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      Paediatric schistosomiasis: What we know and what we need to know

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          Abstract

          Schistosomiasis affects over 200 million people worldwide, most of whom are children. Research and control strategies directed at preschool-aged children (PSAC), i.e., ≤5 years old, have lagged behind those in older children and adults. With the recent WHO revision of the schistosomiasis treatment guidelines to include PSAC, and the recognition of gaps in our current knowledge on the disease and its treatment in this age group, there is now a concerted effort to address these shortcomings. Global and national schistosome control strategies are yet to include PSAC in treatment schedules. Maximum impact of schistosome treatment programmes will be realised through effective treatment of PSAC. In this review, we (i) discuss the current knowledge on the dynamics and consequences of paediatric schistosomiasis and (ii) identify knowledge and policy gaps relevant to these areas and to the successful control of schistosome infection and disease in this age group. Herein, we highlight risk factors, immune mechanisms, pathology, and optimal timing for screening, diagnosis, and treatment of paediatric schistosomiasis. We also discuss the tools required for treating schistosomiasis in PSAC and strategies for accessing them for treatment.

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          Most cited references84

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          Protection against a malaria challenge by sporozoite inoculation.

          An effective vaccine for malaria is urgently needed. Naturally acquired immunity to malaria develops slowly, and induction of protection in humans can be achieved artificially by the inoculation of radiation-attenuated sporozoites by means of more than 1000 infective mosquito bites. We exposed 15 healthy volunteers--with 10 assigned to a vaccine group and 5 assigned to a control group--to bites of mosquitoes once a month for 3 months while they were receiving a prophylactic regimen of chloroquine. The vaccine group was exposed to mosquitoes that were infected with Plasmodium falciparum, and the control group was exposed to mosquitoes that were not infected with the malaria parasite. One month after the discontinuation of chloroquine, protection was assessed by homologous challenge with five mosquitoes infected with P. falciparum. We assessed humoral and cellular responses before vaccination and before the challenge to investigate correlates of protection. All 10 subjects in the vaccine group were protected against a malaria challenge with the infected mosquitoes. In contrast, patent parasitemia (i.e., parasites found in the blood on microscopical examination) developed in all five control subjects. Adverse events were mainly reported by vaccinees after the first immunization and by control subjects after the challenge; no serious adverse events occurred. In this model, we identified the induction of parasite-specific pluripotent effector memory T cells producing interferon-gamma, tumor necrosis factor alpha, and interleukin-2 as a promising immunologic marker of protection. Protection against a homologous malaria challenge can be induced by the inoculation of intact sporozoites. (ClinicalTrials.gov number, NCT00442377.) 2009 Massachusetts Medical Society
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            Soil-transmitted helminth infections: updating the global picture.

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              Chronic helminth infections induce immunomodulation: consequences and mechanisms.

              Worldwide, more than a billion people are infected with helminths. These worm infections generally do not lead to mortality, however, they are chronic in nature and can lead to considerable morbidity. Immunologically these infections are interesting; chronic helminth infections are characterized by skewing towards a T helper 2 type response as well as regulatory responses. The regulatory network is associated with chronic helminth infections and is thought to prevent strong immune responses against parasitic worms, allowing their long-term survival and restricting pathology. This regulatory network is thought to also temper responses to non-helminth antigens, like allergens or self-antigens, possibly leading to lower prevalence of allergies and autoimmune diseases in subjects that are chronically infected with helminths. This raises the interesting idea that helminths may bear molecules that have potential therapeutic action against allergies and possibly other inflammatory diseases. However, on the other side of the coin, this would predict that helminth infected subjects might not respond strongly to third party antigens like vaccines. This is an important issue, since most vaccines that are being developed against diseases such as HIV, tuberculosis or malaria will be introduced in areas where helminth infections are highly prevalent. Moreover, these vaccines are proving difficult to develop and are often weak, thus any confounder that would affect their efficacy needs to be taken into consideration. Helminth derived molecules have been identified that induce T helper 2 and regulatory responses via modulation of dendritic cells and some appear to do so via Toll like receptor (TLR) signaling. New insights into these pathways could be useful to antagonize suppression and hence boost vaccine efficacy or to optimize suppression induced by helminth derived molecules and control inflammatory diseases.
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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, CA USA )
                1935-2727
                1935-2735
                8 February 2018
                February 2018
                : 12
                : 2
                : e0006144
                Affiliations
                [1 ] Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom
                [2 ] Centre for Immunity, Infection and Evolution, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom
                [3 ] NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA), University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom
                Swiss Tropical and Public Health Institute, SWITZERLAND
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-4853-5384
                Article
                PNTD-D-17-01239
                10.1371/journal.pntd.0006144
                5805162
                29420537
                36064301-63ac-4b5c-8129-428f5085dc59
                © 2018 Osakunor et al

                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
                Page count
                Figures: 1, Tables: 0, Pages: 16
                Funding
                Our ongoing paediatric schistosomiasis project is funded by the Thrasher Research Fund 12440 and the Wellcome Trust 108061/Z/15/Z. Our research is also commissioned by the National Institute of Health Research, using Official Development Assistance (ODA) funding 16/136/33. DNMO is supported by the Darwin Trust of Edinburgh. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute of Health Research, or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Medicine and Health Sciences
                Parasitic Diseases
                Helminth Infections
                Schistosomiasis
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Schistosomiasis
                Medicine and Health Sciences
                Health Care
                Health Statistics
                Morbidity
                Medicine and Health Sciences
                Pediatrics
                Pediatric Infections
                Medicine and Health Sciences
                Pediatrics
                Medicine and Health Sciences
                Parasitic Diseases
                Medicine and Health Sciences
                Parasitic Diseases
                Helminth Infections
                Biology and Life Sciences
                Immunology
                Immune Response
                Medicine and Health Sciences
                Immunology
                Immune Response

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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