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      Meningoencefalitis por cándida en paciente inmunocompetente: Reporte de caso Translated title: Candida meningoencephalitis in an immunocompetent patient: Case report

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          Abstract

          RESUMEN INTRODUCCIÓN: Las infecciones por hongos en el sistema nervioso central son cada vez más frecuentes debido al aumento de las poblaciones en riesgo; son principalmente de carácter oportunista y poco comunes en pacientes sin inmunocompromiso. PRESENTACIÓN DE CASO: Un hombre de 28 años, sin antecedentes medicoquirúrgicos de importancia, consultó al servicio de urgencias por cefalea refractaria, precedida de picos febriles y signos meníngeos, se le hizo punción lumbar con posterior hallazgo microbiológico de Candida glabrata en líquido cefalorraquídeo. Se descartó previamente causal de inmunocompromiso incluyendo coinfección por VIH, colagenosis, neoplasias e incluso falta de inmunización durante la infancia. DISCUSIÓN: Se estiman cerca de 70.000 especies de hongos formalmente descritas, de las cuales 300 podrían mostrar virulencia en los humanos, con múltiples formas de presentación en sistema nervioso central, principalmente meningitis, encefalitis, hidrocéfalo, absceso cerebral e ictus, todos condicionados por un factor predisponente u estado inmunológico del hospedero, planteándose incluso algún grado de inmunodeficiencia sobre receptores tipo Toll like, que limiten la unión a PAMPs y posterior progresión de infección.

          Translated abstract

          SUMMARY INTRODUCTION: Fungal infections of the central nervous system are increasingly frequent due to the increase in populations at risk. They are mainly opportunistic, and uncommon in non-immunocompromise patients. CASE PRESENTATION: A 28-year-old man, without a significant medical and surgical history, consulted the emergency department for refractory headache, accompanied by fever and meningeal signs, a lumbar puncture lead to the subsequent microbiological finding of Candida glabrata in cerebrospinal fluid. Immunocompromise was ruled out, including HIV coinfection, collagen, neoplasms and even lack of immunization during childhood. DISCUSSION: About 70,000 formally described fungal species are estimated, of which 300 could show virulence in humans, with multiple forms of presentation in the central nervous system, mainly meningitis, encephalitis, hydrocephalus, brain abscess and stroke, all conditioned due to a predisposing factor or immune status of the host, even considering some degree of immunodeficiency on Toll like receptors, which limit the binding to PAMPs and subsequent progression of infection at the height of the CNS.

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          Most cited references12

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          Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision

          Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.
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            A homozygous CARD9 mutation in a family with susceptibility to fungal infections.

            Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant inheritance and autosomal recessive inheritance have been described. We performed genetic studies in 36 members of a large, consanguineous five-generation family, in which 4 members had recurrent fungal infections and an additional 3 members died during adolescence, 2 after invasive infection of the brain with candida species. All 36 family members were enrolled in the study, and 22 had blood samples taken for DNA analysis. Homozygosity mapping was used to locate the mutated gene. In the 4 affected family members (patients) and the 18 unaffected members we sequenced CARD9, the gene encoding the caspase recruitment domain-containing protein 9, carried out T-cell phenotyping, and performed functional studies, with the use of either leukocytes from the patients or a reconstituted murine model of the genetic defect. We found linkage (lod score, 3.6) to a genomic interval on chromosome 9q, including CARD9. All four patients had a homozygous point mutation in CARD9, resulting in a premature termination codon (Q295X). Healthy family members had wild-type expression of the CARD9 protein; the four patients lacked wild-type expression, which was associated with low numbers of Th17 cells (helper T cells producing interleukin-17). Functional studies based on genetic reconstitution of myeloid cells from Card9(-/-) mice showed that the Q295X mutation impairs innate signaling from the antifungal pattern-recognition receptor dectin-1. An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9. 2009 Massachusetts Medical Society
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              Neuroinfections caused by fungi

              Background Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. Methods One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: “fungi and CNS mycoses”, CNS fungal infections”, “fungal brain infections”, " fungal cerebritis”, fungal meningitis”, “diagnostics of fungal infections”, and “treatment of CNS fungal infections”. All were published in English with the majority in the period 2000–2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS. Results The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS. Conclusion Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.
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                Author and article information

                Journal
                anco
                Acta Neurológica Colombiana
                Acta Neurol Colomb.
                Asociación Colombiana de Neurología (Bogotá, Distrito Capital, Colombia )
                0120-8748
                2422-4022
                December 2020
                : 36
                : 4
                : 243-246
                Affiliations
                [3] Sincelejo Sucre orgnameIPS vida Plena Colombia
                [1] Sincelejo Sucre orgnameClínica Salud Social y Neurosabanas Colombia
                [2] Sincelejo Sucre orgnameClínica Salud Social Colombia
                Article
                S0120-87482020000400243 S0120-8748(20)03600400243
                10.22379/24224022329
                b6e23a41-3a71-4d63-97a7-650fd8e533c9

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 03 July 2020
                : 27 November 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 12, Pages: 4
                Product

                SciELO Colombia

                Categories
                Caso clínico

                Encephalitis,Meningoencefalitis,Meningitis fúngica,Encefalitis,Candidiasis (DeCS),Meningoencephalitis,Fungal meningitis,Candidiasis (MeSH)

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