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BACKGROUND: Influenza-Associated Encephalopathy/Encephalitis (IAE) is characterized by high incidence and poor prognosis. The aim of this study is to describe the clinical features and outcomes of IAE in pediatric patients. METHODS: We performed a retrospective review of hospitalized cases of laboratory-confirmed influenza infection between January 2018 and December 2021. Demographic, clinical, imaging, treatment and outcome data were collected. Statistical analysis was performed using SPSS software. RESULTS: Of 446 children hospitalized with influenza, 71 cases were identified with a diagnosis of IAE. The median age was 3 years and 46 (64.8 %) were younger than 5 years. Only one patient was vaccinated for seasonal influenza. 46 (64.8 %) patients had abnormal electroencephalogram examination and 47 (66.2 %) had abnormal brain MRI or CT findings. 68 (95.8 %) patients were treated with oseltamivir/peramivir. 12 (16.9 %) patients suffered mortality. Non-survivors were more likely to have lower Glasgow coma score (median 7), longer duration of fever (median 3 days), with underlying medical conditions (P = 0.006), and complications including sepsis (P = 0.003), shock (P < 0.001), respiratory failure (P = 0.006), acute renal failure (P = 0.001), myocardial damage (P < 0.001), coagulation disorders (P = 0.03), electrolyte disturbance (P = 0.001) and hyperlactacidemia (P = 0.003). Non-survivors had higher percentages of corticosteroids (P = 0.003) and immunoglobulin (P = 0.003) treatments compared to survivors. CONCLUSIONS: Children with IAE have a high mortality rate. Lower Glasgow coma score, longer duration of fever, with underlying medical conditions and complications pose a great risk to poor prognosis. Influenza vaccination is recommended to all eligible children.
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Influenza Humana , Humanos , Feminino , Estudos Retrospectivos , Masculino , Influenza Humana/complicações , Pré-Escolar , China/epidemiologia , Criança , Lactente , Antivirais/uso terapêutico , Encefalite Viral , Oseltamivir/uso terapêutico , Prognóstico , Adolescente , Eletroencefalografia , Resultado do Tratamento , Imageamento por Ressonância MagnéticaRESUMO
Western equine encephalitis (WEE) is vector-borne infection caused by an RNA virus of the genus Alphavirus, disseminated by mosquitoes that can cause WEE in humans. There are two cycles of transmission, a maintenance cycle and an occasional amplification with vector augmentation, where equines and humans are terminal hosts. In Argentina, no human cases had been reported since 1983. Here we describe 2 pediatric patients with brain symptoms and serological diagnosis of WEE. Both samples of cerebrospinal fluid (CSF) showed pleocytosis, while the neuroimaging test showed alterations in the basal ganglia. The serological diagnosis was based on the detection of specific IgM in serum and CSF and neutralizing antibodies 14 days after symptom onset. The patients were managed with supportive treatment. One patient recovered his normal neurological status without seizures before discharge, while the other was discharged with right hemiparesis, which resolved after 2 months, and continued with anticonvulsants due to a pathological EEG.
La encefalitis equina del oeste (EEO) es una infección causada por un virus ARN del género Alphavirus, de transmisión vectorial por mosquitos que pueden causar la enfermedad en humanos. Hay dos ciclos de transmisión, de mantenimiento y de amplificación ocasional con aumento de vectores, donde equinos y seres humanos son huéspedes terminales. En Argentina no se reportaban casos humanos desde 1983. Se presentan dos pacientes pediátricos con síntomas encefálicos y diagnóstico por serología de EEO. Ambos líquidos cefalorraquídeos (LCR) evidenciaron pleocitosis y las neuroimágenes, alteraciones en ganglios de la base. Se arribó al diagnóstico por serología con detección de IgM específica en suero y LCR, y anticuerpos neutralizantes 14 días después del inicio de síntomas. El tratamiento fue de sostén. Un paciente recuperó el estado neurológico habitual previo al alta sin crisis comiciales y el otro egresó con hemiparesia derecha, que se resolvió luego de dos meses, y continuó con anticonvulsivantes por EEG patológico.
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Rasmussen's encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherotomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Furthermore, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expression of cell-cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest the potential involvement of cell cycle regulators in the progression of RE.
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Encefalite , Humanos , Encefalite/genética , Encefalite/patologia , Encefalite/metabolismo , Masculino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Feminino , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Ciclo Celular/genéticaRESUMO
Acanthamoeba genus can affect humans with diseases such as granulomatous amebic encephalitis (GAE), a highly lethal neuroinfection. Several aspects of the disease still need to be elucidated. Animal models of GAE have advanced our knowledge of the disease. This work tested Wistar rats (Rattus norvegicus albinus) as an animal model of GAE. For this, 32 animals were infected with 1 × 106A. castellanii trophozoites of the T4 genotype. Ameba recovery tests were carried out using agar plates, vascular extravasation assays, behavioral tests, and histopathological technique with H/E staining. Data were subjected to linear regression analysis, one-way ANOVA, and Tukey's test, performed in the GraphPad Prism® 8.0 program, with a significance level of p < 0.05. The results revealed the efficiency of the model. Amebae were recovered from the liver, lungs, and brain of infected animals, and there were significant encephalic vascular extravasations and behavioral changes in these animals, but not in the control animals. However, not all infected animals showed positive histopathology for the analyzed organs. Nervous tissues were the least affected, demonstrating the role of the BBB in the defense of the CNS. Supported by the demonstrated evidence, we confirm the difficulties and the feasibilities of using rats as an animal model of GAE.
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The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. The disease caused by this virus has been associated with a diverse range of symptoms, including common neurological manifestations such as dysgeusia, anosmia, and myalgias. Additionally, numerous cases of severe neurological complications associated with this disease have been reported, including encephalitis, stroke, seizures, and Guillain-Barré syndrome, among others. Given the high prevalence of neurological manifestations in this disease, the objective of this review is to analyze the mechanisms by which this virus can affect the nervous system, from its direct invasion to aberrant activation of the immune system and other mechanisms involved in the symptoms, including neuropsychiatric manifestations, to gain a better understanding of the disease and thus facilitate the search for effective therapeutic strategies.
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OBJECTIVES: Encephalitis is a severe neurological syndrome for which herpesvirus and enteroviruses are the most common etiological agents. Arboviruses, a wildly diverse group of pathogens, are also critical epidemiological agents associated with encephalitis. In Brazil, little is known about the causative agents of encephalitis. METHODS: We conducted a hospital surveillance for encephalitis between 2020 and 2022. Molecular (RT-PCR and qPCR) and serological (virus-specific IgM and viral antigens) techniques were performed in cerebrospinal fluid and serum samples obtained from study participants. RESULTS: In the 43 participants evaluated, the etiologic agent or the presence of IgM was detected in 16 (37.2%). Nine (20.9%) cases were positive for chikungunya virus (CHIKV), three (7.0%) for dengue virus, two (4.7%) for human adenovirus, one (2.3%) for varicella-zoster virus, and one (2.3%) for enterovirus. Whole-genome sequencing revealed that the CHIKV identified belongs to the East/Central/South African lineage. CONCLUSION: Herein, CHIKV is a common pathogen identified in encephalitis cases. Our results reinforce previous evidence that chikungunya represents a significant cause of encephalitis during CHIKV outbreaks and epidemics and add to existing information on the epidemiology of encephalitis in Brazil.
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Febre de Chikungunya , Vírus Chikungunya , Humanos , Brasil/epidemiologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Masculino , Feminino , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/sangue , Adulto , Adolescente , Criança , Adulto Jovem , Pessoa de Meia-Idade , Pré-Escolar , Anticorpos Antivirais/sangue , Encefalite Viral/epidemiologia , Encefalite Viral/virologia , Encefalite Viral/diagnóstico , Imunoglobulina M/sangue , Idoso , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Lactente , Filogenia , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/isolamento & purificação , Enterovirus/isolamento & purificação , Enterovirus/genética , Sequenciamento Completo do GenomaRESUMO
A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.
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Doenças dos Símios Antropoides , Cegueira , Meningoencefalite , Mycobacterium tuberculosis , Pan troglodytes , Animais , Feminino , Doenças dos Símios Antropoides/diagnóstico , Doenças dos Símios Antropoides/microbiologia , Doenças dos Símios Antropoides/patologia , Mycobacterium tuberculosis/isolamento & purificação , Cegueira/veterinária , Cegueira/etiologia , Cegueira/microbiologia , Cegueira/diagnóstico , Meningoencefalite/veterinária , Meningoencefalite/microbiologia , Meningoencefalite/diagnóstico , Granuloma/veterinária , Granuloma/microbiologia , Granuloma/patologia , Granuloma/diagnóstico , Tuberculose/veterinária , Tuberculose/diagnóstico , Tuberculose/complicaçõesRESUMO
Introducción: El herpes connatal es una entidad infrecuente asociada a elevada morbimortalidad. La probabilidad de transmisión al recién nacido va de 5% al 85%. El diagnóstico se dificulta por falta de clínica, serología no confiable y por la no disponibilidad de PCR en los servicios públicos de países en vías de desarrollo. La IgM en gestantes podría ser utilizada como un marcador de sospecha para evaluar al neonato. Objetivo: Caracterizar a los recién nacidos, hijos de gestantes con IgM positiva para HVS 1-2 y la frecuencia de encefalitis en los infantes. Materiales y métodos : Estudio observacional, descriptivo, prospectivo, realizado de mayo de 2020 a octubre de 2021. Se incluyeron recién nacidos (RN) de madres con IgM positiva para Herpes Virus Simplex (HVS) a partir de la segunda mitad del embarazo. En el RN se realizó serología IgG e IgM, y además, PCR- RT para HVS 1-2 en sangre y/o LCR, excluyéndose los nacidos en otras maternidades y/o sin datos de serología materna. Resultados: 36 pacientes. Edad materna 28 años (DS + 4), 5% con antecedentes de HVS, 61% cesárea. 36% prematuros, 13% RCIU. Síntomas agudos en el RN 22%. De ellos, 19% plaquetopenia, 44% alteración de GOT. 63% PCR HVS en sangre y 44% en LCR. Se encontró hemorragia, hidrocefalia, leucomalacia en 27%. No se encontró diferencias en la expresión clínica por tipo de parto. Conclusiones: Los RN hijos de gestantes con IgM positiva para VHS desde la segunda mitad del embarazo o periparto, presentaron infección por VHS determinada por PCR en sangre o LCR, independiente de la vía del parto. El diagnóstico serológico en embarazadas permite la pesquisa, diagnóstico y tratamiento temprano del RN.
Introduction: neonatal herpes is a rare entity associated with high morbidity and mortality. The probability of transmission to the newborn ranges from 5% to 85%. The diagnosis is difficult due to the lack of clinical signs, unreliable serology and the non-availability of PCR in public services in developing countries. IgM in pregnant women could be used as a suspected marker to evaluate the neonate. Objective: To characterize newborn children of pregnant women with positive IgM for HSV 1-2 and the prevalence of encephalitis in infants. Materials and methods: Observational, descriptive, prospective study, carried out from May 2020 to October 2021. Newborns (NB) of mothers with positive IgM for Herpes Virus Simplex (HSV) from the second half of pregnancy were included. In newborns, IgG and IgM were performed, and in addition, PCR-RT for HSV 1-2 in blood and/or CSF, excluding those born in other hospitales and/or without maternal serology data. Results: We included 36 patients. Maternal age was 28 years (DS + 4), 5% with a history of HSV. 61% were delivered via cesarean section, 36% were premature, 13% had IUGR. 22% of the newborns had acute symptoms. 19% had thrombocytopenia, 44% had GOT alteration. 63% were PCR positive for HSV in serum and 44% were CSF-positive. Hemorrhage, hydrocephalus and leukomalacia were found in 27%. No differences were found in clinical expression by type of delivery. Conclusions: Newborns born to pregnant women with positive IgM for HSV from the second half of pregnancy or peripartum, presented HSV infection as determined by PCR in blood or CSF, regardless of the route of delivery. Serological diagnosis in pregnant women allows early screening, diagnosis and treatment of the NB.
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Herpes simplex virus 1 (HSV-1) or simplexvirus humanalpha 1 is a neurotropic virus that is responsible for orofacial infections in humans. More than 70% of the world's population may have seropositivity for HSV-1, and this virus is a leading cause of sporadic lethal encephalitis in humans. The role of toll-like receptors (TLRs) in defending against HSV-1 infection has been explored, including the consequences of lacking these receptors or other proteins in the TLR pathway. Cell and mouse models have been used to study the importance of these receptors in combating HSV-1, how they relate to the innate immune response, and how they participate in the orchestration of the adaptive immune response. Myeloid differentiation factor 88 (MyD88) is a protein involved in the downstream activation of TLRs and plays a crucial role in this signaling. Mice with functional MyD88 or TLR2 and TLR9 can survive HSV-1 infection. However, they can develop encephalitis and face a 100% mortality rate in a dose-dependent manner when MyD88 or TLR2 plus TLR9 proteins are non-functional. In TLR2/9 knockout mice, an increase in chemokines and decreases in nitric oxide (NO), interferon (IFN) gamma, and interleukin 1 (IL-1) levels in the trigeminal ganglia (TG) have been correlated with mortality.
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Encefalite , Herpes Simples , Herpesvirus Humano 1 , Humanos , Animais , Camundongos , Herpesvirus Humano 1/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Gânglio Trigeminal/metabolismo , Receptores Toll-Like/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BLRESUMO
Introducción: La encefalitis por anticuerpos contra el receptor N-metil.D.aspartato (NMDA-R) es un trastorno inflamatorio del sistema nervioso central (SNC) en el cual autoanticuerpos dirigidos hacia la subunidad NR1 del receptor N-metil-D aspartato (NMDA) desarrollan un conjunto de síntomas neuropsiquiátricos, convulsiones y movimientos anormales. El tratamiento recomendado incluye metilprednisolona (MP) y gamaglobulina (IVIg), y/o recambio plasmático terapéutico (RPT); y en caso de no respuesta: rituximab (RTX) y/o ciclofosfamida (CFM). Objetivos: Analizar características clínicas, bioquímicas, electroencefalograma (EEG), resonancia magnética (RM) cerebral, tratamientos recibidos y resultados observados en una serie de pacientes con encefalitis autoinmune (EA) probable o confirmada. Materiales y métodos: Analizamos las historias clínicas de pacientes menores a 17 años que cumplían criterios diagnósticos de Graus (2016) para EA probable, con seguimiento mayor a 6 meses, internados en el Hospital Garrahan entre 2008 y 2023. El diagnóstico se definió por la identificación de anticuerpos anti-NMDAR (N-metil D-aspartato) en líquido cefalorraquídeo (LCR) por ensayo basado en células - cell bassed assay (CBA). Resultados: Reunieron criterios de EA probable 94 pacientes con una edad media de 89.5 meses, 51% mujeres. Se dividieron en dos grupos: seropositivos y seronegativos de acuerdo al resultado del biomarcador. Seropositivos 45/94. El síntoma inicial más frecuente fue: convulsiones. El 28% requirió ingreso a Unidad de Cuidados Intensivos (UCI). 4 pacientes seropositivos y 1 seronegativo tuvieron encefalitis por el virus del herpes simple (Om) previamente. En una paciente seronegativa se diagnosticó teratoma ovárico. Hallazgos de estudios complementarios: LCR patológico en el 29%, RM cerebral en el 52%, EEG en el 74%. El tratamiento de primera línea más empleado fue MP + IVIg. El 46% de los pacientes presentó recuperación completa. Entre los pacientes que recibieron RTX, el 65% tuvo una recuperación completa. Ningún paciente que recibió RTX presentó recaída. Conclusión: Ante la sospecha de EA se debe considerar el inicio temprano de inmunoterapia para favorecer la rápida recuperación funcional. Se recomienda el uso temprano de RTX en los casos con presentación grave o respuesta subóptima al tratamiento de primera línea para beneficiar la respuesta clínica y reducir el riesgo de recaída (AU)
Introduction: Encephalitis due to antibodies against the N-methyl-D-aspartate receptor (NMDA-R) is an inflammatory disorder of the central nervous system (CNS) in which autoantibodies directed against the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor develop a set of neuropsychiatric symptoms, seizures, and abnormal movements. The recommended treatment includes methylprednisolone (MP) and intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE); and in case of non-response: rituximab (RTX) and/or cyclophosphamide (CFM). Objectives: To analyze clinical, biochemical, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, treatments received, and outcomes observed in a series of patients with probable or confirmed autoimmune encephalitis (AE). Materials and methods: We analyzed the medical records of patients under 17 years of age who met Graus' diagnostic criteria (2016) for probable AE, with follow-up of more than 6 months, hospitalized at Hospital Garrahan between 2008 and 2023. Diagnosis was defined by the identification of anti-NMDAR antibodies (N-methyl D-aspartate) in cerebrospinal fluid (CSF) by cell-based assay (CBA). Results: Ninety-four patients met criteria for probable AE with a mean age of 89.5 months, 51% female. They were divided into two groups: seropositive and seronegative according to the biomarker result. Seropositive 45/94. The most frequent initial symptom was seizures. Twenty-eight percent required admission to the Intensive Care Unit (ICU). Four seropositive patients and one seronegative patient had previously had herpes simplex encephalitis (Om). Ovarian teratoma was diagnosed in one seronegative patient. Findings of complementary studies: Pathological CSF in 29%, brain MRI in 52%, EEG in 74%. The most commonly used first-line treatment was MP + IVIg. Forty-six percent of patients experienced complete recovery. Among patients who received RTX, 65% had complete recovery. No patient who received RTX experienced relapse. Conclusion: In the suspicion of AE, early initiation of immunotherapy should be considered to promote rapid functional recovery. Early use of RTX is recommended in cases with severe presentation or suboptimal response to first-line treatment to benefit clinical response and reduce the risk of relapse (AU)
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Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Autoanticorpos , Encefalite , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Imunoterapia , Convulsões , Espectroscopia de Ressonância Magnética , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Anthropogenic activities are altering ecosystem stability and climate worldwide, which is disturbing and shifting arbovirus vector distributions. Although the overall geographic range of some epidemiologically important species is recognized, the spatiotemporal variation for other species in the context of climate change remains poorly understood. Here we predict the current potential distribution of 9 species of Culex (Melanoconion) based on an ecological niche modeling (ENM) approach and assess spatiotemporal variation in future climate change in the Neotropics. The most important environmental predictors were the mean temperature of the warmest season (27 °C), precipitation during the driest month (50 mm), and precipitation during the warmest season (>200 mm). The best current model for each species was transferred to the future general circulation model IPSL-CM6A-LR, using 2 shared socioeconomic pathway scenarios (ssp1-2.6, ssp5-8.5). Under both scenarios of climatic change, an expansion of suitable areas can be observed followed by a strong reduction for the medium-long future under the worst scenario. The multivariate environmental similarity surface analysis indicated future novel climates outside the current range. However, none of the species would occur in those areas. Even if many challenges remain in improving methods for forecasting species responses to global climate change and arbovirus transmission, ENM has strong potential to be applied to the geographic characterization of these systems. Our study can be used for the monitoring of Culex (Melanoconion) species populations and their associated arboviruses, contributing to develop region-specific public health surveillance programs.
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Arbovírus , Culex , Culicidae , Animais , Ecossistema , Saúde Pública , Mosquitos Vetores , Arbovírus/fisiologia , Mudança ClimáticaRESUMO
Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, there are limited clinical and epidemiological reports available, and outbreaks are occurring at an increasing frequency. We addressed this gap by analyzing all the available clinical and epidemiological data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 of human alphavirus encephalitis cases were detected in Panama from 1961 to 2023. Here we describe the clinical signs and symptoms and epidemiological characteristics of these cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection when compared to those of other arbovirus infections occurring in the region. Our results highlight the challenges clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.
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Three outbreaks of herpesvirus meningoencephalitis in cattle have been reported in three municipalities in the northern region of the State of Tocantins, Brazil. In one outbreak, 41 predominantly young bovines were affected, with 2-3 deaths in some cases. The animals showed neurological signs of incoordination, blindness, and recumbency, with death occurring within approximately 4-5 d. At necropsy, hyperemia and leptomeningeal hemorrhages were observed in the brain. Histology revealed more intense lesions in the rostral portions of the brain, mainly affecting the frontoparietal cerebral cortex, with nonsuppurative encephalitis and meningitis, glial nodules, neuronophagia, and eosinophilic intranuclear inclusion bodies in the astrocytes and neurons. This study shows the presence of bovine herpesvirus in Tocantins, probably the highly neurotropic type 5 strain, and emphasizes its importance in the differential diagnosis of bovine neuropathies.
Três surtos de meningoencefalite por herpesvírus em bovinos são relatados em três municípios da região norte do Estado do Tocantins, Brasil. Num surto, 41 animais predominantemente jovens foram afetados, com 2-3 mortes nos outros casos. Os animais apresentaram sinais neurológicos de incoordenação, cegueira e decúbito, com a morte ocorrendo em aproximadamente 4 a 5 dias. Na necropsia foram observadas hiperemia e hemorragias leptomeníngeas no encéfalo. A histologia revelou lesões mais intensas nas porções rostrais do encéfalo, principalmente no córtex cerebral frontoparietal, com encefalite e meningite não supurativas, nódulos gliais, neuronofagia e corpúsculos de inclusão intranucleares eosinofílicos nos astrócitos e neurônios. Este estudo demonstra a presença do herpesvírus bovino no Tocantins, provavelmente a cepa tipo 5 altamente neurotrópica, e enfatiza sua importância no diagnóstico diferencial das neuropatias bovinas.
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The Saint Louis encephalitis virus (SLEV) is an encephalitogenic arbovirus (Flaviviridae family) that has a wide geographical distribution in the western hemisphere, especially in the Americas. The negevirus Brejeira (BREV) was isolated for the first time in Brazil in 2005. This study aimed to verify the existence of a possible interfering effect of BREV on the course of SLEV infection and vice versa. We used clone C6/36 cells. Three combinations of MOIs were used (SLEV 0.1 × BREV 1; SLEV 1 × BREV 0.1; SLEV 1 × BREV 1) in the kinetics of up to 7 days and then the techniques of indirect immunofluorescence (IFA), a plaque assay on Vero cells, and RT-PCR were performed. Our results showed that the cytopathic effect (CPE) caused by BREV was more pronounced than the CPE caused by SLEV. Results of IFA, the plaque assay, and RT-PCR showed the suppression of SLEV replication in the co-infection condition in all the MOI combinations used. The SLEV suppression was dose-dependent. Therefore, the ISV Brejeira can suppress SLEV replication in Aedes albopictus cells, but SLEV does not negatively interfere with BREV replication.
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Aedes , Vírus da Encefalite de St. Louis , Interferência Viral , Animais , Chlorocebus aethiops , Vírus da Encefalite de St. Louis/genética , Células Vero , InsetosRESUMO
Las enfermedades causadas por amebas de vida libre son infecciones oportunistas que pueden tener un curso fatal. Pueden producir afecciones diseminadas graves con compromiso del sistema nervioso central, como la encefalitis amebiana granulomatosa. Esta infección es cada vez más frecuente en América Latina, aunque se reconocen tardíamente debido a la similitud con otras patologías o porque es inusual incluirla en el diagnóstico diferencial. Comunicamos un caso fatal de una encefalitis amebiana granulomatosa por Balamuthia mandrillaris en una niña de 10 años. Destacamos la gravedad de la afectación cerebral y la falta de esquemas antimicrobianos validados para su tratamiento. Hoy en el mundo esta infección es considerada una enfermedad emergente, influenciada por el cambio climático, lo que llama a estar atentos a su presencia.
Diseases caused by free-living amoebae are opportunistic infections that can have a fatal course. They can cause very serious disseminated conditions with involvement of the central nervous system such as granulomatous amoebic encephalitis. This infection has become more common in Latin America, although its recognition is late due to the similarity with other pathological conditions or because it is unusual to include it in the differential diagnosis. We report a fatal case of granulomatous amoebic encephalitis due to Balamuthia mandrillaris in a 10-year-old girl. We highlight the severity of the brain involvement and the lack of validated schemes for its treatment. Today in the world this infection is considered an emerging disease, influenced by climate change, which calls for being attentive to its presence.
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Humanos , Feminino , Criança , Encefalite Infecciosa/diagnóstico , Amebíase/diagnóstico , Tomografia Computadorizada por Raios X , Análise de Sequência de DNA , Evolução Fatal , Balamuthia mandrillaris/isolamento & purificação , Balamuthia mandrillaris/genética , Encefalite Infecciosa/diagnóstico por imagem , Amebíase/diagnóstico por imagemRESUMO
The development of specific, safe, and potent monoclonal antibodies (Abs) has led to novel therapeutic options for infectious disease. In addition to preventing viral infection through neutralization, Abs can clear infected cells and induce immunomodulatory functions through engagement of their crystallizable fragment (Fc) with complement proteins and Fc receptors on immune cells. Little is known about the role of Fc effector functions of neutralizing Abs in the context of encephalitic alphavirus infection. To determine the role of Fc effector function in therapeutic efficacy against Venezuelan equine encephalitis virus (VEEV), we compared the potently neutralizing anti-VEEV human IgG F5 (hF5) Ab with intact Fc function (hF5-WT) or containing the loss of function Fc mutations L234A and L235A (hF5-LALA) in the context of VEEV infection. We observed significantly reduced binding to complement and Fc receptors, as well as differential in vitro kinetics of Fc-mediated cytotoxicity for hF5-LALA compared to hF5-WT. The in vivo efficacy of hF5-LALA was comparable to hF5-WT at -24 and + 24 h post infection, with both Abs providing high levels of protection. However, when hF5-WT and hF5-LALA were administered + 48 h post infection, there was a significant decrease in the therapeutic efficacy of hF5-LALA. Together these results demonstrate that optimal therapeutic Ab treatment of VEEV, and possibly other encephalitic alphaviruses, requires neutralization paired with engagement of immune effectors via the Fc region.
Assuntos
Anticorpos Antivirais , Vírus da Encefalite Equina Venezuelana , Animais , Cavalos , Humanos , Vírus da Encefalite Equina Venezuelana/genética , Anticorpos Neutralizantes/farmacologia , Receptores Fc , Imunoglobulina GRESUMO
Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. The immune response elicited by neurotropic viruses in the CNS is commanded mainly by microglia, which, together with other local cells, can secrete inflammatory cytokines to fight the infection. The most relevant neurotropic viruses are adenovirus (AdV), cytomegalovirus (CMV), enterovirus (EV), Epstein-Barr Virus (EBV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2), lymphocytic choriomeningitis virus (LCMV), and the newly discovered SARS-CoV-2. Several studies have associated a viral infection with systemic lupus erythematosus (SLE) and neuropsychiatric lupus (NPSLE) manifestations. This article will review the knowledge about viral infections, CNS pathologies, and the immune response against them. Also, it allows us to understand the relevance of the different viral proteins in developing neuronal pathologies, SLE and NPSLE.
RESUMO
Saint Louis encephalitis virus (SLEV) infection is an arbovirosis associated with a broad spectrum of neurological complications. We present a case of a 55-year-old man hailing from Manaus, a city situated in the heart of the Amazon Rainforest, who exhibited symptoms of vertigo, tremors, urinary and fecal retention, compromised gait, and encephalopathy 3 weeks following SLEV infection. Neuroaxis MRI revealed diffuse, asymmetric, and poorly defined margins hyperintense lesions with peripheral and ring enhancement in subcortical white matter, as well as severe spinal cord involvement. Serology for SLEV was positive both on serum and cerebrospinal fluid. To the best of our knowledge, the present report is the first to show brain lesions along with myelitis as a post-infectious complication of SLEV infection.