Comparación de las características clínicas y diagnósticas de los subgrupos A y B del virus respiratorio sincitial / Comparison of clinical features and diagnosis between the A and B subgroups of respiratory syncytial virus

Fundamento: La infección del tracto respiratorio inferior por virus respiratorio sincitial (VRS) es la causa más frecuente de ingreso en menores de 2 años. Los subgrupos de VRS A y B pueden circular indistintamente. Nuestro objetivo fue determinar si existían diferencias clínicas entre los VRS subgrupo A y B, y si la sensibilidad del test de detección rápida de antígeno del VRS por inmunocromatografía difiere de la técnica de referencia (RT-PCR). Material y métodos: Estudio retrospectivo, observacional realizado en el hospital terciario desde octubre de 2013 a marzo de 2014. Se consultó la historia clínica y las analíticas de los niños menores de 5 años ingresados en por infección respiratoria de vías bajas con RT-PCR positivo a VRS en una muestra de lavado nasal. De la misma muestra previamente se había realizado el test de detección rápida de antígeno de VRS. Resultados: Se confirmaron 198 niños menores de 5 años para VRS mediante RT-PCR: 55 (28%) fueron VRS-A, 132 (67%) VRS-B y 11 (5%) fueron positivos para ambos subgrupos. No encontramos diferencias entre subgrupos en antecedentes, clínica, radiología, analítica y gravedad. La sensibilidad del test de detección rápida fue 52%, mayor para VRS-A (69%) que para VRS-B (44%, p=0,001). Conclusiones: Los dos subgrupos de VRS fueron indistinguibles por su presentación clínica y pronóstico. La sensibilidad del test rápido en comparación con la RT-PCR fue baja, lo que limita su utilidad en la toma de decisiones clínicas (AU)

Background: Lower respiratory tract infection by respiratory syncytial virus (RSV) is the most frequent cause of admission in children under 2 years old. The RSV subgroups A and B may circulate simultaneously. We aimed to determine whether clinical differences exist between RSV subgroups A and B. Additionally, we tested the sensitivity of the rapid antigen detection test (RADT) based on immunochromatography in diagnosing subgroups A and B, taking the polymerase chain reaction assay (RT-PCR) as reference. Methods: A retrospective observational study was performed in a tertiary hospital from October 2013 to March 2014. Clinical records and analytical variables of all children under 5 admitted with lower respiratory tract infection and RT-PCR positive for RSV in nasal lavage were consulted. Previously, the RADT for RSV had been performed from the same sample. Results: A total of 198 children under 5 were diagnosed with RSV by RT-PCR: 55 (28%) were RSV-A, 132 (67%) RSVB and 11 (5%) were positive for both subgroups. No differences were observed between subgroups in medical history, symptoms, radiological and analytical findings, and severity. The sensitivity of RADT for RSV was 52%, higher for RSV-A (69%) than for RSV-B (44%, p=0.001). Conclusions: The two RSV subgroups were indistinguishable in symptoms and prognosis. The sensitivity of RADT compared to RT-PCR was low and limits its usefulness for clinical decision-making (AU)

Classification of acute encephalopathy in respiratory syncytial virus infection.

Infection with respiratory syncytial virus (RSV) is known to be associated with central nervous system symptoms such as convulsions. We investigated cytokines, nitrogen oxide (NO)( x ), and the viral genome in cerebrospinal fluid (CSF) obtained from children with RSV infection-related convulsions or central nervous symptoms and compared the data with type of encephalopathy. Of nine patients enrolled (six boys and three girls; aged 10 days-3 years), one metabolic error, five excitotoxicity, one cytokine storm, and two hypoxia cases were found. The patients presented with unilateral convulsions, generalized convulsions, and convulsions following cardiopulmonary arrest, apnea, and nuchal rigidity. In all patients, a rapid check for RSV of nasal fluid was positive. The RSV genome (subgroup A) was detected in the CSF of five of the nine patients; two patients with hypoxic encephalopathy were negative for the RSV genome. The CSF interleukin (IL)-6 levels were high only in patients with the excitotoxicity and cytokine storm type of encephalopathy. NO( x ) levels were high in all the subject cases. In the excitotoxicity type, NO( x ) levels were significantly higher than those in the control and other groups. NO( x ) level may become an important parameter for the diagnosis and classification of acute encephalopathy in RSV. Strategies to treat each type of encephalopathy, targeting cytokines and free radicals, should be established.

[Clinical characteristics of 12 persistently wheezing children with human bocavirus infection].

OBJECTIVE: The impact of human bocavirus (HBoV), a newly identified human parvovirus, on childhood persistent wheezing has not been identified. In this study, the clinical features of infantile persistent wheezing induced by HBoV was analyzed. METHODS: Tracheal aspirates were collected by bronchofibroscope or nasopharyngeal (NP) aspirates from April, 2006 to January, 2007. HBoV DNA in the tracheal aspirates of 33 children with persistent wheezing and in NP aspirates of 6 children with persistent wheezing, who had at least or more than four weeks wheezing. RSV was identified by virus isolation in Hep-2 cells and antigen detetion by direct immunofluorescence assay (DIFA) which was also used for diagnosis of adenovirus, influenza A and B, parainfluenza 1, 2, 3 infection. RESULTS: Of the 39 children with persistent wheezing, 12 cases (31%) were positive for HBoV DNA. Age of HBoV-positive patients ranged from 2 month to 1 year. The results of sequencing of PCR products proved that sequences of HBoV DNA from these 12 samples were exactly identical to the those of HBoV stored in GeneBank (accession numbers DQ000495 and DQ000496). Two cases with HBoV infection were found to be co-infected with RSV. Ten of the 12 HBoV-positive samples were collected during the period from winter to spring (1 in November, 4 in December, 2 in January and 3 in April), the other two HBoV-positive samples were collected during the period from summer to autumn (1 in May and the other in July). Seven of the 12 HBoV DNA-positive patients had fever, 5 of them had high fever. Significantly more patients with HBoV infection had fever as compared to patients with RSV infection. All the HBoV positive patients showed abnormal findings on chest X ray such as interstitial infiltrates, lung infiltration and hyperinflation. Abnormal findings on chest X ray were found in higher proportion of HBoV positive patients as compared with RSV positive patients. And other manifestations such as wheezing, cough and respiratory distress had no significant difference between HBoV and RSV infected patients. CONCLUSIONS: This study further demonstrated that HBoV probably is a common pathogen of lower respiratory infection in children and might particularly be associated with persistent wheezing.

Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy.

OBJECTIVE: Respiratory syncytial virus (RSV) bronchiolitis is a common cause of hospitalizations in children and has been increasingly identified as a risk factor in the development of asthma. Little is known about what determines the severity of RSV bronchiolitis, which may be helpful in the initial assessment of these children. DESIGN: We evaluated a variety of environmental and host factors that may contribute to the severity of RSV bronchiolitis in the RSV Bronchiolitis in Early Life prospective cohort study. Severity of bronchiolitis was based on the quantization of lowest O(2) saturation and the length of stay. These factors included the child's and family's demographics, presence of household allergens (dust mite, cat, dog, and cockroach), peripheral blood eosinophil count, immunoglobulin E level, infant feeding, prior illnesses, exposure to intrauterine and postnatal cigarette smoke, and family history of atopy. PATIENTS: We prospectively enrolled 206 hospitalized infants, all under 12 months old (4.0 +/- 3.3 months old), with their first episode of severe RSV bronchiolitis (mean O(2) saturation: 91.6 +/- 7.3%; length of stay: 2.5 +/- 2.5 days; presence of radiographic opacities: 75%). Patients were excluded for a variety of reasons including previous wheezing, regular use of bronchodilator or antiinflammatory medications, any preexisting lung disease including asthma, chronic lung disease of prematurity/bronchopulmonary dysplasia, or cystic fibrosis; gastroesophageal reflux disease on medical therapy; or congenital anomalies of the chest or lung. RESULTS: Age was found to be a significant factor in the severity of infection. The younger an infant was, the more severe the infection tended to be as measured by the lowest oxygen (O(2)) saturation. We also found that infants exposed to postnatal cigarette smoke from the mother had a lower O(2) saturation than those not exposed. However, there was no significant difference in RSV bronchiolitis severity between infants exposed only to intrauterine smoke and those infants never exposed to cigarette smoke. Infants with a family history of atopy, especially a maternal history of asthma or hay fever, had a higher O(2) saturation. Although a history of maternal atopy seemed to be protective, there was no association between allergens and bronchiolitis severity, although 25% of households had elevated allergen levels. Black infants demonstrated less severe RSV bronchiolitis than their white counterparts. Multivariate analysis revealed age, race, maternal atopy, and smoking to be associated with severity of RSV bronchiolitis. CONCLUSION: The severity of RSV bronchiolitis early in life seems modified by postnatal maternal cigarette smoke exposure and atopy and age of the infant, not by levels of allergens in the home environment.

The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy.

OBJECTIVE: Neuroendocrine hormones have profound effects on the immune system. The immune response is a major factor in the pathogenesis of acute respiratory syncytial virus (RSV) infection. We hypothesised that there is a relationship between the neuroendocrine response in acute RSV infection, the severity of illness, and the degree of lymphopenia. DESIGN: Prospective, non-randomised cohort study of infants hospitalised for RSV infection requiring mechanical ventilation or managed conservatively. The study assessed the effect of age, gender, birth gestation, and severity of illness on stress hormone profile and its relationship to lymphocyte count. SETTING: Regional Paediatric Intensive Care Unit (PICU) and children's wards. PATIENTS: Thirty-two consecutive infants with RSV infection were enrolled, of which thirteen were mechanically ventilated on PICU (study subjects) and nineteen treated on the ward (comparison group). Twenty-three children (72%) returned for follow-up. MEASUREMENTS AND MAIN RESULTS: A specific neuroendocrine profile was found in PICU patients compared to ward patients (Wilks Lambda = 0.36, F = 9.05, P =.03). PICU patients had significantly higher prolactin and growth hormone, and significantly lower leptin and IGF-1. Cortisol levels were the same. PICU patients were more lymphopenic compared to ward patients (P =.0001). On multiple regression analysis, prolactin and leptin levels accounted for 57% of the variation in lymphocyte count. CONCLUSIONS: Whereas the effect of intensive care (mechanical ventilation and medication) could not be controlled for, our results suggest that there is an association between the neuroendocrine hormone response, severity of illness and degree of lymphopenia.

Risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract infection that can be a life-threatening disease in infants and children. This study was conducted to look for independent risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection (RSV-LRI) that required oxygen supplementation or mechanical ventilation. METHODS: Medical records of patients younger than 4 years hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from July 1, 1995 to June 30, 1999 were reviewed. The patients were compared using univariate and multivariate logistic regression analysis. RESULTS: A total of 157 patients were hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from the study time period. Of these, 20 patients (12.7%) were diagnosed with severe RSV-LRI. Subjects younger than 3 months of age had an odds ratio (OR) of 59.9 (95% confidence interval (CI) 14.7_244.0) for the dependent variable of severe RSV-LRI (P<0.0001). Subjects with a history of congenital heart disease also had an OR of 99.2 (95% C1 8.5-1160.1) (P<0.0005). CONCLUSIONS: Infants younger than 3 months without any underlying diseases may be at high risk for severe RSV-LRI. Respiratory syncytial virus prophylaxis is needed not only for high-risk patients, but for healthy early infants.

Severity of illness models for respiratory syncytial virus-associated hospitalization.

The objective of this investigation was to examine the feasibility of multivariate severity of illness models for pediatric patients hospitalized with respiratory syncytial virus (RSV) infection. From a preexisting retrospective cohort study database, all infants and children 2 yr of age or younger with community-acquired RSV infection admitted to the University of Michigan's C. S. Mott Children's Hospital during nine epidemics were examined. The study group consisted of 802 hospitalized patients younger than 2 yr of age with community-acquired RSV infection; 182 (23%) patients had prolonged hospital length of stay defined as 7 d or greater. Multivariate logistic regression modeling of nine variables measurable during the first hospital day was strongly associated with prolonged hospitalization (p < 0.0001). Receiver operator characteristic curve analysis resulted in an area under the curve of 0.894, indicating excellent model discrimination. Goodness-of-fit testing indicated excellent model calibration for observed versus predicted outcomes (p = 0.216). We conclude that severity of illness models for RSV-associated hospitalization with excellent predictive properties in terms of classification, discrimination, and calibration are possible. Further study is required to determine if such models are generalizable across multiple centers and epidemics.

Does ribavirin impact on the hospital course of children with respiratory syncytial virus (RSV) infection? An analysis using the pediatric investigators collaborative network on infections in Canada (PICNIC) RSV database.

OBJECTIVES: To determine the relationship between receipt of aerosolized ribavirin and the hospital course of high-risk infants and children with respiratory syncytial virus (RSV) lower respiratory infection (LRI). METHODS: The 1993-1994 Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) RSV database consists of prospectively enrolled children with acute RSV LRI, admitted to nine Canadian pediatric tertiary care centers. After excluding cases with compromised immunity and/or nosocomial infection, subsets with any congenital heart disease (CHD), chronic lung disease (CLD), age .35 (EARLY HYPOXIA) were studied in two ways. First, each risk group subset was analyzed separately to assess the association between ribavirin receipt and measures of disease severity including duration of intensive care, mechanical ventilation, hypoxia and RSV-attributable hospital stay. Secondly, ribavirin was added as an independent variable to a previously described multiple regression model for RSV-attributable length of hospital stay and two mutually exclusive subsets were analyzed: 1) previously healthy patients with >/=1 of: INFANT, PREM, or EARLY HYPOXIA; 2) patients with CHD and/or CLD. RESULTS: Between January 1993 and June 1994, 1425 community-acquired hospitalized cases of RSV LRI were entered into the RSV database. Among these 750 (52.6%) fit into one or more of the defined subsets including 97 CHD, 134 CLD, 213 INFANT, 211 PREM, and 463 EARLY HYPOXIA. The proportion ventilated in each group was 20.6%, 20.9%, 15.5%, 15.2%, and 13.3%, respectively. Across the subsets ribavirin use ranged from 36% to 57% of ventilated patients and 6% to 39% of nonventilated patients. For nonventilated patients in each subset the median RSV-attributable hospital length of stay (RSV-LOS) was 2 to 3 days longer for ribavirin recipients and the duration of hypoxia was significantly increased. Duration of intensive care unit (ICU) stay was also increased for all ribavirin-treated subgroups except those with CHD. In contrast, for ventilated patients, ribavirin therapy was not significantly associated with any of the outcome measures regardless of risk group. In the multiple regression model, ribavirin was significantly associated with a prolonged RSV-LOS both for children with CHD and/or CLD as well as for those whose only risk factors included INFANT, PREM, and/or EARLY HYPOXIA. CONCLUSIONS: These data raise further doubts about the clinical effectiveness of ribavirin in infants and children with risk factors for severe disease. Selection bias, with ribavirin used for sicker children, may have influenced outcome. Nevertheless the long durations of hospitalization, ICU, ventilation, and oxygen supplementation in nonventilated ribavirin recipients stress the need for further randomized trials to assess its efficacy.

PICNIC (Pediatric Investigators Collaborative Network on Infections in Canada) study of the role of age and respiratory syncytial virus neutralizing antibody on respiratory syncytial virus illness in patients with underlying heart or lung disease.

OBJECTIVE: To determine the effects of age and respiratory syncytial virus (RSV) antibody status on frequency and severity of RSV infections in children with underlying heart or lung disease. DESIGN: Cohort study conducted during two consecutive RSV seasons. SETTING: Ambulatory patients at eight Canadian pediatric tertiary care centers. METHODS: Subjects under 3 years old with underlying heart disease who were digoxin-dependent or had not received corrective cardiac surgery or with underlying lung disease were enrolled. Demographic information and an acute sera for RSV neutralizing antibody was obtained on enrollment. Weekly telephone follow-up consisting of a respiratory illness questionnaire was followed with a home visit to obtain a nasopharyngeal aspirate when there was new onset of respiratory symptoms. The specimen was used to detect RSV antigen. RSV illnesses were grouped as upper or lower respiratory tract infection (LRI) based on clinical and radiographic findings. RSV hospitalizations were considered to be those RSV infections that resulted in hospitalization. RESULTS: Of 427 enrolled subjects, 160 had underlying lung disease only, 253 had underlying heart disease only, and 14 had both. Eleven percent and 12% of lung and heart disease groups, respectively, had an RSV LRI. Three percent and 6% of lung and heart disease groups, respectively, were hospitalized with RSV infection. A significant decrease in frequency of RSV LRI and RSV hospitalization occurred with increasing age, with a major drop in those older than 1 year vs those younger than 1 year. Acute sera were available from 422 subjects. Geometric mean RSV antibody titers demonstrated a U-shaped distribution with increasing age. The trend to lower antibody concentrations in premature infants did not reach statistical significance. The frequency of RSV infection and RSV LRI was lower in patients with antibody at a titer more than 100, although the difference for RSV hospitalization was not statistically significant. These differences remained significant after age adjustment. CONCLUSION: Both age and RSV antibody status impact on RSV illness and LRI. Reduction in illness frequency with increasing age may lead to more informed targeting of those children most likely to benefit from RSV immune globulin prophylaxis.

Respiratory syncytial virus subgroup B dominance during one winter season between 1987 and 1992 in Vancouver, Canada.

A subgroup analysis of 613 specimens submitted to the British Columbia's Children's Hospital from 1987 to 1992 revealed that subgroups A and B of respiratory syncytial virus (RSV) were both circulating in our community, with some predominance for subgroup A during the period from October 1987 to September 1988 (the 1987-88 season) (64%), 1990-91 (60%), and 1991-92 (62%). During 1989-90 subgroup A represented the majority of isolates (80%). Subgroup B predominated during only one season, 1988-89 (94%). No microheterogeneity within subgroups was apparent as judged by the monoclonal antibody reactivity pattern. More male than female children were affected overall, but no sex-related difference between subgroup infections could be detected (P = 0.28). The majority of patients were less than 1 year of age, and no significant association between age and subgroup was detected after stratifying for year (P = 0.64). This is, to our knowledge, the first comprehensive longitudinal RSV subgroup prevalence study from the Pacific Northwest and from Canada.