythrocyte ghosts.

    PubMed

    Basch, P F

    1984-09-01

    Schistosomula and adults of Schistosoma mansoni were grown from cercariae in cultures differing only in the treatment of the red blood cells fed to the organisms. "Pink ghosts," containing about 5% of the original hemoglobin, were produced by hemolysis in water; "white ghosts" with no detectable hemoglobin were made in 5 mM phosphate buffer, pH 8. Early growth and development were more rapid and vigorous, and pairs formed more readily when pink ghosts, rather than intact erythrocytes were fed. Schistosomula remained stunted and undeveloped when fed with white ghosts. Attempts at reconstitution of the latter by addition of hemoglobin, concentrated erythrocyte lysate, or pressure-liquefied pink ghosts did not restore growth-promoting activity. Pink ghost-fed worms, particularly paired males, attached to the dish bottom by their acetabulum and oral sucker and travelled by an active looping motion. Substrates of collagen or fibrin or a mammalian cell monolayer did not affect this behavior. Such attachment and locomotion are interpreted as instinctive migratory behavior of schistosomes. PMID:6486300

  4. Evaluation of the CCA Immuno-Chromatographic Test to Diagnose Schistosoma mansoni in Minas Gerais State, Brazil

    PubMed Central

    Silveira, Alda Maria Soares; Costa, Emanuele Gama Dutra; Ray, Debalina; Suzuki, Brian M.; Hsieh, Michael H.; Fraga, Lucia Alves de Oliveira; Caffrey, Conor R.

    2016-01-01

    Background The Kato-Katz (KK) stool smear is the standard test for the diagnosis of Schistosoma mansoni infection, but suffers from low sensitivity when infections intensities are moderate to low. Thus, misdiagnosed individuals remain untreated and contribute to the disease transmission, thereby forestalling public health efforts to move from a modality of disease control to one of elimination. As an alternative, the urine-based diagnosis of schistosomiasis mansoni via the circulating cathodic antigen immuno-chromatographic test (CCA-ICT) has been extensively evaluated in Africa with the conclusion that it may replace the KK test in areas where prevalences are moderate or high. Methods and Findings The objective was to measure the performance of the CCA-ICT in a sample study population composed of residents from non-endemic and endemic areas for schistosomiasis mansoni in two municipalities of Minas Gerais state, Brazil. Volunteers (130) were classified into three infection status groups based on duplicate Kato-Katz thick smears from one stool sample (2KK test): 41 negative individuals from non-endemic areas, 41 negative individuals from endemic areas and 48 infected individuals from endemic areas. Infection status was also determined by the CCA-ICT and infection exposure by antibody ELISA (enzyme-linked immunosorbent assay) to S. mansoni soluble egg antigen (SEA) and soluble (adult) worm antigen preparation (SWAP). Sensitivity and specificity were influenced by whether the trace score visually adjudicated in the CCA-ICT was characterized as positive or negative for S. mansoni infection. An analysis of a two-graph receiver operating characteristic was performed to change the cutoff point. When the trace score was interpreted as a positive rather than as a negative result, the specificity decreased from 97.6% to 78.0% whereas sensitivity increased from 68.7% to 85.4%. A significantly positive correlation between the CCA-ICT scores and egg counts was identified (r

  5. Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel

    PubMed Central

    Pinto-Almeida, António; Mendes, Tiago; de Oliveira, Rosimeire Nunes; Corrêa, Sheila de Andrade Penteado; Allegretti, Silmara Marques; Belo, Silvana; Tomás, Ana; Anibal, Fernanda de Freitas; Carrilho, Emanuel; Afonso, Ana

    2016-01-01

    Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants. PMID:27199925

  6. Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel.

    PubMed

    Pinto-Almeida, António; Mendes, Tiago; de Oliveira, Rosimeire Nunes; Corrêa, Sheila de Andrade Penteado; Allegretti, Silmara Marques; Belo, Silvana; Tomás, Ana; Anibal, Fernanda de Freitas; Carrilho, Emanuel; Afonso, Ana

    2016-01-01

    Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants. PMID:27199925

  7. Immunization with recombinantly expressed glycan antigens from Schistosoma mansoni induces glycan-specific antibodies against the parasite

    PubMed Central

    Prasanphanich, Nina Salinger; Luyai, Anthony E; Song, Xuezheng; Heimburg-Molinaro, Jamie; Mandalasi, Msano; Mickum, Megan; Smith, David F; Nyame, A Kwame; Cummings, Richard D

    2014-01-01

    Schistosomiasis caused by infection with parasitic helminths of Schistosoma spp. is a major global health problem due to inadequate treatment and lack of a vaccine. The immune response to schistosomes includes glycan antigens, which could be valuable diagnostic markers and vaccine targets. However, no precedent exists for how to design vaccines targeting eukaryotic glycoconjugates. The di- and tri-saccharide motifs LacdiNAc (GalNAcβ1,4GlcNAc; LDN) and fucosylated LacdiNAc (GalNAcβ1,4(Fucα1-3)GlcNAc; LDNF) are the basis for several important schistosome glycan antigens. They occur in monomeric form or as repeating units (poly-LDNF) and as part of a variety of different glycoconjugates. Because chemical synthesis and conjugation of such antigens is exceedingly difficult, we sought to develop a recombinant expression system for parasite glycans. We hypothesized that presentation of parasite glycans on the cell surface would induce glycan-specific antibodies. We generated Chinese hamster ovary (CHO) Lec8 cell lines expressing poly-LDN (L8-GT) and poly-LDNF (L8-GTFT) abundantly on their membrane glycoproteins. Sera from Schistosoma mansoni-infected mice were highly cross-reactive with the cells and with cell-surface N-glycans. Immunizing mice with L8-GT and L8-GTFT cells induced glycan-specific antibodies. The L8-GTFT cells induced a sustained booster response, with antibodies that bound to S. mansoni lysates and recapitulated the exquisite specificity of the anti-parasite response for particular presentations of LDNF antigen. In summary, this recombinant expression system promotes successful generation of antibodies to the glycans of S. mansoni, and it can be adapted to study the role of glycan antigens and anti-glycan immune responses in many other infections and pathologies. PMID:24727440

  8. Role of adult worm antigen-specific immunoglobulin E in acquired immunity to Schistosoma mansoni infection in baboons.

    PubMed

    Nyindo, M; Kariuki, T M; Mola, P W; Farah, I O; Elson, L; Blanton, R E; King, C L

    1999-02-01

    Allergic-type immune responses, particularly immunoglobulin E (IgE), correlate with protective immunity in human schistosomiasis. To better understand the mechanisms of parasite elimination we examined the immune correlates of protection in baboons (Papio cynocephalus anubis), which are natural hosts for Schistosoma mansoni and also develop allergic-type immunity with infection. In one experiment, animals were exposed to a single infection (1,000 cercariae) or were exposed multiple times (100 cercariae per week for 10 weeks) and subsequently were cured with praziquantel prior to challenge with 1, 000 cercariae. Singly and multiply infected animals mounted 59 and 80% reductions in worm burden, respectively (P < 0.01). In a second experiment, animals were inoculated with S. mansoni ova and recombinant human interleukin 12 (IL-12). This produced a 37 to 39% reduction in adult worm burden after challenge (P < 0.05). Parasite-specific IgG, IgE, IgM, and peripheral blood cytokine production were evaluated. The only immune correlate of protection in both experiments was levels of soluble adult worm antigen (SWAP)-specific IgE in serum at the time of challenge infection and/or 6 weeks later. Baboons repeatedly infected with cercariae or immunized with ova and IL-12 developed two- to sixfold-greater levels of SWAP-specific IgE in serum than did controls, and this correlated with reductions in worm burden (r2, -0.40 to -0.64; P, <0. 01). Thus, in baboons and unlike mice, adult worm-specific IgE is uniquely associated with acquired immunity to S. mansoni infection. This similar association of parasite-specific IgE and protection among primates infected with schistosomiasis, along with similar pathology, anatomy, and genetic make-up, indicates that baboons provide an excellent permissive experimental model for better understanding the mechanisms of innate and acquired immunity to schistosomiasis in humans. PMID:9916070

  9. Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni

    PubMed Central

    Pereira, Thiago A.; Syn, Wing-Kin; Machado, Mariana V.; Vidigal, Paula V.; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M.; Santos, Elisângela T.; Chan, Isaac S.; Trindade, Guilherme V.M.; Choi, Steve S.; Witek, Rafal P.; Pereira, Fausto E.; Secor, William E.; Andrade, Zilton A.; Lambertucci, José Roberto

    2015-01-01

    Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity. PMID:26201095

  10. The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development

    PubMed Central

    Ziniel, Peter D.; Karumudi, Bhargava; Barnard, Andrew H.; Fisher, Ethan M. S.; Thatcher, Gregory R. J.; Podust, Larissa M.; Williams, David L.

    2015-01-01

    Schistosomiasis affects millions of people in developing countries and is responsible for more than 200,000 deaths annually. Because of toxicity and limited spectrum of activity of alternatives, there is effectively only one drug, praziquantel, available for its treatment. Recent data suggest that drug resistance could soon be a problem. There is therefore the need to identify new drug targets and develop drugs for the treatment of schistosomiasis. Analysis of the Schistosoma mansoni genome sequence for proteins involved in detoxification processes found that it encodes a single cytochrome P450 (CYP450) gene. Here we report that the 1452 bp open reading frame has a characteristic heme-binding region in its catalytic domain with a conserved heme ligating cysteine, a hydrophobic leader sequence present as the membrane interacting region, and overall structural conservation. The highest sequence identity to human CYP450s is 22%. Double stranded RNA (dsRNA) silencing of S. mansoni (Sm)CYP450 in schistosomula results in worm death. Treating larval or adult worms with antifungal azole CYP450 inhibitors results in worm death at low micromolar concentrations. In addition, combinations of SmCYP450-specific dsRNA and miconazole show additive schistosomicidal effects supporting the hypothesis that SmCYP450 is the target of miconazole. Treatment of developing S. mansoni eggs with miconazole results in a dose dependent arrest in embryonic development. Our results indicate that SmCYP450 is essential for worm survival and egg development and validates it as a novel drug target. Preliminary structure-activity relationship suggests that the 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol moiety of miconazole is necessary for activity and that miconazole activity and selectivity could be improved by rational drug design. PMID:26713732

  11. An epidemiological study of Schistosoma haematobium and S. mansoni infection in thirty-five rural Egyptian villages.

    PubMed

    Miller, F; Hussein, M; Mancy, K H; Hilbert, M S; Monto, A S; Barakat, R M

    1981-12-01

    Probability samples of individuals from 35 village communities in the rural Egyptian Nile Valley were examined for the presence of schistosome ova by sedimentation of urine and by the MIFC technique for stools. In all there were 12,933 persons selected of which 11,337 provided specimens for examination from a total population of 66,768 persons divided among three governorates: 37% in North Central Delta, 31% in Upper-Middle Egypt and 32% in the Upper Egypt. After controlling the differences attributed to sampling methods, 30% of the villagers from Kafr El Sheikh, were found positive for S. haematobium and 20% for S. mansoni. The prevalence of schistosomiasis in the Kafr El Sheikh villages was 42%. South of the Nile Delta in the Beni Suef villages, 27% were found positive for S. haematobium and less than 1% positive for S. mansoni. In Aswan, prevalence was associated with the type and location of the village. Prevalence was low (4%) in villages located on high barren ground, but elevated (25%) in a village built within cropped and irrigated land. S. mansoni cases were also in the Aswan villagers; however, local acquisition of this infection was not substantiated. The specific age-sex distributions for both schistosomes species were characteristic with a notable difference in the male-female infection ratio that increased from north to south. The source of domestic water supply and prevalence of infection were consistently associated. These results were compared to past findings in order to provide a frame of reference to aid in the development of future surveillance and investigations. PMID:7342382

  12. Trace elements in the human scalp hair and finger nails as affected by infection with Schistosoma mansoni

    NASA Astrophysics Data System (ADS)

    El-Khatib, Ahmed M.; Bahnassy, Ahmed A.; Denton, M.

    1995-01-01

    The concentration of 13 elements has been determined in finger nail and scalp hair of 4 groups representing normal and infected Schistosoma mansoni subjects. Samples were irradiated by thermal neutrons from a Triga Mark III Reactor, for 10 min. Measurements were made using a HPGe detector coupled with ADC and PDP {11}/{34} data processing equipment. The results showed significant increases of Al, Cl, I and Br in both finger nails and scalp hair of bilharzial patients above those of normal subjects while Mg, Ca, V, Mn, Cu, Sr, K, S and Na showed significant decreases. Most of the elements showed a higher concentration in finger nails than in hair.

  13. Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris

    PubMed Central

    Pearson, Mark S.; Giacomin, Paul R.; Becker, Luke; Sotillo, Javier; Pickering, Darren

    2016-01-01

    Background Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Methodology/Principal Findings Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds—luteolin (3) and (3R,6R)-linalool oxide acetate (1)—showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8–36.9 μg/mL) and T. muris (IC50 range = 9.7–20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Conclusions/Significance Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths—T. muris and S. mansoni—and was

  14. The detection limits for estimates of infection intensity in schistosomiasis mansoni established by a study in non-human primates.

    PubMed

    Alan Wilson, R; van Dam, Govert J; Kariuki, Thomas M; Farah, Idle O; Deelder, André M; Coulson, Patricia S

    2006-10-01

    In human schistosomiasis mansoni, it is impossible to directly determine worm burden and hence infection intensity, so surrogates must be used. Studies on non-human primates revealed a linear relationship between worm burden and three surrogates, faecal egg output, circulating anodic and circulating cathodic antigens. By regression, the thresholds of detection were determined as 40, 24 and 47 worms, respectively. These observations provide a quantitative basis for the contention that low intensity infections in humans are being missed. The significance for estimates of disease prevalence, evaluation of the effects of chemotherapy and the implementation of vaccine trials is emphasised. PMID:16930605

  15. Schistosoma mansoni: anomalous immunogenic properties of a 27 kDa larval serine protease associated with protective immunity.

    PubMed

    Darani, H Y; Curtis, R H; McNeice, C; Price, H P; Sayers, J R; Doenhoff, M J

    1997-09-01

    A cationic Schistosoma mansoni cercarial antigen was shown to be a serine protease as it was capable of hydrolysing N-acetyl-DL-phenylalanine beta-naphthyl ester (NAPBNE) after precipitation by immunoelectrophoresis, and this reaction was modulated by the serine protease inhibitors phenylmethanesulfonyl fluoride (PMSF) and diisopropylfluorophosphate (DEP). The antigen in the immunoprecipitin arcs could also be radio-isotope labelled with tritiated DFP. The peptidolytic enzyme identified in immunoelectrophoresis with polyspecific sera and radio-isotope labelled with tritiated DFP had a relative molecular size of approximately 27 kDa in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and evidence obtained after partial purification, SDS-PAGE and immunoblotting supported this size estimate for the enzyme. A rabbit antiserum raised against the peptidolytic antigen reacted against a doublet of antigens at 27/28 kDa in immunoelectrophoresis arcs and against an antigen of 60 kDa in Western immunoblots of crude cercarial homogenate. However, the latter serum precipitated the cationic antigen in immunoelectrophoresed cercarial homogenates only after pre-incubation of the homogenates with PMSF. Fractions containing the partially purified protease also degraded radio-isotope labelled human IgG. The reactivity of a range of polyspecific and monospecific rabbit antisera in Western blots with larval extracts indicated that antibody responses against the 27/28 kDa doublet may be modulated. When immunized with material which contained the 27 kDa enzyme as a major constituent, and which was secreted by S. mansoni cercariae during transformation, only 5 of 16 mice produced antibody to this antigen that was detectable in Western blots. The 5 antibody 'responder' mice were significantly (P < 0.001) protected against challenge with a percutaneous infection of S. mansoni cercariae compared with a group of a mice also immunized with CTF, but which had not produced

  16. Effects of Plagiorchis elegans (Digenea: Plagiorchiidae) infection of Biomphalaria glabrata (Pulmonata: Planorbidae) on a challenge infection with Schistosoma mansoni (Digenea: Schistosomatidae).

    PubMed

    Zakikhani, M; Smith, J M; Rau, M E

    2003-02-01

    Prior exposure of Biomphalaria glabrata to the eggs of an incompatible digenean, Plagiorchis elegans, rendered this snail host less suitable to a compatible species, Schistosoma mansoni. Although P. elegans failed to develop patent infections in B. glabrata, it reduced the production of S. mansoni cercariae by 88%. Concomitantly, host attributes such as reproduction, growth, and survival were compromised. The effect of P. elegans infection was most severe among snails that, in addition, had developed patent schistosome infections. Although few S. mansoni cercariae were produced, egg production by B. glabrata was only 4% of control values. Furthermore, no doubly infected snails survived for more than 3 wk after patency, whereas controls experienced no mortality during the same time period. The above effects were attributable to the establishment and persistence of P. elegans sporocysts in the tissues of the incompatible snail host. Their indirect antagonistic interaction with thelarval stages of S. mansoni may be mediated, in part, through their long-term stimulation of the host's internal defense mechanisms. These findings are discussed with a view to use P. elegans and other plagiorchiid digeneans as agents in the biological control of snails and snail-borne diseases. PMID:12659305

  17. Dynamics of glutathione regulation in Schistosoma mansoni: correlations with the acute effects of oltipraz

    SciTech Connect

    Morrison, D.D.

    1984-01-01

    Glutathione is present in adult Schistosoma mansoni (0.336 +/- 0.012 nmol/mg protein) at significantly lower levels than uninfected host tissues (1.051 +/- 0.013 nmol/mg protein, liver; 0.627 +/- 0.013 nmol/mg protein, kidney). Host hepatic glutathione levels decline significantly during the course of infection, while renal cortical glutathione levels are unaffected. Of the enzymes regulating glutathione utilization, glutathione reductase in the male parasite exhibits a specific activity of 10.3 +/- 4.2 nmol/mg protein, 15% of hepatic values. The apparent glutathione S-transferase activity was 26 +/- 7 ..mu..mol conjugate formed/min/mg protein with p-nitrobenzyl chloride as substrate (13% of hepatic values) and 526 +/- 18 ..mu..mol conjugate formed/min/mg protein with 1-chloro-2,4-dinitrobenzene as substrate (43% of hepatic values). Male schistosomes exhibited negligible glutathione peroxidase activity. Oltipraz, an antischistosomal compound, effected a significant depletion of parasite and host glutathione levels within 1 h of exposure in vivo and in vitro (at 250 mg/kg and 10 ..mu..M, respectively). Host tissue glutathionine levels returned to, or above, control levels by 6 h after oltipraz administration, while parasite glutathione levels remained significantly depressed. Uptake of (/sup 35/S) cysteine or (/sup 35/S) cystine by schistosomes was inhibited by oltipraz. However, the drug did not alter the relative distribution of label once incorporated into the parasite, indicating that the enzymes of glutathione synthesis were not directly inhibited.

  18. In-silico analysis of Sirt2 from Schistosoma mansoni: structures, conformations, and interactions with inhibitors.

    PubMed

    Singh, Raghvendra; Singh, Swadha; Pandey, Paras Nath

    2016-05-01

    Sirtuins are NAD+-dependent lysine deacetylases member of the class III HDAC family. These are demonstrated to be therapeutic targets in parasitic diseases like schistosomiasis. Observations suggested that sirtuin enzyme is necessary for the functionality of fe/male reproductive system, due to which SmSirt2 is treated as a potential therapeutic target. There are no structural and molecular features of SmSirt2 have been reported yet. In this study, homology modeling has been used to determine the three-dimensional features of the SmSITRT2. Further, structure validation has been performed by energy minimization and Ramachandran plot. Validated structures are further subjected to molecular docking and virtual screening to find the best lead molecules for downstream analysis. Ten lead molecules were selected while comparing virtual screening of hSirt2 and SmSirt2 both. These leads are further compared with AKG2 which is known inhibitor of hSirt2 (-8.8 kcal/mol). Out of selected 10 leads, four of them (ZINC23995485 (-9.5 kcal/mol), ZINC53298162 (-9.4 kcal/mol), ZINC70927268 (-10.0 kcal/mol), ZINC89878705 (-11.2 kcal/mol)) have shown better interaction with SmSirt2, in which ZINC89878705 (-11.2 kcal/mol) shows a more compact packing as compared to AKG2 and rest of ligands. These molecules could be further subject to in vitro study and model of SmSirt2 has been proposed for further structure-based drug design projects concerning sirtuins from Schistosoma mansoni. PMID:26108803

  19. Evidence for Novel Pharmacological Sensitivities of Transient Receptor Potential (TRP) Channels in Schistosoma mansoni

    PubMed Central

    Bais, Swarna; Churgin, Matthew A.; Fang-Yen, Christopher; Greenberg, Robert M.

    2015-01-01

    Schistosomiasis, caused by parasitic flatworms of the genus Schistosoma, is a neglected tropical disease affecting hundreds of millions globally. Praziquantel (PZQ), the only drug currently available for treatment and control, is largely ineffective against juvenile worms, and reports of PZQ resistance lend added urgency to the need for development of new therapeutics. Ion channels, which underlie electrical excitability in cells, are validated targets for many current anthelmintics. Transient receptor potential (TRP) channels are a large family of non-selective cation channels. TRP channels play key roles in sensory transduction and other critical functions, yet the properties of these channels have remained essentially unexplored in parasitic helminths. TRP channels fall into several (7–8) subfamilies, including TRPA and TRPV. Though schistosomes contain genes predicted to encode representatives of most of the TRP channel subfamilies, they do not appear to have genes for any TRPV channels. Nonetheless, we find that the TRPV1-selective activators capsaicin and resiniferatoxin (RTX) induce dramatic hyperactivity in adult worms; capsaicin also increases motility in schistosomula. SB 366719, a highly-selective TRPV1 antagonist, blocks the capsaicin-induced hyperactivity in adults. Mammalian TRPA1 is not activated by capsaicin, yet knockdown of the single predicted TRPA1-like gene (SmTRPA) in S. mansoni effectively abolishes capsaicin-induced responses in adult worms, suggesting that SmTRPA is required for capsaicin sensitivity in these parasites. Based on these results, we hypothesize that some schistosome TRP channels have novel pharmacological sensitivities that can be targeted to disrupt normal parasite neuromuscular function. These results also have implications for understanding the phylogeny of metazoan TRP channels and may help identify novel targets for new or repurposed therapeutics. PMID:26655809

  20. Antischistosomal activity of ginger (Zingiber officinale) against Schistosoma mansoni harbored in C57 mice.

    PubMed

    Mostafa, Osama M S; Eid, Refaat A; Adly, Mohamed A

    2011-08-01

    The repeated chemotherapy of schistosomiasis has resulted in the emergence of drug-resistant schistosome strains. The development of such resistance has drawn the attention of many authors to alternative drugs. Many medicinal plants were studied to investigate their antischistosomal potency. The present work aimed to evaluate antischistosomal activity of crude aqueous extract of ginger against Schistosoma mansoni. Sixteen mice of C57 strain were exposed to 100 ± 10 cercariae per mouse by the tail immersion method; the mice were divided into two groups: untreated group and ginger-treated one. All mice were sacrificed at the end of 10th week post-infection. Worm recovery and egg counting in the hepatic tissues and faeces were determined. Surface topography of the recovered worms was studied by scanning electron microscopy. Histopathological examination of liver and intestine was done using routine histological procedures. The worm burden and the egg density in liver and faeces of mice treated with ginger were fewer than in non-treated ones. Scanning electron microscopical examination revealed that male worms recovered from mice treated with ginger lost their normal surface architecture, since its surface showed partial loss of tubercles' spines, extensive erosion in inter-tubercle tegumental regions and numerous small blebs around tubercles. Histopathological data indicated a reduction in the number and size of granulomatous inflammatory infiltrations in the liver and intestine of treated mice compared to non-treated mice. The results of the present work suggested that ginger has antischistosomal activities and provided a basis for subsequent experimental and clinical trials. PMID:21327992

  1. Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

    PubMed Central

    de Oliveira, Sheilla Andrade; de Oliveira Filho, Gevânio Bezerra; Moreira, Diogo Rodrigo Magalhaes; Gomes, Paulo André Teixeira; da Silva, Anekécia Lauro; de Barros, Andréia Ferreira; da Silva, Aline Caroline; dos Santos, Thiago André Ramos; Pereira, Valéria Rêgo Alves; Gonçalves, Gabriel Gazzoni Araújo; Brayner, Fábio André; Alves, Luiz Carlos; Wanderley, Almir Gonçalves; Leite, Ana Cristina Lima

    2014-01-01

    Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni. Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-α), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials. PMID:24165185

  2. Ligation of RNA Oligomers by the Schistosoma mansoni Hammerhead Ribozyme in Frozen Solution.

    PubMed

    Lie, Lively; Biliya, Shweta; Vannberg, Fredrik; Wartell, Roger M

    2016-03-01

    The interstitial liquid phase within frozen aqueous solutions is an environment that minimizes RNA degradation and facilitates reactions that may have relevance to the RNA World hypothesis. Previous work has shown that frozen solutions support condensation of activated nucleotides into RNA oligomers, RNA ligation by the hairpin ribozyme, and RNA synthesis by a RNA polymerase ribozyme. In the current study, we examined the activity of a hammerhead ribozyme (HHR) in frozen solution. The Schistosoma mansoni hammerhead ribozyme, which predominantly cleaves RNA, can ligate its cleaved products (P1 and P2) with yields up to ~23 % in single turnover experiments at 25 °C in the presence of Mg(2+). Our studies show that this HHR ligates RNA oligomers in frozen solution in the absence of divalent cations. Citrate and other anions that exhibit strong ion-water affinity enhanced ligation. Yields up to 43 % were observed in one freeze-thaw cycle and a maximum of 60 % was obtained after several freeze-thaw cycles using wild-type P1 and P2. Truncated and mutated P1 substrates were ligated to P2 with yields of 14-24 % in one freeze-thaw cycle. A pool of P2 substrates with mixtures of all four bases at five positions were ligated with P1 in frozen solution. High-throughput sequencing indicated that 70 of the 1024 possible P2 sequences were represented in ligated products at 1000 or more read counts per million reads. The results indicate that the HHR can ligate a range of short RNA oligomers into an ensemble of diverse sequences in ice. PMID:26897022

  3. In vitro cellular and humoral responses to Schistosoma mansoni vaccine candidate antigens.

    PubMed

    Al-Sherbiny, Maged; Osman, Ahmed; Barakat, Rashida; El Morshedy, Hala; Bergquist, Robert; Olds, Richard

    2003-10-01

    Few studies comparing schistosomiasis vaccine candidate antigens between laboratories have been carried out and published. Generally, only the investigators who discovered the molecules have evaluated them in either experimental animal models or in human correlate studies. In an attempt to identify responses against specific antigens and investigate their association with resistance versus susceptibility to re-infection, we studied the serological reactions and the cytokine responses stimulated by a panel of 10 candidate vaccine molecules in 225 long-term residents of an area endemic for Schistosoma mansoni in Egypt. The panel consisted of four recombinant antigens (Sm62-Irv5, Sm37-G3PDH, Sm28-GST and Sm14-FABP), one full-length native protein (Sm97-paramyosin), two synthetic peptides (MAP3 and MAP4) and three unpublished antigens (PR52-filamin, PL45-phosphoglycerate kinase, PN18-cyclophilin). Two different study designs, one based on retrospective and the other on prospective parasitological data were applied in the evaluation of the immune responses. Using historical data collected over the previous 5 years, correlations between frequency of re-infection and antigen-specific immune responses were investigated. In the prospective arm of the study, the subjects were followed over time after treatment with praziquantel with periodic immunological tests and stool examinations. Thus, highly specific humoral and cellular immune reactions in response to the 10 antigens described above could be correlated, both prospectively and retrospectively, with detailed epidemiological data covering a 66-month period. The immune response profiles produced were unique to each antigen but no clear "winner" or "winners" were identified. However, markers for both resistance and susceptibility to re-infection were identified for each molecule indicating which types of responses to aim for in vaccination and which ones to avoid. The insights gained from this approach should be useful for

  4. Quantitative High-Throughput Screen Identifies Inhibitors of the Schistosoma mansoni Redox Cascade

    PubMed Central

    Simeonov, Anton; Jadhav, Ajit; Sayed, Ahmed A.; Wang, Yuhong; Nelson, Michael E.; Thomas, Craig J.; Inglese, James; Williams, David L.; Austin, Christopher P.

    2008-01-01

    Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR) and peroxiredoxin (Prx) and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS) experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 µL reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC50s ranging from micromolar to the assay response limit (∼25 nM). This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump-start development of novel

  5. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

    PubMed Central

    Fajtová, Pavla; Štefanić, Saša; Hradilek, Martin; Dvořák, Jan; Vondrášek, Jiří; Jílková, Adéla; Ulrychová, Lenka; McKerrow, James H.; Caffrey, Conor R.; Mareš, Michael; Horn, Martin

    2015-01-01

    Background Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP) from the serine peptidase family S9, which has not been investigated in detail in trematodes. Methodology/Principal Findings We demonstrate that SmPOP is expressed in adult worms and schistosomula in an enzymatically active form. By immunofluorescence microscopy, SmPOP is localized in the tegument and parenchyma of both developmental stages. Recombinant SmPOP was produced in Escherichia coli and its active site specificity investigated using synthetic substrate and inhibitor libraries, and by homology modeling. SmPOP is a true oligopeptidase that hydrolyzes peptide (but not protein) substrates with a strict specificity for Pro at P1. The inhibition profile is analogous to those for mammalian POPs. Both the recombinant enzyme and live worms cleave host vasoregulatory, proline-containing hormones such as angiotensin I and bradykinin. Finally, we designed nanomolar inhibitors of SmPOP that induce deleterious phenotypes in cultured schistosomes. Conclusions/Significance We provide the first localization and functional analysis of SmPOP together with chemical tools for measuring its activity. We briefly discuss the notion that SmPOP, operating at the host-parasite interface to cleave host bioactive peptides, may contribute to the survival of the parasite. If substantiated, SmPOP could be a new target for the development of anti-schistosomal drugs. PMID:26039195

  6. Praziquantel: physiological evidence for its site(s) of action in magnesium-paralysed Schistosoma mansoni.

    PubMed

    Blair, K L; Bennett, J L; Pax, R A

    1992-02-01

    The mechanism whereby praziquantel produces a contraction and subsequent flaccid paralysis (a loss of sensitivity to subsequent stimuli) of Schistosoma mansoni in a medium containing an elevated Mg2+:Ca2+ ratio was investigated. In RPMI, praziquantel produced a concentration-dependent tonic contraction of the parasite with an EC50 of 200 nM. Magnesium inhibited the contraction in such a manner as to convert the tonic contraction to a phasic one without altering the peak force generated. The Mg(2+)-dependent block was non-competitive with praziquantel but was competitive with extracellular Ca2+, ratios of 7.5:1;Mg2+:Ca2+ being needed to inhibit the tonic contraction and to induce flaccid paralysis. Flaccid paralysis was associated with a reduced ability of the parasite to take up 45Ca2+ from the bath compared to parasites that had not entered into flaccid paralysis and flaccid paralysis was reversible. Recovery from flaccid paralysis was accelerated by treatments that are expected to increase Ca2+ uptake by the parasite. At a concentration of 500 nM, praziquantel produced 2 distinct phasic contractions in intact parasites incubated in an elevated [Mg2+] medium but only 1 phasic contraction in parasites lacking their surface tegumental membranes. In zero Ca2+ I-RPMI, 10 microM praziquantel produced a phasic contraction of intact parasites but did not stimulate contraction of detegumented parasites until Ca2+ was reintroduced into the bath. These results indicate that praziquantel interacts with specific Ca(2+)-permeable sites in the tegumental and sarcoplasmic membranes of the parasite and that under these conditions of elevated Mg2+:Ca2+ ratios, these sites become blocked by Mg2+, leading to flaccid paralysis of the parasite. PMID:1614741

  7. The efficacy of antihelminthic compound; Clorsulon against experimental Schistosoma mansoni infection.

    PubMed

    Mossallam, Shereen F; Ali, Safia M; El Zawawy, Lobna A; Said, Doaa E

    2007-04-01

    The efficacy of Clorsulon (CLS) against experimental schistosomiasis mansoni, using Praziquantel (PZQ) as a therapeutic control was evaluated. Swiss Albino mice were divided into infected non-treated control, PZQ-treated group given a single dose of 500 mg/kg four weeks post infection (PI), and infected mice treated with single, double, and triple doses of 5 mg/kg CLS per dose, one week apart starting from the 4th week PI. All animals were perfused for adults count. Parts of livers and intestines were examined for granulomata number and sizes. Pathological changes in hepatic parenchyma by H&E and Masson trichrome stains were also examined. Results revealed that a single treatment with PZQ caused a significant percentage reduction (%R) of worm load (92.68%), mean egg count in liver and intestine (91.20 & 94.01% respectively), and mean size of liver granulomata was reduced (92.06%). Regarding CLS, the worm burden was reduced proportionally with number of doses given; 87.80, 96.34 & 97.56% in single, double and triple exposures successively. Egg count in liver was decreased by 85.90, 97.01 & 96.23% respectively in treated mice. Number of intestinal granulomata was decreased by 85.28, 94.24 & 95.49% in a similar way. Size of hepatic granulomata was decreased by 89.02, 94.51 & 95.05% by 1, 2 & 3 doses consecutively. All parameters reflected non significant difference between 2 & 3 dose of CLS. The results were critically discussed. PMID:17580576

  8. Anthelmintic Activity In Vivo of Epiisopiloturine against Juvenile and Adult Worms of Schistosoma mansoni

    PubMed Central

    Guimarães, Maria A.; de Oliveira, Rosimeire N.; Véras, Leiz M. C.; Lima, David F.; Campelo, Yuri D. M.; Campos, Stefano Augusto; Kuckelhaus, Selma A. S.; Pinto, Pedro L. S.; Eaton, Peter; Mafud, Ana C.; Mascarenhas, Yvonne P.; Allegretti, Silmara M.; de Moraes, Josué; Lolić, Aleksandar; Verbić, Tatjana; Leite, José Roberto S. A.

    2015-01-01

    Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported. PMID:25816129

  9. Assessment of toxicity of Moringa oleifera flower extract to Biomphalaria glabrata, Schistosoma mansoni and Artemia salina.

    PubMed

    Rocha-Filho, Cláudio A A; Albuquerque, Lidiane P; Silva, Luanna R S; Silva, Patrícia C B; Coelho, Luana C B B; Navarro, Daniela M A F; Albuquerque, Monica C P A; Melo, Ana Maria M A; Napoleão, Thiago H; Pontual, Emmanuel V; Paiva, Patrícia M G

    2015-08-01

    This study reports the effect of an aqueous extract from Moringa oleifera Lam. flowers on Biomphalaria glabrata embryos and adults and on Schistosoma mansoni adult worms. The extract contains tannins, saponins, flavones, flavonols, xanthones, and trypsin inhibitor activity. The toxicity of the extract on Artemia salina larvae was also investigated to determine the safety of its use for schistosomiasis control. After incubation for 24h, the flower extract significantly (p<0.05) delayed the development of B. glabrata embryos and promoted mortality of adult snails (LC50: 2.37±0.5mgmL(-1)). Furthermore, treatment with the extract disrupted the development of embryos generated by snails, with most of them remaining in the blastula stage while control embryos were already in the gastrula stage. Flower extract killed A. salina larvae with a LC50 value (0.2±0.015mgmL(-1)) lower than that determined for snails. A small reduction (17%) in molluscicidal activity was detected when flower extract (2.37mgmL(-1)) was exposed to tropical environmental conditions (UVI index ranging from 1 to 14, temperature from 25 to 30°C, and 65% relative humidity). Toxicity to A. salina was also reduced (LC50 value of 0.28±0.01mgmL(-1)). In conclusion, M. oleifera flower extract had deleterious effects on B. glabrata adults and embryos. However, unrestricted use to control schistosomiasis should be avoided due to the toxicity of this extract on A. salina. PMID:25867917

  10. Functional changes in regulatory T cells during an experimental infection with sparganum (plerocercofid of Spirometra mansoni).

    PubMed

    Kim, Hyung-Ran; Lee, Su-Min; Won, Jong-Wha; Lim, Woosung; Moon, Byung-In; Yang, Hyun-Jong; Seoh, Ju-Young

    2013-01-01

    Regulatory T (Treg) cells are important in the regulation of immune response, but the exact regulation of Treg-cell function in vivo is still not well known. In the present study, we investigated the functional activity of CD4(+) CD25(+) Treg cells as well as the frequency and number of CD4(+) CD25(+) FoxP3(+) Treg cells in the spleens of experimentally infected mice with a tissue-migrating parasite, sparganum (plerocercoid of Spirometra mansoni) for 3 weeks. The results demonstrated fluctuations in the Treg-cell function during the parasite infection, being up-regulated at day 3, down-regulated until day 14, and thereafter up-regulated again at day 21. We also investigated the cytokine-producing capability of the splenocytes to study the pattern of immune response of the mice to the parasite. The results showed decreased capabilities of interleukin-2 (IL-2), interferon-γ (IFN-γ) and IL-17α production, whereas IL-4-producing and IL-10-producing capabilities were increased along with the parasitic infection. Meanwhile, IL-6-producing capability was increased to reach a peak at week 2, and thereafter was decreased to the baseline level. As a regulatory mechanism, we found that Treg-cell function was attenuated in the presence of the crude extracts of sparganum, but was enhanced in the presence of the excretory-secretory products, suggesting that sparganum products were involved in the triggering and regulation of immune response in the acute and chronic phases, respectively. Results show that Treg cells are central in the immune homeostasis in vivo that is maintained by host-parasite interactions during the parasitic infection. PMID:23078673

  11. Gene Expression Patterns in Larval Schistosoma mansoni Associated with Infection of the Mammalian Host

    PubMed Central

    Parker-Manuel, Sophia J.; Ivens, Alasdair C.; Dillon, Gary P.; Wilson, R. Alan

    2011-01-01

    Background The infective schistosome cercaria develops within the intramolluscan daughter sporocyst from an undifferentiated germ ball, during which synthesis of proteins essential for infection occurs. When the aquatic cercaria locates the mammalian host it rapidly penetrates into the epidermis using glandular secretions. It then undergoes metamorphosis into the schistosomulum, including replacement of its tegument surface membranes, a process taking several days before it exits the skin. Patterns of gene expression underlying this transition have been characterised. Methods and Principal Findings All gene models from the S. mansoni genome (www.GeneDB.org) were incorporated into a high-density oligonucleotide array. Double-stranded cDNA from germ balls, cercariae, and day 3 schistosomula was hybridised to the array without amplification. Statistical analysis was performed using Bioconductor to reveal differentially transcribed loci. Genes were categorised on the basis of biological process, tissue association or molecular function to aid understanding of the complex processes occurring. Genes necessary for DNA replication were enriched only in the germ ball, while those involved in translation were up-regulated in the germ ball and/or day 3 schistosomulum. Different sets of developmental genes were up-regulated at each stage. A large number of genes encoding elastases and invadolysins, and some venom allergen-like proteins were up-regulated in the germ ball, those encoding cysteine and aspartic proteases in the cercaria and schistosomulum. Micro exon genes encoding variant secreted proteins were highly up-regulated in the schistosomulum along with tegument and gut-associated genes, coincident with remodelling of the parasite body. Genes encoding membrane proteins were prominently up-regulated in the cercaria and/or day 3 schistosomulum. Conclusions/Significance Our study highlights an expanded number of transcripts encoding proteins potentially involved in skin

  12. Passive transfer with serum and IgG antibodies of irradiated cercaria-induced resistance against Schistosoma mansoni in mice

    SciTech Connect

    Mangold, B.L.; Dean, D.A.

    1986-04-01

    The role of humoral immunity to Schistosoma mansoni infection in C57BL/6J mice was examined by employing a passive transfer system. Sera from highly resistant mice that had been exposed to two or three immunizations with 50-kilorad-gamma-irradiated cercariae were tested for their ability to transfer protection against S. mansoni challenge. All five batches of serum tested were observed to have protective activity. Immune serum recipients exhibited statistically significant reductions in challenge worm burdens of 20 to 50% compared with recipients of normal serum or no serum. The most consistent level of resistance was obtained when immune serum was administered several days post-challenge, i.e., at a time coincident with schistosomulum residence in the lungs. Furthermore, it was shown that the protective activity in immune serum was associated with factors that bind to staphylococcal protein A and that are precipitated by 50% ammonium sulfate; thus it appears that the protective factors in immune serum are IgG antibodies.

  13. Immunocapture of circulating Schistosoma mansoni cathepsin B antigen (Sm31) by anti-Sm31 polyclonal antibodies.

    PubMed

    González, Amelia Y; Sulbarán, Guidenn S; Ballen, Diana E; Cesari, Italo M

    2016-06-01

    Adult Schistosoma mansoni parasites have the capacity to degrade ingested host hemoglobin and other host plasma proteins by using a series of gut proteolytic enzymes, including cathepsin B; this enzyme is released to the host intravascular environment during regurgitations of adult worms. Cathepsin B becomes thus a circulating parasite component that has been shown to be specifically recognized as the Sm31 antigen by antibodies present in most S. mansoni infected patients. Taking advantage of this immunological property, we attempted here to immunocapture Sm31 from sera of infected patients using specific polyclonal rabbit antibodies raised against a highly enriched preparation of Sm31 and detect its intrinsic proteolytic activity using a previously described solid-phase procedure called Cysteine Protease Immuno Assay (CPIA). To produce highly specific anti-Sm31/cathepsin B antibodies, cathepsin B (Sm31 or SmCB) was enriched more than 3000-folds from an adult worm preparation using a series of conventional biochemical steps including ion exchange and affinity chromatography. Anti-cathepsin B antibodies were generated by immunizing rabbits with the enriched cathepsin B fraction; these antibodies recognized a band of Mr.~31 kDa in Western-blot (WB) analysis of this fraction and were able to capture, in a modified CPIA procedure, Sm31/SmCB present in sera from infected Venezuelan patients living in low endemic areas for schistosomiasis. CPIA showed 100% sensitivity and 100% specificity; representing a new diagnostic tool to detect circulating Sm31 antigen in actual infections. PMID:26709076

  14. Effects of aestivation and starvation on the neutral lipid and phospholipid content of Biomphalaria glabrata infected with Schistosoma mansoni.

    PubMed

    White, Meredith M; Fried, Bernard; Sherma, Joseph

    2007-02-01

    The effects of aestivation or starvation on the neutral lipid and phospholipid content of Biomphalaria glabrata patently infected with Schistosoma mansoni were determined by high-performance thin-layer chromatography-densitometry. Infected-aestivated snails were maintained in a moist chamber at 24 +/- 1 C and a relative humidity of 98 +/- 1%. Infected-starved snails were maintained in artificial spring water (ASW) at 23 +/- 1 C without exogenous food. Infected snails (the controls) were maintained in ASW at 23 +/- 1 C and fed lettuce ad libitum. The 3 groups were maintained in the laboratory for 7 days, and then the lipids from the digestive gland-gonad complex (DGG) were extracted and analyzed by class. Infected-aestivated snails exhibited greater mortality rate and weight loss after 7 days than did the infected-starved snails. The steryl ester concentration in the infected-starved snails was significantly increased (P = 0.010) compared with the controls but not compared with infected-aestivated snails; the concentration of phosphatidylcholine in infected-aestivated snails was significantly decreased (P = 0.007) compared with the controls but not when compared with the infected-starved snails. Aestivation or starvation had a significant effect on the concentration of certain lipid classes in the DGG of B. glabrata infected with S. mansoni. PMID:17436935

  15. Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

    PubMed

    Tweyongyere, R; Namanya, H; Naniima, P; Cose, S; Tukahebwa, E M; Elliott, A M; Dunne, D W; Wilson, S

    2016-08-01

    High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated. PMID:27169695

  16. Schistosoma mansoni induces in the Kenyan baboon a novel intestinal pathology that is manifestly modulated by an irradiated cercarial vaccine.

    PubMed

    Farah, I O; Nyindo, M

    1996-08-01

    Light and scanning electron microscopic study of intestines of 5 baboons (Papio anubis) in a state of acute schistosomiasis mansoni after exposure to 800 cercariae was made. In addition to overt granulomatous inflammation in the mucosa of the colon and ileum, more subtle microscopic lesions consisting of smooth muscle hypertrophy and villous atrophy were present. The intensity and distribution of these lesions were less marked in 5 baboons previously vaccinated with 40,000 30-krad-attenuated cercariae and presenting a 39% mean protection level measured as a percent reduction in adult worms recovered from mesenteric vasculature at perfusion. No similar lesions were observed in 2 normal uninfected and nonvaccinated baboons. These results are comparable to what has been reported in mice infected by Schistosoma mansoni. The data indicate that villous atrophy, hypertrophy of muscularis mucosa, nd goblet cell hyperplasia are important pathological changes to be included in the evaluation of the efficacy of schistosomiasis vaccines in the baboon model, together with the routine adult worm recovery from mesenteric blood vessels and the overt liver and bowel pathology. PMID:8691367

  17. Cross-species protection: Schistosoma mansoni Sm-p80 vaccine confers protection against Schistosoma haematobium in hamsters and baboons.

    PubMed

    Karmakar, Souvik; Zhang, Weidong; Ahmad, Gul; Torben, Workineh; Alam, Mayeen U; Le, Loc; Damian, Raymond T; Wolf, Roman F; White, Gary L; Carey, David W; Carter, Darrick; Reed, Steven G; Siddiqui, Afzal A

    2014-03-01

    The ability of the Schistosoma mansoni antigen, Sm-p80, to provide cross-species protection against Schistosoma haematobium challenge was evaluated in hamster and baboon models. Pronounced reduction in worm burden (48%) and in tissue egg load (64%) was observed in hamsters vaccinated with recombinant Sm-p80 admixed with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Similarly, in baboons, the Sm-p80/GLA-SE vaccine produced a 25% reduction in S. haematobium adult worms and decreased the egg load in the urinary bladder by 64%. A 40% and 53% reduction in fecal and urine egg output, respectively, was observed in vaccinated baboons. A balanced pro-inflammatory (Th17 and Th1) and Th2 type of response was generated after vaccination and appears indicative of augmented prophylactic efficacy. These data on cross-species protection coupled with the prophylactic, therapeutic and antifecundity efficacy against the homologous parasite, S. mansoni, reinforces Sm-p80 as a promising vaccine candidate. It is currently being prepared for GMP-compliant manufacture and for further pre-clinical development leading to human clinical trials. These results solidify the expectation that the Sm-p80 vaccine will provide relief for both the intestinal and the urinary schistosomiasis and thus will be greatly beneficial in reducing the overall burden of schistosomiasis. PMID:24397898

  18. Cloning, expression and preliminary crystallographic studies of the potential drug target purine nucleoside phosphorylase from Schistosoma mansoni.

    PubMed

    Pereira, Humberto M; Cleasby, Anne; Pena S, Sérgio D J; Franco G, Glória R; Garratt, Richard C

    2003-06-01

    The parasite Schistosoma mansoni, unlike its mammalian hosts, lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. The gene encoding one enzyme of this pathway, purine nucleoside phosphorylase from S. mansoni (SmPNP) was identified, fully sequenced and cloned into the bacterial expression vector pMAL c2G to produce a protein in fusion with maltose-binding protein. The recombinant fusion protein was expressed at high levels and was purified in a single step by amylose resin affinity chromatography. After factor Xa cleavage, SmPNP was purified using a cation-exchange column and crystallized by hanging-drop vapour diffusion using polyethylene glycol 1500 as precipitant in the presence of 20% glycerol in acetate buffer. The use of the non-detergent sulfobetaine 195 (NDSB 195) as an additive had a marked effect on the size of the resulting crystals. Two data sets were obtained, one from a crystal grown in the absence of NDSB 195 and one from a crystal grown in its presence. The crystals are isomorphous and belong to the space group P2(1)2(1)2(1). It is intended to use the structures in the discovery and development of specific inhibitors of SmPNP. PMID:12777786

  19. Early Differential Gene Expression in Haemocytes from Resistant and Susceptible Biomphalaria glabrata Strains in Response to Schistosoma mansoni

    PubMed Central

    Lockyer, Anne E.; Emery, Aidan M.; Kane, Richard A.; Walker, Anthony J.; Mayer, Claus D.; Mitta, Guillaume; Coustau, Christine; Adema, Coen M.; Hanelt, Ben; Rollinson, David; Noble, Leslie R.; Jones, Catherine S.

    2012-01-01

    The outcome of infection in the host snail Biomphalaria glabrata with the digenean parasite Schistosoma mansoni is determined by the initial molecular interplay occurring between them. The mechanisms by which schistosomes evade snail immune recognition to ensure survival are not fully understood, but one possibility is that the snail internal defence system is manipulated by the schistosome enabling the parasite to establish infection. This study provides novel insights into the nature of schistosome resistance and susceptibility in B. glabrata at the transcriptomic level by simultaneously comparing gene expression in haemocytes from parasite-exposed and control groups of both schistosome-resistant and schistosome-susceptible strains, 2 h post exposure to S. mansoni miracidia, using an novel 5K cDNA microarray. Differences in gene expression, including those for immune/stress response, signal transduction and matrix/adhesion genes were identified between the two snail strains and tests for asymmetric distributions of gene function also identified immune-related gene expression in resistant snails, but not in susceptible. Gene set enrichment analysis revealed that genes involved in mitochondrial electron transport, ubiquinone biosynthesis and electron carrier activity were consistently up-regulated in resistant snails but down-regulated in susceptible. This supports the hypothesis that schistosome-resistant snails recognize schistosomes and mount an appropriate defence response, while in schistosome-susceptible snails the parasite suppresses this defence response, early in infection. PMID:23300533

  20. Role of epidermal Langerhans' cells in the induction of protective immunity to Schistosoma mansoni in guinea-pigs.

    PubMed Central

    Sato, H; Kamiya, H

    1995-01-01

    Percutaneous exposure of guinea-pigs to attenuated or normal larvae of Schistosoma mansoni induced proliferative T-cell responses in the skin-draining lymph nodes (SLN). The responses elicited by attenuated larvae were stronger and more prolonged [2-12 days post-infection (p.i.)] than those by normal larvae (3-8 days p.i.). The former were coincident with greater and more sustained increases in numbers of SLN dendritic cells. During this event, epidermal Langerhans' cells (LC) showed marked changes in their distribution and morphology. Resident LC were similarly exhausted by either attenuated or normal larvae between 12 hr and 1 day p.i., but thereafter more blood-borne LC were recruited around the former, since reaggregation of LC around these persisted larvae was more frequent and intensive, and enhanced replenishment of epidermal LC was achieved by 8 days p.i. When the skin depleted of epidermal LC by short-wavelength ultraviolet (UVC) irradiation was exposed to attenuated larvae, consequent T-cell responses were delayed. Excision of the whole exposed skin on day 4 p.i. also reduced T-cell responses to marginal levels. These results indicate that during the afferent phase of immunity to S. mansoni, efficient T-cell responses in the SLN need an active involvement of not only resident LC but also blood-borne LC as immunostimulatory cells. Images Figure 3 Figure 5 PMID:7750999

  1. High prevalence of Schistosoma mansoni in six health areas of - Kasansa health zone, Democratic Republic of the Congo: short report.

    PubMed

    Linsuke, Sylvie; Nundu, Sabin; Mupoyi, Sylvain; Mukele, Rodin; Mukunda, Faustin; Kabongo, Madeleine Mbuyi; Inocêncio da Luz, Raquel; Van Geertruyden, Jean-Pierre; Van Sprundel, Marc; Boelaert, Marleen; Polman, Katja; Lutumba, Pascal

    2014-12-01

    School-aged children suffer the most from schistosomiasis infection in sub Saharan Africa due to poverty and limited sanitary conditions. Mapping of disease burden is recommended and there is a need of updating prevalence data which is as old as 20 years in the Democratic Republic of Congo. An epidemiological and parasitological study was carried out in 2011 in the health zone of Kasansa. Six health areas (HA) were included in the study. In each health area, one primary school was selected. School-aged children were screened for S. mansoni infection using parallel Kato-Katz and direct microscopy techniques. A total of 335 school-aged children were screened. The average prevalence was 82.7% and ranged between 59.5-94.9%. Four of the six HAs had a prevalence level over 91%. Of all infected children, about half 112 (43.2%) had light parasite density. These results demonstrate that Schistosoma mansoni infection is a bigger problem than anticipated and there is an urgent need to implement effective control measures. PMID:25521351

  2. New Approaches with Different Types of Circulating Cathodic Antigen for the Diagnosis of Patients with Low Schistosoma mansoni Load

    PubMed Central

    Grenfell, Rafaella; Harn, Donald A.; Tundup, Smanla; Da'dara, Akram; Siqueira, Liliane; Coelho, Paulo Marcos Zech

    2013-01-01

    Background Schistosomiasis mansoni is a debilitating and sometimes fatal disease. Accurate diagnosis plays a key role in patient management and infection control. However, currently available parasitological methods are laborious and lack sensitivity. The selection of target antigen candidates has turned out to be a promising tool for the development of more sensitive diagnostic methods. In our previous investigations, the use of crude antigens led to false-positive results. Recently, focus has been given to highly purified Schistosoma mansoni antigens, especially to circulating antigens. Method Thus, our main goal was to test different types of circulating cathodic antigen glycoprotein (CCA), as “crude antigen,” the protein chain of recombinant CCA and two individual peptides. These schistosome proteins/peptides were tested in a new diagnostic method employing immunomagnetic separation based on the improvement of antigen–antibody binding. Principal Findings Use of recombinant CCA as a diagnostic antigen allowed us to develop a diagnostic assay with high sensitivity and specificity with no false-negative results. Interestingly, the “crude antigen” worked as a good marker for control of cure after praziquantel treatment. Conclusions/Significance Our new diagnostic method was superior to enzyme-linked immunosorbent assay in diagnosing low endemicity patients. PMID:23469295

  3. Therapeutic Potential of Bone Marrow-Derived Mesenchymal Stem Cells on Experimental Liver Injury Induced by Schistosoma mansoni: A Histological Study

    PubMed Central

    Fikry, Heba; Gawad, Sara Abdel; Baher, Walaa

    2016-01-01

    Background and Objectives Bone marrow derived mesenchymal stem cells (BM-MSCs) have been proposed as effective treatment of many diseases owing to their unique ability to differentiate into other cell types in vivo. Schistosoma mansoni (S. mansoni) infection is characterized by hepatic granuloma formation around schistosome eggs at acute stage of infection, followed by hepatic fibrosis at chronic and advanced stages. Whether BM-MSCs have an ameliorative effect on hepatic tissue injury caused by S. mansoni infection or not, was inspected in the current study. Materials and Results Female Swiss Albino mice were divided into a control group and an experimental group. Half of control animals served as donors for bone marrow stem cells, and the other half was used to collect liver samples. Experimental group was injected with circariae of S. mansoni, and then subdivided into three subgroups; Subgroup B1, sacrificed after eight weeks of infection without treatment, subgroup B2, received BM-MSCs at the eighth week and sacrificed four weeks later, and subgroup B3, was untreated till the twelfth week of infection. Histological examination of liver samples showed the formation of granulomas and liver fibrosis which were extensive in subgroup B3. However, treated subgroup illustrated improvement of liver histology, signs of hepatocytes regeneration, and possible contribution of oval cell in the process of hepatic and biliary regeneration. Conclusion BM-MSCs decreased liver fibrosis and contributed to an increase in oval cells, generation of new hepatocytes and/or to the improvement of resident hepatocytes in S. mansoni infected mice. PMID:27426091

  4. Effect of different stages of Schistosoma mansoni infection on the parasite burden and immune response to Strongyloides venezuelensis in co-infected mice.

    PubMed

    de Rezende, Michelle Carvalho; Araújo, Emília Souza; Moreira, João Marcelo Peixoto; Rodrigues, Vanessa Fernandes; Rodrigues, Jailza Lima; Pereira, Cíntia A de Jesus; Negrão-Corrêa, Deborah

    2015-12-01

    Multiple schistosome and soil-transmitted nematode infections are frequently reported in human populations living in tropical areas of developing countries. In addition to exposure factors, the host immune response plays an important role in helminth control and morbidity in hosts with multiple infections; however, these aspects are difficult to evaluate in human populations. In the current study, female Swiss mice were simultaneously co-infected with Strongyloides venezuelensis and Schistosoma mansoni or infected with St. venezuelensis at 2, 4, or 14 weeks after Sc. mansoni infection. The simultaneously infected mice showed a similar parasite burden for St. venezuelensis compared with mono-infected mice. In contrast, there was a significant reduction of St. venezuelensis burden (primarily during the migration of the larvae) in mice that were previously infected with Sc. mansoni at the acute or chronic phase. Independent of the stage of Sc. mansoni infection, the St. venezuelensis co-infection was capable of inducing IL-4 production in the small intestine, increasing the IgE concentration in the serum and increasing eosinophilia in the lungs and intestine. This result suggests that the nematode infection stimulates local type 2 immune responses independently of the schistosomiasis stage. Moreover, previous Sc. mansoni infection stimulated early granulocyte infiltration in the lungs and trematode-specific IgM and IgG1 production that recognized antigens from St. venezuelensis infective larvae; these immune responses would act in the early control of St. venezuelensis larvae. Our data suggest that the effect of multiple helminth infections on host susceptibility and morbidity largely depends on the species of parasite and the immune response. PMID:26350380

  5. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology

    PubMed Central

    Oliveira, Matheus P.; Correa Soares, Juliana B. R.; Oliveira, Marcus F.

    2016-01-01

    Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute

  6. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology.

    PubMed

    Oliveira, Matheus P; Correa Soares, Juliana B R; Oliveira, Marcus F

    2016-01-01

    Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute

  7. Long-term effect of mass chemotherapy, transmission and risk factors for Schistosoma mansoni infection in very low endemic communities of Venezuela.

    PubMed

    Hofstede, Stefanie N; Tami, Adriana; van Liere, Genevieve A F S; Ballén, Diana; Incani, Renzo N

    2014-12-01

    The prevalence of Schistosoma mansoni infection in Venezuela has changed from high to low due mostly to successful control activities, including mass chemotherapy and molluscicide applications. This study examined the impact of mass chemotherapy on S. mansoni transmission and risk factors for infection 12 years after administration of praziquantel in Venezuela. Two relatively isolated rural communities were studied, one with snail control (Manuare) and the second without (Los Naranjos). A cross-sectional survey of randomly selected households included 226 (Manuare) and 192 (Los Naranjos) consenting participants. S. mansoni prevalence was determined using a combination of coprological (Kato-Katz) and serological (circumoval precipitin test, alkaline phosphatase immunoassay and Western blot) tests. Data on epidemiological and socioeconomic risk factors were obtained through individual structured interviews. Univariate analysis and multivariate logistic regression models identified independent risk factors for infection. Water sites were examined for the presence of Biomphalaria glabrata snails. Only one participant was positive by coprology. The overall prevalences according to the combined tests were 32.7% in Manuare and 26.6% in Los Naranjos. Lower prevalences (12.7% in Manuare and 13.2% in Los Naranjos) were found in children <12 years of age representing those born after mass chemotherapy. Social demographic variables associated with infection in both communities were older age (>25 years), contact with specific water sites, and being a farmer/non-specialised worker. Mass treatment with praziquantel applied once to endemic communities led to an important and long-lasting sustained reduction of S. mansoni infections independent of the application of snail control. A degree of low active transmission of S. mansoni persisted in the treated areas which was associated with similar factors in both communities. PMID:25128702

  8. Use of Humanised Rat Basophilic Leukaemia Cell Line RS-ATL8 for the Assessment of Allergenicity of Schistosoma mansoni Proteins

    PubMed Central

    Alanine, Daniel G. W.; Stretton, Owen; Ali Ali, Eman; Al-Barwary, Nafal; Wang, Xiaowei; Doenhoff, Michael J.; Mari, Adriano; Fitzsimmons, Colin M.; Dunne, David W.; Nakamura, Ryosuke; Oliveira, Guilherme C.; Alcocer, Marcos J. C.; Falcone, Franco H.

    2014-01-01

    Background Parasite-specific IgE is thought to correlate with protection against Schistosoma mansoni infection or re-infection. Only a few molecular targets of the IgE response in S. mansoni infection have been characterised. A better insight into the basic mechanisms of anti-parasite immunity could be gained from a genome-wide characterisation of such S. mansoni allergens. This would have repercussions on our understanding of allergy and the development of safe and efficacious vaccinations against helminthic parasites. Methodology/Principal Findings A complete medium- to high-throughput amenable workflow, including important quality controls, is described, which enables the rapid translation of S. mansoni proteins using wheat germ lysate and subsequent assessment of potential allergenicity with a humanised Rat Basophilic Leukemia (RBL) reporter cell line. Cell-free translation is completed within 90 minutes, generating sufficient amounts of parasitic protein for rapid screening of allergenicity without any need for purification. Antigenic integrity is demonstrated using Western Blotting. After overnight incubation with infected individuals' serum, the RS-ATL8 reporter cell line is challenged with the complete wheat germ translation mixture and Luciferase activity measured, reporting cellular activation by the suspected allergen. The suitability of this system for characterization of novel S. mansoni allergens is demonstrated using well characterised plant and parasitic allergens such as Par j 2, SmTAL-1 and the IgE binding factor IPSE/alpha-1, expressed in wheat germ lysates and/or E. coli. SmTAL-1, but not SmTAL2 (used as a negative control), was able to activate the basophil reporter cell line. Conclusion/Significance This method offers an accessible way for assessment of potential allergenicity of anti-helminthic vaccine candidates and is suitable for medium- to high-throughput studies using infected individual sera. It is also suitable for the study of the

  9. Impact of two rounds of praziquantel mass drug administration on Schistosoma mansoni infection prevalence and intensity: a comparison between community wide treatment and school based treatment in western Kenya.

    PubMed

    Onkanga, Isaac O; Mwinzi, Pauline N M; Muchiri, Geoffrey; Andiego, Kennedy; Omedo, Martin; Karanja, Diana M S; Wiegand, Ryan E; Secor, W Evan; Montgomery, Susan P

    2016-06-01

    This study compared the effectiveness of the community-wide treatment and school-based treatment approaches in the control of Schistosoma mansoni infections in villages with ⩾25% prevalence in western Kenya. Stool samples from first year students, 9-12year olds and adults (20-55years) were analyzed by the Kato-Katz technique for S. mansoni eggs. After two rounds of treatment, S. mansoni prevalence and intensity levels significantly declined in both treatment approaches. Prevalence comparisons between the two approaches did not show any significant differences following treatment. However, infection intensity levels in the 9-12year old school-attending pupils were significantly higher in the community-wide treatment arm than in the school-based treatment arm. Nevertheless, significant reductions in S. mansoni infection prevalence and intensity levels were achieved among school-age children regardless of the treatment approach used. PMID:26940547

  10. Additional Evaluation of the Point-of-Contact Circulating Cathodic Antigen Assay for Schistosoma mansoni Infection

    PubMed Central

    Mwinzi, Pauline N. M.; Kittur, Nupur; Ochola, Elizabeth; Cooper, Philip J.; Campbell, Carl H.; King, Charles H.; Colley, Daniel G.

    2015-01-01

    Studies of the urine-based point-of-contact cathodic circulating antigen test (POC-CCA) in Schistosoma mansoni-endemic settings in Africa indicate it has good sensitivity in detecting infections, but in areas of low prevalence, the POC-CCA can be positive for persons who are egg-negative by Kato-Katz stool assays. We examined the POC-CCA assay for: (a) batch-to-batch stability; (b) intra-reader and inter-reader variability; (c) day-to-day variability compared to Kato-Katz stool assays, and (d) to see if praziquantel (PZQ) treatment converted Kato-Katz-negative/POC-CCA positive individuals to POC-CCA negativity. We found essentially no batch-to-batch variation, negligible intra-reader variability (2%), and substantial agreement for inter-reader reliability. Some day-to-day variation was observed over 5 days of urine collection, but less than the variation in Kato-Katz stool assays over 3 days. To evaluate the effect of treatment on Kato-Katz(−)/POC-CCA(+) children, 149 children in an area of 10–15% prevalence who were Kato-Katz(−) based on 3 stool samples but POC-CCA(+) were enrolled. Seven days after treatment (PZQ 40 mg/kg) samples were again collected and tested. Almost half (47%) POC-CCA positive children turned negative. Those still POC-CCA positive received a second treatment, and 34% of them turned POC-CCA negative upon this second treatment. Most who remained POC-CCA positive shifted each time to a “lesser” POC-CCA “level of positivity.” The data suggest that most Kato-Katz-negative/POC-CCA positive individuals harbor low-intensity infections, and each treatment kills all or some of their adult worms. The data also suggest that when evaluated by a more sensitive assay, the effective cure rates for PZQ are significantly less than those inferred from fecal testing. These findings have public health significance for the mapping and monitoring of Schistosoma infections and in planning the transition from schistosomiasis morbidity control to

  11. Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

    PubMed Central

    Mohamed, Wael S.; Nasr, Hanaa E.; El-Lakkany, Naglaa M.; Seif el-Din, Sayed H.; Botros, Sanaa S.

    2015-01-01

    Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and its in vivo efficacy against Schistosoma mansoni were investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0–8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different

  12. Infection with Salmonella typhimurium modulates the immune response to Schistosoma mansoni glutathione-S-transferase.

    PubMed Central

    Comoy, E E; Vendeville, C; Capron, A; Thyphronitis, G

    1997-01-01

    Immune response polarization is controlled by several factors, including cytokines, antigen-presenting cells, antigen dose, and others. We have previously shown that adjuvants and live vectors play a critical role in polarization. Thus, immunization with the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28-GST) in aluminum hydroxide induced a type 2 cytokine profile and the production of immunoglobulin G1 (IgG1)- and IgE-specific antibodies. In contrast, mice infected with recombinant Salmonella typhimurium expressing Sm28-GST developed a type 1 cytokine profile and produced IgG2a-specific antibodies against Sm28-GST and Salmonella antigens. In this study, to determine if S. typhimurium not expressing Sm28-GST would still influence the type of the response against this antigen, we compared the profiles of the immune responses generated against Sm28-GST administered in alum in mice infected and not infected with S. typhimurium. Infected mice generated both IgG1 and IgG2a antibodies against Sm28-GST, while noninfected mice produced only IgG1 anti-Sm28-GST antibodies. Moreover, interleukin-4 (IL-4) mRNA expression in infected mice was near background levels, while gamma interferon (IFN-gamma) mRNA expression in coinfected mice was significantly higher than in mice immunized with Sm28-GST in alum only. However, after antigen-specific stimulation in vitro with Sm28-GST, levels of IL-4 and IFN-gamma cytokine production were similar in the two groups of mice. These results suggest that (i) the immune milieu produced during an infection may modify the response against an irrelevant antigen and (ii) isotype switching may be influenced by the cytokine environment of a bystander immune response, even though the specific antigen-driven cytokine production is not modified. Thus, the isotypic profile is not always an absolute reflection of the cytokines produced by antigen-specific Th cells. PMID:9234784

  13. Relationship between serum cytokines profiles and hepatic fibrosis in schistosomiasis mansoni: an experimental study.

    PubMed

    El-Gamal, Reda R; Nada, Soad M; Moustafa, Nahed E; Afify, Hany A; Fathy, Ghada M; Ashraf; Metwally, S; Hamza, Rania S

    2009-12-01

    Forty of eighty mice (10 each group) were infected with S. mansoni cercariae and sacrificed at 3 weeks (G-A), 6 weeks (G-B), 12 weeks (G-C) and 16 weeks (G-D) post infection (P.I). The other forty mice were used as control groups of ten mice each. There were highly significant difference between egg counts after 12 weeks & 16 weeks of infection compared to 6 weeks P.I. The maximum egg count and mature eggs were in 6th week P.I while dead eggs reached the peak at 16th weeks P.I. Liver egg counts showed maximum followed by intestinal and then, stool egg counts. A highly significant differences in hydroxyproline, TGF-Bland IL-4 of infected than in controls and their peak at 16 weeks P.I. A significant difference in the IFN-gamma in the infected than in controls with peak occurred at 6 weeks P.I. and declined after that reaching a low level at 16 weeks P.I. A highly significant positive correlation was between TGF-Bland IL4 and significant negative correlation between IFN-gamma and both IL4 & TGF-B1. A highly significant and significant negative correlation between TGF-B1 and egg count at 12 & 16 weeks P.I respectively. Negative correlation was between IL-4 and egg count at 16 weeks P.I. But, significant positive correlation was between IFN-gamma with the egg count at 16 weeks P.I. A significant negative correlation was between TGF-B1 and oogram at 6 & 16 weeks P.I, but highly significant positivity was between IFN-gamma and oogram at 16 weeks P.I. A significant negative correlation was between IL-4 and oogram at 16 weeks P.I. A significant positive correlation was between levels of hydroxyproline and TGF-B1 at 12 & 16 weeks P.I. Highly significant negative correlation between hydroxyproline and IFN-gamma was at 12 weeks P.I with significant and highly significant positive correlation between hydroxyproline and IL4 at 12 & 16 weeks P.I. PMID:20120754

  14. Proteomic analysis of Schistosoma mansoni proteins released during in vitro miracidium-to-sporocyst transformation

    PubMed Central

    Wu, Xiao-Jun; Sabat, Greg; Brown, James F.; Zhang, Mengzi; Taft, Andrew; Peterson, Nathan; Harms, Amy; Yoshino, Timothy P.

    2009-01-01

    Free-living miracidia of Schistosoma mansoni, upon penetration of the their snail intermediate host, undergo dramatic morphological and physiological changes as they transform to the parasitic sporocyst stage. During this transformation process, developing larvae release a diverse array of proteins, herein referred to as larval transformation proteins (LTPs), some of which are postulated to serve a parasite protective function. In the present study, nanoLC-tandem MS analysis was performed on all proteins represented in entire 1-dimensional SDS-PAGE-separated samples in order to gain a more comprehensive picture of the protein constituents associated with miracidium-to-sporocyst transformation and thus, their potential role in influencing establishment of intramolluscan infections. Of 127 proteins with sufficient peptide/sequence information, specific identifications were made for 99, while 28 represented unknown or hypothetical proteins. Nineteen percent of identified proteins possessed signal peptides constituting a cohort of classical secretory proteins, while 22% were identified as putative nonclassically-secreted leaderless proteins based on SecretomeP analysis. Proteins comprising these groups consisted mainly of proteases/protease inhibitors, small HSPs, redox/antioxidant enzymes, ion-binding proteins including those with anti-oxidant Fe-binding activities (ferritins, heme-binding protein), and venom allergen-like (VAL) proteins. A polyclonal antibody generated against whole LTPs recognized proteins primarily associated with the cilia, ciliated epidermal plates and intercellular ridges of miracidia and the tegument of fully-transformed sporocysts, identifying these structures as sources of a subset of LTPs. Thus lysis of plates and/or leakage during formation of the sporocyst syncytium likely represent significant contributors to the overall LTP makeup, especially identified nonsecretory proteins. However, as plate release/degradation and tegument formation

  15. Imatinib Treatment Causes Substantial Transcriptional Changes in Adult Schistosoma mansoni In Vitro Exhibiting Pleiotropic Effects

    PubMed Central

    Oliveira, Katia C.; Dissous, Colette; Cailliau, Katia; Marhöfer, Richard J.; Selzer, Paul M.; Verjovski-Almeida, Sergio; Grevelding, Christoph G.

    2014-01-01

    Background Schistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ) is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs) demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec). Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites. Methodology/Principal Findings Here we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common targets. Conclusions

  16. Schistosoma mansoni Egg, Adult Male and Female Comparative Gene Expression Analysis and Identification of Novel Genes by RNA-Seq

    PubMed Central

    Anderson, Letícia; Amaral, Murilo S.; Beckedorff, Felipe; Silva, Lucas F.; Dazzani, Bianca; Oliveira, Katia C.; Almeida, Giulliana T.; Gomes, Monete R.; Pires, David S.; Setubal, João C.; DeMarco, Ricardo; Verjovski-Almeida, Sergio

    2015-01-01

    Background Schistosomiasis is one of the most prevalent parasitic diseases worldwide and is a public health problem. Schistosoma mansoni is the most widespread species responsible for schistosomiasis in the Americas, Middle East and Africa. Adult female worms (mated to males) release eggs in the hepatic portal vasculature and are the principal cause of morbidity. Comparative separate transcriptomes of female and male adult worms were previously assessed with using microarrays and Serial Analysis of Gene Expression (SAGE), thus limiting the possibility of finding novel genes. Moreover, the egg transcriptome was analyzed only once with limited bacterially cloned cDNA libraries. Methodology/Principal findings To compare the gene expression of S. mansoni eggs, females, and males, we performed RNA-Seq on these three parasite forms using 454/Roche technology and reconstructed the transcriptome using Trinity de novo assembly. The resulting contigs were mapped to the genome and were cross-referenced with predicted Smp genes and H3K4me3 ChIP-Seq public data. For the first time, we obtained separate, unbiased gene expression profiles for S. mansoni eggs and female and male adult worms, identifying enriched biological processes and specific enriched functions for each of the three parasite forms. Transcripts with no match to predicted genes were analyzed for their protein-coding potential and the presence of an encoded conserved protein domain. A set of 232 novel protein-coding genes with putative functions related to reproduction, metabolism, and cell biogenesis was detected, which contributes to the understanding of parasite biology. Conclusions/Significance Large-scale RNA-Seq analysis using de novo assembly associated with genome-wide information for histone marks in the vicinity of gene models constitutes a new approach to transcriptome analysis that has not yet been explored in schistosomes. Importantly, all data have been consolidated into a UCSC Genome Browser search

  17. Specific Schistosoma mansoni rat T cell clones. I. Generation and functional analysis in vitro and in vivo.

    PubMed

    Pestel, J; Dissous, C; Dessaint, J P; Louis, J; Engers, H; Capron, A

    1985-06-01

    In an attempt to determine the role of schistosome-specific T cells in the immune mechanisms developed during schistosomiasis, Schistosoma mansoni-specific T cells and clones were generated in vitro and some of their functions analyzed in vitro and in vivo in the fischer rat model. The data presented here can be summarized as follows: a) Lymph node cells (LNC) from rats primed with the excretory/secretory antigens-incubation products (IPSm) of adult worms proliferate in vitro only in response to the homologous schistosome antigens and not to unrelated antigens (Ag) such as ovalbumin (OVA) or Dipetalonema viteae and Fasciola hepatica parasite extracts. b) After in vitro restimulation of the primed LNC population with IPSm in the presence of antigen-presenting cells (APC) and maintenance in IL 2-containing medium, the frequency of IPSm-specific T cells is increased and the T cells can be restimulated only in the presence of APC possessing the same major histocompatibility complex (MHC) antigens. c) Following appropriate limiting dilution assays (LDA) (1 cell/well), 10 IPSm-specific T cell clones were obtained, and two of four maintained in culture were tested for their helper activity because they expressed only the W3/13+ W3/25+ surface phenotypes. d) The two highly proliferating IPSm-specific T cell clones (G5 and E23) exhibit an IPSm-dependent helper activity, as shown by the increase in IgG production by IPSm-primed B cells. e) IPSm-T cell clone (G5) as well as IPSm-T cell lines when injected in S. mansoni-infested rats can exert an in vivo helper activity, which is characterized by an accelerated production of IgG antibodies specific for the previously identified 30 to 40 kilodaltons (kd) schistosomula surface antigens (Ag). As recent studies have demonstrated that rat monoclonal antibodies recognize some incubation products of adult S. mansoni as well as one of the 30 to 40 kd schistosomula surface antigens, and taking into account the fact that the T cell

  18. The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica

    PubMed Central

    Edwards, Jennifer; Brown, Martha; Peak, Emily; Bartholomew, Barbara; Nash, Robert J.; Hoffmann, Karl F.

    2015-01-01

    Background Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. Methodology/ Principle Findings Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and

  19. Epigenetic modulation, stress and plasticity in susceptibility of the snail host, Biomphalaria glabrata, to Schistosoma mansoni infection.

    PubMed

    Knight, Matty; Ittiprasert, Wannaporn; Arican-Goktas, Halime D; Bridger, Joanna M

    2016-06-01

    Blood flukes are the causative agent of schistosomiasis - a major neglected tropical disease that remains endemic in numerous countries of the tropics and sub-tropics. During the past decade, a concerted effort has been made to control the spread of schistosomiasis, using a drug intervention program aimed at curtailing transmission. These efforts notwithstanding, schistosomiasis has re-emerged in southern Europe, raising concerns that global warming could contribute to the spread of this disease to higher latitude countries where transmission presently does not take place. Vaccines against schistosomiasis are not currently available and reducing transmission by drug intervention programs alone does not prevent reinfection in treated populations. These challenges have spurred awareness that new interventions to control schistosomiasis are needed, especially since the World Health Organization hopes to eradicate the disease by 2025. For one of the major species of human schistosomes, Schistosoma mansoni, the causative agent of hepatointestinal schistosomiasis in Africa and the Western Hemisphere, freshwater snails of the genus Biomphalaria serve as the obligate intermediate host of this parasite. To determine mechanisms that underlie parasitism by S. mansoni of Biomphalaria glabrata, which might be manipulated to block the development of intramolluscan larval stages of the parasite, we focused effort on the impact of schistosome infection on the epigenome of the snail. Results to date reveal a complex relationship, manifested by the ability of the schistosome to manipulate the snail genome, including the expression of specific genes. Notably, the parasite subverts the stress response of the host to ensure productive parasitism. Indeed, in isolates of B. glabrata native to central and South America, susceptible to infection with S. mansoni, the heat shock protein 70 (Bg-HSP70) gene of this snail is rapidly relocated in the nucleus and transcribed to express HSP70

  20. Prevalence of Intestinal Parasitic Infections among Children under Five Years of Age with Emphasis on Schistosoma mansoni in Wonji Shoa Sugar Estate, Ethiopia

    PubMed Central

    G/hiwot, Yirgalem; Degarege, Abraham; Erko, Berhanu

    2014-01-01

    Intestinal parasite infections are major public health problems of children in developing countries causing undernutrition, anemia, intestinal obstruction and mental and physical growth retardation. This study was conducted to assess the prevalence of intestinal helminthic infections among children under five years of age with emphasis on Schistosoma mansoni in Wonji Shoa Sugar Estate, Ethiopia. A cross-sectional parasitological survey was conducted in under-five children living in Wonji Shoa Sugar Estate Ethiopia, April, 2013. Stool samples were collected and examined for intestinal parasites using single Kato-Katz and single Sodium acetate-acetic acid-formalin (SAF) solution concentration methods. Out of 374 children examined using single Kato-Katz and single SAF-concentration methods, 24.3% were infected with at least one intestinal parasite species. About 10.4%, 8.8%, 4.6%, 2.9%, 1.6% and 0.8% of the children were infected with Hymenolepis nana, Schistosoma mansoni, Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis and hookworm, respectively. Prevalence of double, triple and quadruple intestinal helminthic infection was 6.4%, 0.54% and 1.1%, respectively. A significant increase in prevalence of S. mansoni (8.3% versus 3.2%) and T. trichiura (2.7% versus 0.5%) infection was observed when determined via the single Kato-Katz method compared to the prevalence of the parasites determined via the single SAF-concentration method. On the other hand, the single SAF-concentration method (9.1%) revealed a significantly higher prevalence of H. nana infection than the single Kato-Katz (1.6%) does. In conclusion, intestinal helminths infections particularly S. mansoni and H. nana were prevalent in under-five children of Wonji Shoa Sugar Estate. Including praziquantel treatment in the deworming program as per the World Health Organization guidelines would be vital to reduce the burden of these diseases in areas where S. mansoni and H. nana infections are

  1. Early detection of circulating anodic antigen (CAA) in a case of acute schistosomiasis mansoni with Katayama fever.

    PubMed

    Gundersen, S G; Ravn, J; Haagensen, I

    1992-01-01

    A 34-year-old male developed acute Katayama fever with fever, diarrhoea, joint pains, headache, urticarial rash and eosinophilia 18 days after falling into and spending 15 min in the water during water-skiing in the outlet of the Volta river. Low anti-schistosomal antibody titres were found by the immunofluorescence assay after 4 weeks, and the first Schistosoma mansoni eggs were found in faeces after 6 weeks. Both symptoms and eosinophilia increased the first days after treatment with oxamniquine, after which he improved gradually. Examination of frozen sera by the newly developed Magnetic Beads Antigen Capture-EIA (MBAC-EIA) later demonstrated a peak in schistosomal circulating anodic antigen (CAA) levels of diagnostic significance already 4 weeks after he was infected. PMID:1411323

  2. Susceptibility and compatibility of Biomphalaria tenagophila from the Río de la Plata basin with Schistosoma mansoni from Brazil.

    PubMed

    Borda, Carlos Edgardo; Rea, María Josefa F

    2010-07-01

    Schistosomiasis has expanded to southern parts of Brazil. Between 2005-2007 the dispersion and the proliferation of Biomphalaria tenagophila was verified in the province of Corrientes near the Brazilian border. In order to study the possibility that schistosomiasis might spread into the basins of the Paraná and Uruguay Rivers, 440 B. tenagophila collected from 10 populations groups were experimentally exposed to infection with Schistosoma mansoni of the SJ2 strain. Snails from five localities were susceptible. Frandsen's index (TCP/100) shows that those snails from Mirungá (11%), Aguacerito (2%) and Curupicay (2%) were Class I and not very compatible. Meanwhile, snails from Copra (6%) and Pay-Ubre (22%), in the Paraná River basin, were Class II and poorly compatible. PMID:20721498

  3. LmSmdB: an integrated database for metabolic and gene regulatory network in Leishmania major and Schistosoma mansoni

    PubMed Central

    Patel, Priyanka; Mandlik, Vineetha; Singh, Shailza

    2015-01-01

    A database that integrates all the information required for biological processing is essential to be stored in one platform. We have attempted to create one such integrated database that can be a one stop shop for the essential features required to fetch valuable result. LmSmdB (L. major and S. mansoni database) is an integrated database that accounts for the biological networks and regulatory pathways computationally determined by integrating the knowledge of the genome sequences of the mentioned organisms. It is the first database of its kind that has together with the network designing showed the simulation pattern of the product. This database intends to create a comprehensive canopy for the regulation of lipid metabolism reaction in the parasite by integrating the transcription factors, regulatory genes and the protein products controlled by the transcription factors and hence operating the metabolism at genetic level. PMID:26981382

  4. Ameliorative effect of bone marrow-derived stem cells on injured liver of mice infected with Schistosoma mansoni.

    PubMed

    El-Mahdi, Magda M; Mansour, Wafaa A; Hammam, Olfat; Mehana, Noha A; Hussein, Taghreed M

    2014-04-01

    The technique of stem cells or hepatocytes transplantation has recently improved in order to bridge the time before whole-organ liver transplantation. In the present study, unfractionated bone marrow stem cells (BMSCs) were harvested from the tibial and femoral marrow compartments of male mice, which were cultured in Dulbecco's modified Eagle's medium (DMEM) with and without hepatocyte growth factor (HGF), and then transplanted into Schistosoma mansoni-infected female mice on their 8th week post-infection. Mice were sacrificed monthly until the third month of bone marrow transplantation, serum was collected, and albumin concentration, ALT, AST, and alkaline phosphatase (ALP) activities were assayed. On the other hand, immunohistopathological and immunohistochemical changes of granuloma size and number, collagen content, and cells expressing OV-6 were detected for identification of liver fibrosis. BMSCs were shown to differentiate into hepatocyte-like cells. Serum ALT, AST, and ALP were markedly reduced in the group of mice treated with BMSCs than in the untreated control group. Also, granuloma showed a marked decrease in size and number as compared to the BMSCs untreated group. Collagen content showed marked decrease after the third month of treatment with BMSCs. On the other hand, the expression of OV-6 increased detecting the presence of newly formed hepatocytes after BMSCs treatment. BMSCs with or without HGF infusion significantly enhanced hepatic regeneration in S. mansoni-induced fibrotic liver model and have pathologic and immunohistopathologic therapeutic effects. Also, this new therapeutic trend could generate new hepatocytes to improve the overall liver functions. PMID:24850958

  5. Analysis of two Schistosoma mansoni uridine phosphorylases isoforms suggests the emergence of a protein with a non-canonical function.

    PubMed

    da Silva Neto, Antônio Marinho; Torini de Souza, Juliana Roberta; Romanello, Larissa; Cassago, Alexandre; Serrão, Vitor Hugo Balasco; DeMarco, Ricardo; Brandão-Neto, José; Garratt, Richard Charles; Pereira, Humberto D'Muniz

    2016-06-01

    Reports of Schistosoma mansoni strains resistant to praziquantel, the only therapeutic strategy available for the treatment of schistosomiasis, have motivated the scientific community towards the search for new possible therapies. Biochemical characterization of the parasite's metabolism is an essential component for the rational development of new therapeutic alternatives. One of the so far uncharacterized enzymes is uridine phosphorylase (UP) (EC 2.4.2.3), for which the parasite genome presents two isoforms (SmUPa and SmUPb) that share 92% sequence identity. In this paper, we present crystal structures for SmUPa and SmUPb in their free states as well as bound to different ligands. This we have complemented by enzyme kinetic characterization and phylogenetic analyses. Both enzymes present an overall fold and active site structure similar to other known UPs. The kinetic analyses showed conclusively that SmUPa is a regular uridine phosphorylase but by contrast SmUPb presented no detectable activity. This is particularly noteworthy given the high level of sequence identity between the two isoforms and is probably the result of the significant differences observed for SmUPb in the vicinity of the active site itself, suggesting that it is not a UP at all. On the other hand, it was not possible to identify an alternative function for SmUPb, although our phylogenetic analyses and expression data suggest that SmUPb is still functional and plays a role in parasite metabolism. The unusual UPb isoform may open up new opportunities for understanding unique features of S. mansoni metabolism. PMID:26898674

  6. Indirect effects of oral tolerance to ovalbumin interfere with the immune responses triggered by Schistosoma mansoni eggs.

    PubMed

    Carvalho, C R; Lenzi, H L; Correa-Oliveira, R; Vaz, N M

    2002-10-01

    The objective of the present study was to investigate whether the injection of a tolerated protein (indirect effects) affects the formation of granulomas around Schistosoma mansoni eggs trapped in the lungs after intravenous (iv) injection into normal (noninfected) C57BL/6 mice (6 animals per group). To induce oral tolerance to chicken egg ovalbumin a 1/5 dilution of egg white in water was offered ad libitum in a drinking bottle for 3 days. Control mice received water. After 7 days, control and experimental animals were injected iv with 2,000 S. mansoni eggs through a tail vein. In some mice of both groups the iv injection of eggs was immediately followed by intraperitoneal (ip) immunization with 10 micro g of dinitrophenylated conjugates of ovalbumin (DNP-Ova) emulsified in complete Freund's adjuvant (CFA) or only CFA; 18 days later, mice were bled and killed by ether inhalation. The lungs were fixed in formalin and embedded in paraffin. Serial sections of 5 m were stained with Giemsa, Gomori's silver reticulin and Sirius red (pH 10.2). Granuloma diameters were measured in histological sections previously stained with Gomori's reticulin. Anti-DNP and anti-soluble egg antigen (SEA) antibodies were analyzed by ELISA. In mice orally tolerant to ovalbumin the concomitant ip injection of DNP-Ova resulted in significantly lower anti-SEA antibodies (ELISA*: 1395 +/- 352 in non-tolerant and 462 +/- 146 in tolerant mice) and affected granuloma formation around eggs, significantly decreasing granuloma size (area: 22,260 +/- 2478 to 12,993 +/- 3242 m ). Active mechanisms triggered by injection of tolerated antigen (ovalbumin) reduce granuloma formation. PMID:12424492

  7. Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni

    PubMed Central

    Nowacki, Fanny C.; Swain, Martin T.; Klychnikov, Oleg I.; Niazi, Umar; Ivens, Alasdair; Quintana, Juan F.; Hensbergen, Paul J.; Hokke, Cornelis H.; Buck, Amy H.; Hoffmann, Karl F.

    2015-01-01

    Background Penetration of skin, migration through tissues and establishment of long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies of larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role of extracellular vesicles (EVs) has yet to be considered. Here, using preparatory ultracentrifugation as well as methodologies to globally analyse both proteins and small non-coding RNAs (sncRNAs), we conducted the first characterization of Schistosoma mansoni schistosomula EVs and their potential host-regulatory cargos. Results Transmission electron microscopy analysis of EVs isolated from schistosomula in vitro cultures revealed the presence of numerous, 30–100 nm sized exosome-like vesicles. Proteomic analysis of these vesicles revealed a core set of 109 proteins, including homologs to those previously found enriched in other eukaryotic EVs, as well as hypothetical proteins of high abundance and currently unknown function. Characterization of E/S sncRNAs found within and outside of schistosomula EVs additionally identified the presence of potential gene-regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived small RNAs (tsRNAs; nineteen 5′ tsRNAs and fourteen 3′ tsRNAs). Conclusions The identification of S. mansoni EVs and the combinatorial protein/sncRNA characterization of their cargo signifies that an important new participant in the complex biology underpinning schistosome/host interactions has now been discovered. Further work defining the role of these schistosomula EVs and the function/stability of intra- and extra-vesicular sncRNA components presents tremendous opportunities for developing novel schistosomiasis diagnostics or interventions. PMID:26443722

  8. Differential transcriptomic responses of Biomphalaria glabrata (Gastropoda, Mollusca) to bacteria and metazoan parasites, Schistosoma mansoni and Echinostoma paraensei (Digenea, Platyhelminthes).

    PubMed

    Adema, Coen M; Hanington, Patrick C; Lun, Cheng-Man; Rosenberg, George H; Aragon, Anthony D; Stout, Barbara A; Lennard Richard, Mara L; Gross, Paul S; Loker, Eric S

    2010-01-01

    A 70-mer-oligonucleotide-based microarray (1152 features) that emphasizes stress and immune responses factors was constructed to study transcriptomic responses of the snail Biomphalaria glabrata to different immune challenges. In addition to sequences with relevant putative ID and Gene Ontology (GO) annotation, the array features non-immune factors and unknown B. glabrata ESTs for functional gene discovery. The transcription profiles of B. glabrata (3 biological replicates, each a pool of 5 snails) were recorded at 12h post-wounding, exposure to Gram negative or Gram positive bacteria (Escherichia coli and Micrococcus luteus, respectively), or infection with compatible trematode parasites (Schistosoma mansoni or Echinostoma paraensei, 20 miracidia/snail), relative to controls, using universal reference RNA. The data were subjected to Significance Analysis for Microarrays (SAM), with a false positive rate (FPR) mansoni exposure yielded a preponderance of up-regulated features (140 up/23 down), with only few known immune genes affected. These observations may reflect the divergent strategies developed by trematodes during their evolution as specialized pathogens of snails to negate host defense responses. Clearly, the immune defenses of B. glabrata distinguish and respond differently to various immune challenges. PMID:19962194

  9. Suppression of Basophil Histamine Release and Other IgE-dependent Responses in Childhood Schistosoma mansoni/hookworm Coinfection

    PubMed Central

    Pinot de Moira, Angela; Fitzsimmons, Colin M.; Jones, Frances M.; Wilson, Shona; Cahen, Pierre; Tukahebwa, Edridah; Mpairwe, Harriet; Mwatha, Joseph K.; Bethony, Jeffrey M.; Skov, Per S.; Kabatereine, Narcis B.; Dunne, David W.

    2014-01-01

    Background. The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment. Results. Nonspecific- and helminth-specific-HR, and associations between helminth-specific IgE and helminth-specific HR increased post-treatment. Hookworm infection appeared to modify the relationship between circulating levels of HDM-IgE and HR: a significant positive association was observed among children without detectable hookworm infection, but no association was observed among infected children. In addition, hookworm infection was associated with a significantly reduced risk of wheeze, and IgG4 to somatic adult hookworm antigen with a reduced risk of HDM-SPT sensitivity. There was no evidence for S. mansoni infection having a similar suppressive effect on HDM-HR or symptoms of allergy. Conclusions. Basophil responsiveness appears suppressed during chronic helminth infection; at least in hookworm infection, this suppression may protect against allergy. PMID:24782451

  10. Differential Anti-Glycan Antibody Responses in Schistosoma mansoni-Infected Children and Adults Studied by Shotgun Glycan Microarray

    PubMed Central

    van Diepen, Angela; Smit, Cornelis H.; van Egmond, Loes; Kabatereine, Narcis B.; Pinot de Moira, Angela; Dunne, David W.; Hokke, Cornelis H.

    2012-01-01

    Background Schistosomiasis (bilharzia) is a chronic and potentially deadly parasitic disease that affects millions of people in (sub)tropical areas. An important partial immunity to Schistosoma infections does develop in disease endemic areas, but this takes many years of exposure and maturation of the immune system. Therefore, children are far more susceptible to re-infection after treatment than older children and adults. This age-dependent immunity or susceptibility to re-infection has been shown to be associated with specific antibody and T cell responses. Many antibodies generated during Schistosoma infection are directed against the numerous glycans expressed by Schistosoma. The nature of glycan epitopes recognized by antibodies in natural schistosomiasis infection serum is largely unknown. Methodology/Principal Findings The binding of serum antibodies to glycans can be analyzed efficiently and quantitatively using glycan microarray approaches. Very small amounts of a large number of glycans are presented on a solid surface allowing binding properties of various glycan binding proteins to be tested. We have generated a so-called shotgun glycan microarray containing natural N-glycan and lipid-glycan fractions derived from 4 different life stages of S. mansoni and applied this array to the analysis of IgG and IgM antibodies in sera from children and adults living in an endemic area. This resulted in the identification of differential glycan recognition profiles characteristic for the two different age groups, possibly reflecting differences in age or differences in length of exposure or infection. Conclusions/Significance Using the shotgun glycan microarray approach to study antibody response profiles against schistosome-derived glycan elements, we have defined groups of infected individuals as well as glycan element clusters to which antibody responses are directed in S. mansoni infections. These findings are significant for further exploration of Schistosoma

  11. Two allelic isoforms of the serotonin transporter from Schistosoma mansoni display electrogenic transport and high selectivity for serotonin

    PubMed Central

    Fontana, Andréia C. K.; Sonders, Mark S.; Pereira-Junior, Olavo S.; Knight, Matty; Javitch, Jonathan A.; Rodrigues, Vanderlei; Amara, Susan G.; Mortensen, Ole V.

    2009-01-01

    The human blood fluke Schistosoma mansoni is the primary cause of schistosomiasis, a debilitating disease that affects 200 million individuals in over 70 countries. The biogenic amine serotonin is essential for the survival of the parasite and serotonergic proteins are potential novel drug targets for treating schistosomiasis. Here we characterize two novel serotonin transporter gene transcripts, SmSERT-A and SmSERT-B, from Schistosoma mansoni. Southern blot analysis shows that the two mRNAs are the products of different alleles of a single SmSERT gene locus. The two SmSERT forms differ in three amino acid positions near the N-terminus of the protein. Both SmSERTs are expressed in the adult form and in the sporocyst form (infected snails) of the parasite, but are absent from all other stages of the parasite’s complex life cycle. Heterologous expression of the two cDNAs in mammalian cells resulted in saturable, sodium-dependent serotonin transport activity with an apparent affinity for serotonin comparable to that of the human serotonin transporter. Although the two SmSERTs are pharmacologically indistinguishable from each other, efflux experiments reveal notably higher substrate selectivity for serotonin compared with their mammalian counterparts. Several well-established substrates for human SERT including (±)MDMA, S-(+)amphetamine, RU 24969, and m-CPP are not transported by SmSERTs, underscoring the higher selectivity of the schistosomal isoforms. Voltage clamp recordings of SmSERT substrate-elicited currents confirm the substrate selectivity observed in efflux experiments and suggest that it may be possible to exploit the electrogenic nature of SmSERT to screen for compounds that target the parasite in vivo. PMID:19549517

  12. Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine

    PubMed Central

    Dougall, Annette M; Dougall, Annette M

    2014-01-01

    The self-adjuvanting lipid core peptide (LCP) system offers a safe alternative vaccine delivery strategy, eliminating the need for additional adjuvants such as CpG Alum. In this study, we adopted the LCP as a scaffold for an epitope located on the surface of the cathepsin D hemoglobinase (Sm-CatD) of the human blood fluke Schistosoma mansoni. Sm-CatD plays a pivotal role in digestion of the fluke’s bloodmeal and has been shown to be efficacious as a subunit vaccine in a murine model of human schistosomiasis. Using molecular modeling we showed that S. mansoni cathepsin D possesses a predicted surface exposed α-helix (A263K) that corresponds to an immunodominant helix and target of enzyme–neutralizing antibodies against Necator americanus APR-1 (Na-APR-1), the orthologous protease and vaccine antigen from blood-feeding hookworms. The A263K epitope was engineered as two peptide variants, one of which was flanked at both termini with a coil maintaining sequence, thereby promoting the helical characteristics of the native A263K epitope. Some of the peptides were fused to a self-adjuvanting lipid core scaffold to generate LCPs. Mice were vaccinated with unadjuvanted peptides, peptides formulated with Freund’s adjuvants, or LCPs. Antibodies generated to LCPs recognized native Sm-CatD within a soluble adult schistosome extract, and almost completely abolished its enzymatic activity in vitro. Using immunohistochemistry we showed that anti-LCP antibodies bound to the native Sm-CatD protein in the esophagus and anterior regions of the gastrodermis of adult flukes. Vaccines offer an alternative control strategy in the fight against schistosomiasis, and further development of LCPs containing multiple epitopes from this and other vaccine antigens should become a research priority. PMID:24231271

  13. Ameliorative Effect of Bone Marrow-Derived Stem Cells on Injured Liver of Mice Infected with Schistosoma mansoni

    PubMed Central

    Mansour, Wafaa A.; Hammam, Olfat; Mehana, Noha A.; Hussein, Taghreed M.

    2014-01-01

    The technique of stem cells or hepatocytes transplantation has recently improved in order to bridge the time before whole-organ liver transplantation. In the present study, unfractionated bone marrow stem cells (BMSCs) were harvested from the tibial and femoral marrow compartments of male mice, which were cultured in Dulbecco's modified Eagle's medium (DMEM) with and without hepatocyte growth factor (HGF), and then transplanted into Schistosoma mansoni-infected female mice on their 8th week post-infection. Mice were sacrificed monthly until the third month of bone marrow transplantation, serum was collected, and albumin concentration, ALT, AST, and alkaline phosphatase (ALP) activities were assayed. On the other hand, immunohistopathological and immunohistochemical changes of granuloma size and number, collagen content, and cells expressing OV-6 were detected for identification of liver fibrosis. BMSCs were shown to differentiate into hepatocyte-like cells. Serum ALT, AST, and ALP were markedly reduced in the group of mice treated with BMSCs than in the untreated control group. Also, granuloma showed a marked decrease in size and number as compared to the BMSCs untreated group. Collagen content showed marked decrease after the third month of treatment with BMSCs. On the other hand, the expression of OV-6 increased detecting the presence of newly formed hepatocytes after BMSCs treatment. BMSCs with or without HGF infusion significantly enhanced hepatic regeneration in S. mansoni-induced fibrotic liver model and have pathologic and immunohistopathologic therapeutic effects. Also, this new therapeutic trend could generate new hepatocytes to improve the overall liver functions. PMID:24850958

  14. Controlled Chaos of Polymorphic Mucins in a Metazoan Parasite (Schistosoma mansoni) Interacting with Its Invertebrate Host (Biomphalaria glabrata)

    PubMed Central

    Roger, Emmanuel; Grunau, Christoph; Pierce, Raymond J.; Hirai, Hirohisa; Gourbal, Benjamin; Galinier, Richard; Emans, Rémi; Cesari, Italo M.; Cosseau, Céline; Mitta, Guillaume

    2008-01-01

    Invertebrates were long thought to possess only a simple, effective and hence non-adaptive defence system against microbial and parasitic attacks. However, recent studies have shown that invertebrate immunity also relies on immune receptors that diversify (e.g. in echinoderms, insects and mollusks (Biomphalaria glabrata)). Apparently, individual or population-based polymorphism-generating mechanisms exists that permit the survival of invertebrate species exposed to parasites. Consequently, the generally accepted arms race hypothesis predicts that molecular diversity and polymorphism also exist in parasites of invertebrates. We investigated the diversity and polymorphism of parasite molecules (Schistosoma mansoni Polymorphic Mucins, SmPoMucs) that are key factors for the compatibility of schistosomes interacting with their host, the mollusc Biomphalaria glabrata. We have elucidated the complex cascade of mechanisms acting both at the genomic level and during expression that confer polymorphism to SmPoMuc. We show that SmPoMuc is coded by a multi-gene family whose members frequently recombine. We show that these genes are transcribed in an individual-specific manner, and that for each gene, multiple splice variants exist. Finally, we reveal the impact of this polymorphism on the SmPoMuc glycosylation status. Our data support the view that S. mansoni has evolved a complex hierarchical system that efficiently generates a high degree of polymorphism—a “controlled chaos”—based on a relatively low number of genes. This contrasts with protozoan parasites that generate antigenic variation from large sets of genes such as Trypanosoma cruzi, Trypanosoma brucei and Plasmodium falciparum. Our data support the view that the interaction between parasites and their invertebrate hosts are far more complex than previously thought. While most studies in this matter have focused on invertebrate host diversification, we clearly show that diversifying mechanisms also exist on

  15. Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

    PubMed

    Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

    2016-05-10

    Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection. PMID:27114544

  16. 5-lipoxygenase pathway is essential for the control of granuloma extension induced by Schistosoma mansoni eggs in lung.

    PubMed

    Toffoli da Silva, Gabriel; Espíndola, Milena Sobral; Fontanari, Caroline; Rosada, Rogerio Silva; Faccioli, Lúcia Helena; Ramos, Simone Gusmão; Rodrigues, Vanderlei; Frantz, Fabiani Gai

    2016-08-01

    According to WHO, it is estimated that approximately 2 billion people are infected with intestinal helminths worldwide and the number of people who are cured of these diseases is relatively low, resulting in a large percentage of chronically infected individuals. Schistosomiasis is one of the most important parasitic diseases present in developing countries configuring it as a serious public health problem, directly related to poverty and social disadvantage. Once the parasite infection is established, Schistosoma mansoni eggs fall into the bloodstream and are trapped in the liver microcirculation where a strong granulomatous response and fibrosis formation occurs. In the experimental model, granulomas develop in the mouse lung after intravenous injection of purified eggs. Here we aim to understand how leukotrienes are involved in the granuloma formation. Leukotrienes are lipid mediators derived from arachidonic acid metabolites via 5-lipoxygenase (5LO) enzyme. They are potent proinflammatory agents and induce recruitment, cell activation, regulation of microbicidal activity of polymorphonuclear and mononuclear cells. In this study, 5LO deficient mice (5LO(-/-)) were inoculated with S. mansoni eggs for evaluation of immunopathological parameters involved in the induction of type 2 granulomas. We showed that in the absence of leukotrienes, the size of granulomas were decreased comparing to the wild type mice and the inflammatory compromised areas had a lower extension. In 5LO(-/-) mice granulomas presented extensive areas of fibrosis, detected by α-SMA expression along the lesions, indicating remodeling in attempt to reestablish the normal tissue. Also, comparing to WT mice we detected decrease of IL-4 and IL-13 and increase of TGF-β in the lung of 5LO(-/-), but these mice failed to produce protective IFN-γ and IL-12. These results evidenced 5-Lipoxygenase as an important pathway during lung injury due to Schistosoma-eggs injection. PMID:27262746

  17. Expression at a 20L scale and purification of the extracellular domain of the Schistosoma mansoni TSP-2 recombinant protein: a vaccine candidate for human intestinal schistosomiasis.

    PubMed

    Curti, Elena; Kwityn, Clifford; Zhan, Bin; Gillespie, Portia; Brelsford, Jill; Deumic, Vehid; Plieskatt, Jordan; Rezende, Wanderson C; Tsao, Eric; Kalampanayil, Bose; Hotez, Peter J; Bottazzi, Maria Elena

    2013-11-01

    A novel recombinant protein vaccine for human schistosomiasis caused by Schistosoma mansoni is under development. The Sm-TSP-2 schistosomiasis vaccine is comprised of a 9 kDa recombinant protein corresponding to the extracellular domain of a unique S. mansoni tetraspanin. Here, we describe the cloning and the expression of the external loop of Sm-TSP-2 recombinant protein secreted by Pichia Pink the process development at 20L scale fermentation, and the two-steps purification, which resulted in a protein recovery yield of 31% and a protein purity of 97%. The developed processes are suitable for the production of purified protein for subsequent formulation and Phase 1 clinical studies. PMID:23899507

  18. The role of the immunological background of mice in the genetic variability of Schistosoma mansoni as detected by random amplification of polymorphic DNA.

    PubMed

    Cossa-Moiane, I L; Mendes, T; Ferreira, T M; Mauricio, I; Calado, M; Afonso, A; Belo, S

    2015-11-01

    Schistosomiasis is a parasitic disease caused by flatworms of the genus Schistosoma. Among the Schistosoma species known to infect humans, S. mansoni is the most frequent cause of intestinal schistosomiasis in sub-Saharan Africa and South America: the World Health Organization estimates that about 200,000 deaths per year result from schistosomiasis in sub-Saharan Africa alone. The Schistosoma life cycle requires two different hosts: a snail as intermediate host and a mammal as definitive host. People become infected when they come into contact with water contaminated with free-living larvae (e.g. when swimming, fishing, washing). Although S. mansoni has mechanisms for escaping the host immune system, only a minority of infecting larvae develop into adults, suggesting that strain selection occurs at the host level. To test this hypothesis, we compared the Belo Horizonte (BH) strain of S. mansoni recovered from definitive hosts with different immunological backgrounds using random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). Schistosoma mansoni DNA profiles of worms obtained from wild-type (CD1 and C57BL/6J) and mutant (Jα18- / - and TGFβRIIdn) mice were analysed. Four primers produced polymorphic profiles, which can therefore potentially be used as reference biomarkers. All male worms were genetically distinct from females isolated from the same host, with female worms showing more specific fragments than males. Of the four host-derived schistosome populations, female and male adults recovered from TGFβRIIdn mice showed RAPD-PCR profiles that were most similar to each other. Altogether, these data indicate that host immunological backgrounds can influence the genetic diversity of parasite populations. PMID:24991919

  19. Bayesian Risk Mapping and Model-Based Estimation of Schistosoma haematobium–Schistosoma mansoni Co-distribution in Côte d′Ivoire

    PubMed Central

    Chammartin, Frédérique; Houngbedji, Clarisse A.; Hürlimann, Eveline; Yapi, Richard B.; Silué, Kigbafori D.; Soro, Gotianwa; Kouamé, Ferdinand N.; N′Goran, Eliézer K.; Utzinger, Jürg; Raso, Giovanna; Vounatsou, Penelope

    2014-01-01

    Background Schistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d′Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species. Methodology We analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d′Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium–S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines. Principal Findings We estimated that 8.9% of school-aged children in Côte d′Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country. Conclusions/Significance We provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d′Ivoire and a strong empirical basis for a rational targeting of control interventions. PMID:25522007

  20. Variations in helminth faecal egg counts in Kato-Katz thick smears and their implications in assessing infection status with Schistosoma mansoni.

    PubMed

    Berhe, Nega; Medhin, Girmay; Erko, Birhanu; Smith, Tara; Gedamu, Selamawitt; Bereded, Dereje; Moore, Rashida; Habte, Endashaw; Redda, Abraham; Gebre-Michael, Teshome; Gundersen, Svein Gunnar

    2004-01-01

    Examination of stool specimens by Kato-Katz (K-K) thick smears is the standard method recommended by the WHO for field diagnosis of intestinal schistosomiasis. However, there is increasing concern that this technique has low diagnostic sensitivity. In 326 study subjects, we compared the diagnostic yield of examining one, three or five Kato-Katz thick smears prepared from one stool specimen using 41.7 mg templates. In a subset of 169 subjects who had no demonstrable Schistosoma mansoni eggs in their first three Kato-Katz thick smears, we assessed the comparative advantage of examining an additional three Kato-Katz thick smears from another stool specimen, taken four weeks later, to that of cumulative yield obtained by examining all five Kato-Katz thick smears derived from the first stool specimen. For all helminth infections, single Kato-Katz thick smear-based prevalence estimates were significantly lower than those obtained from triplet or quintet Kato-Katz thick smears. Prevalence of S. mansoni infection based on single, triplet and quintet Kato-Katz thick smears from one stool specimen were 31.3%, 45.7% and 52.1%, respectively. Prevalence estimate of S. mansoni based on quintet Kato-Katz thick smears from the first day stool specimens was not different from cumulative estimate obtained with two triplet Kato-Katz thick smears from two stool specimens, 52.1% and 52.8%, respectively. In conclusion, either examination of quintet Kato-Katz thick smears from one stool specimen using 41.7 mg template or initial triplet Kato-Katz thick smears from one stool specimen, and if these are negative, followed by examination of additional triplet Kato-Katz thick smears from subsequent day stool specimen can adequately assess individuals for infection status with S. mansoni. PMID:15533288

  1. FoxP3+ T regulatory cells and immunomodulation after Schistosoma mansoni egg antigen immunization in experimental model of inflammatory bowel disease.

    PubMed

    Hasby, Eiman A; Hasby Saad, Marwa A; Shohieb, Zeinab; El Noby, Kholoud

    2015-05-01

    To assess the effect of Schistosoma mansoni egg antigen immunization on the immunomodulation in dextran sodium sulfate (DSS) induced colitis as an experimental model of IBD in comparison to non immunization and healthy control. The study was performed on 180 mice; 25 healthy control, 15 to identify the inflammatory peak of DSS, 25 received DSS for 7 days; 90 infected with S. mansoni cercariae to collect eggs for antigen preparation, and 25 immunized with the prepared antigen then received DSS course. Disease activity index, macroscopic & microscopic inflammatory scores, FoxP3+ T regulatory cell count, myeloperoxidase activity, and Th1/Th2 cytokine profile were compared in studied groups. Immunization induced both FoxP3+ T(regs) and Th2 cytokines to establish a state of immune homeostasis and create a quiescent steadier immune response to DSS. S. mansoni egg antigen succeeded in acting like a prophylactic helminthic therapy as it has a profitable modulatory effect on DSS-induced colitis model. PMID:25766778

  2. Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity

    SciTech Connect

    Ch'ang, L.Y.; Colley, D.G.

    1986-06-01

    Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy/sup -1 +/, Lyt/sup 1 +/, Lyt/sup 2 -/, surface Ig/sup -/ lymphocytes.

  3. Cross-Reactivity between Schistosoma mansoni Antigens and the Latex Allergen Hev b 7: Putative Implication of Cross-Reactive Carbohydrate Determinants (CCDs)

    PubMed Central

    Doenhoff, Michael J.; El-Faham, Marwa; Liddell, Susan; Fuller, Heidi R.; Stanley, Ronald G.; Schramm, Gabriele; Igetei, Joseph E.

    2016-01-01

    IgG antibodies produced by rabbits immunized against S. mansoni antigens cross-reacted with aqueous soluble constituents of a variety of allergens. The antibody cross-reactivity was largely sensitive to degradation by treatment of the target antigens with sodium meta-periodate, suggesting the cross-reactivity was due to carbohydrate determinants that were common to both the schistosome and the allergens (CCDs). The reaction between the rabbit antibodies and a 43 kDa molecule in a rubber latex extract was analysed further: tandem mass spectrometry identified the latex molecule as allergen Hev b 7. Rabbit anti-schistosome IgG antibodies purified by acid-elution from solid-phase latex Hev b 7 reacted with the S. mansoni egg antigens IPSE/alpha-1 and kappa-5 and cercarial antigens SPO-1 and a fatty acid-binding protein. Moreover, purified anti-S. mansoni egg, latex cross-reactive antibodies reacted with antigenic constituents of some fruits, a result of potential relevance to the latex-fruit syndrome of allergic reactions. We propose that IgG anti-schistosome antibodies that cross-react with allergens may be able to block IgE-induced allergic reactions and thus provide a possible explanation for the hygiene hypothesis. PMID:27467385

  4. In vivo immunomodulatory effects of Antrodia camphorata polysaccharides in a T1/T2 doubly transgenic mouse model for inhibiting infection of Schistosoma mansoni

    SciTech Connect

    Cheng, P.-C.; Hsu, C.-Y.; Chen, C.-C.; Lee, K.-M.

    2008-03-01

    Antrodia camphorata (A. camphorata) is a fungus commonly used for treatment of viral hepatitis and cancer in Chinese folk medicine. Extract of A. camphorate is reported to possess anti-inflammatory, antihepatitis B virus and anticancer activities. In this study, we tested the in vivo effects of polysaccharides derived from A. camphorata (AC-PS) on immune function by detection of cytokine expression and evaluation of the immune phenotype in a T1/T2 doubly transgenic mouse model. The protective effect of AC-PS in mice was tested by infection with Schistosoma mansoni. The induction of large amounts of IFN-{gamma}, IL-2 and TNF-a mRNA were detected after 2 and 4 weeks of oral AC-PS administration in BALB/c and C57BL/6 mice. In transgenic mice, 3 to 6 weeks of oral AC-PS administration increased the proportion of CD4{sup +} T cells and B cells within the spleen. More specifically, there was an increase of Th1 CD4{sup +} T cells and Be1 cells among spleen cells as observed by detection the of Type1/Type2 marker molecules. By using a disease model of parasitic infection, we found that AC-PS treatment inhibited infection with S. mansoni in BALB/C and C57BL/6 mice. AC-PS appears to influence the immune system of mice into developing Th1 responses and have potential for preventing infection with S. mansoni.

  5. Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1.

    PubMed

    Fonseca, Nayara Cristina; da Cruz, Luana Faria; da Silva Villela, Filipe; do Nascimento Pereira, Glaécia Aparecida; de Siqueira-Neto, Jair Lage; Kellar, Danielle; Suzuki, Brian M; Ray, Debalina; de Souza, Thiago Belarmino; Alves, Ricardo José; Sales Júnior, Policarpo Ademar; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; McKerrow, James H; Caffrey, Conor R; de Oliveira, Renata Barbosa; Ferreira, Rafaela Salgado

    2015-05-01

    The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤ 10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series. PMID:25712353

  6. Sustaining the Control of Schistosoma mansoni in Western Côte d'Ivoire: Baseline Findings Before the Implementation of a Randomized Trial.

    PubMed

    Assaré, Rufin K; Hürlimann, Eveline; Ouattara, Mamadou; N'Guessan, Nicaise A; Tian-Bi, Yves-Nathan T; Yapi, Ahoua; Yao, Patrick K; Coulibaly, Jean T; Knopp, Stefanie; N'Goran, Eliézer K; Utzinger, Jürg

    2016-02-01

    We report baseline findings before the implementation of a 4-year intervention trial designed to assess the impact of three different school-based treatment schedules with praziquantel to sustain the control of intestinal schistosomiasis. The baseline survey was conducted in 75 schools of western Côte d'Ivoire previously identified with moderate Schistosoma mansoni endemicity (prevalence: 10-24% in children aged 13-14 years). Three stool samples collected over consecutive days were subjected to duplicate Kato-Katz thick smears each. A questionnaire was administered to collect village-specific information that is relevant for schistosomiasis transmission. Overall, 4,953 first graders (aged 5-8 years) and 7,011 school children (aged 9-12 years) had complete parasitologic data. The overall prevalence of S. mansoni was 5.4% among first graders and 22.1% in 9- to 12-year-old children. Open defecation was practiced in all villages. The current baseline findings will be important to better understand the dynamics of S. mansoni prevalence and intensity over the course of this trial that might be governed by village characteristics and specific treatment interventions. PMID:26598571

  7. Predicting frequency distribution and influence of sociodemographic and behavioral risk factors of Schistosoma mansoni infection and analysis of co-infection with intestinal parasites.

    PubMed

    Rollemberg, Carla V V; Silva, Marília M B L; Rollemberg, Karla C; Amorim, Fábio R; Lessa, Nayanna M N; Santos, Marcos D S; Souza, Acácia M B; Melo, Enaldo V; Almeida, Roque P; Silva, Ângela M; Werneck, Guilherme L; Santos, Mario A; Almeida, José A P; Jesus, Amélia R

    2015-01-01

    Geospatial analysis was used to study the epidemiology of Schistosoma mansoni, intestinal parasites and co-infections in an area (Ilha das Flores) in Sergipe, Brazil. We collected individually georeferenced sociodemographic, behavioral and parasitological data from 500 subjects, analyzed them by conventional statistics, and produced risk maps by Kernel estimation. The prevalence rates found were: S. mansoni (24.0%), Trichuris trichiura (54.8%), Ascaris lumbricoides (49.2%), Hookworm (17.6%) and Entamoeba histolytica (7.0%). Only 59/500 (11.8%) individuals did not present any of these infections, whereas 279/500 (55.8%) were simultaneously infected by three or more parasites. We observed associations between S. mansoni infection and various variables such as male gender, being rice farmer or fisherman, low educational level, low income, water contact and drinking untreated water. The Kernel estimator indicated that high-risk areas coincide with the poorest regions of the villages as well as with the part of the villages without an adequate sewage system. We also noted associations between both A. lumbricoides and hookworm infections with low education and low income. A. lumbricoides infection and T. trichiura infection were both associated with drinking untreated water and residential open-air sewage. These findings call for an integrated approach to effectively control multiple parasitic infections. PMID:26054512

  8. Synthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity Relationship versus the Parasite Cysteine Proteases Rhodesain, Cruzain, and Schistosoma mansoni Cathepsin B1

    PubMed Central

    Fonseca, Nayara Cristina; da Cruz, Luana Faria; da Silva Villela, Filipe; do Nascimento Pereira, Glaécia Aparecida; de Siqueira-Neto, Jair Lage; Kellar, Danielle; Suzuki, Brian M.; Ray, Debalina; de Souza, Thiago Belarmino; Alves, Ricardo José; Júnior, Policarpo Ademar Sales; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; McKerrow, James H.; Caffrey, Conor R.; de Oliveira, Renata Barbosa

    2015-01-01

    The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series. PMID:25712353

  9. Molecular evidence supports an african affinity of the neotropical freshwater gastropod, Biomphalaria glabrata, say 1818, an intermediate host for Schistosoma mansoni.

    PubMed

    Campbell, G; Jones, C S; Lockyer, A E; Hughes, S; Brown, D; Noble, L R; Rollinson, D

    2000-12-01

    Freshwater snails of the genus Biomphalaria, Preston 1910, are the most important and widely distributed intermediate hosts of Schistosoma mansoni, the blood fluke responsible for human intestinal schistosomiasis, in Africa and the Neotropics. S. mansoni is thought to have been imported repeatedly into the Americas during the last 500 years with the African slave trade. Surprisingly considering that the New and Old World separated 95-106 million years (Myr) ago, the disease rapidly became established due to the presence of endemic susceptible hosts. Reconstructing the phylogenetic relationships within Biomphalaria may provide insights into the successful intercontinental spread of S. mansoni. Parsimony and distance analyses of mitochondrial and nuclear sequences show African taxa to be monophyletic and Neotropical species paraphyletic, with Biomphalaria glabrata forming a separate clade from other Neotropical Biomphalaria, and ancestral to the African taxa. A west to east trans-Atlantic dispersal of a B. glabrata-like taxon, possibly as recently as the Plio-Pleistocene (1.8-3.6 Myr ago) according to a general mitochondrial clock, would fit these observations. Vicariance or an African origin for B. glabrata followed by multiple introductions to South America over the past 500 years with the African slave trade seem unlikely explanations. Knowledge of the phylogenetic relationships among important intermediate host species may prove useful in furthering control measures which exploit genetic differences in susceptibility to parasites, and in elucidating the evolution of schistosome resistance. PMID:11133023

  10. Monoclonal antibody-based dipstick assay: a reliable field applicable technique for diagnosis of Schistosoma mansoni infection using human serum and urine samples.

    PubMed

    Demerdash, Zeinab; Mohamed, Salwa; Hendawy, Mohamed; Rabia, Ibrahim; Attia, Mohy; Shaker, Zeinab; Diab, Tarek M

    2013-02-01

    A field applicable diagnostic technique, the dipstick assay, was evaluated for its sensitivity and specificity in diagnosing human Schistosoma mansoni infection. A monoclonal antibody (mAb) against S. mansoni adult worm tegumental antigen (AWTA) was employed in dipstick and sandwich ELISA for detection of circulating schistosome antigen (CSA) in both serum and urine samples. Based on clinical and parasitological examinations, 60 S. mansoni-infected patients, 30 patients infected with parasites other than schistosomiasis, and 30 uninfected healthy individuals were selected. The sensitivity and specificity of dipstick assay in urine samples were 86.7% and 90.0%, respectively, compared to 90.0% sensitivity and 91.7% specificity of sandwich ELISA. In serum samples, the sensitivity and specificity were 88.3% and 91.7% for dipstick assay vs. 91.7% and 95.0% for sandwich ELISA, respectively. The diagnostic efficacy of dipstick assay in urine and serum samples was 88.3% and 90.0%, while it was 90.8% and 93.3% for sandwich ELISA, respectively. The diagnostic indices of dipstick assay and ELISA either in serum or in urine were statistically comparable (P>0.05). In conclusion, the dipstick assay offers an alternative simple, rapid, non-invasive technique in detecting CSA or complement to stool examinations especially in field studies. PMID:23467705

  11. Cross-Reactivity between Schistosoma mansoni Antigens and the Latex Allergen Hev b 7: Putative Implication of Cross-Reactive Carbohydrate Determinants (CCDs).

    PubMed

    Doenhoff, Michael J; El-Faham, Marwa; Liddell, Susan; Fuller, Heidi R; Stanley, Ronald G; Schramm, Gabriele; Igetei, Joseph E

    2016-01-01

    IgG antibodies produced by rabbits immunized against S. mansoni antigens cross-reacted with aqueous soluble constituents of a variety of allergens. The antibody cross-reactivity was largely sensitive to degradation by treatment of the target antigens with sodium meta-periodate, suggesting the cross-reactivity was due to carbohydrate determinants that were common to both the schistosome and the allergens (CCDs). The reaction between the rabbit antibodies and a 43 kDa molecule in a rubber latex extract was analysed further: tandem mass spectrometry identified the latex molecule as allergen Hev b 7. Rabbit anti-schistosome IgG antibodies purified by acid-elution from solid-phase latex Hev b 7 reacted with the S. mansoni egg antigens IPSE/alpha-1 and kappa-5 and cercarial antigens SPO-1 and a fatty acid-binding protein. Moreover, purified anti-S. mansoni egg, latex cross-reactive antibodies reacted with antigenic constituents of some fruits, a result of potential relevance to the latex-fruit syndrome of allergic reactions. We propose that IgG anti-schistosome antibodies that cross-react with allergens may be able to block IgE-induced allergic reactions and thus provide a possible explanation for the hygiene hypothesis. PMID:27467385

  12. Epidemiology of Schistosoma mansoni infection and its relationship to snail distribution in a village at the Nile bank south to Cairo.

    PubMed

    Sayed, Hanan A; El-Ayyat, Afaf; Kader, Ahmed Abdel; Sabry, Hoda Y; Amer, Neimat M

    2004-01-01

    The relationship between epidemiology of S. mansoni infection and snail distribution at a village, related to Guiza Governorate and lies south to Cairo, was investigated. A systematic random sample of houses was selected. All inhabitants of the houses were invited to share in the study. The Number examined was 704. Urine and stools were examined using Nucleopore filtration and standard Kato-Katz techniques, respectively. Snail collection was done from 35 sites along the water bodies related to the village. Snails collected were examined by cercariae shedding under light. Snail differentiation was done. The results showed that the prevalence of Schistosoma mansoni human infection was 25.1 % and GMEC was 2.4 +/- 5.5. Schistosoma haematobium infection was zero percent. Biomphlaria alexandrina snail infection rate was 3.7% with density equal 0.5 +/- 1.3. Bulinus truncatus snail infection rate was zero percent. The pattern of S. mansoni human infection was closely related to snail distribution and infection. Presence of a hybrid species of B. alexandrina and B. glabrata may explain the epidemiological pattern found in the studied village. PMID:16916052

  13. Fecal Occult Blood and Fecal Calprotectin as Point-of-Care Markers of Intestinal Morbidity in Ugandan Children with Schistosoma mansoni Infection

    PubMed Central

    Bustinduy, Amaya L.; Sousa-Figueiredo, José C.; Adriko, Moses; Betson, Martha; Fenwick, Alan; Kabatereine, Narcis; Stothard, J. Russell

    2013-01-01

    Background Calprotectin is a calcium-binding cytoplasmic protein found in neutrophils and increasingly used as a marker of bowel inflammation. Fecal occult blood (FOB) is also a dependable indicator of bowel morbidity. The objective of our study was to determine the applicability of these tests as surrogate markers of Schistosoma mansoni intestinal morbidity before and after treatment with praziquantel (PZQ). Methods 216 children (ages 3–9 years old) from Buliisa District in Lake Albert, Uganda were examined and treated with PZQ at baseline in October 2012 with 211 of them re-examined 24 days later for S. mansoni and other soil transmitted helminths (STH). POC calprotectin and FOB assays were performed at both time points on a subset of children. Associations between the test results and infection were analysed by logistic regression. Results Fecal calprotectin concentrations of 150–300 µg/g were associated with S. mansoni egg patent infection both at baseline and follow up (OR: 12.5 P = 0.05; OR: 6.8 P = 0.02). FOB had a very strong association with baseline anemia (OR: 9.2 P = 0.03) and medium and high egg intensity schistosomiasis at follow up (OR: 6.6 P = 0.03; OR: 51.3 P = 0.003). Both tests were strongly associated with heavy intensity S. mansoni infections. There was a significant decrease in FOB and calprotectin test positivity after PZQ treatment in those children who had egg patent schistosomiasis at baseline. Conclusions Both FOB and calprotectin rapid assays were found to correlate positively and strongly with egg patent S. mansoni infection with a positive ameloriation response after PZQ treatment indicative of short term reversion of morbidity. Both tests were appropriate for use in the field with excellent operational performance and reliability. Due to its lower-cost which makes its scale-up of use affordable, FOB could be immediately adopted as a monitoring tool for PC campaigns for efficacy evaluation before and after

  14. Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

    PubMed Central

    Lamberton, Poppy H. L.; Kabatereine, Narcis B.; Oguttu, David W.; Fenwick, Alan; Webster, Joanne P.

    2014-01-01

    Background Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings. Method/Principle Findings In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive. Conclusions

  15. Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment

    PubMed Central

    Chalmers, Iain W.; Fitzsimmons, Colin M.; Brown, Martha; Pierrot, Christine; Jones, Frances M.; Wawrzyniak, Jakub M.; Fernandez-Fuentes, Narcis; Tukahebwa, Edridah M.; Dunne, David W.; Khalife, Jamal; Hoffmann, Karl F.

    2015-01-01

    Background The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored. Methodology/Principal Findings Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0

  16. Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection

    PubMed Central

    2013-01-01

    Background Hepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The demonstration of the pro-fibrogenic role of angiotensin (Ang) II in chronic liver disease brought up the idea that anti-Ang II agents may be effective in improving hepatic fibrosis by either blocking Ang II type 1 (AT1) receptors or inhibiting the angiotensin converting enzyme. Peroxisome proliferator-activated receptors gamma (PPARγ) activation has been also shown to inhibit hepatic stellate cell activation and progression of fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice. Methods To achieve the aim of the study, two sets of experiments were performed in which telmisartan was initiated at the 5th (set 1) and the 10th (set 2) weeks post infection to assess drug efficacy in both acute and chronic stages of liver fibrosis, respectively. Schistosoma mansoni-infected mice were randomly divided into the following four groups: infected-control (I), telmisartan-treated (II), PZQ-treated (III), and telmisartan+PZQ-treated (IV). In addition, a normal non-infected group was used for comparison. Parasitological (hepatomesenteric worm load and oogram pattern), histopathological, morphometric, immunohistochemical (hepatic expressions of matrix metalloproteinase-2; MMP-2 and tissue inhibitor of metalloproteinase-2; TIMP-2), and biochemical (serum transforming growth factor beta 1; TGF-β1 and liver function tests) studies were performed. Results Telmisartan failed to improve the parasitological parameters, while it significantly (P<0.05) decreased the mean granuloma diameter, area of fibrosis, and serum TGF-β1. Additionally, telmisartan increased MMP-2 and decreased TIMP-2 hepatic expression. Combined treatment

  17. Factors associated with schistosomiasis mansoni in a population from the municipality of Jaboticatubas, State of Minas Gerais, Brazil.

    PubMed

    Massara, Cristiano Lara; Peixoto, Sérgio Viana; Barros, Héliton da Silva; Enk, Martin Johannes; Carvalho, Omar dos Santos; Schall, Virgínia

    2004-01-01

    Jaboticatubas is a municipality in the metropolitan region of Belo Horizonte which has been a target of a wide media release as "the capital of schistosomiasis" since the 1960's. In order to give support to a work based on an integrated control, we sought to identify the disease determinants at the site. A transversal study was carried out aimed at identifying prevalence rates of the disease and factors associated with the infection in the district of São José de Almeida, and two close localities, Cipó Velho and São José da Serra, all of them located in the municipality of Jaboticatubas. A parasitological survey was performed, applying the Kato-Katz method with two slides per sample in 1186 schoolchildren which represents 77% of all registered pupils in four public schools in 2001. Among these schoolchildren a number of 101 (8.6%) proved positive for Schistosoma mansoni eggs in their stool samples. A total of 64 families, whose schoolchildren had shown to be positive for schistosomiasis, also undertook examinations. As negative control, a random sample was collected from the 206 families, whose children had proven negative for schistosomiasis. The prevalence among 270 families (1304 people) was 12%. To assess those who continued to have contact with possibly contaminated water, 1061 (81.4%) people of the 270 families were interviewed. A multivariate analysis identified the following factors associated with the infection: time of residence in the area (short period), garbage disposal (use of deserted areas), gender (male), age (from 10 to 29 years), and water contact (daily and weekly). Further analysis of these factors revealed a close correlation between water contact and the disease, with a positive significant frequency concerning almost all those items. Depending on gender and age significant variations of water contact patterns associated with leisure and professional activities were found. A malacological survey on water collections in the area

  18. Cloning of a cDNA encoding a surface antigen of Schistosoma mansoni schistosomula recognized by sera of vassinated mice

    SciTech Connect

    Dalton, J.P.; Tom, T.D.; Strand, M.

    1987-06-01

    Spleen cells of mice vaccinated with radiation-attenuated Schistosoma mansoni cercariae were used to produce monoclonal antibodies directed against newly transformed schistosomular surface antigens. One of these monoclonal antibodies recognized a polypeptide of 18 kDa. Binding was measured by radioimmunoassay. This glycoprotein was purified by monoclonal antibody immunoaffinity chromatography and a polyclonal antiserum was prepared against it. Immunofluorescence assays showed that the polyclonal antiserum bound to the surface of newly transformed schistosomula and lung-stage organisms but not to the surface of liver-stage and adult worms. Using this polyclonal antiserum we isolated recombinant clones from an adult worm cDNA expression library constructed in lambdagt11. Clone 654.2 contained an insert of 0.52 kilobase and hybridized to a 1.2-kilobase mRNA species from adult worms. Most importantly, clone 654.2 produced a fusion protein of 125 kDa that was reactive with sera of vaccinated mice that are capable of transferring resistance. This result encourages future vaccination trials with the fusion protein.

  19. Schistosoma mansoni: radiation dose and morphologic integrity of schistosomules as factors for an effective cryopreserved live vaccine

    SciTech Connect

    Lewis, F.A.; Stirewalt, M.; Leef, J.L.

    1984-01-01

    The effectiveness of a cryopreserved, irradiated schistosomule vaccine against an homologous Schistosoma mansoni cercarial challenge was tested in C57B1/6 mice. Highly significant levels of protection developed consistently when mice were immunized with the vaccine irradiated at 10-20 Krad, i.e., doses below that considered optimal for irradiated cercariae (50 Krad). Cryopreserved schistosomules irradiated at 10 or 20 Krad induced greater levels of protection than did schistosomules irradiated at 2, 5, 30, or 50 Krad. Protective immunity developed as early as 3 weeks post-immunization. When immunizing inocula were injected at various times post-thaw, or when schistosomule subpopulations of normal-appearing, damaged or dead organisms were injected, those populations which had appeared to sustain the least degree of damage were those most capable of stimulating protective immunity. These findings highlight the hazards of extrapolating conditions considered standard for an irradiated cercarial vaccine to one in which cryopreservation, for storage of the schistosomules, is an added stress.

  20. Evidence against the existence of specific Schistosoma mansoni subpopulations which are resistant to irradiated vaccine-induced immunity

    SciTech Connect

    Lewis, F.A.; Hieny, S.; Sher, A.

    1985-01-01

    When mice are immunized with irradiated Schistosoma mansoni cercariae a proportion of the subsequent cercarial challenge always escapes killing and matures to egg-laying adults. This report investigates the possibility that incomplete immunity in this system is governed by a genetically-determined insusceptibility of a particular schistosome subpopulation. To do this the authors tested whether more immunoresistant schistosomes would develop following successive passages of progeny of the resistant worms through immunized mice. Mice were immunized with 500 50 Krad-irradiated cercariae, and challenged with normal cercariae when immunity was at its peak. After five successive passages through snails and immune mice, progeny of those parasites which escaped immune killing were no more refractory to vaccine-induced resistance than the original stock maintained in nonimmune mice. Additionally, the passaged isolates did not differ from the original stock in their ability to induce protection following irradiation. The results indicate that with this model of acquired resistance incomplete immunity is unlikely to be due to a subpopulation of the parasites possessing a genetically-determined insusceptibility to killing.

  1. In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni.

    PubMed

    Neves, Bruno J; Braga, Rodolpho C; Bezerra, José C B; Cravo, Pedro V L; Andrade, Carolina H

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

  2. Factors associated with Schistosoma mansoni infection 5 years after selective treatment in a low endemic area in Brazil.

    PubMed

    Disch, Jolande; Katz, Naftale; Pereira e Silva, Yerkes; de Gouvêa Viana, Luciana; Andrade, Marcela Orsini; Rabello, Ana

    2002-02-01

    Five years after a single dose treatment, prevalence, intensity and morbidity of schistosomiasis mansoni were evaluated in Agua Branca, a low endemic community in the South East Brazil (cure rate 94%). At community level, prevalence showed a decrease from 38.9 to 24.5% and the intensity of infection dropped from 119.5 to 38.9 eggs per g of faeces (epg). However, after the exclusion of immigrants, newborn children and individuals that had left the area after the first evaluation, the prevalence among the treated and followed population was not significantly affected. Multivariate analysis showed that the 10-29 age group and water contact for agricultural purposes were independently associated with the presence of infection on post treatment evaluation [OR 3.9 and 5.09, respectively]. A previous treatment among subjects older than 15 years was inversely associated [OR 0.58]. The authors wish to draw attention to the fact that mobility may lead to a serious bias in evaluating the impact of the control programme. PMID:11801220

  3. Ionotropic Receptors Identified within the Tentacle of the Freshwater Snail Biomphalaria glabrata, an Intermediate Host of Schistosoma mansoni.

    PubMed

    Liang, Di; Wang, Tianfang; Rotgans, Bronwyn A; McManus, Donald P; Cummins, Scott F

    2016-01-01

    Biomphalaria glabrata (B. glabrata) is an air-breathing aquatic mollusc found in freshwater habitats across the Western Hemisphere. It is most well-known for its recognized capacity to act as a major intermediate host for Schistosoma mansoni, the human blood fluke parasite. Ionotropic receptors (IRs), a variant family of the ionotropic glutamate receptors (iGluR), have an evolutionary ancient function in detecting odors to initiate chemosensory signaling. In this study, we applied an array of methods towards the goal of identifying IR-like family members in B. glabrata, ultimately revealing two types, the iGluR and IR. Sequence alignment showed that three ligand-binding residues are conserved in most Biomphalaria iGluR sequences, while the IRs did exhibit a variable pattern, lacking some or all known glutamate-interactingresidues, supporting their distinct classification from the iGluRs. We show that B. glabrata contains 7 putative IRs, some of which are expressed within its chemosensory organs. To further investigate a role for the more ancient IR25a type in chemoreception, we tested its spatial distribution pattern within the snail cephalic tentacle by in situ hybridization. The presence of IR25a within presumptive sensory neurons supports a role for this receptor in olfactory processing, contributing to our understanding of the molecular pathways that are involved in Biomphalaria olfactory processing. PMID:27253696

  4. Role of antibody dependent cell mediated cytotoxicity (ADCC) in Sm-p80-mediated protection against Schistosoma mansoni

    PubMed Central

    Torben, Workineh; Ahmad, Gul; Zhang, Weidong; Nash, Stewart; Le, Loc; Karmakar, Souvik; Siddiqui, Afzal A.

    2012-01-01

    Schistosomiasis is a major health problem in the developing world and for international travelers to the endemic countries. Existing strategies to control schistosomiasis have had limited successes so far. The addition of an effective vaccine in existing control measures would be greatly beneficial in reducing the impact of the disease. In this regard, Sm-p80 mediated protection against intestinal schistosomiasis caused by Schistosoma mansoni has been observed to be promising in two animal models of infection and disease. In this study, the role of antibody dependent cell mediated cytotoxcity (ADCC) was deciphered in Sm-p80-mediated protection especially in the elimination of lung stage schistosomula. This was achieved using lung lavage cells and lung cells that were isolated from mice immunized with and without Sm-p80 formulated in a recombinant vaccine formulation. Significant differences were observed in cytotoxicity assays using immune sera with the lung lavage cells which showed 51% more killing of schistosomula and elevated levels of nitric oxide in the supernatants were detected compared to controls. PMID:23000221

  5. The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni*

    PubMed Central

    Merceron, Romain; Awama, Ayman M.; Montserret, Roland; Marcillat, Olivier; Gouet, Patrice

    2015-01-01

    The taurocyamine kinase from the blood fluke Schistosoma mansoni (SmTK) belongs to the phosphagen kinase (PK) family and catalyzes the reversible Mg2+-dependent transfer of a phosphoryl group between ATP and taurocyamine. SmTK is derived from gene duplication, as are all known trematode TKs. Our crystallographic study of SmTK reveals the first atomic structure of both a TK and a PK with a bilobal structure. The two unliganded lobes present a canonical open conformation and interact via their respective C- and N-terminal domains at a helix-mediated interface. This spatial arrangement differs from that observed in true dimeric PKs, in which both N-terminal domains make contact. Our structures of SmTK complexed with taurocyamine or l-arginine compounds explain the mechanism by which an arginine residue of the phosphagen specificity loop is crucial for substrate specificity. An SmTK crystal was soaked with the dead end transition state analog (TSA) components taurocyamine-NO32−-MgADP. One SmTK monomer was observed with two bound TSAs and an asymmetric conformation, with the first lobe semiclosed and the second closed. However, isothermal titration calorimetry and enzyme kinetics experiments showed that the two lobes function independently. A small angle x-ray scattering model of SmTK-TSA in solution with two closed active sites was generated. PMID:25837252

  6. In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

    PubMed Central

    Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

  7. Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis.

    PubMed

    Heimburg, Tino; Chakrabarti, Alokta; Lancelot, Julien; Marek, Martin; Melesina, Jelena; Hauser, Alexander-Thomas; Shaik, Tajith B; Duclaud, Sylvie; Robaa, Dina; Erdmann, Frank; Schmidt, Matthias; Romier, Christophe; Pierce, Raymond J; Jung, Manfred; Sippl, Wolfgang

    2016-03-24

    Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (1 and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture. PMID:26937828

  8. Schistosoma mansoni: is acquired immunity induced by highly x-irradiated cercariae dependent on the size of the challenging dose

    SciTech Connect

    Hsue, S.Y.; Hsue, H.F.; Osborne, J.W.; Johnson, S.C.

    1982-04-01

    A high degree of immunity, as shown by a 91% reduction of the number of worms recovered was found in five groups of mice that were immunized five times with highly X-irradiated cercariae and then challenged with 10, 20, 50, 100, or 500 normal Schistosoma mansoni cercariae. The results indicated that there were no significant differences in worm reduction in immunized mice challenged with different numbers of cercariae; consequently the immunity induced by this immunization method did not appear to be challenge-dose-dependent. However, the results also showed that when immunized mice were challenged with 500, 100, 50, 20, and 10 cercariae, 0, 13, 26, 56, and 68%, respectively, of the experimental animals were free of worms. Thus, the percentage of worm-negative cases increased as the number of challenge cercariae decreased. When viewed in this manner, the acquired immunity may be considered challenge-dose-dependent as well. If this method of vaccination is used for schistosomiasis control, we may anticipate that in both hypo- and hyperendemic areas, the intensity of infection and the severity of the disease will be reduced owing to a reduction in worms burdens, and in hypoendemic areas, there will be a number of worm-free cases.

  9. Major role for carbohydrate epitopes preferentially recognized by chronically infected mice in the determination of Schistosoma mansoni schistosomulum surface antigenicity

    SciTech Connect

    Omer-ali, P.; Magee, A.I.; Kelly, C.; Simpson, A.J.G.

    1986-12-01

    A radioimmunoassay that makes use of whole Schistosomula and /sup 125/I-labeled protein A has been used to characterize and to quantify the binding of antisera to the surface of 3 hr mechanically transformed schistosomula of Schistosoma mansoni. This technique facilitates the determination of epitopes on the schistosomula in addition to those detected by surface labeling and immunoprecipitation. By using this technique, it has been demonstrated that there is a much greater binding to the parasite surface of antibodies from chronically infected mice (CMS) than of antibodies from mice infected with highly irradiated cercariae (VMS), and CMS recognizes epitopes that VMS does not. Treatment of the surface of the schistosomula with trifluoromethanesulphonic acid and sodium metaperiodate has suggested that the discrepancy of the binding between the two sera is due to the recognition of a large number of additional epitopes by CMS, which are carbohydrate in nature. Some of the carbohydrate epitopes are expressed on the previously described surface glycoprotein antigens of M/sub r/ 200,000, 38,000, and 17,000.

  10. Evaluation of lung recovery assay for schistosomula in mice immunized with x-irradiated cercariae of Schistosoma mansoni.

    PubMed

    Hsü, S Y; Hsü, H F; Burmeister, L F; Osborne, J W

    1979-09-01

    The lung recovery assay for schistosomula has recently been used as a rapid method for measuring the state of immunity of a challenged animal. Its merit rests on the fact that the peak day of schistosomular recovery in the lungs of both normal and immune hosts falls on the same day and the degree of immunity can be measured by the percent of schistosomular recovery on this particular day. An evaluation of this method for mice immunized with highly X-irradiated cercariae of Schistosoma mansoni was made. The results indicate that in the immunized mice the peak day for the schistosomular recovery was delayed and the number of schistosomula recovered on the peak day was decreased. The delay of the peak day was increased by the degree of host immunity, so its identification for a host of an unknown immunologic status was not a simple matter. In addition, this method measured only the immune effect which took place in the skin and on prepeak days in the lungs. It was not as competent as the conventional liver perfusion method which measures the total result of the immune effect of the skin, lungs, and liver. Our conclusion is that for measuring the immunizing effect of irradiated cercariae, the lung recovery method is not suitable for the determination of the state of immunity induced. PMID:395784

  11. Ionotropic Receptors Identified within the Tentacle of the Freshwater Snail Biomphalaria glabrata, an Intermediate Host of Schistosoma mansoni

    PubMed Central

    Liang, Di; Wang, Tianfang; Rotgans, Bronwyn A.; McManus, Donald P.; Cummins, Scott F.

    2016-01-01

    Biomphalaria glabrata (B. glabrata) is an air-breathing aquatic mollusc found in freshwater habitats across the Western Hemisphere. It is most well-known for its recognized capacity to act as a major intermediate host for Schistosoma mansoni, the human blood fluke parasite. Ionotropic receptors (IRs), a variant family of the ionotropic glutamate receptors (iGluR), have an evolutionary ancient function in detecting odors to initiate chemosensory signaling. In this study, we applied an array of methods towards the goal of identifying IR-like family members in B. glabrata, ultimately revealing two types, the iGluR and IR. Sequence alignment showed that three ligand-binding residues are conserved in most Biomphalaria iGluR sequences, while the IRs did exhibit a variable pattern, lacking some or all known glutamate-interactingresidues, supporting their distinct classification from the iGluRs. We show that B. glabrata contains 7 putative IRs, some of which are expressed within its chemosensory organs. To further investigate a role for the more ancient IR25a type in chemoreception, we tested its spatial distribution pattern within the snail cephalic tentacle by in situ hybridization. The presence of IR25a within presumptive sensory neurons supports a role for this receptor in olfactory processing, contributing to our understanding of the molecular pathways that are involved in Biomphalaria olfactory processing. PMID:27253696

  12. Inhibitory activities of the marine streptomycete-derived compound SF2446A2 against Chlamydia trachomatis and Schistosoma mansoni.

    PubMed

    Reimer, Anastasija; Blohm, Ariane; Quack, Thomas; Grevelding, Christoph G; Kozjak-Pavlovic, Vera; Rudel, Thomas; Hentschel, Ute; Abdelmohsen, Usama Ramadan

    2015-11-01

    Infectious diseases caused by chlamydia or schistosomes are a major health problem worldwide, and particularly so in developing countries. The lack of appropriate vaccines renders the search for potent natural products against these disease-causing agents an urgent endeavor. Sponge-associated actinomycetes represent a rich reservoir for natural products. Among them, members of the genus Streptomyces are capable of synthesizing an impressive array of diverse natural products with a wide variety of biological activities. The naphthacene glycoside SF2446A2 was isolated from the calcium alginate beads culture of Streptomyces sp. strain RV15 that had originally been obtained from the Mediterranean sponge Dysidea tupha. Its structure was identified by spectroscopic analysis and MS and comparison with the literature data. SF2446A2 showed inhibitory activity against Chlamydia trachomatis and was able to inhibit the primary infection in a dose-dependent manner, as well as progeny formation. Moreover, it caused disruptive effects on the surface area of Schistosoma mansoni and affected the gonads by impairing oogenesis and spermatogenesis. Our current study demonstrates that sponge-associated actinomycetes are capable of providing compounds with new pharmacological activities and with relevance to drug discovery. PMID:25990954

  13. Efficient trans-cleavage by the Schistosoma mansoni SMα1 hammerhead ribozyme in the extreme thermophile Thermus thermophilus

    PubMed Central

    Vazquez-Tello, Alejandro; Castán, Pablo; Moreno, Renata; Smith, James M.; Berenguer, José; Cedergren, Robert

    2002-01-01

    The catalytic hammerhead structure has been found in association with repetitive DNA from several animals, including salamanders, crickets and schistosomes, and functions to process in cis the long multimer transcripts into monomer RNA in vivo. The cellular role of these repetitive elements and their transcripts is unknown. Moreover, none of these natural hammerheads have been shown to trans-cleave a host mRNA in vivo. We analyzed the cis- and trans-cleavage properties of the hammerhead ribozyme associated with the SMα DNA family from the human parasite Schistosoma mansoni. The efficiency of trans-cleavage of a target RNA in vitro was affected mainly by both the temperature-dependent chemical step and the ribozyme–product dissociation step. The optimal temperature for trans-cleavage was 70°C. This result was confirmed when both the SMα1 ribozyme and the target RNA were expressed in the extreme thermophile Thermus thermophilus. Moreover, SMα1 RNA showed a remarkable thermostability, equal or superior to that of the most stable RNAs in this species, suggesting that SMα1 RNA has been selected for stability. Computer analysis predicts that the monomer and multimer transcripts fold into highly compact secondary structures, which may explain their exceptional stability in vivo. PMID:11917021

  14. Screening the Schistosoma mansoni transcriptome for genes differentially expressed in the schistosomulum stage in search for vaccine candidates.

    PubMed

    Farias, Leonardo P; Tararam, Cibele A; Miyasato, Patricia A; Nishiyama, Milton Y; Oliveira, Katia C; Kawano, Toshie; Verjovski-Almeida, Sergio; Leite, Luciana Cezar de Cerqueira

    2011-01-01

    Schistosomiasis affects more than 200 million people worldwide; another 600 million are at risk of infection. The schistosomulum stage is believed to be the target of protective immunity in the attenuated cercaria vaccine model. In an attempt to identify genes up-regulated in the schistosomulum stage in relation to cercaria, we explored the Schistosoma mansoni transcriptome by looking at the relative frequency of reads in EST libraries from both stages. The 400 genes potentially up-regulated in schistosomula were analyzed as to their Gene Ontology categorization, and we have focused on those encoding-predicted proteins with no similarity to proteins of other organisms, assuming they could be parasite-specific proteins important for survival in the host. Up-regulation in schistosomulum relative to cercaria was validated with real-time reverse transcription polymerase chain reaction (RT-PCR) for five out of nine selected genes (56%). We tested their protective potential in mice through immunization with DNA vaccines followed by a parasite challenge. Worm burden reductions of 16-17% were observed for one of them, indicating its protective potential. Our results demonstrate the value and caveats of using stage-associated frequency of ESTs as an indication of differential expression coupled to DNA vaccine screening in the identification of novel proteins to be further investigated as potential vaccine candidates. PMID:20852890

  15. Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment.

    PubMed

    Pica-Mattoccia, Livia; Cioli, Donato

    2004-03-29

    The efficacy of praziquantel against a Puerto Rican strain of Schistosoma mansoni was assessed using both in vivo and in vitro approach. The drug effective dose (50%) in the infected mouse model was about 30 times higher when determined against 28-day-old infections than against 7-week-old parasites. Single-sex female infections were also largely refractory to treatment and single-sex male infections moderately refractory, in comparison with bisexual infections. The in vitro approach consisted of overnight exposure of parasite cultures to various drug concentrations, followed by several days of culture in drug-free medium. In vitro results confirmed in vivo data and allowed for the observation of schistosome morphological phenomena after praziquantel exposure. Early worm contraction was observed in all cases, even after exposure to sub-lethal concentrations of praziquantel or upon exposure of the largely refractory 28-day-old schistosomes. In these instances, however, worms resumed movements and normal shape upon drug removal and were able to survive. The inference of these observations on the clinical use of praziquantel and on its mechanism of action is discussed. PMID:15013742

  16. Flow-cytometric evaluation of lymphocyte subpopulations in synchronously developing Schistosoma mansoni egg and Sephadex bead pulmonary granulomas.

    PubMed Central

    Remick, D. G.; Chensue, S. W.; Hiserodt, J. C.; Higashi, G. I.; Kunkel, S. L.

    1988-01-01

    Synchronous models of T-cell-mediated and foreign body granulomas were induced in mice by intravenous embolization of Schistosoma mansoni eggs and Sephadex beads, respectively. The authors then performed flow-cytometric analysis of lymphocytes from dispersed granulomas, spleens, and peripheral blood at 4, 8, 16, and 32 days corresponding to the induction, growth, and maintenance, and resolution of these lesions. Lymphocytes were identified on the basis of light scatter characteristics, and the nature of the cells was confirmed by cell sorting and electron-microscopic examination. Lymphocyte subpopulations were characterized with antibodies to lymphocyte surface markers, specifically Ig, Thy 1.2, Lyt 1, Lyt 2, and L3T4. Natural killer cells were identified with anti-asialo GM1. Egg-induced granulomas had more lymphocytes of all phenotypes at all time points. Surprisingly, there was a significant number of cells staining positive for asialo GM1. On Day 16 after embolization there was a greater percentage of helper T cells, as defined by positive staining with L3T4, in the egg model, compared with the bead model. There was no obvious shift of lymphocytes from either the blood or spleen into the granuloma. These data confirm the importance of T cells in the direct participation of granulomatous inflammation, and the large numbers of asialo GM1-positive cells suggest a role for natural killer cells. Images Figure 4 PMID:2451888

  17. Degradation of extracellular matrix by larvae of Schistosoma mansoni. II. Degradation by newly transformed and developing schistosomula

    SciTech Connect

    Keene, W.E.; Jeong, K.H.; McKerrow, J.H.; Werb, Z.

    1983-01-01

    The ability of schistosomula of Schistosoma mansoni to degrade an extracellular connective tissue matrix synthesized by rat vascular smooth muscle cells in culture was investigated. Six to 12% of the total matrix was degraded by schistosomula from the time of transformation from cercariae to adult development in vitro. Most matrix degradation occurred during the first 24 hours of incubation and was dependent on the number of schistosomula and the type of medium in which they were incubated. The use of proteinase inhibitors indicated that schistosomula activity was distinctly different from that of cercariae. Newly transformed schistosomula expressed one activity that was similar in inhibition characteristics to that of cercarial preacetabular gland secretions and another activity that was unique to schistosomula. From 1 day after transformation to adulthood, the schistosomula-derived activity was the predominant activity detected. Schistosomula degraded a smaller percentage of the total matrix than did cercariae and showed a different substrate profile. Schistosomula degraded glycoprotein components of extracellular matrix but showed little or no activity against elastin or collagen. Matrix-degrading activity was also detected in schistosomula-conditioned medium. Sedimentation of the activity and lack of permeability through filter barriers suggest that the enzyme may be initially associated with membrane and then sloughed with membrane fragments. Since the schistosomula-derived activity initially overlaps with cercarial preacetabular gland proteolytic activity, the two activities may act in concert to facilitate skin penetration by newly transformed schistosomula. However, schistosomula activity probably serves some, as yet undetermined, function later in development.

  18. Schistosoma haematobium hotspots in south Nyanza, western Kenya: prevalence, distribution and co-endemicity with Schistosoma mansoni and soil-transmitted helminths

    PubMed Central

    2014-01-01

    Background Schistosomiasis studies in western Kenya have mainly focused on the intestinal form, with evidence of urinary schistosomiasis remaining anecdotal. Detailed disease mapping has been carried out predominantly along the shores of Lake Victoria, but there is a paucity of information on intestinal and urinary schistosomiasis in inland sites. Methods This cross-sectional survey of 3,487 children aged 7–18 years from 95 schools in south Nyanza, western Kenya determined the prevalence, infection intensity, and geographical distribution of Schistosoma haematobium, evaluating its co-endemicity with Schistosoma mansoni and soil-transmitted helminths (STHs). Helminth eggs were analyzed from single urine (for S. haematobium) and stool (for S. mansoni and STHs) samples by centrifugation and Kato-Katz, respectively. Hematuria was used as a proxy indicator for S. haematobium. Schools and water bodies (ponds, water-points, streams, dams and rivers) were mapped using Geographical Information System and prevalence maps obtained using ArcView GIS Software. Results S. haematobium infections with an overall prevalence of 9.3% (95% CI = 8.4-10.2%) were mostly prevalent in Rachuonyo, 22.4% (95% CI = 19.2-25.9% and 19.7 eggs/10 ml) and Migori, 10.7% (95% CI = 9.2-12.3% and 29.5 eggs/10 ml) districts, particularly around Kayuka pond and Ongoche river respectively. Overall infections correlated with hematuria (r = 0.9, P < 0.0001) and were more likely in boys (P < 0.0001, OR = 0.624). S. mansoni infections with an overall prevalence of 13% (95% CI =11.9-14.1%) were majorly confined along the shores of Lake Victoria. STH infections were homogenously distributed with A. lumbricoides occurring in 5.4% (95% CI = 4.7-6.3%) and T. trichiura in 2.8% (95% CI = 2.3-3.4%) of the children. Although S. mansoni infections were more co-endemic with S. haematobium, only A. lumbricoides infections were positively associated with S. haematobium (P = 0

  19. Field evaluation of a new antibody-based diagnostic for Schistosoma haematobium and S. mansoni at the point-of-care in northeast Zimbabwe

    PubMed Central

    2014-01-01

    Background Rapid diagnostic tests (RDTs) for use at the point-of-care (POC) are likely to become increasingly useful as large-scale control programmes for schistosomiasis get underway. Given the low sensitivity of the reference standard egg count methods in detecting light infections, more sensitive tests will be required to monitor efforts aimed at eliminating schistosomiasis as advocated by the World Health Assembly Resolution 65.21 passed in 2012. Methods A recently developed RDT incorporating Schistosoma mansoni cercarial transformation fluid (SmCTF) for detection of anti-schistosome antibodies in human blood was here evaluated in children (mean age: 7.65 years; age range: 1-12 years) carrying light S. mansoni and S. haematobium infections in a schistosome-endemic area of Zimbabwe by comparison to standard parasitological techniques (i.e. the Kato-Katz faecal smear and urine filtration). Enzyme-linked immunosorbent assays (ELISAs) incorporating S. haematobium antigen preparations were also employed for additional comparison. Results The sensitivity of the SmCTF-RDT compared to standard parasitological methods was 100% while the specificity was 39.5%. It was found that the sera from RDT “false-positive” children showed significantly higher antibody titres in IgM-cercarial antigen preparation (CAP) and IgM-soluble egg antigen (SEA) ELISA assays than children identified by parasitology as “true-negatives”. Conclusions Although further evaluations are necessary using more accurate reference standard tests, these results indicate that the RDT could be a useful tool for the rapid prevalence-mapping of both S. mansoni and S. haematobium in schistosome-endemic areas. It is affordable, user-friendly and allows for diagnosis of both schistosome species at the POC. PMID:24666689

  20. Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems

    PubMed Central

    Perlas, Emerald; Bolasco, Giulia; Nibbio, Martina; Monteagudo, Edith; Bresciani, Alberto; Ruberti, Giovina

    2016-01-01

    Background Schistosomiasis, one of the world’s greatest human neglected tropical diseases, is caused by parasitic trematodes of the genus Schistosoma. A unique feature of schistosome biology is that the induction of sexual maturation as well as the maintenance of the differentiation status of female reproductive organs and egg production, necessary for both disease transmission and pathogenesis, are strictly dependent on the male. The treatment and most control initiatives of schistosomiasis rely today on the long-term application of a single drug, praziquantel (PZQ), mostly by campaigns of mass drug administration. PZQ, while very active on adult parasites, has much lower activity against juvenile worms. Monotherapy also favors the selection of drug resistance and, therefore, new drugs are urgently needed. Methods and Findings Following the screening of a small compound library with an ATP-based luminescent assay on Schistosoma mansoni schistosomula, we here report the identification and characterization of novel antischistosomal properties of the anti-anginal drug perhexiline maleate (PHX). By phenotypic worm survival assays and confocal microscopy studies we show that PHX, in vitro, has a marked lethal effect on all S. mansoni parasite life stages (newly transformed schistosomula, juvenile and adult worms) of the definitive host. We further demonstrate that sub-lethal doses of PHX significantly impair egg production and lipid depletion within the vitellarium of adult female worms. Moreover, we highlighted tegumental damage in adult male worms and remarkable reproductive system alterations in both female and male adult parasites. The in vivo study in S. mansoni-patent mice showed a notable variability of worm burdens in the individual experiments, with an overall minimal schistosomicidal effect upon PHX treatment. The short PHX half-life in mice, together with its very high rodent plasma proteins binding could be the cause of the modest efficacy of PHX in the

  1. Study of the snail intermediate hosts for Schistosoma mansoni on Itamaracá Island in northeast Brazil: spatial displacement of Biomphalaria glabrata by Biomphalaria straminea.

    PubMed

    Barbosa, Constança S; Barbosa, Verônica S; Nascimento, Wheverton C; Pieri, Otavio S; Araújo, Karina C G M

    2014-05-01

    In 2012 a malacological survey of the breeding sites of Biomphalaria glabrata and B. straminea , the two intermediate host snails of Schistosoma mansoni , was carried out on Itamaraca Island in Pernambuco, Brazil. This study has now been extended by studying the competition between the two species. Snails were collected and dissected to identify the species and tests were performed to verify S. mansoni infection. Student's t test was used to compare the proportion between the two species and their breeding sites and a parasitological survey was conducted among local residents, using the Kato-Katz method. The spatial distribution of the two snail species was determined using TerraView, while a snail density map was constructed by Kernel estimate. The survey identified two breeding sites for B. glabrata with 17 specimens and 19 breeding sites for B. straminea with 459 snails, all of them negative for S. mansoni infection. The statistical analysis revealed that the proportion of the numbers of specimens and breeding sites of B. straminea (37.84 ± 9.01) were significantly greater than those of B. glabrata (8.50 ± 6.50). Parasitological examinations from 41 residents diagnosed two cases of schistosomiasis with parasite loads of 60 and 84 eggs per 1 g of stool, respectively. This indiction of a competitive process between the two snail species requires monitoring of schistosomiasis in the resident and travelling human populations occupying this environment, which could potentially result in social and economic changes on the island risking its attraction as a centre for eco-tourism. PMID:24893012

  2. Differences in the Gene Expression Profiles of Haemocytes from Schistosome-Susceptible and -Resistant Biomphalaria glabrata Exposed to Schistosoma mansoni Excretory-Secretory Products

    PubMed Central

    Davies, Angela J.; Kirk, Ruth S.; Emery, Aidan M.; Rollinson, David; Jones, Catherine S.; Noble, Leslie R.; Walker, Anthony J.

    2014-01-01

    During its life cycle, the helminth parasite Schistosoma mansoni uses the freshwater snail Biomphalaria glabrata as an intermediate host to reproduce asexually generating cercariae for infection of the human definitive host. Following invasion of the snail, the parasite develops from a miracidium to a mother sporocyst and releases excretory-secretory products (ESPs) that likely influence the outcome of host infection. To better understand molecular interactions between these ESPs and the host snail defence system, we determined gene expression profiles of haemocytes from S. mansoni-resistant or -susceptible strains of B. glabrata exposed in vitro to S. mansoni ESPs (20 μg/ml) for 1 h, using a 5K B. glabrata cDNA microarray. Ninety-eight genes were found differentially expressed between haemocytes from the two snail strains, 57 resistant specific and 41 susceptible specific, 60 of which had no known homologue in GenBank. Known differentially expressed resistant-snail genes included the nuclear factor kappa B subunit Relish, elongation factor 1α, 40S ribosomal protein S9, and matrilin; known susceptible-snail specific genes included cathepsins D and L, and theromacin. Comparative analysis with other gene expression studies revealed 38 of the 98 identified genes to be uniquely differentially expressed in haemocytes in the presence of ESPs, thus identifying for the first time schistosome ESPs as important molecules that influence global snail host-defence cell gene expression profiles. Such immunomodulation may benefit the schistosome, enabling its survival and successful development in the snail host. PMID:24663063

  3. Novel Non-Peptide Inhibitors against SmCL1 of Schistosoma mansoni: In Silico Elucidation, Implications and Evaluation via Knowledge Based Drug Discovery

    PubMed Central

    Zafar, Atif; Ahmad, Sabahuddin; Rizvi, Asim; Ahmad, Masood

    2015-01-01

    Schistosomiasis is a major endemic disease known for excessive mortality and morbidity in developing countries. Because praziquantel is the only drug available for its treatment, the risk of drug resistance emphasizes the need to discover new drugs for this disease. Cathepsin SmCL1 is the critical target for drug design due to its essential role in the digestion of host proteins for growth and development of Schistosoma mansoni. Inhibiting the function of SmCL1 could control the wide spread of infections caused by S. mansoni in humans. With this objective, a homology modeling approach was used to obtain theoretical three-dimensional (3D) structure of SmCL1. In order to find the potential inhibitors of SmCL1, a plethora of in silico techniques were employed to screen non-peptide inhibitors against SmCL1 via structure-based drug discovery protocol. Receiver operating characteristic (ROC) curve analysis and molecular dynamics (MD) simulation were performed on the results of docked protein-ligand complexes to identify top ranking molecules against the modelled 3D structure of SmCL1. MD simulation results suggest the phytochemical Simalikalactone-D as a potential lead against SmCL1, whose pharmacophore model may be useful for future screening of potential drug molecules. To conclude, this is the first report to discuss the virtual screening of non-peptide inhibitors against SmCL1 of S. mansoni, with significant therapeutic potential. Results presented herein provide a valuable contribution to identify the significant leads and further derivatize them to suitable drug candidates for antischistosomal therapy. PMID:25933436

  4. Diagnostic Accuracy and Applicability of a PCR System for the Detection of Schistosoma mansoni DNA in Human Urine Samples from an Endemic Area

    PubMed Central

    Enk, Martin Johannes; Oliveira e Silva, Guilherme; Rodrigues, Nilton Barnabé

    2012-01-01

    Schistosomiasis caused by Schistosoma mansoni, one of the most neglected human parasitoses in Latin America and Africa, is routinely confirmed by microscopic visualization of eggs in stool. The main limitation of this diagnostic approach is its lack of sensitivity in detecting individual low worm burdens and consequently data on infection rates in low transmission settings are little reliable. According to the scientific literature, PCR assays are characterized by high sensitivity and specificity in detecting parasite DNA in biological samples. A simple and cost effective extraction method for DNA of Schistosoma mansoni from urine samples in combination with a conventional PCR assay was developed and applied in an endemic area. This urine based PCR system was tested for diagnostic accuracy among a population of a small village in an endemic area, comparing it to a reference test composed of three different parasitological techniques. The diagnostic parameters revealed a sensitivity of 100%, a specificity of 91.20%, positive and negative predictive values of 86.25% and 100%, respectively, and a test accuracy of 94.33%. Further statistical analysis showed a k index of 0.8806, indicating an excellent agreement between the reference test and the PCR system. Data obtained from the mouse model indicate the infection can be detected one week after cercariae penetration, opening a new perspective for early detection and patient management during this stage of the disease. The data indicate that this innovative PCR system provides a simple to handle and robust diagnostic tool for the detection of S. mansoni DNA from urine samples and a promising approach to overcome the diagnostic obstacles in low transmission settings. Furthermore the principals of this molecular technique, based on the examination of human urine samples may be useful for the diagnosis of other neglected tropical diseases that can be detected by trans-renal DNA. PMID:22701733

  5. Diagnostic accuracy and applicability of a PCR system for the detection of Schistosoma mansoni DNA in human urine samples from an endemic area.

    PubMed

    Enk, Martin Johannes; Oliveira e Silva, Guilherme; Rodrigues, Nilton Barnabé

    2012-01-01

    Schistosomiasis caused by Schistosoma mansoni, one of the most neglected human parasitoses in Latin America and Africa, is routinely confirmed by microscopic visualization of eggs in stool. The main limitation of this diagnostic approach is its lack of sensitivity in detecting individual low worm burdens and consequently data on infection rates in low transmission settings are little reliable. According to the scientific literature, PCR assays are characterized by high sensitivity and specificity in detecting parasite DNA in biological samples. A simple and cost effective extraction method for DNA of Schistosoma mansoni from urine samples in combination with a conventional PCR assay was developed and applied in an endemic area. This urine based PCR system was tested for diagnostic accuracy among a population of a small village in an endemic area, comparing it to a reference test composed of three different parasitological techniques. The diagnostic parameters revealed a sensitivity of 100%, a specificity of 91.20%, positive and negative predictive values of 86.25% and 100%, respectively, and a test accuracy of 94.33%. Further statistical analysis showed a k index of 0.8806, indicating an excellent agreement between the reference test and the PCR system. Data obtained from the mouse model indicate the infection can be detected one week after cercariae penetration, opening a new perspective for early detection and patient management during this stage of the disease. The data indicate that this innovative PCR system provides a simple to handle and robust diagnostic tool for the detection of S. mansoni DNA from urine samples and a promising approach to overcome the diagnostic obstacles in low transmission settings. Furthermore the principals of this molecular technique, based on the examination of human urine samples may be useful for the diagnosis of other neglected tropical diseases that can be detected by trans-renal DNA. PMID:22701733

  6. Polymerase chain reaction for the amplification of the 121-bp repetitive sequence of Schistosoma mansoni: a highly sensitive potential diagnostic tool for areas of low endemicity.

    PubMed

    Ferrer, E; Pérez, F; Bello, I; Bolívar, A; Lares, M; Osorio, A; León, L; Amarista, M; Incani, R N

    2015-11-01

    Schistosomiasis is a disease caused by parasitic flatworms of the genus Schistosoma, whose diagnosis has limitations, such as the low sensitivity and specificity of parasitological and immunological methods, respectively. In the present study an alternative molecular technique requiring previous standardization was carried out using the polymerase chain reaction (PCR) for the amplification of a 121-bp highly repetitive sequence for Schistosoma mansoni. DNA was extracted from eggs of S. mansoni by salting out. Different conditions were standardized for the PCR technique, including the concentration of reagents and the DNA template, annealing temperature and number of cycles, followed by the determination of the analytical sensitivity and specificity of the technique. Furthermore, the standardized PCR technique was employed in DNA extracted, using Chelex®100, from samples of sera of patients with an immunodiagnosis of schistosomiasis. The optimal conditions for the PCR were 2.5 mm MgCl2, 150 mm deoxynucleoside triphosphates (dNTPs), 0.4 μm primers, 0.75 U DNA polymerase, using 35 cycles and an annealing temperature of 63°C. The analytical sensitivity of the PCR was 10 attograms of DNA and the specificity was 100%. The DNA sequence was successfully detected in the sera of two patients, demonstrating schistosomiasis transmission, although low, in the community studied. The standardized PCR technique, using smaller amounts of reagents than in the original protocol, is highly sensitive and specific for the detection of DNA from S. mansoni and could be an important tool for diagnosis in areas of low endemicity. PMID:25141275

  7. Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl and Thymyl Cinnamate Induce Cytoplasmic Vacuoles and Death in Schistosomula of Schistosoma mansoni.

    PubMed

    Glaser, Jan; Schurigt, Uta; Suzuki, Brian M; Caffrey, Conor R; Holzgrabe, Ulrike

    2015-01-01

    Bornyl caffeate (1) was previously isolated by us from Valeriana (V.) wallichii rhizomes and identified as an anti-leishmanial substance. Here, we screened a small compound library of synthesized derivatives 1-30 for activity against schistosomula of Schistosoma (S.) mansoni. Compound 1 did not show any anti-schistosomal activity. However, strong phenotypic changes, including the formation of vacuoles, degeneration and death were observed after in vitro treatment with compounds 23 (thymyl cinnamate) and 27 (eugenyl cinnamate). Electron microscopy analysis of the induced vacuoles in the dying parasites suggests that 23 and 27 interfere with autophagy. PMID:26076109

  8. Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals

    PubMed Central

    Wiszniewsky, Anna; Ritter, Manuel; Goreish, Ibtisam A.; Atti El Mekki, Misk El Yemen A.; Arriens, Sandra; Pfarr, Kenneth; Fimmers, Rolf; Doenhoff, Mike; Hoerauf, Achim; Layland, Laura E.

    2016-01-01

    Background In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways

  9. Worm Proteins of Schistosoma mansoni Reduce the Severity of Experimental Chronic Colitis in Mice by Suppressing Colonic Proinflammatory Immune Responses

    PubMed Central

    Heylen, Marthe; Ruyssers, Nathalie E.; De Man, Joris G.; Timmermans, Jean-Pierre; Pelckmans, Paul A.; Moreels, Tom G.; De Winter, Benedicte Y.

    2014-01-01

    Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon. PMID:25313594

  10. Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni.

    PubMed Central

    Sher, A; Coffman, R L; Hieny, S; Scott, P; Cheever, A W

    1990-01-01

    Eosinophils are thought to play a major role in the immunobiology of schistosomiasis. To investigate the immunologic basis of the eosinophil response and directly assess the function of eosinophils in egg-induced pathology, mice infected with Schistosoma mansoni were injected with a monoclonal antibody produced against interleukin 5 (IL-5), a cytokine previously shown to stimulate eosinophil differentiation in vitro. This treatment suppressed the generation of eosinophil myelocyte precursors in the bone marrow and reduced to background levels the numbers of mature eosinophils in the marrow, in circulation, and within acute schistosome egg granulomas. Nevertheless, granulomas in the anti-IL-5-treated/eosinophil-depleted mice at 8 weeks of infection were only marginally smaller than those in animals injected with control monoclonal antibody, and hepatic fibrosis was comparable in the two groups. Additional parameters such as worm burden, egg output, and serum IgE levels were unaltered by the anti-IL-5 treatment. In contrast, infected animals injected with monoclonal antibody against gamma interferon (IFN-gamma) displayed circulating eosinophil levels that were elevated with respect to control mice, possibly because of an enhanced release of mature eosinophils from the marrow, and developed egg granulomas that were indistinguishable in size and cellular composition from those in control animals. Immunologic assays revealed that lymphocytes from acutely infected mice produce large quantities of IL-5 but minimal IFN-gamma when stimulated with either egg antigen or mitogen. Taken together, these results indicate that neither IL-5 nor eosinophils are essential for egg-induced pathology but suggest that lymphocytes that belong to the IL-5-producing TH2 subset predominate during acute infection and may induce granuloma formation by the production of other cytokines. Images PMID:2104985

  11. Evaluation of the Schistosoma mansoni Y-box-binding protein (SMYB1) potential as a vaccine candidate against schistosomiasis.

    PubMed

    Dias, Sílvia R C; Boroni, Mariana; Rocha, Elizângela A; Dias, Thomaz L; de Laet Souza, Daniela; Oliveira, Fabrício M S; Bitar, Mainá; Macedo, Andrea M; Machado, Carlos R; Caliari, Marcelo V; Franco, Glória R

    2014-01-01

    Schistosomiasis is a neglected tropical disease, and after malaria, is the second most important tropical disease in public health. A vaccine that reduces parasitemia is desirable to achieve mass treatment with a low cost. Although potential antigens have been identified and tested in clinical trials, no effective vaccine against schistosomiasis is available. Y-box-binding proteins (YBPs) regulate gene expression and participate in a variety of cellular processes, including transcriptional and translational regulation, DNA repair, cellular proliferation, drug resistance, and stress responses. The Schistosoma mansoni ortholog of the human YB-1, SMYB1, is expressed in all stages of the parasite life cycle. Although SMYB1 binds to DNA or RNA oligonucleotides, immunohistochemistry assays demonstrated that it is primarily localized in the cytoplasm of parasite cells. In addition, SMYB1 interacts with a protein involved in mRNA processing, suggesting that SMYB1 functions in the turnover, transport, and/or stabilization of RNA molecules during post-transcriptional gene regulation. Here we report the potential of SMYB1 as a vaccine candidate. We demonstrate that recombinant SMYB1 stimulates the production of high levels of specific IgG1 antibodies in a mouse model. The observed levels of specific IgG1 and IgG2a antibodies indicate an actual protection against cercariae challenge. Animals immunized with rSMYB1 exhibited a 26% reduction in adult worm burden and a 28% reduction in eggs retained in the liver. Although proteins from the worm tegument are considered optimal targets for vaccine development, this study demonstrates that unexposed cytoplasmic proteins can reduce the load of intestinal worms and the number of eggs retained in the liver. PMID:24966869

  12. Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

    PubMed Central

    Sabra, Abdel-Nasser Abdel-Aal; Hammam, Olfat Ali; El-Lakkany, Naglaa Mohamed

    2013-01-01

    The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF. PMID:23710083

  13. The Syk Kinase SmTK4 of Schistosoma mansoni Is Involved in the Regulation of Spermatogenesis and Oogenesis

    PubMed Central

    Beckmann, Svenja; Buro, Christin; Dissous, Colette; Hirzmann, Jörg; Grevelding, Christoph G.

    2010-01-01

    The signal transduction protein SmTK4 from Schistosoma mansoni belongs to the family of Syk kinases. In vertebrates, Syk kinases are known to play specialized roles in signaling pathways in cells of the hematopoietic system. Although Syk kinases were identified in some invertebrates, their role in this group of animals has not yet been elucidated. Since SmTK4 is the first Syk kinase from a parasitic helminth, shown to be predominantly expressed in the testes and ovary of adult worms, we investigated its function. To unravel signaling cascades in which SmTK4 is involved, yeast two-/three-hybrid library screenings were performed with either the tandem SH2-domain, or with the linker region including the tyrosine kinase domain of SmTK4. Besides the Src kinase SmTK3 we identified a new Src kinase (SmTK6) acting upstream of SmTK4 and a MAPK-activating protein, as well as mapmodulin acting downstream. Their identities and colocalization studies pointed to a role of SmTK4 in a signaling cascade regulating the proliferation and/or differentiation of cells in the gonads of schistosomes. To confirm this decisive role we performed biochemical and molecular approaches to knock down SmTK4 combined with a novel protocol for confocal laser scanning microscopy for morphological analyses. Using the Syk kinase-specific inhibitor Piceatannol or by RNAi treatment of adult schistosomes in vitro, corresponding phenotypes were detected in the testes and ovary. In the Xenopus oocyte system it was finally confirmed that Piceatannol suppressed the activity of the catalytic kinase domain of SmTK4. Our findings demonstrate a pivotal role of SmTK4 in gametogenesis, a new function for Syk kinases in eukaryotes. PMID:20169182

  14. Preliminary crystallographic studies of a Schistosoma mansoni antigen (Sm21.7) dynein light-chain (DLC) domain

    PubMed Central

    Costa, M. A. F.; Rodrigues, F. T. G.; Chagas, B. C. A.; Rezende, C. M. F.; Goes, A. M.; Nagem, R. A. P.

    2014-01-01

    Schistosomiasis is an inflammatory chronic disease that represents a major health problem in tropical and subtropical countries. The drug of choice for treatment, praziquantel, is effective in killing adult worms but fails to kill immature forms and prevent reinfection. One prominent antigen candidate for an anti-schistosomiasis vaccine is the protein Sm21.7 (184 amino-acid residues) from Schistosoma mansoni, a tegumental protein capable of reducing the worm burden in a murine immunization model. In the present work, the Sm21.7 gene was cloned and expressed in Escherichia coli and the full-length protein was purified to homogeneity. Crystals of recombinant Sm21.7 suitable for X-ray diffraction were obtained using PEG monomethyl ether 2000 as a precipitant. X-ray diffraction images of a native crystal (at 2.05 Å resolution) and a quick-cryosoaked NaI derivative (at 1.95 Å resolution) were collected on the W01B-MX2 beamline at the Laboratório Nacional de Luz Síncrotron (LNLS, Brazilian Synchrotron Light Laboratory/MCT). Both crystals belonged to the hexagonal space group P6122, with similar unit-cell parameters a = b = 108.5, c = 55.8 Å. SIRAS-derived phases were used to generate the first electron-density map, from which a partial three-dimensional model of Sm21.7 (from Gln89 to Asn184) was automatically constructed. Anaysis of dissolved crystals by SDS–PAGE confirmed that the protein was cleaved in the crystallization drop and only the Sm21.7 C-terminal domain was crystallized. The structure of the Sm21.7 C-terminal domain will help in the localization of the epitopes responsible for its protective immune responses, constituting important progress in the development of an anti-schistosomiasis vaccine. PMID:24915098

  15. Surface expression patterns of defined glycan antigens change during Schistosoma mansoni cercarial transformation and development of schistosomula.

    PubMed

    Smit, Cornelis H; Homann, Arne; van Hensbergen, Vincent P; Schramm, Gabriele; Haas, Helmut; van Diepen, Angela; Hokke, Cornelis H

    2015-12-01

    During the complex lifecycle of Schistosoma mansoni, a large variety of glycans is expressed. To many of these glycans, antibodies are induced by the infected host and some might be targets for vaccines or diagnostic tests. Spatial changes in glycan expression during schistosome development are largely unexplored. To study the surface-exposed glycans during the important initial stages of infection, we analyzed the binding of a panel of anti-glycan monoclonal antibodies (mAbs) to cercariae and schistosomula up to 72 h after transformation by immunofluorescence microscopy. The mAb specificity toward their natural targets was studied using a microarray containing a wide range of schistosomal N-glycans, O-glycans and glycosphingolipid glycans. With the exception of GalNAcβ1-4(Fucα1-3)GlcNAc (LDN-F), mono- and multifucosylated GalNAcβ1-4GlcNAc (LDN)-motifs were exposed at the surface of all developmental stages studied. Multifucosylated LDN-motifs were present on cercarial glycocalyx-derived O-glycans as well as cercarial glycolipids. In contrast, the Galβ1-4(Fucα1-3)GlcNAc (Lewis X) and LDN-F-motifs, also expressed on cercarial glycolipids, and in addition on a range of cercarial N- and O-glycans, became surface expressed only after transformation of cercariae to schistosomula. In line with the documented shedding of the O-glycan-rich cercarial glycocalyx after transformation these observations suggest that surface accessible multifucosylated LDN-motifs are mostly expressed by O-glycans in cercariae, but principally by glycosphingolipids in schistosomula. We hypothesize that these temporal changes in surface exposure of glycan antigens are relevant to the interaction with the host during the initial stages of infection with schistosomes and discuss the potential of these glycan antigens as intervention targets. PMID:26347524

  16. Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection.

    PubMed

    Santos, Patrícia d'Emery Alves; Lorena, Virgínia Maria Barros de; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; Nascimento, Wheverton Ricardo Correia do; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; Souza, Valdênia Maria Oliveira de

    2016-02-01

    Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

  17. Environmental epidemiology of intestinal schistosomiasis and genetic diversity of Schistosoma mansoni infections in snails at Bugoigo village, Lake Albert.

    PubMed

    Levitz, Sarah; Standley, Claire J; Adriko, Moses; Kabatereine, Narcis B; Stothard, J Russell

    2013-11-01

    Intestinal schistosomiasis continues to be hyper-endemic in the fishing community of Bugoigo located on the eastern shore of Lake Albert, Uganda. Our study aimed to identify the factors that determine the local distribution and abundance of Biomphalaria, as well as infection(s) with Schistosoma mansoni inclusive of their genetic diversity. In addition, a DNA barcoding approach was taken to genotype schistosome cercariae, exploring the micro-epidemiology of infections. Over a 3-week period in June-July 2010, several hundred Biomphalaria spp. were collected, together with environmental information, from 10 selected sites, representative of both putative wave-exposed (n=5) and wave-sheltered shorelines (n=5). A Mann-Whitney U-test and a generalized linear model were used to assess associations with snail abundance and parasite infections across the shoreline. Levels of local wave action were recorded over the 19-day period using digital accelerometers. The general absence of wave action on the sheltered shoreline likely helped to raise and focalize other environmental parameters, such as water conductivity by lack of mixing, that foster transmission of intestinal schistosomiasis. Over the study period, a total of 10 infected snails were encountered and a selection of schistosome cercariae from each infected snail was harvested for analysis by DNA barcoding. In total, 91 DNA barcodes were generated with 15 unique barcode types identified. Of these, 4 barcodes had been found previously in Lake Albert and (or) Victoria, the remaining 11 were newly encountered here and described. The distribution of DNA barcodes across infected snails and sampled locations revealed a complicated spatial sub-structuring. By shedding new light on the fine-scale patterning of infections, DNA barcoding has revealed a rather heterogeneous landscape of cercariae, likely inclusive of multi-miracidial infections within the snail, which will in turn interplay with human water contact activities to

  18. Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

    PubMed Central

    Santos, Patrícia d‘Emery Alves; de Lorena, Virgínia Maria Barros; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; do Nascimento, Wheverton Ricardo Correia; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; de Souza, Valdênia Maria Oliveira

    2016-01-01

    Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

  19. Combining process-based and correlative models improves predictions of climate change effects on Schistosoma mansoni transmission in eastern Africa.

    PubMed

    Stensgaard, Anna-Sofie; Booth, Mark; Nikulin, Grigory; McCreesh, Nicky

    2016-01-01

    Currently, two broad types of approach for predicting the impact of climate change on vector-borne diseases can be distinguished: i) empirical-statistical (correlative) approaches that use statistical models of relationships between vector and/or pathogen presence and environmental factors; and ii) process-based (mechanistic) approaches that seek to simulate detailed biological or epidemiological processes that explicitly describe system behavior. Both have advantages and disadvantages, but it is generally acknowledged that both approaches have value in assessing the response of species in general to climate change. Here, we combine a previously developed dynamic, agentbased model of the temperature-sensitive stages of the Schistosoma mansoni and intermediate host snail lifecycles, with a statistical model of snail habitat suitability for eastern Africa. Baseline model output compared to empirical prevalence data suggest that the combined model performs better than a temperature-driven model alone, and highlights the importance of including snail habitat suitability when modeling schistosomiasis risk. There was general agreement among models in predicting changes in risk, with 24-36% of the eastern Africa region predicted to experience an increase in risk of up-to 20% as a result of increasing temperatures over the next 50 years. Vice versa the models predicted a general decrease in risk in 30-37% of the study area. The snail habitat suitability models also suggest that anthropogenically altered habitat play a vital role for the current distribution of the intermediate snail host, and hence we stress the importance of accounting for land use changes in models of future changes in schistosomiasis risk. PMID:27063739

  20. Evaluation of a 25-Year-Program for the Control of Schistosomiasis Mansoni in an Endemic Area in Brazil

    PubMed Central

    Sarvel, Ana K.; Oliveira, Áureo A.; Silva, Alexandre R.; Lima, Anna C. L.; Katz, Naftale

    2011-01-01

    Background Various studies showed that chemotherapy can control schistosomiasis morbidity, but association of measures (water supply, sewage disposal and increase of socioeconomic conditions) is necessary for transmission control. Methodology/Principal Findings A survey dealing with socioeconomic conditions, snail survey, contact with natural waters, and clinical and stool examinations was undertaken at an endemic area in the State of Minas Gerais, Brazil. The methodology used was the same for both evaluations (1981 and 2005). Four hundred and seventy-five out of 1,474 individuals studied in 1981 could be contacted. From these, 358 were submitted to stool examination, and 231 of them were clinically examined. Patients eliminating S. mansoni eggs in their stools were treated. The results showed that the prevalence rate in Comercinho, a municipality of the State of Minas Gerais, Brazil, was substantially reduced to 70.4% and 1.7% in 1981 and 2005, respectively, as well as the frequency of the hepatosplenic form (7% to 1.3%) after five treatments effectuated between 1981 and 1992. No other new case of this form was detected from 1981 onwards. Another important aspect to be considered was the improvement of people's living standard that occurred in the region after more than two decades' efforts (better housing, professional skill and adequate basic sanitation). Conclusion/Significance The control of morbidity and very significant decrease of schistosomiasis transmission in an area until then considered as hyperendemic was possible by means of association of successive specific treatments of the local population, together with the construction of privies, water supply in the houses and improvement of socioeconomic conditions. PMID:21423644

  1. Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties

    PubMed Central

    Thomas, Charlotte M.; Fitzsimmons, Colin M.; Dunne, David W.; Timson, David J.

    2015-01-01

    The tegumental allergen-like (TAL) proteins from Schistosoma mansoni are part of a family of calcium binding proteins found only in parasitic flatworms. These proteins have attracted interest as potential drug or vaccine targets, yet comparatively little is known about their biochemistry. Here, we compared the biochemical properties of three members of this family: SmTAL1 (Sm22.6), SmTAL2 (Sm21.7) and SmTAL3 (Sm20.8). Molecular modelling suggested that, despite similarities in domain organisation, there are differences in the three proteins’ structures. SmTAL1 was predicted to have two functional calcium binding sites and SmTAL2 was predicted to have one. Despite the presence of two EF-hand-like structures in SmTAL3, neither was predicted to be functional. These predictions were confirmed by native gel electrophoresis, intrinsic fluorescence and differential scanning fluorimetry: both SmTAL1 and SmTAL2 are able to bind calcium ions reversibly, but SmTAL3 is not. SmTAL1 is also able to interact with manganese, strontium, iron(II) and nickel ions. SmTAL2 has a different ion binding profile interacting with cadmium, manganese, magnesium, strontium and barium ions in addition to calcium. All three proteins form dimers and, in contrast to some Fasciola hepatica proteins from the same family; dimerization is not affected by calcium ions. SmTAL1 interacts with the anti-schistosomal drug praziquantel and the calmodulin antagonists trifluoperazine, chlorpromazine and W7. SmTAL2 interacts only with W7. SmTAL3 interacts with the aforementioned calmodulin antagonists and thiamylal, but not praziquantel. Overall, these data suggest that the proteins have different biochemical properties and thus, most likely, different in vivo functions. PMID:25447146

  2. Schistosoma mansoni soluble egg antigens enhance Listeria monocytogenes vector HIV-1 vaccine induction of cytotoxic T cells.

    PubMed

    Bui, Cac T; Shollenberger, Lisa M; Paterson, Yvonne; Harn, Donald A

    2014-09-01

    Vaccines are an important public health measure for prevention and treatment of diseases. In addition to the vaccine immunogen, many vaccines incorporate adjuvants to stimulate the recipient's immune system and enhance vaccine-specific responses. While vaccine development has advanced from attenuated organism to recombinant protein or use of plasmid DNA, the development of new adjuvants that safely increase immune responses has not kept pace. Previous studies have shown that the complex mixture of molecules that comprise saline soluble egg antigens (SEA) from Schistosoma mansoni eggs functions to promote CD4(+) T helper 2 (Th2) responses. Therefore, we hypothesized that coadministration of SEA with a Listeria vector HIV-1 Gag (Lm-Gag) vaccine would suppress host cytotoxic T lymphocyte (CTL) and T helper 1 (Th1) responses to HIV-1 Gag epitopes. Surprisingly, instead of driving HIV-1 Gag-specific responses toward Th2 type, we found that coadministration of SEA with Lm-Gag vaccine significantly increased the frequency of gamma interferon (IFN-γ)-producing Gag-specific Th1 and CTL responses over that seen in mice administered Lm-Gag only. Analysis of the functionality and durability of vaccine responses suggested that SEA not only enlarged different memory T cell compartments but induced functional and long-lasting vaccine-specific responses as well. These results suggest there are components in SEA that can synergize with potent inducers of strong and durable Th1-type responses such as those to Listeria. We hypothesize that SEA contains moieties that, if defined, can be used to expand type 1 proinflammatory responses for use in vaccines. PMID:24990901

  3. Discovery of Platyhelminth-Specific α/β-Integrin Families and Evidence for Their Role in Reproduction in Schistosoma mansoni

    PubMed Central

    Beckmann, Svenja; Quack, Thomas; Dissous, Colette; Cailliau, Katia; Lang, Gabriele; Grevelding, Christoph G.

    2012-01-01

    In all metazoa, the response of cells to molecular stimuli from their environment represents a fundamental principle of regulatory processes controlling cell growth and differentiation. Among the membrane-linked receptors mediating extracellular communication processes are integrin receptors. Besides managing adhesion to the extracellular matrix or to other cells, they arrange information flow into the cells by activating intracellular signaling pathways often acting synergistically through cooperation with growth factor receptors. Although a wealth of information exists on integrins in different model organisms, there is a big gap of knowledge for platyhelminths. Here we report on the in silico detection and reconstruction of α and β integrins from free-living and parasitic platyhelminths, which according to structural and phylogenetic analyses form specific clades separate from each other and from further metazoan integrins. As representative orthologs of parasitic platyhelminths we have cloned one beta-integrin (Smβ-Int1) and four alpha-integrins (Smα-Int1 - Smα-Int4) from Schistosoma mansoni; they were characterized by molecular and biochemical analyses. Evidence is provided that Smβ-Int1 interacts and co-localizes in the reproductive organs with known schistosome cellular tyrosine kinases (CTKs), of which the Syk kinase SmTK4 appeared to be the strongest interaction partner as shown by yeast two-hybrid analyses and coimmunoprecipitation experiments. By a novel RNAi approach with adult schistosomes in vitro we demonstrate for the first time multinucleated oocytes in treated females, indicating a decisive role Smβ-Int1 during oogenesis as phenotypically analyzed by confocal laser scanning microscopy (CLSM). Our findings provide a first comprehensive overview about platyhelminth integrins, of which the parasite group exhibits unique features allowing a clear distinction from the free-living groups. Furthermore, we shed first lights on the functions of

  4. Impact of the age of Biomphalaria alexandrina snails on Schistosoma mansoni transmission: modulation of the genetic outcome and the internal defence system of the snail

    PubMed Central

    Abou-El-Naga, Iman Fathy; Sadaka, Hayam Abd El-Monem; Amer, Eglal Ibrahim; Diab, Iman Hassan; Khedr, Safaa Ibrahim Abd El-Halim

    2015-01-01

    Of the approximately 34 identified Biomphalaria species,Biomphalaria alexandrina represents the intermediate host of Schistosoma mansoni in Egypt. Using parasitological and SOD1 enzyme assay, this study aimed to elucidate the impact of the age of B. alexandrina snails on their genetic variability and internal defence against S. mansoni infection. Susceptible and resistant snails were reared individually for self-reproduction; four subgroups of their progeny were used in experiment. The young susceptible subgroup showed the highest infection rate, the shortest pre-patent period, the highest total cercarial production, the highest mortality rate and the lowest SOD1 activity. Among the young and adult susceptible subgroups, 8% and 26% were found to be resistant, indicating the inheritance of resistance alleles from parents. The adult resistant subgroup, however, contained only resistant snails and showed the highest enzyme activity. The complex interaction between snail age, genetic background and internal defence resulted in great variability in compatibility patterns, with the highest significant difference between young susceptible and adult resistant snails. The results demonstrate that resistance alleles function to a greater degree in adults, with higher SOD1 activity and provide potential implications for Biomphalaria control. The identification of the most susceptible snail age enables determination of the best timing for applying molluscicides. Moreover, adult resistant snails could be beneficial in biological snail control. PMID:26061235

  5. Validation of a Point-of-Care Circulating Cathodic Antigen Urine Cassette Test for Schistosoma mansoni Diagnosis in the Sahel, and Potential Cross-Reaction in Pregnancy.

    PubMed

    Greter, Helena; Krauth, Stefanie J; Ngandolo, Bongo N R; Alfaroukh, Idriss O; Zinsstag, Jakob; Utzinger, Jürg

    2016-02-01

    On the shores of Lake Chad, schistosomiasis among mobile pastoralists was investigated in a field laboratory. Point-of-care circulating cathodic antigen (POC-CCA) cassette test, reagent strip, and filtration were conducted on urine samples. Fresh stool samples were subjected to the Kato-Katz technique, and fixed samples were examined with an ether-concentration method at a reference laboratory. POC-CCA urine cassette tests revealed a Schistosoma mansoni prevalence of 6.9%, compared with only 0.5% by stool microscopy. Three pregnant women with otherwise negative urine and stool testing had positive POC-CCA. This observation raises concern of cross-reactivity in pregnancy. Hence, two pregnant women in Switzerland with no history of schistosomiasis were subjected to POC-CCA and one tested positive. Our data suggest that POC-CCA can be performed under extreme Sahelian conditions (e.g., temperatures > 40°C), and it is more sensitive than stool microscopy for S. mansoni diagnosis. However, potential cross-reactivity in pregnancy needs further investigation. PMID:26556831

  6. Prevalence and Morbidity Data on Schistosoma mansoni Infection in Two Rural Areas of Jequitinhonha and Rio Doce Valleys in Minas Gerais, Brazil

    PubMed Central

    Conceição, Maria José; Carlôto, Aline Eduardo; de Melo, Eric Vinaud; da Silva, Iran Mendonça; Coura, José Rodrigues

    2013-01-01

    Objective. This study aimed to compare the prevalence and morbidity data on Schistosoma mansoni infection in two rural areas: the Jequitinhonha valley (area 1) and the Rio Doce valley (area 2) in the state of Minas Gerais, Brazil, covering the period from 2007 to 2010. Material and Methods. The parasitological stool tests were based on the quantitative method of Kato modified by Katz et al. Three clinical forms were considered: type I—schistosomiasis infection, type II—hepatointestinal form, and type III—hepatosplenic form. Results. The prevalence of infection among inhabitants of area 1 was 22.9%, with 2.1% presenting the hepatosplenic form and two cases of schistosomal myeloradiculopathy. The infection prevalence rate in area 2 was 20.2%, with 3.3% presenting the hepatosplenic form. Conclusion and Recommendation. There was no difference in the prevalence and in the morbidity of Schistosoma mansoni infection between the two areas, but it was predominant in young men with a low intensity of infection. The cases of schistosomal myeloradiculopathy in area 1 can be highlighted: these emphasize that schistosomiasis should not be neglected in Brazil. The lack of infection control in both areas may be related to the poor sanitation system, the absence of previous treatment, and the reinfection process. PMID:27335859

  7. A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation*

    PubMed Central

    Meyer, N. Helge; Mayerhofer, Hubert; Tripsianes, Konstantinos; Blindow, Silke; Barths, Daniela; Mewes, Astrid; Weimar, Thomas; Köhli, Thies; Bade, Steffen; Madl, Tobias; Frey, Andreas; Haas, Helmut; Mueller-Dieckmann, Jochen; Sattler, Michael; Schramm, Gabriele

    2015-01-01

    The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/α-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/α-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSEΔNLS, a monomeric IPSE/α-1 mutant, revealed that IPSE/α-1 is a new member of the βγ-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEΔNLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/α-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/α-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism. PMID:26163514

  8. A Five-Country Evaluation of a Point-of-Care Circulating Cathodic Antigen Urine Assay for the Prevalence of Schistosoma mansoni

    PubMed Central

    Colley, Daniel G.; Binder, Sue; Campbell, Carl; King, Charles H.; Tchuem Tchuenté, Louis-Albert; N'Goran, Eliézer K.; Erko, Berhanu; Karanja, Diana M. S.; Kabatereine, Narcis B.; van Lieshout, Lisette; Rathbun, Stephen

    2013-01-01

    We evaluated a commercial point-of-care circulating cathodic antigen (POC-CCA) test for assessing Schistosoma mansoni infection prevalence in areas at risk. Overall, 4,405 school-age children in Cameroon, Côte d'Ivoire, Ethiopia, Kenya, and Uganda provided urine for POC-CCA testing and stool for Kato-Katz assays. By latent class analysis, one POC-CCA test was more sensitive (86% versus 62%) but less specific (72% versus ∼100%) than multiple Kato-Katz smears from one stool. However, only 1% of POC-CCA tests in a non-endemic area were false positives, suggesting the latent class analysis underestimated the POC-CCA specificity. Multivariable modeling estimated POC-CCA as significantly more sensitive than Kato-Katz at low infection intensities (< 100 eggs/gram stool). By linear regression, 72% prevalence among 9–12 year olds by POC-CCA corresponded to 50% prevalence by Kato-Katz, whereas 46% POC-CCA prevalence corresponded to 10% Kato-Katz prevalence. We conclude that one urine POC-CCA test can replace Kato-Katz testing for community-level S. mansoni prevalence mapping. PMID:23339198

  9. Expression of a 28-kilodalton glutathione S-transferase antigen of Schistosoma mansoni on the surface of filamentous phages and evaluation of its vaccine potential.

    PubMed

    Rao, Kakuturu V N; He, Yi-Xun; Kalyanasundaram, Ramaswamy

    2003-07-01

    A cloning and expression system that allows display of proteins on the surface of filamentous phages was exploited to display a 28-kDa glutathione S-transferase (Sm28GST) antigen of the human parasite Schistosoma mansoni. The phage-displayed Sm28GST (pdGST) was immunoreactive and was recognized by immune sera, suggesting that the Sm28GST protein displayed on the surface of phages potentially maintains native conformation. Subsequent immunization studies showed that mice can develop high titers of antibodies against pdGST and do not require any additional adjuvant for immunization. Isotype analysis suggested that the pdGST immunization predominantly induced immunoglobulin G2b (IgG2b), IgG3, and IgM anti-GST antibodies in mice. Furthermore, the pdGST immunization was found to confer about 30% protection after a challenge infection with 100 cercariae of S. mansoni in BALB/c mice. These findings suggest that phage display is a simple, efficient, and promising tool to express candidate vaccine antigens for immunization against infectious agents. PMID:12853382

  10. Evaluation of the protective immune response induced in mice by immunization with Schistosoma mansoni schistosomula tegument (Smteg) in association with CpG-ODN.

    PubMed

    Teixeira de Melo, Tatiane; Araujo, Juliano Michel; Campos de Sena, Isabela; Carvalho Alves, Clarice; Araujo, Neusa; Toscano Fonseca, Cristina

    2013-01-01

    In schistosomiasis, the current control strategy does not prevent reinfection, therefore, vaccine strategies are essential to combat the Schistosoma mansoni. The efficacy vaccine depends on parasite stage and effective adjuvant. We have recently demonstrated that S. mansoni schistosomula tegument (Smteg) is able to activate dendritic cells up regulate CD40 and CD86 molecules and induce a partial protection in mice (43-48%) when formulated with Freund's adjuvant. In this study we evaluated the ability of Smteg + alum or Smteg + alum + CpG-ODN to induce protection in mice. Our results demonstrate that Smteg + alum + CpG-ODN induced a partial reduction in worm burden (43.1%), reduction in the number of eggs eliminated in the feces. The protective response was associated with a predominant Th1 type of immune response, with increased production of specific IgG2c, IFN-γ and TNF-α, B cells proliferation and CD4 cells and macrophages activation. PMID:23099420

  11. An oligonucleotide microarray for transcriptome analysis of Schistosoma mansoni and its application/use to investigate gender-associated gene expression.

    PubMed

    Fitzpatrick, Jennifer M; Johnston, David A; Williams, Gary W; Williams, Debbie J; Freeman, Tom C; Dunne, David W; Hoffmann, Karl F

    2005-05-01

    Global profiling transcriptomes of parasitic helminths offers the potential to simultaneously identify co-ordinately expressed genes, novel genetic programs and uniquely utilized metabolic pathways, which together provide an extensive and new resource for vaccine and drug discovery. We have exploited this post-genomic approach to fabricate the first oligonucleotide DNA microarray for gene expression analysis of the parasitic trematode Schistosoma mansoni. A total of 17,329 S. mansoni DNA sequences were used to design a microarray consisting of 7335 parasite elements or approximately 50% of this parasite's transcriptome. Here, we describe the design of this new microarray resource and its evaluation by extending studies into gender-associated gene expression in adult schistosomes. We demonstrate a high degree of reproducibility in detecting transcriptional differences among biologically replicated experiments and the ability of the microarray to distinguish between the expression of closely related gene family members. Importantly, for issues related to sexual dimorphism, labour division, gamete production and drug target discovery, 197 transcripts demonstrated a gender-biased pattern of gene expression in the adult schistosome, greatly extending the number of sex-associated genes. These data demonstrate the power of this new resource to facilitate a greater understanding into the biological complexities of schistosome development and maturation useful for identifying novel intervention strategies. PMID:15811522

  12. Purification and characterization of 3-hydroxymethylglutaryl-coenzyme A reductase of Schistosoma mansoni: regulation of parasite enzyme activity differs from mammalian host.

    PubMed

    Chen, G Z; Foster, L; Bennett, J L

    1991-07-01

    The enzyme 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase plays a critical role in regulating the production of cholesterol, dolichols, and ubiquinones in mammals. The inhibition of this enzyme in Schistosoma mansoni is accompanied by a cessation of egg production by the female parasite and a reduced ability of the parasite to properly glycoslyate their proteins. Furthermore, we recently demonstrated that mevinolin, if given continuously over a period of 10-14 days, is a potent antischistosomal drug. In this paper, we describe the properties of purified HMG-CoA reductase from S. mansoni. Using affinity chromatography, we were able to obtain a 417-fold purification of the enzyme which had Km values similar to the rat enzyme for HMG-CoA and NADPH. The Ki value for mevinolin, a potent and selective inhibitor of the rat reductase (Ki = 0.6 nM), was significantly higher (Ki = 46 nM) for the schistosome enzyme. SDS-PAGE and HPLC of the purified enzyme resulted in the appearance of a single protein, which had a molecular weight (66,000) in the range reported for the rat enzyme. Parasite reductase activity, unlike that of its host, did not display a circadian rhythm. Furthermore, agents which elevate (cholestyramine) or decrease (cholesterol) mammalian reductase activity had no effect on the parasite enzyme. Our results suggest that the mechanism which regulates production of the parasite's enzyme may differ from its mammalian host. PMID:1905241

  13. Enzyme-linked immunosorbent assay with worm vomit and cercarial secretions of Schistosoma mansoni to detect infections in an endemic focus of Burkina Faso.

    PubMed

    Bahgat, M; Sorgho, H; Ouédraogo, J B; Poda, J N; Sawadogo, L; Ruppel, A

    2006-03-01

    Cercariae and adult Schistosoma mansoni were used to prepare, respectively, cercarial secretions (CS) and worm vomit (WoV). These were used as antigens in an enzyme-linked immunosorbent assay (ELISA) to test the IgG-reactivity of sera obtained in an S. mansoni-endemic area of Burkina Faso. Among the egg-excreting individuals (n = 240), 94.6% reacted positively with WoV, but only 62.9% with CS, thus suggesting a high diagnostic sensitivity of WoV, but not of CS. Among those individuals without detectable eggs in two Kato-Katz thick smears from different stool specimens (n = 215), the respective percentages of positive IgG reactivity were 78.1% and 63.3%. These positive reactions in the absence of detectable eggs are interpreted in terms of limited sensitivity of parasitological stool examinations. Optical density values in ELISA with CS, but not with WoV, correlated negatively with age, which may reflect decreasing exposure to cercariae in older individuals. PMID:16469168

  14. Purification of a chymotrypsin-like enzyme present on adult Schistosoma mansoni worms from infected mice and its characterization as a host carboxylesterase.

    PubMed

    Igetei, Joseph E; Liddell, Susan; El-Faham, Marwa; Doenhoff, Michael J

    2016-04-01

    A serine protease-like enzyme found in detergent extracts of Schistosoma mansoni adult worms perfused from infected mice has been purified from mouse blood and further characterized. The enzyme is approximately 85 kDa and hydrolyses N-acetyl-DL-phenylalanine β-naphthyl-ester, a chromogenic substrate for chymotrypsin-like enzymes. The enzyme from S. mansoni worms appears to be antigenically and enzymatically similar to a molecule that is present in normal mouse blood and so is seemingly host-derived. The enzyme was partially purified by depleting normal mouse serum of albumin using sodium chloride and cold ethanol, followed by repeated rounds of purification by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis. The purified material was subjected to tandem mass spectrometry and its derived peptides found to belong to mouse carboxylesterase 1C. Its ability to hydrolyse α- or β-naphthyl acetates, which are general esterase substrates, has been confirmed. A similar carboxylesterase was purified and characterized from rat blood. Additional evidence to support identification of the enzyme as a carboxylesterase has been provided. Possible roles of the enzyme in the mouse host-parasite relationship could be to ease the passage of worms through the host's blood vessels and/or in immune evasion. PMID:26924446

  15. Study of the Activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis Mansoni in Mice

    PubMed Central

    da Silva, Andréa Cristina Apolinário; Neves, Juliana Kelle de Andrade Lemoine; Irmão, João Inácio; Costa, Vláudia Maria Assis; Souza, Valdênia Maria Oliveira; de Medeiros, Paloma Lys; da Silva, Eliete Cavalcanti; de Lima, Maria do Carmo Alves; Pitta, Ivan da Rocha; Albuquerque, Mônica Camelo Pessoa de Azevedo; Galdino, Suely Lins

    2012-01-01

    Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity against adult Schistosoma mansoni worms in vitro. In the first phase of this study, S. mansoni-infected mice were treated, orally, with 100 mg/Kg of the LPSF-PT05 in three formulations: Tween 80 and saline solution, oil/water (70 : 30) emulsion, and solid dispersion with polyethylene glycol (PEG). In the second phase, three other doses of the LPSF-PT05 in PEG were tested: 3, 10, 30 mg/kg. These treatment regimens significantly reduced the number of recovered worms due to increases in the solubility of the compound in this formulation; the greatest reduction (70.5%) was observed at the dose of 100 mg/kg. There was no changes in the pattern of mature egg compared to immature eggs; however there was a significant increase in the number of dead eggs. Histopathological analysis of liver tissue showed changes in morphological aspects of the hepatic parenchyma with decrease exudative-productive hepatic granuloma stages, although we found no significant differences in IFN-γ, IL-4, IL-10, or NO production in response to the specific antigen SEA. The results show the derivative LPSF-PT05 to be a potential candidate in the etiological treatment of schistosomiasis with a possible dampening effect of the granulomatous process. PMID:22623908

  16. Evaluation of the use of C-terminal part of the Schistosoma mansoni 200kDa tegumental protein in schistosomiasis diagnosis and vaccine formulation.

    PubMed

    Carvalho, Gardênia Braz Figueiredo de; Pacífico, Lucila Gonçalves Grossi; Pimenta, Deborah Laranjeira Ferreira; Siqueira, Liliane Maria Vidal; Teixeira-Carvalho, Andréa; Coelho, Paulo Marcos Zech; Pinheiro, Carina da Silva; Fujiwara, Ricardo Toshio; Oliveira, Sergio Costa; Fonseca, Cristina Toscano

    2014-04-01

    Schistosoma mansoni tegument is involved in essential functions for parasite survival and represents a target for screening candidates for vaccine and diagnosis. Our group using reverse vaccinology selected six candidates, previously demonstrated by proteomics studies to be expressed in the parasite tegument, among them was Sm200. In this work we have cloned and expressed a recombinant form of Sm200 C-terminal (1069-1520) region. The efficacy of rSm200 (1069-1520) in the diagnosis of schistosomiasis and in the formulation of a vaccine against S. mansoni was assessed respectively in an ELISA based diagnostic assay and immunization protocols in mice. Significant differences between non-infected and acutely infected or chronically infected animals were observed and no cross-recognition was observed with sera from Ascaris suum or Ancylostoma ceylanicum infected mice. rSm200-ELISA test could also discriminate infected individuals from healthy donors not living in endemic area for schistosomiasis but failed to discriminate between individuals from a low endemic area for schistosomiasis known to have positive or negative stools after examination. Recombinant Sm200 also failed to induce protection against schistosomiasis, demonstrating that the C-terminal part of Sm200 is unable to induce protective immune response in mice. Therefore rSm200 (1069-1520)-ELISA represents an important tool to be used in the diagnosis of schistosomiasis. PMID:24560833

  17. Post lung-stage schistosomula of Schistosoma mansoni exhibit transient susceptibility to macrophage-mediated cytotoxicity in vitro that may relate to late phase killing in vivo.

    PubMed

    Pearce, E J; James, S L

    1986-09-01

    Studies of protective immunity against Schistosoma mansoni in immunized mice suggest that a proportion of challenge parasites may be eliminated after they have passed through the lungs of the host several days after infection; however, no potential immune effector mechanism of resistance against this stage of the parasite has yet been identified, since schistosomes have been shown to rapidly become resistant to antibody-dependent killing mechanisms. In this study, different development stages of S. mansoni were examined for their susceptibility to in vitro cytotoxicity by lymphokine-activated macrophages. As previously shown, newly transformed larvae were readily killed by lymphokine-treated peritoneal macrophages or the macrophage cell line IC-21 (80% mortality over 48 h in vitro), whereas 7 and 10 day old lung-stage parasites had become refractory to macrophage effects. However, after 2 to 2 1/2 weeks of development in vivo, juvenile parasites recovered from the liver were again susceptible to activated macrophage-mediated cytotoxicity (25-65% mortality). Ultrastructural studies of 2 1/2 week old parasites co-cultured with activated IC-21 cells revealed that damage was largely restricted to the areas beneath the parasite surface and gut syncitia; surface membrane disruption was not evident. This late stage of susceptibility was transient and by 4 to 6 weeks liver-stage worms had again become refractory to macrophage killing. The interaction of post lung-stage parasites with activated macrophages was antibody independent. Furthermore, schistosomes isolated from the portal circulation 2 1/2 weeks after infection showed no evidence of surface-bound immunoglobulin in a quantitative immunofluorescence assay, nor did antisera from chronically infected mice (CIS) or mice vaccinated with irradiated cercariae (VS) react with the surface of these parasites in vitro, making the possibility of direct antibody-dependent killing mechanisms unlikely. However, both CIS and VS

  18. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection

    SciTech Connect

    Correa-Oliveira, R.; Sher, A.; James, S.L.

    1984-03-01

    Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model.

  19. Resistance induced by normal and irradiated Schistosoma mansoni: ability of various worm stages to serve as inducers and targets in mice

    SciTech Connect

    Dean, D.A.; Cioli, D.; Bukowski, M.A.

    1981-09-01

    Lung stage schistosomula exposed to 50 kilorads of gamma irradiation induced significant resistance to challenge infection with Schistosoma mansoni following intravenous (tail or mesenteric vein), intramuscular, or intraperitoneal injection into mice. Similar or higher levels were induced with irradiated cercariae, while irradiated 3- or 4-week-old worms induced little resistance. Non-irradiated day 6 and day 12 lung schistosomula injected into mice immunized with irradiated cercariae were susceptible to elimination, though to a lesser extent than a challenge infection administered at the cercarial stage. Day 20 liver worms injected into a mesenteric vein were not susceptible to irradiated cercaria-induced resistance. In contrast, cercariae, day 6 lung schistosomula, day 12 lung schistosomula and day 20 liver worms were all susceptible to the resistance induced by a chronic (non-irradiated) infection.

  20. Schistosoma mansoni Infection in Preschool-Aged Children: Development of Immunoglobulin E and Immunoglobulin G4 Responses to Parasite Allergen-Like Proteins

    PubMed Central

    Pinot de Moira, Angela; Sousa-Figueiredo, Jose C.; Jones, Frances M.; Fitzsimmons, Colin M.; Betson, Martha; Kabatereine, Narcis B.; Stothard, J. Russell; Dunne, David W.

    2013-01-01

    Specific immunoglobulin E (IgE) responses are upregulated during chronic schistosome infection and during allergy. These responses are tightly regulated during schistosomiasis. We have previously shown that IgE regulation depends on the extent and length of exposure to individual parasite allergen-like proteins. Here we compare the development of IgE and immunoglobulin G4 (IgG4) responses to the differentially expressed allergen-like proteins SmTAL1 and SmTAL2 among preschool-aged children from 2 villages with different levels of Schistosoma mansoni transmission. We found a lack of SmTAL1 responsiveness among all children, but evidence for IgG4-dependent IgE-SmTAL2 desensitization in both villages, occurring earlier among children from the village where the level of transmission was greater. Findings provide insights into the development and regulation of allergic-type immune responses. PMID:23125445

  1. Time course of the effect of praziquantel on Schistosoma mansoni attachment in vitro: comparison with its effects on worm length and motility.

    PubMed

    da Silva, S P; Noël, F

    1995-01-01

    We report herein that praziquantel inhibits the capacity of adult male Schistosoma mansoni to attach to the bottom of a glass dish and produces a diminution of worm length and motility, acting under a similar concentration and time dependency. After removal of 1 microM praziquantel from the medium, the worms progressively recuperated their initial length and motility without recovering their attachment capability. The absence of calcium or presence of 1 microM verapamil did not change the praziquantel-induced effect on worm attachment, causing only a transient decrease in worm length and motility. The present data indicate that the diminution of motility induced by praziquantel results from the progressive contraction of the longitudinal musculature of the worm. In contrast, the loss of attachment should not be causally related to the contraction of the worm since these two praziquantel-induced effects have distinct patterns of response under some experimental conditions. PMID:7479644

  2. Parasitological, Pathological, and Immunological Parameters Associated with Schistosoma mansoni Infection and Reinfection in BALB/c AND C57BL/6 Mice.

    PubMed

    Alves, Clarice Carvalho; Araujo, Neusa; Cassali, Geovanni Dantas; Fonseca, Cristina Toscano

    2016-06-01

    Schistosome-host interaction is influenced by multiple factors, such as the type of immune response developed by the host, host genetic background, intensity, and number of infections. Those factors not only affect the development and elimination of Schistosoma mansoni , but also the pathology triggered by infection with this parasite. In the present study, we assessed the parasitological, pathological, and immunological aspects elicited by infection and reinfection in 2 different mouse strains commonly used as models in studies on schistosomiasis: BALB/c and C57BL/6. No differences in worm burden recovery or in the number of eggs per gram of intestine or feces were observed between the strains or between infected and reinfected mice from the same strain. However, the number of eggs trapped in the liver of the reinfected mice was significantly higher than the number of eggs in the liver of the infected animals. But, the granulomatous area was significantly lower in reinfected animals than in infected ones. Additionally, granuloma in the infected BALB/c mice was greater than in infected C57BL/6 animals. Regarding the cytokine profile, spleen cells from the infected/reinfected C57BL/6 mice produced higher interleukin 10 (IL-10) levels against egg antigens than BALB/c-infected/reinfected mice. BALB/c mice, in contrast, produced significantly higher IL-4 and IL-13 cytokines after infection/reinfection than the C57BL/6 mice, with the highest levels of IL-13 being observed after reinfection. Our results demonstrate that, although different host backgrounds did not impact resistance to S. mansoni , they result in different immunological profiles that suggest different pathological impacts on the liver. PMID:26928866

  3. Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni

    PubMed Central

    Tennessen, Jacob A.; Bonner, Kaitlin M.; Bollmann, Stephanie R.; Johnstun, Joel A.; Yeh, Jan-Ying; Marine, Melanie; Tavalire, Hannah F.; Bayne, Christopher J.; Blouin, Michael S.

    2015-01-01

    Background New strategies to combat the global scourge of schistosomiasis may be revealed by increased understanding of the mechanisms by which the obligate snail host can resist the schistosome parasite. However, few molecular markers linked to resistance have been identified and characterized in snails. Methodology/Principal Findings Here we test six independent genetic loci for their influence on resistance to Schistosoma mansoni strain PR1 in the 13-16-R1 strain of the snail Biomphalaria glabrata. We first identify a genomic region, RADres, showing the highest differentiation between susceptible and resistant inbred lines among 1611 informative restriction-site associated DNA (RAD) markers, and show that it significantly influences resistance in an independent set of 439 outbred snails. The additive effect of each RADres resistance allele is 2-fold, similar to that of the previously identified resistance gene sod1. The data fit a model in which both loci contribute independently and additively to resistance, such that the odds of infection in homozygotes for the resistance alleles at both loci (13% infected) is 16-fold lower than the odds of infection in snails without any resistance alleles (70% infected). Genome-wide linkage disequilibrium is high, with both sod1 and RADres residing on haplotype blocks >2Mb, and with other markers in each block also showing significant effects on resistance; thus the causal genes within these blocks remain to be demonstrated. Other candidate loci had no effect on resistance, including the Guadeloupe Resistance Complex and three genes (aif, infPhox, and prx1) with immunological roles and expression patterns tied to resistance, which must therefore be trans-regulated. Conclusions/Significance The loci RADres and sod1 both have strong effects on resistance to S. mansoni. Future approaches to control schistosomiasis may benefit from further efforts to characterize and harness this natural genetic variation. PMID:26372103

  4. Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs

    SciTech Connect

    Kelleher, Alan; Darwiche, Rabih; Rezende, Wanderson C.; Farias, Leonardo P.; Leite, Luciana C. C.; Schneiter, Roger; Asojo, Oluwatoyin A.

    2014-08-01

    The first structure of an S. mansoni venom allergen-like protein is presented. Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic α/β-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residues and is missing the histidines that coordinate divalent cations such as Zn{sup 2+} in other SCP/TAPS proteins. SmVAL4 has a cavity between α-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1.

  5. Induction of cytotoxic T-cell activity by the protective antigen of Schistosoma mansoni Sm28GST or its derived C-terminal lipopeptide.

    PubMed

    Pancré, V; Gras-Masse, H; Delanoye, A; Herno, J; Capron, A; Auriault, C

    1996-11-01

    In a previous work the authors demonstrated that immunization with Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST) was able to reduce hepatic damage in infected mice and that the adoptive transfer of Sm28GST-specific T cells reproduced the protective effect obtained with the recombinant molecule. In the present paper, the authors show that Sm28GST is also able to stimulate an antigen-specific, cytotoxic T-cell response against Sm28GST-pulsed P815 target cells in normal mice and that effector cells induced in vivo were classical Class I MHC-restricted CD8+ lymphocytes. The authors found no spontaneous CTL activity against Sm28GST-pulsed target cells during the course of the infection by S. mansoni although Sm28GST is expressed at different developmental stages of the parasite. It was observed, however, that immunization with Sm28GST is sufficient to elicit a significant level of CTL response for 6 weeks in infected mice. The role of these Class I MHC-restricted CD8+ lymphocytes in the protection observed precisely at the same period in immunized mice remains to be elucidated. The authors also observe that immunization with the lipopeptide form of the C-terminal peptide of the molecule (190-211 peptide) led to a CTL activation comparable to that observed after immunization with the whole molecule demonstrating the feasibility of using a synthetic lipopeptide as immunogen for a CTL response against Sm28GST epitopes. Moreover, like Sm28GST-specific CTLs, 190-211 lipopeptide-specific cells were also Class I MHC-restricted lymphocytes. PMID:8947600

  6. Resistance induced by drug abbreviated Schistosoma mansoni infections: treatment with the drug Ro11-3128 leads to enhanced antigen presentation.

    PubMed Central

    Smith, D A; Bickle, Q D; Kaye, P M

    1994-01-01

    Treatment of mice with the benzodiazepine derivative Ro11-3128 1-2 days post-infection with Schistosoma mansoni leads to arrest of virtually all schistosomula at the skin stage, and results in the development of protective immunity to challenge infection. A characteristic feature of Ro11-3128 treatment in vitro is the formation of exudates and membranous blebs at the schistosomular surface; other drugs tested, such as Ro15-5458 and oxamniquine which are also effective against the skin stages but relatively ineffective in inducing protection, do not induce this reaction. Here, we have examined whether such in vitro treatment causes enhanced presentation of schistosomular antigens by host antigen-presenting cells (APC) using an in vitro assay with activated peritoneal adherent cells as APC and T cells from S. mansoni antigen-sensitized mice. We have shown that viable mechanically transformed schistosomula (MS) can be processed and presented with similar kinetics to soluble antigen. However, in vitro drug treatment leads to enhanced presentation of MS. Experiments in which membranous blebs and antigen released by Ro11-3128-treated parasites during in vitro culture were separated from the remaining intact schistosomula, demonstrated significant stimulatory activity in the soluble and particulate-released antigen fractions. Filtration, antigen transfer experiments and SDS-PAGE analysis of the released material further suggested that most of the activity resided in the particulate fraction. Thus, quantitative and qualitative changes to antigen presentation by Ro11-3128 treatment early after infection may underlie the immunoprotective efficacy of Ro11-3128-abbreviated infections. Images Figure 3 Figure 9 PMID:7959877

  7. Schistosoma mansoni Soluble Egg Antigens Induce Expression of the Negative Regulators SOCS1 and SHP1 in Human Dendritic Cells via Interaction with the Mannose Receptor

    PubMed Central

    Klaver, Elsenoor J.; Kuijk, Loes M.; Lindhorst, Thisbe K.; Cummings, Richard D.; van Die, Irma

    2015-01-01

    Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. In addition, SEA induces the secretion of transforming growth factor β (TGF-β), and the surface expression of the costimulatory molecules Programmed Death Ligand-1 (PD-L1) and OX40 ligand (OX40L), which are known phenotypic markers for the capacity of DCs to polarize naïve T cells into Th2/Treg cell subsets. Inhibition of mannose receptor (MR)-mediated internalization of SEA into DCs by blocking with allyl α-D-mannoside or anti-MR antibodies, significantly reduced SOCS1 and SHP1 expression. In conclusion, we demonstrate that SEA glycans are essential for induction of enhanced SOCS1 and SHP1 levels in DCs via the MR. Our data provide novel mechanistic evidence for the potential of S. mansoni SEA glycans to modulate human DCs, which may contribute to the capacity of SEA to down-regulate inflammatory responses. PMID:25897665

  8. Parasitological and biochemical parameters in Schistosoma mansoni-infected mice treated with methanol extract from the plants Chenopodium ambrosioides, Conyza dioscorides and Sesbania sesban.

    PubMed

    Kamel, E G; El-Emam, M A; Mahmoud, S S M; Fouda, F M; Bayaumy, F E

    2011-12-01

    This study aims to detect the antischistosomal properties of the plants' Chenopodium ambrosioides, Conyza dioscorides and Sesbania sesban methanol extract against Schistosoma mansoni in infected mice, including determination of total protein and albumin levels and the activities of alanine and aspartate transaminases (AlT, AsT) and acid and alkaline phosphatases (AcP and AkP) enzymes in the serum of infected treated mice. Male Swiss albino mice were infected with S. mansoni and orally treated with methanol extract of the plants C. ambrosioides (1250 mg/kg/day), C. dioscorides and S. sesban (1000 mg/kg/day from each) for 2 consecutive days 7 weeks post infection (PI). In addition, treatment of mice with the tested dose of each plant extract was successively done (i.e. the 1st extract followed by the 2nd and 3rd one with an hour interval). Parasitological and biochemical parameters were assessed. Nine weeks PI, the reduction rates of worm load/mouse treated with either C. dioscorides (1000 mg/kg), C. ambrosioides (1250 mg/kg) or S. sesban (1000 mg/kg) were 40.9%, 53.7% and 54.4%, respectively. Successive treatment raised the reduction rates of worm load/mouse to 66.3% and the ova/g tissue in liver to 76.9%. Moreover, serum total protein and albumin levels and activities of AlT, Ast, AcP and AkP enzymes of infected treated mice were improved in comparison with those of infected untreated ones. It is concluded that administration of C. dioscorides, C. ambrosioides and S. sesban methanol extract to infected mice exhibited a moderate antischistosomal effect. Successive treatment improved the antischistosomal properties of these plant species, hence ameliorated the liver functions of treated mice that may suggest degenerations of liver granulomas and regenerative changes. PMID:21740980

  9. Systematic Review and Meta-analysis of the Impact of Chemical-Based Mollusciciding for Control of Schistosoma mansoni and S. haematobium Transmission

    PubMed Central

    King, Charles H.; Sutherland, Laura J.; Bertsch, David

    2015-01-01

    Background Programs for schistosomiasis control are advancing worldwide, with many benefits noted in terms of disease reduction. Yet risk of reinfection and recurrent disease remain, even in areas with high treatment coverage. In the search for means to better prevent new Schistosoma infections, attention has returned to an older strategy for transmission control, i.e., chemical mollusciciding, to suppress intermediate host snail species responsible for S. mansoni and S. haematobium transmission. The objective of this systematic review and meta-analysis was to summarize prior experience in molluscicide-based control of Bulinus and Biomphalaria spp. snails, and estimate its impact on local human Schistosoma infection. Methodology/Principal Findings The review was registered at inception with PROSPERO (CRD42013006869). Studies were identified by online database searches and hand searches of private archives. Eligible studies included published or unpublished mollusciciding field trials performed before January 2014 involving host snails for S. mansoni or S. haematobium, with a primary focus on the use of niclosamide. Among 63 included papers, there was large variability in terms of molluscicide dosing, and treatment intervals varied from 3–52 weeks depending on location, water source, and type of application. Among 35 studies reporting on prevalence, random effects meta-analysis indicated that, on average, odds of infection were reduced 77% (OR 0.23, CI95% 0.17, 0.31) during the course of mollusciciding, with increased impact if combined with drug therapy, and progressively greater impact over time. In 17 studies reporting local incidence, risk of new infection was reduced 64% (RR 0.36 CI95% 0.25, 0.5), but additional drug treatment did not appear to influence incidence effects. Conclusion/Significance While there are hurdles to implementing molluscicide control, its impact on local transmission is typically strong, albeit incomplete. Based on past experience

  10. Comparison of Schistosoma mansoni Prevalence and Intensity of Infection, as Determined by the Circulating Cathodic Antigen Urine Assay or by the Kato-Katz Fecal Assay: A Systematic Review.

    PubMed

    Kittur, Nupur; Castleman, Jennifer D; Campbell, Carl H; King, Charles H; Colley, Daniel G

    2016-03-01

    The relationship between results from Kato-Katz (KK) fecal microscopy and urine-based point-of-care circulating cathodic antigen (POC-CCA) assays for Schistosoma mansoni infection remains a critical issue. This systematic literature review of 25 published papers compares prevalence of S. mansoni infection by KK with that by the POC-CCA assay. Nineteen published studies met our inclusion criteria for data extraction and analysis. Above a prevalence of 50% by KK, KK and POC-CCA results yielded essentially the same prevalence. Below 50% prevalence by KK, the prevalence by the POC-CCA assay was between 1.5- and 6-fold higher and increased as prevalence by KK decreased. Five of nine publications met inclusion criteria for extractable data on intensity of S. mansoni infection by KK assay and visual band density using the POC-CCA assay. A clear positive relationship exists between intensity by the KK and POC-CCA assays. This systematic review indicates that below 50% prevalence, the POC-CCA assay is much more sensitive than the KK assay. However, the existing data are inadequate to precisely define the relationship between POC-CCA and KK at lower levels of KK prevalence. More studies directly comparing the two assays in low-prevalence areas are essential to inform decision-making by national schistosomiasis control programs. PMID:26755565

  11. Comparison of Schistosoma mansoni Prevalence and Intensity of Infection, as Determined by the Circulating Cathodic Antigen Urine Assay or by the Kato-Katz Fecal Assay: A Systematic Review

    PubMed Central

    Kittur, Nupur; Castleman, Jennifer D.; Campbell, Carl H.; King, Charles H.; Colley, Daniel G.

    2016-01-01

    The relationship between results from Kato-Katz (KK) fecal microscopy and urine-based point-of-care circulating cathodic antigen (POC-CCA) assays for Schistosoma mansoni infection remains a critical issue. This systematic literature review of 25 published papers compares prevalence of S. mansoni infection by KK with that by the POC-CCA assay. Nineteen published studies met our inclusion criteria for data extraction and analysis. Above a prevalence of 50% by KK, KK and POC-CCA results yielded essentially the same prevalence. Below 50% prevalence by KK, the prevalence by the POC-CCA assay was between 1.5- and 6-fold higher and increased as prevalence by KK decreased. Five of nine publications met inclusion criteria for extractable data on intensity of S. mansoni infection by KK assay and visual band density using the POC-CCA assay. A clear positive relationship exists between intensity by the KK and POC-CCA assays. This systematic review indicates that below 50% prevalence, the POC-CCA assay is much more sensitive than the KK assay. However, the existing data are inadequate to precisely define the relationship between POC-CCA and KK at lower levels of KK prevalence. More studies directly comparing the two assays in low-prevalence areas are essential to inform decision-making by national schistosomiasis control programs. PMID:26755565

  12. Effective anthelmintic therapy of residents living in endemic area of high prevalence for Hookworm and Schistosoma mansoni infections enhances the levels of allergy risk factor anti-Der p1 IgE

    PubMed Central

    Campolina, Sabrina S.; Araujo, Marcio S.S.; Rezende, Tércia M.R.L.; Matoso, Leonardo; Quites, Humberto F.O.; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo A.; Gazzinelli, Andrea; Correa-Oliveira, Rodrigo

    2013-01-01

    In this work were investigated the relationship between Hookworm/Schistosoma mansoni infections and allergy related risk factors in two endemic areas with distinct prevalence of infections and co-infection. The intensity of infections, eosinophilia, allergy risk factors, infections status and anti-Der p1 IgE levels before and 2 years (population 1) and 3 years (population 2) after anthelmintic treatment, were evaluated. It was observed that the population with lower prevalence and intensity of infection (population 2) had lower eosinophils counts (>600/mm3) and higher animal contact than the population with higher parasites intensity (population 1). After anthelmintic treatment the intensity of S. mansoni single infection decreased, but no changes were observed in Hookworm and co-infected individuals. The anthelmintic treatment also enhanced anti-Der p1 IgE optical density in ELISA on the subgroups that became negative for helminth infection regardless of their previous infection condition in population 1. Facing that, we evaluated the anti-Der p1 IgE reactivity index, and the ratio (after/before treatment) was significantly higher in patients co-infected before treatment. On the other hand, no association between anti-Der p1 IgE reactivity index and the intensity of infections were observed. In conclusion, effective anthelmintic therapy of subjects from endemic areas with high prevalence of Hookworm and S. mansoni infections enhances anti-Der p1 IgE levels. PMID:25905031

  13. Effective anthelmintic therapy of residents living in endemic area of high prevalence for Hookworm and Schistosoma mansoni infections enhances the levels of allergy risk factor anti-Der p1 IgE.

    PubMed

    Campolina, Sabrina S; Araujo, Marcio S S; Rezende, Tércia M R L; Matoso, Leonardo; Quites, Humberto F O; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo A; Gazzinelli, Andrea; Correa-Oliveira, Rodrigo

    2015-01-01

    In this work were investigated the relationship between Hookworm/Schistosoma mansoni infections and allergy related risk factors in two endemic areas with distinct prevalence of infections and co-infection. The intensity of infections, eosinophilia, allergy risk factors, infections status and anti-Der p1 IgE levels before and 2 years (population 1) and 3 years (population 2) after anthelmintic treatment, were evaluated. It was observed that the population with lower prevalence and intensity of infection (population 2) had lower eosinophils counts (>600/mm(3)) and higher animal contact than the population with higher parasites intensity (population 1). After anthelmintic treatment the intensity of S. mansoni single infection decreased, but no changes were observed in Hookworm and co-infected individuals. The anthelmintic treatment also enhanced anti-Der p1 IgE optical density in ELISA on the subgroups that became negative for helminth infection regardless of their previous infection condition in population 1. Facing that, we evaluated the anti-Der p1 IgE reactivity index, and the ratio (after/before treatment) was significantly higher in patients co-infected before treatment. On the other hand, no association between anti-Der p1 IgE reactivity index and the intensity of infections were observed. In conclusion, effective anthelmintic therapy of subjects from endemic areas with high prevalence of Hookworm and S. mansoni infections enhances anti-Der p1 IgE levels. PMID:25905031

  14. The Effect of Increasing Water Temperatures on Schistosoma mansoni Transmission and Biomphalaria pfeifferi Population Dynamics: An Agent-Based Modelling Study

    PubMed Central

    McCreesh, Nicky; Booth, Mark

    2014-01-01

    Introduction There is increasing interest in the control and elimination of schistosomiasis. Little is known, however, about the likely effects of increasing water-body temperatures on transmission. Methods We have developed an agent-based model of the temperature-sensitive stages of the Schistosoma and intermediate host snail life-cycles, parameterised using data from S. mansoni and Biomphalaria pfeifferi laboratory and field-based observations. Infection risk is calculated as the number of cercariae in the model, adjusted for their probability of causing infection. Results The number of snails in the model is approximately constant between 15–31°C. Outside this range, snail numbers drop sharply, and the snail population cannot survive outside the range 14–32°C. Mean snail generation time decreases with increasing temperature from 176 days at 14°C to 46 days at 26°C. Human infection risk is highest between 16–18°C and 1 pm and 6–10 pm in calm water, and 20–25°C and 12–4 pm in flowing water. Infection risk increases sharply when temperatures increase above the minimum necessary for sustained transmission. Conclusions The model suggests that, in areas where S. mansoni is already endemic, warming of the water at transmission sites will have differential effects on both snails and parasites depending on abiotic properties of the water-body. Snail generation times will decrease in most areas, meaning that snail populations will recover faster from natural population reductions and from snail-control efforts. We suggest a link between the ecological properties of transmission sites and infection risk which could significantly affect the outcomes of interventions designed to alter water contact behaviour – proposing that such interventions are more likely to reduce infection levels at river locations than lakes, where infection risk remains high for longer. In cooler areas where snails are currently found, increasing temperatures may significantly

  15. Safety and efficacy of praziquantel syrup (Epiquantel®) against Schistosoma haematobium and Schistosoma mansoni in preschool-aged children in Niger.

    PubMed

    Garba, Amadou; Lamine, Mariama S; Djibo, Ali; Tahirou, Almoustapha; Aouami, Mahamadou Aboubacar; Alfari, Aichatou; Phillips, Anna E; Fenwick, Alan; Utzinger, Jürg

    2013-11-01

    Given the characteristic age-prevalence curve of Schistosoma infection, preventive chemotherapy with praziquantel is primarily targeted at school-aged children, whilst, in highly endemic areas, other high-risk groups might be included for regular treatment. Nevertheless, schistosomiasis can affect children well before they reach school-age, but this population group is usually excluded from preventive chemotherapy. We assessed the safety and efficacy of praziquantel syrup (Epiquantel®) in preschool-aged children in three villages of Niger. Children aged ≤72 months provided multiple urine and stool samples that were microscopically examined using standard protocols. Schistosoma-positive children were treated with praziquantel syrup at a dose of 40 mg/kg after a meal of millet porridge. Children remained under medical supervision for 4h and adverse events were recorded. Additionally, a questionnaire was administrated to the mothers/guardians 24h post-treatment for further probing of adverse events. Treatment efficacy was evaluated 3 and 6 weeks post-treatment using multiple stool and urine samples. A third of the 243 treated children reported adverse events within 4h, whilst a further 6.2% reported adverse events upon probing 24h post-treatment. Abdominal pain, bloody diarrhoea and sleepiness were the most common adverse events, but these were transient and self-limiting. Praziquantel syrup showed moderate-to-high efficacy against Schistosoma haematobium with egg reduction rates of 69.4% and 71.2% 3 and 6 weeks post-treatment and cure rates of 85.7% (95% confidence interval (CI) 79.7-90.5%) and 94.9% (95% CI 90.5-97.6%), respectively. Considerably lower cure and egg reduction rates were observed against Schistosoma mansoni (e.g. cure rate at 6-week post-treatment follow-up was only 50.6% (95% CI 39.9-61.2%). Concluding, praziquantel syrup is well tolerated in preschool-aged children with moderate-to-high efficacy against S. haematobium, but considerably lower

  16. Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni

    PubMed Central

    Long, Thavy; Neitz, R. Jeffrey; Beasley, Rachel; Kalyanaraman, Chakrapani; Suzuki, Brian M.; Jacobson, Matthew P.; Dissous, Colette; McKerrow, James H.; Drewry, David H.; Zuercher, William J.; Singh, Rahul; Caffrey, Conor R.

    2016-01-01

    Background Schistosoma flatworm parasites cause schistosomiasis, a chronic and debilitating disease of poverty in developing countries. Praziquantel is employed for treatment and disease control. However, its efficacy spectrum is incomplete (less active or inactive against immature stages of the parasite) and there is a concern of drug resistance. Thus, there is a need to identify new drugs and drug targets. Methodology/Principal Findings We show that RNA interference (RNAi) of the Schistosoma mansoni ortholog of human polo-like kinase (huPLK)1 elicits a deleterious phenotypic alteration in post-infective larvae (schistosomula or somules). Phenotypic screening and analysis of schistosomula and adult S. mansoni with small molecule inhibitors of huPLK1 identified a number of potent anti-schistosomals. Among these was a GlaxoSmithKline (GSK) benzimidazole thiophene inhibitor that has completed Phase I clinical trials for treatment of solid tumor malignancies. We then obtained GSKs Published Kinase Inhibitor Sets (PKIS) 1 and 2, and phenotypically screened an expanded series of 38 benzimidazole thiophene PLK1 inhibitors. Computational analysis of controls and PLK1 inhibitor-treated populations of somules demonstrated a distinctive phenotype distribution. Using principal component analysis (PCA), the phenotypes exhibited by these populations were mapped, visualized and analyzed through projection to a low-dimensional space. The phenotype distribution was found to have a distinct shape and topology, which could be elicited using cluster analysis. A structure-activity relationship (SAR) was identified for the benzimidazole thiophenes that held for both somules and adult parasites. The most potent inhibitors produced marked phenotypic alterations at 1–2 μM within 1 h. Among these were compounds previously characterized as potent inhibitors of huPLK1 in cell assays. Conclusions/Significance The reverse genetic and chemical SAR data support a continued investigation of Sm

  17. Cloning of a protein arginine methyltransferase PRMT1 homologue from Schistosoma mansoni: Evidence for roles in nuclear receptor signaling and RNA metabolism

    SciTech Connect

    Mansure, Jose Joao; Furtado, Daniel Rodrigues; Bastos de Oliveira, Francisco Meirelles; Rumjanek, Franklin David; Franco, Gloria Regina; Fantappie, Marcelo Rosado . E-mail: fantappie@bioqmed.ufrj.br

    2005-10-07

    The most studied arginine methyltransferase is the type I enzyme, which catalyzes the transfer of an S-adenosyl-L-methionine to a broad spectrum of substrates, including histones, RNA-transporting proteins, and nuclear hormone receptor coactivators. We cloned a cDNA encoding a protein arginine methyltransferase in Schistosoma mansoni (SmPRMT1). SmPRMT1 is highly homologous to the vertebrate PRMT1 enzyme. In vitro methylation assays showed that SmPRMT1 recombinant protein was able to specifically methylate histone H4. Two schistosome proteins likely to be involved in RNA metabolism, SMYB1 and SmSmD3, that display a number of RGG motifs, were strongly methylated by SmPRMT1. In vitro GST pull-down assays showed that SMYB1 and SmSmD3 physically interacted with SmPRMT1. Additional GST pull-down assay suggested the occurrence of a ternary complex including SmPRMT1, SmRXR1 nuclear receptor, and the p160 (SRC-1) nuclear receptor coactivator. Together, these data suggest a mechanism by which SmPRMT1 plays a role in nuclear receptor-mediated chromatin remodeling and RNA transactions.

  18. The Use of Reverse Vaccinology and Molecular Modeling Associated with Cell Proliferation Stimulation Approach to Select Promiscuous Epitopes from Schistosoma mansoni.

    PubMed

    Oliveira, Flávio M; Coelho, Ivan E V; Lopes, Marcelo D; Taranto, Alex G; Junior, Moacyr C; Santos, Luciana L D; Villar, José A P F; Fonseca, Cristina T; Lopes, Débora D O

    2016-07-01

    Schistosomiasis remains an important parasitic disease that affects millions of individuals worldwide. Despite the availability of chemotherapy, the occurrence of constant reinfection demonstrates the need for additional forms of intervention and the development of a vaccine represents a relevant strategy to control this disease. With the advent of genomics and bioinformatics, new strategies to search for vaccine targets have been proposed, as the reverse vaccinology. In this work, computational analyses of Schistosoma mansoni membrane proteins were performed to predict epitopes with high affinity for different human leukocyte antigen (HLA)-DRB1. Ten epitopes were selected and along with murine major histocompatibility complex (MHC) class II molecule had their three-dimensional structures optimized. Epitope interactions were evaluated against murine MHC class II molecule through molecular docking, electrostatic potential, and molecular volume. The epitope Sm141290 and Sm050890 stood out in most of the molecular modeling analyses. Cellular proliferation assay was performed to evaluate the ability of these epitopes to bind to murine MHC II molecules and stimulate CD4+ T cells showing that the same epitopes were able to significantly stimulate cell proliferation. This work showed an important strategy of peptide selection for epitope-based vaccine design, achieved by in silico analyses that can precede in vivo and in vitro experiments, avoiding excessive experimentation. PMID:26979443

  19. Partial purification and characterization of an inhibitor from newborn-rat epidermis with activity against the proteinase of Schistosoma mansoni cercariae.

    PubMed Central

    Tzeng, S; McKerrow, J H; Jeong, K; Fukuyama, K; Epstein, W L

    1982-01-01

    The penetration of cercariae through the skin initiates infection of the host with the human trematode parasite Schistosoma mansoni. Many larvae fail to migrate into the living epidermal cell layer. In order to determine if chemical as well as mechanical barriers to cercarial skin penetration exist, inhibitory activity of epidermal cell extracts against the proteinase obtained from cercarial secretions was assayed. An inhibitor was purified 50-fold by gel filtration on Sephadex G 75 and cation exchange chromatography at pH 5.8 and 4.9. The inhibitor has a relative molecular mass (Mr) of approx. 40 000-53 000. Oxidation of the inhibitor with N-chlorosuccinimide eliminated its inhibitory activity and thus indicated a critical methionine residue. The inhibitor was active against a wide spectrum of serine proteinases: porcine pancreatic elastase, human granulocyte elastase, bovine trypsin, and bovine alpha-chymotrypsin. However, no inhibition was detected against papain or clostridial collagenase. The inhibitor did not cross react with antiserum to human or rat serum alpha 1-proteinase inhibitor. Images Fig. 3. PMID:7165704

  20. A unique nuclear receptor direct repeat 17 (DR17) is present within the upstream region of Schistosoma mansoni female-specific p14 gene

    SciTech Connect

    Fantappie, Marcelo Rosado Furtado, Daniel Rodrigues; Rumjanek, Franklin David; LoVerde, Philip T.

    2008-07-11

    The eggs produced by sexually mature female Schistosma mansoni are responsible for the pathogenesis of the disease. The eggshell precursor gene p14 is expressed only in the vitelline cells of sexually mature female worms in response to a yet unidentified male stimulus. Herein, we report the identification of a novel nuclear receptor response element in the upstream region of the p14 gene. This element contains the canonical hexameric DNA core motif, 5'-PuGGTCA, composed of an atypically spaced direct repeat (DR17). Schistosome nuclear receptors SmRXR1 and SmNR1 specifically bound to the p14-DR17 element as a heterodimer. SmRXR1, but not SmNR1, bound to the motif as a monomer. Introduction of mutations in the TCA core sequence completely abolished the binding by SmRXR1/SmNR1 heterodimer. This finding supports our hypothesis that the expression of Schistosoma mansonip14 gene is regulated through the nuclear receptor signaling pathway.

  1. Distribution and Schistosoma mansoni infection of Biomphalaria glabrata in different habitats in a rural area in the Jequitinhonha Valley, Minas Gerais, Brazil: environmental and epidemiological aspects.

    PubMed

    Kloos, Helmut; Passos, Liana Kanovaloff Janotti; Loverde, Philip; Oliveira, Rodrigo Correa; Gazzinelli, Andréa

    2004-11-01

    This paper examines the distribution and infection of Biomphalaria glabrata with Schistosoma mansoni in all aquatic snail habitats in a rural area in the state of Minas Gerais, Brazil, in relation to physico/biotic and behavioral factors. Snail and environmental surveys were carried out semi-annually between July 2001 and November 2002 at 106 sites. Collected snails were examined in the laboratory for infection. B. glabrata densities were highest in overflow ponds, irrigation ponds, springs, canals and wells, and lowest in fishponds and water tanks. Snail densities were higher during the hot, rainy season except for streams and canals and were statistically associated with the presence of fish, pollution, and vegetation density. Tilapia fish and an unidentified Diptera larva were found to be predators of B. glabrata but ducks were not. Twenty-four of the 25 infected snails were collected in 2001(1.4% infection rate) and only one in 2002, after mass chemotherapy. The occurrence of B. glabrata in all 11 snail habitats both at and away from water contact sites studied indicates widespread risk of human infection in the study area. In spite of the strong association between B. glabrata and tilapia in fishponds we do not recommend its use in schistosomiasis control for ecological reasons and its relative inefficiency in streams and dams. PMID:15654420

  2. Schistosoma mansoni PIII antigen modulates in vitro granuloma formation by regulating CD28, CTLA-4, and CD86 expression in humans.

    PubMed

    Zouain, C S; Falcão, P L; Goes, T S; Leite, M F; Goes, A M

    2004-02-15

    We investigated the in vitro responses of peripheral blood mononuclear cells (PBMC) from intestinal chronic schistosomiasis patients to PIII, a multivalent antigen prepared from Schistosoma mansoni adult worm. PIII decreased cellular proliferation and granulomatous reaction. Moreover, induced the reduction of IFN-gamma levels and increased IL-10 production. To better understand the mechanism through which the observed suppression occurs, the present study focused on the phenotypic pattern displayed by PBMC treated with PIII in an in vitro granuloma assay. Expression of the surface markers CD28, CTLA-4 and CD86 by lymphocytes and monocytes were analyzed by flow cytometry. Our results demonstrated a significant decrease of CD28+CD4+ and CD28+CD8+ T-cell percentage stimulated by PIII compared to its non-infected counterparts. This suppressive effect was related to a significant increase in the percentage of T-cells expressing CTLA-4. PIII also promoted a significant increase in the percentage of cells expressing CD86. Indeed, our results demonstrated that PIII was capable of modulating in vitro granuloma reaction, and this event was related to the balance of IL-10, IFN-gamma and CD28, CTLA-4, CD86 bringing new insight to the immunoregulation of granulomatous hypersensitivity in human schistosomiasis. PMID:15019278

  3. Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

    SciTech Connect

    Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.; James, S. )

    1991-03-01

    Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production, whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.

  4. Evaluation of the immune response and protective efficacy of Schistosoma mansoni Cathepsin B in mice using CpG dinucleotides as adjuvant.

    PubMed

    Ricciardi, Alessandra; Dalton, John P; Ndao, Momar

    2015-01-01

    Schistosomiasis is the most important human helminth infection due to its impact on public health. Worldwide, schistosomiasis is estimated to infect at least 200 million individuals while 700 million are at risk. The clinical manifestations are chronic and significantly decrease an individual's quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. Our group has chosen to target Schistosoma mansoni Cathepsin B as a prospective vaccine candidate. The recombinant protein was tested in the presence of synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides, which are Toll-like receptor 9 agonists known to stimulate a Th1 response. This formulation conferred a 59% decrease in worm burden as well as a reduction in egg burden. Hepatic egg burden and intestinal egg burden were decreased by 56% and 54% respectively. Immunizations with the formulation elicited robust production of Sm-Cathepsin B specific antibodies, both IgG1 and IgG2c but with the latter predominating. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, had increased secretion levels of key Th1 cytokines, IFN-γ and TNF-α, as well as the chemokine CCL5 when stimulated with recombinant Sm-Cathepsin B. These results highlight the potential of Sm-Cathepsin B/CpG as a vaccine candidate against schistosomiasis. PMID:25448114

  5. Avidity of immunoglobulin G antibody response to the different antigenic fractions of soluble Schistosoma mansoni adult worm antigen preparation (SWAP) using avidity immunoblotting assay.

    PubMed

    Tawfeek, Gihan M; Hameed, Dina M Abdel; el-Hoseiny, Laila M

    2004-08-01

    The detection of IgG antibodies against the different SWAP antigenic fractions plus the determination of their avidity in avidity immunoblotting assay using 6 M urea wash, presents a novel alternative for the characterization of optimal antigenic markers for acute and chronic phases of Schistosoma mansoni infection and for vaccine development. Human serum samples from 25 acute schistosomiasis patients, 20 chronic cases and 15 normal healthy controls were analysed by IgG avidity enzyme linked immunosorbent assay (ELISA) and IgG avidity immunoblotting assay. Using avidity ELISA, a pronounced overlap of avidity index values was observed between acute and chronic infections with a range of uncertainty (0.86-1) which was encountered in both groups. Using avidity immunoblotting assay, antigenic bands at >116, 84, 48, 40 & 34 KDa were exclusive for the acute phase. From these bands, 34 KDa was recognized mostly by low-avidity antibodies and showed a high sensitivity (96%) and specificity (100%) making it an optimal marker for the acute phase. 40 KDa band was recognized mostly by high-avidity antibodies even during acute infection. Bands of 80, 70, 42, 36, 30 & 26 KDa were exclusive for the chronic phase. Only 70 KDa band was recognized by high-avidity antibodies yet, with low sensitivity (35%), that limits its use as an optimal marker for the chronic infection. Meanwhile, 70 and 40 KDa bands, recognized by high-avidity antibodies, are considered as potential vaccine antigen candidates. PMID:15287177

  6. Crystal structure of a Schistosoma mansoni septin reveals the phenomenon of strand slippage in septins dependent on the nature of the bound nucleotide.

    PubMed

    Zeraik, Ana E; Pereira, Humberto M; Santos, Yuri V; Brandão-Neto, José; Spoerner, Michael; Santos, Maiara S; Colnago, Luiz A; Garratt, Richard C; Araújo, Ana P U; DeMarco, Ricardo

    2014-03-14

    Septins are filament-forming GTP-binding proteins involved in important cellular events, such as cytokinesis, barrier formation, and membrane remodeling. Here, we present two crystal structures of the GTPase domain of a Schistosoma mansoni septin (SmSEPT10), one bound to GDP and the other to GTP. The structures have been solved at an unprecedented resolution for septins (1.93 and 2.1 Å, respectively), which has allowed for unambiguous structural assignment of regions previously poorly defined. Consequently, we provide a reliable model for functional interpretation and a solid foundation for future structural studies. Upon comparing the two complexes, we observe for the first time the phenomenon of a strand slippage in septins. Such slippage generates a front-back communication mechanism between the G and NC interfaces. These data provide a novel mechanistic framework for the influence of nucleotide binding to the GTPase domain, opening new possibilities for the study of the dynamics of septin filaments. PMID:24464615

  7. Evaluation of parasitological and molecular techniques for the diagnosis and assessment of cure of schistosomiasis mansoni in a low transmission area

    PubMed Central

    Siqueira, Liliane Maria Vidal; Gomes, Luciana Inácia; Oliveira, Edward; de Oliveira, Eduardo Ribeiro; de Oliveira, Áureo Almeida; Enk, Martin Johannes; Carneiro, Nídia Figueiredo; Rabello, Ana; Coelho, Paulo Marcos Zech

    2015-01-01

    This study evaluated parasitological and molecular techniques for the diagnosis and assessment of cure of schistosomiasis mansoni. A population-based study was performed in 201 inhabitants from a low transmission locality named Pedra Preta, municipality of Montes Claros, state of Minas Gerais, Brazil. Four stool samples were analysed using two techniques, the Kato-Katz® (KK) technique (18 slides) and the TF-Test®, to establish the infection rate. The positivity rate of 18 KK slides of four stool samples was 28.9% (58/201) and the combined parasitological techniques (KK+TF-Test®) produced a 35.8% positivity rate (72/201). Furthermore, a polymerase chain reaction (PCR)-ELISA assay produced a positivity rate of 23.4% (47/201) using the first sample. All 72 patients with positive parasitological exams were treated with a single dose of Praziquantel® and these patients were followed-up 30, 90 and 180 days after treatment to establish the cure rate. Cure rates obtained by the analysis of 12 KK slides were 100%, 100% and 98.4% at 30, 90 and 180 days after treatment, respectively. PCR-ELISA revealed cure rates of 98.5%, 95.5% and 96.5%, respectively. The diagnostic and assessment of cure for schistosomiasis may require an increased number of KK slides or a test with higher sensitivity, such as PCR-ELISA, in situations of very low parasite load, such as after therapeutic interventions. PMID:25946244

  8. Curupira-1 and Curupira-2, two novel Mutator-like DNA transposons from the genomes of human parasites Schistosoma mansoni and Schistosoma japonicum.

    PubMed

    Jacinto, Daniele S; Muniz, Heloisa Dos Santos; Venancio, Thiago M; Wilson, R Alan; Verjovski-Almeida, Sergio; Demarco, Ricardo

    2011-08-01

    Transposons of the Mutator superfamily have been widely described in plants, but only recently have metazoan organisms been shown to harbour them. In this work we describe novel Mutator superfamily transposons from the genomes of the human parasites Schistosoma mansoni and S. japonicum, which we name Curupira-1 and Curupira-2. Curupira elements do not have Terminal Inverted Repeats (TIRs) at their extremities and generate Target Site Duplications (TSDs) of 9 base pairs. Curupira-2 transposons code for a conserved transposase and SWIM zinc finger domains, while Curupira-1 elements comprise these same domains plus a WRKY zinc finger. Alignment of transcript sequences from both elements back to the genomes indicates that they are subject to splicing to produce mature transcripts. Phylogenetic analyses indicate that these transposons represent a new lineage of metazoan Mutator-like elements with characteristics that are distinct from the recently described Phantom elements. Description of these novel schistosome transposons provides new insights in the evolution of transposable elements in schistosomes. PMID:21756422

  9. Degradation of extracellular matrix by larvae of Schistosoma mansoni. I. Degradation by cercariae as a model for initial parasite invasion of host

    SciTech Connect

    McKerrow, J.H.; Keene, W.E.; Jeong, K.H.; Werb, Z.

    1983-01-01

    The ability of cercariae of Schistosoma mansoni to degrade a model extracellular connective tissue matrix produced by rat vascular smooth muscle cells in culture was investigated. In this model, connective tissue macromolecules are present in the interactive framework that characterizes their structure in vivo. Cercariae were stimulated to degrade the matrix by skin lipid or linoleic acid. At the maximally stimulating concentration of linoleic acid (25 ..mu..g/cm/sup 2/), 68% of the total matrix was degraded, including 57% of the glycoprotein, 79% of the elastin, and 8% of the collagen. Degradation of matrix was inhibited by ..cap alpha../sub 1/-proteinase inhibitor and soybean trypsin inhibitor. Ethylenediaminetetraacetic acid inhibited degradation by unstimulated but not linoleic acid-stimulated cercariae. Preacetabular gland secretions collected from cercariae also degraded the matrix with an activity 86% of that of live cercariae. Preacetabular gland proteolytic activity was also inhibited by ..cap alpha../sub 1/-proteinase inhibitor, soybean trypsin inhibitor, and ethylenediaminetetraacetic acid. The similar characteristics of matrix degradation by both live cercariae and cercarial preacetabular gland secretions support the idea that a proteinase secreted from cercarial preacetabular glands facilitates invasion of skin and connective tissue by these larvae. Degradation of elastin and glycoprotein constituentes of extracellular matrix is probably essential for skin penetration.

  10. Release of leukotriene C4 (LTC4) from human eosinophils following adherence to IgE- and IgG-coated schistosomula of Schistosoma mansoni.

    PubMed Central

    Moqbel, R; Macdonald, A J; Cromwell, O; Kay, A B

    1990-01-01

    The release of leukotriene C4 (LTC4) from human low-density eosinophils following adherence to live or formalin-fixed schistosomula of Schistosoma mansoni coated with parasite-specific IgE or IgG obtained from pooled human anti-S. mansoni serum has been studied. IgE-rich fractions were obtained after fractionation of pooled immune sera on fast-protein liquid chromatography (FPLC; polyanion SI-17 column) and were identified by parasite-specific RAST. Contaminating IgG was removed by adsorption on a Staphylococcus aureus-protein A affinity column. IgG-rich FPLC fractions were identified by a specific ELISA assay. IgG-dependent activities were confirmed by protein A adsorption. Low-density eosinophils adhered to live and formalin-fixed schistosomula coated with specific antisera and released 11.7 +/- 2.7 and 16.5 +/- 3.5 pmoles of LTC4/10(6) cells, respectively. LTC4 release induced by A23187 (5 x 10(-6) M) from the same cells was 80 +/- 24 pmoles/10(6) cells and 9.9 +/- 1 pmoles/10(6) cells in the presence of Sepharose particles (CNBr-activated 4B beads) covalently coated with normal human IgG. Fixed schistosomula coated with FPLC-purified IgE and IgG gave 7.6 +/- 0.4 and 6.0 +/- 0.1 pmoles of LTC4 per 10(6) low-density eosinophils, respectively. The same IgE- and IgG-rich fractions induced eosinophil-mediated cytotoxicity of live schistosomula in vitro. Removal of IgE by an anti-IgE affinity column abolished both the IgE-dependent release of LTC4 and the in vitro killing of larvae. Conversely, IgG-dependent activities were abolished by protein A, but not anti-IgE, adsorption. Normal density eosinophils generated undetectable amounts of LTC4 when incubated with IgE-coated schistosomula, whereas with IgG-coated larvae 4.6 pmoles/10(6) cells were obtained. Following preincubation with platelet-activating factor (PAF) (10(-7) M) and leukotriene B4 (LTB4) (10(-7) M), normal density eosinophils released LTC4 when in contact with larvae coated with antigen-specific Ig

  11. A novel G protein-coupled receptor of Schistosoma mansoni (SmGPR-3) is activated by dopamine and is widely expressed in the nervous system.

    PubMed

    El-Shehabi, Fouad; Taman, Amira; Moali, Lorena S; El-Sakkary, Nelly; Ribeiro, Paula

    2012-01-01

    Schistosomes have a well developed nervous system that coordinates virtually every activity of the parasite and therefore is considered to be a promising target for chemotherapeutic intervention. Neurotransmitter receptors, in particular those involved in neuromuscular control, are proven drug targets in other helminths but very few of these receptors have been identified in schistosomes and little is known about their roles in the biology of the worm. Here we describe a novel Schistosoma mansoni G protein-coupled receptor (named SmGPR-3) that was cloned, expressed heterologously and shown to be activated by dopamine, a well established neurotransmitter of the schistosome nervous system. SmGPR-3 belongs to a new clade of "orphan" amine-like receptors that exist in schistosomes but not the mammalian host. Further analysis of the recombinant protein showed that SmGPR-3 can also be activated by other catecholamines, including the dopamine metabolite, epinine, and it has an unusual antagonist profile when compared to mammalian receptors. Confocal immunofluorescence experiments using a specific peptide antibody showed that SmGPR-3 is abundantly expressed in the nervous system of schistosomes, particularly in the main nerve cords and the peripheral innervation of the body wall muscles. In addition, we show that dopamine, epinine and other dopaminergic agents have strong effects on the motility of larval schistosomes in culture. Together, the results suggest that SmGPR-3 is an important neuronal receptor and is probably involved in the control of motor activity in schistosomes. We have conducted a first analysis of the structure of SmGPR-3 by means of homology modeling and virtual ligand-docking simulations. This investigation has identified potentially important differences between SmGPR-3 and host dopamine receptors that could be exploited to develop new, parasite-selective anti-schistosomal drugs. PMID:22389736

  12. A Novel G Protein-Coupled Receptor of Schistosoma mansoni (SmGPR-3) Is Activated by Dopamine and Is Widely Expressed in the Nervous System

    PubMed Central

    El-Shehabi, Fouad; Taman, Amira; Moali, Lorena S.; El-Sakkary, Nelly; Ribeiro, Paula

    2012-01-01

    Schistosomes have a well developed nervous system that coordinates virtually every activity of the parasite and therefore is considered to be a promising target for chemotherapeutic intervention. Neurotransmitter receptors, in particular those involved in neuromuscular control, are proven drug targets in other helminths but very few of these receptors have been identified in schistosomes and little is known about their roles in the biology of the worm. Here we describe a novel Schistosoma mansoni G protein-coupled receptor (named SmGPR-3) that was cloned, expressed heterologously and shown to be activated by dopamine, a well established neurotransmitter of the schistosome nervous system. SmGPR-3 belongs to a new clade of “orphan” amine-like receptors that exist in schistosomes but not the mammalian host. Further analysis of the recombinant protein showed that SmGPR-3 can also be activated by other catecholamines, including the dopamine metabolite, epinine, and it has an unusual antagonist profile when compared to mammalian receptors. Confocal immunofluorescence experiments using a specific peptide antibody showed that SmGPR-3 is abundantly expressed in the nervous system of schistosomes, particularly in the main nerve cords and the peripheral innervation of the body wall muscles. In addition, we show that dopamine, epinine and other dopaminergic agents have strong effects on the motility of larval schistosomes in culture. Together, the results suggest that SmGPR-3 is an important neuronal receptor and is probably involved in the control of motor activity in schistosomes. We have conducted a first analysis of the structure of SmGPR-3 by means of homology modeling and virtual ligand-docking simulations. This investigation has identified potentially important differences between SmGPR-3 and host dopamine receptors that could be exploited to develop new, parasite-selective anti-schistosomal drugs. PMID:22389736

  13. In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance

    SciTech Connect

    Kelly, E.A.; Colley, D.G.

    1988-04-15

    Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component.

  14. Migration and survival of gamma-irradiated Schistosoma mansoni larvae and the duration of host-parasite contact in relation to the induction of resistance in mice

    SciTech Connect

    Mangold, B.L.; Dean, D.A.

    1984-01-01

    The migration in mice of 20-, 50-, and 90-krad /sup 60/Co-irradiated Schistosoma mansoni larvae, biosynthetically radioisotope labeled with /sup 75/Se-selenomethionine, was evaluated by autoradiography of compressed tissues and compared to the migration of non-irradiated 75 Se-labeled larvae. By day 8 over 90% of both non-irradiated and 20 krad-irradiated organisms were located in the lungs. In contrast to non-irradiated organisms, however, only a small proportion of 20-krad organisms migrated to the liver. The delay in migration between skin and lungs was more pronounced with 50-krad-irradiated schistosomula. No more than an occasional 50-krad-irradiated organism was ever detected in the liver. In three experiments, over 85% of the 90-krad-irradiated organisms were retained in the skin; in a fourth experiment about half of the 90-krad-irradiated organisms migrated as far as the lungs. Only an occasional 90-krad organism was ever detected in the liver. In three experiments, over 85% of the 90 Krad.-irradiated organisms were retained in the skin, in a fourth experiment about half of the 90 Krad.-irradiated organisms migrated as far as the lungs. Only an occasional 90 Krad. organism was ever detected in the liver. Removal of the skin exposure site within the first 4 days of immunization with either 50- or 90-krad-irradiated cercariae completely blocked the induction of resistance. Removal between the 4th and the 6th days gave variable results.

  15. Identification of surface antigens of schistosomula of Schistosoma mansoni recognized by antibodies from mice immunized by chronic infection and by exposure to highly irradiated cercariae

    SciTech Connect

    Simpson, A.J.; James, S.L.; Sher, A.

    1983-08-01

    Surface components of mechanically transformed schistosomula of Schistosoma mansoni were labeled by lactoperoxidase-catalyzed iodination. After solubilization with Triton X-100, antigens were identified by immunoprecipitation. Serum from chronically infected Swiss mice reproducibly precipitated seven major polypeptides with approximate molecular weights (X 10/sup 3/) of 94, 68, 45, 40 to 32, 22, and 16. The antigens of molecular weights (X 10/sup 3/) of 94, 40 to 32, 22, and 16 were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. Sera from several strains of infected inbred mice precipitated the same polypeptides. The antibodies produced during chronic infection were found to be stimulated by adult worms since sera from 6-week-infected animals precipitated none of the surface antigens, and the pattern produced by precipitation with antibodies from a mouse infected with male worms only was indistinguishable from the pattern obtained with sera from mice with bisexual infections. Antibodies from mice immunized with highly irradiated cercariae reproducibly precipitated major polypeptides of approximately (X 10/sup 3/) 94, 68, 45, 32, 22, 19, and 15 daltons. The antigens of (X 10/sup 3/) 94, 43, 32, 22, and 15 daltons were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. The 15 X 10(3)-dalton surface protein was recognized by sera from vaccinated, but not chronically infected, mice, suggesting that it represents a stage-specific immunogen present on schistosomula but not on adult worms. Sera from two inbred strains of mice which develop different degrees of immunity recognized the same antigens.

  16. Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs

    PubMed Central

    Kelleher, Alan; Darwiche, Rabih; Rezende, Wanderson C.; Farias, Leonardo P.; Leite, Luciana C. C.; Schneiter, Roger; Asojo, Oluwatoyin A.

    2014-01-01

    Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic α/β-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residues and is missing the histidines that coordinate divalent cations such as Zn2+ in other SCP/TAPS proteins. SmVAL4 has a cavity between α-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1. PMID:25084337

  17. A combined proteomic and immunologic approach for the analysis of Schistosoma mansoni cercariae and adult worm protein extracts and the detection of one of the vaccine candidates, Sm28GST, from a Venezuelan parasite isolate.

    PubMed

    Losada, Sandra; Sabatier, Laurence; Hammann, Philippe; Guillier, Christelle; Matos, César; Bermúdez, Henry; Lorenzo, María Angelita; Noya, Oscar

    2011-06-01

    Understanding the mode of Schistosoma mansoni larval invasion and the mechanism of immune evasion utilized by larvae and adult worms is essential for a rational development of vaccines or drugs to prevent or cure the disease. This parasite has a very complex molecular organization in all parasite stages, and identifying the major parasite proteins would give clues to schistosome metabolism and to the interaction of the parasite with the host immune system. Our goal was the evaluation of the protein parasite repertoire using a proteomic approach, and the characterization of protein extracts from two different parasite stages of a Venezuelan isolate, such as cercariae and adult worms, previously performed by other authors in some other strains. A comparison among authors was made. Besides, we aimed to identify different isoforms of one of the vaccine candidates, the gluthation-S-transferase protein (Sm28GST), by 2D SDS-PAGE and mass spectrometry, and to achieve its immunologic detection using sera from rabbits immunized with synthetic peptides derived from the Sm28GST protein. These techniques allowed the identification of some of the target molecules of the protective immune response that are being evaluated as potential members of a multi-component and multi-stage anti-S. mansoni vaccine and to clarify if the selected peptides induce antibodies that are able to recognize different isoforms of the Sm28GST. PMID:21866785

  18. Schistosoma mansoni in a low-prevalence area in Brazil: the importance of additional methods for the diagnosis of hard-to-detect individual carriers by low-cost immunological assays

    PubMed Central

    Grenfell, Rafaella Fortini Queiroz; Martins, Watson; Enk, Martin; Almeida, Áureo; Siqueira, Liliane; Silva-Moraes, Vanessa; Oliveira, Edward; Carneiro, Nídia Francisca de Figueiredo; Coelho, Paulo Marcos Zech

    2013-01-01

    Schistosomiasis diagnosis is based on the detection of eggs in the faeces, which is laborious and lacks sensitivity, especially for patients with a low parasite burden. Immunological assays for specific antibody detection are available, but they usually demonstrate low sensitivity and/or specificity. In this study, two simple immunological assays were evaluated for the detection of soluble Schistosoma mansoni adult worm preparation (SWAP) and egg-specific IgGs. These studies have not yet been evaluated for patients with low parasite burdens. Residents of an endemic area in Brazil donated sera and faecal samples for our study. The patients were initially diagnosed by a rigorous Kato-Katz analysis of 18 thick smears from four different stool samples. The ELISA-SWAP was successful for human diagnosis with 90% sensitivity and specificity, confirming the Kato-Katz diagnosis with nearly perfect agreement, as seen by the Kappa index (0.85). Although the ELISA-soluble S. mansoni egg antigen was 85% sensitive, it exhibited low specificity (80%; Kappa index: 0.75) and was more susceptible to cross-reactivity. We believe that immunological assays should be used in conjunction with Kato-Katz analysis as a supplementary tool for the diagnosis of schistosomiasis for patients with low infection burdens, which are usually hard to detect. PMID:23778663

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

    PubMed Central

    Smit, Cornelis H.; van Diepen, Angela; Nguyen, D. Linh; Wuhrer, Manfred; Hoffmann, Karl F.; Deelder, André M.; Hokke, Cornelis H.

    2015-01-01

    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

  20. Long term study on the effect of mollusciciding with niclosamide in stream habitats on the transmission of schistosomiasis mansoni after community-based chemotherapy in Makueni District, Kenya

    PubMed Central

    2013-01-01

    Background Schistosoma mansoni infection is a persistent public health problem in many Kenyan communities. Although praziquantel is available, re-infection after chemotherapy treatment is inevitable, especially among children. Chemotherapy followed by intermittent mollusciciding of habitats of Biomphalaria pfeifferi, the intermediate host snail, may have longer term benefits, especially if timed to coincide with natural fluctuations in snail populations. Methods In this cohort study, the Kambu River (Intervention area) was molluscicided intermittently for 4 years, after mass chemotherapy with praziquantel in the adjacent community of Darajani in January 1997. The nearby Thange River was selected as a control (Non-intervention area), and its adjacent community of Ulilinzi was treated with praziquantel in December 1996. Snail numbers were recorded monthly at 9–10 sites along each river, while rainfall data were collected monthly, and annual parasitological surveys were undertaken in each village. The mollusciciding protocol was adapted to local conditions, and simplified to improve prospects for widespread application. Results After the initial reduction in prevalence attributable to chemotherapy, there was a gradual increase in the prevalence and intensity of infection in the non-intervention area, and significantly lower levels of re-infection amongst inhabitants of the intervention area. Incidence ratio between areas adjusted for age and gender at the first follow-up survey, 5 weeks after treatment in the non-intervention area and 4 months after treatment in the intervention area was not significant (few people turned positive), while during the following 4 annual surveys these ratios were 0.58 (0.39-0.85), 0.33 (0.18-0.60), 0.14 (0.09-0.21) and 0.45 (0.26-0.75), respectively. Snail numbers were consistently low in the intervention area as a result of the mollusciciding. Following termination of the mollusciciding at the end of 2000, snail populations and

  1. Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs.

    PubMed

    Smit, Cornelis H; van Diepen, Angela; Nguyen, D Linh; Wuhrer, Manfred; Hoffmann, Karl F; Deelder, André M; Hokke, Cornelis H

    2015-07-01

    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

  2. Nucleolar localization of SmMAK16 protein from Schistosoma mansoni is regulated by three distinct signals that function independent of pH or phosphorylation status.

    PubMed

    Hoellerich, Elisa; Dunagan, Christie; Maring, Daniel; Wong, Yun-Lan C; Shouldice, Daniel; Stripe, Jennifer; Kline, Tayah; Albert, Thomas J; Milhon, Jon L

    2014-01-01

    SmMAK16 from the trematode Schistosoma mansoni is a protein that is known to localize in the nucleolus. Recent findings show that SmMAK16 is involved in 60S ribosomal subunit synthesis. Although the SmMAK16 protein contains putative nuclear localization signals (NLS), little is known about their precise function, redundancy or regulation. The goal of the current study was to identify and characterize the presence and functional regulation of the localization signals in SmMAK16. The SmMAK16 coding sequence and specific fragments were individually cloned in-frame into the pEGFP-C2 expression vector to encode Green Fluorescent Protein (GFP) fusion proteins. Constructs were individually transfected into COS-7 cells and fluorescent microscopy used to determine the cellular location and thus the presence of signals regulating nuclear and nucleolar localization. SmMAK16 was found to contain two NLSs and one nucleolar localization signal (NoLS). One of the signals contains a sequence identical to an established nucleolar detention signal that reportedly functions only under acidic cellular conditions. The localization of the SmMAK16-GFP constructs was analyzed under acidic conditions; however, altering pH did not influence the localization of SmMAK16. It has been previously reported that casein kinase 2 (CK2) can phosphorylate SmMAK16 at serines adjacent to one of the NLSs. One of these CK2 sites and the adjacent NLS are conserved with that of the SV40 Large T Antigen (LTA) and phosphorylation of this site in the SV40 LTA regulates the kinetics of the NLS. To discover if kinetic regulation also occurs in SmMAK16, mutant and wild type SmMAK16-GFP proteins were purified and injected into individual COS-7 cells. No difference in the rate of transport was found between wt and mutant SmMAK16 proteins. Therefore, SmMAK16 localizes to the nucleolus using three separate signals, two NLSs and one NoLS, however, these signals appear to function independently of pH and

  3. The uptake of tritiated hycanthone by male and female Schistosoma mansoni worms and distribution of the drug in plasma and whole blood of mice following a single intramuscular injection*

    PubMed Central

    Yarinsky, A.; Hernandez, P.; Dennis, E. W.

    1970-01-01

    Mice infected with Schistosoma mansoni were given an intramuscular injection of a single 80 mg/kg dose of randomly tritiated hycanthone. The uptake of the drug in male and female worms, as well as its concentration in the red blood cells and plasma of the mice, was followed for a period of 24 hours. Blood and plasma drug levels reached maximum values within 30 minutes. During the postmedication period, plasma concentrations were consistently higher than red blood cell concentrations. At 2-6 hours, when blood levels were declining, peak uptake was reached in the female schistosome worms; the concentration in the female worm was 5 times higher than in the male worm. At 24 hours the schistosomes contained appreciably more drug than was present in the blood. PMID:5310210

  4. Schistosoma mansoni infection in mice augments the capacity for interleukin 3 (IL-3) and IL-9 production and concurrently enlarges progenitor pools for mast cells and granulocytes-macrophages.

    PubMed Central

    Khalil, R M; Luz, A; Mailhammer, R; Moeller, J; Mohamed, A A; Omran, S; Dörmer, P; Hültner, L

    1996-01-01

    Mast cells and granulocytes-macrophages (GM) are components of the host defense system against worm infections, including schistosomiasis. Here we report the kinetics of changes in the number of colony-forming cells (CFC) for mast cells and GM during the course of a primary experimental infection of mice with Schistosoma mansoni cercariae over a period of 24 weeks postinfection (p.i.). Concurrently, we measured known myelopoietic and/or mast cell-stimulating cytokines (i.e., interleukin 3 [IL-3] and IL-9) in pokeweed mitogen-activated spleen cell-conditioned medium. Our results show that during the acute phase of the hepatic granulomatous reaction, the numbers of both mast-CFC and GM-CFC were significantly elevated in bone marrow. However, while femoral GM-CFC numbers had returned to normal control values at week 16 p.i., femoral and splenic mast-CFC numbers remained significantly elevated until week 20 p.i., which corresponds to the chronic fibrotic phase of hepatic granulomatous inflammation. Increased GM-CFC numbers correlated with elevated IL-3 levels, while increased mast-CFC numbers paralleled the increased IL-9 concentrations in spleen cell-conditioned medium. By the reverse transcription-PCR method, enhanced expression of IL-3 and IL-9 transcripts was found in RNA samples obtained from livers and spleens of infected mice. Our data demonstrate that during the course of infection of mice with S. mansoni, the coordinate need for mast cells and GM is at least partly regulated at the stage of progenitor cell commitment in the bone marrow and spleen. It appears that IL-3 and IL-9 help to promote at this stage the ultimate generation of mature effector cells. PMID:8945533

  5. CT of hepatic schistosomiasis mansoni

    SciTech Connect

    Fataar, S.; Bassiony, H.; Satyanath, S.; Rudwan, M.A.; Khaffaji, S.; El Magdy, W.; Al-Ansari, A.G.; Hanna, R.

    1985-07-01

    Schistosomal periportal fibrosis produced a typical pattern on computed tomography in five patients. Low-density periportal tissue, present throughout the liver, enhanced strongly after the administration of contrast medium. While rounded in cross section, the thickened periportal tissue produced linear and branching patterns when imaged in longitudinal section. In all cases, the sonographic features were typical of schistosomal periportal fibrosis. A lack of awareness of the distinctive features of periportal fibrosis may result in a mistaken diagnosis of hepatic metastases.

  6. IL-4Rα Responsiveness of Non-CD4 T Cells Contributes to Resistance in Schistosoma mansoni Infection in Pan-T Cell-Specific IL-4Rα-Deficient Mice

    PubMed Central

    Dewals, Benjamin; Hoving, Jennifer C.; Leeto, Mosiuoa; Marillier, Reece G.; Govender, Umeshree; Cutler, Antony J.; Horsnell, William G.C.; Brombacher, Frank

    2009-01-01

    Interleukin (IL)-4 and IL-13 are T helper 2 cytokines whose biological functions are induced through a common IL-4 receptor α chain (IL-4Rα). CD4+ T cell-specific IL-4Rα-mediated signaling drives susceptibility to Leishmania major infection, but is not essential to host survival following Schistosoma mansoni infection. Here we generated a novel mouse model lacking IL-4Rα expression specifically on all T cells (iLckcreIl4ra−/lox), which was compared with CD4+ T cell-specific IL-4Rα-deficient mice (LckcreIl4ra−/lox), to investigate the possible roles of IL-4Rα responsive non-CD4+ T cells during either L. major or S. mansoni infection. Our results demonstrate a successful generation of transgene-bearing hemizygous iLckcreIl4ra−/lox BALB/c mice that have effective deletion of IL-4Rα on all T-cell populations. We show that iLckcreIl4ra−/lox mice infected with L. major developed a healing disease phenotype as previously observed in LckcreIl4ra−/lox mice, demonstrating that absence of IL-4Rα-responsive non-CD4+ in addition to CD4+ T cells does not further affect transformation of BALB/c to a healer phenotype. In acute schistosomiasis, however, iLckcreIl4ra−/lox mice showed enhanced mortality compared with Il4ra−/lox and LckcreIl4ra−/lox mice. iLckcreIl4ra−/lox mice died with similar kinetics to highly susceptible Il4ra−/− mice, despite controlling gut inflammation. In addition, iLckcreIl4ra−/lox mice presented increased liver granuloma sizes, as compared with LckcreIl4ra−/lox mice, with similar eosinophils, fibrosis, and liver damage. In conclusion, IL-4Rα-responsive non-CD4+ T cells prolong survival to acute schistosomiasis and contribute to the better control of hepatic granulomatous inflammation. PMID:19628763

  7. Combined immunization using DNA-Sm14 and DNA-Hsp65 increases CD8+ memory T cells, reduces chronic pathology and decreases egg viability during Schistosoma mansoni infection

    PubMed Central

    2014-01-01

    Background Schistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide. The development of an efficient vaccination strategy is essential for the control of this disease. Previous work showed partial protection induced by DNA-Sm14 against Schistosoma mansoni infection, whereas DNA-Hsp65 showed immunostimulatory properties against infectious diseases, autoimmune diseases, cancer and antifibrotic properties in an egg-induced granuloma model. Methods C57BL/6 mice received 4 doses of DNA-Sm14 (100 μg/dose) and DNA-Hsp65 (100 μg/dose), simultaneously administrated, or DNA-Sm14 alone, once a week, during four weeks. Three groups were included: 1- Control (no immunization); 2- DNA-Sm14; 3- DNA-Sm14/DNA-Hsp65. Two weeks following last immunization, animals were challenged subcutaneously with 30 cercariae. Fifteen, 48 and 69 days after infection splenocytes were collected to evaluate the number of CD8+ memory T cells (CD44highCD62low) using flow cytometry. Forty-eight days after challenge adult worms were collected by portal veins perfusion and intestines were collected to analyze the intestinal egg viability. Histological, immunohistochemical and soluble quantification of collagen and α-SMA accumulation were performed on the liver. Results In the current work, we tested a new vaccination strategy using DNA-Sm14 with DNA-Hsp65 to potentiate the protection against schistosomiasis. Combined vaccination increased the number of CD8+ memory T cells and decreased egg viability on the intestinal wall of infected mice. In addition, simultaneous vaccination with DNA-Sm14/DNA-Hsp65 reduced collagen and α-SMA accumulation during the chronic phase of granuloma formation. Conclusion Simultaneous vaccination with DNA-Sm14/DNA-Hsp65 showed an immunostimulatory potential and antifibrotic property that is associated with the reduction of tissue damage on Schistosoma mansoni experimental infection. PMID

  8. Identification and characterisation of functional expressed sequence tags-derived simple sequence repeat (eSSR) markers for genetic linkage mapping of Schistosoma mansoni juvenile resistance and susceptibility loci in Biomphalaria glabrata

    PubMed Central

    Ittiprasert, Wannaporn; Miller, André; Su, Xin-zhuan; Mu, Jianbing; Bhusudsawang, Ganlayarat; Ukoskit, Kitipat; Knight, Matty

    2013-01-01

    Biomphalaria glabrata susceptibility to Schistosoma mansoni has a strong genetic component, offering the possibility for investigating host–parasite interactions at the molecular level, perhaps leading to novel control approaches. The identification, mapping and molecular characterisation of genes that influence the outcome of parasitic infection in the intermediate snail host is, therefore, seen as fundamental to the control of schistosomiasis. To better understand the evolutionary processes driving disease resistance/susceptibility phenotypes, we previously identified polymorphic random amplification of polymorphic DNA and genomic simple sequence repeats from B. glabrata. In the present study we identified and characterised polymorphic expressed simple sequence repeats markers (Bg-eSSR) from existing B. glabrata expressed sequence tags. Using these markers, and with previously identified genomic simple sequence repeats, genetic linkage mapping for parasite refractory and susceptibility phenotypes, the first known for B. glabrata, was initiated. Data mining of 54,309 expressed sequence tag, produced 660 expressed simple sequence repeats of which dinucleotide motifs (TA)n were the most common (37.88%), followed by trinucleotide (29.55%), mononucleotide (18.64%) and tetranucleotide (10.15%). Penta- and hexanucleotide motifs represented <3% of the Bg-eSSRs identified. While the majority (71%) of Bg-eSSRs were monomorphic between resistant and susceptible snails, several were, however, useful for the construction of a genetic linkage map based on their inheritance in segregating F2 progeny snails derived from crossing juvenile BS-90 and NMRI snails. Polymorphic Bg-eSSRs assorted into six linkage groups at a logarithm of odds score of 3. Interestingly, the heritability of four markers (Prim1_910, Prim1_771, Prim6_1024 and Prim7_823) with juvenile snail resistance were, by t-test, significant (P < 0.05) while an allelic marker, Prim24_524, showed linkage with the

  9. Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella.

    PubMed Central

    Khan, C M; Villarreal-Ramos, B; Pierce, R J; Riveau, G; Demarco de Hormaeche, R; McNeill, H; Ali, T; Fairweather, N; Chatfield, S; Capron, A

    1994-01-01

    A vector has been constructed to allow genetic fusions of guest antigens via a hinge domain to the C terminus of the highly immunogenic C fragment of tetanus toxin. A fusion has been constructed with the gene encoding the protective 28-kDa glutathione S-transferase (EC 2.5.1.18) from Schistosoma mansoni. The recombinant vector has been electroporated into the nonvirulent Salmonella typhimurium aroA live vaccine strain SL3261. The corresponding chimeric protein is stably expressed in a soluble form in Salmonella as evaluated by Western blotting with fragment C and glutathione S-transferase antisera. Mice immunized intravenously with a single dose of the live recombinant bacteria elicit antibodies to both fragment C and glutathione S-transferase as detected by enzyme-linked immunosorbent assays. Furthermore, all of the mice were solidly protected when challenged with lethal doses of either tetanus toxin or the virulent Salmonella typhimurium strain C5. Mice have also elicited antibodies to fragment C and glutathione S-transferase after oral immunization. It may be that a live trivalent vaccine against typhoid, tetanus, and schistosomiasis is feasible. Images PMID:7972044

  10. Improvement of POC-CCA Interpretation by Using Lyophilization of Urine from Patients with Schistosoma mansoni Low Worm Burden: Towards an Elimination of Doubts about the Concept of Trace

    PubMed Central

    Coelho, Paulo Marcos Zech; Siqueira, Liliane Maria Vidal; Grenfell, Rafaella Fortini Queiroz; Almeida, Nathalie Bonatti Franco; Katz, Naftale; Almeida, Áureo; Carneiro, Nídia Francisca de Figueiredo; Oliveira, Edward

    2016-01-01

    Background Accurate diagnostic techniques for schistosomiasis are essential for prevalence determination and identification of positive patients. A point-of-care test for detecting schistosome circulating cathodic antigen (POC-CCA) has been evaluated for its accuracy in different endemic regions. This reagent strip/dipstick based assay has showed high sensitivity for individuals with high or moderate worm burden, but the interpretation of light infections is less clear, especially for trace readings. Methodology/Principal Findings We introduced a urine lyophilization step to the POC-CCA assay to improve its sensitivity and clarify the interpretation of traces. We evaluated POC-CCA sensitivity and specificity within individuals with low parasite burdens in a Brazilian endemic area where a high number of traces were detected. Patients that were positive for other helminths were also evaluated for cross reactions. In all cases, a combined parasitological diagnosis using Kato-Katz (24 slides) and Saline Gradient (1 g of feces) were used as reference. At baseline, diagnosis by POC-CCA (1–2 cassettes) showed 6% sensitivity, inaccurately predicting a low prevalence of Schistosoma mansoni infections (2 POC-CCA positives/32 egg positives). After urine lyophilization, the sensitivity was increased significantly (p < 0.05). Prevalence rates changed from 2% to 32% (27 POC-CCA positives/32 egg positives), equivalent to parasitological techniques. Most of the trace readings changed to positive after lyophilization while some negatives turned into traces. Cross reaction analysis confirmed the specificity of POC-CCA. Conclusions/Significance Trace readings cannot be primarily defined as positive or negative cases. It is critical to verify case-by-case by concentrating urine 10 fold by lyophilization for the diagnosis. Following lyophilization, persistent trace readings should be read as negatives. No trained technician is needed and cost is restricted to the cost of a

  11. Alternatively Activated Mononuclear Phagocytes from the Skin Site of Infection and the Impact of IL-4Rα Signalling on CD4+T Cell Survival in Draining Lymph Nodes after Repeated Exposure to Schistosoma mansoni Cercariae.

    PubMed

    Prendergast, Catriona T; Sanin, David E; Mountford, Adrian P

    2016-08-01

    In a murine model of repeated exposure of the skin to infective Schistosoma mansoni cercariae, events leading to the priming of CD4 cells in the skin draining lymph nodes were examined. The dermal exudate cell (DEC) population recovered from repeatedly (4x) exposed skin contained an influx of mononuclear phagocytes comprising three distinct populations according to their differential expression of F4/80 and MHC-II. As determined by gene expression analysis, all three DEC populations (F4/80-MHC-IIhigh, F4/80+MHC-IIhigh, F4/80+MHC-IIint) exhibited major up-regulation of genes associated with alternative activation. The gene encoding RELMα (hallmark of alternatively activated cells) was highly up-regulated in all three DEC populations. However, in 4x infected mice deficient in RELMα, there was n