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      An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment Translated title: Mise au point sur la kératite à Acanthamoeba : diagnostic, pathogenèse et traitement

      1 , * , 2 , 3

      Parasite

      EDP Sciences

      Acanthamoeba, keratitis, diagnosis, therapy, pathogenesis

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          Abstract

          Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the number of reported cases worldwide is increasing year after year, mostly in contact lens wearers, although cases have also been reported in non-contact lens wearers. Interestingly, Acanthamoeba keratitis has remained significant, despite our advances in antimicrobial chemotherapy and supportive care. In part, this is due to an incomplete understanding of the pathogenesis and pathophysiology of the disease, diagnostic delays and problems associated with chemotherapeutic interventions. In view of the devastating nature of this disease, here we present our current understanding of Acanthamoeba keratitis and molecular mechanisms associated with the disease, as well as virulence traits of Acanthamoeba that may be potential targets for improved diagnosis, therapeutic interventions and/or for the development of preventative measures. Novel molecular approaches such as proteomics, RNAi and a consensus in the diagnostic approaches for a suspected case of Acanthamoeba keratitis are proposed and reviewed based on data which have been compiled after years of working on this amoebic organism using many different techniques and listening to many experts in this field at conferences, workshops and international meetings. Altogether, this review may serve as the milestone for developing an effective solution for the prevention, control and treatment of Acanthamoeba infections.

          Translated abstract

          Les amibes à vie libre du genre Acanthamoeba sont les agents causant une infection sévère de la cornée, dangereuse pour la vue, appelée kératite à Acanthamoeba. De plus, le nombre de cas signalés à travers le monde est en augmentation année après année, principalement chez les porteurs de lentilles de contact, bien que des cas de kératite à Acanthamoeba aient également été signalés chez les non-porteurs de lentilles. Fait intéressant, la kératite à Acanthamoeba est restée significative, en dépit de nos progrès dans la chimiothérapie antimicrobienne et les soins de soutien. En partie, cela est dû à une compréhension incomplète de la pathogenèse et la physiopathologie de la maladie, aux retards du diagnostic et aux problèmes associés aux interventions chimiothérapeutiques. Compte tenu de la nature dévastatrice de cette maladie, nous présentons ici notre compréhension actuelle de la kératite à Acanthamoeba et des mécanismes moléculaires associés à la maladie, ainsi que les traits de virulence de Acanthamoeba qui peuvent être des cibles potentielles pour l’amélioration du diagnostic, les interventions thérapeutiques et/ou pour l’élaboration de mesures préventives. Des approches moléculaires comme la protéomique, l’ARNi et des approches consensuelles de diagnostic pour un cas suspecté de kératite à Acanthamoeba sont proposées et examinées sur la base des données qui ont été compilées après des années de travail sur cet organisme amibien, utilisant de nombreuses techniques différentes et l’écoute de nombreux experts sur ce domaine à des conférences, ateliers et réunions internationales. Au total, cette étude peut servir de jalon pour développer une solution efficace pour la prévention, le contrôle et le traitement des infections à Acanthamoeba.

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          Most cited references 110

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          Acanthamoeba spp. as agents of disease in humans.

          Acanthamoeba spp. are free-living amebae that inhabit a variety of air, soil, and water environments. However, these amebae can also act as opportunistic as well as nonopportunistic pathogens. They are the causative agents of granulomatous amebic encephalitis and amebic keratitis and have been associated with cutaneous lesions and sinusitis. Immuno compromised individuals, including AIDS patients, are particularly susceptible to infections with Acanthamoeba. The immune defense mechanisms that operate against Acanthamoeba have not been well characterized, but it has been proposed that both innate and acquired immunity play a role. The ameba's life cycle includes an active feeding trophozoite stage and a dormant cyst stage. Trophozoites feed on bacteria, yeast, and algae. However, both trophozoites and cysts can retain viable bacteria and may serve as reservoirs for bacteria with human pathogenic potential. Diagnosis of infection includes direct microscopy of wet mounts of cerebrospinal fluid or stained smears of cerebrospinal fluid sediment, light or electron microscopy of tissues, in vitro cultivation of Acanthamoeba, and histological assessment of frozen or paraffin-embedded sections of brain or cutaneous lesion biopsy material. Immunocytochemistry, chemifluorescent dye staining, PCR, and analysis of DNA sequence variation also have been employed for laboratory diagnosis. Treatment of Acanthamoeba infections has met with mixed results. However, chlorhexidine gluconate, alone or in combination with propamidene isethionate, is effective in some patients. Furthermore, effective treatment is complicated since patients may present with underlying disease and Acanthamoeba infection may not be recognized. Since an increase in the number of cases of Acanthamoeba infections has occurred worldwide, these protozoa have become increasingly important as agents of human disease.
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            Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea.

            Among the many genera of free-living amoebae that exist in nature, members of only four genera have an association with human disease: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri and Sappinia diploidea. Acanthamoeba spp. and B. mandrillaris are opportunistic pathogens causing infections of the central nervous system, lungs, sinuses and skin, mostly in immunocompromised humans. Balamuthia is also associated with disease in immunocompetent children, and Acanthamoeba spp. cause a sight-threatening infection, Acanthamoeba keratitis, mostly in contact-lens wearers. Of more than 30 species of Naegleria, only one species, N. fowleri, causes an acute and fulminating meningoencephalitis in immunocompetent children and young adults. In addition to human infections, Acanthamoeba, Balamuthia and Naegleria can cause central nervous system infections in animals. Because only one human case of encephalitis caused by Sappinia diploidea is known, generalizations about the organism as an agent of disease are premature. In this review we summarize what is known of these free-living amoebae, focusing on their biology, ecology, types of disease and diagnostic methods. We also discuss the clinical profiles, mechanisms of pathogenesis, pathophysiology, immunology, antimicrobial sensitivity and molecular characteristics of these amoebae.
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              Structures and mechanisms of glycosyl hydrolases.

              The wealth of information provided by the recent structure determinations of many different glycosyl hydrolases shows that the substrate specificity and the mode of action of these enzymes are governed by exquisite details of their three-dimensional structures rather than by their global fold.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2015
                18 February 2015
                : 22
                : ( publisher-idID: parasite/2015/01 )
                Affiliations
                [1 ] University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Avda. Astrofísico Fco. Sánchez, S/N 38203 La Laguna, Tenerife, Canary Islands Spain
                [2 ] Department of Biological and Biomedical Sciences, Aga Khan University Karachi Pakistan
                [3 ] Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna Vienna Austria
                Author notes
                [a]

                All authors contributed equally to this manuscript.

                [* ]Corresponding author: jmlorenz@ 123456ull.edu.es
                Article
                parasite140120 10.1051/parasite/2015010
                10.1051/parasite/2015010
                4330640
                25687209
                © J. Lorenzo-Morales et al., published by EDP Sciences, 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 8, Tables: 3, Equations: 0, References: 118, Pages: 20
                Categories
                Review Article

                pathogenesis, acanthamoeba, keratitis, diagnosis, therapy

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