Transient Neutropenia in Immunocompetent Infants with Respiratory Syncytial Virus Infection.

The incidence of neutropenia and the association between neutropenia and severity of respiratory symptoms among infants with respiratory syncytial virus (RSV) infections remain to be elucidated. This single-center, retrospective study included immunocompetent infants (<10 months old) with laboratory-confirmed RSV infection admitted to our center between January 2012 and December 2019. Incidence of neutropenia (<1.0 × 109/L) within 10 days of onset and risk factors associated with subsequent neutropenia were evaluated. Among the 292 infants with RSV infection, including 232 (79%) with mild infection, neutropenia was observed in 31 (11%), with severe neutropenia (<0.5 × 109/L) in 3 (1.0%). No neutropenic infants developed serious infection or hematological disorder. Infants without neutropenia showed age <3 months at onset in 34%, C-reactive protein level <1.0 mg/L in 27%, and nasopharyngeal microbiota composition with any of Moraxella catarrhalis, Streptococcus pneumoniae, or Haemophilus influenzae in 63%. In comparison, infants with neutropenia showed age <3 months at onset in 74% (relative risk [RR] 2.15; 95% confidence interval [CI] 1.65-2.81), C-reactive protein level <1.0 mg/L in 55% (RR 2.02; 95% CI 1.38-2.94), and microbiota including Moraxella catarrhalis, Streptococcus pneumoniae, or Haemophilus influenzae in 15% (RR 0.24; 95% CI 0.10-0.61). Multiple logistic regression analyses showed that younger age at onset and absence of that nasopharyngeal microbiota profile were associated with development of neutropenia. In conclusion, age and airway microbiota are considered as risk factors for the development of transient neutropenia among infants with RSV infection. However, the neutropenia seems not to develop serious infection or hematological disorder.

Utilidad de la vigilancia microbiológica del virus respiratorio sincitial en Galicia (España): 2008-2017 / Usefulness of the microbiological surveillance of respiratory syncytial virus in Galicia (Spain): 2008-2017

OBJETIVO: Describir si la información microbiológica del virus respiratorio sincitial (VRS) facilitada semanalmente por cuatro hospitales captura adecuadamente la estacionalidad del VRS en toda la comunidad. MÉTODO: Estudio descriptivo retrospectivo. Se compararon las detecciones de VRS en muestras respiratorias de pacientes (ingresados y no), de todos los grupos de edad, de los cuatro hospitales que forman parte del sistema de vigilancia microbiológica (SVM), con datos del Conjunto Mínimo Básico de Datos de hospitalización por bronquiolitis causada por VRS u otro microorganismo infeccioso, en pacientes menores de 5 años ingresados en cualquier hospital público de Galicia (temporadas 2008/2009 a 2016/2017). Se consideró como periodo de onda epidémica cuando la positividad de detecciones de VRS en el total de muestras respiratorias del SVM superó el 10%. Se calculó la sensibilidad del SVM como el porcentaje de ingresos ocurridos en la onda epidémica. RESULTADOS: La sensibilidad del SVM fue del 92% (86-96%) para los ingresos por bronquiolitis por VRS en cada temporada y del 79% (75-84%) para los ingresos por bronquiolitis totales. CONCLUSIONES: El SVM del VRS, basado en información de solo cuatro hospitales, mostró muy buena sensibilidad para predecir el inicio y el final de la onda anual de VRS en toda la comunidad autónoma. Estos resultados respaldan la utilización de esta información para alertar a todo el sistema sanitario del inicio de la onda

OBJECTIVE: To describe whether the microbiological information of the respiratory syncytial virus (RSV), provided by four hospitals on a weekly basis, adequately captures the seasonality of the RSV in the entire community. METHOD: Retrospective descriptive study. We compared the detection of RSV in respiratory samples of patients (hospitalized and not) from all age groups, from the 4 hospitals that are part of the microbiological surveillance system (MSS), with data from the Minimum Basic Data Set of hospitalization for bronchiolitis by RSV or another infectious organism, in patients under 5 years of age, admitted to any public hospital in Galicia (seasons 2008/2009 to 2016/2017). An epidemic wave period was considered when the positivity of RSV detections in the total respiratory samples of the SVM exceeded 10%. The sensitivity of the MSS was calculated as a percentage of admissions occurring in the epidemic wave. RESULTS: MSS sensitivity was 92% (86%-96%) for RSV bronchiolitis admissions in each season and 79% (75%-84%) for total bronchiolitis admissions. CONCLUSIONS: The RSV microbiological surveillance system, based on data from only 4 hospitals, showed very good sensitivity to predict the start and end of the annual RSV wave throughout the Galician region. These results support the use of this information to alert the entire health system of the onset of the wave

Altres tests de diagnòstic ràpid respiratori: VRS, adenovirus, pneumococ, Mycoplasma pneumoniae I mononucleosi infecciosa / No disponible

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Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity.

BACKGROUND: Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants. There are still no vaccines or specific antiviral therapies against RSV, mainly due to the inadequate understanding of RSV pathogenesis. Recent data suggest a role for gut microbiota community structure in determining RSV disease severity. Our objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection. RESULTS: We enrolled 95 infants from Le Bonheur during the 2014 to 2016 RSV season. Of these, 37 were well-babies and 58 were hospitalized with RSV. Of the RSV infected babies, 53 remained in the pediatric ward (moderate) and 5 were moved to the pediatric intensive care unit at a later date (severe). Stool samples were collected within 72 h of admission; and the composition of gut microbiota was evaluated via 16S sequencing of fecal DNA. There was a significant enrichment in S24_7, Clostridiales, Odoribacteraceae, Lactobacillaceae, and Actinomyces in RSV (moderate and severe) vs. controls. Patients with severe RSV disease had slightly lower alpha diversity (richness and evenness of the bacterial community) of the gut microbiota compared to patients with moderate RSV and healthy controls. Beta diversity (overall microbial composition) was significantly different between all RSV patients (moderate and severe) compared to controls and had significant microbial composition separating all three groups (control, moderate RSV, and severe RSV). CONCLUSIONS: Collectively, these data demonstrate that a unique gut microbial profile is associated with RSV disease and with severe RSV disease with admission to the pediatric intensive care unit. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of severe RSV disease.

Bacterial colonization dynamics associated with respiratory syncytial virus during early childhood.

Respiratory syncytial virus (RSV) is an important cause of early life acute respiratory infections. Potentially pathogenic respiratory bacteria, including Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are frequently detected during RSV infections and associated with increased illness severity. However, the temporal dynamics of bacterial colonization associated with RSV infection remain unclear. We used weekly nasal swab data from a prospective longitudinal birth cohort in Brisbane, Australia, to investigate bacterial colonization patterns within children aged less than 2 years in the 4-week period before and after an RSV infection. During 54 RSV infection episodes recorded in 47 children, both S. pneumoniae and M. catarrhalis were detected frequently (in 33 [61.1%] and 26 [48.1%] RSV infections, respectively). In most cases, S. pneumoniae and M. catarrhalis colonization preceded the viral infection, with the nasal load of each increasing during RSV infection. Generally, the dominant serotype of S. pneumoniae remained consistent in the 1 to 2 weeks immediately before and after RSV infection. Little evidence was found to indicate that prior colonization with either bacteria predisposed participants to developing RSV infection during the annual seasonal epidemic. Possible coacquisition events, where the bacteria species was first detected with RSV and not in the preceding 4 weeks, were observed in approximately 20% of RSV/S. pneumoniae and RSV/M. catarrhalis codetections. Taken together our results indicate that RSV generally triggered an outgrowth, rather than a new acquisition, of S. pneumoniae and M. catarrhalis from the resident microbial community.

Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort.

BACKGROUND: The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS: Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS: One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS: Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.

Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Early interactions between respiratory viruses and microbiota might modulate host immune responses and subsequently contribute to later development of recurrent wheezing and asthma in childhood. We aimed to study the possible association between respiratory microbiome, host immune response, and the development of recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis. METHODS: Seventy-four infants who were hospitalized at Beijing Children's Hospital during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed up until the age of 3 years. Sputum samples were collected, and their microbiota profiles, LPS, and cytokines were analyzed by 16S rRNA-based sequencing, ELISA, and multiplex immunoassay, respectively. RESULTS: Twenty-six (35.1%) infants developed recurrent wheezing by the age of 3 years, and 48 (64.9%) did not. The relative abundance of Haemophilus, Moraxella, and Klebsiella was higher in infants who later developed recurrent wheezing than in those who did not (LDA score >3.5). Airway levels of LPS (P = .003), CXCL8 (P = .004), CCL5 (P = .029), IL-6 (P = .004), and IL-13 (P < .001) were significantly higher in infants who later developed recurrent wheezing than in those who did not. Moreover, high airway abundance of Haemophilus was associated with CXCL8 (r = 0.246, P = .037) level, and that of Moraxella was associated with IL-6 level (r = 0.236, P = .046) and IL-10 level (r = 0.266, P = .024). CONCLUSION: Our study suggests that higher abundance of Haemophilus and Moraxella in airway microbiome might modulate airway inflammation during severe RSV bronchiolitis in infancy, potentially contributing to the development of subsequent recurrent wheezing in later childhood.

Respiratory Syncityal Virus A and B: three bronchiolitis seasons in a third level hospital in Italy.

BACKGROUND: Respiratory syncytial virus (RSV) is the main cause of hospitalization for bronchiolitis among infants. RSV is classified into two subtypes, A and B, whose predominance alternates during different epidemic seasons. The clinical impact of viral factors is controversial and many evidences suggest a critical role for the immune host response. Premature children are at the highest risk for severe RSV infection. The main aim of this study is to identify the different RSV subtypes circulating in the last three epidemic seasons and to evaluate whether any of them was associated with poor prognosis in term and preterm infants. METHODS: We performed a retrospective analysis of medical records for all patients aged less than one year which were hospitalized during the winter season between November 2015 and April 2018 with clinical diagnosis of bronchiolitis and nasopharyngeal aspirates positive for RSV. RESULTS: We enrolled 422 children, of which 50 were born preterm. During the analysis period, we observed a significant increase in the rates of oxygen supplementation and admission to intensive care unit. The evidence shows an alternating pattern in the prevalence of RSV subtypes among term born; in each epidemic season, the prevalent serotype is the cause of the majority of the cases requiring intensive care. Conversely, RSV-A is always prevalent in preterm children and caused most of the cases requiring intensive care. CONCLUSIONS: During the 3 seasons analyzed, we observed an alternating prevalence of RSV A and B. While there are no differences in severity between RSV A and B in term population, RSV-A is prevalent and causes most of the severe cases in the premature group. Furthermore, an increase in RSV-related oxygen therapy and PICU admission has been documented not only in the premature population. Considering the absence of appropriate therapeutic strategies, our work emphasizes the importance of implementing prophylaxis measures against RSV and highlights the urgent need to gain knowledge about immune response to the virus, also in premature children.

Co-infection of epithelial cells established from the upper and lower bovine respiratory tract with bovine respiratory syncytial virus and bacteria.

Bovine respiratory disease complex is a major disease affecting the global cattle industry. Multiple infections by viruses and bacteria increase disease severity. Previously, we reported that bovine respiratory syncytial virus (BRSV) infection increases adherence of Pasteurella multocida to human respiratory and bovine kidney epithelial cells. To examine the interaction between the virus and bacteria in bovine respiratory cells, we generated respiratory epithelial cell lines from bovine trachea (bTEC), bronchus (bBEC), and lung (bLEC). Although all established cell lines were infected by BRSV and P. multocida susceptibility differed according to site of origin. The cells derived from the lower respiratory tract (bBEC and bLEC) were significantly more susceptible to BRSV than those derived from the upper respiratory tract (bTEC). Pre-infection of bBEC and bLEC with BRSV increased adherence of P. multocida; this was not the case for bTEC. These results indicate that BRSV may reproduce better in the lower respiratory tract and encourage adherence of bacteria. Thus, we identify one possible mechanism underlying severe pneumonia.

Viral Bacterial Interactions in Children: Impact on Clinical Outcomes.

Respiratory viral infections are associated with significant morbidity and mortality in children < 5 years of age worldwide. Among all respiratory viruses, respiratory syncytial virus (RSV) is the world's leading cause of bronchiolitis and pneumonia in young children. There are known populations at risk for severe disease but the majority of children who require hospitalization for RSV infection are previously healthy. Viral and host factors have been associated with the pathogenesis of RSV disease; however, the mechanisms that explain the wide variability in the clinical presentation are not completely understood. Recent studies suggest that the complex interaction between the respiratory microbiome, the host's immune response and the virus may have an impact on the pathogenesis and severity of RSV infection. In this review, we summarize the current evidence regarding the epidemiologic link, the mechanisms of viral-bacterial interactions, and the associations between the upper respiratory tract microbiome and RSV disease severity.

Microorganisms associated with respiratory syncytial virus pneumonia in the adult population.

Respiratory syncytial virus (RSV) has been recognized as responsible for severe respiratory illness in adults, especially in the elderly. While pneumonia is commonly observed during RSV infection, the burden and epidemiology of bacterial superinfection is poorly understood. The aim of this study was to identify microorganisms associated with RSV-positive pneumonia in adults. A retrospective study was conducted during three consecutive winters (October to April 2013-2016) in the University Hospital of Lyon, France. During RSV circulation periods, a systematic RSV screening was performed by reverse-transcription PCR on all respiratory samples collected from adults. Records of RSV-positive patients were subsequently analyzed to identify radiologically confirmed pneumonia cases. Bacteria were identified by standard bacteriology cultures or urinary antigen screening and classified as potentially causative of pneumonia if quantification was above the specific threshold as defined by the European Manual of Clinical Microbiology. Overall, 14,792 adult respiratory samples were screened for RSV detection by PCR. In total, 292 had a positive RSV detection (2.0%) among which 89 presented with pneumonia including 27 bacterial superinfections (9.3%) with Streptococcus pneumonia, Haemophilus influenza, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis. Most patients were elderly (55.6%) and patients with comorbidities (77.8%). A more severe outcome was observed for RSV-bacteria-associated pneumonia compared with RSV pneumonia: length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). In conclusion, we did not observe major differences in the epidemiology of bacterial superinfections in RSV-positive pneumonia compared to reports on post-influenza pneumonia.

Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy.

BACKGROUND: Early life acute respiratory infection (ARI) with respiratory syncytial virus (RSV) has been strongly associated with the development of childhood wheezing illnesses, but the pathways underlying this association are poorly understood. OBJECTIVE: To examine the role of the nasopharyngeal microbiome in the development of childhood wheezing illnesses following RSV ARI in infancy. METHODS: We conducted a nested cohort study of 118 previously healthy, term infants with confirmed RSV ARI by RT-PCR. We used next-generation sequencing of the V4 region of the 16S ribosomal RNA gene to characterize the nasopharyngeal microbiome during RSV ARI. Our main outcome of interest was 2-year subsequent wheeze. RESULTS: Of the 118 infants, 113 (95.8%) had 2-year outcome data. Of these, 46 (40.7%) had parental report of subsequent wheeze. There was no association between the overall taxonomic composition, diversity, and richness of the nasopharyngeal microbiome during RSV ARI with the development of subsequent wheeze. However, the nasopharyngeal detection and abundance of Lactobacillus was consistently higher in infants who did not develop this outcome. Lactobacillus also ranked first among the different genera in a model distinguishing infants with and without subsequent wheeze. CONCLUSIONS: The nasopharyngeal detection and increased abundance of Lactobacillus during RSV ARI in infancy are associated with a reduced risk of childhood wheezing illnesses at age 2 years.

Streptococcus pneumoniae colonization of the nasopharynx is associated with increased severity during respiratory syncytial virus infection in young children.

BACKGROUND AND OBJECTIVE: Respiratory syncytial virus (RSV) is the most significant cause of acute respiratory infection (ARI) in early life. RSV and other respiratory viruses are known to stimulate substantial outgrowth of potentially pathogenic bacteria in the upper airways of young children. However, the clinical significance of interactions between viruses and bacteria is currently unclear. The present study aimed to clarify the effect of viral and bacterial co-detections on disease severity during paediatric ARI. METHODS: Nasopharyngeal aspirates from children under 2 years of age presenting with ARI to the emergency department were screened by quantitative PCR for 17 respiratory viruses and the bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Associations between pathogen detection and clinical measures of disease severity were investigated. RESULTS: RSV was the most common virus detected, present in 29 of 58 samples from children with ARI (50%). Detection of S. pneumoniae was significantly more frequent during RSV infections compared to other respiratory viruses (adjusted effect size: 1.8, P: 0.03), and co-detection of both pathogens was associated with higher clinical disease severity scores (adjusted effect size: 1.2, P: 0.03). CONCLUSION: Co-detection of RSV and S. pneumoniae in the nasopharynx was associated with more severe ARI, suggesting that S. pneumoniae colonization plays a pathogenic role in young children.

Viral-Bacterial Co-infections in the Cystic Fibrosis Respiratory Tract.

A majority of the morbidity and mortality associated with the genetic disease Cystic Fibrosis (CF) is due to lung disease resulting from chronic respiratory infections. The CF airways become chronically colonized with bacteria in childhood, and over time commensal lung microbes are displaced by bacterial pathogens, leading to a decrease in microbial diversity that correlates with declining patient health. Infection with the pathogen Pseudomonas aeruginosa is a major predictor of morbidity and mortality in CF, with CF individuals often becoming chronically colonized with P. aeruginosa in early adulthood and thereafter having an increased risk of hospitalization. Progression of CF respiratory disease is also influenced by infection with respiratory viruses. Children and adults with CF experience frequent respiratory viral infections with respiratory syncytial virus (RSV), rhinovirus, influenza, parainfluenza, and adenovirus, with RSV and influenza infection linked to the greatest decreases in lung function. Along with directly causing severe respiratory symptoms in CF populations, the impact of respiratory virus infections may be more far-reaching, indirectly promoting bacterial persistence and pathogenesis in the CF respiratory tract. Acquisition of P. aeruginosa in CF patients correlates with seasonal respiratory virus infections, and CF patients colonized with P. aeruginosa experience increased severe exacerbations and declines in lung function during respiratory viral co-infection. In light of such observations, efforts to better understand the impact of viral-bacterial co-infections in the CF airways have been a focus of clinical and basic research in recent years. This review summarizes what has been learned about the interactions between viruses and bacteria in the CF upper and lower respiratory tract and how co-infections impact the health of individuals with CF.

Métodos de diagnóstico rápido de las infecciones respiratorias / Rapid diagnostic test for respiratory infections

Las infecciones respiratorias agudas son la segunda causa de morbimortalidad tanto en niños como adultos a nivel mundial en cuya etiología se implican virus, bacterias y hongos. Su diagnóstico rápido permite un mejor manejo clínico del paciente, adoptar medidas de salud pública y controlar posibles brotes. Los principales microorganismos responsables pueden diagnosticarse en las primeras horas tras el inicio del cuadro con técnicas de detección de antígeno, fundamentalmente inmunocromatografícas. Se obtienen resultados en 15-30 min, con una sensibilidad del 70-90% y especificidad superior al 95% para el diagnóstico de infecciones por Streptococcus pneumoniae y Legionella pneumophila serogrupo O1 a partir de orina, Streptococcus pyogenes en exudados faríngeos y virus respiratorio sincitial en aspirados nasofaríngeos. En infecciones por los virus de la gripe y por Pneumocystis jirovecii, los resultados con estas técnicas son peores; no obstante, existen técnicas moleculares de fácil ejecución para el diagnóstico rápido de estos microorganismos. En general, estas técnicas no deben utilizarse para control evolutivo ni para valorar respuesta al tratamiento

Acute respiratory infections are the second cause of morbidity and mortality in children and adults worldwide, being viruses, bacteria and fungi involved in their etiology. The rapid diagnosis allows for a better clinical management of the patient, for adopting public health measures and for controlling possible outbreaks. The main etiologic agents can be diagnosed within the first hours after the onset of symptoms with antigen detection techniques, primarily immunochromatography. Results are obtained in 15-30 minutes, with 70-90% sensitivity and > 95% specificity for the diagnosis of Streptococcus pneumoniae and Legionella pneumophila serogroup O1 infections from urine, Streptococcus pyogenes from throat swabs and respiratory syncytial virus from nasopharyngeal aspirates. Worse results are obtained for influenza viruses and Pneumocystis jirovecii with these techniques; however, other easy-to-perform molecular techniques are available for the rapid diagnosis of these microorganisms. In general, these techniques should not be used for monitoring the outcome or response to treatment

Retrospective Parameter Estimation and Forecast of Respiratory Syncytial Virus in the United States.

Recent studies have shown that systems combining mathematical modeling and Bayesian inference methods can be used to generate real-time forecasts of future infectious disease incidence. Here we develop such a system to study and forecast respiratory syncytial virus (RSV). RSV is the most common cause of acute lower respiratory infection and bronchiolitis. Advanced warning of the epidemic timing and volume of RSV patient surges has the potential to reduce well-documented delays of treatment in emergency departments. We use a susceptible-infectious-recovered (SIR) model in conjunction with an ensemble adjustment Kalman filter (EAKF) and ten years of regional U.S. specimen data provided by the Centers for Disease Control and Prevention. The data and EAKF are used to optimize the SIR model and i) estimate critical epidemiological parameters over the course of each outbreak and ii) generate retrospective forecasts. The basic reproductive number, R0, is estimated at 3.0 (standard deviation 0.6) across all seasons and locations. The peak magnitude of RSV outbreaks is forecast with nearly 70% accuracy (i.e. nearly 70% of forecasts within 25% of the actual peak), four weeks before the predicted peak. This work represents a first step in the development of a real-time RSV prediction system.

Rapid diagnostic methods for acute viral respiratory infections / Técnicas de diagnóstico rápido para infecciones respiratorias agudas de etiología viral

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