Faculty Bibliography

INTRODUCTION/BACKGROUND:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and elderly and to date, there is no safe or effective vaccine against RSV. Areas Covered: This review provides a roadmap to RSV vaccine development. It is a journey spanning over more than half a century from the initial disappointment with inactivated formalin vaccine to the current advancements in vaccine technology. We highlight the important aspects of RSV structural biology and protective immune response. We include discussion of newer fusion glycoprotein immune targets and current vaccine candidates. We used Pub Med and Medline resources for literature search. Expert opinion: A resurgence of information on the burden related to RSV infection coupled with the newer understanding of the molecular mechanism of RSV infection has reignited a tremendous activity in RSV vaccine discovery. The vaccine pipeline is diverse and target populations are varied, thus making the goal of a safe and effective RSV vaccine in the future within reach.

OBJECTIVE: The objective of this study was to compare risk for respiratory syncytial virus (RSV) hospitalizations (RSVH) for preterm infants 29 to 34 weeks gestational age (wGA) versus term infants before and after 2014 guidance changes for immunoprophylaxis (IP), using data from the 2012 to 2016 RSV seasons. STUDY DESIGN/METHODS: Using commercial and Medicaid claims databases, infants born between July 1, 2011 and June 30, 2016 were categorized as preterm or term. RSVH during the RSV season (November-March) were identified for infants aged <6 months and rate ratios (RRs) for hospitalization comparing preterm and term infants were calculated. Difference-in-difference models were fit to evaluate the changes in hospitalization risks in preterm versus term infants from 2012 to 2014 seasons to 2014 to 2016 seasons. RESULTS:<0.0001 for commercial and Medicaid samples). CONCLUSION/CONCLUSIONS: In infants aged <6 months, the risk for RSVH for infants 29 to 34 wGA compared with term infants increased significantly after the RSV IP recommendations became more restrictive.

Background. In 2014, the American Academy of Pediatrics recommended against the use of respiratory syncytial virus (RSV) immunoprophylaxis in infants 29-34 weeks gestational age (wGA) at birth without chronic lung disease/bronchopulmonary dysplasia (CLD/BPD) or congenital heart disease (CHD). To inform discussions of the clinical and economic value of RSV immunoprophylaxis in these infants, we compared RSV hospitalization (RSVH) severity and costs incurred by infants hospitalized from 2014-2016 at <6 months chronologic age (CA) for two groups: 29-34 wGA infants without CLD/BPD or CHD and term infants (>=37 wGA) without major health problems. Methods. Births were identified in the MarketScan Commercial (COM) and Multistate Medicaid (MED) databases. Term and 29-34 wGA infants without CLD/BPD or CHD were selected using DRG and ICD-9/10-CM diagnosis codes. RSVH occurring from Julu 1, 2014 to June 30, 2016 while infants were <6 months CA (the period of highest RSVH incidence) were identified by ICD-9/10-CM diagnosis codes. Severity measures were length of stay (LOS) in days, intensive care unit (ICU) admissions, and healthcare costs (paid amounts on reimbursed hospital claims in 2016 US$). Comparisons between term and 29-34 wGA infants were made with t-tests and chi-squared tests. Results. There were 1,114 RSVH in the COM data and 3,167 RSVH in the MED data during the study period. Mean LOS was longer for 29-34 wGA infants than term infants for each age category (P < 0.05) and tended to be longer for MED infants vs. COM infants (Figure 1). Thirty-eight percent of COM 29-34 wGA infants and 52% of MED 29-34 wGA infants hospitalized for RSV at <3 months CA were admitted to the ICU (Figure 2). RSVH costs for 29-34 wGA infants were greater than term RSVH costs for each age category (P < 0.05) and were greatest among 29-34 wGA infants hospitalized at <3 months CA: $41,104 for 29-34 wGA COM infants and $24,049 for 29-34 wGA MED infants (Figure 3). Conclusion. RSVH severity and costs were significantly higher for 29-34 wGA infants without CLD/BPD or CHD relative to term infants. Infants hospitalized at <3 months CA experienced the most severe hospitalizations and incurred the highest costs. (Figure Presented)

Background. In 2014, the American Academy of Pediatrics stopped recommending RSV immunoprophylaxis (RSV IP) for otherwise healthy infants 29-34 weeks gestational age (wGA), while continuing to recommend RSV IP for infants born at <29 wGA. The decline in RSV IP and associated increase in RSV hospitalizations (RSVH) among infants 29-34 wGA have been described previously, but potential effects of the 2014 guidance change on preterm infants <29 wGA are unknown. This study compared 2012-2014 and 2014-2016 outpatient RSV IP use as well as RSVH rates relative to term infants among otherwise healthy <29 wGA infants. Methods. Infants born from July 1, 2011 to June 30, 2016 were followed from birth hospitalization discharge through their first year of life in the MarketScan Commercial (COM) and Multistate Medicaid (MED) databases. DRG and ICD codes identified term and <29 wGA infants at birth. RSV IP receipt was derived from pharmacy and outpatient medical claims (inpatient RSV IP data were unavailable). RSVH were derived from inpatient medical claims. RSVH IP use and RSVH were assessed across three chronologic age (CA) groups: <3 months, 3-<6 months, and 6-<12 months. RSVH rate ratios for 2012-2014 and 2014-2016 were calculated for <29 wGA infants using healthy term infants 0-<12 months of age as a reference category. Results. Outpatient RSV IP receipt fell after 2014 for <29 wGA infants across all CA categories, with the greatest decline observed among infants <3 months CA (Table 1). Greater RSVH rates for <29 wGA infants relative to term infants were observed after 2014 (Figures 1 and 2), with infants <3 months CA experiencing the greatest percentage increases in relative RSVH risks. Conclusion. Outpatient RSV IP decreased and RSVH relative to term infants increased among otherwise healthy <29 wGA infants following the 2014 policy change, even though RSV IP continued to be recommended. The effects were greatest for infants <3 months CA and those insured by Medicaid. (Figure Presented)

Background. In 2014, the American Academy of Pediatrics (AAP) stopped recommending respiratory syncytial virus (RSV) immunoprophylaxis in infants 29-34 weeks gestational age (wGA) without chronic lung disease (CLD) or congenital heart disease (CHD). This study examined the impact of this guidance change on the severity and costs of first year of life RSV hospitalizations (RSVH) and all-cause bronchiolitis hospitalizations (BH) among preterm (PT) vs. term infants in the 2014-2016 seasonal years relative to the 2011-2014 seasonal years. Methods. Infants aged <1 year between July 1, 2011 and June 31, 2016 were identified from commercial insurance claims in the Optum Research Database. Diagnosis codes identified births of term and 29-34 wGA infants without CLD, CHD, or other health problems, RSVH, and BH. Length of stay (LOS), admission to the intensive care unit (ICU), and use of mechanical ventilation (MV) captured RSVH and BH severity. Costs were adjusted to 2015 USD. Results. A total of 362,382 births (29-34 wGA and term without major health problems) were identified, of which 13,666 (3.8%) were PT. RSVH and BH were more severe among PT infants in 2014-2016 vs. 2011-2014, with a greater mean LOS (RSVH: 6.8 vs. 4.7 days, P = 0.008; BH: 7.2 vs. 4.6, P = 0.021), a higher proportion of infants admitted to the ICU (RSVH: 42.4% vs. 25.3%, P = 0.014; BH: 39.1% vs. 23.7%, P = 0.009), and increased use of MV (RSVH: 14.1% vs. 6.1%, P = 0.067; BH: 14.8% vs. 5.3%, P = 0.013). Among term infants, LOS and ICU admissions were similar between 2014-2016 and 2011-2014 (P > 0.05), but there was an increased use of MV in the 2014-2016 season (RSVH: 6.9% vs. 4.2%, P = 0.009; BH: 6.3% vs. 3.7%, P = 0.003). Mean costs per hospitalization were greater for PT infants in 2014-2016 compared with 2011-2014 (RSVH: $29,382 vs. $16,572, P = 0.059; BH: $26,101 vs. $15,896, P = 0.047), whereas mean term hospitalization costs were similar (RSVH: $15,011 vs. $15,472, P = 0.705; BH: $14,555 vs. $14,603, P = 0.957). Conclusion. RSVH and BH severity and per-hospitalization costs (higher among PT infants relative to term infants) increased following the 2014 AAP immunoprophylaxis guidance change. The increases are likely explained by more frequent RSV hospitalizations among higher-risk 29-34 wGA infants in 2014-2016

Clostridium difficile is an important cause of health care associated infections. The epidemiology of C. difficile infection (CDI) in children has changed over the past few decades. There is now a higher incidence in hospitalized children, and there has been an emergence of community-onset infection. A hypervirulent strain, North American pulse type 1, has also developed. Neonates and young infants have high rates of colonization but rarely have symptoms. The well-known risk factor for CDI in children age 2 years or older is antibiotic use. Inflammatory bowel disease and cancer are associated with increased incidence and severity of CDI. Nucleic acid amplification tests are now widely used for diagnosis given their rapid turnover and higher sensitivity and specificity. The treatment for an initial episode and first recurrence is oral metronidazole. Oral vancomycin is reserved for second recurrence or severe cases. A new treatment option, fecal bowel transplant, has been reported to be safe and effective in adults, and studies are now being conducted in children. [Pediatr Ann. 2018;47(9):e359-e365.].