A Historical Perspective on Respiratory Syncytial Virus Prevention: A Journey Spanning Over Half a Century From the Setback of an Inactive Vaccine Candidate to the Success of Passive Immunization Strategy.

The efforts to prevent respiratory syncytial virus (RSV) infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment after testing a formalin-inactivated RSV (FI RSV) vaccine candidate. This inactivated RSV vaccine was not protective. A large number of the vaccinated RSV-naive children, when subsequently exposed to natural RSV infection from wild-type virus in the community, developed severe lung inflammation termed enhanced respiratory disease. This resulted in a halt in RSV vaccine development. In the 1990s, attention turned to the potential for passive protection against severe RSV disease with immunoglobulin administration. This led to studies on using standard intravenous immunoglobulins in high-risk infants, followed by high-titer RSV immunoglobulin preparation and, subsequently, the development of RSV monoclonal antibodies. Over the past 25 years, palivizumab has been recognized as a safe and effective monoclonal antibody as a prevention strategy for RSV in high-risk children. Its high cost and need for monthly administration, however, has hindered its use to ~2% of the birth cohort, neglecting the vast majority of newborns, including healthy full-term infants who comprise the largest portion of RSV hospitalizations and the greatest part of the burden of RSV disease. Still these efforts, helped pave the way for the present advances in RSV prevention that hold promise for mitigating severe RSV disease for all infants.

Respiratory Syncytial Virus Infection and Apnea Risk As Criteria for Hospitalization in Full Term Healthy Infants.

Introduction Apnea is recognized as a serious and potentially life-threatening complication associated with Respiratory Syncope Virus (RSV). The literature reports a wide range of apnea rates for infants with comorbid factors. Prematurity and young chronological age have been historically associated with the risk of apnea in hospitalized infants. Few studies have specifically examined the risk of apnea in healthy infants presenting to the emergency department. Methods This is a retrospective review of infants diagnosed with RSV using a PCR assay. Patients were divided into "mild" and "severe" cohorts based on symptoms at presentation. This study occurred in the NYU Langone Long Island (NYULI) pediatric emergency department (ED), a midsize academic hospital in the Northeast United States. The study included infants <6 months of age, born full term without comorbid conditions such as chronic lung or cardiac conditions, seen in NYULI ED over three consecutive RSV seasons (2017-2020). The primary outcome was the risk of apneic events. Secondary outcomes included hospital admission, ICU admission, length of stay, and supplemental oxygen support. Results The risk of apnea was <2%, regardless of disease severity. There were no significant differences in demographics between mild and severe disease. Cohorts differed significantly in the number of hospitalizations (41 milds vs. 132 severe), ICU admissions (2 milds vs. 27 severe), need for oxygen support (17 milds vs. 92 severe), hospital readmissions (2 milds vs. 42 severe), and length of stay (2 days milds vs. 3 days severe). Conclusions Apnea does not pose a significant risk for healthy full-term infants with RSV disease of any severity. The decision to admit this population to the hospital should be based on clinical presentation and not solely on the perceived risk of apnea.

Impact of COVID-19 on HPV Vaccination Rates in New York City and Long Island.

BACKGROUND: In the United States, uptake of human papillomavirus (HPV) vaccination has been exceptionally low as compared with other vaccines. During the coronavirus disease (COVID-19) pandemic, routine vaccinations were deferred or delayed, further exacerbating HPV vaccine hesitancy. The specific effect of the pandemic on HPV vaccination rates in the United States has not been yet described. METHODS: We aimed to determine the percentage of children achieving full HPV vaccination (2 doses) by age 15 years and to compare prepandemic to pandemic rates of HPV vaccination at pediatric practices across our institution. A retrospective chart review was performed to compare HPV vaccination rates in the "prepandemic" and "pandemic" periods for all children 9 through 14 years of age. Additionally, peaks in COVID-19 positivity were compared with HPV vaccination rates. RESULTS: Of children 9-14 years old, 49.3% received at least 1 dose of HPV vaccine in the prepandemic period, compared with 33.5% during the pandemic ( P < 0.0001). Only 33.5% of patients received the full 2-dose series of HPV prepandemic, compared with 19.0% of patients during the pandemic ( P < 0.0001). When COVID-19 positivity rates peaked, HPV vaccination also declined. CONCLUSIONS: The issue of low HPV vaccination rates was amplified due to the COVID-19 pandemic, as illustrated by the correlation between peaks in COVID-19 positivity and low rates of HPV vaccination.

Increasing Rates of RSV Hospitalization among Preterm Infants: A Decade of Data.

OBJECTIVE: In 2014, the American Academy of Pediatrics (AAP) changed its policy on the use of respiratory syncytial virus immunoprophylaxis (RSV-IP) so that RSV-IP was no longer recommended for use among infants without other medical conditions born >29 weeks of gestational age (wGA). This study examines 10-year trends in RSV-IP and RSV hospitalizations among term infants and preterm infants born at 29 to 34 wGA, including the 5 RSV seasons before and 5 RSV seasons after the AAP guidance change. STUDY DESIGN: A retrospective observational cohort study of a convenience sample of infants less than 6 months of age during RSV season (November-March) born between July 1, 2008, and June 30, 2019, who were born at 29 to 34 wGA (preterm) or >37 wGA (term) in the IBM MarketScan Commercial and Multi-State Medicaid databases. We excluded infants with medical conditions that would independently qualify them for RSV-IP. We identified RSV-IP utilization along with RSV and all-cause bronchiolitis hospitalizations during each RSV season. A difference-in-difference model was used to determine if there was a significant change in the relative rate of RSV hospitalizations following the 2014 policy change. RESULTS: There were 53,535 commercially insured and 85,099 Medicaid-insured qualifying preterm infants and 1,111,670 commercially insured and 1,492,943 Medicaid-insured qualifying term infants. Following the 2014 policy change, RSV-IP utilization decreased for all infants, while hospitalization rates tended to increase for preterm infants. Rate ratios comparing preterm to term infants also increased. The relative rate for RSV hospitalization for infants born at 29 to 34 wGA increased significantly for both commercially and Medicaid-insured infants (1.95, 95% CI: 1.67-2.27, p <0.001; 1.70, 95% CI: 1.55-1.86, p <0.001, respectively). Findings were similar for all-cause bronchiolitis hospitalizations. CONCLUSION: We found that the previously identified increase in RSV hospitalization rates among infants born at 29 to 34 wGA persisted for at least 5 years following the policy change. KEY POINTS: · Immunoprophylaxis rates decreased after the 2014 American Academy of Pediatrics guidelines update.. · Rate of RSV hospitalization increased among preterm infants after the 2014 AAP guidelines update.. · Increase in RSV hospitalization persisted for at least 5 years after AAP guidelines update..

Clinical Outcomes of Children With Extended-spectrum ß -Lactamase Urinary Tract Infection Receiving Discordant Empiric Antibiotic: A Comparative Study of Fever Duration, Length of Stay, and Readmissions.

There has been a recent increase in the incidence of urinary tract infections (UTIs) caused by extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, which are resistant to third-generation cephalosporins. Our goal was to compare the clinical responses of patients with ESBL UTI and non-ESBL UTI who received empiric third-generation cephalosporins. A retrospective analysis was performed on data collected between June 1, 2013, and June 30, 2017, from children aged 0 days to 19 years old who presented to NYU Langone Long Island Hospital's pediatric ED and/or were admitted with a UTI caused by Enterobacteriaceae. There was no significant difference in median length of fever duration. However, ESBL patients had significantly longer hospital stays, higher 30-day readmission rate, and higher 7-day revisit rate. It is reasonable to maintain an empiric UTI antibiotic choice rather than selecting a broad-spectrum antibiotic, such as carbapenem for children at high risk of ESBL UTI.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Respiratory Syncytial Virus (RSV) Update.

Since the initial identification of respiratory syncytial virus (RSV) in 1956, much has been learned about the epidemiological impact and clinical manifestations of RSV infections [...].

Children Lagging with COVID-19 Vaccination.

Children account for a growing share of coronavirus disease 2019 (COVID-19) infections in the United States. Since the widespread availability of COVID-19 vaccine in adults, there has been an upward trend of cases in children, accounting for approximately 20% of the weekly new cases. The majority (38.3%) reported in high school students age 14 to 17 years. Children are also at risk of a postinflammatory condition, known as multisystem inflammatory syndrome in children, after COVID-19. In addition, infected children could transmit the virus to vulnerable adults, contributing to ongoing pandemic. We believe that children need to be vaccinated against COVID-19 and review the available evidence. [Pediatr Ann. 2022;51(5):e180-e185.].

Diurnal Temperature Variation: Addressing Once-Daily Nighttime Fevers in the Era of COVID-19.

Pediatric patients with "once-daily" fevers are often referred to pediatric infectious disease specialists for evaluation. Often, these fevers occur at nighttime in the absence of additional symptoms and come to the caregiver's attention after a viral illness. It is crucial for caregivers and providers to be able to define and measure fever accurately when trying to ascertain the true etiology of this clinical picture. Fever education is critical in providing reassurance to parents, and fever diaries should be encouraged. In a well-appearing child without any additional symptoms, at least a percentage of these fevers can be explained by normal diurnal variation of temperature. [Pediatr Ann. 2022;51(5):e202-e205.].

The Continued Threat of Influenza A Viruses.

Influenza A virus (IAV) is a major cause of respiratory infections worldwide, with the most severe cases occurring in the very young and in elderly individuals [...].

Human Papillomavirus Knowledge and Communication Skills: A Role-Play Activity for Providers.

Introduction: Human papillomavirus (HPV) infection and related cancers are a major cause of morbidity and mortality worldwide. Routine vaccination against HPV is recommended for patients starting at age 9-12 years. Discussing this vaccine with parents of young children can be challenging for clinicians. Barriers include parental beliefs, strength and quality of clinician recommendations, physician knowledge of HPV disease and vaccines, and provider comfort levels with discussing sexuality. Methods: Our interactive workshop began with a predidactic role-play session addressing common concerns about the HPV vaccine where participants took turns playing a concerned parent or provider. We then gave a 30-minute didactic lecture and conducted a postdidactic role-play session to practice communication skills in promoting the HPV vaccine. All participants completed pre- and postintervention knowledge and skill self-assessments. Results: Twenty-eight pediatric residents and medical students participated. We observed significant improvement in their ability to appropriately recommend the HPV vaccine in the postdidactic role-play (all ps < .02). Learner knowledge improved from pre- to postintervention (from 34% to 100%, p < .0025, based on average score), as did self-perceived comfort and confidence levels (from 3.6 to 4.3, p < .0001, average score based on a 5-point Likert scale). Discussion: An interactive workshop utilizing role-play supplemented by a didactic lecture was effective in improving participants' knowledge, communication skills, comfort levels, and confidence levels regarding HPV disease and vaccines. The workshop offers a practical and interpersonal approach to improving learners' skills in discussing the HPV vaccine with parents.

Impact of the 2014 American Academy of Pediatrics Policy on RSV Hospitalization in Preterm Infants in the United States.

Despite being a leading cause of hospitalization due to lower respiratory tract infections, the treatment of respiratory syncytial virus (RSV) infection is primarily supportive. Palivizumab is the only licensed immunoprophylaxis (IP) available for preventing severe RSV infection in high-risk populations including ≤ 35 weeks' gestational age (wGA) infants and children with chronic lung disease of prematurity or congenital heart disease. The American Academy of Pediatrics (AAP) has published its IP recommendations since the approval of palivizumab. In 2014, the AAP stopped recommending RSV IP in 29-34 wGA infants without comorbidities and stated that RSV hospitalization (RSVH) risk in otherwise healthy ≥ 29 wGA infants and term infants was similar. Since then, experts in the field have debated the appropriateness of the 2014 policy change, and several real-world evidence studies at the national and regional levels in the US have examined the impact of the AAP policy on 29-34 wGA infants. Overall, these studies showed a significant decline in RSV IP use and a concurrent increase in RSVH risk among 29-34 wGA infants relative to term infants in the seasons after the 2014 policy change. A similar decrease in IP use and increase in RSVH risk was also observed among < 29 wGA infants relative to term infants after the 2014 policy change. This decrease could be an unintended consequence as < 29 wGA infants are an in-policy population recommended to receive RSV IP. According to the National Perinatal Association, strong evidence exists to support the use of RSV IP in all ≤ 32 wGA and 32-35 wGA infants with risk factors such as attending day care, having ≥ 1 school-aged siblings, twin or greater multiple gestation, younger age, and exposure to parental smoking. Until new preventive and treatment options become available, palivizumab can help prevent and mitigate RSV disease burden among high-risk preterm infants.