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      Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?

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          Abstract

          The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on preventive chemotherapy with praziquantel. There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years. We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance. Repositioning drugs already approved for other diseases provides a shortcut to clinical trials, as it is expected that such drugs rapidly pass the regulatory authorities. The antischistosomal properties of antimalarial drugs (e.g., semisynthetic artemisinins, synthetic trioxolanes, trioxaquines and mefloquine) and of drugs being developed or registered for other purposes (e.g., moxidectin and miltefosin), administered alone or in combination with praziquantel, have been tested in the laboratory and clinical trials. Another avenue to follow is the continued search for new antischistosomal properties in plants. Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s40249-017-0286-2) contains supplementary material, which is available to authorized users.

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          Most cited references97

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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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            Qinghaosu (artemisinin): the price of success.

            N. White (2008)
            Artemisinin and its derivatives have become essential components of antimalarial treatment. These plant-derived peroxides are unique among antimalarial drugs in killing the young intraerythrocytic malaria parasites, thereby preventing their development to more pathological mature stages. This results in rapid clinical and parasitological responses to treatment and life-saving benefit in severe malaria. Artemisinin combination treatments (ACTs) are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries. Improved agricultural practices, selection of high-yielding hybrids, microbial production, and the development of synthetic peroxides will lower prices. A global subsidy would make these drugs more affordable and available. ACTs are central to current malaria elimination initiatives, but there are concerns that tolerance to artemisinins may be emerging in Cambodia.
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              Whole-genome sequence of Schistosoma haematobium.

              Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.
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                Author and article information

                Contributors
                jennifer.keiser@unibas.ch
                Journal
                Infect Dis Poverty
                Infect Dis Poverty
                Infectious Diseases of Poverty
                BioMed Central (London )
                2049-9957
                28 March 2017
                28 March 2017
                2017
                : 6
                : 74
                Affiliations
                [1 ]Ingerod, Brastad, Sweden
                [2 ]ISNI 0000 0004 0587 0574, GRID grid.416786.a, , Swiss Tropical and Public Health Institute, ; P.O. Box, CH-4002 Basel, Switzerland
                [3 ]ISNI 0000 0004 1937 0642, GRID grid.6612.3, , University of Basel, ; P.O. Box, CH-4003 Basel, Switzerland
                Article
                286
                10.1186/s40249-017-0286-2
                5371198
                28351414
                bcc81736-77b6-48af-a8d2-a048a7073215
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 January 2017
                : 14 March 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100010663, H2020 European Research Council;
                Award ID: ERC-2013-CoG 614739-A_HERO
                Award Recipient :
                Categories
                Scoping Review
                Custom metadata
                © The Author(s) 2017

                chemotherapy,drug repositioning,elimination,morbidity control,praziquantel,schistosomiasis

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