The importance of viral load in the severity of acute bronchiolitis in hospitalized infants

OBJECTIVE: The relationship between viral load and the clinical evolution of bronchiolitis is controversial. Therefore, we aimed to analyze viral loads in infants hospitalized for bronchiolitis. METHODS: We tested for the presence of human respiratory syncytial virus (HRSV) or human rhinovirus (HRV) using quantitative molecular tests of nasopharyngeal secretions and recorded severity outcomes. RESULTS: We included 70 infants [49 (70%) HRSV, 9 (13%) HRV and 12 (17%) HRSV+HRV]. There were no differences among the groups according to the outcomes analyzed individually. Clinical scores showed greater severity in the isolated HRSV infection group. A higher isolated HRSV viral load was associated with more prolonged ventilatory support, oxygen therapy, and hospitalization days, even after adjustment for the age and period of nasopharyngeal secretion collection. In the co-infection groups, there was a longer duration of oxygen therapy when the HRSV viral load was predominant. Isolated HRV infection and co-infection with a predominance of HRV were not associated with severity. CONCLUSION: Higher HRSV viral load in isolated infections and the predominance of HRSV in co-infections, independent of viral load, were associated with greater severity. These results contribute to the development of therapeutic and prophylactic approaches and a greater understanding of the pathophysiology of bronchiolitis.

Lack of association between viral load and severity of acute bronchiolitis in infants / Falta de associação entre carga viral e gravidade da bronquiolite aguda em lactentes

ABSTRACT Objective: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. Methods: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period) by direct immunofluorescence and (in the second year of the study) by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. Results: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9%) were positive for a single virus, and 16 (14.5%) were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8%) were positive for a single virus, and 1 (1.7%) was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. Conclusions: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants.

RESUMO Objetivo: Investigar a correlação entre a carga viral do vírus sincicial respiratório e o tempo de internação hospitalar em lactentes com episódios de sibilância aguda. Métodos: Este foi um estudo transversal de dois anos envolvendo lactentes de até 12 meses de idade com bronquiolite no momento da internação em um hospital terciário. Para a identificação dos vírus respiratórios foram coletadas secreções nasofaríngeas. As amostras foram analisadas (por todo o período do estudo) por imunofluorescência direta e (no segundo ano do estudo) por PCR quantitativa em tempo real para três vírus humanos (rinovírus, vírus sincicial respiratório e metapneumovírus). Resultados: Das 110 amostras avaliadas por imunofluorescência direta, 56 (50,9%) foram positivas para um único vírus, e 16 (14,5%) foram positivas para dois ou mais vírus. Nessas 72 amostras, o vírus mais prevalente foi o vírus sincicial respiratório, seguido por influenza. Das 56 amostras avaliadas por PCR quantitativa em tempo real, 24 (42,8%) foram positivas para um único vírus, e 1 (1,7%) foi positiva para dois vírus. Nessas 25 amostras, o vírus mais prevalente foi o vírus sincicial respiratório, seguido por rinovírus humano. A coinfecção não influenciou o tempo de internação ou outros desfechos. Além disso, não houve associação entre a carga viral de vírus sincicial respiratório e o tempo de internação. Conclusões: A coinfecção e a carga viral do vírus sincicial respiratório não parecem influenciar os desfechos em lactentes com bronquiolite aguda.

Ventilação não invasiva na insuficiência respiratória aguda na bronquiolite por vírus sincicial respiratório / Noninvasive ventilation in acute respiratory failure from respiratory syncytial virus bronchiolitis

OBJETIVOS: Analisar se a ventilação não invasiva diminui a necessidade de intubação endotraqueal e se alterou a evolução clínica, relativamente a complicações infecciosas, da bronquiolite por vírus sincicial respiratório com insuficiência respiratória. MÉTODOS: Estudo retrospectivo de coortes: cohorte A, de crianças internadas na unidade de cuidados intensivos e especiais pediátrica antes da introdução da ventilação não invasiva (2003-2005); cohorte B, de crianças internadas após a introdução de ventilação não invasiva (2006-2008). Excluindo a ventilação não invasiva, a terapêutica de suporte foi igual nos dois grupos. Foram incluídas crianças com o diagnóstico de bronquiolite por vírus sincicial respiratório e insuficiência respiratória entre novembro 2003 e março 2008. Analisaram-se variáveis demográficas, clínicas e gasimétricas. RESULTADOS: Incluídas 162 crianças, 75% com idade <3 meses. Grupo A: 64 crianças; Grupo B: 98 (34 necessitaram de ventilação não invasiva). Ambos os grupos apresentaram distribuição semelhante relativamente à idade, antecedentes de prematuridade, cardiopatia congénita, paralisia cerebral e doença pulmonar crónica. Na admissão, os valores da gasimetria e o número de apneias não apresentaram diferenças estaticamente significativas nos dois grupos. No Grupo B, o número de crianças que necessitou de ventilação invasiva foi menor (Grupo A: 12 versus Grupo B: 7; p=0,02), verificando-se uma diminuição do número de casos de pneumonia bacteriana (Grupo A:19/64 versus Grupo B:12/98; p=0,008). Não se registou mortalidade. CONCLUSÃO: Neste trabalho, comparando crianças com a mesma patologia, antes e depois da introdução de ventilação não invasiva como apoio ventilatório inicial, verificou-se diminuição das complicações infecciosas e da necessidade de entubação.

OBJECTIVES: The present study focused on respiratory syncytial virus bronchiolitis with respiratory failure. The aim of the study was to determine whether noninvasive ventilation reduces the need for endotracheal intubation or slows the clinical progression of acute respiratory syncytial virus bronchiolitis by reducing the incidence of infectious complications. METHODS: The present study was a retrospective cohort study. Cohort A was comprised of children who were admitted to the pediatric intensive and special care unit from 2003-2005 before starting noninvasive ventilation; cohort B was comprised of children who were admitted to the pediatric intensive and special care unit from 2006-2008 after starting noninvasive ventilation. With the exception of noninvasive ventilation, the therapeutic support was the same for the two groups. All children who were diagnosed with respiratory syncytial virus bronchiolitis and respiratory failure between November 2003 and March 2008 were included in the cohort. Demographic, clinical and blood gas variables were analyzed. RESULTS: A total of 162 children were included; 75% of the subjects were less than 3 months old. Group A included 64 children, and group B included 98 children. In group B, 34 of the children required noninvasive ventilation. The distributions of the variables age, preterm birth, congenital heart disease, cerebral palsy and chronic lung disease were similar between the two groups. On admission, the data for blood gas analysis and the number of apneas were not significantly different between the groups. In group B, fewer children required invasive ventilation (group A: 12/64 versus group B: 7/98; p=0.02), and there was a reduction in the number of cases of bacterial pneumonia (group A: 19/64 versus group B: 12/98; p=0.008). There was no record of mortality in either of the groups. CONCLUSION: By comparing children with the same disease both before and after noninvasive ventilation was used for ventilation support, we verified a reduction in infectious complications and cases requiring intubation.

Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença / Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity

OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10) na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI) por vírus sincicial respiratório (VSR) apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.

OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. CONCLUSIONS: At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.

A clinical study on the respiratory tract infections with human metapneumovirus and respiratory syncytial virus / 中华传染病杂志

Objective To investigate the prevalence of human metapneumovirus (HMPV)infection in patients with respiratory infection in Fuzhou area and compare their epidemic features and clinical characteristics with those of infected with respiratory syncytial virus (RSV). Methods A total of 153 sputum or pharyngeal swab samples from patients with respiratory tract infection were collected in Fujian Provincial Hospital in consecutive winter and spring seasons from 2005 to 2007. HMPV was detected by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and RSV was tested by RT-PCR. Parts of PCR products were sequenced and analyzed using DNAMAN software. The clinical symptoms, signs and epidemiology of the respiratory tract infections caused by HMPV and RSV were compared. Results In the 153 specimens, 32 (20.9%) were positive for H MPV, 26 (17.0%) were positive for RSV, and 8 were both HMPV and RSV positive. Nucleotide sequences of three 432-bp PCR products were 100% identical and submitted to GenBank (the accession No. DQ887758).Phylogenetic tree analysis of nucleotide sequences revealed that the three isolates clustered in HMPV belonged to genotype A with part of mutation. Twenty-six samples (26. 7%) were HMPV positive from Dec 2005 to Apr 2006 and 6 (10.7%) were positive from Dec 2006 to Apr 2007. The RSV detection rate was opposite of HMPV. The mean age of RSV infection in children was (2.65±2.65)years old and HMPV infection was (4.58 ±3.35) years old. The main clinical manifestations of both RSV and HMPV infections were cough, sore throat and fever. Conclusions Both HMPV and RSV are the major pathogens of respiratory tract infection in Fuzhou area and HMPV and RSV coinfection could be detected. HMPV infected children are older. The clinical features of HMPV and RSV infections are similar. Single genotype of HMPV is detected in Fuzhou area in this study.

Mortalidad asociada con las temporadas de mayor circulación de los virus de la influenza en Bogotá, Colombia, 1997-2005 / Mortality associated with peak seasons of influenza virus circulation in Bogotá, Colombia, 1997-2005

OBJETIVO: Estimar el exceso de mortalidad potencialmente atribuible a los virus de la influenza A y B y al virus sincitial respiratorio humano (VSRH) en las temporadas de mayor circulación de los virus de la influenza en Bogotá, Colombia entre 1997 y 2005. MÉTODOS: Se relacionaron las tasas mensuales de mortalidad general, por neumonía en menores de 5 años y por neumonía y afecciones cardiovasculares en mayores de 60 años, en Bogotá, Colombia, con las temporadas de mayor circulación de los virus de la influenza en esa ciudad. Los datos de mortalidad se obtuvieron del Departamento Nacional de Estadísticas de Colombia; las temporadas de mayor circulación de los virus se definieron como los meses contiguos en los que el número de aislamientos era igual o superior a la mitad del total de los aislamientos del año. Se calcularon las razones de tasas de incidencia (RTI) y sus intervalos de confianza de 95 por ciento (IC95 por ciento). RESULTADOS: El virus de la influenza A mostró un patrón de circulación estacional, pero no el de la influenza B y el VSRH. La mayor circulación de los virus de la influenza se asoció con un incremento promedio anual de 5 por ciento en la mortalidad general durante el período estudiado (RTI = 1,05; IC95 por ciento: 1,046 a 1,064). En las temporadas de mayor circulación de los virus de la influenza, la mortalidad combinada por neumonía e influenza en todas las edades fue mayor en 11 por ciento que en el resto del período (RTI = 1,11; IC95 por ciento: 1,051 a 1,178). CONCLUSIONES: En las temporadas de mayor circulación de los virus de la influenza en Colombia puede aumentar la mortalidad, en particular por neumonía y afecciones cardiovasculares en mayores de 60 años. Deben emprenderse acciones de prevención específicas para prevenir la influenza, especialmente en estos dos grupos de edad.

OBJECTIVE: To estimate potential excess mortality attributable to influenza viruses A and B and human respiratory syncytial virus (HRSV) during peak seasons of influenza virus circulation in Colombia from 1997 to 2005. METHODS: A comparison of monthly, general mortality rates from pneumonia in children under 5 years of age and from pneumonia and cardiovascular disease in those more than 60 years of age in Bogota, Colombia, were compared to the city's peak seasons of influenza virus circulation. Mortality data were obtained from the National Bureau of Statistics of Colombia; peak seasons of virus circulation were defined as contiguous months in which the number of isolates was equal to or greater than half the total number of isolates for the year. Incidence rate ratios (IRR) and their 95 percent confidence intervals (95 percentCI) were determined. RESULTS: Influenza A demonstrated a pattern of seasonal circulation, but influenza B and HRSV did not. The increased circulation of influenza virus was associated with an average annual increase of 5 percent in overall mortality during the study period (IRR = 1.05; 95 percentCI: 1.046-1.064). During seasons of increased circulation of influenza viruses, the combined mortality from pneumonia and influenza for all ages was 11 percent higher than it was at other times (IRR = 1.11; 95 percentCI: 1.051-1.178). CONCLUSIONS: During peak seasons of influenza virus circulation in Colombia, there can be increased mortality, particularly from pneumonia and cardiovascular disease among those more than 60 years of age. Preventive actions specific to protecting against influenza should be taken, especially in these two age groups.

Normalización de un ensayo de ultramicroELISA para la detección de anticuerpos IgG al virus sincitial respiratorio

Se normalizó un ensayo de ultramicroELISA de doble anticuerpo para la detección de anticuerpos IgG al virus sincitial respiratorio (VSR), para ello se dispuso de un anticuerpo monoclonal antiproteína F del VSR, producido por el Centro de Ingeniería Genética y Biotecnología de La Habana (CIGB). La utilización de este anticuerpo posibilitó la inclusión de preparaciones antigénicas crudas en lugar de fracciones purificadas, lo que disminuye notablemente la reactividad obtenida con el control de antígeno. Las condiciones del ensayo fueron determinadas mediante titulación cruzada y se obtuvo una sensibilidad de 97,2 %, un 91 % de coincidencia y una especificidad 83,3 % del UMELISA con respecto a la fijación del complemento. Los resultados pueden ser expresados cualitativamente o en títulos de anticuerpos empleando una sola dilución de suero (1:40) y una curva patrón.

An ultramicroELISA assay of double antibody for the detection of IgG antibodies to the respiratory syncytial virus (RSV) wasstandardized. It was used a RVS antiprotein F monoclonal antibody produced by the Genetic Engineering and Biotechnology Center (GEBC) in Havana. The use of this antibody allowed to include crude antigenic preparations instead of purified fractions, which caused a significant reduction of the reactivity obtained with the antigen control. The assay conditions were determined by crossed titration. It was obtained a sensitivity of 97.2 %, a coincidence of 91 %, and a specificity of 83.3 % of the UMELISA as regards the complement fixation. The results may be qualitatively expressed or by antibody titres using only one serum dillution (1:40) and a pattern curve.