Cell-free DNA blood test for the diagnosis of pediatric tuberculous meningitis.

Pediatric tuberculous meningitis (TBM) is a severe form of tuberculosis that may present in children. The current diagnostic methods may have a limited impact on initial clinical decision-making. We present three children with tuberculous meningitis who had Mycobacterium tuberculosis complex cell-free DNA (cfDNA) detected in their blood within three days of sampling. Our cases described here illustrate for the first time the potential role of cfDNA blood tests in the rapid diagnosis of TBM.

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..

COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review.

Although pediatric populations experienced lower COVID-19 severity and mortality than adults, the epidemiology of this disease continues to evolve. COVID-19 clinical manifestations in pediatrics commonly include fever and cough, but may differ from adults and by variant. Serious complications, including MIS-C, rarely occur. Although early data showed a decreased likelihood of COVID-19 transmission from children versus adults, outbreaks and viral shedding studies support pediatric transmission potential. Children may mount more robust initial immune responses to SARS-CoV-2 versus adults. COVID-19 vaccines with available pediatric data include BNT162b2, mRNA-1273, CoronaVac, and BBIBP-CorV. Depending on age group and jurisdiction, BNT162b2 and mRNA-1273 have received full approval or emergency/conditional authorization in the United States and European Union from 6 months of age. Clinical trials have shown BNT162b2 and mRNA-1273 safety and high efficacy in pediatric populations, with demonstrably noninferior immune responses versus young adults. Real-world studies further support BNT162b2 safety and effectiveness against the Delta variant. mRNA vaccination benefits are considered to outweigh risks, including myocarditis; however, pediatric vaccination rates remain relatively low. Given a growing body of clinical trial and real-world data showing vaccine safety and effectiveness, pediatric vaccination should be prioritized as an important strategy to control the pandemic.

Recognition & management of varicella infections and accuracy of antimicrobial recommendations: Case vignettes study in the US.

BACKGROUND: In 1995, the CDC recommended one-dose routine varicella immunization for children <12 years of age, expanding its recommendation to two doses in 2006. Today, with widespread varicella vaccination coverage, an estimated 3.5 million cases of varicella, 9,000 hospitalizations, and 100 deaths are prevented annually in the United States. Since varicella infections are now uncommon, health care providers (HCPs) may not recognize varicella infections and may prescribe inappropriate treatment. METHODS: An online survey of HCPs was conducted to assess recognition and management of varicella infections. Responses to eight varicella vignettes describing patients with varying varicella symptoms were analyzed and descriptive analyses performed. Stratified analysis comparing responses of those licensed before and in/after 1996 was also performed. RESULTS: 153 HCPs (50 nurse practitioners, 103 doctors) completed the survey. Mean age of respondents was 44 years. 62% were female, and 82% were licensed before 1996. Varicella infection was correctly diagnosed 79% of the time. HCPs correctly recognized uncomplicated varicella vignettes 85% of the time versus 61% of the time for complicated varicella vignettes. Antibiotics were recommended 17% of the time and antivirals 18% of the time, of which 25% and 69% (respectively) were not appropriate per guidelines. HCPs licensed before 1996 were better able to recognize varicella compared to those licensed later, but prescribed more antimicrobials medications to treat varicella. CONCLUSIONS: Although most HCPs recognized varicella infection, a sizable proportion could not recognize cases with complications, and some of the varicella cases were inappropriately treated with antibiotics and/or antivirals. Additional HCP training and high vaccination coverage are important strategies to avoid inaccurate diagnoses and minimize unnecessary exposure to antimicrobial/antiviral therapies.

Impact of universal varicella vaccination on the use and cost of antibiotics and antivirals for varicella management in the United States.

BACKGROUND: Our objective was to estimate the impact of universal varicella vaccination (UVV) on the use and costs of antibiotics and antivirals for the management of varicella among children in the United States (US). METHODS: A decision tree model of varicella vaccination, infections and treatment decisions was developed. Results were extrapolated to the 2017 population of 73.5 million US children. Model parameters were populated from published sources. Treatment decisions were derived from a survey of health care professionals' recommendations. The base case modelled current vaccination coverage rates in the US with additional scenarios analyses conducted for 0%, 20%, and 80% coverage and did not account for herd immunity benefits. RESULTS: Our model estimated that 551,434 varicella cases occurred annually among children ≤ 18 years in 2017. Antivirals or antibiotics were prescribed in 23.9% of cases, with unvaccinated children receiving the majority for base case. The annual cost for varicella antiviral and antibiotic treatment was approximately $14 million ($26 per case), with cases with no complications accounting for $12 million. Compared with the no vaccination scenario, the current vaccination rates resulted in savings of $181 million (94.7%) for antivirals and $78 million (95.0%) for antibiotics annually. Scenario analyses showed that higher vaccination coverage (from 0% to 80%) resulted in reduced annual expenditures for antivirals (from $191 million to $41 million), and antibiotics ($82 million to $17 million). CONCLUSIONS: UVV was associated with significant reductions in the use of antibiotics and antivirals and their associated costs in the US. Higher vaccination coverage was associated with lower use and costs of antibiotics and antivirals for varicella management.

Relative efficacy of varicella vaccines: network meta-analysis of randomized controlled trials.

OBJECTIVE: Although varicella vaccination is highly effective, no head-to-head randomized controlled trials (RCTs) have compared the efficacy of different vaccine formulations. This study assessed the relative efficacy of different varicella vaccines using network meta-analysis (NMA). METHODS: We estimated the relative efficacies of varicella vaccines and dosing regimens from RCTs using Bayesian NMA. Modeling-based time-series NMA (MBNMA) was performed, accounting for differences in time since vaccination, to extrapolate long-term vaccine efficacy (VE). RESULTS: Eight RCTs were included based on systematic review of biomedical databases. Efficacy data were reported for four varicella-containing vaccines: Varivax (V-MSD, one and two dose), Varilrix (V-GSK, one dose), Priorix-Tetra (MMRV-GSK, one dose), and Sinovac (V-Sinovac, one dose). All varicella vaccines were effective versus no vaccination. Two-dose V-MSD (98.29%, 95% credible interval [CrI] 96.08-99.23) showed significantly higher VE versus all one-dose varicella-containing vaccines, but no significant difference versus two-dose MMRV-GSK (95.19%, 95% CrI 90.3-97.63). Two-dose MMRV-GSK showed higher VE than one-dose V-GSK (66.47%; 95% CrI 43.02-79.43), but no significant differences in VE versus one-dose V-MSD or one-dose V-Sinovac. In one-dose comparisons, V-MSD showed significantly higher VE (93.09%, 95% CrI 89.13-95.96) than V-GSK, but no significant difference versus V-Sinovac (89.22%; 95% CrI 67.1-96.5). MBNMA indicated that protection against varicella was sustained without waning over the 10 year follow-up. CONCLUSIONS: Our study reported higher VE for two-dose V-MSD and MMRV-GSK. Among one-dose formulations, one-dose V-MSD was more efficacious than one-dose V-GSK. Policymakers should take into consideration differences in VE when implementing one- versus two-dose strategies in universal vaccination programs.

Congenital Syphilis and the Prozone Phenomenon: Case Report.

Congenital syphilis represents an important public health challenge in the United States, and its prevalence has been increasing for the past 10 years because of many factors. The diagnosis can be difficult given its various and nonspecific clinical manifestations in newborns, and the possibility of false negative results during prenatal care. The prozone phenomenon, caused by an excess of antibody, which interferes with the regular screening tests, is a cause of false negative tests. This could delay the diagnosis and increase morbidity and mortality in the newborn. We present a case of congenital syphilis in a 3-month-old infant whose mother had prenatal care and negative tests for syphilis, which contributed to the late diagnosis. In the face of clinical findings suggestive of congenital syphilis and negative maternal syphilis tests healthcare providers should consider the possibility of maternal false negative test caused by the prozone phenomenon.

Rationale for the Development of a Pentavalent Meningococcal Vaccine: A US-Focused Review.

While invasive meningococcal disease (IMD) is uncommon, it can result in serious sequelae and even death. In 2018 in the United States, the incidence of IMD per 100,000 people was 0.03 among adolescents 11-15 years of age, 0.10 among persons 16-23 years of age, and 0.83 among infants < 1 year of age. Serogroup B accounted for 86%, 62%, and 66% of cases, respectively, in those age groups. Currently, routine meningococcal vaccination covering serogroups ACWY (MenACWY) is recommended in the United States for all adolescents at 11-12 years of age, with a booster dose at 16 years of age, whereas a meningococcal serogroup B (MenB) vaccine series is recommended for persons 16-23 years of age under the shared clinical decision-making paradigm. The MenACWY vaccination program in adolescents has been successful in reducing disease burden, but does not prevent disease caused by serogroup B, which accounts for more than half of IMD cases. There are currently no approved vaccines that cover all of the most common disease-causing meningococcal serogroups, which are A, B, C, W, and Y. A pentavalent MenABCWY vaccine that is constituted from 2 licensed meningococcal vaccines-MenB-FHbp and MenACWY-TT-is being investigated in healthy persons ≥ 10-25 years of age. The addition of a MenABCWY vaccine is the next natural step in the incremental meningococcal immunization program in the United States to improve protection against the most common serogroup causing IMD, with no increase in the number of immunizations needed. With high uptake, routine use of MenABCWY could reduce IMD cases and associated mortality, the rate of long-term physical and psychosocial sequelae in survivors, and costs associated with controlling outbreaks, particularly on college campuses. A MenABCWY vaccine would also reduce the number of injections required for adolescents, potentially improving compliance.

Respiratory Syncytial Virus and All-Cause Bronchiolitis Hospitalizations Among Preterm Infants Using the Pediatric Health Information System (PHIS).

BACKGROUND: In 2014, the American Academy of Pediatrics stopped recommending palivizumab to otherwise healthy 29-34 weeks' gestational age (wGA) infants aged <12 months at respiratory syncytial virus (RSV) season start. Here, we compare the burden of RSV hospitalizations (RSVH) and all-cause bronchiolitis hospitalizations (BH) before and after 2014 among otherwise healthy 29-34 wGA infants hospitalized at ≤6 months of age. METHODS: A historical, observational cohort study was conducted to evaluate RSVH and BH in 29-34 wGA infants during the 2010-2017 RSV seasons using encounter data from 51 United States children's hospitals that comprise the Pediatric Health Information System. RESULTS: The overall cohort included 67 570 RSVH out of 96 281 patients with BH. wGA was known for 22 937 RSVH and 33 289 BH. For 29-34 wGA infants, there were 8.7% and 14.2% RSVH before and after 2014, respectively (P < .0001). Intensive care unit admissions increased for RSVH (from 54.5% to 64.2%; P = .0002) and BH (from 46.7% to 54.5%; P = .0005) after controlling for sex, race, comorbidity, and cluster. The total cost of care increased for RSVH from $37 million to nearly $60 million. CONCLUSIONS: RSVH, BH, and their severity increased among 29-34 wGA infants in the 3 RSV seasons following 2014.

Use of M-M-R II outside of the routinely recommended age range - a systematic literature review.

M-M-R®II (M-M-R II) is routinely used in many countries at 12-15 months with a second dose at 4 to 6 years of age. However, the vaccine may need to be administered at other ages due to delays in the immunization schedule or in certain situations such as outbreaks or international travel. A systematic literature review was conducted to evaluate efficacy, immunogenicity and safety of M-M-R II among 6- to 11-month-olds and persons ≥7 years of age. A search for randomized controlled trials (RCTs) was conducted in 2019 including Medline, Embase and Cochrane CENTRAL. Only one study reported seroconversion rates after one dose in infants at 9 months of age: 87.4% (measles), 92.3% (mumps), and 91.2% (rubella); no safety data were reported. Seven studies reported immunogenicity and safety data for M-M-R II at ≥7 years of age. Seroconversion rates ranged from 96%-100% (measles), 65%-100% (mumps), and 91%-100% (rubella). Rates of selected adverse events ranged from 5.2%-8.7% for fever (≥38°C or ≥38.1°C), 2%-33.3% for injection site reactions, and 0.4% for measles/rubella-like rash (one study). No efficacy studies were found. This literature review identified RCTs with evidence to support that M-M-R II is immunogenic and well tolerated in individuals ≥7 years of age.

Immunity to SARS-CoV-2: Lessons Learned.

In the year since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and with understanding of the etiology of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that most infected individuals achieve some form of immunity against the virus with relatively few reported reinfections. A number of vaccines have already achieved emergency use authorization based on data from large phase 3 field efficacy clinical trials. However, our knowledge about the extent and durability of this immunity, and the breadth of vaccine coverage against SARS-CoV-2 variants is still evolving. In this narrative review, we summarize the latest and rapidly developing understanding of immunity to SARS-CoV-2 infection, including what we have learned about the key antigens of SARS-CoV-2 (i.e., the spike protein and its receptor-binding domain), their importance in vaccine development, the immediate immune response to SARS-CoV-2, breadth of coverage of emerging SARS-CoV-2 variants, contributions of preexisting immunity to related coronaviruses, and duration of immunity. We also discuss lessons from newer approaches, such as systems serology, that provide insights into molecular and cellular immune responses elicited and how they relate to the trajectory of infection, and potentially inform immune correlates of protection. We also briefly examine the limited research literature on immune responses in special populations, such as pregnant women and children.

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.

Implementation Experience With Meningococcal Serogroup B Vaccines in the United States: Impact of a Nonroutine Recommendation.

BACKGROUND: Meningococcal serogroup B (MenB) is the leading cause of invasive meningococcal disease among US adolescents and young adults, accounting for 62% of cases in 16-23-year-olds in 2018. Since 2015, the Advisory Committee on Immunization Practices (ACIP) has recommended vaccination of healthy adolescents against MenB based on shared clinical decision-making (previously called "Category B" or individual clinical decision-making). However, MenB vaccine coverage and series completion rates remain low. Herein we examine implementation experience of adolescent MenB vaccination in the United States under this nonroutine ACIP recommendation. METHODS: PubMed was searched for English-language articles published after 2015 examining MenB vaccination implementation in the United States. Studies reporting MenB vaccination awareness, coverage, knowledge of recommendations and implementation barriers or access disparities were included. RESULTS: Identified studies provided evidence that ACIP's MenB vaccination recommendation is poorly understood and prone to misinterpretation by US healthcare providers. Parental awareness of MenB vaccines is low, and racial and socioeconomic disparities exist regarding vaccine receipt. Parents rely on providers to learn about MenB disease risk and benefits of vaccination, with provider recommendations carrying substantial weight in vaccination decisions. CONCLUSIONS: Five years of evidence regarding the MenB vaccination implementation experience suggest that the nonstandard recommendation for MenB vaccines is partly responsible for low vaccine coverage. Further, inconsistent implementation of ACIP recommendations could be limiting access to MenB vaccines. Providers need additional support and guidance to implement the shared clinical decision-making recommendation, in turn ensuring equitable access for vaccine-eligible adolescents to enable comprehensive protection against meningococcal disease.

Prevention of measles, mumps and rubella: 40 years of global experience with M-M-RII.

Measles, mumps, and rubella are highly contagious diseases that caused significant global mortality and morbidity in the pre-vaccine era. Since its first approval in the United States over 40 years ago, M-M-RII has been used in >75 countries for prevention of these diseases. The vaccine has been part of immunization programs that have achieved dramatic global reductions in case numbers and mortality rates, as well as the elimination of measles and rubella in several countries and regions. This report summarizes over four decades of global safety, immunogenicity, efficacy, and effectiveness data for the vaccine. We include studies on the use of M-M-RII in different age groups, concomitant use with other routine childhood vaccines, administration via different routes, persistence of immunity, and vaccine effectiveness during outbreaks of measles and mumps. We conclude that M-M-RII is well tolerated and has shown consistently high performance during routine use in multiple countries, in randomized controlled trials with diverse designs, and in outbreak settings, including use as measles postexposure prophylaxis. Physicians, parents, and the public can continue to have a high degree of confidence in the use of M-M-RII as a vital part of global public health programs.

Unintended Consequences Following the 2014 American Academy of Pediatrics Policy Change for Palivizumab Prophylaxis among Infants Born at Less than 29 Weeks' Gestation.

OBJECTIVE: The aim of this study is to compare outpatient respiratory syncytial virus (RSV) immunoprophylaxis (IP) use and relative RSV hospitalization (RSVH) rates for infants <29 weeks' gestational age (wGA) versus term infants before and after the 2014 American Academy of Pediatrics (AAP) policy change. STUDY DESIGN: Infants were identified in the MarketScan Commercial and Multi-State Medicaid databases. Outpatient RSV IP receipt and relative <29 wGA/term hospitalization risks in 2012 to 2014 and 2014 to 2016 were assessed using rate ratios and a difference-in-difference model. RESULTS: Outpatient RSV IP receipt by infants <29 wGA and aged <3 months in the Commercial and Medicaid populations and those aged 3 to <6 months in the Medicaid population declined after 2014. Relative RSVH risks for infants <29 wGA were numerically greater after 2014, with infants aged <3 months and Medicaid infants experiencing the greatest increases. Difference-in-difference results indicated a significantly increased relative risk of RSVH for infants <29 wGA versus term (both cohorts aged 0 to <6 months) in the Medicaid-insured population (1.68, p = 0.0054). A nonsignificant increase of similar magnitude occurred in the commercially insured population (1.57, p = 0.2867). CONCLUSION: The 2014 policy change was associated with a decrease in RSV IP use and an increase in RSVH risk among otherwise healthy infants <29 wGA.

Update on respiratory syncytial virus hospitalizations among U.S. preterm and term infants before and after the 2014 American Academy of Pediatrics policy on immunoprophylaxis: 2011-2017.

Palivizumab is the only licensed respiratory syncytial virus (RSV) immunoprophylaxis (IP) available to prevent severe RSV disease in high-risk pediatric populations, including infants born at 29-34 weeks' gestational age (wGA). In 2014, the American Academy of Pediatrics (AAP) stopped recommending RSV IP use for otherwise healthy 29-34 wGA infants and stated that 29-34 wGA infants and term infants have similar RSV hospitalization (RSVH) rates. This study aimed to compare RSV IP use and RSVH rates in 29-34 wGA infants and term infants during the 3 RSV seasons before and after the 2014 AAP policy change. RSV IP use in otherwise healthy infants 29-30, 31-32, and 33-34 wGA was estimated from pharmacy or outpatient medical claims for palivizumab. RSVH rates in the first 6 months of life were calculated per 100 infant-seasons. RSVH rate ratios were used to compare preterm infants and term infants before and after the policy change. Across infant cohorts (29-34 wGA) and chronologic age groups (<3 months and 3-<6 months), absolute decreases in RSV IP use between the combined 2011-2014 seasons and 2014-2017 seasons ranged from 7% to 38% and from 68% to 97%, respectively. Compared with 2011-2014, the RSVH risk increased 2.09-fold (P< .001) and 1.76-fold (P< .001) in 2014-2017 for infants born at 29-34 wGA and aged <6 months with commercial and Medicaid insurance, respectively. Overall, RSV IP use declined in the RSV seasons following the 2014 RSV IP policy change, and RSVH increased among 29-34 wGA infants aged <6 months.

Impact of the 2014 American Academy of Pediatrics Immunoprophylaxis Policy on the Rate, Severity, and Cost of Respiratory Syncytial Virus Hospitalizations among Preterm Infants.

OBJECTIVE: This study examined the rate, severity, and cost of respiratory syncytial virus (RSV) hospitalizations among preterm infants 29 to 34 weeks gestational age (wGA) versus term infants before and after a 2014 change in the American Academy of Pediatrics policy for RSV immunoprophylaxis. STUDY DESIGN: Preterm (29-34 wGA) and term infants born from July 2011 to March 2017 and aged < 6 months were identified in a U.S. commercial administrative claims database. RSV hospitalization (RSVH) rate ratios, severity, and costs were evaluated for the 2011 to 2014 and 2014 to 2017 RSV seasons. Postpolicy changes in RSVH risks for preterm versus term infants were assessed with difference-in-difference (DID) modeling to control for patient characteristics and temporal trends. RESULTS: In the DID analysis, prematurity-associated RSVH risk was 55% greater in 2014 to 2017 versus 2011 to 2014 (relative risk = 1.55, 95% confidence interval: 1.10-2.17, p = 0.011). RSVH severity increased among preterm infants after 2014 and was highest among those aged < 3 months. Differences in mean RSVH costs for preterm infants in 2014 to 2017 versus 2011 to 2014 were not statistically significant. CONCLUSION: RSVH risk for preterm versus term infants increased after the policy change, confirming previous national analyses. RSVHs after the policy change were more severe, particularly among younger preterm infants.

Decrease in the Prevalence of Methicillin-Resistant Staphylococcus Aureus Nasal Colonization of Children Admitted to Driscoll Children's Hospital.

Compared with a similar 2005 study, this 2016 study showed a significant decrease from 22% to 3% in the prevalence of methicillin-resistant Staphylococcus aureus nasal colonization in children admitted to our facility. Of the sampled 360 children, 21% were colonized with S. aureus and 14% of those isolates were methicillin-resistant S. aureus, whereas 61% of the isolates in 2005 were methicillin-resistant S. aureus.

Respiratory Syncytial Virus Hospitalizations among U.S. Preterm Infants Compared with Term Infants Before and After the 2014 American Academy of Pediatrics Guidance on Immunoprophylaxis: 2012-2016.

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: 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: In all seasons, preterm infants had higher RSVH rates than term infants. Seasonal RRs prior to the guidance change for preterm wGA categories versus term infants ranged from 1.6 to 3.4. After the guidance change, the seasonal RRs ranged from 2.6 to 5.6. In 2014 to 2016, the risk associated with prematurity of 29 to 34 wGA versus term was significantly higher than in 2012 to 2014 (P<0.0001 for commercial and Medicaid samples). CONCLUSION: 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.

Influenza-Associated Acute Necrotizing Encephalopathy in Siblings.

Encephalopathy is an important complication associated with influenza, most frequently observed in young children, with a wide range of severity. The most severe category of influenza-associated encephalopathy (IAE) is acute necrotizing encephalopathy (ANE), characterized by high frequency of neurologic sequelae and fatal outcomes. We report two young siblings who developed fever and seizures with altered mental status. Influenza A(H1N1)pdm09 virus infection was identified in upper respiratory tract specimens from both patients, and neuroimaging revealed bilateral inflammatory lesions, consistent with acute necrotizing encephalopathy. Neither child had received influenza vaccination. Both children progressed to critical illness and required invasive mechanical ventilation. In addition to critical care management, both patients received high-dose corticosteroids, mannitol, anticonvulsants, and antiviral treatment of influenza. The older child recovered fully and was discharged 2 weeks after illness onset, but the younger sibling developed severe brainstem edema and cerebellar tonsillar herniation, and died on illness day 11. Both children tested positive for Ran Binding Protein 2 (RANBP2) gene mutations. RANBP2 is a genetic polymorphism associated with recurrent episodes of necrotizing encephalitis with respiratory viral infections. Annual influenza vaccination is especially important for ANE survivors, with or without RANBP2 mutations, their household contacts, and caregivers. During influenza season, close monitoring of any child with a history of neurological complications associated with respiratory illness is indicated, with prompt initiation of antiviral treatment with onset of acute respiratory illness, and influenza testing performed by molecular assay.