Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants.

BackgroundLongitudinal respiratory syncytial virus (RSV) dynamics have not been well studied despite the existence of factors favoring prolonged RSV replication including high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naive infants over prolonged time spans.MethodsDuring 2014-2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time quantitative reverse transcriptase polymerase chain reaction assay. After observing viral load rebound phenomenon in some infants, the viral dynamics of 27 infants with sufficient longitudinal viral load data points were analyzed using the pre-defined criteria for viral rebound. Additional analyses were performed comparing age with viral rebound, viral clearance rates, and viral load area-under-the-curve (AUCVL).ResultsThe 51 infants (303 nasal aspirate samples; mean of 5.9 per patient) exhibited slower than expected viral clearance. Lower age trended toward slower viral clearance and greater AUCVL. Six infants had detectable viral loads ≥1 month after symptom onset. Ten of twenty-seven evaluable subjects exhibited viral rebound and this rebound was age-dependent (P=0.0259). All but one rebounder were <70 days old.ConclusionInfants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.

Relating plaque morphology to respiratory syncytial virus subgroup, viral load, and disease severity in children.

BACKGROUND: Viral culture plaque morphology in human cell lines are markers for growth capability and cytopathic effect, and have been used to assess viral fitness and select preattenuation candidates for live viral vaccines. We classified respiratory syncytial virus (RSV) plaque morphology and analyzed the relationship between plaque morphology as compared to subgroup, viral load and clinical severity of infection in infants and children. METHODS: We obtained respiratory secretions from 149 RSV-infected children. Plaque morphology and viral load was assessed within the first culture passage in HEp-2 cells. Viral load was measured by polymerase chain reaction (PCR), as was RSV subgroup. Disease severity was determined by hospitalization, length of stay, intensive care requirement, and respiratory failure. RESULTS: Plaque morphology varied between individual subjects; however, similar results were observed among viruses collected from upper and lower respiratory tracts of the same subject. Significant differences in plaque morphology were observed between RSV subgroups. No correlations were found among plaque morphology and viral load. Plaque morphology did not correlate with disease severity. CONCLUSION: Plaque morphology measures parameters that are viral-specific and independent of the human host. Morphologies vary between patients and are related to RSV subgroup. In HEp-2 cells, RSV plaque morphology appears unrelated to disease severity in RSV-infected children.

Characteristics of Academic Detailing: Results of a Literature Review.

BACKGROUND: Academic detailing is an evidence-based strategy to improve patient care. Efforts to understand the intervention and to use it strategically require an understanding of its important characteristics. A recent systematic review and a subsequent reporting framework call for more accurate and complete reporting of continuing medical education interventions. OBJECTIVES: Building on a previously published systematic review of 69 studies, we sought to determine how an expanded set of 106 academic detailing studies, including many recently published articles, fared with respect to reporting of important data about this intervention. METHODS: We conducted a search of MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (clinical) database, and Scopus, from which we identified 38 additional randomized controlled trials published from August 2007 through March 2013. Including the original 69 studies, we abstracted 106 available English-language studies and quantitatively analyzed information about 4 important characteristics of academic detailing: content of visits, clinicians being visited, communication process underlying visits, and outreach workers making visits. RESULTS: We found considerable variation (36.5%-100%) in the extent of reporting intervention characteristics, especially about the communication process underlying visits and the outreach workers making visits. The best overall documentation of intervention characteristics of any single study was 68%. Results also demonstrate wide variation in the approach to academic detailing. CONCLUSIONS: This study demonstrates the need for a standardized approach to collecting and reporting data about academic detailing interventions. Our findings also highlight opportunities for using academic detailing more effectively in research and quality-improvement efforts.

Opportunities for early therapy of respiratory syncytial virus (RSV) infection: what happens before hospitalization.

RSV loads of infants are already declining near the time of hospitalization. For optimal effect, antiviral and other RSV therapeutics therefore may need to be applied before this occurs. 134 RSV-hospitalized infants were studied to determine the timing of events and their healthcare seeking behavior prior to hospitalization. Sixty-two percent of infants had contact with a health care professional > or = 1 day prior to hospitalization and 46% had such a contact on > or = 2 different days prior to hospitalization. The mean (S.D.) duration of RSV symptoms prior to hospitalization was 3.9 +/- 2.3 days and prior to first health care contact was 2.6 +/- 1.8 days. RSV-hospitalized infants routinely have contact with health care professionals at significantly early time points in their illness. These contacts are potential opportunities for initiation of early anti-RSV therapy.