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1.
Microbiol Spectr ; 11(3): e0535222, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37227147

RESUMO

Enteroviruses are a group of positive single-stranded viruses that belong to the Picornaviridae family. They regularly infect humans and cause symptoms ranging from the common cold and hand-foot-and-mouth disease to life-threatening conditions, such as dilated cardiomyopathy and poliomyelitis. Enteroviruses have also been associated with chronic immune-mediated diseases, such as type 1 diabetes, celiac disease, and asthma. Studying these disease-pathogen connections is challenging due to the high prevalence of enterovirus infections in the population and the transient appearance of the virus during the acute infection phase, which limit the identification of the causative agent via methods based on the virus genome. Serological assays can detect the antibodies induced by acute and past infections, which is useful when direct virus detection is not possible. We describe in this immuno-epidemiological study how the antibody levels against VP1 proteins from eight different enterovirus types, representing all seven of the human infecting enterovirus species, vary over time. VP1 responses first significantly (P < 0.001) decline until 6 months of age, reflecting maternal antibodies, and they then start to increase as the infections accumulate and the immune system develops. All 58 children in this study were selected from the DiabImmnune cohort for having PCR-confirmed enterovirus infections. Additionally, we show that there is great, although not complete, cross-reactivity of VP1 proteins from different enteroviruses and that the response against 3C-pro could reasonably well reflect the recent Enterovirus infection history (ρ = 0.94, P = 0.017). The serological analysis of enterovirus antibodies in sera from children paves the way for the development of tools for monitoring the Enterovirus epidemics and associated diseases. IMPORTANCE Enteroviruses cause a wide variety of symptoms ranging from a mild rash and the common cold to paralyzing poliomyelitis. While enteroviruses are among the most common human pathogens, there is a need for new, affordable serological assays with which to study pathogen-disease connections in large cohorts, as enteroviruses have been linked to several chronic illnesses, such as type 1 diabetes mellitus and asthma exacerbations. However, proving causality remains an issue. In this study, we describe the use of an easily customizable multiplexed assay that is based on structural and nonstructural enterovirus proteins to study antibody responses in a cohort of 58 children from birth to 3 years of age. We demonstrate how declining maternal antibody levels can obscure the serological detection of enteroviruses before the age of six months and how antibody responses to nonstructural enterovirus proteins could be interesting targets for serodiagnosis.


Assuntos
Resfriado Comum , Infecções por Enterovirus , Enterovirus , Poliomielite , Criança , Animais , Humanos , Pré-Escolar , Lactente , Enterovirus/genética , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/epidemiologia , Antígenos Virais , Anticorpos Antivirais , Imunoensaio
2.
Clin Microbiol Infect ; 28(1): 79-84, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34015534

RESUMO

OBJECTIVES: In central nervous system infections, early and correct management is of utmost importance. Rapid syndromic panel testing can potentially provide valuable guidance. The FilmArray meningitis/encephalitis (ME) panel detects 14 pathogens through multiplex PCR. Our study objectives were to assess its performance compared with established diagnostic procedures, especially real-time quantitative PCR for detection of viruses, and to determine the diagnostic and clinical significance of discrepant results. METHODS: All cerebrospinal fluid samples sent for viral diagnostics to our microbiological laboratory over 34 months were analysed with the ME panel and in-house real-time PCR for herpes simplex virus type 1 (HSV-1), HSV-2, varicella zoster virus and enteroviruses. Other pathogens detected by the panel were confirmed by routine diagnostic procedures. Discrepant results were analysed through interpretation of biological and clinical data, and performance data were calculated for individual pathogens. RESULTS: Altogether, 315 pathogens were detected by the ME panel in 4199 cerebrospinal fluid samples (7.5%) and an additional 21 viral targets were identified using real-time PCR. Thirty-four ME panel detections were not confirmed, totalling 55 discrepant results. After discrepancy analysis, 20 false-positive and 21 false-negative ME panel results remained. Performance varied between pathogens. Sensitivity for HSV-1 was calculated at 82.4% (59.0%-93.8%) with three false-negative results. Also noteworthy were 13 false-negative enterovirus and eight false-positive Streptococcus pneumoniae results. CONCLUSIONS: Our analysis shows good performance for the ME panel in diagnosing central nervous system infection. The risk of false-negative HSV-1 results, however, warrants additional testing when encephalitis is suspected. Uncertainties in interpretation of enterovirus and S. pneumoniae results represent other limitations.


Assuntos
Infecções do Sistema Nervoso Central , Encefalite , Meningite , Vírus , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/diagnóstico , Líquido Cefalorraquidiano , Encefalite/líquido cefalorraquidiano , Encefalite/diagnóstico , Infecções por Enterovirus/diagnóstico , Humanos , Meningite/líquido cefalorraquidiano , Meningite/diagnóstico , Reação em Cadeia da Polimerase Multiplex , Vírus/genética , Vírus/isolamento & purificação
3.
Biomed Res Int ; 2021: 5519436, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395616

RESUMO

Bacterial meningitis (BM) is a public health burden in developing countries, including Central Asia. This disease is characterized by a high mortality rate and serious neurological complications. Delay with the start of adequate therapy is associated with an increase in mortality for patients with acute bacterial meningitis. Cerebrospinal fluid culture, as a gold standard in bacterial meningitis diagnosis, is time-consuming with modest sensitivity, and this is unsuitable for timely decision-making. It has been shown that bacterial meningitis differentiation from viral meningitis could be done through different parameters such as clinical signs and symptoms, laboratory values, such as PCR, including blood and cerebrospinal fluid (CSF) analysis. In this study, we proposed the method for distinguishing the bacterial form of meningitis from enteroviral one. The method is based on the machine learning process deriving making decision rules. The proposed fast-and-frugal trees (FFTree) decision tree approach showed an ability to determine procalcitonin and C-reactive protein (CRP) with cut-off values for distinguishing between bacterial and enteroviral meningitis (EVM) in children. Such a method demonstrated 100% sensitivity, 96% specificity, and 98% accuracy in the differentiation of all cases of bacterial meningitis in this study. These findings and proposed method may be useful for clinicians to facilitate the decision-making process and optimize the diagnostics of meningitis.


Assuntos
Proteína C-Reativa/metabolismo , Infecções por Enterovirus/diagnóstico , Meningites Bacterianas/diagnóstico , Meningite Viral/diagnóstico , Pró-Calcitonina/sangue , Biomarcadores/sangue , Proteína C-Reativa/líquido cefalorraquidiano , Criança , Pré-Escolar , Tomada de Decisão Clínica/métodos , Árvores de Decisões , Diagnóstico Diferencial , Infecções por Enterovirus/sangue , Feminino , Humanos , Lactente , Aprendizado de Máquina , Masculino , Meningites Bacterianas/sangue , Meningite Viral/sangue , Pró-Calcitonina/líquido cefalorraquidiano , Sensibilidade e Especificidade
4.
Eur J Clin Microbiol Infect Dis ; 39(5): 945-954, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31933018

RESUMO

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.


Assuntos
Gerenciamento Clínico , Infecções por Enterovirus/líquido cefalorraquidiano , Meningite Viral/líquido cefalorraquidiano , Reação em Cadeia da Polimerase/métodos , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Enterovirus , Infecções por Enterovirus/diagnóstico , Feminino , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Meningite Viral/diagnóstico , Estudos Retrospectivos , Fatores de Tempo
5.
Lancet Infect Dis ; 18(12): 1385-1396, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30389482

RESUMO

BACKGROUND: Enteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR. METHODS: We did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens. FINDINGS: Between June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 [99%] of 71 vs 62 [87%] of 71; p=0·011) and infants (76 [92%] of 83 vs 62 [75%] of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 [55%] of 163 vs 148 [91%] of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 [100%] of 55 vs 41 [75%] of 55; p=0·0002) or with sepsis-like disease (16 [100%] of 16 vs nine [56%] of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 [67%] of 246 vs 222 [90%] of 246; p<0·0001). INTERPRETATION: Testing for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness. FUNDING: University Hospital Clermont-Ferrand.


Assuntos
Sangue/virologia , Infecções por Enterovirus/diagnóstico , Enterovirus/isolamento & purificação , Febre de Causa Desconhecida/diagnóstico , Meningite/diagnóstico , Reação em Cadeia da Polimerase/métodos , Sepse/diagnóstico , Adolescente , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Enterovirus/genética , Infecções por Enterovirus/virologia , Feminino , Febre de Causa Desconhecida/virologia , França , Humanos , Lactente , Recém-Nascido , Masculino , Meningite/virologia , Técnicas de Diagnóstico Molecular/métodos , Estudos Prospectivos , Sepse/virologia
6.
Euro Surveill ; 22(45)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29162204

RESUMO

Enteroviruses (EVs) cause severe outbreaks of respiratory and neurological disease as illustrated by EV-D68 and EV-A71 outbreaks, respectively. We have mapped European laboratory capacity for identification and characterisation of non-polio EVs to improve preparedness to respond to (re)-emerging EVs linked to severe disease. An online questionnaire on non-polio EV surveillance and laboratory detection was submitted to all 30 European Union (EU)/European Economic Area (EEA) countries. Twenty-nine countries responded; 26 conducted laboratory-based non-polio EV surveillance, and 24 included neurological infections in their surveillance. Eleven countries have established specific surveillance for EV-D68 via sentinel influenza surveillance (n = 7), typing EV-positive respiratory samples (n = 10) and/or acute flaccid paralysis surveillance (n = 5). Of 26 countries performing non-polio EV characterisation/typing, 10 further characterised culture-positive EV isolates, whereas the remainder typed PCR-positive but culture-negative samples. Although 19 countries have introduced sequence-based EV typing, seven still rely entirely on virus isolation. Based on 2015 data, six countries typed over 300 specimens mostly by sequencing, whereas 11 countries characterised under 50 EV-positive samples. EV surveillance activity varied between EU/EEA countries, and did not always specifically target patients with neurological and/or respiratory infections. Introduction of sequence-based typing methods is needed throughout the EU/EEA to enhance laboratory capacity for the detection of EVs.


Assuntos
Surtos de Doenças/prevenção & controle , Enterovirus Humano D/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Enterovirus/isolamento & purificação , Infecções Respiratórias/virologia , Vigilância de Evento Sentinela , Adolescente , Proteínas do Capsídeo/genética , Criança , Notificação de Doenças , Enterovirus/genética , Enterovirus Humano D/genética , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Infecções Respiratórias/epidemiologia , Adulto Jovem
7.
BMC Infect Dis ; 17(1): 153, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28212620

RESUMO

BACKGROUND: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. METHODS: This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. RESULTS: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. CONCLUSIONS: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.


Assuntos
Encefalite Viral/diagnóstico , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/virologia , Hemorragia/diagnóstico , Edema Pulmonar/diagnóstico , Transtornos Respiratórios/diagnóstico , Autopsia , Criança , Pré-Escolar , China/epidemiologia , Coma , Surtos de Doenças , Progressão da Doença , Encefalite Viral/mortalidade , Encefalite Viral/fisiopatologia , Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/mortalidade , Infecções por Enterovirus/fisiopatologia , Feminino , Hemorragia/mortalidade , Hemorragia/fisiopatologia , Humanos , Lactente , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Edema Pulmonar/mortalidade , Edema Pulmonar/fisiopatologia , Transtornos Respiratórios/mortalidade , Transtornos Respiratórios/fisiopatologia , Taxa Respiratória/fisiologia
8.
Hosp Pediatr ; 7(2): 96-102, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28082417

RESUMO

CONTEXT: Enterovirus infection commonly causes fever in infants aged 0 to 90 days and, without testing, is difficult to differentiate from serious bacterial infection. OBJECTIVE: To determine the cost savings of routine enterovirus testing and identify subgroups of infants with greater potential impact from testing among infants 0 to 90 days old with fever. DATA SOURCES: Studies were identified systematically from published and unpublished literature by using Embase, Medline, the Cochrane database, and conference proceedings. STUDY SELECTION: Inclusion criteria were original studies, in any language, of enterovirus infection including the outcomes of interest in infants aged 0 to 90 days. DATA EXTRACTION: Standardized instruments were used to appraise each study. The evidence quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation criteria. Two investigators independently searched the literature, screened and critically appraised the studies, extracted the data, and applied the Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Of the 257 unique studies identified and screened, 32 were completely reviewed and 8 were included. Routine enterovirus testing was associated with reduced hospital length of stay and cost savings during peak enterovirus season. Cerebrospinal fluid pleocytosis was a poor predictor of enterovirus meningitis. The studies were all observational and the evidence was of low quality. CONCLUSIONS: Enterovirus polymerase chain reaction testing, independent of cerebrospinal fluid pleocytosis, can reduce length of stay and achieve cost savings, especially during times of high enterovirus prevalence. Additional study is needed to identify subgroups that may achieve greater cost savings from testing to additionally enhance the efficiency of testing.


Assuntos
Infecções Bacterianas/diagnóstico , Infecções por Enterovirus , Enterovirus , Febre/etiologia , Alocação de Recursos para a Atenção à Saúde/métodos , Hospitais Pediátricos/estatística & dados numéricos , Diagnóstico Diferencial , Enterovirus/genética , Enterovirus/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/fisiopatologia , Infecções por Enterovirus/virologia , Humanos , Lactente , Estudos Observacionais como Assunto , Reação em Cadeia da Polimerase
9.
Singapore Med J ; 58(4): 189-195, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27245861

RESUMO

INTRODUCTION: Enterovirus infections in childhood can be associated with significant neurological morbidity. This study aimed to describe the prevalence and range of neurological manifestations, determine the clinical characteristics and assess differences in clinical outcomes for Singaporean children diagnosed with enterovirus infections. METHODS: In this single-centre, case-control study, clinical data was collected retrospectively from patients admitted to National University Hospital, Singapore, from August 2007 to October 2011 and diagnosed with enterovirus infection, based on the enterovirus polymerase chain reaction test, or cultures from throat and rectal swabs or cerebrospinal fluid samples. The occurrence of neurological manifestations was reviewed and clinical outcomes were assessed. RESULTS: A total of 48 patients (age range: six days-17.8 years) were included in the study. Neurological manifestations were seen in 75.0% of patients, 63.9% of whom presented with aseptic meningitis. Other neurological manifestations included encephalitis, acute cerebellitis, transverse myelitis and autonomic dysfunction. The incidence of neurological manifestations was significantly higher in patients aged > 1 year as compared to younger patients (p = 0.043). In patients without neurological manifestations, a significantly higher proportion presented with hand, foot and mouth disease and poor feeding. Long-term neurological sequelae were seen in 16.7% of patients with neurological manifestations. CONCLUSION: A wide spectrum of neurological manifestations resulting in a relatively low incidence of long-term neurological sequelae was observed in our study of Singaporean children with enterovirus infections. As some of these neurological morbidities were severe, careful evaluation of children with neurological involvement is therefore necessary.


Assuntos
Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/virologia , Infecções por Enterovirus/complicações , Adolescente , Distribuição por Idade , Estudos de Casos e Controles , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Criança , Pré-Escolar , Enterovirus/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/epidemiologia , Feminino , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Singapura/epidemiologia
10.
Pediatr Crit Care Med ; 17(11): 1023-1031, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27505715

RESUMO

OBJECTIVE: In 2014, the Unites States experienced an outbreak of enterovirus D68 associated with severe respiratory illness. The clinical characteristics associated with severe illness from enterovirus D68 during this outbreak compared with those associated with the 2009 H1N1 influenza virus outbreak are unknown. DESIGN AND SETTING: In this retrospective cohort study, we characterized the clinical features of children with enterovirus D68 admitted to the PICU between August 1, 2014, and November 1, 2014, and compared them with critically ill children infected with H1N1 influenza during the pandemic admitted between May 1, 2009, and January 31, 2010. PATIENTS: PICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-seven severely ill children with enterovirus D68 infections were compared with 68 children infected with H1N1 influenza during the 2009 pandemic. Children with enterovirus D68 were more likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway disease exacerbations, with greater receipt of albuterol (94% vs 49%) and steroids (89% vs 40%; p < 0.0001 for both). Although more children with enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza, they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05 for all). Compared with children with other enteroviruses and rhinoviruses, children with enterovirus D68 were more likely to have a history of asthma (64% vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both). CONCLUSIONS: Critically ill children with enterovirus D68 were more likely to present with reactive airway disease exacerbations, whereas children with H1N1 influenza were more likely to present with pneumonia. Compared with the pandemic H1N1 influenza outbreak, the enterovirus D68 outbreak resulted in more children requiring admission to the ICU, but was associated with less severe outcomes.


Assuntos
Enterovirus Humano D , Infecções por Enterovirus/diagnóstico , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico , Adolescente , Criança , Pré-Escolar , Colorado/epidemiologia , Efeitos Psicossociais da Doença , Estado Terminal , Surtos de Doenças , Infecções por Enterovirus/epidemiologia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Influenza Humana/epidemiologia , Unidades de Terapia Intensiva Pediátrica , Modelos Logísticos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença
11.
J Clin Virol ; 77: 15-20, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26875098

RESUMO

BACKGROUND: Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens of viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children. OBJECTIVES: To compare the clinical symptoms and laboratory data of children with different EV and HPeV genotypes. STUDY DESIGN: This study is part of a multicenter prospective cohort study. Children were included in 3 different hospitals in The Netherlands from 2008 to 2011. RESULTS: Of 285 included patients, 140 (49%) had EV and 44 (15%) HPeV infection. Of children with EV infection 9 (6%) had EV-A, 109 (78%) EV-B, 12 (9%) had a non-type able EV and in 10 (7%) no genotyping was performed. Of children with HPeV infection, 24 (55%) had HPeV-3, 6 (14%) HPeV-1, 2 (5%) HPeV-4 and 1 (2%) HPeV-6. Meningitis was more frequent in EV than in HPeV infected children (54% vs. 36%, p=0.046), and in EV-B than EV-A infected children (60 vs. 33%). In contrast gastroenteritis was more frequent in HPeV than EV infected children (30% vs. 15%, p=0.030), and significantly more in HPeV-1 than HPeV-3 infected children (p<0.001). CONCLUSIONS: EV infection is more often associated with meningitis and HPeV infection more often with a gastro-enteritis. EV genotype B infection is more often associated with meningitis than EV genotype A infection. HPeV-1 infection was more often associated with gastroenteritis than HPeV-3 infection.


Assuntos
Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/virologia , Enterovirus/genética , Genótipo , Parechovirus/genética , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/virologia , Adolescente , Criança , Pré-Escolar , Enterovirus/classificação , Infecções por Enterovirus/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Leucocitose , Masculino , Meningite Viral/diagnóstico , Meningite Viral/epidemiologia , Meningite Viral/virologia , Países Baixos/epidemiologia , Parechovirus/classificação , Infecções por Picornaviridae/epidemiologia , Estudos Prospectivos , Estações do Ano
12.
PLoS One ; 10(4): e0122865, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25875080

RESUMO

School children may transmit pathogens with cluster cases occurring on campuses and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City Government officials developed a School-based Infectious Disease Syndromic Surveillance System (SID-SSS). Teachers and nurses from preschools to universities in all 12 districts within Taipei are required to daily report cases of symptomatic children or sick leave requests through the SID-SSS. The pre-diagnosis at schools is submitted firstly as common pediatric disease syndrome-groups and re-submitted after confirmation by physicians. We retrieved these data from January 2010 to August 2011 for spatio-temporal analysis and evaluated the temporal trends with cases obtained from both the Emergency Department-based Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and influenza-like illness (ILI) were the two most reported syndrome groups (77.6% and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis judgments made by school teachers and nurses showed high consistency with physicians' clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly, the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance systems had the best correlation reaching 0.98 and 0.95, respectively (p<0.01). Spatio-temporal analysis observed the patterns of EVI and ILI both diffuse from the northern suburban districts to central Taipei, with ILI spreading faster. This novel system can identify early suspected cases of two important pediatric infections occurring at schools, and clusters from schools/families. It was also cost-effective (95.5% of the operation cost reduced and 59.7% processing time saved). The timely surveillance of mild EVI and ILI cases integrated with spatial analysis may help public health decision-makers with where to target for enhancing surveillance and prevention measures to minimize severe cases.


Assuntos
Diagnóstico Precoce , Infecções por Enterovirus/diagnóstico , Influenza Humana/diagnóstico , Vigilância da População/métodos , Análise Custo-Benefício , Diarreia/diagnóstico , Diarreia/epidemiologia , Surtos de Doenças/economia , Surtos de Doenças/prevenção & controle , Enterovirus/fisiologia , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Docentes/estatística & dados numéricos , Geografia , Interações Hospedeiro-Patógeno , Humanos , Incidência , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Enfermeiras e Enfermeiros/estatística & dados numéricos , Instituições Acadêmicas/estatística & dados numéricos , Estações do Ano , Análise Espaço-Temporal , Síndrome , Taiwan/epidemiologia , Universidades/estatística & dados numéricos
14.
Pediatr Crit Care Med ; 16(2): 119-23, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25647121

RESUMO

OBJECTIVES: To investigate the impact of human rhino/enteroviruses on morbidity and mortality outcomes in children with severe viral respiratory infection. DESIGN: Retrospective cohort study. SETTING: The ICU, either PICU or cardiac ICU, at three urban academic tertiary-care children's hospitals. PATIENTS: All patients with laboratory-confirmed human rhino/enteroviruses infection between January 2010 and June 2011. INTERVENTIONS: We captured demographic and clinical data and analyzed associated morbidity and mortality outcomes. MEASUREMENTS AND MAIN RESULTS: There were 519 patients included in our analysis. The median patient age was 2.7 years. The median hospital and ICU lengths of stay were 4 days and 2 days, respectively. Thirty-four percent of patients had a history of asthma, and 25% of patients had a chronic medical condition other than asthma. Thirty-two percent of patients required mechanical ventilation. Eleven patients (2.1%) did not survive to hospital discharge. The rate of viral coinfection was 12.5% and was not associated with mortality. Predisposing factors associated with increased mortality included immunocompromised state (p < 0.001), ICU admission severity of illness score (p < 0.001), and bacterial coinfection (p = 0.003). CONCLUSIONS: There is substantial morbidity associated with severe respiratory infection due to human rhino/enteroviruses in children. Mortality was less severe than reported in other respiratory viruses such as influenza and respiratory syncytial virus. The burden of illness from human rhino/enteroviruses in the ICU in terms of resource utilization may be considerable.


Assuntos
Enterovirus , Infecções por Picornaviridae/mortalidade , Infecções Respiratórias/mortalidade , Rhinovirus , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Efeitos Psicossociais da Doença , Cuidados Críticos/estatística & dados numéricos , District of Columbia/epidemiologia , Enterovirus/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/mortalidade , Infecções por Enterovirus/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Maryland/epidemiologia , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/terapia , Respiração Artificial/estatística & dados numéricos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/terapia , Estudos Retrospectivos , Rhinovirus/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento
15.
J Clin Virol ; 62: 58-62, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25542472

RESUMO

BACKGROUND: Enterovirus (EV) is the most frequent cause of aseptic meningitis (AM). Lack of microbiological documentation results in unnecessary antimicrobial therapy and hospitalization. OBJECTIVES: To assess the impact of rapid EV detection in cerebrospinal fluid (CSF) by a fully-automated PCR (GeneXpert EV assay, GXEA) on the management of AM. STUDY DESIGN: Observational study in adult patients with AM. Three groups were analyzed according to EV documentation in CSF: group A = no PCR or negative PCR (n=17), group B = positive real-time PCR (n = 20), and group C = positive GXEA (n = 22). Clinical, laboratory and health-care costs data were compared. RESULTS: Clinical characteristics were similar in the 3 groups. Median turn-around time of EV PCR decreased from 60 h (IQR (interquartile range) 44-87) in group B to 5h (IQR 4-11) in group C (p<0.0001). Median duration of antibiotics was 1 (IQR 0-6), 1 (0-1.9), and 0.5 days (single dose) in groups A, B, and C, respectively (p < 0.001). Median length of hospitalization was 4 days (2.5-7.5), 2 (1-3.7), and 0.5 (0.3-0.7), respectively (p < 0.001). Median hospitalization costs were $5458 (2676-6274) in group A, $2796 (2062-5726) in group B, and $921 (765-1230) in group C (p < 0.0001). CONCLUSIONS: Rapid EV detection in CSF by a fully-automated PCR improves management of AM by significantly reducing antibiotic use, hospitalization length and costs.


Assuntos
Infecções por Enterovirus/líquido cefalorraquidiano , Infecções por Enterovirus/virologia , Enterovirus/genética , Meningite Asséptica/líquido cefalorraquidiano , Meningite Asséptica/virologia , Adulto , Gerenciamento Clínico , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/tratamento farmacológico , Feminino , Hospitalização , Humanos , Masculino , Meningite Asséptica/diagnóstico , Meningite Asséptica/tratamento farmacológico , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/métodos , RNA Viral/genética , Adulto Jovem
17.
J Virol Methods ; 179(2): 330-4, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22155579

RESUMO

Reverse transcription loop-mediated isothermal amplification (RT-LAMP), which is a visual assay for nucleic acids, is performed in a single step using one tube at 65 °C for 1.5 h. In this study, RT-LAMP was established as a method for the detection of enterovirus 71 (EV71). The detection limit of the assay was approximately 10 copies, and no cross-reactivity was noted with Coxsackievirus A16, echovirus, human rotavirus (HRV) or norovirus. This assay, which offers greater sensitivity at a lower cost compared with the conventional reverse transcription polymerase chain reaction (RT-PCR), was validated using 252 clinical specimens that had been confirmed by laboratory diagnosis using RT-PCR. Both methods produced the same results with 52 positive samples. The RT-LAMP-based assay does not require specialised equipment, and therefore, it can be performed conveniently during an outbreak or under field conditions. In brief, the RT-LAMP-based assay provided a simple, rapid and efficient method for the detection of EV71 nucleic acid under field conditions.


Assuntos
Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Virologia/métodos , Adolescente , Criança , Pré-Escolar , Infecções por Enterovirus/virologia , Humanos , Lactente , Técnicas de Diagnóstico Molecular/economia , Sensibilidade e Especificidade , Temperatura , Virologia/economia
18.
J Clin Microbiol ; 49(10): 3591-5, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21865426

RESUMO

Three armored RNAs (virus-like particles [VLPs]) containing target sequences from enterovirus 71 (EV71) and coxsackievirus A16 (CA16) and a pan-enterovirus (pan-EV) sequence were constructed and used in an external quality assessment (EQA) to determine the performance of laboratories in the detection of EV71 and CA16. The EQA panel, which consisted of 20 samples, including 14 positive samples with different concentrations of EV and either EV71 or CA16 armored RNAs, 2 samples with all 3 armored RNAs, and 4 negative-control samples (NaN(3)-preserved minimal essential medium [MEM] without VLPs), was distributed to 54 laboratories that perform molecular diagnosis of hand, foot, and mouth disease (HFMD) virus infections. A total of 41 data sets from 41 participants were returned; 5 (12.2%) were generated using conventional in-house reverse transcription-PCR (RT-PCR) assays, and 36 (87.8%) were generated using commercial real-time RT-PCR assays. Performance assessments of laboratories differed; 12 (29.3%) showed a need for improvement. Surprisingly, 4 laboratories were unable to detect EV71 RNA in any samples, even those containing the highest concentration of 10(7) IU/ml. Furthermore, the detection sensitivity for EV71 among all laboratories (82.1%) was substantially lower than that for EV (97.4%) or CA16 (95.1%). Overall, the results of the present study indicate that EQA should be performed periodically to help laboratories monitor their ability to detect HFMD viruses and to improve the comparability of results from different laboratories.


Assuntos
Infecções por Enterovirus/diagnóstico , Enterovirus/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Padrões de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Enterovirus/classificação , Enterovirus/genética , Humanos , RNA/genética , Virologia/métodos , Virologia/normas
19.
J Virol Methods ; 175(2): 283-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21621554

RESUMO

A sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for rapid visual detection of human enterovirus 71 subgenotype C4 (EV71-C4) and Coxsackievirus A16 (CVA16) infection, respectively. The reaction was performed in one step in a single tube at 65°C for 60 min with the addition of the hydroxynaphthol blue (HNB) dye prior to amplification. The detection limits of the RT-LAMP assay were 0.33 and 1.58 of a 50% tissue culture infective dose (TCID(50)) per reaction based on 10-fold dilutions of a titrated EV71 or CVA16 strain, respectively. No cross-reaction was observed with Coxsackievirus A (CVA) viruses (CVA2, 4, 5, 7, 9, 10, 14, and 24), Coxsackievirus B (CVB) viruses (CVB1,2,3,4, and 5) or ECHO viruses (ECHO3, 6, 11, and 19). The assay was further evaluated with 47 clinical stool specimens diagnosed previously with EV71, CVA16 or other human enterovirus infections. Virus isolates from stool samples were confirmed by virus neutralization testing and sequencing. RT-LAMP with HNB dye was demonstrated to be a sensitive and cost-effective assay for rapid visual detection of human EV71-C4 and CVA16.


Assuntos
Infecções por Coxsackievirus/diagnóstico , Infecções por Enterovirus/diagnóstico , Enterovirus/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Coloração e Rotulagem/métodos , Enterovirus/genética , Fezes/virologia , Humanos , Técnicas de Diagnóstico Molecular/economia , Naftalenossulfonatos/metabolismo , Técnicas de Amplificação de Ácido Nucleico/economia , Sensibilidade e Especificidade , Coloração e Rotulagem/economia
20.
Clin Microbiol Infect ; 16(6): 651-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20015267

RESUMO

Enteroviruses are frequent aetiological agents of central nervous system infections in humans. In 2000 and 2005, two large outbreaks of Echovirus 30 (a member of species human enterovirus B) were observed in the University Hospitals of Marseilles (France). Between the two epidemics, the diagnostic protocols for enterovirus infection were modified, moving from viral cultures and classic RT-PCR in 2000 to real-time RT-PCR in 2005. We compared some viral and epidemiological characteristics of the 2000 and 2005 outbreaks with special attention to diagnostic procedures and to the subsequent clinical management of patients. Despite similar virological and epidemiological characteristics during both outbreaks, our results show that real-time RT-PCR techniques used in 2005 noticeably shortened the period of time necessary to deliver diagnostic results and suggest that this was associated with a decrease in the duration of hospitalization for positive cases. In conclusion, this study suggests that the improvement of enterovirus diagnosis had a major financial impact on the management of the 2005 epidemic in Marseilles and may constitute an interesting example of how new diagnostic methods in microbiology can be self-financed through improvement in patient management.


Assuntos
Técnicas de Laboratório Clínico/métodos , Surtos de Doenças , Infecções por Enterovirus/diagnóstico , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Reação em Cadeia da Polimerase/métodos , Virologia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Técnicas de Laboratório Clínico/economia , Infecções por Enterovirus/economia , Infecções por Enterovirus/terapia , Feminino , França/epidemiologia , Hospitalização/economia , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/economia , Fatores de Tempo , Virologia/economia , Adulto Jovem
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