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

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          Abstract

          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.

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          Most cited references41

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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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            Control of neglected tropical diseases.

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              The global status of schistosomiasis and its control.

              Schistosomiasis is being successfully controlled in many countries but remains a major public health problem, with an estimated 200 million people infected, mostly in Africa. Few countries in this region have undertaken successful and sustainable control programmes. The construction of water schemes to meet the power and agricultural requirements for development have lead to increasing transmission, especially of Schistosoma mansoni. Increasing population and movement have contributed to increased transmission and introduction of schistosomiasis to new areas. Most endemic countries are among the least developed whose health systems face difficulties to provide basic care at the primary health level. Constraints to control include, the lack of political commitment and infrastructure for public health interventions. Another constraint is that available anti-schistosomal drugs are expensive and the cost of individual treatment is a high proportion of the per capita drug budgets. There is need for increased support for schistosomiasis control in the most severely affected countries.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                26 April 2016
                2016
                : 7
                : 594
                Affiliations
                [1] 1Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto Porto, Portugal
                [2] 2Medical Parasitology Unit, Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa Lisbon, Portugal
                [3] 3Bioanalytical, Microfabrication, and Separations Group, Instituto de Química de São Carlos, Universidade de São Paulo São Carlos, Brazil
                [4] 4Departamento De Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas Campinas, Brazil
                [5] 5Laboratory of Parasitology, Department of Morphology and Pathology, Universidade Federal de São Carlos São Carlos, Brazil
                Author notes

                Edited by: Octavio Luiz Franco, Universidade Catolica de Brasilia, Brazil

                Reviewed by: Osmar Nascimento Silva, Dom Bosco Catholic University, Brazil; Ramar Perumal Samy, National University of Singapore, Singapore

                *Correspondence: Ana Afonso anaafonso74@ 123456hotmail.com

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2016.00594
                4844704
                27199925
                47f356f7-80d3-4d35-868f-910a4b730537
                Copyright © 2016 Pinto-Almeida, Mendes, de Oliveira, Corrêa, Allegretti, Belo, Tomás, Anibal, Carrilho and Afonso.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 December 2015
                : 11 April 2016
                Page count
                Figures: 12, Tables: 1, Equations: 0, References: 61, Pages: 11, Words: 7871
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 10.13039/501100003593
                Award ID: 400168/2013-8
                Award ID: 375781/2013-7
                Funded by: Fundação para a Ciência e a Tecnologia 10.13039/501100001871
                Award ID: UID/Multi/04413/2013
                Award ID: SFRH/BD/51697/2011
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 10.13039/501100002322
                Award ID: CAPES PhD program for funding
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                schistosoma mansoni,schistosomiasis,praziquantel,resistance,morphology,eggs,tegument

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