Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial vir... more Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial virus (RSV) disease in preterm infants ≤ 35 wGA. However, some RSV guidelines currently recommend stopping palivizumab after 3 months of age in the midst of the RSV season. This article evaluates the need for full-season dosing by reviewing the pharmacokinetic properties of palivizumab and RSV hospitalization (RSVH) risk as a function of chronologic age. Precise human palivizumab protective levels are not established. Clinical trials show significant interpatient variability in palivizumab serum trough concentrations. Partial season dosing is associated with increased risk of RSVH. For late-preterm infants, data suggest that the risk of RSVH remains elevated through at least 6 months of age. Monthly, full-season palivizumab dosing provides the only empirically proven protection from RSVH. In conclusion, late-preterm infants are at significant risk for RSVH through at least 6 months of age and would benefit from dosing throughout the RSV season.
The objective of this study was to quantify time spent plus out-of-pocket costs associated with c... more The objective of this study was to quantify time spent plus out-of-pocket costs associated with confirmed respiratory syncytial virus (RSV) hospitalization of infants not prophylaxed against RSV. A prospective survey was carried out at multiple tertiary care hospitals in the United States. The patients consisted of a consecutive sample of infants <12 months, born between 33 and 35 weeks of gestation. One site also enrolled full-term infants hospitalized with confirmed RSV. Daily patient census identified eligible patients. Consenting caregivers of eligible subjects (n=84, 1 refusal) were interviewed on discharge day and by telephone approximately 30 days following discharge regarding time and out-of-pocket costs due to RSV. Total average out of pocket expenses were 643.69 US dollars (range 21-16,867 US dollars; SD 2,403 US dollars) for premature and 214.42 US dollars (range 6-827 US dollars; SD 218 US dollars) (P=.0158) for full-term subjects. Total average economic burden per admission was 4517.07 US dollars for premature and 2135.30 US dollars for full-term infants, including the value of lost productivity but excluding inpatient hospital and physician bills and lost income. Premature infants (n=48) had longer hospital stays (mean 6.9 days; SD 7.5 vs. 3.4 days; SD 2.6 days) (P=.001) with an associated mean total time spent by up to 5 adults of 281.7 hours (range 25-2819.7 hours; SD 465.8 hours) versus a mean of 139.7 hours (range 31.8-561.3 hours; SD 118.1 hours) for term infants (P=.109). Time and out-of-pocket costs continued after discharge. RSV hospitalization of infants is associated with substantial, previously unmeasured time and monetary losses. These losses continued following discharge. The economic burden on families and society appears heavier for infants born at 33 to 35 weeks of gestation than for full-term infants.
Viral culture plaque morphology in human cell lines are markers for growth capability and cytopat... more 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. 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. 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. 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.
Background. New aerosol drugs for infants may require more efficient delivery systems, including ... more Background. New aerosol drugs for infants may require more efficient delivery systems, including face masks. Maximizing delivery efficiency requires tight-fitting masks with minimal internal mask volumes, which could cause carbon dioxide (CO2) retention. An RNA-interference-based antiviral for treatment of respiratory syncytial virus in populations that may include young children is designed for aerosol administration. CO2accumulation within inhalation face masks has not been evaluated.Methods. We simulated airflow and CO2concentrations accumulating over time within a new facemask designed for infants and young children (PARI SMARTMASK®Baby). A one-dimensional model was first examined, followed by 3-dimensional unsteady computational fluid dynamics analyses. Normal infant breathing patterns and respiratory distress were simulated.Results. The maximum average modeled CO2concentration within the mask reached steady state (3.2% and 3% for normal and distressed breathing patterns resp.)...
Heterogeneity in respiratory syncytial virus (RSV) disease severity likely is due to a combinatio... more 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 RSV-hospitalized infants <2 y of age were studied. Nasal washes were collected in a standardized manner and were cultured in <3 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.
This report presents three cases of neonatal group B streptococcal ventriculitis and assesses sev... more This report presents three cases of neonatal group B streptococcal ventriculitis and assesses seven others identified by a literature review. In contrast to the well described acute manifestations of group B streptococcal meningitis, disease onset tended to be insidious with four of seven cases presenting over a period of 1 to 6 weeks and six cases presenting with nonspecific signs and symptoms without fever. Persistent protein content elevation and low glucose level in the cerebrospinal fluid was observed, indicating chronic inflammation. All patients developed obstructive hydrocephalus requiring ventriculoperitoneal shunt placement. One child died, and six of nine survivors were left with significant neurologic deficits. Physicians should be aware of this indolent but serious manifestation of group B streptococcal infection.
A plethora of clinical experience exists defining the factors associated with differences in seve... more A plethora of clinical experience exists defining the factors associated with differences in severity of childhood respiratory syncytial virus (RSV) infections. These clinical severity factors reveal a wealth of information about the pathogenesis of this disease. Reviewing and interpreting the clinical risk factors to gain an insight into RSV pathogenesis is important, especially considering the relative lack of parallel between many animal models of RSV infection and observed human disease. Existing and unpublished data on severity risk factors are reviewed and placed into a working pathogenesis model. Important factors discussed are: (1) the critical role of the timing of the infection; (2) its rapidity of progression to involve the lower respiratory tract; (3) factors limiting this spread; (4) the nature of the pathogenic immune response; and (5) the host genetic and other factors that alter this immune response. Pending new data involving these and other processes will more fully illuminate the spectrum of childhood RSV disease.
... Respiratory syncytial virus (RSV) is a ubiquitous, seasonal virus infecting over half of all ... more ... Respiratory syncytial virus (RSV) is a ubiquitous, seasonal virus infecting over half of all ... This free extracellular virus is exposed to passive neutralizing antibody. ... to other respiratory viruses, statistically significant protection against non-RSV respiratory hospitalizations was also ...
Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial vir... more Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial virus (RSV) disease in preterm infants ≤ 35 wGA. However, some RSV guidelines currently recommend stopping palivizumab after 3 months of age in the midst of the RSV season. This article evaluates the need for full-season dosing by reviewing the pharmacokinetic properties of palivizumab and RSV hospitalization (RSVH) risk as a function of chronologic age. Precise human palivizumab protective levels are not established. Clinical trials show significant interpatient variability in palivizumab serum trough concentrations. Partial season dosing is associated with increased risk of RSVH. For late-preterm infants, data suggest that the risk of RSVH remains elevated through at least 6 months of age. Monthly, full-season palivizumab dosing provides the only empirically proven protection from RSVH. In conclusion, late-preterm infants are at significant risk for RSVH through at least 6 months of age and would benefit from dosing throughout the RSV season.
The objective of this study was to quantify time spent plus out-of-pocket costs associated with c... more The objective of this study was to quantify time spent plus out-of-pocket costs associated with confirmed respiratory syncytial virus (RSV) hospitalization of infants not prophylaxed against RSV. A prospective survey was carried out at multiple tertiary care hospitals in the United States. The patients consisted of a consecutive sample of infants <12 months, born between 33 and 35 weeks of gestation. One site also enrolled full-term infants hospitalized with confirmed RSV. Daily patient census identified eligible patients. Consenting caregivers of eligible subjects (n=84, 1 refusal) were interviewed on discharge day and by telephone approximately 30 days following discharge regarding time and out-of-pocket costs due to RSV. Total average out of pocket expenses were 643.69 US dollars (range 21-16,867 US dollars; SD 2,403 US dollars) for premature and 214.42 US dollars (range 6-827 US dollars; SD 218 US dollars) (P=.0158) for full-term subjects. Total average economic burden per admission was 4517.07 US dollars for premature and 2135.30 US dollars for full-term infants, including the value of lost productivity but excluding inpatient hospital and physician bills and lost income. Premature infants (n=48) had longer hospital stays (mean 6.9 days; SD 7.5 vs. 3.4 days; SD 2.6 days) (P=.001) with an associated mean total time spent by up to 5 adults of 281.7 hours (range 25-2819.7 hours; SD 465.8 hours) versus a mean of 139.7 hours (range 31.8-561.3 hours; SD 118.1 hours) for term infants (P=.109). Time and out-of-pocket costs continued after discharge. RSV hospitalization of infants is associated with substantial, previously unmeasured time and monetary losses. These losses continued following discharge. The economic burden on families and society appears heavier for infants born at 33 to 35 weeks of gestation than for full-term infants.
Viral culture plaque morphology in human cell lines are markers for growth capability and cytopat... more 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. 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. 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. 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.
Background. New aerosol drugs for infants may require more efficient delivery systems, including ... more Background. New aerosol drugs for infants may require more efficient delivery systems, including face masks. Maximizing delivery efficiency requires tight-fitting masks with minimal internal mask volumes, which could cause carbon dioxide (CO2) retention. An RNA-interference-based antiviral for treatment of respiratory syncytial virus in populations that may include young children is designed for aerosol administration. CO2accumulation within inhalation face masks has not been evaluated.Methods. We simulated airflow and CO2concentrations accumulating over time within a new facemask designed for infants and young children (PARI SMARTMASK®Baby). A one-dimensional model was first examined, followed by 3-dimensional unsteady computational fluid dynamics analyses. Normal infant breathing patterns and respiratory distress were simulated.Results. The maximum average modeled CO2concentration within the mask reached steady state (3.2% and 3% for normal and distressed breathing patterns resp.)...
Heterogeneity in respiratory syncytial virus (RSV) disease severity likely is due to a combinatio... more 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 RSV-hospitalized infants <2 y of age were studied. Nasal washes were collected in a standardized manner and were cultured in <3 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.
This report presents three cases of neonatal group B streptococcal ventriculitis and assesses sev... more This report presents three cases of neonatal group B streptococcal ventriculitis and assesses seven others identified by a literature review. In contrast to the well described acute manifestations of group B streptococcal meningitis, disease onset tended to be insidious with four of seven cases presenting over a period of 1 to 6 weeks and six cases presenting with nonspecific signs and symptoms without fever. Persistent protein content elevation and low glucose level in the cerebrospinal fluid was observed, indicating chronic inflammation. All patients developed obstructive hydrocephalus requiring ventriculoperitoneal shunt placement. One child died, and six of nine survivors were left with significant neurologic deficits. Physicians should be aware of this indolent but serious manifestation of group B streptococcal infection.
A plethora of clinical experience exists defining the factors associated with differences in seve... more A plethora of clinical experience exists defining the factors associated with differences in severity of childhood respiratory syncytial virus (RSV) infections. These clinical severity factors reveal a wealth of information about the pathogenesis of this disease. Reviewing and interpreting the clinical risk factors to gain an insight into RSV pathogenesis is important, especially considering the relative lack of parallel between many animal models of RSV infection and observed human disease. Existing and unpublished data on severity risk factors are reviewed and placed into a working pathogenesis model. Important factors discussed are: (1) the critical role of the timing of the infection; (2) its rapidity of progression to involve the lower respiratory tract; (3) factors limiting this spread; (4) the nature of the pathogenic immune response; and (5) the host genetic and other factors that alter this immune response. Pending new data involving these and other processes will more fully illuminate the spectrum of childhood RSV disease.
... Respiratory syncytial virus (RSV) is a ubiquitous, seasonal virus infecting over half of all ... more ... Respiratory syncytial virus (RSV) is a ubiquitous, seasonal virus infecting over half of all ... This free extracellular virus is exposed to passive neutralizing antibody. ... to other respiratory viruses, statistically significant protection against non-RSV respiratory hospitalizations was also ...
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Papers by J. Devincenzo