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Meningococcal vaccination is recommended for patients with complement component deficiencies (CDs) in the United States. In this retrospective database study, only 4.6% and 2.2% of patients received MenACWY and MenB vaccination, respectively, within 3 years of CD diagnosis. Thus, meningococcal vaccination rates among patients with CDs need to be improved.

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 th...

Significance In this report we identify genetic susceptibility variants for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, the most common periodic fever syndrome in children. PFAPA shares risk loci at IL12A, STAT4, IL10, and CCR1-CCR3 with Behçet’s disease and recurrent aphthous stomatitis, defining a family of Behçet’s spectrum disorders. Differential HLA associations along this spectrum may determine where individual phenotypes fall among the Behçet’s spectrum disorders., Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. The disease appears to cluster in families, but the pathogenesis is unknown. We queried two European–American cohorts and one Turkish cohort (total n = 231) of individuals with PFAPA for common variants previously associated with two other oropharyngeal ulcerative disorders, Behçet’s disease and recurrent aphthous stomatitis. In a metaanalysis, we found that a variant upstream of IL12A (rs17753641) is strongly associated with PFAPA (OR 2.13, P = 6 × 10−9). We demonstrated that monocytes from individuals who are heterozygous or homozygous for this risk allele produce significantly higher levels of IL-12p70 upon IFN-γ and LPS stimulation than those from individuals without the risk allele. We also found that variants near STAT4, IL10, and CCR1-CCR3 were significant susceptibility loci for PFAPA, suggesting that the pathogenesis of PFAPA involves abnormal antigen-presenting cell function and T cell activity and polarization, thereby implicating both innate and adaptive immune responses at the oropharyngeal mucosa. Our results illustrate genetic similarities among recurrent aphthous stomatitis, PFAPA, and Behçet’s disease, placing these disorders on a common spectrum, with recurrent aphthous stomatitis on the mild end, Behçet’s disease on the severe end, and PFAPA intermediate. We propose naming these disorders Behçet’s spectrum disorders to highlight their relationship. HLA alleles may be factors that influence phenotypes along this spectrum as we found new class I and II HLA associations for PFAPA distinct from Behçet’s disease and recurrent aphthous stomatitis.

Worldwide, lifestyle and resource disparities among adolescents contribute to unmet health needs, which have crucial present and future public health implications for both adolescents and broader communities. Risk of infection among adolescents is amplified by biological, behavioral, and environmental factors; however, infectious diseases to which adolescents are susceptible are often preventable with vaccines. Beyond these concerns, there is a lack of knowledge regarding adolescent vaccination and disease risk among parents and adolescents, which can contribute to low vaccine uptake. Promising efforts have been made to improve adolescent vaccination by programs with motivational drivers and comprehensive communication with the public. In May 2017, a multidisciplinary group of experts met in Amsterdam, Netherlands, to discuss adolescent vaccine uptake, as part of an educational initiative called the Advancing Adolescent Health Spring Forum. This article presents consensus opinions resulting from the meeting, which pertain to the burden of vaccine-preventable diseases among adolescents, reasons for low vaccine uptake, and common characteristics of successful strategies for improving adolescent vaccination.Conclusion: There is an urgent “call to action,” particularly targeting healthcare providers and public health authorities, for the prioritization of adolescent vaccination as a necessary element of preventive healthcare in this age group. What is Known:• Despite increased risk of certain infectious diseases, adolescent vaccination uptake remains low. What is New:• Barriers to adolescent vaccine uptake include lack of information regarding vaccines and disease risk, health system inadequacies, and insufficient healthcare follow-up.• Successful efforts to improve adolescent vaccine uptake need cohesive leadership and involvement of multiple stakeholders, as well as youth-friendly messaging; healthcare providers and policymakers should prioritize adolescent vaccination and implement proven program strategies to improve adolescent health worldwide.

To determine if training residents in a structured communication method elicits specific behaviors in a laboratory model of interaction with vaccine-hesitant parents.Standardized patients portraying vaccine-hesitant parents were used to assess the effectiveness of training in the Announce, Inquire, Mirror, Secure (AIMS) Method for Healthy Conversations. Blinded pediatric residents were pseudorandomized to receive AIMS or control training and underwent pre- and post-training encounters with blinded standardized patients. Encounters were assessed by blinded raters using a novel tool. Participant confidence and standardized patient evaluations of the participants' general communication skills were assessed.Ratings were available for 27 AIMS and 26 control participants. Statistically significant increases in post-training scores (maximum = 30) were detected in AIMS, but not in control, participants (median, 21.3 [IQR, 19.8-24.8] vs 18.8 [IQR, 16.9-20.9]; P .001). Elements (maximum score = 6) with significant increases were Inquire (0.67 [IQR, 0-1.76] vs -0.33 [IQR, -0.67 to 0.33]; P .001); Mirror (1.33 [IQR, 0 to 2] vs -0.33 [IQR, -0.92 to 0]; P .001) and Secure (0.33 [IQR, 0 to 1.67] vs -0.17 [IQR, -0.67 to 0.33]; P = .017). Self-confidence increased equally in both groups. Standardized patients did not detect a difference in communication skills after training and between groups. Internal consistency and inter-rater reliability of the assessment tool were modest.Standardized patients proved useful in studying the effectiveness of structured communication training, but may have been limited in their ability to perceive a difference between groups owing to the predetermined encounter outcome of vaccine refusal. AIMS training should be studied in real-world scenarios to determine if it impacts vaccine acceptance.

Publicly available surveillance data, Centers for Disease Control and Prevention reports, and other sources suggest that college students in the United States are at increased risk for meningococcus serogroup B (MenB) disease. US surveillance data from 2015 to 2017 show that the incidence of invasive meningococcal disease (IMD) was greater among college students than among those not attending college; the average annual incidence of MenB disease was >5-fold higher among college students, and all college IMD outbreaks between 2011 and March 2019 were caused by MenB.

Background In the Southern Hemisphere 2010 influenza season, Seqirus’ split-virion, trivalent inactivated influenza vaccine was associated with increased reports of fevers and febrile reactions in young children. A staged clinical development program of a quadrivalent vaccine (Seqirus IIV4 [S-IIV4]; Afluria® Quadrivalent/Afluria Quad™/Afluria Tetra™), wherein each vaccine strain is split using a higher detergent concentration to reduce lipid content (considered the cause of the increased fevers and febrile reactions), is now complete. Methods Children aged 6–59 months were randomized 3:1 and stratified by age (6–35 months/36–59 months) to receive S-IIV4 (n = 1684) or a United States (US)-licensed comparator IIV4 (C-IIV4; Fluzone® Quadrivalent; n = 563) during the Northern Hemisphere 2016–2017 influenza season. The primary objective was to demonstrate noninferior immunogenicity of S-IIV4 versus C-IIV4. Immunogenicity was assessed by hemagglutination inhibition (baseline, 28 days postvaccination). Solicited, unsolicited, and serious adverse events were assessed for 7, 28, and 180 days postvaccination, respectively. Results S-IIV4 met the immunogenicity criteria for noninferiority. Adjusted geometric mean titer ratios (C-IIV4/S-IIV4) for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 0.79 (95% CI: 0.72, 0.88), 1.27 (1.15, 1.42), 1.12 (1.01, 1.24), and 0.97 (0.86, 1.09), respectively. Corresponding values for differences in seroconversion rates (C-IIV4 minus S-IIV4) were −10.3 (−15.4, −5.1), 2.6 (−2.5, 7.8), 3.1 (−2.1, 8.2), and 0.9 (−4.2, 6.1). Solicited, unsolicited, and serious adverse events were similar between vaccines in both age cohorts, apart from fever. Fever rates were lower with S-IIV4 (5.8%) than C-IIV4 (8.4%), with no febrile convulsions reported with either vaccine during the 7 days postvaccination. Conclusion S-IIV4, manufactured with a higher detergent concentration, demonstrated noninferior immunogenicity to the US-licensed C-IIV4, with similar postvaccination safety and tolerability, in children aged 6–59 months. This completes the program demonstrating the immunogenicity and safety of S-IIV4 in participants aged 6 months and older. Funding Seqirus Pty Ltd; ClinicalTrials.gov identifier: NCT02914275 .

Background Patients with asplenia are recommended to receive meningococcal ACWY (MenACWY) and B (MenB) vaccines in the United States (US). Objectives To examine uptake and time to receipt of meningococcal vaccines in newly diagnosed asplenia patients, and identify factors associated with vaccination. Methods For this retrospective database analysis, patients were identified from 1/1/2010 (MenACWY) or 1/1/2015 (MenB) through 3/31/2018 from an administrative claims database including commercially insured US patients with ≥1 inpatient or ≥2 outpatient claims with evidence of a new asplenia diagnosis (sickle cell disease was excluded); continuous enrollment for ≥12 months before and ≥6 months after the index date; and age ≥2 (MenACWY) or ≥10 (MenB) years. Co-primary outcomes were uptake and time to receipt of ≥1 dose, separately for MenACWY and MenB, by Kaplan–Meier analysis. Cox proportional hazards regression models were used to identify characteristics associated with vaccination. Results Among 2,273 and 741 patients eligible for the MenACWY and MenB analyses, respectively, 28.1% and 9.7% received MenACWY and MenB in the first 3 years after a new asplenia diagnosis. Patients were more likely to receive meningococcal vaccines if they had received pneumococcal vaccines (MenACWY: hazard ratio [HR] 26.02; 95% confidence interval [CI] 21.01–32.22; MenB: HR 3.89; 95% CI 2.07–7.29) or attended ≥1 well-care visit (MenACWY: HR 6.63; 95% CI 4.84–9.09; MenB: HR 11.17; 95% CI 3.02–41.26). Conclusions Meningococcal vaccination rates among newly diagnosed asplenia patients were low, highlighting the need to educate providers about the recommendations for high-risk conditions and ensure healthcare access for vulnerable patients.

Background In response to the detection of porcine circovirus type 1 (PCV-1) in the human rotavirus vaccine (HRV), a PCV-free HRV (no detection of PCV-1 and PCV-2 according to the detection limit of tests used) was developed. Liquid (Liq) PCV-free HRV previously showed immunogenicity and safety profiles comparable to lyophilized (Lyo) HRV. Methods This was a phase 3a, randomized, single-blind study (NCT03207750) conducted in the United States. Healthy infants aged 6–12 weeks received 2 doses (0, 2 months) of either Liq PCV-free HRV or Lyo HRV with routine vaccines (0, 2, 4 months): diphtheria-tetanus-acellular pertussis, hepatitis B and inactivated poliovirus combination vaccine (DTaP-HBV-IPV), monovalent tetanus toxoid-conjugated vaccine against Haemophilus influenzae type b (Hib-TT), and 13-valent pneumococcal conjugate vaccine. Co-primary objectives were: (i) to assess non-inferiority of immune responses to routine vaccine antigens 1 month post-dose 3 following co-administration with Liq PCV-free HRV compared to Lyo HRV; (ii) to rule out a 10% decrease in seroresponse to pertussis antigens after dose 3. Other objectives were to evaluate immunogenicity and safety of HRV vaccines. Results Of 1272 vaccinated infants, 990 (489 in Liq PCV-free HRV and 501 in Lyo HRV group) were included in the per-protocol set. All statistical criteria were met, thus co-primary objectives were demonstrated. Seroprotection/seropositivity rates in both groups were high: 100% for diphtheria/tetanus, ≥99.3% for HBV, ≥99.8% for polio, ≥99.8% for each pertussis antigen, ≥90.8% for all pneumococcal serotypes except serotype 3 (≥69.1%), and ≥ 97.4% for Hib. Most infants seroconverted for anti-RV antibodies (76.3% of Liq PCV-free HRV and 78.9% of Lyo HRV recipients). Geometric mean concentrations/titers were comparable between groups. Incidences of adverse events and serious adverse events were similar between groups. Conclusion Routine pediatric vaccines co-administered with Liq PCV-free HRV showed non-inferior immune responses and similar safety profiles to those following co-administration with Lyo HRV.

Background MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this study, we assessed the immunogenicity and safety of another MMR vaccine (MMR-RIT [Priorix, GlaxoSmithKline]) compared with those of the MMR II in 12- to 15-month-old children who received it as a first dose. Methods In this phase III, observer-blinded, noninferiority, lot-to-lot consistency clinical trial (ClinicalTrials.gov identifier NCT01702428), 5003 healthy children were randomly assigned to receive 1 dose of MMR-RIT (1 of 3 production lots) or MMR II along with other age-recommended routine vaccines. We evaluated the immunogenicity of all vaccines in terms of antibody concentrations (by using an enzyme-linked immunosorbent assay or electrochemiluminescence assay) and/or seroresponse rates 43 days after vaccination. We also assessed the reactogenicity and safety of the vaccines. Results Immunoresponses after vaccination with MMR-RIT were robust and noninferior to those after vaccination with the MMR II. Immunogenicity of the 3 production lots of MMR-RIT was consistent; more than 97% of the children had a seroresponse to MMR components. The coadministered vaccines elicited similar immunoresponses in the MMR-RIT and MMR II groups. Both MMR vaccines resulted in comparable reactogenicity profiles, and no safety concerns were detected. Conclusions If licensed, the MMR-RIT could provide a valid option for the prevention of measles, mumps, and rubella in children in the United States and would reduce potential risks of a vaccine shortage., When compared with the MMR II vaccine (M-M-R-II) currently available in the United States, a first dose of MMR-RIT (Priorix) given to 1-year-old children elicited robust immunoresponses and raised no safety concerns.

Background Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. Methods The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement. Results The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study. Conclusion The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease.

We describe the first 2 cases from the United States, of human parechovirus infection in infants manifesting a distinct rash of the hands and feet. We propose the term "Mittens and Booties Syndrome" and provide a review of the literature of all published cases.

Background Combination vaccines reduce the number of injections and improve the timeliness of vaccination coverage. US Advisory Committee on Immunization Practices (ACIP) recommendations state that combination vaccines are generally preferred over equivalent individual component vaccines. Healthcare providers strongly influence parental decisions about vaccination. We sought a contemporary understanding of physician’s attitudes towards combination vaccine use in infants. Methods We conducted an online survey of US physicians (70 pediatricians and 30 family practitioners) who administer vaccines to infants aged 0-24 months and spend at least 2 days a week providing patient care. Information was collected on attitudes towards combination vaccines and factors that influence the choice of combination vaccine used in clinical practice. Descriptive analyses were performed. Results Physicians (mean age=50.2 years, range 30.0-70.0; 66% white; 37% women) reported a median of 4 injections (range 2-9) as the maximum that parents would accept at a single visit, and 71% routinely explained what combination vaccines are to parents. When deciding which pentavalent vaccine to use, physicians considered how the brand fits into the current vaccine schedule (71%); upfront purchase costs (64%); and availability as a prefilled syringe (61%). The main reasons for using combination vaccines were to reduce the number of injections (96%); ensure the infant is up-to-date with vaccinations (86%); and reduce the pain that the infant experiences with multiple injections (68%). More than half reported that their institution or practice has a program to incentivize infant vaccination according to schedule. If a hexavalent vaccine-based schedule was available, 76% of physicians said they would choose it over their current schedule comprising pentavalent or equivalent component vaccines. Conclusion Choice of pentavalent combination vaccine among pediatricians and family practitioners was largely dependent on convenience and cost-related factors. Over three-quarters would be inclined to use a hexavalent vaccine schedule if available. Disclosures Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Background Vaccine hesitancy (VH) is one of the top 10 threats to global public health. While VH is common among parents, there are no accepted best practices for counseling, and training in this area is not required in residency. Strategies are needed to help providers address VH in practice. Methods The AIMS (Announce, Inquire, Mirror, Secure) Method for Healthy Conversations is a structured communication strategy that attempts to build trust between provider and patient (or parent), inviting receptivity to healthcare recommendations. To assess whether relatively inexperienced providers exhibit AIMS behaviors after training, blinded pediatric residents were pseudo-randomized to receive either AIMS or control training. Subjects underwent pre- and post-training clinical encounters with blinded standardized patients (SPs) portraying vaccine-hesitant parents; encounters were video-recorded and assessed by 3 blinded raters using the Vaccine Hesitancy Communication Assessment (VHCA) tool, which was developed by an iterative process and validated in pilot testing. Subject confidence was assessed pre- and post-training. Results Overall VHCA intraclass correlation was 0.273 for pre and 0.681 for post encounters (2-way mixed averages); reliability varied with AIMS phases. Fifty-eight subjects completed the protocol, and VHCA ratings for 29 subjects were available for this analysis. AIMS behaviors were more commonly detected among AIMS-trained subjects than control (median change in score [scale 0–30]=4.5 versus 0 for control) (Figure 1). Confidence improved in both groups (Figure 2). SPs perceived no differences between groups, nor between pre and post within groups, in aspects of subject performance such as respect, empathy, and promotion of trust (P=0.936 [ANCOVA]; partial eta-squared 0.0). Figure 1 Figure 2 Conclusion Pediatric residents can be trained in AIMS behaviors, and an SP model of VH can be used to assess performance. AIMS training results in similar gains in self-confidence compared to control training. SP perceptions may be colored by their script, which in this case was to exhibit adamant vaccine refusal. Testing of AIMS training in longitudinal experimental scenarios and in real-world settings is warranted. Disclosures Kristina A. Bryant, MD, Pfizer (Research Grant or Support, Investigator on multi-center clinical trials) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

A telephone interview was conducted with parents of 120 children seen in a pediatric infectious diseases clinic for unexplained fever who received no definitive diagnosis or were thought to have recurrent self-limited illnesses. Only 3 were diagnosed with a fever-related condition after 8 years of follow-up. The majority remained well.

Background The US vaccination schedule includes DTaP, IPV, Hib and HepB doses in the first 6 months of life. A previous analysis found variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. We explored factors associated with co-administration of DTaP-IPV/Hib and HepB on the same day. Methods This was a retrospective study using the MarketScan® commercial claims and encounters database. Infants born from 1 July 2010 - 30 June 2016, continuously enrolled in an insurance plan for ≥ 13 months and receiving ≥ 3 DTaP-IPV/Hib doses were included. Infants were assessed for HepB claims relative to the first and third DTaP-IPV/Hib doses. Because a HepB birth dose was assumed, the first HepB claim from 29 - 169 days following birth was counted as Dose 2, and the second claim from 170 days - 12 months as Dose 3. Associations between demographic, provider, and insurance characteristics, receipt of other pediatric vaccines, and co-administration of DTaP-IPV/Hib and HepB were analyzed using multivariate logistic regression. Results Among 165,553 infants who received a first DTaP-IPV/Hib dose, 60.7% received HepB Dose 2 on the same day. Among 162,217 infants who received a third DTaP-IPV/Hib dose, 45.1% received HepB Dose 3 on the same day. Infants in the Northeast were less likely (OR=0.38, 95%CI=0.36-0.39), while those in the West were more likely (OR=1.41, 95%CI=1.36-1.46) than infants in the South to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day. Infants vaccinated by pediatricians (OR=0.54, 95%CI=0.53-0.55) were less likely to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day compared to infants vaccinated by family physicians. Infants who received PCV on the same day as the first dose of DTaP-IPV/Hib were more likely to receive HepB Dose 2 (OR=6.96, 95%CI=6.30-7.70) that day. These factors were also associated with co-administration of the third dose of DTaP-IPV/Hib and HepB Dose 3. Conclusion Differences in co-administration of DTaP-IPV/Hib and HepB were associated with region of residence, provider type and co-administration of PCV. The reasons underlying these differences merit exploration. A hexavalent vaccine containing DTaP, IPV, Hib, and HepB could improve timeliness of HepB vaccination, while reducing the number of injections during infancy. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Practice variation exists in the management of children with bacterial pneumonia complicated by empyema. The success of video-assisted thoracoscopic surgery (VATS) versus chest tube insertion for drainage and fibrinolysis may be dependent on the stage of disease. There is little published experience with early transition to oral (PO) antibiotics, and many children are treated with intravenous (IV) antibiotics at home. To describe a cohort of children with pneumonia and empyema in a primarily rural state managed with early VATS and transition to PO antibiotics. This was a retrospective medical record review of children managed by the pediatric infectious diseases and surgery services at Kosair Children's Hospital from 2008 through 2012. Sixty-one children met inclusion criteria. The majority underwent VATS on the first or second hospital day. No organism was identified in 67 per cent of cases. All patients received IVantibiotics at admission and all were discharged on PO antibiotics. The median time to transition was five days (interquartile range [IQR], 4–6), and the median duration of PO therapy was 16 days (IQR, 14–21). Ninety-eight per cent did not require further IV therapy. There were no deaths and clinical outcomes were good. In conclusion, children with pneumonia and empyema can be managed effectively with early VATS and early transition from IV to PO antibiotic therapy.

Background Routine immunizations for children aged 10 years and younger in the United States (US) currently cover 14 diseases. Updated estimates of public health impact are needed, given changes in disease epidemiology, evolving recommendations, and the dynamic nature of compliance with the immunization schedule. Methods Pre-vaccine disease incidence was estimated before each routine vaccine was recommended, with average values across multiple years obtained directly from published literature or calculated based on disease surveillance data or annual case estimates from the published literature. Pre-vaccine incidence then was compared to current, post-vaccine incidence, which was generally calculated as average values over the most recent 5 years of available incidence data. Overall incidence estimates and estimates by age group were calculated. Differences in pre- and post-vaccine disease incidence rates were used to calculate the annual number of cases averted, based on 2019 US population estimates. This analysis did not separately estimate the proportion of disease incidence reduction that may be attributed to adult vaccines or booster doses. Results Post-vaccine disease incidence decreased overall and for all age groups across all diseases evaluated (Table 1). Decreases ranged from 17.4% for influenza to 100.0% for polio (Figure 1). Over 90% reduction in incidence was achieved for 10 of the 14 diseases evaluated (including reduction in incidence of rotavirus hospitalizations). Overall post-vaccine disease incidence estimates were highest for influenza, rotavirus, and varicella. Estimated annual cases averted by vaccination in 2019 ranged from 1,269 for tetanus to more than 4.2 million for varicella. Table 1. Pre- and Post-Vaccine Disease Incidence Estimates, Annual Cases, and 2019 Cases Averted, by Disease Figure 1. Percentage Reduction in Disease Incidence Post-Vaccine, by Disease Conclusion Routine childhood immunization in the US continues to result in high, sustained reduction in disease across all vaccines and for all age groups evaluated. Disclosures Elizabeth M. La, PhD, RTI Health Solutions (Employee) Justin Carrico, BS, GlaxoSmithKline (Consultant) Sandra E. Talbird, MSPH, RTI Health Solutions (Employee) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Mawuli K. Nyaku, DrPh, Merck & Co. Inc. (Employee, Shareholder) Cristina Carias, PhD, Merck (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator) Craig S. Roberts, PharmD, MPA, MBA, Merck & Co., Inc (Employee, Shareholder)

Background Vaccination is recommended for persons at increased risk for invasive meningococcal disease (IMD) due to complement component deficiency (CD), asplenia or human immunodeficiency virus (HIV) infection. However, uptake of quadrivalent conjugate and polysaccharide meningococcal vaccines (MenACWY) one year following a new high-risk diagnosis is very low (doi:10.1093/ofid/ofz360.2403). This retrospective cohort study identified factors associated with MenACWY vaccination among patients newly diagnosed with CD or HIV. Methods Patients identified from a large US commercial administrative claims database (Optum Research Database) with continuous enrollment for ≥12 months before and ≥6 months after appearance of an incident high-risk diagnosis through the end of the study period (3/31/2018) were considered eligible (Figure). Cox proportional hazards regression models were used to identify characteristics associated with time to receipt of ≥1 dose of MenACWY during time periods corresponding with Advisory Committee on Immunization Practices (ACIP) recommendations. Results The CD cohort consisted of 1,470 (mean=40.9 years of age) patients and the HIV cohort of 1,208 (38.8 years). Only 7.9% and 20.8% of patients with CD or HIV, respectively, received ≥1 dose of MenACWY between their index date and the end of the study period. A strong association between receipt of MenACWY and pneumococcal vaccines was seen for CD [hazard ratio (HR): 3.2; 95% CI: 1.8–5.7] and HIV [23.0; 13.9–38.1]. Age (11–18 years; for CD only) and having a well-care visit after the index date (for CD and HIV) was associated with higher likelihood of vaccination. Vaccination rates for HIV were lowest in the South. Conclusion The association of MenACWY vaccination with age in patients with CD suggests confusion between routine age-based and high-risk recommendations, whereas in patients with CD or HIV, the association with pneumococcal vaccines suggests that providers recognize the overlap in risk factors for IMD and pneumococcal disease. Ensuring healthcare access for these vulnerable patients and educating providers about high-risk recommendations is crucial. Funding GlaxoSmithKline Biologicals SA (study identifier: HO-18-19581) Disclosures Parinaz Ghaswalla, PhD, ORCID: 0000-0002-2883-5590, GlaxoSmithKline (Employee, Shareholder) Lindsay Bengtson, PhD, MPH, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator) Ami R. Buikema, MPH, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Tim Bancroft, PhD, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Krista Schladweiler, PhD, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Eleena Koep, MS, Optum (Employee) Patricia Novy, PhD, GSK (Employee, Shareholder) Cosmina Hogea, PhD, GlaxoSmithKline (Employee, Shareholder)

Background Ten different vaccine series are recommended by the US Advisory Committee on Immunization Practices from birth to 18 months. Combination vaccines can reduce the number of injections and visits required to complete the schedule in a timely manner. There is limited current information on parents’ perception of the vaccine schedule and combination vaccines. Methods An online survey was completed by 100 parents who had at least one child under 2 years, were involved in vaccination decisions, and had accompanied their child to a vaccination appointment. Parents who reported not ever vaccinating their children were excluded. Parents’ perception of, and adherence to, the recommended schedule, communication with providers, and knowledge of combination vaccines were collected. Descriptive analyses were performed. Results Ninety-six percent of parents (mean age=30.7 years; range 19.0-50.0; 91% white) reported their provider as a source of vaccination information, followed by internet searches (63%), family and friends (45%). Most (84%) followed all their provider’s recommendations and trusted the information given to them (87%). State day care and pre-school requirements influenced vaccination decisions for nearly 80% of parents. Over 80% of parents thought it is important to protect against diseases covered by the vaccination schedule. One-third had at some time asked to delay or not administer vaccines; depending on the vaccine, up to 50% ultimately had their child vaccinated as recommended. Top reasons for delaying vaccination were to avoid crying and pain from multiple injections (82%), and the concern that too many vaccines would overwhelm the immune system (64%). Top reasons for refusal were religious views (57%) and the belief that the vaccine was not needed (52%). On average, parents would accept their child receiving 3 injections in one visit. Most parents were aware of combination vaccines (84%); however, one-third reported that their child had not received, or they were unaware of their child receiving, a combination vaccine. Conclusion Providers are in a strong position to influence vaccination decisions by parents. Whereas parents are motivated to avoid the pain of multiple injections, many are unaware that their children are receiving combination vaccines. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Fever is a common symptom in children. Some children may present to their primary care physician with undifferentiated fever; that is, fever for which there is no obvious source from the history or physical examination. Undifferentiated fevers may be prolonged or recurrent. Distinguishing between the two is helpful for narrowing the differential diagnosis, which can be broad and include infections and inflammatory diseases and, rarely, malignancies and autoinflammatory disorders. The evaluation of such children requires a step-wise approach. Taking a detailed history, performing a thorough physical examination, and reviewing a fever and symptom diary is crucial in recognizing clues that may ultimately lead to a diagnosis. Some children who look good and whose fever disappears may never have a diagnosis, whereas referral to a specialist may be prudent for others. [ Pediatr Ann. 2018;47(9):e347–e353.]

Navigating the waters of vaccine hesitancy requires a view towards history and a deep understanding of how humans think. Getting children vaccinated is as much, or more, about connecting with people as it is about communicating scientific information.

Background Quadrivalent conjugate and polysaccharide meningococcal vaccines (MenACWY) have been recommended in the United States for patients at high-risk due to functional or anatomic asplenia, complement component deficiency (CD) and human immunodeficiency virus (HIV) infection. Serogroup B vaccines (MenB) are recommended for patients ≥10 years of age with asplenia or CD. Little is currently known about meningococcal vaccine uptake and time to vaccination among patients with incident high-risk diagnoses. Methods Patients newly diagnosed (1 inpatient or ≥2 outpatient medical claims with evidence of the condition ≥30 days apart) with functional or anatomic asplenia (excluding sickle cell disease), CD or HIV infection were identified in the Optum Research Database. Continuous enrollment for ≥12 months before and ≥6 months after the diagnosis date (index date) was required. Patients with evidence of pre-existing conditions were excluded. MenACWY uptake was assessed among patients ≥2 years of age at index date from January 1, 2010 for asplenia and CD, and January 1, 2016 for HIV infection, through March 31, 2018; and MenB uptake among patients ≥10 years of age at index date from January 1, 2015 through March 31, 2018. Current Procedural Terminology and National Drug Codes on medical claims were used to capture vaccinations. For each condition, Kaplan–Meier analysis was used to estimate uptake and time to receipt of ≥1 dose of each vaccine for up to 5 years post-index date; vaccinations within 90 days before the index date were also included in calculations. Results Among asplenia patients, the percentage with receipt of ≥1 dose of MenACWY at 1, 2.5, and 5 years post-index date was 6.6%, 9.4%, and 13.3%, respectively; for CD patients the corresponding percentages were 2.2%, 4.8%, and 8.3%; and for HIV patients at 1 and 2.5 years post-index date the percentages were 10.8% and 19.8% (Figure 1). Receipt of ≥1 dose of MenB at 1 and 2.5 years post-index date was 1.7% and 3.1%, respectively, for asplenia patients and 1.1% and 2.5%, respectively, for CD patients (Figure 2). Conclusion Uptake of meningococcal vaccines in patients newly diagnosed with high-risk conditions is very low and the time to vaccination is long, leaving patients vulnerable to invasive meningococcal disease for extended periods of time. Disclosures All authors: No reported disclosures.

Background The recommended US infant immunization schedule includes doses of DTaP, IPV, Hib and HepB during the first 6 months of life. The majority of infants receive DTaP as one of the two pentavalent combination vaccines (DTaP-IPV/Hib or DTaP-HepB-IPV); standalone HepB or Hib are used to complement these combinations in compliance with the recommendations. Little is known about the timing of standalone vaccine administration in relation to DTaP-based combination vaccines. Methods This was a retrospective observational cohort study using the US MarketScan commercial claims and encounters database. Infants included in the study were continuously enrolled in the same insurance plan for ≥13 months after birth, born from 1 July 2010 through 30 June 2016, and had received ≥3 doses of a pentavalent vaccine. Outcomes included the proportion of infants receiving concomitant pentavalent and standalone vaccines, and the deviation in days when these vaccines were not administered on the same date. Birth doses of HepB were not registered in the database but were presumed to have been received; therefore, the first registered HepB claim was considered to be HepB Dose-2, and the second claim was presumed to be HepB Dose-3. Results Among infants who received DTaP-IPV/Hib (n = 175,574), 94.8% had claims for ≥3 doses of HepB. Although coverage was high, only 60.7% received HepB Dose-2 on the same day as DTaP-IPV/Hib Dose-1 (around 2 months of age), and only 45.1% received HepB Dose-3 on the same day as DTaP-IPV/Hib Dose-3 (around 6 months of age) (Figure 1). Many infants (46.2%) received HepB Dose-3 after the third dose of DTaP-IPV/Hib. Among infants who received DTaP-HepB-IPV (n = 97,206), 89.9% had claims for the recommended number of Hib doses; most (91% to 98%) of these doses were administered on the same day as doses of DTaP-HepB-IPV (Figure 2). Conclusion There was variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. A newly licensed hexavalent vaccine, DTaP-IPV-Hib-HepB, could synchronize and simplify the HepB administration schedule ensuring that more infants have completed the series by 6 months of age. Disclosures All authors: No reported disclosures.

Background Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. Methods We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to 99% in both groups. Conclusions A second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults.

In this cohort of nearly 15000 11-year-old girls with insurance (commercial or Medicaid), the human papillomavirus vaccine was administered at only 1 in 4 well-adolescent visits and approximately one-third of vaccine-related visits, which suggests a substantial number of missed opportunities., Background This study assessed the initiation of HPV vaccination in insured adolescent females in relation to physician visits and receipt of other vaccines routinely given at the same age. Methods January 1, 2010, and September 31, 2015. Vaccination administration was determined by using Current Procedural Terminology codes. A missed opportunity was defined as the absence of an HPV vaccine at the following encounter types: visits with a 4-valent meningococcal conjugate vaccine (MenACWY) or tetanus, diphtheria, and acellular pertussis (Tdap) vaccine claim; well adolescent visits; or any encounter with a primary care provider (PCP). Missed opportunities were stratified by type of provider (pediatrician or nonpediatrician). Results Among 14588 adolescent girls, only 6098 (41.8%) initiated the HPV vaccine series. HPV vaccine was given at 37.1% of visits when a Tdap or MenACWY vaccine was administered, 26.0% of well adolescent visits and 41.8% of PCP visits. Pediatricians had fewer missed opportunities than nonpediatricians to administer HPV (50.7% vs 60.8%), as well as Tdap, although the difference was larger for Tdap (7.0% vs 29.6%). Conclusions These data indicate that pediatricians and nonpediatricians alike are missing opportunities to administer the HPV vaccine when other adolescent vaccines are given. Efforts should be focused on converting these missed vaccination opportunities into cancer-prevention visits.

Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.)

Combination vaccines reduce the 'shot burden' and simplify the childhood immunization schedule. Only 5-valent DTaP-based vaccines are licensed in the U.S. Areas covered: A new combination vaccine - DTaP5-IPV-Hib-HepB - is described, which induces antibody responses in infants (given in different schedules, including a 2, 4, and 6-month schedule) that are similar to the respective component vaccines. The vaccine appears to be safe and would be expected to protect against six diseases: diphtheria, tetanus, pertussis, hepatitis B, H influenzae type b, and polio. Administration is associated with higher rates of mild fever, but without significant safety signals. Expert commentary: Incorporation of this hexavalent vaccine into the U.S. schedule could improve coverage rates and timeliness, and addition to the E.U. market would add depth to the available repertoire of combination vaccines.

* Abbreviations: AAP — : American Academy of Pediatrics ACIP — : Advisory Committee on Immunization Practices MenB — : serogroup B meningococcal Published recommendations of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention, which carry the approval of the Secretary of Health and Human Services, provide guidance on how licensed vaccines should be used. Professional organizations such as the American Academy of Family Physicians and the American Academy of Pediatrics (AAP) also develop immunization recommendations. Since 1995, the recommendations of the ACIP, the American Academy of Family Physicians, and the AAP have been harmonized, although minor differences have surfaced from time to time. In the end, some vaccines are recommended for universal use and some are not, despite approval from the US Food and Drug Administration and commercial availability. Deliberations of the recommending bodies have always been methodical, data-driven, and comprehensive, but they were not always codified or, for that matter, entirely transparent. A change in that direction took place in 2010, when the ACIP adopted the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.1 In this formal process, the evidence germane to a particular disease and vaccine is ranked according to type and quality (Table 1). Key factors (eg, the balance between benefits and harm, the evidence type, values and preferences, health economic analyses) are used to refine the … Address correspondence to Gary S. Marshall, MD, 571 S. Floyd St, Suite 321, Louisville, KY 40202. E-mail: gary.marshall{at}louisville.edu

A 4-dose series of recently licensed Haemophilus influenzae type b-meningococcal serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) was immunogenic with a clinically acceptable safety profile in infants, with antibodies persisting in most participants for 1 year following dose 4. This study assessed antibody persistence up to 5 years after vaccination.Participants had received HibMenCY-TT or Hib-TT at 2, 4 and 6 months of age. At age 12-15 months, HibMenCY-TT vaccinees received a fourth HibMenCY-TT dose (HibMenCY x 4 group), whereas those who received Hib-TT received a fourth dose of either Hib-TT (Hib) or HibMenCY-TT (HibMenCY x 1). Blood samples were collected 1 month and 1, 3 and 5 years after the last dose for measurement of antipolyribosylribitol phosphate (the Hib capsular polysaccharide) antibodies and serum bactericidal activity (human complement source) against meningococcal serogroups C and Y.Five years after the fourth dose, the percentages of children with antipolyribosylribitol phosphate ≥0.15 μg/mL in HibMenCY x 4, HibMenCY x 1 and Hib groups were 98.8% (95% confidence interval: 93.5%-100%), 97.3% (85.8%-99.9%) and 92.3% (79.1%-98.4%), respectively. The percentages with human complement serum bactericidal activity ≥1:8 for meningococcal serogroup C were 82.9% (72.5%-90.6%), 73.5% (55.6%-87.1%) and 21.1% (9.6%-37.3%), respectively. The percentages with human complement serum bactericidal activity ≥1:8 for serogroup Y were 69.5% (58.4%-79.2%), 54.3% (36.6%-71.2%) and 18.4% (7.7%-34.3%), respectively.HibMenCY-TT given as a 4-dose series or as a single dose at 12-15 months of age induced immune responses for all 3 antigens that lasted for up to 5 years after vaccination in more than half of recipients.

Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRVAMP) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRVAMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRVAMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRVAMP. Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRVAMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases.

Wholesale revision of the Pediatric Infectious Diseases Developmental Screening Test (PIDDST) was imperative, given the sea change that has occurred in academic medicine and subspecialty practice in the last two decades. The PIDDST 2.0 tracks expected milestones along the continuum from fellow to full professor in today's complex health care environment. Effective use of this instrument in training programs and pediatric departments could help shape the future of the field.

In the United States, invasive meningococcal disease occurs at the highest rates in infants, with a second peak in adolescents. Early symptoms are nonspecific and may resemble viral infection, which poses a diagnostic challenge for clinicians. Moreover, the stakes of diagnostic confusion may be high because the disease may become life threatening within hours. Sequelae among survivors may be profound. In adolescent age groups, control of meningococcal disease caused by serogroups A, C, W-135, and Y rests upon universal vaccination beginning at 11–12 years of age; vaccines for serogroup B are not currently available. One 4-valent vaccine is licensed for use in infants beginning at 9 months of age but is only recommended for those at high risk. Licensure of new vaccines for infants is expected soon, and a universal immunization program is being debated. A wide range of bacteria can cause meningitis in infants and young children. In neonates aged

A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR.

A combined immunization strategy for administration of human papillomavirus (HPV) vaccine with other routine vaccines may lead to better compliance. Reactions and immunologic interference with concomitantly administered vaccines are unpredictable, necessitating clinical evaluation.This was a randomized, open study conducted at 48 centers in the United States (NCT00369824). Healthy girls 11 to 18 years of age were randomized equally to 1 of 6 groups to receive 3 doses of HPV-16/18 AS04-adjuvanted vaccine administered at 0, 1, and 6 or 1, 2, and 7 months, with or without 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) and/or 1 dose of meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MCV4) in different coadministration regimens (1283 girls vaccinated). Coadministered vaccines were injected at separate sites. Antibodies were measured for all vaccine components. Reactogenicity and safety were monitored.The prespecified criteria for noninferiority were met for all primary and secondary immunogenicity end points, demonstrating similar immunogenicity of Tdap and MCV4 when given alone or coadministered with the HPV vaccine. Immunogenicity of the HPV vaccine (in terms of seroconversion rates and geometric mean antibody titers to HPV antigens) was similar, regardless of whether it was given alone or coadministered with Tdap and/or MCV4. No differences were observed in the reactogenicity profile of the HPV vaccine administered alone or coadministered with either Tdap and/or MCV4 in different regimens.Concomitant administration of HPV-16/18 AS04-adjuvanted vaccine with Tdap and/or MCV4 in different regimens did not interfere with the immune response to any of the vaccines and had an acceptable safety profile.

BACKGROUND: Meningococcal disease incidence is highest in children younger than 2 years of age, yet there is no US-licensed vaccine for this age group. A phase III study evaluated the immunogenicity and safety of an investigational Haemophilus influenzae type b (Hib)–Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY). MATERIALS AND METHODS: A total of 4180 infants were randomly assigned to receive the HibMenCY at the ages of 2, 4, 6, and 12 to 15 months or the licensed Hib tetanus toxoid conjugate vaccine (ActHIB) at 2, 4, and 6 months and Hib conjugated to N meningitidis outer membrane protein (PedvaxHIB) at 12 to 15 months. Routinely scheduled vaccines were coadministered. Serum bactericidal activity using human complement and anti–polyribosylribitol phosphate antibodies were assessed in 991 subjects. Local and systemic adverse reactions were recorded for 4 days after each dose. RESULTS: The percentage of HibMenCY recipients with serum bactericidal assay using human complement titers of 1:8 or higher after dose 3 was 98.8% for N meningitidis serogroup C (MenC) and 95.8% for N meningitidis serogroup Y (MenY). After dose 4, the percentages were 98.5% and 98.8%, respectively. The percentage of HibMenCY recipients with postdose 3 anti-polyribosylribitol phosphate antibody levels of ≥1.0 μg/mL was noninferior to that of control (96.3% vs 91.2%). After dose 4, MenC and MenY serum bactericidal assay using human complement antibody titers increased 12-fold over pre–dose 4 levels. Incidence of pain, redness, and swelling at the HibMenCY injection sites tended to be lower than with Hib type b after the first 3 doses and after the fourth dose. Rates of systemic symptoms were similar across groups. CONCLUSIONS: The HibMenCY was immunogenic against MenC and MenY and induced anti–polyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine. The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine.

Background Unexplained fever is a common reason for outpatient referral to pediatric infectious diseases (PID) subspecialists. A previous study at our center concluded that most children referred to PID for prolonged or recurrent unexplained fever have self-limited illnesses and receive no specific diagnosis. Studies looking at long-term outcomes of such patients have not been published. Methods The study cohort consisted of 156 patients seen in the PID clinic for unexplained fever from 2008 through 2012 who were not given a definitive diagnosis or were thought to have sequential self-limited illnesses, plus 20 patients seen during that time who were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. A scripted telephone interview with consenting parents or guardians who could be reached was conducted in 2018. Results Attempts were made to contact all 176 families; to date, 100 interviews have been completed. Thirteen of the children initially had prolonged, 45 recurrent, and 25 periodic fever; 17 had PFAPA. The mean follow-up period was 8 years. Only 2 patients developed new diagnoses in the interval since their initial PID visit. One who was thought to have PFAPA developed genital ulcers and was diagnosed with Behcet’s disease 4 years after the PID visit. Another who was thought to have self-limited, prolonged fever was eventually diagnosed with juvenile idiopathic arthritis. None of the remaining 98 children developed serious diagnoses. However, 14 of these children reportedly have continued fevers; 9 of the children suffer from anxiety, and 4 of the remaining 5 report good general health. Conclusion Most children seen in PID clinic for unexplained fever who were not given a specific diagnosis remained well after their initial visit. Two were diagnosed with autoinflammatory diseases after the appearance of telltale signs and symptoms, and none were diagnosed with immunodeficiency or cancer. The children who reportedly continue having fevers but are otherwise healthy warrant further study, with particular attention to their families’ health and illness beliefs. Disclosures All authors: No reported disclosures.

Background: The number of shots represented by the routine childhood immunization schedule poses a logistical challenge for providers and a potential deterrent for parents. By reducing the number of injections, use of combination vaccines could lead to fewer deferred doses and improved coverage rates. Objective: To determine the effect of combination vaccines on coverage rates. Methods: This was a retrospective study of administrative claims data from the Georgia Department of Community Health Medicaid program conducted from January through September of 2003. Coverage rates were compared between children who received at least 1 dose of HepB/Hib (COMVAX) or DTaP/HepB/IPV (PEDIARIX) (the combination cohort) and children who received no doses of either combination (the reference cohort). Infants with fewer than 4 vaccination visits were excluded from the analysis. Multivariate logistic regression was performed on the whole study population to assess the effect of combination vaccines while controlling for potential confounders. Hepatitis B and pneumococcal conjugate vaccine coverage rates were not included as outcomes. Results: The study population consisted of 18,821 infants, 16,007 in the combination cohort and 2814 in the reference cohort. Unadjusted coverage rates for DTaP, IPV and the 4 DTaP:3 IPV:1 MMR, 4 DTaP: 3 IPV: 1 MMR: 3 Hib: 1 varicella, and 3 DTaP:3 IPV: 3 Hib series were higher in the combination cohort. Receipt of at least 1 dose of a combination vaccine was independently associated with increased coverage for each of these vaccines and vaccine series when controlling for gender, birth quarter, race, rural versus urban residence and historical provider immunization quality. Conclusions: Use of combination vaccines in this Medicaid population was associated with improved coverage rates. Additional studies are warranted, including those examining private sector populations and outcomes such as timeliness and cost.

We used a claims database to assess coverage for rotavirus (RV), diphtheria-tetanus-acellular pertussis, and pneumococcal conjugate vaccines among infants in the United States. Similar coverage was seen until 7 months of age, after which RV coverage lagged. Missed opportunities for vaccination at well-child visits were found to vary by age.

BACKGROUND: DTaP5-IPV-Hib-HepB is a fully liquid investigational hexavalent vaccine directed against 6 diseases. METHODS: This multicenter, open-label, comparator-controlled, phase III study randomly assigned healthy infants 2-to-1 as follows: group 1 received DTaP5-IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6 months of age followed by DTaP5, Hib-OMP, and PCV13 at 15 months of age; group 2 received DTaP5-IPV/Hib, PCV13, and RV5 at 2, 4, and 6 months of age, with HepB at 2 and 6 months of age, followed by DTaP5, Hib-TT, and PCV13 at 15 months of age. RESULTS: Overall, 981 participants were vaccinated in group 1 and 484 in group 2. Immune responses in group 1 to all antigens contained in DTaP5-IPV-Hib-HepB 1 month after dose 3 and for concomitant rotavirus vaccine were noninferior to those in group 2, with the exception of antipertussis filamentous hemagglutinin (FHA) geometric mean concentrations (GMCs). Vaccine response rates for FHA were noninferior to control. After the toddler dose, group 1 immune responses were noninferior to group 2 for all pertussis antigens. Solicited adverse event rates after any dose were similar in both groups, with the exceptions of increased injection-site erythema, increased fever, and decreased appetite in group 1. Fever was not associated with hospitalization or seizures. CONCLUSIONS: The safety and immunogenicity of DTaP5-IPV-Hib-HepB are comparable with the analogous licensed component vaccines. Decreased FHA GMCs and increased injection-site reactions and fever are unlikely to be clinically significant. DTaP5-IPV-Hib-HepB provides a new combination vaccine option aligned with the recommended US infant immunization schedule.

Rotavirus is a major worldwide cause of infant morbidity and mortality, and disease burden in the US is substantial. Vaccination is the only practical way to gain control over rotavirus disease. Prevention through the universal use of improved live oral vaccines is on the horizon.

BACKGROUND Older case series established diagnostic considerations for children meeting a priori definitions of fever of unknown origin (FUO). No recent study has examined the final diagnoses of children referred for unexplained fever. METHODS This study was conducted with a retrospective chart review of patients referred to a pediatric infectious diseases clinic from 2008 to 2012 for unexplained fever. RESULTS Sixty-nine of 221 patients were referred for "prolonged" unexplained fever. Ten of these were not actually having fever, and 11 had diagnoses that were readily apparent at the initial visit. The remaining 48 were classified as having FUO. The median duration of reported fever for these patients was 30 days; 15 had a diagnosis made, 5 of which were serious. None of the serious FUO diagnoses were infections. Of 152 patients with "recurrent" unexplained fever, 92 had an "intermittent" fever pattern, and most of these had sequential, self-limited viral illnesses or no definitive diagnosis made. Twenty of the 60 patients with a "periodic" fever pattern were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Overall, 166 patients either were not having fever, had self-limited illnesses, or ultimately had no cause of fever discovered. Only 12 had a serious illness, 2 of which were infections (malaria and typhoid fever). CONCLUSIONS Most children referred with unexplained fever had either self-limited illnesses or no specific diagnosis established. Serious diagnoses were unusual, suggesting that these diagnoses rarely present with unexplained fever alone, or that, when they do, the diagnoses are made by primary care providers or other subspecialists.

As new combination vaccines are approved, practices must consider whether to switch. The decision is likely to be complex, involving everything from re-education of staff to recalculating the bottom line. At some point, however, change will be inevitable, driven principally by the need to add new vaccines to the schedule. In fall 2004, practitioners will be adding two doses of inactivated influenza vaccine to the infant schedule. More communities will be adding two doses of hepatitis A vaccine, which may become routine for all children at some point. We can hope as well for a meningococcal conjugate vaccine series, which, like Hib and PCV-7, would be administered by an infant's first birthday. In addition, there's the pentavalent bovine reassortant rotavirus vaccine (Rotateq) which, although given orally, will further crowd the schedule. The sooner we become comfortable with combination vaccines, the better.

The authors are concerned that a remaining refuge of substantive democracy in America, the public sector, is in danger of abandoning it in favor of the market model of management. They argue that contemporary American democracy is confined to a shrunken procedural remnant of its earlier substantive form. The classical republican model of citizen involvement faded with the rise of liberal capitalist society in the late nineteenth and early twentieth centuries. Capitalism and democracy coexist in a society emphasizing procedural protection of individual liberties rather than substantive questions of individual development. Today’s market model of government in the form of New Public Management goes beyond earlier “reforms,” threatening to eliminate democracy as a guiding principle in public-sector management. The authors discuss the usefulness of a collaborative model of administrative practice in preserving the value of democracy in public administration.