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      Serological Screening of the Schistosoma mansoni Adult Worm Proteome

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          Abstract

          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.

          Author Summary

          Despite intensive efforts towards disease control, schistosomiasis is still highly prevalent in most endemic countries. Although effective treatment is available and widely used, it does not prevent reinfection, as it could be achieved with the use of a vaccine. Efforts to control and eradicate schistosomiasis rely on praziquantel, the only drug available for treatment. Therefore, the identification of antigens that can induce protective immunity is highly desirable, as well as the need for more sensitive assays, useful to detect low intensity infections and treatment follow-up. The occurrence of natural resistance in schistosome endemic areas suggests that there is protective immunity. However, the mechanisms involved in protection, or the proteins that induce this protective immunity, are not yet known. These proteins, once identified, may constitute the basis for a successful vaccine. In this study, we compared the profile of reactive proteins to the serum antibodies of infected and non-infected individuals residing in a schistosomiasis endemic area using two-dimensional western blotting. The association of proteomic and serological screening methodologies enabled the identification of immunogenic proteins of the parasite, which could be an informative source for the development of vaccines and new diagnostic assays. In this manuscript we describe the discovery of potential candidate proteins for subsequent testing as protective or diagnostic antigens.

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          Most cited references87

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          Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.

          An estimated 779 million people are at risk of schistosomiasis, of whom 106 million (13.6%) live in irrigation schemes or in close proximity to large dam reservoirs. We identified 58 studies that examined the relation between water resources development projects and schistosomiasis, primarily in African settings. We present a systematic literature review and meta-analysis with the following objectives: (1) to update at-risk populations of schistosomiasis and number of people infected in endemic countries, and (2) to quantify the risk of water resources development and management on schistosomiasis. Using 35 datasets from 24 African studies, our meta-analysis showed pooled random risk ratios of 2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among people living adjacent to dam reservoirs. The risk ratio estimate for studies evaluating the effect of irrigation on urinary schistosomiasis was in the range 0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed important spatial differences, idiosyncratic to the type of water resources development. We conclude that the development and management of water resources is an important risk factor for schistosomiasis, and hence strategies to mitigate negative effects should become integral parts in the planning, implementation, and operation of future water projects.
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            Filamins as integrators of cell mechanics and signalling.

            Filamins are large actin-binding proteins that stabilize delicate three-dimensional actin webs and link them to cellular membranes. They integrate cellular architectural and signalling functions and are essential for fetal development and cell locomotion. Here, we describe the history, structure and function of this group of proteins.
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              Human schistosomiasis.

              Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus Schistosoma. The transmission cycle requires contamination of surface water by excreta, specific freshwater snails as intermediate hosts, and human water contact. The main disease-causing species are S haematobium, S mansoni, and S japonicum. According to WHO, 200 million people are infected worldwide, leading to the loss of 1.53 million disability-adjusted life years, although these figures need revision. Schistosomiasis is characterised by focal epidemiology and overdispersed population distribution, with higher infection rates in children than in adults. Complex immune mechanisms lead to the slow acquisition of immune resistance, though innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is mostly seen in travellers after primary infection. Chronic schistosomal disease affects mainly individuals with long-standing infections in poor rural areas. Immunopathological reactions against schistosome eggs trapped in the tissues lead to inflammatory and obstructive disease in the urinary system (S haematobium) or intestinal disease, hepatosplenic inflammation, and liver fibrosis (S mansoni, S japonicum). The diagnostic standard is microscopic demonstration of eggs in the excreta. Praziquantel is the drug treatment of choice. Vaccines are not yet available. Great advances have been made in the control of the disease through population-based chemotherapy but these required political commitment and strong health systems.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                March 2014
                20 March 2014
                : 8
                : 3
                : e2745
                Affiliations
                [1 ]Centro de Pesquisas René Rachou-Fiocruz/MG, Genomics and Computational Biology Group, Belo Horizonte, Minas Gerais, Brazil
                [2 ]National Institute of Science and Technology in Tropical Diseases – INCT-DT, Brazil
                [3 ]Centro de Pesquisas René Rachou-Fiocruz/MG, Cellular and Molecular Immunology Laboratory, Belo Horizonte, Minas Gerais, Brazil
                [4 ]Universidade Federal de Minas Gerais, Nursing School, Belo Horizonte, Minas Gerais, Brazil
                [5 ]The University of Nottingham, School of Pharmacy, Division of Molecular and Cellular Science, Nottingham, East Midlands, United Kingdom
                [6 ]Fiocruz/RJ, Department of Physiology and Pharmacodynamics, Toxicology Laboratory, Rio de Janeiro, Rio de Janeiro, Brazil
                Swiss Tropical and Public Health Institute, Switzerland
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: FL FHF GCO RASP. Performed the experiments: FL PRP ATF RASP. Analyzed the data: FL FHF GCO RASP. Contributed reagents/materials/analysis tools: AG RCO JP FHF GCO RASP. Wrote the paper: FL RCO FHF GCO RASP.

                Article
                PNTD-D-13-01627
                10.1371/journal.pntd.0002745
                3961189
                24651847
                8749f1b0-ba07-44fe-be79-df8a1b043a73
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 October 2013
                : 1 February 2014
                Page count
                Pages: 16
                Funding
                This work was supported by CNPq/PAPES V-FIOCRUZ (403532/2008-6), CNPq/PROEP-RIPAg/CPqRR/FIOCRUZ (402000/2012-9, 402010/2012-4), CNPq (309312/2012-4), FAPEMIG (573839/2008-5, PPM-00439-10). It was also supported by the following fellowships: CNPq (FL), FAPEMIG (FL, PRP), Boehringer Ingelheim Fonds (FL), ISID/ESCMID (FL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Proteins
                Proteome
                Recombinant Proteins
                Immunology
                Immunity
                Immunity to Infections
                Molecular Cell Biology
                Gene Expression
                Proteomics
                Spectrometric Identification of Proteins

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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