RESUMO
Despite scarcity of data, in recent years, human parvovirus B19 (PVB19) has been emerging as an important pathogen in acute encephalitis syndrome (AES). But, PVB19 virus is mostly looked for only after the exclusion of other common pathogens implicated in AES. Hence, this study was conducted to correlate clinical, radiological, and sequencing data to establish the crucial role of PVB19 in AES. Cerebrospinal fluid and/or serum samples were collected from AES patients as per WHO criteria and tested by ELISA, real-time PCR and bacterial culture sensitivity for various pathogens. PVB19 positive samples were subjected to sequencing. PVB19 attributed to 5% of total AES cases in the present study with fatalities in two of eight cases. Two isolates of PVB19 belonged to Genotype 1 A whereas one belonged to Genotype 3B. On multivariate analysis of predictive symptoms of PVB19 AES cases, blurring of vision (odds ratio [OR] 20.67; p = 0.001) was found to be significant independent predictor of PVB19 AES. Six of eight patients (two encephalitis specific and four nonspecific) had abnormal radiological findings. Hence, being an emerging viral pathogen, PVB19 should be included in the diagnostic algorithm of AES for prompt diagnosis and definitive management to prevent undesired neurological sequelae.
Assuntos
Infecções por Parvoviridae , Parvovirus B19 Humano , Humanos , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/isolamento & purificação , Masculino , Feminino , Infecções por Parvoviridae/virologia , Infecções por Parvoviridae/complicações , Criança , Adolescente , Adulto Jovem , Pré-Escolar , Genótipo , Adulto , Encefalopatia Aguda Febril/virologia , Análise de Sequência de DNA , DNA Viral/líquido cefalorraquidiano , DNA Viral/genética , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática , Encefalite Viral/virologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
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.
Assuntos
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
Dengue virus is an endemic virus in Argentina that, although it was initially considered to be non-neurotropic, it is currently recognized to be neuroinvasive; thus conditioning a prevalence of neurological manifestations of up to 15% among patients. Even being considered severe symptoms, there is underdiagnoses of dengue encephalitis due to its varied clinical presentation. Neurological manifestations of dengue encephalitis can range from fever and headache to altered levels of consciousness and seizures. Although the cerebrospinal fluid may be normal in up to a third of cases, it usually presents increased protein concentration and pleocytosis. Regarding neuroimaging methods, the findings are usually varied and nonspecific, and can even be normal in up to 40-50% of cases. We present three cases of dengue encephalitis diagnosed in a university hospital in Buenos Aires, Argentina, where the clinical presentation varied from temporal-spatial disorientation to refractory convulsive status with different presentations in the cerebrospinal fluid but all with positive PCR for dengue in it and with normal neuroimaging.
El virus dengue es un virus endémico en Argentina que, si bien inicialmente se consideró que no era neurotrópico, actualmente se reconoce que tiene neuroinvasión, condicionando así una prevalencia de manifestaciones neurológicas de hasta el 15% entre los enfermos. Aun siendo considerados síntomas de gravedad, existe subdiagnóstico de encefalitis por dengue debido a su variada forma de presentación clínica. Las manifestaciones neurológicas de la encefalitis por dengue pueden abarcar desde fiebre y cefalea hasta alteraciones del nivel de conciencia y convulsiones. Si bien el líquido cefalorraquídeo (LCR) puede hallarse normal en hasta un tercio de los casos, lo habitual es que presente aumento de concentración de proteínas y pleocitosis. En cuanto a los métodos de neuroimagen, los hallazgos suelen ser variados e inespecíficos, e incluso pueden ser normales hasta en 40-50% de los casos. Se presentan 3 casos de encefalitis por dengue diagnosticados en un hospital universitario de Buenos Aires, Argentina, en donde la presentación clínica varió desde desorientación témporo-espacial hasta estatus convulsivo refractario con diferentes presentaciones en el LCR pero todos con PCR positivo para dengue y con neuroimágenes sin alteraciones.
Assuntos
Dengue , Encefalite Viral , Humanos , Argentina , Masculino , Dengue/diagnóstico , Dengue/líquido cefalorraquidiano , Feminino , Encefalite Viral/líquido cefalorraquidiano , Encefalite Viral/diagnóstico , Adulto , Vírus da Dengue , Pessoa de Meia-IdadeRESUMO
Microglia serve as a front-line defense against neuroinvasive viral infection, however, determination of their actual transcriptional profiles under conditions of health and disease is challenging. Here, we used various experimental approaches to delineate the transcriptional landscape of microglia during viral infection. Intriguingly, multiple activation genes were found to be artificially induced in sorted microglia and we demonstrated that shear stress encountered during cell sorting was one of the key inducers. Post-hoc analysis revealed that publicly available large-scale single-cell RNA sequencing datasets were significantly tainted by aberrant signatures that are associated with cell sorting. By exploiting the ribosomal tagging approach, we developed a strategy to enrich microglia-specific transcripts by comparing immunoprecipitated RNA with total RNA. Such enriched transcripts were instrumental in defining bona fide signatures of microglia under conditions of health and virus infection. These unified microglial signatures may serve as a benchmark to retrospectively assess ex vivo artefacts from available atlases. Leveraging the microglial translatome, we found enrichment of genes implicated in T-cell activation and cytokine production during the course of VSV infection. These data linked microglia with T-cell re-stimulation and further underscored that microglia are involved in shaping antiviral T-cell responses in the brain. Collectively, our study defines the transcriptional landscape of microglia under steady state and during viral encephalitis and highlights cellular interactions between microglia and T cells that contribute to the control of virus dissemination.
Assuntos
Encefalite Viral , Perfilação da Expressão Gênica , Homeostase , Microglia , Microglia/metabolismo , Microglia/virologia , Animais , Encefalite Viral/genética , Encefalite Viral/imunologia , Encefalite Viral/virologia , Homeostase/fisiologia , Homeostase/genética , Camundongos , Perfilação da Expressão Gênica/métodos , Transcriptoma , Camundongos Endogâmicos C57BLRESUMO
Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.
Assuntos
Tronco Encefálico , COVID-19 , Neurônios , SARS-CoV-2 , Humanos , Masculino , SARS-CoV-2/genética , COVID-19/genética , COVID-19/virologia , Tronco Encefálico/patologia , Tronco Encefálico/virologia , Tronco Encefálico/metabolismo , Adolescente , Neurônios/metabolismo , Neurônios/patologia , Encefalite Viral/genética , Encefalite Viral/patologia , Encefalite Viral/virologia , Fibroblastos/metabolismo , Rombencéfalo/metabolismoRESUMO
INTRODUCTION: Posterior leukoencephalopathy syndrome (PRES) is a rare neurological disease possibly associated with the use of calcineurin inhibitors like cyclosporine A (CSA). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the outbreak of coronavirus disease 19 (COVID-19) can cause neurological manifestations. We described a case of CSA-related PRES whose diagnosis was difficult due to a concurrent infection with SARS-CoV-2. OBSERVATION: The 16-year-old patient was known to have corticosteroid-resistant nephrotic syndrome secondary to minimal change disease. CSA was introduced, and on the fifth day of treatment, the patient presented with seizures followed by fever. Biological and magnetic resonance imaging data were in favor of SARS-CoV-2 encephalitis. Relief of immunosuppression by discontinuation of CSA was decided and the patient was put on anticonvulsants. After being declared cured of COVID-19, which was without other clinical signs, the CSA was reintroduced but the patient presented with seizures the next day. This allowed the physicians to rectify the diagnosis and relate the seizures to a CSA-related PRES. CONCLUSION: Infection with SARS-CoV-2 could be a differential diagnosis of a PRES related to calcineurin inhibitors.
Assuntos
COVID-19 , Ciclosporina , Síndrome da Leucoencefalopatia Posterior , Humanos , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Síndrome da Leucoencefalopatia Posterior/diagnóstico , COVID-19/complicações , COVID-19/diagnóstico , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Diagnóstico Diferencial , Adolescente , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Convulsões/etiologia , Convulsões/diagnóstico , Inibidores de Calcineurina/efeitos adversos , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Imageamento por Ressonância MagnéticaRESUMO
Many newly emerging and re-emerging viruses have neuroinvasive potential, underscoring viral encephalitis as a global research priority. Upon entry of the virus into the CNS, severe neurological life-threatening conditions may manifest that are associated with high morbidity and mortality. The currently available therapeutic arsenal against viral encephalitis is rather limited, emphasizing the need to better understand the conditions of local antiviral immunity within the infected CNS. In this review, we discuss new insights into the pathophysiology of viral encephalitis, with a focus on myeloid cells and CD8+ T cells, which critically contribute to protection against viral CNS infection. By illuminating the prerequisites of myeloid and T cell activation, discussing new discoveries regarding their transcriptional signatures, and dissecting the mechanisms of their recruitment to sites of viral replication within the CNS, we aim to further delineate the complexity of antiviral responses within the infected CNS. Moreover, we summarize the current knowledge in the field of virus infection and neurodegeneration and discuss the potential links of some neurotropic viruses with certain pathological hallmarks observed in neurodegeneration.
Assuntos
Sistema Nervoso Central , Humanos , Animais , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/virologia , Sistema Nervoso Central/patologia , Encefalite Viral/imunologia , Encefalite Viral/virologia , Linfócitos T CD8-Positivos/imunologia , Replicação Viral , Antivirais/uso terapêuticoRESUMO
BACKGROUND Cytomegalovirus (CMV) is a common herpesvirus that often causes asymptomatic or mild infections. In immunocompromised patients, CMV can lead to severe complications, including Guillain-Barre syndrome (GBS) and encephalitis. While these conditions have been described in the immunocompetent population, simultaneous presentation of CMV-associated GBS and encephalitis in such individuals has not been previously reported. CASE REPORT We present a case of a 58-year-old woman with poorly controlled diabetes who developed concurrent GBS and encephalitis following a CMV infection. The patient experienced bilateral ascending paraparesis 1 week after self-limited gastrointestinal symptoms. Despite initial treatment with plasma exchange therapy, her condition deteriorated with altered mental status and generalized tonic-clonic seizures, necessitating orotracheal intubation. Laboratory analysis revealed the presence of CMV in her cerebrospinal fluid. After treatment with further sessions of plasma exchange therapy and ganciclovir, her muscular strength in the extremities improved. However, she developed acute lung edema and failed extubation, leading to cardiorespiratory arrest with neurological sequelae. Palliative care was institutionalized, and she died 2 weeks later due to pneumonia. CONCLUSIONS This case highlights an unusual clinical presentation of overlapping CMV-associated GBS and encephalitis in an immunocompetent individual, with diabetes as the only identified risk factor. It underscores the importance of considering CMV as a potential etiological factor in such complex cases and the need for prompt diagnosis to improve patient outcomes. Further research is warranted to explore the underlying mechanisms and implications of this rare overlapping neurological manifestation.
Assuntos
Infecções por Citomegalovirus , Síndrome de Guillain-Barré , Imunocompetência , Humanos , Feminino , Pessoa de Meia-Idade , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapia , Síndrome de Guillain-Barré/etiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Evolução Fatal , Encefalite Viral/diagnósticoRESUMO
Human herpesviruses (HHVs) cause a wide variety of central nervous system (CNS) infections including meningitis and encephalitis. While HHV-8 is not typically associated with neurological diseases, several studies have indicated a relationship, such as secondary central nervous system (CNS) metastases and a few isolated cases of HHV-8 encephalitis in acquired immunodeficiency syndrome (HIV). However, it has not been previously linked to encephalitis in solid organ transplantation (SOT). This case presents the first-ever instance of HHV-8 encephalitis in a SOT recipient. Our case highlights the association of HHV-8-related diseases, such as post-transplant Kaposi's Sarcoma (KS), with encephalitis. The patient was diagnosed with KS before developing neurological symptoms and received a prompt clinical response through intravenous foscarnet and ganciclovir treatment for 14 days. It is important to note that HHV-8 is a rare cause of encephalitis, and diagnosis requires a high index of suspicion in the appropriate clinical context, allowing for the use of antiviral therapy. This case also underscores the importance of considering the possibility of HHV-8-related diseases in SOT recipients, as they are at risk of developing such infections.
Assuntos
Antivirais , Encefalite Viral , Ganciclovir , Infecções por Herpesviridae , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/isolamento & purificação , Sarcoma de Kaposi/virologia , Antivirais/uso terapêutico , Masculino , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/diagnóstico , Encefalite Viral/virologia , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Ganciclovir/uso terapêutico , Foscarnet/uso terapêutico , Pessoa de Meia-Idade , Transplantados , Transplante de Órgãos/efeitos adversosRESUMO
BACKGROUND: Distinguishing between viral encephalitis (VE) and autoimmune limbic encephalitis (ALE) presents a clinical challenge due to the overlap in symptoms. We aimed to develop and validate a diagnostic prediction model to differentiate VE and ALE. METHODS: A prospective observational multicentre cohort study, which continuously enrolled patients diagnosed with either ALE or VE from October 2011 to April 2023. The demographic data, clinical features, and laboratory test results were collected and subjected to logistic regression analyses. The model was displayed as a web-based nomogram and then modified into a scored prediction tool. Model performance was assessed in both derivation and external validation cohorts. RESULTS: A total of 2423 individuals were recruited, and 1001 (496 VE, 505 ALE) patients were included. Based on the derivation cohort (389 VE, 388 ALE), the model was developed with eight variables including age at onset, acuity, fever, headache, nausea/vomiting, psychiatric or memory complaints, status epilepticus, and CSF white blood cell count. The model showed good discrimination and calibration in both derivation (AUC 0.890; 0.868-0.913) and external validation (107 VE, 117 ALE, AUC 0.872; 0.827-0.917) cohorts. The scored prediction tool had a total point that ranged from - 4 to 10 also showing good discrimination and calibration in both derivation (AUC 0.885, 0.863-0.908) and external validation (AUC 0.868, 0.823-0.913) cohorts. CONCLUSIONS: The prediction model provides a reliable and user-friendly tool for differentiating between the VE and ALE, which would benefit early diagnosis and appropriate treatment and alleviate economic burdens on both patients and society.
Assuntos
Encefalite Viral , Encefalite Límbica , Humanos , Encefalite Límbica/diagnóstico , Encefalite Límbica/imunologia , Encefalite Límbica/líquido cefalorraquidiano , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Diagnóstico Diferencial , Encefalite Viral/diagnóstico , Doenças Autoimunes/diagnóstico , Estudos de Coortes , Idoso , Adulto Jovem , NomogramasRESUMO
BACKGROUND: Viral encephalitis (VE) is a common infectious disease of the central nervous system in children. Children with severe disease may have progressive neurological damage and even lead to death. AIMS: To assess the serum miR-142-3p levels in children with VE and the correlation between miR-142-3p and the severity and prognosis of VE. Besides, its relationship with nerve injury and inflammatory response was assessed. METHODS: Children with VE were regarded as a case group and healthy children served as control. The content of serum miR-142-3p was determined using real-time quantitative PCR. The risk factors associated with severity and prognosis of cases were evaluated using logistic analysis. The discrepancy in miR-142-3p levels, nerve injury-related indicators, and inflammatory cytokines were contrasted among groups. The ROC curve was conducted to assess the diagnostic performance of serum miR-142-3p in predicting prognosis of children with VE. RESULTS: The altered expression of miR-142-3p in serum of children with VE was enhanced in contrast to healthy control. Serum nerve injury indicators MBP, ß-EP, and NSE levels and serum inflammatory cytokines IL-6, IL-18, and IFN-γ were high in children with VE in contrast to healthy control, and had positive relevance with serum miR-142-3p. Besides, serum miR-142-3p was a risk factor associated with the severity and prognosis of children with VE. Serum miR-142-3p had diagnostic performance in predicting the prognosis of children with VE. CONCLUSION: Serum miR-142-3p content is high in children with VE and maybe a diagnosis marker for predicting prognosis. The specific miR-142-3p expression may be directly related to the severity of nerve injury and inflammatory response for VE.
Assuntos
Encefalite Viral , MicroRNAs , Humanos , Masculino , Feminino , MicroRNAs/sangue , MicroRNAs/genética , Criança , Pré-Escolar , Encefalite Viral/sangue , Encefalite Viral/virologia , Encefalite Viral/genética , Estudos de Casos e Controles , Prognóstico , Biomarcadores/sangue , Interleucina-6/sangue , Interleucina-6/genética , Interferon gama/sangue , Interferon gama/genética , Interleucina-18/sangue , Interleucina-18/genética , Citocinas/sangue , Citocinas/genética , Índice de Gravidade de Doença , LactenteRESUMO
BACKGROUND: A case-control study was conducted to analyze the role of cerebrospinal fluid immunoglobulin in the differential diagnosis of autoimmune encephalitis and viral encephalitis in children. METHODS: One hundred and twenty patients with autoimmune encephalitis (AE) treated in our hospital from February 2021 to February 2022 were included as the observation group (AE group). 100 patients with viral encephalitis (VE group) were selected as the control group. The clinical data of all patients were collected and analyzed retrospectively. Immunoglobulin G (IgG) and immunoglobulin A (IgA)in cerebrospinal fluid of the two patients were measured by immune turbidimetry. Immunoglobulin M (IgM), and the diagnostic value of immunoglobulin in cerebrospinal fluid (CSF) in patients with AE was analyzed by receiver working curve (ROC). RESULTS: The level of IgG in the cerebrospinal fluid of the AE group was higher than that of the VE group, and the level of IgM was lower than that of the VE group, and the difference was statistically significant (P < 0.05). There was no significant difference in IgA levels between the two groups (P > 0.05). In terms of Magnetic Resonance (MR) features, the paraventricular, hippocampal, occipital and parietal lobes were more involved in AE patients, frontal and temporal lobes were more involved in VE patients, and paraventricular and occipital lobes were involved in MS. The proportion of bilateral extensive lesions in both groups was significantly higher than 50%. The proportions of patients in the AE group involving the lateral ventricle, insula, and parietal lobes were significantly higher than those in the VE group, and the proportions involving the basal ganglia, temporal lobes, and frontal lobes were significantly lower than those in the VE group, and the differences were statistically significant (All P < 0.05). The Area Under Curve (AUC) of IgG, IgA and IgM alone in the diagnosis of AE were 0.795(0.587-0.762), 0.602(0.502-0.631) and 0.627(0.534-0.708), respectively with the sensitivity values of 81.24% and 65.608, respectively and the specificity values of 65.08%, 57.54% and 75.01% respectively. The AUC of IgA + IgM in the diagnosis of AE was 0.733(0.617-0.849), and the sensitivity and specificity are 62.58% and 75.07% respectively. The AUC of IgA + IgG in the diagnosis of AE was 0.823(0.730-0.917), and the sensitivity and specificity were 81.24% and 67.54% respectively. The AUC of IgG + IgM in the diagnosis of AE was 0.886(0.814 ~ 0.958), and the sensitivity and specificity were 84.48% and 77.59% respectively. The AUC of IgA + IgM + IgG in the diagnosis of AE was 0.924 (0.868-0.981) with the sensitivity of 93.82%, and the specificity of 77.56%. CONCLUSION: The level of immunoglobulin in cerebrospinal fluid can be used as an effective reference index for the diagnosis of AE. The combined detection of IgA, IgM and IgG can improve the accuracy, sensitivity and specificity of AE.
Assuntos
Encefalite Viral , Encefalite , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Humanos , Diagnóstico Diferencial , Masculino , Feminino , Encefalite Viral/diagnóstico , Encefalite Viral/líquido cefalorraquidiano , Criança , Estudos de Casos e Controles , Pré-Escolar , Estudos Retrospectivos , Imunoglobulina A/líquido cefalorraquidiano , Encefalite/diagnóstico , Encefalite/líquido cefalorraquidiano , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M/líquido cefalorraquidiano , Imunoglobulina M/sangue , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/líquido cefalorraquidiano , Imageamento por Ressonância Magnética , Adolescente , Lactente , Curva ROC , Biomarcadores/líquido cefalorraquidianoRESUMO
Objective: To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023. Methods: The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases. Results: A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years (χ2=5.33,P=0.021; χ2=48.14,P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions: From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.
Assuntos
Encefalite Viral , Humanos , Criança , Adolescente , Encefalite Viral/epidemiologia , Encefalite Viral/virologia , Masculino , Feminino , China/epidemiologia , Pré-Escolar , Lactente , Distribuição por IdadeRESUMO
Human herpesvirus 6 (HHV-6) is a widely spread DNA virus that is ubiquitous and persistent with primary infection occurring in early childhood, with reactivation of the infection a common phenomenon in severely immunocompromised hosts, including hematopoietic stem cell transplant (HSCT) patients, influencing morbidity and mortality. A wide spectrum of clinical presentations is reported in the literature with HHV-6 reactivation including post-transplant limbic encephalitis (PALE). We report the unusual case of a 6-year-old female 107 days postallogenic HSCT due to transfusion dependent beta thalassemia major who developed acute cerebellitis with secondary supratentorial hydrocephalus that required invasive surgical intervention. In addition to accompanying imaging findings, the patient tested positive for HHV-6 by PCR from both serum and CSF samples and demonstrated dramatic improvement with the institution of steroid therapy in addition to ganciclovir treatment. The availability of rapid diagnostic measures in addition to a multidisciplinary approach is crucial to manage HHV-6 encephalitis and associated complications in HSCT patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Hidrocefalia , Infecções por Roseolovirus , Humanos , Herpesvirus Humano 6/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Feminino , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Criança , Infecções por Roseolovirus/virologia , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/complicações , Infecções por Roseolovirus/tratamento farmacológico , Antivirais/uso terapêutico , Encefalite Viral/etiologia , Encefalite Viral/virologia , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Talassemia beta/complicações , Talassemia beta/terapia , Hospedeiro ImunocomprometidoRESUMO
COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly influenza viruses, is a global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected with influenza A virus (IAV) followed by SARS-CoV-2 and the host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 alone. The sequentially infected mice showed reduced SARS-CoV-2 RNA synthesis, yet exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to the singly infected or control mice. Sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz Tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis, albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by IAV inhibits SARS-CoV-2. Interestingly, infection with an attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest coinfection ('twinfection') is deleterious and mitigation steps should be instituted as part of the comprehensive public health and management strategy of COVID-19.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Modelos Animais de Doenças , Vírus da Influenza A , Camundongos Transgênicos , Infecções por Orthomyxoviridae , SARS-CoV-2 , Animais , COVID-19/imunologia , COVID-19/virologia , Camundongos , SARS-CoV-2/imunologia , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Humanos , Coinfecção/virologia , Pulmão/virologia , Pulmão/patologia , Encefalite Viral/virologia , Encefalite Viral/imunologia , Vacinas contra Influenza/imunologia , Feminino , Imunidade InataRESUMO
Acute encephalitis syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ~5-20% of AES cases, but ~75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from an 8-year-old male patient with AES using metagenomic next-generation sequencing. Gemykibiviruses are single stranded, circular DNA viruses in the family Genomoviridae. The complete genome of 2,211 nucleotides was sequenced, which shared 98.69% nucleotide identity to its closest relative, Human associated gemykibivirus 2 isolate SAfia-449D. Two real-time PCR assays were designed, and screening of 337 cerebrospinal fluid (CSF) and 164 serum samples from AES patients in Nepal collected in 2020 and 2022 yielded 11 CSF and 1 serum sample that were positive in both PCR assays. Complete genomes of seven of the positives were sequenced. These results identify a potential candidate etiologic agent of encephalitis in Nepal. IMPORTANCE: Viral encephalitis is a devastating disease, but unfortunately, worldwide, the causative virus in many cases is unknown. Therefore, it is important to identify viruses that could be responsible for cases of human encephalitis. Here, using metagenomic sequencing of CSF, we identified a gemykibivirus in a male child from Nepal with acute encephalitis syndrome (AES). We subsequently detected gemykibivirus DNA in CSF or serum of 12 more encephalitis patients by real-time PCR. The virus genomes we identified are highly similar to gemykibiviruses previously detected in CSF of three encephalitis patients from Sri Lanka. These results raise the possibility that gemykibivirus could be an underrecognized human pathogen.
Assuntos
Genoma Viral , Filogenia , Humanos , Nepal/epidemiologia , Masculino , Criança , Genoma Viral/genética , Metagenômica , Sequenciamento de Nucleotídeos em Larga Escala , Pré-Escolar , Reação em Cadeia da Polimerase em Tempo Real , Encefalite Viral/virologia , Adolescente , Vírus de DNA/genética , Vírus de DNA/isolamento & purificação , Vírus de DNA/classificação , FemininoRESUMO
Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections.
Assuntos
Lipopeptídeos , Neurônios , Febre do Vale de Rift , Vírus da Febre do Vale do Rift , Animais , Vírus da Febre do Vale do Rift/efeitos dos fármacos , Camundongos , Lipopeptídeos/farmacologia , Febre do Vale de Rift/virologia , Febre do Vale de Rift/prevenção & controle , Neurônios/metabolismo , Neurônios/virologia , Camundongos Endogâmicos C57BL , Humanos , Imunidade Inata/efeitos dos fármacos , Encefalite Viral/virologia , Encefalite Viral/imunologia , Encefalite Viral/prevenção & controle , Encefalite Viral/tratamento farmacológico , Antivirais/farmacologiaAssuntos
Fator 15 de Diferenciação de Crescimento , Influenza Humana , Feminino , Humanos , Encefalopatias/etiologia , Encefalopatias/virologia , Encefalopatias/diagnóstico , Encefalite Viral/diagnóstico , Fator 15 de Diferenciação de Crescimento/sangue , Influenza Humana/complicações , Imageamento por Ressonância Magnética , Pré-EscolarRESUMO
BACKGROUND: A score to differentiate autoimmune (AE) and viral encephalitis (VE) early upon admission has recently been developed but needed external validation. The objective of this study was to evaluate the performance of the score in a larger and more diagnostically diverse patient cohort. METHODS: We conducted a retrospective nationwide and population-based cohort study including all adults with encephalitis of definite viral (2015-2022) or autoimmune aetiology (2009-2022) in Denmark. Variables included in the score-model were extracted from patient records and individual risk scores were assessed. The performance of the score was assessed by receiver-operating characteristics (ROC) curve analyses and calculation of the area under the curve (AUC). RESULTS: A total of 496 patients with encephalitis [AE n = 90, VE n = 287 and presumed infectious encephalitis (PIE) n = 119] were included in the study. The score was highly accurate in predicting cases of AE reaching an AUC of 0.94 (95% CI 0.92-0.97). Having a score ≥ 3 predicted AE with a PPV of 87% and an NPV of 91%. The risk score was found to perform well across aetiological subgroups and applied to the PIE cohort resulted in an AUC of 0.88 (95% CI 0.84-0.93). CONCLUSION: The excellent performance of the score as reported in the development study was confirmed in this significantly larger and more diverse cohort of patients with encephalitis in Denmark. These results should prompt further prospective testing with wider inclusion criteria.