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      Genetic Diversity within Schistosoma haematobium: DNA Barcoding Reveals Two Distinct Groups

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          Abstract

          Background

          Schistosomiasis in one of the most prevalent parasitic diseases, affecting millions of people and animals in developing countries. Amongst the human-infective species S. haematobium is one of the most widespread causing urogenital schistosomiasis, a major human health problem across Africa, however in terms of research this human pathogen has been severely neglected.

          Methodology/Principal Findings

          To elucidate the genetic diversity of Schistosoma haematobium, a DNA ‘barcoding’ study was performed on parasite material collected from 41 localities representing 18 countries across Africa and the Indian Ocean Islands. Surprisingly low sequence variation was found within the mitochondrial cytochrome oxidase subunit I ( cox1) and the NADH-dehydrogenase subunit 1 s nad1). The 61 haplotypes found within 1978 individual samples split into two distinct groups; one (Group 1) that is predominately made up of parasites from the African mainland and the other (Group 2) that is made up of samples exclusively from the Indian Ocean Islands and the neighbouring African coastal regions. Within Group 1 there was a dominance of one particular haplotype (H1) representing 1574 (80%) of the samples analyzed. Population genetic diversity increased in samples collected from the East African coastal regions and the data suggest that there has been movement of parasites between these areas and the Indian Ocean Islands.

          Conclusions/Significance

          The high occurrence of the haplotype (H1) suggests that at some point in the recent evolutionary history of S. haematobium in Africa the population may have passed through a genetic ‘bottleneck’ followed by a population expansion. This study provides novel and extremely interesting insights into the population genetics of S. haematobium on a large geographic scale, which may have consequence for control and monitoring of urogenital schistosomiasis.

          Author Summary

          Schistosomiasis is a disease caused by parasitic blood flukes of the genus Schistosoma. Species that infect humans are prevalent in developing countries, having a major impact on public health and well-being as well as an impediment to socioeconomic development. More people are infected with Schistosoma haematobium than with all the other schistosome species combined, however mainly due to the inability to maintain S. haematobium in the laboratory system empirical studies on this parasite are minimal. The genetic variation of this Schistosoma species on a wide geographical scale has never been investigated. In this study, we have used a DNA ?barcoding? approach to document the genetic variation and population structure of S. haematobium sampled from 18 countries across Africa and the Indian ocean Islands. The study revealed a distinct genetic separation of S. haematobium from the Indian Ocean Islands and the closely neighbouring coastal regions from S. haematobium found throughout the African mainland, the latter of which exhibited extremely low levels of mitochondrial diversity within and between populations of parasites sampled. The data from this study provides a novel insight into the population genetics of S. haematobium and will have an impact on future research strategies.

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          Most cited references28

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          Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis.

          Schistosomiasis is one of the world's most prevalent infections, yet its effect on the global burden of disease is controversial. Published disability-adjusted life-year (DALY) estimates suggest that the average effect of schistosome infection is quite small, although this is disputed. To develop an evidenced-based reassessment of schistosomiasis-related disability, we did a systematic review of data on disability-associated outcomes for all forms of schistosomiasis. We did structured searches using EMBASE, PUBMED, and Cochrane electronic databases. Published bibliographies were manually searched, and unpublished studies were obtained by contacting research groups. Reports were reviewed and abstracted independently by two trained readers. All randomised and observational studies of schistosomiasis morbidity were eligible for inclusion. We calculated pooled estimates of reported disability-related effects using weighted odds ratios for categorical outcomes and standardised mean differences for continuous data. 482 published or unpublished reports (March, 1921, to July, 2002) were screened. Of 135 selected for inclusion, 51 provided data for performance-related symptoms, whereas 109 reported observed measures of disability-linked morbidities. Schistosomiasis was significantly associated with anaemia, chronic pain, diarrhoea, exercise intolerance, and undernutrition. By contrast with WHO estimates of 0.5% disability weight assigned to schistosomiasis, 2-15% disability seems evident in different functional domains of a person with schistosomiasis. This raised estimate, if confirmed in formal patient-preference studies, indicates a need to reassess our priorities for treating this silent pandemic of schistosomiasis.
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            Drug-resistant schistosomiasis: resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific.

            Schistosoma mansoni infections in mice were treated with subcurative multiple doses of either praziquantel (PZQ) or oxamniquine (OX). With an early exception, the drug treatments commenced when the worms were adult, but before the infections had become fully patent, and the eggs subsequently produced by worms that had survived the drug treatments were used to infect snails. Six or seven drug-treated passages of S. mansoni in mice were completed for each of the drugs, with the amount of drug administered to the infected mice generally being increased with each passage. Eighty percent of the worms of the sixth passage selected for PZQ resistance survived three doses of 300 mg/kg of PZQ given between days 28 and 37 after infection, and 93% of those of the seventh passage survived the same drug dose. In contrast, only 13% of worms of the sixth PZQ-selected passage survived three doses of 200mg/kg of OX given during the same period after infection. Only 11% or fewer worms derived from S. mansoni infections that had not been subjected to any drug pressure survived the 3 x 300 mg/kg PZQ treatments. Worms selected for OX resistance over six passages were completely resistant to three doses of 200 mg/kg, but only 26% survived three doses of 300 mg/kg of PZQ. Therefore, the results indicate that S. mansoni subjected to drug pressure may develop resistance to schistosomicidal drugs over the course of relatively few passages, but that cross-resistance between PZQ and OX does not occur. This is the first demonstration of drug resistance to PZQ, the current drug of choice for human schistosomiasis.
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              The phylogeny of the Schistosomatidae based on three genes with emphasis on the interrelationships of Schistosoma Weinland, 1858.

              Schistosomes are digenean flukes, parasitic of birds, mammals and crocodiles. The family Schistosomatidae contains species of considerable medical and veterinary importance, which cause the disease schistosomiasis. Previous studies, both morphological and molecular, which have provided a good deal of information on the phylogenetics of this group, have been limited in the number of species investigated or the type or extent of molecular data used. This paper presents the most comprehensive phylogeny to date, based on the sequences of 3 genes, complete ribosomal small subunit rRNA and large ribosomal subunit rRNA, and mitochondrial cytochrome oxidase 1, sequenced from 30 taxa including at least 1 representative from 10 of the 13 known genera of the Schistosomatidae and 17 of the 20 recognized Schistosoma species. The phylogeny is examined using morphological characters, intermediate and definitive host associations and biogeography. Theories as to the origins and spread of Schistosoma are also explored. The principal findings are that Ornithobilharzia and Austrobilharzia form a sister group to the Schistosoma; mammalian schistosomes appear paraphyletic and 2 Trichobilharzia species, T. ocellata and T. szidati, seem to be synonymous. The position of Orientobilharzia within the Schistosoma is confirmed, as is an Asian origin for the Schistosoma, followed by subsequent dispersal through India and Africa.
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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
                October 2012
                25 October 2012
                : 6
                : 10
                : e1882
                Affiliations
                [1 ]Wolfson Wellcome Biomedical Laboratories, Department of Zoology, Natural History Museum, London, United Kingdom
                [2 ]Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, St Mary's Campus, London, United Kingdom
                [3 ]Réseau International Schistosomoses, Environnement, Aménagement et Lutte (RISEAL-Niger), Niamey, Niger
                [4 ]Institut Sénégalais de Recherches Agricoles (ISRA), Bel Air, Dakar, Senegal
                [5 ]Laboratoire de Parasitologie et Ecologie, Université de Yaoundé I, Yaoundé, Cameroon
                [6 ]Center for Schistosomiasis and Parasitology, Yaoundé, Cameroon
                [7 ]University of Zambia, Lusaka, Zambia
                [8 ]National Institute for Medical Research, Mwanza, Tanzania
                [9 ]Department of Invertebrate Zoology, National Museums of Kenya, Nairobi, Kenya
                [10 ]Helminth Control Laboratory Unguja, Ministry of Health and Social Welfare, Zanzibar, Tanzania
                [11 ]Disease Control Strategy Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
                University of Melbourne, Australia
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BLW DR. Performed the experiments: BLW. Analyzed the data: BLW. Contributed reagents/materials/analysis tools: BLW AME JPW A. Gouvras A. Garba OD MMS LATT CS JM CL CK KAM JRS DR. Wrote the paper: BLW JPW DR.

                [¤]

                Current address: Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, St Mary's Campus, London, United Kingdom

                Article
                PNTD-D-12-00604
                10.1371/journal.pntd.0001882
                3493392
                23145200
                b5a49c71-8780-49c0-abf5-c85cd08c18ff
                Copyright @ 2012

                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
                : 11 May 2012
                : 12 September 2012
                Page count
                Pages: 10
                Funding
                This research was funded by an FP6 (European Community Framework Programme for Research, Technological Development and Demonstration) grant from the European Union. The programme was called CONTRAST (FP6 STREP contract no: 032203), http://www.eu-contrast.eu. This research was funded by the EU grant CONTRAST (FP6 STREP contract no: 032203), http://www.eu-contrast.eu. The authors were supported by The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) during the writing of the manuscript and from SCAN ( http://www.nhm.ac.uk/research-curation/collections/curation-groups/scan/) for covering the publication costs, which is funded by the Wellcome Trust. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Genetics
                Population Genetics
                Haplotypes
                Zoology
                Parasitology

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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