Natural Infection of Infants with Respiratory Syncytial Virus Subgroups A and B: A Study of Frequency, Disease Severity, and Viral Load

Abstract

Heterogeneity in respiratory syncytial virus (RSV) disease severity likely is due to a combination of host and viral factors. Infection with RSV subgroup A is thought to produce more severe disease than RSV-B. Higher RSV loads correlate with greater disease severity in hospitalized infants. Whether subgroup-specific variations in disease severity result from differences in RSV load has not been studied. A total of 102 RSVhospitalized infants Ͻ2 y of age were studied. Nasal washes were collected in a standardized manner and were cultured in Ͻ3 h in parallel with an RSV quantitative standard in a HEp-2 plaque assay. RSV-A (72%) was more frequent than RSV-B. Disease severity risk factors were similar between subgroups. RSV loads were similar between A and B subgroups (4.77 versus 4.68 log PFU/mL). Measures of disease severity were also similar between subgroups. There is extreme variability in respiratory syncytial virus (RSV) disease severity evidenced in previously healthy infants. Approximately 50% of infants are infected during their first year of life (1,2), yet only 3% of infants Ͻ1 y of age are hospitalized for RSV (3). Of RSV-hospitalized infants and children, only 10% require mechanical ventilation (4). In addition, 5-10% of those who require mechanical ventilation die (5). Furthermore, more than half of RSV-hospitalized infants and a large percentage of infants who require mechanical ventilation and even die from RSV infection are previously healthy (3,5). These striking disease severity differences cannot be explained by existing neutralizing antibody titers alone (6) and are likely due to a combination of host factors and viral factors. Although this finding is not universally confirmed (7), RSV subgroup A has been shown in several studies to produce more severe disease than RSV-B (8 -12). We previously demonstrated that RSV load measured from nasal wash parallels that in the lower respiratory tracts of previously healthy infected infants in the age range for primary RSV infection (13). We also previously correlated higher nasal wash RSV loads with greater disease severity in hospitalized previously healthy infants. Infants who experience RSV infection severe enough to cause respiratory failure have~1 log PFU/mL greater nasal RSV load than those who do not (14). Although the relationship between RSV concentrations and disease severity is controversial (15,16), higher viral loads measured near the time of admission have also been shown to correlate with longer durations of hospitalization (17,18). Whether RSV loads vary by subgroup and whether RSV subgroup-specific variations in disease severity are the result of differences in RSV load have not been studied. METHODSWe conducted a prospective observational study of infants who were hospitalized with RSV infection during three successive winter seasons (1997)(1998)(1999)(2000). Clinical data were obtained through interviews of each infant's caregiver at the time of enrollment. Patients were included in the study when they were Ͻ2 y of age and had RSV dete...

Comparison of a Real-Time Reverse Transcriptase PCR Assay and a Culture Technique for Quantitative Assessment of Viral Load in Children Naturally Infected with Respiratory Syncytial Virus

“…A single other report of RSV subgroup quantification in natural human infection has been published (6). Using quantitative culture, this smaller, previous study failed to show a significant difference between RSV subgroups.…”

“…The study was conducted with the approval of the University of Tennessee Institutional Review Board and included appropriate informed consent, complying with all relevant federal guidelines and institutional policies. Nasal washes and tracheal aspirates were collected by study team members using a quantified-collection method as previously described (6). Briefly, secretions were collected into 4°C sucrosecontaining RSV transport media and placed into the plaque assays within 3 h. Other individual aliquots of each respiratory secretion sample were then snap frozen on dry ice and frozen at Ϫ80°C until thawing for the RTrtPCR assay.…”

Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs

“…The natural individual susceptibiliy of hRSV infection in the lambs may explain part of this observation. Similarly, most clinicians recognize bronchiolitis as a “constellation of clinical signs and symptoms occurring in children younger than 2 years, including a viral upper respiratory tract prodrome followed by increased respiratory effort and wheezing” 27 with a high heterogeneity in disease severity likely due to a combination of host and viral factors 45 . Study procedures may also explain part of the variability seen in the clinical parameters as the procedures for clinical assessments were adapted for study 3, allowing for increased observation times and more robust scoring of lamb behavioral changes.…”

A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus

“…Nasal washes were collected into cold RSV stabilization media (25), transported on ice, and placed onto HEp-2 cell monolayers within 30 min of collection. Quantitative culture in HEp-2 cell plaque assays was performed in 12-well plates using triplicate 10-fold dilutions of nasal wash as previously described (25). RSV quantitative standards (RSV-A Long ATCC VR-26) were run in parallel with each plaque assay.…”