Evidence Of Respiratory Syncytial Virus Infection Research Articles

Estimating the burden of respiratory syncytial virus infection in young children in England: a novel approach to community-based serological surveys through data linkage

BackgroundBronchiolitis caused by respiratory syncytial virus (RSV) is the most common reason for hospital admissions in infants. The community burden of RSV is less well understood. We used a unique dataset linking serial serological data, questionnaires, and routinely collected health records to undertake the first community-based serological survey of RSV in England. MethodsWe used stored blood samples, tested for immunoglobulin G RSV postfusion F antibody, linked to questionnaires and primary and secondary care records from the Born in Bradford cohort study, collected at birth, and ages 1 and 2 years. We used finite mixture models to classify children as RSV infected or not infected according to their antibody concentrations. We fitted multivariable Poisson regression models with robust error variances to identify factors associated with increased risk of primary RSV infection at ages younger than 1 year and 1–2 years. FindingsThe study included 490 children. By their first birthday, 258 children (53%, 95% CI 48–57%) had serological evidence of past RSV infection, 99 (38%) of whom contacted health-care services during peak RSV season (November–January) due to a respiratory tract infection. Having older siblings (adjusted risk ratio [aRR] 1·52, 95% CI 1·21–1·92, comparing one to no older siblings), Pakistani ethnicity (1·31, 1·04–1·65, compared with White British), blood sample taken outside October–December (1·74, 1·35–2·24 for January–March and 1·60, 1·23–2·08 for April–June, compared with October–December), and attending formal childcare (1·40, 1·12–1·75, compared with no formal childcare) were predictive of RSV infection in infancy. A further 164 children (33%, 95% CI 29–38%) were newly infected at ages 1–2 years, 58 (35%) of whom had contact with health-care services. 14% (95% CI 11–17%) had no evidence of RSV infection by age 2 years. InterpretationAround half of children are infected with RSV during the first year of life, and one in seven children remain unexposed after their second year. Our findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes. Our novel approach reusing stored blood samples and linked data present a time-efficient and cheap method for future serological surveys of RSV. FundingWellcome Trust Seed Award In Science (grant reference number 207673/Z/17/Z).

Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique.

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group- and strain-specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross-reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains.

An epidemiological study of RSV infection in the Gambia.

To describe the epidemiology of respiratory syncytial virus (RSV) infection in a developing country. The work was carried out in three hospitals for primary cases and in the community for secondary cases in the western region of the Gambia, West Africa. RSV infection was diagnosed by immunofluorescence of nasopharyngeal aspirate samples in children younger than two years admitted to hospital with acute lower respiratory infection (ALRI). Routine records of all children with ALRI were analysed, and the incidence rates of ALRI, severe RSV-associated respiratory illness and hypoxaemic RSV infections were compared. A community-based study was undertaken to identify secondary cases and to obtain information about spread of the virus. 4799 children with ALRI who were younger than two years and lived in the study area were admitted to the study hospitals: 421 had severe RSV-associated respiratory illness; 55 of these were hypoxaemic. Between 1994 and 1996, the observed incidence rate for ALRI in 100 children younger than one year living close to hospital was 9.6 cases per year; for severe RSV-associated respiratory illness 0.83; and for hypoxaemic RSV-associated respiratory illness 0.089. The proportion of all ALRI admissions due to RSV was 19%. Overall, 41% of children younger than five years in compounds in which cases lived and 42% in control compounds had evidence of RSV infection during the surveillance period. RSV is an important cause of ALRI leading to hospital admission in the Gambia. Morbidity is considerable and efforts at prevention are worthwhile.

A monoclonal antibody pool for routine immunohistochemical detection of human respiratory syncytial virus antigens in formalin-fixed, paraffin-embedded tissue.

Four monoclonal antibodies (MAbs) with specificities for epitopes on human respiratory syncytial virus (RSV) proteins preserved after formalin fixation and paraffin embedding were identified in fixed and embedded virus-infected HEp-2 cell pellets. The MAbs bound epitopes on the fusion protein, the nucleoprotein, the phosphoprotein, and the M2 protein of the virus. Following high-temperature antigen unmasking, immunohistochemical staining revealed RSV antigens in the lungs of five of seven children who died with confirmed RSV infection and in none of nine children who died for other reasons, with no evidence of RSV infection. Staining was cytoplasmic, granular, and confined to epithelial cells. Intense staining was seen at the apex of ciliated bronchial and bronchiolar epithelial cells in all five positive cases. In one case, of pneumonitis, infected pneumocytes were present in the alveoli and in several cases, CD68-positive, cytokeratin-negative alveolar macrophages stained for viral antigens. These antibodies may prove useful in studies of the pathogenesis of RSV infection.

Bacterial coinfection in children hospitalized with respiratory syncytial virus infections.

Clinical and bacterial findings were prospectively studied in 90 children hospitalized because of middle or lower respiratory tract infection caused by respiratory syncytial virus (RSV) during a surveillance period of 12 months. The results were compared with those of RSV-negative children hospitalized with identical indications during the 3 peak months of the RSV epidemic (N = 91) or for the 3 months after the outbreak (N = 99). A high frequency of pneumonia and acute otitis media were found in both RSV-positive and RSV-negative children during the epidemic, but not in control patients after the epidemic. Bacterial infection, based on a significant rise of antibody titer and/or on detection of pneumococcal antigen in serum or urine, was observed in 39% of the children with RSV infection. The respective figures were 24% in RSV-negative children hospitalized during the epidemic and 8% after the epidemic. Our observations stress the role of RSV as a predisposing agent for secondary bacterial infection in the airways of children. The most common bacteria involved in the mixed RSV-bacterial infections were Streptococcus pneumoniae and Haemophilus influenzae, the latter being found only in pneumonic patients. The presence or absence of pneumonia or acute otitis media was not significantly correlated with evidence of pneumococcal infection. We conclude that a bacterial pathogen should be actively sought when managing patients with lower respiratory tract syndromes, especially in those who have evidence of RSV infection.