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      Current Understanding of Immunity Against Schistosomiasis: Impact on Vaccine and Drug Development

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          Abstract

          Schistosomiasis is a neglected tropical disease inflicting significant morbidity in humans worldwide. The disease is caused by infections with a parasitic trematode belonging to the genus Schistosoma. Over 250 million people are currently infected globally, with an estimated disability-adjusted life-years of 1.9 million attributed to the disease. Current understanding, based on several immunological studies using experimental and human models of schistosomiasis, reveals that complex immune mechanisms play off each other in the acquisition of immune resistance to infection/reinfection. Nevertheless, the precise characteristics of these responses, the specific antigens against which they are elicited, and how these responses are intricately regulated are still being investigated. What is apparent is that immunity to schistosome infections develops slowly and over a prolonged period of time, augmented by the death of adult worms occurring naturally or by praziquantel therapy. In this review, aspects of immunity to schistosomiasis, host–parasite interactions and their impact on schistosomiasis vaccine development are discussed.

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          Human schistosomiasis.

          Human schistosomiasis--or bilharzia--is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

            Summary Background Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9–78·6) for females and 72·0 years (68·8–75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0–49·5]) and for males was in Lesotho (41·5 years [39·0–44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97–6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74–6·27) for males and 6·49 years (6·08–6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61–1·93) for males and 1·96 years (1·69–2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (–2·3% [–5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. Funding Bill & Melinda Gates Foundation.
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              Schistosomiasis

              Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms (blood flukes) of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia and, particularly, in sub-Saharan Africa. Infective larvae grow in an intermediate host (fresh-water snails) before penetrating the skin of the definitive human host. Mature adult worms reside in the mesenteric (Schistosoma mansoni and Schistosoma japonicum) or pelvic (Schistosoma haematobium) veins, where female worms lay eggs, which are secreted in stool or urine. Eggs trapped in the surrounding tissues and organs, such as the liver and bladder, cause inflammatory immune responses (including granulomas) that result in intestinal, hepato-splenic or urogenital disease. Diagnosis requires the detection of eggs in excreta or worm antigens in the serum, and sensitive, rapid, point-of-care tests for populations living in endemic areas are needed. The anti-schistosomal drug praziquantel is safe and efficacious against adult worms of all the six Schistosoma spp. infecting humans; however, it does not prevent reinfection and the emergence of drug resistance is a concern. Schistosomiasis elimination will require a multifaceted approach, including: treatment; snail control; information, education and communication; improved water, sanitation and hygiene; accurate diagnostics; and surveillance-response systems that are readily tailored to social-ecological settings.
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                Author and article information

                Journal
                Res Rep Trop Med
                Res Rep Trop Med
                rrtm
                Research and Reports in Tropical Medicine
                Dove
                1179-7282
                02 November 2020
                2020
                : 11
                : 119-128
                Affiliations
                [1 ]Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center , Lubbock, TX 79430, USA
                [2 ]Center for Tropical Medicine and Infectious Diseases, School of Medicine, Texas Tech University Health Sciences Center , Lubbock, TX 79430, USA
                Author notes
                Correspondence: Adebayo J Molehin Department of Internal Medicine, School of Medicine,Texas Tech University Health Sciences Center , Lubbock, TX79430, USATel +1 (806) 743 2639 Email adebayo.molehin@ttuhsc.edu
                Author information
                http://orcid.org/0000-0002-6262-1529
                Article
                274518
                10.2147/RRTM.S274518
                7646453
                33173371
                d3cdede8-edb8-4808-b6b3-4d7422b40baa
                © 2020 Molehin.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 26 August 2020
                : 29 September 2020
                Page count
                Figures: 1, References: 107, Pages: 10
                Categories
                Review

                schistosomiasis,immunity,schistosomiasis vaccine development,resistance to reinfection

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