RESUMO
BACKGROUND: Infectious meningoencephalitis (ME) is a major global health concern. Viruses are the most frequently implicated etiologies, whereas bacterial causes, although life-threatening, constitute a lesser proportion of ME cases, together with other pathogens. The strict implementation of COVID-19 mitigation measures led to the decreased viral and non-viral infectious diseases. Therefore, this study aimed to investigate the effect of these mea-sures on ME-causing pathogens by age groups. METHODS: This retrospective study aimed to determine and compare the rates of pathogen-positive ME cases during the pre-pandemic (P-1) and pandemic (P-2) periods. Molecular diagnostic methods using the cerebrospinal fluid of patients from all age groups were included. The positivity rate difference of the ME-causing pathogens between the two study periods was compared and the distribution pattern of the pathogens among the age groups was determined. RESULTS: The overall positivity rate for at least one ME-causing pathogen during P-1 was 22.0% (503/2,284), which significantly declined to 7.3% (83/1,141) during P-2 (p < 0.001). Particularly, a statistically significant decline in the pathogen positivity was observed in the groups 4 - 6 (≥ 3 years) (p < 0.001, p < 0.001, and p = 0.041, respectively). Specifically, the enterovirus cases decreased significantly, whereas the varicella zoster virus and herpes simplex virus-2 cases increased. Among bacterial causes, the S. agalactiae, S. pneumoniae, and E. coli K1 ME cases significantly increased. Men and women had no significant differences in the positivity rate during either study period. CONCLUSIONS: COVID-19 mitigation measures significantly impacted the positivity rates and the distribution of ME-causing agents, especially in the age groups ≥ 3 years, although not uniformly.
Assuntos
COVID-19 , Meningoencefalite , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , Estudos Retrospectivos , Meningoencefalite/epidemiologia , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/virologia , Meningoencefalite/diagnóstico , Adulto , Criança , Pré-Escolar , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Lactente , Masculino , Feminino , Idoso , Pandemias , SARS-CoV-2/isolamento & purificação , Idoso de 80 Anos ou mais , Recém-NascidoRESUMO
Chikungunya disease typically presents with the fever-arthralgia-rash symptom triad. However, an increase in the number of atypical clinical manifestations, particularly neurological disorders, has occurred. The current evidence regarding the pooled prevalence of Chikungunya virus (CHIKV)-associated neurological cases (CANCs) suspected of having an arboviral aetiology is not well-understood. Therefore, this meta-analysis included 19 studies (n = 7319 patients) and aimed to determine the pooled rate of exposure to CANC. The pooled positivity rate of CANC was 12 % (95 % CI: 6-19), and Brazil was overrepresented (11/19). These estimations varied between 3 and 14 % based on the diagnostic method (real-time PCR vs. ELISA-IgM) and biological samples (cerebrospinal fluid or blood specimens) used for detection of CHIKV. Regarding the frequency of CHIKV in neurological clinical subgroups, the rates were higher among patients with myelitis (27 %), acute disseminated encephalomyelitis (27 %), Guillain-Barré syndrome (15 %), encephalitis (12 %), and meningoencephalitis (7 %). Our analysis highlights the significant burden of CANC. However, the data must be interpreted with caution due to the heterogeneity of the results, which may be related to the location of the studies covering endemic periods and/or outbreaks of CHIKV. Current surveillance resources should also focus on better characterizing the epidemiology of CHIKV infection in neurological disorders. Additionally, future studies should investigate the interactions between CHIKV and neurological diseases with the aim of gaining deeper insight into the mechanisms underlying the cause-and-effect relationship between these two phenomena.
Assuntos
Febre de Chikungunya , Vírus Chikungunya , Síndrome de Guillain-Barré , Doenças do Sistema Nervoso , Humanos , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/isolamento & purificação , Encefalomielite Aguda Disseminada/epidemiologia , Encefalomielite Aguda Disseminada/virologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/virologia , Meningoencefalite/epidemiologia , Meningoencefalite/virologia , Mielite/epidemiologia , Mielite/virologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/virologia , PrevalênciaRESUMO
OBJECTIVE: Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs). METHODS: Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis. RESULTS: Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5-10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3-6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown. CONCLUSION: EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.
Assuntos
Anticorpos Monoclonais , Antígenos CD20 , Infecções por Enterovirus , Humanos , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/diagnóstico , Masculino , Feminino , Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Pessoa de Meia-Idade , Adulto , Meningoencefalite/imunologia , Meningoencefalite/virologia , Meningoencefalite/etiologia , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , Idoso , Rituximab/uso terapêutico , Linfócitos B/imunologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/complicações , Inflamação/imunologiaRESUMO
BACKGROUND: Non-polio enteroviruses (EV) and human parechoviruses (HPeV) are known etiological agents of meningoencephalitis in neonates. However, reports of neuroradiological findings and neurodevelopmental outcomes in this population are scarce. OBJECTIVES: to describe clinical characteristics, neuroradiological findings and, in a subset of patients, neurodevelopmental outcomes in a cohort of infants with EV or HPeV meningoencephalitis within 60 days of life. STUDY DESIGN: clinical/laboratory data, neuroradiological findings (cranial ultrasound, cUS, brain magnetic resonance imaging, MRI), and neurodevelopmental outcomes assessed by Ages and Stages Questionnaires - third edition were prospectively collected. RESULTS: overall, 32 infants with EV (21, 67.8 %) or HPeV (11, 28.2 %) meningoencephalitis were enrolled. Infants with HPeV (73 %: type 3 HPeV) presented more frequently with seizures (18.2 % vs. 0, p value=0.03), lymphopenia (1120 vs. 2170 cells/mm3, p = 0.02), focal anomalies at electroencephalography (EEG) (63.6 vs. 23.8 %, p = 0.03), and pathological findings at MRI (72.7 % vs. 15.8 %, p value=0.004) compared to those affected by EV. cUS was not significantly altered in any of the enrolled infants. All infants with EV meningoencephalitis evaluated at 12-24 months and at 30-48 months were normal. Two out of the 7 infants with HPeV meningoencephalitis showed some concerns in gross motor (1/7, 14.3 %) or in problem solving (1/7, 14.3 %) function at 30-48 months of age. CONCLUSIONS: In our cohort, neonates infected by HPeV had more severe clinical manifestations, more alterations at brain MRI, and some signs of long-term neurodevelopmental delay. Our data highlight the heterogeneity of manifestations in infants with EV or HPeV meningoencephalitis, and the need for long-term follow-up of those infected by HPeV in the neonatal period.
Assuntos
Infecções por Enterovirus , Enterovirus , Unidades de Terapia Intensiva Neonatal , Imageamento por Ressonância Magnética , Meningoencefalite , Parechovirus , Infecções por Picornaviridae , Humanos , Meningoencefalite/virologia , Meningoencefalite/diagnóstico por imagem , Estudos Prospectivos , Infecções por Picornaviridae/patologia , Infecções por Picornaviridae/virologia , Infecções por Enterovirus/virologia , Infecções por Enterovirus/patologia , Masculino , Recém-Nascido , Enterovirus/isolamento & purificação , Feminino , Lactente , Eletroencefalografia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/virologiaAssuntos
Transtorno Bipolar , Encefalite por Varicela Zoster , Humanos , Transtorno Bipolar/diagnóstico , Encefalite por Varicela Zoster/diagnóstico , Encefalite por Varicela Zoster/complicações , COVID-19 , Herpesvirus Humano 3/patogenicidade , Masculino , Meningoencefalite/diagnóstico , Meningoencefalite/virologiaRESUMO
Viral nervous necrosis (viral encephalopathy and retinopathy) is caused by piscine nodavirus (Nodaviridae, Betanodavirus). Since 1986, this highly infectious virus has caused mass mortalities of up to 100% in farmed saltwater and freshwater fish around the world (with the exception of South America and Antarctica), affecting >60 species across 10 orders. The Atlantic blue marlin (Makaira nigricans Lacépède, 1802) is a top-level predator found throughout the tropical waters of the Atlantic and Indo-Pacific oceans. Despite their popularity as a sportfish, relatively little is known about the Atlantic blue marlin and other billfish. We describe here chronic betanodavirus infection in a juvenile Atlantic blue marlin, which is, to our knowledge, the first report of disease in M. nigricans.
Assuntos
Doenças dos Peixes , Meningoencefalite , Nodaviridae , Animais , Doenças dos Peixes/virologia , Doenças dos Peixes/patologia , Meningoencefalite/veterinária , Meningoencefalite/virologia , Meningoencefalite/patologia , Infecções por Mononegavirales/veterinária , Infecções por Mononegavirales/virologia , Infecções por Mononegavirales/patologia , Nodaviridae/isolamento & purificação , Perciformes/virologiaRESUMO
BACKGROUND: The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age. MATERIALS AND METHODS: The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR. RESULTS: Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides , and H. Influenzae were tested but not detected in any of the cases. CONCLUSION: We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.
Assuntos
Meningoencefalite , Humanos , Meningoencefalite/virologia , Meningoencefalite/epidemiologia , Pré-Escolar , Lactente , Feminino , Masculino , Índia/epidemiologia , Vírus/isolamento & purificação , Vírus/classificação , Vírus/patogenicidade , Vírus/genética , Recém-Nascido , VirosesRESUMO
We have read with interest the article by Watroba and Bryda on a new-born male with SARS-CoV-2 associated meningo-encephalitis, post-inflammatory hydrocephalus and seizures [1]. Neuro-COVID in this patient was treated with a polypragmatic approach, including phenobarbital, acetazolamide, fluconazole, acyclovir, cefotaxime, and vancomycin [1]. The study is appealing but has limitations that raise concerns and should be discussed.
Assuntos
COVID-19 , Meningoencefalite , SARS-CoV-2 , Humanos , Masculino , Acetazolamida/uso terapêutico , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/tratamento farmacológico , Meningoencefalite/virologia , SARS-CoV-2/isolamento & purificação , ConvulsõesAssuntos
Meningoencefalite , Parechovirus , Infecções por Picornaviridae , Adulto , Paralisia Cerebral , Cesárea , Feminino , Humanos , Recém-Nascido , Meningoencefalite/congênito , Meningoencefalite/terapia , Meningoencefalite/virologia , Parechovirus/genética , Parechovirus/isolamento & purificação , Infecções por Picornaviridae/congênito , Infecções por Picornaviridae/terapia , Infecções por Picornaviridae/virologia , Gravidez , Convulsões , TaquicardiaAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Infecções por Enterovirus/diagnóstico , Enterovirus/isolamento & purificação , Meningoencefalite/virologia , Adulto , Enterovirus/genética , Infecções por Enterovirus/líquido cefalorraquidiano , Infecções por Enterovirus/etiologia , Feminino , Humanos , Linfoma Folicular/tratamento farmacológico , Meningoencefalite/etiologiaRESUMO
Neurological diseases in cattle can be caused by several infectious agents. Astroviruses are increasingly recognized as the causative agent of encephalitis in various animals, including humans. In this study, a neuroinvasive astrovirus (BoAstV 20B05) was discovered in the brain tissues of an 81-month-old Korean native cattle with neurological symptoms. Lymphocyte infiltration and multifocal perivascular cuffing were observed in the cerebrum and brain stem, and viral antigens were also detected in the meninges. In particular, the concentration of the astroviral genome was high in the brain tissues. Korean BoAstV 20B05 was classified into the CH13/NeuroS1 clade and was closely related to the Neuro-Uy and KagoshimaSR28-462 strains. Our evolutionary analysis showed that Korean BoAstV 20B05 belongs to the sub-lineage NeuroS1 and evolved independently of BoAstV KagoshimaSR28-462. These results suggest that neuroinvasive astroviruses were first introduced in Korea. However, analysis is limited by the lack of reference astrovirus sequences reported in various countries within Asia, and further analysis should be performed using more strains. In this study, we identified a neuroinvasive astrovirus infection with neurological symptoms for the first time in South Korea and confirmed that BoAstV 20B05 may have been introduced in South Korea a long time ago.
Assuntos
Infecções por Astroviridae/diagnóstico , Encefalite Viral/diagnóstico , Encefalite Viral/veterinária , Meningoencefalite/veterinária , Animais , Infecções por Astroviridae/complicações , Infecções por Astroviridae/mortalidade , Encéfalo/patologia , Encéfalo/virologia , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/virologia , Encefalite Viral/classificação , Encefalite Viral/mortalidade , Meningoencefalite/mortalidade , Meningoencefalite/virologia , Filogenia , República da CoreiaRESUMO
INTRODUCTION: Meningoencephalitis patients are often severely impaired and benefit from early etiological diagnosis, though many cases remain without identified cause. Metagenomics as pathogen agnostic approach can result in additional etiological findings; however, the exact diagnostic yield when used as a secondary test remains unknown. AREAS COVERED: This review aims to highlight recent advances with regard to wet and dry lab methodologies of metagenomic testing and technical milestones that have been achieved. A selection of procedures currently applied in accredited diagnostic laboratories is described in more detail to illustrate best practices. Furthermore, a meta-analysis was performed to assess the additional diagnostic yield utilizing metagenomic sequencing in meningoencephalitis patients. Finally, the remaining challenges for successful widespread implementation of metagenomic sequencing for the diagnosis of meningoencephalitis are addressed in a future perspective. EXPERT OPINION: The last decade has shown major advances in technical possibilities for using mNGS in diagnostic settings including cloud-based analysis. An additional advance may be the current established infrastructure of platforms for bioinformatic analysis of SARS-CoV-2, which may assist to pave the way for global use of clinical metagenomics.
Assuntos
Genoma Viral/genética , Meningoencefalite/diagnóstico , Meningoencefalite/virologia , Metagenoma/genética , Testes Diagnósticos de Rotina , Humanos , Metagenômica/métodosRESUMO
We present the case of a young woman being treated with rituximab for rheumatoid arthritis who developed a severe enteroviral meningoencephalitis and acute flaccid myelitis (AFM). Cerebrospinal fluid (CSF) and stool reverse transcription-polymerase chain reaction (RT-PCR) testing confirmed the diagnosis and additional sequencing studies performed at the CDC further characterized the enterovirus as enterovirus A71 (EV-A71). After treatment with intravenous immunoglobulin (IVIg) and fluoxetine (based on previous reports of possible efficacy) the patient experienced a remarkable improvement over time. This case highlights the importance of considering enteroviral infection in patients treated with rituximab, depicts a possible clinical course of enteroviral meningoencephalitis and AFM, and illustrates the importance of testing multiple sites for enterovirus infection (CSF, stool, nasopharyngeal swab, blood). Here we present the case with a brief review of the literature pertaining to EV-A71.
Assuntos
Viroses do Sistema Nervoso Central/diagnóstico por imagem , Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/diagnóstico por imagem , Fatores Imunológicos/uso terapêutico , Meningoencefalite/diagnóstico por imagem , Mielite/diagnóstico por imagem , Doenças Neuromusculares/diagnóstico por imagem , Rituximab/uso terapêutico , Adulto , Viroses do Sistema Nervoso Central/tratamento farmacológico , Viroses do Sistema Nervoso Central/virologia , Infecções por Enterovirus/tratamento farmacológico , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Meningoencefalite/tratamento farmacológico , Meningoencefalite/virologia , Mielite/tratamento farmacológico , Mielite/virologia , Doenças Neuromusculares/tratamento farmacológico , Doenças Neuromusculares/virologia , Rituximab/efeitos adversosRESUMO
Rift Valley fever (RVF) is a zoonotic, viral, mosquito-borne disease that causes considerable morbidity and mortality in humans and livestock in Africa and the Arabian Peninsula. In June 2018, 4 alpaca inoculated subcutaneously with live attenuated RVF virus (RVFV) Smithburn strain exhibited pyrexia, aberrant vocalization, anorexia, neurologic signs, and respiratory distress. One animal died the evening of inoculation, and 2 at ~20 d post-inoculation. Concern regarding potential vaccine strain reversion to wild-type RVFV or vaccine-induced disease prompted autopsy of the latter two. Macroscopically, both alpacas had severe pulmonary edema and congestion, myocardial hemorrhages, and cyanotic mucous membranes. Histologically, they had cerebral nonsuppurative encephalomyelitis with perivascular cuffing, multifocal neuronal necrosis, gliosis, and meningitis. Lesions were more severe in the 4-mo-old cria. RVFV antigen and RNA were present in neuronal cytoplasm, by immunohistochemistry and in situ hybridization (ISH) respectively, and cerebrum was also RVFV positive by RT-rtPCR. The virus clustered in lineage K (100% sequence identity), with close association to Smithburn sequences published previously (identity: 99.1-100%). There was neither evidence of an aberrant immune-mediated reaction nor reassortment with wild-type virus. The evidence points to a pure infection with Smithburn vaccine strain as the cause of the animals' disease.
Assuntos
Camelídeos Americanos , Meningoencefalite/veterinária , Vírus da Febre do Vale do Rift/imunologia , Vacinação/veterinária , Vacinas Atenuadas/administração & dosagem , Vacinas Virais/efeitos adversos , Animais , Feminino , Masculino , Meningoencefalite/diagnóstico , Meningoencefalite/virologia , África do Sul , Vacinação/efeitos adversosRESUMO
Zika virus (ZIKV) is a mosquito-borne neurotropic flavivirus. ZIKV infection may lead to microcephaly in developing fetus and Guillain-Barré Syndrome (GBS) like symptoms in adults. ZIKV was first reported in humans in 1952 from Uganda and the United Republic of Tanzania. Later, ZIKV outbreak was reported in 2007 from the Yap Island. ZIKV re-emerged as major outbreak in the year 2013 from French Polynesia followed by second outbreak in the year 2015 from Brazil. ZIKV crosses the blood-tissue barriers to enter immune-privileged organs. Clinical manifestations in ZIKV disease includes rash, fever, conjunctivitis, muscle and joint pain, headache, transverse myelitis, meningoencephalitis, Acute Disseminated Encephalomyelitis (ADEM). The understanding of the molecular mechanism of ZIKV pathogenesis is very important to develop potential diagnostic and therapeutic interventions for ZIKV infected patients.
Assuntos
Encefalomielite Aguda Disseminada/virologia , Meningoencefalite/virologia , Infecção por Zika virus/patologia , Infecção por Zika virus/transmissão , Zika virus/imunologia , Animais , Culicidae/virologia , Encefalomielite Aguda Disseminada/patologia , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Meningoencefalite/patologia , Placenta/virologia , Gravidez , Doenças Transmitidas por Vetores/virologia , Zika virus/crescimento & desenvolvimento , Zika virus/patogenicidadeRESUMO
The etiology of viral meningoencephalitis is frequently unidentified. Chikungunya virus (CHIKV) and Zika virus (ZIKV) are known to affect the central nervous system and should therefore be considered in the diagnosis of meningoencephalitis, as its outcome may be influenced by the etiologic agent, age, and immunological condition of the patient. In this study, we aimed to determine whether CHIKV and ZIKV were the etiological agents of viral encephalitis in patients with meningoencephalitis admitted to the main hospital of infectious diseases in the city of Salvador, Brazil. Of the 1,049 patients with neurological symptoms who were admitted to the hospital during the study period, 149 were enrolled and 20 (13.34%) tested positive for ZIKV (12%) or CHIKV (1.34%). No specific clinical manifestations were observed to be associated with ZIKV or CHIKV infections. Determination of the etiological agent of meningitis and encephalitis is important for patient management and appropriate treatment.
Assuntos
Febre de Chikungunya/complicações , Vírus Chikungunya/isolamento & purificação , Meningoencefalite/diagnóstico , Meningoencefalite/virologia , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Brasil/epidemiologia , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Dengue , Humanos , Meningoencefalite/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologiaRESUMO
Tick-borne encephalitis (TBE) is a relatively severe and clinically variable central nervous system (CNS) disease with a significant contribution of a secondary immunopathology. Monocytes/macrophages play an important role in the CNS inflammation, but their pathogenetic role and migration mechanisms in flavivirus encephalitis in humans are not well known. We have retrospectively analyzed blood and cerebrospinal fluid (CSF) monocyte counts in 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114), or meningoencephalomyelitis (n = 16), searching for associations with other laboratory parameters, clinical presentation, and severity. We have measured concentrations of selected monocytes-attracting chemokines (CCL7, CXCL12, CCL20) in serum and CSF of the prospectively recruited patients with TBE (n = 15), with non-TBE aseptic meningitis (n = 6) and in non-infected controls (n = 8). The data were analyzed with non-parametric tests, p < 0.05 considered significant. Monocyte CSF count correlated with other CSF inflammatory parameters, but not with the peripheral monocytosis, consistent with an active recruitment into CNS. The monocyte count did not correlate with a clinical presentation. The median CSF concentration of CCL7 and CXCL12 was increased in TBE, and that of CCL7 was higher in TBE than in non-TBE meningitis. The comparison of serum and CSF concentrations pointed to the intrathecal synthesis of CCL7 and CXCL12, but with no evident concentration gradients toward CSF. In conclusion, the monocytes are recruited into the intrathecal compartment in concert with other leukocyte populations in TBE. CCL7 and CXCL12 have been found upregulated intrathecally but are not likely to be the main monocyte chemoattractants.
Assuntos
Quimiocina CCL7/genética , Quimiocina CXCL12/genética , Encefalite Transmitida por Carrapatos/genética , Macrófagos/virologia , Meningoencefalite/genética , Monócitos/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/virologia , Estudos de Casos e Controles , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/virologia , Quimiocina CCL20/sangue , Quimiocina CCL20/líquido cefalorraquidiano , Quimiocina CCL20/genética , Quimiocina CCL7/sangue , Quimiocina CCL7/líquido cefalorraquidiano , Quimiocina CXCL12/sangue , Quimiocina CXCL12/líquido cefalorraquidiano , Quimiotaxia/imunologia , Encefalite Transmitida por Carrapatos/sangue , Encefalite Transmitida por Carrapatos/líquido cefalorraquidiano , Encefalite Transmitida por Carrapatos/virologia , Feminino , Regulação da Expressão Gênica , Humanos , Macrófagos/imunologia , Masculino , Meningoencefalite/sangue , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/virologia , Pessoa de Meia-Idade , Monócitos/imunologia , Estudos RetrospectivosRESUMO
A 78-year-old woman was diagnosed with herpes zoster in the first branch of the trigeminal nerve and was treated with amenamevir. Subsequently, she was hospitalized for postherpetic neuralgia. Fever and unconsciousness were observed, and a diagnosis of varicella-zoster virus meningoencephalitis and vasculitis was made. In addition to the antithrombotic therapy, she was treated with intravenous acyclovir and steroid pulse therapy; however, her unconsciousness persisted. Amenamevir was not transferrable to the spinal fluid and resulted in an incomplete treatment of herpes zoster in the cerebral nerve region, suggesting that this case may be related to the severe course of the disease.
Assuntos
Aciclovir/administração & dosagem , Antivirais/uso terapêutico , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/etiologia , Oxidiazóis/uso terapêutico , Nervo Trigêmeo , Vasculite/tratamento farmacológico , Vasculite/etiologia , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/líquido cefalorraquidiano , Feminino , Humanos , Infusões Intravenosas , Imageamento por Ressonância Magnética , Meningoencefalite/diagnóstico , Meningoencefalite/virologia , Metilprednisolona/administração & dosagem , Oxidiazóis/efeitos adversos , Oxidiazóis/líquido cefalorraquidiano , Pulsoterapia , Índice de Gravidade de Doença , Vasculite/diagnóstico , Vasculite/virologiaRESUMO
Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82-6190.50; serum median 24.48, IQR 11.93-49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.
Assuntos
Citocinas/líquido cefalorraquidiano , Meningite/imunologia , Meningoencefalite/imunologia , Febre do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/imunologia , Idoso , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Interleucina-17/sangue , Interleucina-17/líquido cefalorraquidiano , Interleucina-17/imunologia , Interleucina-4/sangue , Interleucina-4/líquido cefalorraquidiano , Interleucina-4/imunologia , Masculino , Meningite/sangue , Meningite/líquido cefalorraquidiano , Meningite/virologia , Meningoencefalite/sangue , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/virologia , Pessoa de Meia-Idade , Células Th17/imunologia , Febre do Nilo Ocidental/genética , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/genética , Vírus do Nilo Ocidental/fisiologiaRESUMO
We investigated the incidence, clinical characteristics, risk factors, and outcome of meningoencephalitis (ME) in patients with COVID-19 attending emergency departments (ED), before hospitalization. We retrospectively reviewed all COVID patients diagnosed with ME in 61 Spanish EDs (20% of Spanish EDs, COVID-ME) during the COVID pandemic. We formed two control groups: non-COVID patients with ME (non-COVID-ME) and COVID patients without ME (COVID-non-ME). Unadjusted comparisons between cases and controls were performed regarding 57 baseline and clinical characteristics and 4 outcomes. Cerebrospinal fluid (CSF) biochemical and serologic findings of COVID-ME and non-COVID-ME were also investigated. We identified 29 ME in 71,904 patients with COVID-19 attending EDs (0.40, 95%CI=0.27-0.58). This incidence was higher than that observed in non-COVID patients (150/1,358,134, 0.11, 95%CI=0.09-0.13; OR=3.65, 95%CI=2.45-5.44). With respect to non-COVID-ME, COVID-ME more frequently had dyspnea and chest X-ray abnormalities, and neck stiffness was less frequent (OR=0.3, 95%CI=0.1-0.9). In 69.0% of COVID-ME, CSF cells were predominantly lymphocytes, and SARS-CoV-2 antigen was detected by RT-PCR in 1 patient. The clinical characteristics associated with a higher risk of presenting ME in COVID patients were vomiting (OR=3.7, 95%CI=1.4-10.2), headache (OR=24.7, 95%CI=10.2-60.1), and altered mental status (OR=12.9, 95%CI=6.6-25.0). COVID-ME patients had a higher in-hospital mortality than non-COVID-ME patients (OR=2.26; 95%CI=1.04-4.48), and a higher need for hospitalization (OR=8.02; 95%CI=1.19-66.7) and intensive care admission (OR=5.89; 95%CI=3.12-11.14) than COVID-non-ME patients. ME is an unusual form of COVID presentation (<0.5 cases), but is more than 4-fold more frequent than in non-COVID patients attending the ED. As the majority of these MEs had lymphocytic predominance and in one patient SARS-CoV-2 antigen was detected in CSF, SARS-CoV-2 could be the cause of most of the cases observed. COVID-ME patients had a higher unadjusted in-hospital mortality than non-COVID-ME patients.