RESUMEN
Enterovirus (EV) infections have various symptoms and severe complications, including death. To determine EV prevalence and EV types in Slovenia, data on over 25 000 EV RNA tests for diagnostics and surveillance from 2014 to 2023 were analyzed. Altogether, 3733 cerebrospinal fluid (CSF) and 21 297 respiratory (sentinel and clinical) samples were tested for EV RNA. EV typing was performed on all residual EV-positive CSF samples and on subset of respiratory specimens. Altogether, 1238 samples tested positive for EV RNA: 238 (6.4%) CSF and 1000 (4.7%) respiratory samples. EV-positive patients were predominantly male (p < 0.001). Many EV-positive CSF samples were from infants under 3 months (33.1%), whereas most EV-positive respiratory samples were from children 1 to 2 years old (49.2%). Echovirus 30 (E-30) was most frequent in CSF (33.0%), followed by CV-B5 (13.8%) and E-6 (13.8%). CV-A6 was most frequent in respiratory samples (16.0%), followed by EV-D68 (7.6%) and CV-A5 (7.4%). EV types in CSF and respiratory samples show diverse dynamics, with some outbreaks indicated. A significant difference was found in the EV detection rate between CSF and respiratory samples by age. Various EV types were characterized, showing that some EV types are more neurotropic or cause more severe infections.
Asunto(s)
Infecciones por Enterovirus , Enterovirus , Epidemiología Molecular , Humanos , Eslovenia/epidemiología , Lactante , Masculino , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virología , Infecciones por Enterovirus/líquido cefalorraquídeo , Femenino , Preescolar , Enterovirus/genética , Enterovirus/aislamiento & purificación , Enterovirus/clasificación , Niño , Adolescente , ARN Viral/genética , ARN Viral/líquido cefalorraquídeo , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/líquido cefalorraquídeo , Recién Nacido , Adulto , Adulto Joven , Prevalencia , Líquido Cefalorraquídeo/virología , Genotipo , Persona de Mediana Edad , Anciano , FilogeniaRESUMEN
PURPOSE: Enteroviruses (EV) comprises many different types and are the most common cause of aseptic meningitis. How the virus affects the brain including potential differences between types are largely unknown. Measuring biomarkers in CSF is a tool to estimate brain damage caused by CNS infections. METHODS: A retrospective study was performed in samples from 38 patients with acute neurological manifestations and positive CSF-EV RNA (n = 37) or serum-IgM (n = 1). The EV in 17 samples were typed by sequencing. The biomarkers neurofilament light (NFL), glial fibrillary acidic protein (GFAP), S-100B protein, amyloid-ß (Aß) 40 and Aß42, total-tau (T-tau) and phosphorylated tau (P-tau) were measured and compared with data derived from a control group (n = 19). RESULTS: There were no increased levels of GFAP (p ≤ 0.1) nor NFL (p ≤ 0.1) in the CSF of patients with EV meningitis (n = 38) compared with controls. However, we found decreased levels of Aß42 (p < 0.001), Aß40 (p < 0.001), T-tau (p ≥ 0.01), P-tau (p ≤ 0.001) and S-100B (p ≤ 0.001). E30 (n = 9) and CVB5 (n = 6) were the most frequent EV-types identified, but no differences in biomarker levels or other clinical parameters were found between the infecting virus type. Seven patients who were followed for longer than one month reported remaining cognitive impairment, although no correlations with biomarker concentrations were observed. CONCLUSION: There are no indication of neuronal or astrocyte damage in patients with EV meningitis. Yet, decreased concentrations of Aß40, Aß42, P-tau and T-tau were shown, a finding of unknown importance. Cognitive impairment after acute disease occurs, but with only a limited number of patients analysed, no conclusion can be drawn concerning any association with biomarker levels or EV types.
Asunto(s)
Péptidos beta-Amiloides , Biomarcadores , Infecciones por Enterovirus , Enterovirus , Proteína Ácida Fibrilar de la Glía , Proteínas tau , Humanos , Biomarcadores/líquido cefalorraquídeo , Masculino , Femenino , Enterovirus/genética , Enterovirus/aislamiento & purificación , Estudios Retrospectivos , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/virología , Adulto , Proteínas tau/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Persona de Mediana Edad , Adolescente , Niño , Genotipo , Subunidad beta de la Proteína de Unión al Calcio S100/líquido cefalorraquídeo , Preescolar , Adulto Joven , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Infecciones del Sistema Nervioso Central/líquido cefalorraquídeo , Infecciones del Sistema Nervioso Central/virología , Anciano , Lactante , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/sangreRESUMEN
BACKGROUND: To investigate the aetiology of acute undifferentiated fever (AUF) among children under the age of five in Vietnam. METHODS: This prospective study was conducted in the Thai Binh paediatric hospital, between July 2020 and July 2021 among children with AUF at admission. Real-time PCR testing 18 microbial pathogens were done on blood samples. RESULTS: 286 children were included, with median age of 16 months. 64.7% were male. 53.9% were positive for at least one pathogen by PCR. Enterovirus, human herpesvirus 6, adenovirus, and varicella zoster virus PCR were positive for 31.1, 12.6, 1.4, and 1.0% patients, respectively. Other pathogens tested negative by PCR. During the hospital stay, based on clinical criteria 47.2% children secondarily presented with signs of respiratory tract infections, 18.9% had hand, foot and mouth disease, 4.6% had chickenpox. 4.2% presented signs of central nervous system infections, 1.0% had dengue (antigenic test) and 1.0% had signs of gastrointestinal infection. Finally, 23.1% patients presented a fever with or without a rash and no other symptoms and ultimately received a diagnosis of AUF. CONCLUSION: Real-time PCR of blood is useful for detecting pathogens and diagnosing infectious causes of AUF. Further prospective studies with blood and urine culture testing and PCR investigation of not only blood but also cerebrospinal fluid, throat, and skin samples according to symptoms would be of interest to confirm the predominance of viral infections in children with AUF and to guide therapeutic options.
Asunto(s)
Infecciones por Enterovirus , Humanos , Niño , Masculino , Lactante , Femenino , Estudios Prospectivos , Vietnam/epidemiología , Infecciones por Enterovirus/líquido cefalorraquídeo , Hospitalización , Tiempo de InternaciónAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Infecciones por Enterovirus/diagnóstico , Enterovirus/aislamiento & purificación , Meningoencefalitis/virología , Adulto , Enterovirus/genética , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/etiología , Femenino , Humanos , Linfoma Folicular/tratamiento farmacológico , Meningoencefalitis/etiologíaRESUMEN
HISTORY: A 35-year-old, previously healthy woman presented with short history of headache and fever. Several other family members reported active hand, foot, and mouth disease. FINDINGS: Clinical findings showed subfebrile temperatures and a prominent meningism. Cerebrospinal fluid and computed tomography of the head were unrevealing. Subsequent PCR-analysis of the cerebrospinal fluid was positive for Enteroviral-RNA. DIAGNOSIS AND THERAPY: Enteroviral-meningitis was diagnosed. The empirically administered antimicrobial therapy was stopped and further diagnostic tests could be withheld. COURSE: Symptom-oriented therapy resulted in complete resolution within the next few days. CONCLUSIONS: Our case emphasizes that, in patients with typical signs of meningeal irritation, normal cellular analysis of the cerebrospinal fluid does not exclude the presence of infectious meningitis. The astute clinician should be reminded that this constellation is highly suggestive of enteroviral meningitis.
Asunto(s)
Líquido Cefalorraquídeo/virología , Infecciones por Enterovirus , Meningitis Viral , Adulto , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/diagnóstico , Femenino , Fiebre/virología , Cefalea/virología , Humanos , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/diagnósticoRESUMEN
New circulating Enterovirus (EV) strains often emerge through recombination. Upsurges of recombinant non-polio enteroviruses (NPEVs) associated with neurologic manifestations such as EVA71 or Echovirus 30 (E30) are a growing public health concern in Europe. Only a few complete genomes of EVs circulating in Spain are available in public databases, making it difficult to address the emergence of recombinant EVs, understand their evolutionary relatedness and the possible implication in human disease. We have used metagenomic (untargeted) NGS to generate full-length EV genomes from CSF samples of EV-positive aseptic meningitis cases in Southern Spain between 2015 and 2018. Our analyses reveal the co-circulation of multiple Enterovirus B (EV-B) types (E6, E11, E13 and E30), including a novel E13 recombinant form. We observed a genetic turnover where emergent lineages (C1 for E6 and I [tentatively proposed in this study] for E30) replaced previous lineages circulating in Spain, some concomitant with outbreaks in other parts of Europe. Metagenomic sequencing provides an effective approach for the analysis of EV genomes directly from PCR-positive CSF samples. The detection of a novel, disease-associated, recombinant form emphasizes the importance of genomic surveillance to monitor spread and evolution of EVs.
Asunto(s)
Enterovirus Humano B/genética , Infecciones por Enterovirus/virología , Genoma Viral , Meningitis Aséptica/virología , ARN Viral/genética , Adolescente , Adulto , Enterovirus Humano B/clasificación , Enterovirus Humano B/aislamiento & purificación , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/epidemiología , Femenino , Genotipo , Humanos , Masculino , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/epidemiología , Filogenia , ARN Viral/líquido cefalorraquídeo , Análisis de Secuencia de ADN , España/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To test the hypothesis that enterovirus meningitis (EM) is a frequent and self-limiting condition, the epidemiology of EM in adults was examined. METHODS: Using a prospective, nationwide, population-based database, all adults with EM confirmed by PCR of the CSF from 2015 to 2019 were included. Unfavorable outcome was defined as Glasgow Outcome Scale scores of 1-4 at discharge. Modified Poisson regression was used to compute adjusted relative risks (RRs). RESULTS: A total of 419 cases of EM in 418 adults (46% female, median age 31 years [interquartile range (IQR) 27-35]) yielded an incidence of 1.80/100,000/year. Admission diagnoses included CNS infection 247/397 (62%), other neurologic conditions 89/397 (22%), and cerebrovascular diseases 33/397 (8%). Genotype was available for 271 cases, of which echovirus 30 accounted for 155 (57%). Patients presented with headache 412/415 (99%), history of fever 303/372 (81%), photophobia 292/379 (77%), and neck stiffness 159/407 (39%). Fever (≥38.0°C) was observed in 192/399 (48%) at admission. The median CSF leukocyte count was 130 106/L (range 0-2,100) with polymorphonuclear predominance (>50%) in 110/396 (28%). Cranial imaging preceded lumbar puncture in 127/417 (30%) and was associated with non-CNS infection admission diagnoses and delayed lumbar puncture (median 4.8 hours [IQR 3.4-7.9] vs 1.5 [IQR 0.8-2.8], p < 0.001). Unfavorable outcome occurred in 99/419 (24%) at discharge; more often in female patients (RR 2.30 [1.58-3.33]) and less frequent in echovirus 30 (RR 0.67 [0.46-1.00]) in adjusted analyses. Outcome remained unfavorable in 22/379 (6%) after 6 months. CONCLUSIONS: EM is common among young, healthy adults. Although the long-term prognosis remains reassuring, a substantial proportion have moderate disability at discharge, especially female patients.
Asunto(s)
Infecciones por Enterovirus/epidemiología , Meningitis Viral/epidemiología , Adolescente , Adulto , Bases de Datos Factuales , Dinamarca/epidemiología , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/virología , Femenino , Escala de Consecuencias de Glasgow , Humanos , Recuento de Leucocitos , Masculino , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/virología , Persona de Mediana Edad , Distribución de Poisson , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Medición de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Aseptic meningitis is most often caused by enteroviruses (EVs), but EVs associated with aseptic meningitis have not yet been reported in Liaocheng. The aim of this study was to determine the prevalence and genetic characteristics of EVs causing aseptic meningitis in children in Liaocheng. METHODS: We reviewed the epidemiological and clinical characteristics of 504 paediatric cases of aseptic meningitis in Liaocheng from 2018 to 2019 and analysed the phylogeny of the predominant EV types causing this disease. RESULTS: A total of 107 children were positive for EV in cerebrospinal fluid samples by nested PCR. Most of the positive patients were children 13 years old or younger and had symptoms such as fever, headache and vomiting (P < 0.05). The seasons with the highest prevalence of EV-positive cases were summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year study period. Phylogenetic analyses demonstrated that the E18 and E6 isolates belonged to subgenotype C2, while the E11 isolates belonged to subgenotype D5. VP1 analysis suggested that only one lineage of these three types was cocirculating in the Liaocheng region. CONCLUSIONS: This study demonstrated the diverse EV genotypes contributing to a large outbreak of aseptic meningitis in Liaocheng. Therefore, large-scale surveillance is required to assess the epidemiology of EVs associated with aseptic meningitis and is important for the diagnosis and treatment of aseptic meningitis in Liaocheng.
Asunto(s)
Infecciones por Enterovirus/virología , Enterovirus/genética , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/epidemiología , Meningitis Viral/líquido cefalorraquídeo , Adolescente , Niño , Preescolar , China/epidemiología , Brotes de Enfermedades , Enterovirus/aislamiento & purificación , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/etiología , Femenino , Genotipo , Humanos , Lactante , Masculino , Meningitis Aséptica/etiología , Meningitis Aséptica/virología , Meningitis Viral/epidemiología , Meningitis Viral/virología , Filogenia , Estaciones del AñoRESUMEN
ABSTRACT: Enteroviruses is a group of positive single-stranded RNA viruses ubiquitous in the environment, which is a causative agent of epidemic diseases in children and infants. But data on neonates are still limited. The present study aimed to describe the clinical characteristics of enterovirus infection in neonates and arise the awareness of this disease to general public.Between March 2018 and September 2019, data from all of the neonates diagnosed with enterovirus infection were collected and analyzed from neonatal intensive care unit of Zhangzhou Hospital in Fujian, China.A total of 23 neonates were enrolled. All of them presented with fever (100%), and some with rashes (39.1%). The incidence of aseptic meningitis was high (91.3%), but only a small proportion (28.6%) presented with cerebrospinal fluid (CSF) leukocytosis. The positive value for nucleic acid detection in CSF was significantly higher than throat swab (91.3% vs 43.5%, Pâ=â.007). Five of the infected neonates presented with aseptic meningitis (23.8%) underwent brain magnetic resonance imaging examination and no craniocerebral injuries were found. Subsequent follow-ups were performed in 15 of them (71.4%) and no neurological sequelae was found.Aseptic meningitis is a common type of enterovirus infection in neonates with a benign course. Nucleic acid detection of CSF has an important diagnostic value. Febrile neonates would be suggested to screen for enterovirus infection in addition to complete septic workup. An unnecessary initiation or earlier cessation of antibiotics could be considered in enterovirus infection, but that indications still need further studies to guarantee the safety.
Asunto(s)
Infecciones por Enterovirus/epidemiología , Enterovirus/aislamiento & purificación , Fiebre/epidemiología , Meningitis Aséptica/epidemiología , Meningitis Viral/epidemiología , Encéfalo/diagnóstico por imagen , China/epidemiología , Enterovirus/genética , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/virología , Exantema/líquido cefalorraquídeo , Exantema/diagnóstico , Exantema/epidemiología , Exantema/virología , Femenino , Fiebre/líquido cefalorraquídeo , Fiebre/diagnóstico , Fiebre/virología , Humanos , Incidencia , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Imagen por Resonancia Magnética , Masculino , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/virología , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/diagnóstico , Meningitis Viral/virología , Faringe/virología , ARN Viral/líquido cefalorraquídeo , ARN Viral/aislamiento & purificación , Estudios Retrospectivos , Enfermedades Cutáneas Virales/líquido cefalorraquídeo , Enfermedades Cutáneas Virales/epidemiología , Enfermedades Cutáneas Virales/virologíaRESUMEN
There are increasing concerns of infections by enteroviruses (EVs) causing severe disease in humans. EV diagnostic laboratory methods show differences in sensitivity and specificity as well as the level of genetic information provided. We examined a detection method for EVs based on next generation sequencing (NGS) analysis of amplicons covering the entire capsid coding region directly synthesized from clinical samples. One hundred and twelve clinical samples from England; previously shown to be positive for EVs, were analyzed. There was high concordance between the results obtained by the new NGS approach and those from the conventional Sanger method used originally with agreement in the serotypes identified in the 83 samples that were typed by both methods. The sensitivity and specificity of the NGS method compared to those of the conventional Sanger sequencing typing assay were 94.74% (95% confidence interval, 73.97% to 99.87%) and 97.85% (92.45% to 99.74%) for Enterovirus A, 93.75% (82.80% to 98.69%) and 89.06% (78.75% to 95.49%) for Enterovirus B, 100% (59.04% to 100%) and 98.10% (93.29% to 99.77%) for Enterovirus C, and 100% (75.29% to 100%) and 100% (96.34% to 100%) for Enterovirus D. The NGS method identified five EVs in previously untyped samples as well as additional viruses in some samples, indicating co-infection. This method can be easily expanded to generate whole-genome EV sequences as we show here for EV-D68. Information from capsid and whole-genome sequences is critical to help identifying the genetic basis for changes in viral properties and establishing accurate spatial-temporal associations between EV strains of public health relevance.
Asunto(s)
Proteínas de la Cápside/genética , Infecciones por Enterovirus/virología , Enterovirus/clasificación , Enterovirus/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuenciación Completa del Genoma , Inglaterra , Enterovirus/aislamiento & purificación , Infecciones por Enterovirus/sangre , Infecciones por Enterovirus/líquido cefalorraquídeo , Heces/virología , Genoma Viral , Humanos , Filogenia , ARN Viral/genética , Sensibilidad y Especificidad , SerogrupoRESUMEN
Human enteroviruses are the most prevalent causes of aseptic meningitis worldwide. However, despite such predominancy, defining the enteroviral etiology of aseptic meningitis remains a diagnostic dilemma for the clinician in Iran. Therefore, this study was conducted to characterize the prevalence and clinical significance of enteroviral aseptic meningitis as well as the predominant enterovirus serotypes among patients with aseptic meningitis in the South of Iran.Cerebrospinal fluid (CSF) specimens were obtained from 73 patients with aseptic meningitis (52.1% males and 47.9% females), ages ranging from 1 month to 88 years. Following the extraction of nucleic acid, the detection of enteroviruses was performed by RT-PCR, targeting the 5' untranslated region of the genome, and sequencing. Enteroviruses were found in 46.6% of samples (34/73). The most predominant serotype was echovirus 30, followed by coxsackievirus B5 and poliovirus type 1 Sabin strain. The enterovirus infections were more prevalent among female patients (58.8%) and those below 5 years of age (52.9%). Although enterovirus infections were observed throughout the year, the infections were more prevalent during autumn with fever as the predominant clinical symptom. The outcomes revealed that enteroviruses are significant causes of aseptic meningitis in the South of Iran, while suspected cases of aseptic meningitis are usually monitored by bacterial culture and biochemical testing of CSF samples. Therefore, the etiology remains unknown in most cases. Molecular detection of viral pathogens should be included as a common approach in the screening of patients with aseptic meningitis to prevent unnecessary treatment and to improve clinical management.
Asunto(s)
Enterovirus Humano B/genética , Infecciones por Enterovirus/epidemiología , Meningitis Aséptica/epidemiología , Meningitis Viral/epidemiología , Poliomielitis/epidemiología , Poliovirus/genética , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Enterovirus Humano B/clasificación , Enterovirus Humano B/aislamiento & purificación , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/virología , Femenino , Genoma Viral , Humanos , Lactante , Recién Nacido , Irán/epidemiología , Masculino , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/diagnóstico , Meningitis Aséptica/virología , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/diagnóstico , Meningitis Viral/virología , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Poliomielitis/líquido cefalorraquídeo , Poliomielitis/diagnóstico , Poliomielitis/virología , Poliovirus/clasificación , Poliovirus/aislamiento & purificación , Prevalencia , ARN Viral/genéticaRESUMEN
BACKGROUND: Enteroviral infections in infants <3 months of age are frequent and under-diagnosed even though they can be life-threatening. Properly conducted subjective examination, which is repeatedly neglected, plays a key role in the diagnosis and treatment of these infections. MATERIALS AND METHODS: Analyses included children <3 months of age with confirmed enterovirus infection, hospitalised in the Department of Paediatrics from January 2019 to February 2020. Infections were confirmed by reverse transcription polymerase chain reaction in the cerebrospinal fluid using Neuro9 FTD set and in the stool using PB-03/Neuro; antibodies were determined in one patient. RESULTS: This study presents a detailed description of three cases with confirmed enterovirus infection and a positive epidemiological history. The cases involve viral sepsis, myocarditis with arrhythmia and circulatory failure, and meningitis with seizures. In addition, the details of 10 patients hospitalised in the Children's Clinic with a confirmed enterovirus infection are presented. Based on these cases, a significant influence of family history-taking on the diagnosis and implementation of appropriate treatment was found. CONCLUSION: In most of the analysed cases, family history of viral infection was positive. In patients with the most severe course of the enterovirus infection, accurate epidemiological history is extremely important, and the suspicion of viral infection and securing appropriate materials for testing may significantly speed up the diagnosis in the newborn and help to implement an appropriate treatment.
Asunto(s)
Pruebas Diagnósticas de Rutina/métodos , Infecciones por Enterovirus/diagnóstico , Anamnesis , Meningitis Viral/diagnóstico , Miocarditis/diagnóstico , Sepsis Neonatal/diagnóstico , Evaluación de Síntomas/métodos , Diagnóstico Diferencial , Infecciones por Enterovirus/líquido cefalorraquídeo , Femenino , Humanos , Recién Nacido , Masculino , Meningitis Viral/líquido cefalorraquídeo , Miocarditis/líquido cefalorraquídeo , Sepsis Neonatal/líquido cefalorraquídeo , Polonia , Resultado del TratamientoRESUMEN
Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.
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Enfermedades Virales del Sistema Nervioso Central/diagnóstico por imagen , Enfermedades Virales del Sistema Nervioso Central/rehabilitación , Infecciones por Enterovirus/epidemiología , Hipotonía Muscular , Debilidad Muscular , Mielitis/diagnóstico por imagen , Mielitis/rehabilitación , Enfermedades Neuromusculares/diagnóstico por imagen , Enfermedades Neuromusculares/rehabilitación , Enfermedades Virales del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades Virales del Sistema Nervioso Central/virología , Niño , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/complicaciones , Salud Global , Humanos , Imagen por Resonancia Magnética , Hipotonía Muscular/etiología , Debilidad Muscular/etiología , Mielitis/líquido cefalorraquídeo , Mielitis/virología , Enfermedades Neuromusculares/líquido cefalorraquídeo , Enfermedades Neuromusculares/virología , Evaluación del Resultado de la Atención al PacienteRESUMEN
Infection-induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6-month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B-cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.
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Artritis Reumatoide/sangre , Infecciones por Enterovirus/complicaciones , Enterovirus/genética , Inmunoglobulinas Intravenosas/uso terapéutico , Paniculitis/etiología , Paniculitis/terapia , Adulto , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Diagnóstico Diferencial , Enterovirus/aislamiento & purificación , Enterovirus Humano B/genética , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/microbiología , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Infecciones Oportunistas/complicaciones , Paniculitis/patología , Paniculitis/virología , Rituximab/efectos adversos , Rituximab/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Viral encephalitis is common in childhood. It is an acute brain parenchymal inflammation caused by a variety of viral infection, and enterovirus accounts for the majority. Due to atypical clinical manifestations, pathogenic testing is important for assisting clinical diagnosis. The purpose of this study was to evaluate the performance of the multiplex PCR assay compared with quantitative real-time PCR for enterovirus detection. METHODS: A prospective case-control study was performed involving 103 pediatric patients suspected for viral encephalitis and cerebrospinal fluid (CSF) samples were collected and tested for 9 pathogens using multiplex PCR assay during April to November in 2018. In parallel, an aliquot of samples was tested for enterovirus infection by real-time PCR assay. RESULTS: There were 85.4% children were confirmed as viral encephalitis on discharge, the remaining ones were diagnosed as other CNS diseases, such as epilepsy. The specificity of the two methods was the same as that of the clinical diagnosis, but the sensitivity and consistency with clinical diagnosis of multiplex PCR were both higher than the real-time PCR. Besides of enterovirus, multiplex PCR could also detect coinfection of enterovirus with Epstein-Barr virus and mumps virus. CONCLUSION: Results of multiplex PCR method are more consistent with the clinical diagnosis and are superior to real-time PCR for detecting enterovirus in CSF.
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Infecciones por Enterovirus/líquido cefalorraquídeo , Enterovirus/genética , Reacción en Cadena de la Polimerasa Multiplex/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estudios de Casos y Controles , Niño , Preescolar , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/virología , Femenino , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Enteroviruses are common causes of infections of the central nervous system (CNS) that in temperate climates tend to peak in the summer. The aim of the study was to describe epidemiology, drivers of seasonality, and types of enteroviruses causing infections of the CNS in children in Northeastern Poland. We prospectively collected data on children hospitalized with infection of the CNS attributed to enteroviruses in Bialystok, Poland, from January 2015 to December 2019. In total, 224 children were included. Nineteen different enterovirus types were identified in isolates collected from 188 children. Coxsackie B5 (32%), echovirus 30 (20%), and echovirus 6 (14%) were the three most common types. Enteroviruses were more prevalent during the summer-fall season. Infections caused by echovirus 30 peaked early in June and coxsackievirus B5 in July, whereas echovirus 6 peaked late in October. Phylogenetic analyses of these three enterovirus types showed multiple lineages co-circulating in this region. Mean air temperatures and precipitation rates were independently associated with monthly number of cases. Considering lack of effective treatment or vaccine, easy transmission of enteroviruses between susceptible individuals, their high mutation rate and prolonged time of viral shedding, continued monitoring and surveillance are imperative to recognize enteroviral infections of the CNS and the changes in circulation of enteroviruses in Poland.
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Infecciones por Enterovirus/epidemiología , Enterovirus/clasificación , Meningitis Viral/epidemiología , Filogenia , Estaciones del Año , Adolescente , Niño , Preescolar , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/transmisión , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Masculino , Meningitis Viral/diagnóstico , Meningitis Viral/transmisión , Polonia/epidemiología , Estudios ProspectivosRESUMEN
INTRODUCTION: In an attempt to identify a wide spectrum of viral infections, cerebrospinal fluid (CSF) specimens were collected from pediatric cases with the preliminary diagnosis of viral encephalitis/meningoencephalitis in two reference hospitals, from October 2011 to December 2015. METHODOLOGY: A combination of nucleic acid-based assays, including in house generic polymerase chain reaction (PCR) assays for enteroviruses, flaviviruses and phleboviruses, a commercial real-time PCR assay for herpesviruses and a commercial real time multiplex PCR, enabling detection of frequently-observed viral, bacterial and fungal agents were employed for screening. RESULTS: The microbial agent could be characterized in 10 (10%) of the 100 specimens. Viral etiology could be demonstrated in 7 (70%) specimens, which comprises Human Herpesvirus 6 (4/7), Herpes Simplex virus type1 (2/7) and Enteroviruses (1/7). In 3 specimens (30%), Streptococcus pneumoniae, Listeria monocytogenes and Staphylococcus aureus were detected via the multiplex PCR, which were also isolated in bacteriological media. All specimens with detectable viral nucleic acids, as well as unreactive specimens via nucleic acid testing remained negative in bacteriological cultures. CONCLUSIONS: Herpes and enteroviruses were identified as the primary causative agents of central nervous system infections in children. Enterovirus testing must be included in the diagnostic work-up of relevant cases.
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Infecciones del Sistema Nervioso Central/etiología , Infecciones del Sistema Nervioso Central/virología , Técnicas de Diagnóstico Molecular/métodos , Virosis/etiología , Virus/genética , Adolescente , Infecciones del Sistema Nervioso Central/líquido cefalorraquídeo , Infecciones del Sistema Nervioso Central/diagnóstico , Niño , Preescolar , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/virología , Femenino , Infecciones por Herpesviridae/líquido cefalorraquídeo , Infecciones por Herpesviridae/virología , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Lactante , Masculino , Técnicas de Diagnóstico Molecular/clasificación , Reacción en Cadena de la Polimerasa Multiplex , Virosis/líquido cefalorraquídeo , Virosis/clasificación , Virosis/diagnóstico , Virus/clasificación , Virus/patogenicidadRESUMEN
BACKGROUND: Enteroviruses are the most common etiological agent for viral encephalitis, but it is uncertain whether the cytokines have the ability to differentiate enteroviral meningitis (EVM) from bacterial meningitis (BM). METHODS: A retrospective study was performed at the Children's Hospital, Zhejiang University School of Medicine from August 2016 and August 2019. CSF and/or blood specimens were collected for microbiological culture, viruses, and cytokine detection. RESULTS: Forty-three patients were confirmed with meningitis, 27 patients with EVM, and 16 with BM. Children with EVM were older compared with BM and Control group (P < .001). The most common presenting symptom in children with EVM was fever (96.3%) followed by headache (88.9%) and vomiting (66.7%). The occurrence of seizure was lower in both EVM and BM groups (P < .001). Serum IL-6 and serum IL-10 were lower in EVM group than BM (P = .02) and control group (IL-6, P = .01; IL-10, P < .001). IL-6, IL-10, and IFN-γ levels showed obviously increase in CSF (P < .001, respectively) in EVM group, while only IL-6 increased in CSF (P < .001) in BM group. CSF concentrations of cytokines IL-6, IL-10, TNF, and IFN-γ in children with EVM and BM were both higher than Control group (P < .001). But compared EVM group to BM group, CSF IL-2 (P = .13), IL-6 (P = .37), IL-10 (P = .98), TNF (P = .54), and IFN-γ (P = .53) showed no difference between two groups. CONCLUSIONS: CSF cytokines elevated in both virus and bacterial meningitis, while serum elevation only occurred in bacterial infection. Still, we could not distinguish enteroviral meningitis from bacterial meningitis with the parameters of CSF cytokines IL-2, IL-6, IL-10, TNF, and IFN-γ.
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Citocinas/líquido cefalorraquídeo , Infecciones por Enterovirus/líquido cefalorraquídeo , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Viral/líquido cefalorraquídeo , Adolescente , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
To estimate the impact of implementing in-hospital enterovirus (EV) polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) with same-day turn-around-time (TAT) on length-of-stay (LOS), antibiotic use and on cost per patient with suspected EV meningitis, compared with testing at an outside reference laboratory. A model-based analysis using a retrospective cohort of all hospitalized children with CSF EV PCR testing done between November 2013 and 2017. The primary outcome measured was the potential date of discharge if the EV PCR result had been available on the same day. Patients with positive EV PCR were considered for potential earlier discharge once clinically stable with no reason for hospitalization other than intravenous antibiotics. Descriptive statistics and cost-sensitivity analyses were performed. CSF EV PCR testing was done on 153 patients, of which 44 (29%) had a positive result. Median test TAT was 5.3 days (IQR 3.9-7.6). Median hospital LOS was 5 days (IQR 3-12). Most (86%) patients received intravenous antibiotics with mean duration of 5.72 ± 6.51 days. No patients with positive EV PCR had a serious bacterial infection. We found that same-day test TAT would reduce LOS and duration of intravenous antibiotics by 0.50 days (95%CI 0.33-0.68) and 0.67 days (95%CI 0.42-0.91), respectively. Same-day test TAT was associated with a cost reduction of 342.83CAD (95%CI 178.14-517.00) per patient with suspected EV meningitis. Compared with sending specimens to a reference laboratory, performing CSF EV PCR in-hospital with same-day TAT was associated with decreased LOS, antibiotic therapy, and cost per patient.
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Manejo de la Enfermedad , Infecciones por Enterovirus/líquido cefalorraquídeo , Meningitis Viral/líquido cefalorraquídeo , Reacción en Cadena de la Polimerasa/métodos , Antibacterianos/uso terapéutico , Niño , Preescolar , Enterovirus , Infecciones por Enterovirus/diagnóstico , Femenino , Humanos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Meningitis Viral/diagnóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM.