Características clínico-etiológicas de pacientes pediátricos hospitalizados con diagnóstico de bronquiolitis. Ciudad de Santa Fe, Argentina

Introducción: La bronquiolitis constituye una de las principales causas de Infecciones Respiratorias Agudas Bajas en Pediatría, y es responsable de una proporción significativa de hospitalizaciones en lactantes, fundamentalmente, en menores de 1 año. Su diagnóstico es clínico, caracterizado por síntomas y signos de amplio grado de gravedad. Objetivo: Describir las características clínico-etiológicas de casos de bronquiolitis en menores de 1 año, internados en un hospital de niños de la ciudad de Santa Fe, durante un periodo de un año. Materiales y Métodos: Estudio observacional, transversal. Se analizaron datos demográficos, clínicos y de laboratorio de fichas médicas de vigilancia epidemiológica. Las técnicas diagnósticas usadas según el agente viral fueron RT-PCR en tiempo real, PCR-punto final e Inmunofluorescencia Indirecta. Resultados: Sobre un total de 108 casos, 90,7% tuvo de 1 a 6 meses de edad. La mediana de internación fue de 5 días, y el nacimiento prematuro fue la condición médica previa más frecuente. Un 78,7% (85) tuvo diagnóstico viral positivo, siendo Rinovirus (hRV) y Virus Sincicial Respiratorio (VSR) los agentes más prevalentes, tanto en infección única como en coinfección. El tiempo de oxigenoterapia fue mayor en los pacientes más graves (p<0,001). El 32,4% (35) recibió alguna medicación que fue, en mayor frecuencia, antibiótico. Se encontró asociación positiva y significativa entre la edad menor de 3 meses y una hospitalización mayor a 5 días (OR=2,5; IC: 1,1-5,8; p=0,02); y entre un diagnóstico VSR positivo y un cuadro grave (OR: 7,7; IC: 1,95-39,6; p<0,001). Conclusión: Las características y condiciones médicas consideradas por la literatura como factores de riesgo para el padecimiento y la gravedad de una IRAB, fueron halladas con mayor frecuencia en la población de estudio. El hRV y el VRS fueron los agentes de mayor rescate viral, encontrándose una asociación positiva entre la infección por VSR y la gravedad del cuadro.

Introduction: Bronchiolitis is one of the main causes of Acute Lower Respiratory Infections in pediatrics, and is responsible for a significant proportion of hospitalizations in infants, mainly in children under 1 year of age. Its diagnosis is clinical. The disease is characterized by a wide variety and degree of signs and symptoms. Objective: To describe the clinical-etiological characteristics of cases of bronchiolitis in children under 1 year of age, admitted to a children's hospital in the city of Santa Fe, over a period of one year. Materials and Methods: This was an observational and cross-sectional study. Demographic, clinical and laboratory data from epidemiological surveillance medical records were analyzed. The diagnostic techniques used, based on the viral agent, were real-time RT-PCR, end-point PCR and Indirect Immunofluorescence. Results: Out of a total of 108 cases, 90.7% were between 1 and 6 months old. The median hospital stay was 5 days, and premature birth was the most common prior medical condition. 78.7% (85) had a positive viral diagnosis, with Rhinovirus (hRV) and Respiratory Syncytial Virus (RSV) being the most prevalent agents, both in single infection and coinfection. Oxygen therapy time was longer in the most seriously ill patients (p<0.001). 32.4% (35) received some medication, which was, most frequently, antibiotics. A positive and significant association was found between age less than 3 months and hospitalization longer than 5 days (OR=2.5; CI: 1.1-5.8; p=0.02); and between a positive RSV diagnosis and a severe condition (OR: 7.7; CI: 1.95-39.6; p<0.001). Conclusions: The characteristics and medical conditions considered by the literature as risk factors for the morbidity and severity of a lower respiratory tract infection were found more frequently in the study population. hRV and RSV were the most commonly-detected viral agents. We found a positive association between RSV infection and the severity of the condition.

Rinovirus y metapneumovirus en pacientes con infección respiratoria aguda grave / Rhinovirus and metapneumovirus in patients with severe acute respiratory infection

Introducción. Los virus son los principales agentes etiológicos en las infecciones respiratorias agudas graves; un alto porcentaje queda sin diagnóstico viral. Objetivo. Describir la frecuencia de rinovirus y metapneumovirus en pacientes pediátricos de una unidad centinela de Mar del Plata con infección respiratoria aguda grave y resultado negativo para virus clásicos por inmunofluorescencia y biología molecular. Población y métodos. Se realizó un estudio descriptivo de corte transversal. Se evaluó la presencia de rinovirus y metapneumovirus por biología molecular en 163 casos negativos para panel respiratorio por técnicas de vigilancia referencial, durante todo el año 2015. Resultados. Se detectó rinovirus en el 51,5 % de los casos, metapneumovirus en el 9,8 % y coinfección rinovirus-metapneumovirus en el 6,1 %. Fueron negativos para ambos virus el 32,5 %. Conclusiones. La selección de muestras sin diagnóstico virológico permitió identificar rinovirus y metapneumovirus como agentes causales de infecciones respiratorias agudas graves pediátricas y su impacto en la morbimortalidad infantil y en nuestro sistema sanitario.

Introduction. Viruses are the main etiologic agents involved in severe acute respiratory tract infections; a viral diagnosis is not established in a high percentage of cases. Objective. To describe the frequency of rhinovirus and metapneumovirus in pediatric patients with severe acute respiratory infection and negative results for typical viruses by immunofluorescence and molecular biology at a sentinel unit of Mar del Plata. Population and methods. This was a descriptive, cross-sectional study. The presence of rhinovirus and metapneumovirus was assessed by molecular biology in 163 cases negative for respiratory panel by referral surveillance techniques throughout 2015. Results. Rhinovirus was detected in 51.5% of cases, metapneumovirus in 9.8%, and coinfection with rhinovirus and metapneumovirus in 6.1%. Results were negative for both viruses in 32.5%. Conclusions. The selection of samples without a viral diagnosis allowed us to identify rhinovirus and metapneumovirus as causative agents of severe acute respiratory infections in children and assess their impact on child morbidity and mortality and on our health care system

Rinovirus en pandemia. Ciudad de Santa Fe, Argentina. Bienio 2020-2021 / Rhinovirus in pandemic. Santa Fe city, Argentina. Biennium 2020-2021

En el contexto de la pandemia de COVID-19, a partir de 2020, la Unidad Centinela de Enfermedades Tipo Influenza (UC-ETI) (Santa Fe, Argentina) integró la vigilancia clínica y por laboratorio de SARS-CoV-2 y rinovirus (HRV) a la habitual vigilancia de influenza y otros virus respiratorios (OVR). El objetivo de este estudio transversal y retrospectivo fue describir las características clínico-epidemiológicas de casos de ETI de la ciudad de Santa Fe, con diagnóstico de HRV confirmado durante 2020-2021, en el marco de la UC-ETI. Del total de 600 casos de ETI cuyas muestras fueron analizadas, más del 50,0% fueron mujeres; y la mayor proporción se concentró en el grupo de 15 a 39 años (40,2%). El 33,7% registró al menos una comorbilidad o factor de riesgo, siendo la hipertensión arterial, asma, diabetes, obesidad y EPOC las más frecuentes. Además de fiebre y tos, los signos/síntomas predominantes fueron odinofagia, mialgia y cefalea. El porcentaje de positividad fue de 41,3% en 2020, 27,8% en 2021 y 35,5% en 2020-2021. De las muestras positivas del bienio (213), 59,0% fue SARS-CoV-2, 40,0% HRV y 1,0% OVR. La mayor proporción de diagnósticos positivos de SARS-CoV-2 se concentró en pacientes de 15 años y más, y la de HRV en menores de 15. Los periodos en los que predominó la circulación de HRV no lo hizo la de SARS-CoV-2, y viceversa. El aporte a la carga real de las infecciones virales respiratorias y su impacto en la salud pública destaca la importancia de sostener la vigilancia de HRV

In the context of the COVID-19 pandemic, in 2020, the influenza-like illness Sentinel Unit (ILI-SU) (Santa Fe, Argentina), integrated clinical and laboratory surveillance of SARS-CoV-2 and Rhinovirus (HRV) to the usual surveillance of Influenza and other respiratory viruses (ORV). The objective of this cross-sectional and retrospective study was to describe the clinical-epidemiological characteristics of ILI cases of Santa Fe city, who had a confirmed HRV diagnosis during 2020-2021, by the ILI-SU. Of a total of 600 ILI cases whose samples were analyzed, more than 50.0% were women; and the highest proportion was concentrated in the group between 15 and 39 years of age (40.2%). 33.7% of the cases registered at least one comorbidity or risk factor, among which arterial hypertension, asthma, diabetes, obesity and COPD were the most frequent. In addition to fever and cough, the predominant signs/symptoms were sore throat, myalgia and headache. The percentage of positivity was 41.3% in 2020, 27.8% in 2021, and 35.5% in 2020-2021. Of the biennium positive samples (213), 59.0% were SARS-CoV-2, 40.0% HRV, and 1.0% ORV. The highest proportion of SARS-CoV-2 positive diagnoses were concentrated in patients 15 years of age and older, while the highest proportion of HRV positive diagnoses were concentrated in patients under 15 years of age. The periods in which the circulation of HRV predominated did not predominated SARS-CoV-2, and vice versa. The contribution to the real burden of respiratory viral infections and its impact on public health, highlight the importance of sustaining HRV surveillance

COVID-19, rinovirus y asma... ¿Una mala combinación? / COVID-19, rhinovirus and asthma... a bad conmbination?

La pandemia de COVID-19 enfrentó a la humanidad a un gran desafío y hemos ido aprendiendo a medida que avanzó. La aparición de este virus, su comportamiento por si solo y en conjunto con los otros virus nos mantuvo alerta.. Los pacientes pediátricos asmáticos, a pesar de lo que se pensó en un principio, son menos afectados y hacen un cuadro clínico más leve. Objetivo: presentar un caso clínico de un paciente asmático, con una evolución tortuosa por co-infección SARS-CoV-2 y Rinovirus (RV) y revisión de la litaratura. Se trata de un escolar de 6 años, asmático con mal control, con 2 dosis de vacuna anti SARS-CoV-2, que presento un estado asmático por rinovirus y posterior evolución con neumonía grave por SARS-CoV-2, requiriendo ventilación mecánica invasiva y estadía en UCI Pediátrica. Es probable que la gravedad del caso presentado se deba al mal control del asma antes de la infección, ya que se ha visto que los niños asmáticos alérgicos presentan un factor protector para infección grave por SARS-CoV-2, lo cual esta supeditado a un buen control de su enfermedad basal.

The COVID-19 pandemic presented a great challenge and we have been learning as it has progressed. The appearance of this virus, its behavior by itself and in conjunction with the other viruses kept us alert. Pediatric asthmatic patients, despite what was initially thought, are less affected and present a milder clinical picture. Objective: to present a clinical case of an asthmatic patient, with a tortuous evolution due to SARS-CoV-2 and Rhinovirus (RV) co-infection and a literature review. This is a 6-year-old schoolboy, asthmatic with poor control, with 2 doses of the SARS-CoV-2 vaccine, who presents asthmatic status due to rhinovirus and subsequent evolution with severe pneumonia due to SARS-CoV-2, requiring invasive mechanical ventilation and stay in Pediatric ICU. It is likely that the severity of the case presented is due to poor asthma control before infection, since it has been seen that allergic asthmatic children present a protective factor for severe infection by SARS-CoV-2, which is subject to good control of his basal disease.

Acute bronchiolitis during the COVID-19 pandemic.

INTRODUCTION: The autumn and winter bronchiolitis epidemics have virtually disappeared in the first year of the COVID-19 pandemic. Our objectives were characterised bronchiolitis during fourth quarter of 2020 and the role played by SARS-CoV-2. METHODS: Prospective multi-centre study performed in Madrid (Spain) between October and December 2020 including all children admitted with acute bronchiolitis. Clinical data were collected and multiplex PCR for respiratory viruses were performed. RESULTS: Thirty-three patients were hospitalised with bronchiolitis during the study period: 28 corresponded to rhinovirus (RV), 4 to SARS-CoV-2, and 1 had both types of infection. SAR-CoV-2 bronchiolitis were comparable to RV bronchiolitis except for a shorter hospital stay. A significant decrease in the admission rate for bronchiolitis was found and no RSV was isolated. CONCLUSION: SARS-CoV-2 infection rarely causes acute bronchiolitis and it is not associated with a severe clinical course. During COVID-19 pandemic period there was a marked decrease in bronchiolitis cases.

Bronquiolitis por rinovirus en menores de 1 año y riesgo de sibilancias recurrentes y asma

RESUMEN Introducción: La Bronquiolitis se ha asociado a sibilancias recurrentes. Objetivo: analizar la incidencia de sibilancias recurrentes, hospitalizaciones y atopia/asma en pacientes con antecedentes de hospitalización por bronquiolitis por RV antes de los 12 meses de edad. Materiales y Métodos: estudio de cohorte retrospectiva. Ingresaron pacientes de 2 a 4 años con sibilancias recurrentes y antecedentes de hospitalización por bronquiolitis antes de los 12 meses de edad, con retorno viral positivo por estudio molecular. Fueron estudiados los datos demográficos, hospitalizaciones, atopia personal y familiar, asma y exposición al humo. Los datos fueron analizados en SPSS utilizando estadísticas descriptivas e inferenciales. Los resultados se expresaron en RR con IC 95%. El protocolo fue aprobado por el comité de ética institucional. Resultados: Ingresaron 120 pacientes. No hubo diferencias en la incidencia de sibilancias recurrentes en el grupo expuesto y el control50,9% vs 49% respectivamente p=0,85. Las hospitalizaciones por sibilancias y la presencia de atopia fueron más frecuentes en el grupo Rinovirus, RR=1,7 (IC 95% 1,2 -2,9) p=0,03 y RR 1,6 (IC 95% 1,2 -2,2) p= 0,005 respectivamente. Conclusiones: la incidencia de sibilancias recurrentes fue similar en ambas cohortes. Las hospitalizaciones por sibilancias y la atopia/asma fue mayor en el grupo Rinovirus.

ABSTRACT Introduction: Bronchiolitis has been associated with recurrent wheezing. Objective: to analyze the incidence of recurrent wheezing, hospitalizations and atopy / asthma in patients with a history of hospitalization for rhinovirus (RV) bronchiolitis before 12 months of age. Materials and Methods: this was a retrospective cohort study. We included patients aged 2 to 4 years with recurrent wheezing and a history of hospitalization for bronchiolitis before 12 months of age, with a positive viral testing by molecular study. Demographic data, hospitalizations, personal and family history of atopy, asthma and exposure to smoke were studied. The data were analyzed in SPSS using descriptive and inferential statistics. The results were expressed in RR with 95% CI. The protocol was approved by the institutional ethics committee. Results: 120 patients were included. There were no differences in the incidence of recurrent wheezing in the exposed and control groups, 50.9% vs 49%, respectively, p = 0.85. Hospitalizations for wheezing and the presence of atopy were more frequent in the Rhinovirus group, RR = 1.7 (95% CI 1.2 -2.9) p = 0.03 and RR 1.6 (95% CI 1, 2 -2.2) p = 0.005 respectively. Conclusions: the incidence of recurrent wheezing was similar in both cohorts. Hospitalizations for wheezing and atopy / asthma were higher in the Rhinovirus group.

Acute bronchiolitis during the COVID-19 pandemic.

INTRODUCTION: The autumn and winter bronchiolitis epidemics have virtually disappeared in the first year of the COVID-19 pandemic. Our objectives were characterised bronchiolitis during fourth quarter of 2020 and the role played by SARS-CoV-2. METHODS: Prospective multi-centre study performed in Madrid (Spain) between October and December 2020 including all children admitted with acute bronchiolitis. Clinical data were collected and multiplex PCR for respiratory viruses were performed. RESULTS: Thirty-three patients were hospitalised with bronchiolitis during the study period: 28 corresponded to rhinovirus (RV), 4 to SARS-CoV-2, and 1 had both types of infection. SAR-CoV-2 bronchiolitis were comparable to RV bronchiolitis except for a shorter hospital stay. A significant decrease in the admission rate for bronchiolitis was found and no RSV was isolated. CONCLUSION: SARS-CoV-2 infection rarely causes acute bronchiolitis and it is not associated with a severe clinical course. During COVID-19 pandemic period there was a marked decrease in bronchiolitis cases.

Respiratory pathogens in infants less than two months old hospitalized with acute respiratory infection.

Lower acute respiratory infections (ARI) are a frequent cause of morbidity and mortality in infants, respiratory viruses being the major causative agents. The aim of this work was to determine the respiratory pathogen frequency, the clinical characteristics and the outcome in infants <2 months old hospitalized with ARI. A retrospective study was performed during a five-year period (2008-2011, 2014-2016). Respiratory viruses and atypical bacteria were studied using the FilmArray-Respiratory Panel. Demographic and clinical characteristics, hospitalization course and outcomes were evaluated. Of the 137 infants <2 months old hospitalized with ARI studied, a 94.9% positivity rate as determined in 117 infants with community-acquired infection and 20.0% in 20 infants who acquired the infection during their birth hospitalization in the neonatal intensive care units (NICU) (nosocomial ARI) (p<0.001). In infants with community-acquired infection, Respiratory syncytial virus (RSV) (52.1%) and Rhinovirus/Enterovirus (RV/EV) (41.0%) were the most frequent detected pathogens. Coinfections were determined in one quarter of the infants, RSV-RV/EV being the most frequent combination. In infants with nosocomial infection, RV/EV, RSV or Parainfluenza-3 were detected as single pathogens. Most infants with community-acquired infection presented lower ARI (81.2%) while most infants in the NICU had upper ARI (55.0%). The median length of stay (LOS) in infants with community-acquired ARI was 4 days (IQR: 2-6). Positive infants with nosocomial infection had longer median LOS (71 days [IQR:42-99]) compared to negative infants (58 days [IQR: 49-71]) (p=0.507). Respiratory viruses were detected as the major causative agents of community-acquired infection in hospitalized infants <2-months old, RSV and RV/EV being the most frequently detected. Although a low pathogen positivity rate was observed in infants with nosocomial infection, they may prolong the LOS.

Virus más frecuentemente aislados en la exacerbación de asma y su correlación con nivelesde eosinófilos e inmunoglobulina E sérica total / Most commonly isolated viruses in asthma exacerbation and their correlation with eosinophil and total serum immunoglobulin E levels

Antecedentes. Las exacerbaciones de asma continúan siendo una causa de hospitalización en el Servicio de Urgencias. Los desencadenantesson alérgenos e infecciones, principalmente, de tipo viral. El objetivo fue determinar la relación entre los virus detectados durante la exacerbación asmática y los niveles de eosinófilos e inmunoglobulina E (IgE) sérica en pacientes pediátricos. Población y métodos. Estudio transversal analítico. Se incluyeron niños de cinco a quince años atendidos en Urgencias de Pediatría con exacerbación de asma, en el período de marzo de 2013 a febrero de 2016. Se obtuvo ácido ribonucleico viral en el aspirado nasofaríngeo con el kit CLART PneumoVir. Se cuantificaron los eosinófilos en la sangre periférica y los niveles de IgE sérica total. Se consideró eosinofilia un conteo ≥ 0,4 x 103/mm3 e IgE elevada, ≥ 350 UI/L. Se realizó la correlación de Pearson. Se definió significancia con valor de p ≤ 0,05.Resultados. De 211 niños con exacerbación de asma, en el 20%, se aisló un virus. Los virus aislados más frecuentemente fueron el rinovirus, el enterovirus y el virus sincitial respiratorio. Se encontró una correlación entre los niveles de eosinófilos e IgE sérica total en los niños con exacerbación de asma y rinovirus de 0,89, con una p= 0,0001.Conclusiones. Las infecciones por rinovirus, enterovirus y virus sincitial respiratorio son más frecuentes en las exacerbaciones de asma en menores de 15 años. Se observó una correlación entre los niveles de eosinófilos e IgE en presencia de rinovirus.

Background. Asthma exacerbations are still a cause of hospitalization at the Emergency Department. The triggers of asthma exacerbations include allergens and infections ­mostly viral­. The objective of this study was to establish the relationship between viruses detected during an asthma exacerbation and eosinophil and serum immunoglobulin E (IgE) levels in pediatric patients. Population and methods. Cross-sectional. analytical study. Children aged 5-15 years seen at the Pediatric Emergency Department with an asthma exacerbation in the period between March 2013 and February 2016 were included. Viral ribonucleic acid was extracted from nasopharyngeal aspirates using the CLART Pneumo Vir kit. Eosinophil levels were measured in peripheral blood and total IgE levels, in serum. Eosinophilia was defined as a count ≥ 0.4 x 103/mm3 and high IgE. as a level ≥ 350 IU/L. The Pearson's correlation was carried out. A value of p ≤ 0.05 was considered significant.Results. Out of 211 children with asthma exacerbation, a virus was isolated in 20%. The most commonly isolated viruses were rhinovirus. enterovirus, and respiratory syncytial virus. A correlation of 0.89 was established between eosinophil and total serum IgE levels in children with asthma exacerbation and rhinovirus, with a p value of 0.0001. Conclusions. Rhinovirus, enterovirus, and respiratory syncytial virus were the most common viruses in asthma exacerbations in children younger than 15 years. A correlation was established between eosinophil and IgE levels in the presence of rhinovirus.

Papel de las infecciones virales en el asma / The role of viral infections in asthma

Respiratory viral infections have been implicated in the origin and exacerbation of asthma symptoms in a variety of ways. A growing body of evidence indicates that viral infections are closely linked to infantile wheezing and suggest that severe bronchiolitis in early infancy may predispose to chronic childhood asthma. Alternatively, it could represent a marker of susceptible individuals. In contrast, mild repetitive infections in early years may provide a protective role against the development of asthma or atopy by switching the immune system towards Th1 responses. However, evidence on this hypothesis is not consistent as far as viruses are concerned. On the other hand, in the presence of asthma, the role of viral infections on exacerbations is well established. Several factors, such as the presence of atopy, timing of the exposure and severity of the infections, interactively contribute to the asthma-infection relationship. In the present report, recent data on the involvement of viral infections in the development and progression of asthma are reviewed

Las infecciones virales respiratorias han sido involucradas en el origen y en las exacerbaciones de los síntomas del asma en una variedad de formas. Cada vez hay más indicios de que las infecciones virales están estrechamente relacionadas con sibilancias en la niñez y sugieren que la bronquiolitis grave en la primera infancia puede predisponer a asma crónica infantil; por otra parte, podría representar un marcador de individuos susceptibles. Por el contrario, las infecciones leves repetidas en los primeros años brindarían un efecto protector contra la aparición de asma o atopia mediante la desviación del sistema inmunitario hacia respuestas Th1. Sin embargo, la información relacionada con esta hipótesis no es firme en lo que a virus se refiere. Por otra parte, en presencia de asma, el papel de las infecciones virales sobre las exacerbaciones está bien establecido. Varios factores, como la presencia de atopia, el momento en el que se produce la exposición y la gravedad de las infecciones, interactúan en la relación entre asma e infección. En este artículo se revisan datos acerca de la participación de las infecciones virales en la aparición y progresión del asma

Impact and seasonality of human rhinovirus infection in hospitalized patients for two consecutive years / Impacto e sazonalidade da infecção por rinovírus humano em pacientes internados por dois anos consecutivos

Abstract Objectives: To report epidemiological features, clinical characteristics, and outcomes of human rhinovirus (HRV) infections in comparison with other community acquired respiratory virus (CRV) infections in patients hospitalized for two consecutive years. Methods: This was a cross-sectional study. Clinical, epidemiological, and laboratory data of patients hospitalized with acute respiratory syndrome in a tertiary care hospital from 2012 to 2013 were reviewed. Results: HRV was the most common CRV observed (36%, 162/444) and was present in the majority of viral co-detections (69%, 88/128), mainly in association with human enterovirus (45%). Most HRV-infected patients were younger than 2 years (57%). Overall, patients infected with HRV had a lower frequency of severe acute respiratory infection than those infected with other CRVs (60% and 84%, respectively, p = 0.006), but had more comorbidities (40% and 27%, respectively; p = 0.043). However, in the adjusted analysis this association was not significant. The mortality rate within the HRV group was 3%. Detection of HRV was more prevalent during autumn and winter, with a moderately negative correlation between viral infection frequency and temperature (r = −0.636, p < 0.001) but no correlation with rainfall (r = −0.036, p = 0.866). Conclusion: HRV is usually detected in hospitalized children with respiratory infections and is often present in viral co-detections. Comorbidities are closely associated with HRV infections. These infections show seasonal variation, with predominance during colder seasons.

Resumo Objetivos: Relatar as características epidemiológicas, as características clínicas e os resultados das infecções por rinovírus humano (RVH) em comparação a outras infecções por vírus respiratórios adquiridos na comunidade (VRCs) em pacientes internados por dois anos consecutivos. Métodos: Este foi um estudo transversal. Foram revisados os dados clínicos, epidemiológicos e laboratoriais de pacientes internados com síndrome respiratória aguda em um hospital terciário de 2012 a 2013. Resultados: O RVH foi o VRC mais comum observado (36%, 162/444) e esteve presente na maior parte das codetecções virais (69%, 88/128), principalmente em associação ao enterovírus humano (45%). A maioria dos pacientes infectados por RVH possuía menos de 2 anos (57%). De modo geral, os pacientes com RVH apresentaram uma menor frequência de infecção respiratória aguda grave que os pacientes infectados por outros VRCs (60% e 84%, respectivamente, p = 0,006), porém mais comorbidades (40% e 27%, respectivamente; p = 0,043). Contudo, em uma análise ajustada, essa associação não foi significativa. A taxa de mortalidade no grupo RVH foi 3%. A detecção de RVH foi mais prevalente durante o outono e inverno, com uma correlação negativa moderada entre a frequência de infecção viral e a temperatura (r = -0,636, p < 0,001), porém nenhuma correlação com a precipitação (r = −0,036, p = 0,866). Conclusão: O RVH é normalmente detectado em crianças internadas com infecções respiratórias e normalmente está presente em codetecções virais. As comorbidades estão estreitamente associadas a infecções por RVH. Essas infecçõesmostram variação sazonal, com predominância durante as estações mais frias.

[Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing]. / Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias.

INTRODUCTION: It is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing. PATIENTS AND METHODS: A total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses. RESULTS: A total of 1,293 samples were analysed (1,005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, P<.001 (OR: 3, 95% CI: 2.4-3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, P<.001 (OR: 2.18; 95% CI: 1.05-4.5). CONCLUSIONS: In our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections.

Impact and seasonality of human rhinovirus infection in hospitalized patients for two consecutive years.

OBJECTIVES: To report epidemiological features, clinical characteristics, and outcomes of human rhinovirus (HRV) infections in comparison with other community acquired respiratory virus (CRV) infections in patients hospitalized for two consecutive years. METHODS: This was a cross-sectional study. Clinical, epidemiological, and laboratory data of patients hospitalized with acute respiratory syndrome in a tertiary care hospital from 2012 to 2013 were reviewed. RESULTS: HRV was the most common CRV observed (36%, 162/444) and was present in the majority of viral co-detections (69%, 88/128), mainly in association with human enterovirus (45%). Most HRV-infected patients were younger than 2 years (57%). Overall, patients infected with HRV had a lower frequency of severe acute respiratory infection than those infected with other CRVs (60% and 84%, respectively, p=0.006), but had more comorbidities (40% and 27%, respectively; p=0.043). However, in the adjusted analysis this association was not significant. The mortality rate within the HRV group was 3%. Detection of HRV was more prevalent during autumn and winter, with a moderately negative correlation between viral infection frequency and temperature (r=-0.636, p<0.001) but no correlation with rainfall (r=-0.036, p=0.866). CONCLUSION: HRV is usually detected in hospitalized children with respiratory infections and is often present in viral co-detections. Comorbidities are closely associated with HRV infections. These infections show seasonal variation, with predominance during colder seasons.

Aporte de la biología molecular en el diagnóstico de infecciones respiratorias agudas / Contribution of multiplex respiratory molecular panel to the diagnosis of acute respiratory infections

Objective: To assess the performance of multiplex-PCR for diagnosis of respiratory viruses in parallel with direct fluorescence assay (DFA). We assessed the performance and co-infection diagnosis of molecular respiratory panel PCR (MRP-PCR) and DFA in hospitalized and outpatients. Results: 8535 samples were included, 1792 tested by MRP-PCR (46.9% positive) and 6743 by DFA (35.1% positive). MRP-PCR diagnosed co-infection in 21.3% and DFA in 1.8% of the samples. Rhinovirus was the most common virus in any age group. In 210 patients both tests were done; 100 were positive by MRP-PCR and 18 by DFA. Positive concordance value was 6.2%. 85 samples were positive only by MRP-PCR and in 42 of them only novel respiratory viruses were identified. Performance of MRP-PCR was statistically significant compared DFA for traditional respiratory viruses. Discussion: Multiplex PCR has shown better sensitivity, may expand the etiologic spectrum of respiratory infections and detect a higher number of co-infections.

Objetivo: Evaluar la contribución del panel respiratorio molecular por reacción en cadena de la polimerasa-multiplex (PRM-RPC) en paralelo a la de inmunofluorescencia directa (IFD) al diagnóstico de infecciones respiratorias. Analizamos y comparamos el rendimiento y diagnóstico de co-infección de PRM-RPC con IFD en pacientes hospitalizados y ambulatorios. Resultados: Se analizaron 8535 muestras; 1792 por PRM-RPC (46,9% positivas) y 6743 por IFD (35,1% positivas). La co-infección fue 21,3% por PRM-RCP y 1,8% por IFD. El virus más frecuente fue rinovirus a toda edad. Se analizaron 210 pacientes por ambos métodos; resultaron positivas 100 por PRM-RPC y 18 por IFD, concordancia positiva de 6,2%. 85 muestras fueron solo positivas por PRM-RPC, 42 diagnosticaron nuevos virus respiratorios. El rendimiento de PRM-RPC fue significativamente mayor que el de IFD para virus respiratorios tradicionalmente diagnosticados. Conclusiones: La RCP-multiplex tiene mejor sensibilidad, podría expandir el espectro etiológico de infecciones respiratorias y detectar un mayor número de co-infecciones comparado a IFD.

Seguimiento de lactantes hospitalizados por bronquiolitis por virus respiratorio sincicial: Evolución clínica, respuesta de atopia inflamatoria y marcadores. Resultados preliminares / Follow-up of infants hospitalized for bronchiolitis by respiratory syncytial virus: Clinical evolution, inflammatory response and markers of atopy. Preliminary results

Background: Respiratory syncytial virus infection (RSV) alone or associated to rhinovirus (RV) in the infant has been linked with more likelihood to develop asthma and atopy. Aim: Analyze clinical and immunological markers of patients with RSV or RV bronchiolitis that determine their evolution. Patients and Methods: We studied previously healthy infants hospitalized for bronchiolitis during the fall-winter period of2009 and 2010. RSV and RV by qPCR, and proinflammatory interleukins (IL). IL-6, IL-8, TNF-a, IL-1fl and IL-12, were determined in nasopharyngeal aspirate (NPA). A follow-up clinical, indoor pollution and immunological study was done at 4 or 5 years. Results are expressed in median and range. Mann-Whitney’s test was used in the nonparametric statistical analysis. Results: Eight out of 22patients (36%) are currently with recurrent wheezing (RW) in treatment with budesonide 400 yg per day as a mean dose. In the IL assessment significant changes were detected only in IL-1fl that was increased and in IL-12 that was decreased in the RWgroup versus the non RW (NRW) group. There were not significant differences in both groups in age at hospitalization, infection severity, presence of personal or family atopy, co-infection with RSV and RV, presence of older siblings or indoor air pollution. Conclusions: The determination of IL-1fl and IL-12 in NPA for bronchiolitis could be an early marker of subsequent inflammation of the airway. Co-infection of RSV and RV does not get worse the clinical evolution. The group RW ofpreschool children had no further development of atopy than the NRW group. There could be other factors that contribute to the manifestation of bronchial inflammation in the RW group.

Introducción: Se ha relacionado la infección por Virus Respiratorio Sincicial (VRS) solo o asociado a Rinovirus (RV) en el período de lactante con mayor probabilidad de desarrollar atopia y asma. Objetivo: Analizar marcadores clínicos e inmunológicos de pacientes con bronquiolitis por VRS y/o RV que determinen su evolución. Material y Método: Lactantes previamente sanos hospitalizados por bronquiolitis, en el hospital Roberto del Río en el período de otoño-invierno de 2009 y 2010. Se determinó en aspirado nasofaríngeo (ANF) VRS y RV por qPCR, e interleuquinas (IL) proinflamatorias (IL-6, IL-8, TNF-a, IL-1fl e IL-12). Seguimiento clínico y estudio inmunológico a los 4 o 5 años. Los resultados se expresan en medianas y rango. Análisis estadístico no paramétrico con test de Mann-Whitney Resultados: 22 pacientes seguidos hasta ahora, 8 (36%) son actualmente sibilantes recurrentes (SR) en tratamiento con budesonida dosis mediana de 400 fg/día. De las ILs evaluadas sólo la elevación de la IL-1fi y la disminución de la IL-12 se objetivaron con diferencias significativas en el grupo de SR versus el grupo No SR. No hubo diferencias significativas en estos dos grupos en edad de hospitalización, gravedad de la infección, presencia de atopia personal o familiar, coinfección de VRS y RV, presencia de hermanos mayores ni contaminación intradomiciliaria. Conclusiones: La determinación de IL-1fi y de IL-12 en ANF durante la bronquiolitis podría ser un marcador precoz de inflamación posterior de la vía aérea. La co-infección de VRS y RV no empeora la evolución clínica. Este grupo de preescolares SR no tiene mayor desarrollo de atopia que los no SR. En este grupo de SR podrían existir otros factores que ayuden a contribuir a la manifestación de inflamación bronquial.

Pediatric Asthma and Viral Infection. / Asma y virus en el niño.

Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma.

High prevalence of common respiratory viruses and no evidence of Middle East respiratory syndrome coronavirus in Hajj pilgrims returning to Ghana, 2013.

OBJECTIVE: The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 on the Arabian Peninsula and has caused severe respiratory disease with more than 800 laboratory-confirmed cases. The return of infected pilgrims to their home countries with a putative spread of MERS-CoV necessitates further surveillance. METHODS: A cross sectional study of 839 adult African Hajj pilgrims returning to Accra in Ghana, West Africa, was conducted in 2013 to assess the prevalence of respiratory symptoms as well as of MERS-CoV, human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus (FLU A) infection. RESULTS: Six hundred and fifty-one (77.6%) pilgrims had respiratory symptoms. Tests were positive for at least one of the viruses other than MERS-CoV in 179 (21.3%) of all pilgrims, with 22.4% detection in symptomatic vs. 17.6% detection in asymptomatic pilgrims. No MERS-CoV was detected, although common respiratory viruses were prevalent, with positive findings for HRV in 141 individuals (16.8%), RSV in 43 individuals (5.1%) and FLU A in 11 individuals (1.3%). Results were positive for more than one virus in 16 (1.9%) individuals, including 14 (1.7%) RSV/HRV co-infections and 2 (0.2%) FLU A/HRV co-infections. A total 146 (22.4%) of the symptomatic returnees tested positive for at least one respiratory virus compared with 33 (17.6%) of the asymptomatic pilgrims who had at least one detectable virus in their sample. CONCLUSIONS: The prevalence of viral respiratory infections among Hajj pilgrims in both symptomatic and asymptomatic subjects was high. Although it is reassuring that MERS-CoV was not detected in the tested population, there is a need for active surveillance of Hajj pilgrims.

[Viral respiratory tract infections in the Neonatal Intensive Care Unit]. / Infecciones virales de las vías respiratorias en la Unidad de Cuidados Intensivos Neonatales.

INTRODUCTION: Viral respiratory infections cause major morbidity and mortality in preterm infants. We have performed a prospective study in our neonatal intensive care unit (NICU) to determine the incidence of respiratory infections, their impact and the epidemiology and outcome in high risk neonates. PATIENTS AND METHODS: From September 2011 to May 2013 a prospective study was conducted in all preterm infants < 32 weeks gestational age and in all term newborns admitted to NICU for any pathology that are anticipated to have an income exceeding two weeks. A nasopharyngeal aspirate (NPA) was collected the first day of life and weekly until discharge for virologic study with polymerase chain reaction. When these babies presented respiratory symptoms a new NPA was collected in this moment. A clinical form was filled by the physician. RESULTS: A total of 60 infants were analyzed: 30 (50%) had a gestational age < 32 weeks and 36 (60%) weighing less than 1500 grams. We collected a total of 256 nasopharyngeal aspirate samples, 24 of them being positive (9.3%). These 24 positive samples corresponded to 13 infants in our cohort (21.6% of the patients). Of them, 9 were symptomatic and had 11 episodes of infection (2 patients had two different episodes with negative control between them). The most frequently identified virus was rhinovirus in (19) 79% of cases. The most frequent clinical data was the presence or increased of apneas (75%) and the needed of oxygenotherapy. CONCLUSIONS: HRV infections are prevalent in the NICU, and preterm infants have a high risk of infections with clinical relevance.

Rhinovirus detection by real-time RT-PCR in children with acute respiratory infection in Buenos Aires, Argentina / Detección de rinovirus por RT-PCR en tiempo real en muestras respiratorias de niños de Buenos Aires, Argentina

Human rhinoviruses (HRV), the major cause of common colds, have a significant genetic diversity and are classified into 3 species (A, B, C) with more than 100 serotypes. HRV species C, described in 2006, can only be detected using molecular methods. The objectives of this paper were to adapt a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for HRV detection and to further determine the frequency of HRV in respiratory samples from children under 2 years of age, with acute respiratory infection (ARI), from Buenos Aires, Argentina. Two real-time RT-PCR assays amplifying the 207 base pair of the 5' non-coding region were compared. The original protocol includes locked nucleic acid analogues and a pyrimidine derivative in the forward primer, while the adapted protocol avoided those molecules. Of 67 respiratory samples, 17 (25.4 %) were positive with the original protocol, and 20 (29.9 %) with the adapted one. Discrepant results were confirmed by sequencing analysis. An expanded gold standard was defined to determine the performance of both assays, and was used to describe the clinical characteristics of positive patients. Better sensitivity and specificity were obtained with the adapted protocol. Considering the expanded gold standard, HRV were detected in 23/67 (34.3 %) patients with ARI: 8/18 (44.4%) outpatients and 15/49 (30.6 %) hospitalized. Wheezing episodes were more frequent in HRV positive patients (43.5 %) than in HRV negative patients (18.2 %) (p = 0.041). This study describes the utility and clinical sensitivity of an adapted real-time RT-PCR assay for HRV detection.

Los rinovirus humanos (RVH) constituyen la principal causa de resfrío común y poseen una gran diversidad genética, con más de 100 serotipos clasificados en tres especies (A, B, C). Los RVH C fueron descritos en 2006 y solo pueden detectarse utilizando métodos moleculares. El objetivo del presente trabajo fue adaptar un protocolo de transcripción reversa seguida de reacción en cadena de polimerasa (RT-PCR) en tiempo real para detectar RVH y posteriormente determinar su frecuencia en muestras de niños menores de 2 años con infección respiratoria aguda (IRA). Se compararon dos protocolos de RT-PCR en tiempo real, que amplifican 207 pares de bases de la región 5' no codificante. El protocolo original incluyó un cebador directo con análogos de nucleótidos bloqueados (LNA) y un derivado pirimidínico en su secuencia, mientras que el protocolo adaptado no los incluyó. De 67 muestras, 17 (25,4 %) fueron positivas con el protocolo original y 20 (29,9 %) con el protocolo adaptado; los resultados discrepantes se confirmaron por secuenciación. Se definió un gold standard expandido para determinar el desempeño de ambos ensayos y describir las características clínicas de los pacientes RVH positivos. La mejor sensibilidad y especificidad se obtuvo con el protocolo adaptado. Considerando el gold standard expandido, se detectó RVH en 23/67 (34,3 %) pacientes con IRA: 44,4 % (8/18) ambulatorios y 30,6 % (15/49) internados. Los episodios de sibilancias fueron más frecuentes en pacientes RVH positivos (43,5 %) que en RVH negativos (18,2 %) (p = 0,041). El presente estudio describe la utilidad y la sensibilidad clínica de esta RT-PCR en tiempo real adaptada para detectar RVH.

Rinovirus: Frecuencia en niños con infección respiratoria aguda, no internados / Rhinoviruses: Frequency in nonhospitalized children with acute respiratory infection

Los métodos moleculares para diagnosticar rinovirus humanos (RVH) han aumentado la sensibilidad de detección. Esto ha permitido documentar la asociación entre los RVH y las infecciones respiratorias agudas (IRA) altas y bajas. La infección por RVH durante la infancia se asoció con posterior desarrollo de asma. Se estudió la frecuencia de RVH en 186 niños menores de 6 años ambulatorios con IRA (alta o baja), durante 2 años consecutivos (1/6/2008 - 31/5/2010). Se correlacionó la presencia de RVH con los antecedentes y características clínico-epidemiológicas. La detección de RVH se realizó con una RT-PCR en tiempo real que amplifica parte de la región 5' no codificante del genoma. Los virus respiratorios clásicos se estudiaron por inmunofluorescencia. En el 61% de los niños se detectó etiología viral. Las frecuencias fueron: RVH 27%, virus sincicial respiratorio (VSR) 16%, influenza A y B 9%, parainfluenza 8%, metapneumovirus 7% y adenovirus 0.5%. Se observaron coinfecciones duales en 8 casos, siendo RVH el más frecuente (en 4 de ellos). Los RVH circularon durante todo el período estudiado, con picos en invierno y primavera. No se observaron diferencias clínico-epidemiológicas significativas entre pacientes con o sin RVH, excepto un mayor porcentaje de niños afebriles con RVH. Los RVH fueron los virus más detectados en niños ambulatorios, principalmente en menores de 2 años, los segundos virus asociados a bronquiolitis, luego del VSR, y detectados tres veces más en los niños expuestos a tabaquismo pasivo (OR: 2,91; p = 0.012) que en el resto. Fueron identificados como único agente en el 28% de las bronquiolitis.

Molecular methods for human rhinoviruses (HRV) have increased the sensitivity in their diagnosis. HRV may cause acute respiratory infections (ARI) of the upper and lower respiratory tract. HRV infection during childhood is a predictor of asthma development. In this study, the HRV frequency in outpatient children with ARI was determined, and their clinical features and previous conditions were evaluated. A total of 186 respiratory samples of children under 6 year old attending the CEMIC pediatric emergency room from June 1, 2008 to May 31, 2010, were studied. Classical respiratory viruses were detected by immunofluorescence. A real time RT-PCR that amplifies part of the 5' non coding genomic region was used for HRV detection. Viral detection was obtained in 61% of children. The frequency was: 27% for HRV, 16% for respiratory syncytial virus (RSV), 9% for influenza, 8% for parainfluenza, 7% for metapneumovirus and 0.5% for adenovirus. Dual coinfection was detected in 8 children and HRV were the most frequent, detected in 4 of them. HRV circulated during the two year period of the study, with peaks during winter and spring. No clinical difference was observed between patients with or without HRV, except an increase percent of children with HRV without fever. HRV were the most frequent viruses detected in this population, mainly in children under 2 year old, the second cause of bronchiolitis after RSV and more frequently detected in children exposed to passive smoking (OR = 2.91; p = 0.012), and were detected as the sole etiologic agent in 28% of bronchiolitis.