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      The kidney–brain pathogenic axis in severe falciparum malaria

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          Abstract

          Severe falciparum malaria is a medical emergency and a leading cause of death and neurodisability in endemic areas. Common complications include acute kidney injury (AKI) and cerebral malaria, and recent studies have suggested links between kidney and brain dysfunction in Plasmodium falciparum infection. Here, we review these new findings and present the hypothesis of a pivotal pathogenic crosstalk between the kidneys and the brain in severe falciparum malaria. We highlight the evidence of a role for distant organ involvement in the development of cerebral malaria and subsequent neurocognitive impairment post-recovery, describe the challenges associated with current diagnostic shortcomings for both AKI and brain involvement in severe falciparum malaria, and explore novel potential therapeutic strategies.

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          Chronic kidney disease

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            Recommendations on Acute Kidney Injury Biomarkers From the Acute Disease Quality Initiative Consensus Conference: A Consensus Statement

            In the last decade, new biomarkers for acute kidney injury (AKI) have been identified and studied in clinical trials. Guidance is needed regarding how best to incorporate them into clinical practice.
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              Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome.

              Cerebral malaria is the most severe neurological complication of infection with Plasmodium falciparum. With >575,000 cases annually, children in sub-Saharan Africa are the most affected. Surviving patients have an increased risk of neurological and cognitive deficits, behavioral difficulties, and epilepsy making cerebral malaria a leading cause of childhood neurodisability in the region. The pathogenesis of neurocognitive sequelae is poorly understood: coma develops through multiple mechanisms and there may be several mechanisms of brain injury. It is unclear how an intravascular parasite causes such brain injury. Understanding these mechanisms is important to develop appropriate neuroprotective interventions. This article examines possible mechanisms of brain injury in cerebral malaria, relating this to the pathogenesis of the disease, and explores prospects for improved neurocognitive outcome.
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                Author and article information

                Journal
                100966034
                21990
                Trends Parasitol
                Trends Parasitol
                Trends in parasitology
                1471-4922
                1471-5007
                21 April 2024
                March 2023
                02 February 2023
                06 May 2024
                : 39
                : 3
                : 191-199
                Affiliations
                [1 ]Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
                [2 ]University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, University of Bern, Bern, Switzerland
                [3 ]Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
                Author notes
                [* ]Correspondence: Sam.Wassmer@ 123456lshtm.ac.uk (S.C. Wassmer).
                Author information
                http://orcid.org/0000-0002-5328-6511
                http://orcid.org/0000-0003-4552-0694
                http://orcid.org/0000-0002-6753-3376
                Article
                NIHMS1987579
                10.1016/j.pt.2023.01.005
                11071448
                36737313
                2dd88100-30b3-462d-a4d7-7721a4d6ed35

                This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/).

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                Parasitology
                Parasitology

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