Identificación etiológica de agentes virales de la encefalitis aguda en Guadalajara, México, 2011-2015 / Etiological identification of viral agents in acute encephalitis in Guadalajara, México, 2011-2015

Resumen Introducción. La encefalitis viral aguda se define como un proceso inflamatorio asociado a disfunción neurológica con desenlace fatal o daño grave permanente. En México no se han hecho estudios de identificación directa de los agentes etiológicos causales de la encefalitis viral aguda. Objetivo. Identificar mediante PCR en tiempo real los principales agentes virales causantes de encefalitis viral aguda en México. Materiales y métodos. Se obtuvo el líquido cefalorraquídeo de pacientes con sospecha de encefalitis viral que ingresaron al servicio de urgencias del Hospital Civil Fray Antonio Alcalde. Se extrajeron ácidos nucleicos para identificar los patógenos mediante PCR y PCR con transcripción inversa en tiempo real. Resultados. Se captaron un total de 66 pacientes entre el 2011 y el 2014. En 16 de los casos (24 %) se identificó el agente viral y se encontró que el principal agente causal fue el enterovirus, con ocho casos (50 %), seguido del virus del herpes simple (HSV: 37 %), con seis casos, y el citomegalovirus (CMV: 12,5 %), con dos casos. El promedio de edad fue de 25 años (0-70 años). Los casos positivos predominaron en los varones (63,3 %) y se estableció un predominio estacional en otoño (37,5 %). La mayoría de los pacientes presentó fiebre (48,4 %) o cefalea (36,3 %) y, en menor proporción, convulsiones, confusión y debilidad muscular (30,3 %) seguidas de desorientación (28,75 %) y apatía (25,7 %). En dos de los casos se observó el signo de Kerning (3 %) y en otros dos, el signo de Brudzinski (3 %). Conclusiones. La PCR en líquido cefalorraquídeo es una técnica de diagnóstico adecuada para la identificación de virus causales de encefalitis viral, lo cual permite prescribir los medicamentos específicos.

Abstract Introduction: Viral encephalitis is a well-known inflammatory process associated with neurological dysfunction that might derive into severe brain damage or a fatal outcome. In México there is no epidemiological data that describes the prevalence of viral agents responsible for acute encephalitis. Objective: To identify the main viral agents by real time PCR involved in acute encephalitis in Mexico. Materials and methods: We obtained cerebral spinal fluid (CSF) samples from all patients with suspected viral encephalitis admitted to the emergency service of the Hospital Civil de Guadalajara "Fray Antonio Alcalde". To identify pathogens, we performed nucleic acid extraction using real-time PCR and RT-PCR. Results: Sixty-six patients were diagnosed with acute encephalitis from 2011 to 2014. A definitive viral etiological diagnosis was established in 16 patients (24%); the main causative agents were enteroviruses in 50% of the 16 positive samples, followed by herpes simplex virus (37%) and cytomegaloviruses (12.5%). Patients with encephalitis were predominantly male (63.3%) and a seasonal predominance was observed during autumn (37.5%). The main clinical characteristics in the acute encephalitis phase were fever (48.45) and cephalea (36.3), followed by seizures, disorientation, and muscular weakness (30.3%). Kerning sign was present in two cases (3%) and other two cases presented Brudzinski's sign (3%). Conclusions: CSF PCR is a suitable diagnostic technique for the identification of viral encephalitis caused by viral infections that allows an appropriate antiviral therapeutic treatment.

Encefalopatía por virus herpes 6 como complicación de exantema súbito / Encephalopathy due to human herpesvirus 6 infection as exanthema subitum complication

La principal manifestación clínica del herpesvirus 6 es el exantema súbito (también conocido como roséola o sexta enfermedad) y el síndrome febril. Las manifestaciones en el sistema nervioso central no son infrecuentes en la infección por herpesvirus 6, y su fisiopatología no está esclarecida, pero precisan diagnóstico y tratamiento temprano para evitar secuelas potencialmente graves. Se presenta el caso de una niña inmunocompetente de 2 años con cuadro de encefalitis como complicación de infección por herpesvirus 6. Se destaca la importancia del diagnóstico oportuno a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la afectación del sistema nervioso central.

The main clinical manifestation of human herpesvirus 6 is exanthema subitum (also known as roseola infantum) and febrile syndrome. Central nervous system manifestations are not unusual in herpesvirus 6 infection, and even though the pathophysiology is not clear, they need to be early diagnosed and treated in order to avoid potentially serious damage. We present the case of an immunocompetent 2-year-old girl with encephalitis as a complication of herpesvirus 6 infection. We want to emphasize the significance of an early diagnosis and treatment in order to prevent further complications due to the central nervous system extension.

Neurological manifestations of dengue in Central Brazil

Abstract INTRODUCTION: The incidence of dengue has increased throughout the 2000s with a consequent global increase in atypical clinical forms. METHODS: This study reports a series of cases of neurological dengue out of 498 confirmed cases of laboratory dengue in Goiânia, Brazil. Cases were confirmed based on viral RNA detection via polymerase chain reaction or IgM antibody capture. RESULTS: Neurological symptoms occurred in 5.6% of cases, including paresthesia (3.8%), encephalitis (2%), encephalopathy (1%), seizure (0.8%), meningoencephalitis (0.4%), and paresis (0.4%). DENV-3 was the predominant circulating serotype (93%). CONCLUSIONS: We reported dengue cases with neurological manifestations in endemic area.

Encephalitis associated with the chikungunya epidemic outbreak in Brazil: report of 2 cases with neuroimaging findings

Abstract Chikungunya, an alphavirus infection presenting with fever, rash, and polyarthritis, is most often an acute febrile illness. Neurologic complications of chikungunya infection have been reported. Here we report the clinical and neuroimaging data of 2 patients with chikungunya-associated encephalitis during the recent Brazilian epidemic.

Encephalitis associated with inappropriate antidiuretic hormone secretion due to chikungunya infection in Recife, State of Pernambuco, Brazil

Abstract The symptoms of chikungunya virus (CHIKV) infection include fever, headache, muscle aches, skin rash, and polyarthralgia, characterized by intense pain, edema, and temporary functional impairment. This is the first report of encephalitis caused by CHIKV infection associated with an atypical presentation of syndrome of inappropriate antidiuretic hormone secretion, evolving to cognitive impairment and apraxia of speech.

Expression of EV71-VP1, PSGL-1 and SCARB2 in Tissues of Infants with Brain Stem Encephalitis / 法医学杂志

OBJECTIVE@#To understand the correlation of enterovirus 71 (EV71), P-selectin glycoprotein ligand-1 (PSGL-1), and scavenger receptor B2 (SCARB2) and to explore the possible pathway and mechanism of EV71 infection by observing the expression of EV71, PSGL-1 and SCARB2 in tissues of infants with brain stem encephalitis.@*METHODS@#The organs and tissues of infants with EV71-VP1 positivity in their brain stems were chosen. Expression and distribution of EV71-VP1, PSGL-1, and SCARB2 were detected and compared by immunohistochemistry.@*RESULTS@#Strong staining of EV71 -VP1 was observed in the neuron, glial cells, the inflammatory cells of perivascular cuffing, parietal cells of the gastric fundus gland while alveolar macrophages, intestinal gland epithelium cells, mucosa lymphoid nodule and lymphocyte of palatine tonsil showed moderate staining and weak staining were displayed in mesenteric lymph nodes and lymphocyte of spleen. PSGL-1 expression was detected in parietal cells of the gastric fundus gland, tonsillar crypt squamous epithelium, alveolar macrophages and leukocytes in each tissue. SCARB2 expression was observed in all the above tissues except the intestines and spleen.@*CONCLUSION@#The distribution of EV71 correlates with SCARB2 expression. SCARB2 plays an important role in virus infection and replication. Stomach may be an important site for EV71 replication.

Viral encephalitis / Encefalites virais

While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

Embora as infecções virais sistêmicas sejam muito comuns, as infecções virais sintomáticas do parênquima cerebral são raras, mas potencialmente graves. Estima-se que a encefalite viral ocorra em 1,4 casos por 100.000 habitantes anualmente. A localização geográfica é um fator determinante a ser levado em consideração frente aos patógenos transmitidos por vetores. O diagnóstico clínico das encefalites virais pode ser um desafio para o clínico, visto que quase 70% dos casos de encefalite viral ficam sem a identificação do agente viral. Nesta revisão, as encefalites virais mais comuns serão discutidas, com interesse especial sobre os aspectos da ecologia, do diagnóstico e do seu manejo clínico.

Encefalitis virales en la infancia / [Viral encephalitis in children].

Viral encephalitis is a severe illness that produces inflammation of the brain. CNS viral infections frequently occur as a complication of systemic viral infections. Over 100 viruses are implicated as causative agents, including herpes simplex virus type I which is the most common agent implied in non-epidemic encephalitis in all population groups in the world, and is responsible for the most severe cases in all ages. Many viruses, for which there are vaccines, may also cause encephalitis: measles, mumps, polio, rabies, rubella, and chickenpox. The virus causes an inflammation of the brain tissue, which may progress to destruction of nerve cells, cause bleeding and brain damage, leading to severe encephalitis, such as hemorrhagic or necrotizing encephalitis, with a worse prognosis, producing serious sequelae or death. The clinical evolution includes the presence of headache, fever and altered consciousness rapidly progressive. The outcome of viral encephalitis is variable, some cases are mild, with full recovery, but there are serious cases that can cause severe sequel in the brain. To diagnose this illness as soon as possible is essential, through laboratory tests (biochemistry, virus PCR, culture) and neuroimaging (CT, MRI) and above all, the establishment of early treatment to prevent the development of the process and possible complications. The prognosis worsens if the initiation of treatment is delayed.

Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism / 法医学杂志

OBJECTIVE@#To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis.@*METHODS@#Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared.@*RESULTS@#(1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with [dark]-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed [dark]-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P < 0.05).@*CONCLUSION@#The brainstem encephalitis can be used to diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.

Importancia de las imágenes y el diagnóstico etiológico en el paciente inmunocomprometido con afección del sistema nervioso central: Segunda parte / Importance of images and etiological diagnosis in the immunocompromised patient with central nervous system envolvement: Part II

We present the case of a 12-year-old boy with acute lymphocytic leukemia who developed pneumonia and multiple brain infarcts compatible with acute necrotic encephalitis. The infectious disease screening tests revealed influenza A H1N1 virus, Staphylococcus aureus in broncho alveolar lavage, E. coli and galactomannan antigen in blood. CNS influenza associated complications are reviewed. This case highlights the importance of magnetic resonance imaging as a diagnostic tool in the assessment of immunocompromised patients with CNS compromise and the value of brain biopsy in the final identification of an infectious disease etiology.

Escolar de 12 años de edad, con Leucemia Linfocítica Aguda en tratamiento que desarrolla una bronconeumonía bilateral, infartos cerebrales compatibles con encefalitis necrosante aguda. El estudio infectológico demostró más de una causas infecciosa que pudiera explicar su evolución destacando influenza A H1N1, Staphylococcus aureus meticilina sensible en lavado bronco alveolar, E. coli y galactomanano en sangre. Se revisa el compromiso del SNC por influenza A H1N1. Se destaca la importancia del uso de resonancia magnética nuclear al evaluar pacientes inmunocomprometidos con complicaciones neurológicas y el aporte de una biopsia cerebral en aclarar la etiología de este compromiso.

Management of acute viral encephalitis in Brazil

The appropriate management of acute viral encephalitis is a challenge. Clinical picture includes general symptoms and a wide range of neurological signs. Etiological diagnosis cannot be performed only by clinical means and depends on neuroimaging studies and cerebrospinal fluid molecular analyses. It is recommended since some of these viruses are treatable and that the prognoses of these infections depend on the prompt administration of antiviral and/or immunomodulatory drugs. The management of acute viral encephalitis in Brazil has some peculiarities. First, the etiological distribution of the viral encephalitis may differ from what is found in other countries. Some viruses, such as dengue virus, are more common in Brazil than in developed countries while others, like West Nile virus, are not found here. Second, there are some regions in Brazil where neuroimaging and laboratorial methods are not available, and a clinical-based decision is the only therapeutic approach. As most of the guidelines in the literature are based on complimentary methods, it is relevant to establish an alternative approach compatible with the Brazilian health system reality. The goal of this study was to review the recent advances in the field of the acute viral encephalitis, to discuss the diagnosis and the treatment of the main etiologies of acute viral encephalitis found in Brazil, and to propose a viable guideline for the evaluation of the suspected acute viral encephalitis cases in the emergence room in Brazil.

Molecular characterization of two rocio flavivirus strains isolated during the encephalitis epidemic in são paulo state, brazil and the development of a one-step rt-pcr assay for diagnosis

Rocio virus (ROCV) was responsible for an explosive encephalitis epidemic in the 1970s affecting about 1,000 residents of 20 coastland counties in São Paulo State, Brazil. ROCV was first isolated in 1975 from the cerebellum of a fatal human case of encephalitis. Clinical manifestations of the illness are similar to those described for St. Louis encephalitis. ROCV shows intense antigenic cross-reactivity with Japanese encephalitis complex (JEC) viruses, particularly with Ilheus (ILHV), St. Louis encephalitis, Murray Valley and West Nile viruses. In this study, we report a specific RT-PCR assay for ROCV diagnosis and the molecular characterization of the SPAn37630 and SPH37623 strains. Partial nucleotide sequences of NS5 and E genes determined from both strains were used in phylogenetic analysis. The results indicated that these strains are closely related to JEC viruses, but forming a distinct subclade together with ILHV, in accordance with results recently reported by Medeiros et al. (2007).

O vírus Rocio (ROCV) foi responsável por uma explosiva epidemia de encefalite que ocorreu nos anos 70 afetando cerca de 1.000 habitantes de 20 municípios litorâneos do Estado de São Paulo, Brasil. ROCV foi isolado em 1975 de cerebelo de caso humano fatal de encefalite. As manifestações clínicas da doença são semelhantes àquelas descritas para encefalite St. Louis. ROCV apresenta intensa reatividade cruzada com os vírus do Complexo da Encefalite Japonesa (JEV), particularmente com o vírus Ilhéus (ILHV) e com os vírus das encefalites St. Louis, Murray Valley e West Nile. Neste estudo, relatamos o desenvolvimento de um teste de RT-PCR específico para diagnóstico de ROCV e a caracterização molecular das cepas SPAn37630 e SPH37623. Foi realizada a análise filogenética das seqüências parciais dos genes NS5 e E, de ambas as cepas. Os resultados indicaram que essas cepas são intimamente relacionadas ao complexo JEV, mas formando um subgrupo com o ILHV, de acordo com os resultados recentemente publicados por MEDEIROS et al. (2007).

Dexamethasone-induced reactivation of bovine herpesvirus type 5 latent infection in experimentally infected rabbits results in a broader distribution of latent viral DNA in the brain

Bovine herpesvirus type 5 (BHV-5) is a major agent of meningoencephalitis in cattle and establishes latent infections mainly in sensory nerve ganglia. The distribution of latent BHV-5 DNA in the brain of rabbits prior to and after virus reactivation was studied using a nested PCR. Fifteen rabbits inoculated intranasally with BHV-5 were euthanized 60 days post-inoculation (group A, N = 8) or submitted to dexamethasone treatment (2.6 mg kg-1 day-1, im, for 5 days) and euthanized 60 days later (group B, N = 7) for tissue examination. Two groups of BHV-1-infected rabbits (C, N = 3 and D, N = 3) submitted to each treatment were used as controls. Viral DNA of group A rabbits was consistently detected in trigeminal ganglia (8/8), frequently in cerebellum (5/8), anterior cerebral cortex and pons-medulla (3/8) and occasionally in dorsolateral (2/8), ventrolateral and posterior cerebral cortices, midbrain and thalamus (1/8). Viral DNA of group B rabbits showed a broader distribution, being detected at higher frequency in ventrolateral (6/7) and posterior cerebral cortices (5/7), pons-medulla (6/7), thalamus (4/7), and midbrain (3/7). In contrast, rabbits inoculated with BHV-1 harbored viral DNA almost completely restricted to trigeminal ganglia and the distribution did not change post-reactivation. These results demonstrate that latency by BHV-5 is established in several areas of the rabbit's brain and that virus reactivation leads to a broader distribution of latent viral DNA. Spread of virus from trigeminal ganglia and other areas of the brain likely contributes to this dissemination and may contribute to the recrudescence of neurological disease frequently observed upon BHV-5 reactivation.

Hemorrhagic encephalopathy in dengue shock syndrome: a case report

Dengue fever is the most important arboviral infection in the world, with an estimated 100 million cases per year and 2.5 billion people at risk. Encephalopathy is a rare complication of dengue virus infection and may occur as a consequence of intracranial hemorrhage, cerebral edema, hyponatremia, cerebral anoxia, fulminant hepatic failure with portosystemic encephalopathy, microcapillary hemorrhage or release of toxic products. We report a rare case of hemorrhagic encephalopathy in dengue shock syndrome caused by type 3 dengue virus.

Enfermedad neurologica por adenovirus / Neurologic disease due to adenovirus infection

El objetivo de este trabajo fue determinar la prevalencia de adenovirus (ADV) en las infecciones del sistema nervioso central (SNC). Se analizaron 108 muestras de líquido cefalorraquídeo (LCR) provenientes de 79 casos de encefalitis, 7 meningitis y 22 de otras patologías neurológicas, recibidas en el período 2000-2002. Cuarenta y nueve (47.35%) se obtuvieron de pacientes inmunocomprometidos. La presencia de ADV se investigó mediante reacción en cadena de la polimerasa en formato anidado (Nested-PCR). La identificación del genogrupo se realizó mediante análisis filogenético de la secuencia nucleotídica parcial de la región que codifica para la proteína del hexón. Se detectó la presencia de ADV en 6 de 108 (5.5%) muestras de LCR analizadas. Todos los casos positivos pertenecieron a pacientes con encefalitis que fueron 79, (6/79, 7.6%). No se observó diferencia estadísticamente significativa entre los casos de infección por ADV en pacientes inmunocomprometidos e inmunocompetentes (p>0.05). Las cepas de ADV detectadas se agruparon en los genogrupos B1 y C. En conclusión, nuestros resultados describen el rol de los ADV en las infecciones neurológicas en Argentina. La información presentada contribuye al conocimiento de su epidemiología, en particular en casos de encefalitis.

Vírus da estomatite vesicular (Sorotipo Indiana 2) como modelo experimental para o estudo de encefalite aguda: aspectos morfológicos / Vesicular stomatitis virus (Indiana 2 Serotype) as experimental model to study acute encephalitis: morphological features

O vírus da estomatite vesicular (VEV) é um vesiculovírus da família Rhabdoviridae que infecta mamíferos e causa lesões vesiculares semelhantes às observadas na febre aftosa. A encefalite experimental pode ser induzida em roedores e os sintomas são semelhantes aos observados na raiva; entretanto, as lesões observadas no encéfalo dos animais são diferentes. Corpúsculos de inclusão não são observados, há necrose especialmente da região do bulbo olfatório e em alguns casos, ventriculite. Observamos que o padrão temporal de disseminação do VEV e os aspectos morfológicos das lesões são similares aos descritos na literatura. O vírus parece se disseminar através dos ventrículos cerebrais, multiplicando-se em células do epêndima e em neurônios, além de utilizar o transporte retrógrado e anterógrado. Constatamos que devido à facilidade de manipulação do vírus, este modelo experimental tem sido utilizado em inúmeros trabalhos de pesquisa em diversas áreas. Se por um lado, os relatos sobre a patogenia da infecção são numerosos, por outro lado, ainda existem muitas lacunas que envolvem, por exemplo, aspectos sobre a transmissão do vírus, a recuperação dos animais infectados e a participação de células gliais durante a fase aguda e a fase de recuperação dos animais

Infecção aguda e latente em ovinos inoculados com o herpesvírus bovino tipo 5 (BHV-5) / Acute and latent infection in sheep inoculated with bovine herpesvirus type-5 (BHV-5)

Infecção experimental de ovinos com o herpesvírus bovino tipo 5 (BHV-5) reproduziu vários aspectos da infecção pelo BHV-5 em bovinos. Inoculação intranasal foi seguida de extensiva replicação viral na cavidade nasal, excreção e transmissão do vírus a outros animais, estabelecimento e reativação de latência, e o desenvolvimento de meningoencefalite clínica em um animal. Ovinos inoculados com a amostra brasileira EVI-88 apresentaram hipertermia transitória, hiperemia da mucosa nasal e corrimento nasal de seroso a muco-purulento. Os animais eliminaram vírus em secreções nasais em títulos de até 107,11DICC50/ml por até 16 dias. Um cordeiro apresentou sinais clínicos de encefalite no dia 10 pós-inoculação, sendo sacrificado in extremis no início do dia 13. Infectividade foi detectada em várias regiões do encéfalo desse animal, incluindo os hemisférios anterior e posterior, córtex dorso- e ventro-lateral, ponte, pedúnculo cerebral, cerebelo e bulbo olfatório. Alterações histológicas foram observadas em várias regiões do encéfalo, principalmente no hemisfério anterior, córtex ventro-lateral e pedúnculos cerebrais, e consistiram de meningite mononuclear, manguitos perivasculares, gliose focal, necrose e inclusões intranucleares em neurônios . Quatro ovinos mantidos como sentinelas adquiriram a infecção e eliminaram vírus a partir do final do segundo dia, até 7 dias. Ovinos inoculados com a amostra argentina A663 apresentaram apenas hiperemia e umidecimento da mucosa nasal, embora eliminassem vírus nas secreções nasais por até 15 dias. Tratamento dos animais com dexametasona a partir do dia 50 pós-inoculação provocou reativação da infecção latente e eliminação viral durante até 11 dias por 76,9% (10/13) dos animais inoculados e por 100% (3/3) dos animais sentinela. Esses resultados demonstram que ovinos são susceptíveis à infecção aguda e latente pelo BHV-5 e sugerem que infecções naturais de ovinos por este vírus podem potencialmente ocorrer. Ness sentido, uma possível participação da espécie ovina como reservatório natural desse vírus deve ser melhor investigada

Use of immunoglobulin M antibody capture enzyme-linked immunosorbent assay in the surveillance of Rocio encephalitis

In 1975-1976 an extensive epidemic of Rocio encephalitis occurred in the South region of the Sao Paulo State, Brazil. Since June 1976 no serological confirmation of this diagnosis has been made. Sera from 90 patients clinically suspected of having contracted Rocio encephalitis between July 1976 and December 1982, were tested with an immunoglobulin M (IgM) antibody capture enzyme immunoassay (MAC ELISA). Only one serum sample was available for each of these patients. Four presumptive cases of Rocio encephalitis were identified. Three of these sera had been collected in August and September of 1976. The fourth one, from a boy one year of age who died from the disease, was collected in April 1980. These results indicate that Rocio virus was circulating in the human population causing severe disease, at least until 1980. MAC ELISA is useful for surveillance of Rocio encephalitis in an area where the collection of paired sera samples is very difficult.