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BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children’s stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year–vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive–vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year–vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive–vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Introduction Immunization education for physicians-in-training is crucial to address vaccine concerns in clinical practice. Vaccine education is not standardized across residency programs. The Collaboration for Vaccination Education and Research (CoVER) team developed an online curriculum for pediatric (Peds) and family medicine (FM) residents. Methods A cluster randomized controlled trial (RCT) was performed during the 2017–2018 academic year to evaluate the CoVER curriculum. A convenience sample of residency institutions were randomly allocated to the intervention or control group, with stratification by residency type. The intervention, the CoVER curriculum, consisted of four online modules and an in-person training guide. Control sites continued with their standard vaccine education. Pre-intervention and post-intervention surveys were emailed to residents in both groups. The primary outcomes compared between groups were changes in “vaccine knowledge,” “vaccine attitudes/hesitancy,” and “self-confidence” in immunization communication. The team assessing outcomes was unblinded to assignments. Hierarchical general linear model was used to adjust for residency type and residency year; residency site was modeled as a random effect. Results Overall, 1444 residents from 31 residency programs were eligible to participate (734 intervention, 710 control). The pre-intervention response rate was 730 (51%) and post-intervention was 526 (36%). Average knowledge scores increased from pre-intervention (control 53%; CoVER 53%) to post-intervention (control 58%; CoVER 60%). Increases in vaccine knowledge among FM residents were greater for CoVER compared to controls (p = 0.041). Vaccine hesitancy was more common among FM (23%) than Peds (10%) residents. In all three residency years, residents in the CoVER group showed greater increases in self-confidence in ability to discuss vaccines with parents/patients (p Conclusion The CoVER curriculum is an effective model to standardize immunization education of physicians-in-training. This RCT demonstrated the effectiveness of the CoVER curriculum to improve resident confidence in their ability to discuss vaccines with parents and patients.

OBJECTIVES: Diagnosing Clostridioides difficile infections in young children with high asymptomatic colonization is challenging. We compared the frequency of C difficile detection by polymerase chain reaction (PCR) in healthy control (HC) children with those with acute gastroenteritis (AGE) and evaluated fecal-lactoferrin and organism load as possible indicators of true C difficile infection disease. METHODS: Stool was collected from children RESULTS: Of 524 stools collected from 524 children (250 with AGE, 274 HCs), C difficile was detected less in children with AGE (14%, 36 of 250) than in HCs (28%, 76 of 274) stools (P < .0001). Among infants CONCLUSIONS: HC children

Background Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. Methods A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. Results During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). Conclusions A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Background The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. Methods In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. Results A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P

Objective In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children. Study design This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6–35 months of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3–17 years of age received 15mcg HA/dose. Safety and reactogenicity were assessed by measuring the occurrence of solicited injection site and systemic reactions in the 7 days after each vaccination; adverse events were assessed for 42 days and serious adverse events for 7 months after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21 days after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated. Results The H3N2v vaccine was well tolerated. Transient mild to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 6–35 months, and headache and fatigue in children 9–17 years old. Children 6–35 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 9–17 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9–17 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses. Conclusion The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered with clinicaltrial.gov: NCT02100436 .

Mucormycosis is a severe infection that affects a variety of patients, including immunocompromised children and neonates. Given improved survival rates from advances in the treatment of malignancies, the population at risk for mucormycosis is increasing. We conducted a systematic review of cases of mucormycosis in children in the English-language literature reported between August 2008 and June 2017 and analyzed the clinical characteristics, diagnosis, management, and outcome of those infections. The most common underlying diagnoses included neutropenia (41%), hematologic malignancy (39%), prematurity (13%), and hematopoietic stem cell transplant (11%). Sinus disease (28%) and disseminated disease (24%) were the most common presentations. Rhizopus spp were the most common organisms isolated (22%). Amphotericin B remains the backbone of treatment and was prescribed in 86% of these cases. The resulting mortality rate remains high (32%). We provide here the results of a literature review of mucormycosis in children, including its epidemiology and clinical manifestations, and describe current advances in its diagnosis and treatment.

We evaluated enterovirus D68 seroprevalence in Kansas City, Missouri, USA, from samples obtained during 2012-2013. Neutralizing antibodies against Fermon and the dominant 2014 Missouri isolate were universally detected. Titers increased with age. Widespread circulation of enterovirus D68 occurred before the 2014 outbreak. Research is needed to determine a surrogate of protection.

BackgroundClinical trials are the gold standard for assessing the effectiveness and safety of treatments. The objective of the current study was to assess provider opinions regarding implementing pediatric clinical trials in various practice settings across Kansas. MethodsThe study was completed within the Sunflower Pediatric Clinical Trials Research Extension (SPeCTRE), an affiliate of the IDeA States Pediatric Clinical Trials Network (ISPCTN). A cross-sectional, 36-item survey was administered to a state-wide convenience sample targeting health care providers and clinic staff. ResultsA total of 119 health care providers and clinic staff completed surveys; 31% were physicians. Physicians were more likely than other clinic staff to have experience with clinical trials (correlation coefficient [CC]=0.270, p=0.004). When compared to urban respondents, rural providers were less supportive of recruitment for clinical trials in their practices (CC=-0.251, p=0.008) and more likely to feel comfortable referring patients for clinical trials involving treatments that their insurance did not cover (CC=0.302, p=0.001).ConclusionA range of rural and urban health care professionals support the performance of pediatric clinical trials but identify several barriers as well. These results will support future pediatric clinical trials across the country including Kansas.TRIAL REGISTRATION: NA

Influenza A(H1N1)pdm09 viruses initially predominated during the US 2018-2019 season, with antigenically drifted influenza A(H3N2) viruses peaking later. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits among children in the New Vaccine Surveillance Network.We tested children 6 months to 17 years with acute respiratory illness for influenza using molecular assays at 7 pediatric hospitals (ED patients5 years at 3 sites). Vaccination status sources were parental report, state immunization information systems and/or provider records for inpatients, and parental report alone for ED patients. We estimated VE using a test-negative design, comparing odds of vaccination among children testing positive versus negative for influenza using multivariable logistic regression.Of 1792 inpatients, 226 (13%) were influenza-positive: 47% for influenza A(H3N2), 36% for A(H1N1)pdm09, 9% for A (not subtyped), and 7% for B viruses. Among 1944 ED children, 420 (22%) were influenza-positive: 48% for A(H3N2), 35% for A(H1N1)pdm09, 11% for A (not subtyped), and 5% for B viruses. VE was 41% (95% confidence interval [CI], 20% to 56%) against any influenza-related hospitalizations, 41% (95% CI, 11% to 61%) for A(H3N2), and 47% (95% CI, 16% to 67%) for A(H1N1)pdm09. VE was 51% (95% CI, 38% to 62%) against any influenza-related ED visits, 39% (95% CI, 15% to 56%) against A(H3N2), and 61% (95% CI, 44% to 73%) against A(H1N1)pdm09.The 2018-2019 influenza vaccine reduced pediatric influenza A-associated hospitalizations and ED visits by 40% to 60%, despite circulation of a drifted A(H3N2) clade.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalized acute respiratory illness (ARI) among young children. With RSV vaccines and immunoprophylaxis agents in clinical development, we sought to update estimates of US pediatric RSV hospitalization burden. METHODS: Children RESULTS: Among 2969 hospitalized children included in analyses, 1043 (35%) tested RSV-positive; 903 (87%) children who were RSV-positive were CONCLUSIONS: During the 2015–2016 season, RSV infection was associated with one-third of ARI hospitalizations in our study population of young children. Hospitalization rates were highest in infants

DiagnosingStool was collected from children2 years old with AGE and from HCs.Of 524 stools collected from 524 children (250 with AGE, 274 HCs),HC children2 years of age had higher rates of

No indigenous cases of poliomyelitis have occurred in the US since 1979; however the risk of importation persists until global eradication is achieved. The seropositivity rate for different age cohorts with exposures to different poliovirus vaccine types and wild virus in the US are not presently known. A convenience sample was conducted in the Kansas City metropolitan area during 2012-2103 with approximately 100 participants enrolled for each of 5 age cohorts categorized based on vaccine policy changes over time in the US. Immunization records for poliovirus vaccination were required for participants

We conducted a qualitative study from 2018 to 2019 to update the reasons why US parents’ refuse or delay vaccines. Four focus groups and 4 semi-structured interviews involving 33 primary care pediatric providers were conducted in Washington and Colorado. A thematic analysis was conducted to identify themes related to reasons for parental refusal or delay. Five predominant themes were identified: (1) vaccine safety, (2) relative influence of information sources, decision-makers, and timing, (3) low perceived risk of contracting vaccine-preventable disease, (4) lack of trust, and (5) religious objection. Vaccine safety was the theme mentioned most frequently by providers (N = 45 times by 26 providers) and religious objection to vaccination was referred to the least (N = 6 times by 6 providers). Provider-reported reasons for parental refusal or delay of childhood vaccines in 2018 to 2019 remain similar to those reported in previous studies.

We evaluated enterovirus D68 seroprevalence in Kansas City, Missouri, USA, from samples obtained during 2012–2013. Neutralizing antibodies against Fermon and the dominant 2014 Missouri isolate were universally detected. Titers increased with age. Widespread circulation of enterovirus D68 occurred before the 2014 outbreak. Research is needed to determine a surrogate of protection.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus (SA) is the second leading cause of late-onset sepsis among infants in the NICU. Because colonization of nasal mucosa and/or skin frequently precedes invasive infection, decolonization strategies, such as mupirocin application, have been attempted to prevent clinical infection, but data supporting this approach in infants are limited. We conducted a phase 2 multicenter, open-label, randomized trial to assess the safety and efficacy of intranasal plus topical mupirocin in eradicating SA colonization in critically ill infants. METHODS: Between April 2014 and May 2016, infants RESULTS: A total of 155 infants were randomly assigned. Mupirocin was generally well tolerated, but rashes (usually mild and perianal) occurred significantly more often in treated versus untreated infants. Primary decolonization occurred in 62 of 66 (93.9%) treated infants and 3 of 64 (4.7%) control infants (P < .001). Twenty-one of 46 (45.7%) treated infants were persistently decolonized compared with 1 of 48 (2.1%) controls (P < .001). CONCLUSIONS: Application of mupirocin to multiple body sites was safe and efficacious in eradicating SA carriage among infants in the NICU; however, after 2 to 3 weeks, many infants who remained hospitalized became recolonized.

This article was migrated. The article was not marked as recommended. Background: Vaccine education during residency is not standardized. Little is known about resident perspectives on vaccines and ideal vaccine training. Methods: A convenience sample of pediatric and family medicine (FM) residents were surveyed using a de novo 22 question survey to understand perspectives on vaccines and current and preferred vaccine education curriculum. Responses were analyzed categorically and compared by resident year using Fisher's Exact test. Results: In October 2016, 126 residents from 9 pediatric and FM programs completed the survey. Resident respondents' training levels varied. Most were 25-29 years old and female. High familiarity with vaccines and agreeing to defer recommended vaccine(s) increased with additional years of training (p

Holodiastolic flow reversal in the descending aorta by spectral Doppler at the level of the diaphragm is indicative of an aortic run-off lesion or severe aortic regurgitation. A 3 year old boy presented with 8 days of fever, conjunctivitis, dry mucous membranes and rash. Labs showed high

[Figure: see text] BACKGROUND AND OBJECTIVES: Staphylococcus aureus (SA) is the second leading cause of late-onset sepsis among infants in the NICU. Because colonization of nasal mucosa and/or skin frequently precedes invasive infection, decolonization strategies, such as mupirocin application, have been attempted to prevent clinical infection, but data supporting this approach in infants are limited. We conducted a phase 2 multicenter, open-label, randomized trial to assess the safety and efficacy of intranasal plus topical mupirocin in eradicating SA colonization in critically ill infants. METHODS: Between April 2014 and May 2016, infants

Supplemental Digital Content is available in the text, Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment. A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment. Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment. While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Human papilloma virus (HPV) infection is the most common sexually transmitted infection in the United States. Some infections will result in anogenital warts and anogenital or oropharyngeal cancers. Preventing HPV infection is a public health priority to reduce cancer and HPV-associated complications. Prevention through vaccination is the most cost-effective and lifesaving intervention to decrease the burden of HPV-related cancers and other HPV-associated diseases. It is critical for pediatricians to make a strong recommendation for early and timely vaccination and completion of the 3-dose series. The goal of early vaccination is to immunize before first exposure to HPV virus.

* Abbreviation: RV5 — : pentavalent rotavirus vaccine The Advisory Committee on Immunization Practices and the American Academy of Pediatrics support rotavirus vaccination of preterm infants according to the same schedule and precautions as term infants with an important stipulation: the requirement that the vaccine should be administered at or after hospital discharge because of the concern for rotavirus vaccine shedding and the unknown impact of potential nosocomial spread.1,2 This requirement leads to unnecessarily missed vaccinations. Some hospitals have opted to immunize premature eligible infants before discharge because they perceive the risk of leaving an infant susceptible to rotavirus disease outweighs the risk of nosocomial spread. Monk et al3 have previously reported their experience immunizing infants in the NICU with pentavalent rotavirus vaccine (RV5) and found that all immunized infants tolerated vaccination: 25% were asymptomatic, 51% were symptomatic but unchanged from baseline, and 24% had clinical status changes that were not attributed to RV5. They examined the clinical status of neighboring unimmunized infants and found that only 1% developed nonspecific gastrointestinal symptoms or fever, not attributed to RV5, although shedding was not evaluated.3 In this issue of Pediatrics , Hofstetter et al … Address correspondence to Barbara Pahud, MD, MPH, Department of Infectious Diseases, Children’s Mercy Hospital Kansas City, 2401 Gillham Rd, Kansas City, MO 64108. E-mail: bapahud{at}cmh.edu

Objectives:Screening of immunization status at each health care encounter is recommended to improve immunization coverage rates but is often limited to primary care practices. A pilot intervention study was performed to ascertain the immunization status of hospitalized children and determine if development of an immunization plan before discharge would improve the vaccination status for such children.Methods:On the basis of power calculations estimated to detect an increase in immunization status from 60% to 70% with 80% power, 356 randomly selected children were enrolled between March 6, 2012 and June 14, 2012. Immunization records were obtained, immunization status determined, and parent/guardian informed if catch-up dose(s) were needed. If parent requested vaccine dose(s), they were administered before discharge.Results:Vaccination status was current per Advisory Committee on Immunization Practices guidelines in 73% of hospitalized children, and 27% children required catch-up dose(s) (200 doses for 95 children). Human papilloma virus vaccine (dose 1), varicella zoster vaccine (dose 2), and meningococcal conjugate vaccine were the most commonly identified dose(s) needed. Of those requiring catch-up dose(s), 25% were caught up, increasing vaccination status to 80% at 1-month post hospital discharge.Conclusions:This is the first study to determine the immunization status of hospitalized pediatric patients of all ages, including adolescents, providing new data on the immunization status of the inpatient pediatric population. A pilot intervention consisting of obtaining immunization records, determining immunization status, and discussing catch-up dose(s) before discharge resulted in improvement of immunization status, suggesting that the inpatient setting may be used along with many other national strategies to help address missed vaccination opportunities.

BACKGROUND The originally recommended dosing schedule, 0, 2, 6 months, for the 3-dose quadrivalent human papillomavirus vaccine (4vHPV) was often not followed, resulting in longer than recommended intervals between doses and interest in the effect of prolonged intervals. Recent two-dose recommendations require investigations into the effect of delaying dose 2. METHODS This multi-site, prospective study enrolled healthy 9-17 year old girls (n = 1321) on the day of or within 28 days following a third dose of 4vHPV vaccination. Antibody titers to 4vHPV types were measured at one and six months post-dose 3 from all participants and post-dose 2 from participants who were on time for dose 3. To compare antibody responses, participants were categorized into groups: second and third doses on time (control group); on-time dose 2, substantially late dose 3 (group 2); substantially late dose 2, on-time dose 3 (group 3); both doses substantially late (group 4). Analyses compared age-adjusted geometric mean titers (GMTs) at one-month and six-months post-dose 3, effect of delaying the second dose, and two versus three doses as well as post-dose 2 GMTs, stratified by age. RESULTS Compared to on-time dosing, one-month post-dose 3 GMTs were non-inferior in groups 2, 3, and 4 and were superior in group 2. Six month post-dose 3 GMTs were superior in groups 2, 3, and 4 for each genotype, except HPV 18 in group 3. Age-adjusted post does 2 titers were significantly lower than post-dose 3 titers when dose 2 was on time but were significantly higher when dose 2 was substantially late. Participants ≥15 years old had no difference in post-dose 2 titers compared to

BACKGROUND: Children with severe influenza infection may require parenteral therapy if oral or inhaled therapies are ineffective or cannot be administered. Results from a study investigating intravenous (IV) zanamivir for the treatment of hospitalized infants and children with influenza are presented. METHODS: This phase II, open-label, multicenter, single-arm study assessed the safety of investigational IV zanamivir in hospitalized children with influenza. Safety outcomes included treatment-emergent adverse events (TEAEs), clinical laboratory measurements, and vital signs. Clinical outcomes, pharmacokinetics, and virologic efficacy data were collected as key secondary outcomes. RESULTS: In total, 71 children received treatment with investigational IV zanamivir (exposure comparable to 600 mg twice daily in adults). TEAEs and serious TEAEs (STEAEs) were reported in 51 (72%) and 15 (21%) patients, respectively. The mortality rate was 7%, and median durations of hospital and ICU stays were 6 and 7.5 days, respectively. No STEAEs or deaths were considered related to IV zanamivir treatment, and no patterns of TEAEs, laboratory abnormalities, or vital signs were observed. The mean zanamivir exposures from 34 patients with normal renal function who received 12 mg/kg, 14 mg/kg, or 600 mg of IV zanamivir ranged from 64.5 to 110 hour·µg/mL. The median change from baseline in the viral load was −1.81 log10 copies per mL after 2 days of treatment. CONCLUSIONS: The safety profile of IV zanamivir was favorable, with no drug-related STEAEs reported. The majority of children experienced virologic response and clinical improvement during the treatment course. Systemic zanamivir exposures in children were consistent with adults.

This article was migrated. The article was marked as recommended. Vaccine education for pediatric and family medicine residents is inadequate. Implementation of evidence-based instructional design methods for medical education is understudied. We conducted four focus groups with residents who had completed a novel immunization curriculum to explore their satisfaction with design, content and impact on confidence. Data were analyzed using thematic content analysis. Overall satisfaction with the curriculum was high. Residents valued the interactive design and content, reported improvement in confidence in discussing vaccines with parents, and shared recommendations for future iterations of the modules. Technical challenges were reported with the learning management system. Medical education modules developed using best practices in instructional design were well-liked by trainees and future modules should be developed using these principles.

Background Hypersensitivity disorders following vaccinations are a cause for concern. Objective To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. Design A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. Setting/patients US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. Measurements Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. Results Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. Limitations Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. Conclusions Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity reactions.

BACKGROUND Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. METHODS A retrospective chart review was performed of children admitted to Children's Mercy Hospital from August 1, 2014, to September 15, 2014, with positive multiplex polymerase chain reaction testing for EV/rhinovirus (RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records. Patients with EV-D68 were compared with children presenting simultaneously with other EV/RV. RESULTS Of 542 eligible specimens, children with EV-D68 were significantly older than children with other EV/RV (4.6 vs. 2.2 years, P < 0.001). Children with EV-D68 were more likely to have a history of asthma (38.6% vs. 30.0%, P = 0.04) or recurrent wheezing (22.1% vs. 14.8%, P = 0.04). EV-D68-positive children more commonly received supplemental oxygen (86.7% vs. 65.0%, P < 0.001), albuterol (91.2% vs. 65.5%, P < 0.001) and corticosteroids (82.9% vs. 58.6%, P < 0.001). Age ≥5 years was an independent risk factor for intensive care unit management in EV-D68-infected children. Children with a history of asthma or recurrent wheezing and EV-D68 received supplemental oxygen (92.7% vs. 82.4%, P = 0.007) and magnesium (42.7% vs. 29.7%, P = 0.03) at higher rates and more continuous albuterol (3 vs. 2 hours, P = 0.03) than those with other EV/RV. CONCLUSIONS EV-D68 causes severe disease in the pediatric population, particularly in children with a history of asthma or recurrent wheezing. EV-D68-positive children are more likely to require therapy for refractory bronchospasm and may need intensive care unit- level care.

Background Kawasaki disease is a complex and potentially serious condition. It has been observed in temporal relation to immunisation. Methods We conducted a systematic literature review using various reference sources to review the available evidence published in the literature. Results We identified twenty seven publications reporting a temporal association between immunisation and Kawasaki disease. We present a systematic review of data drawn from randomised controlled trials, observational studies, case series and reports, and reviews. Overall there was a lack of standardised case definitions, making data interpretation and comparability challenging. Conclusions Although a temporal relationship between immunisation and Kawasaki disease is suggested, evidence for an increased risk or a causal association is lacking. Implementation of a standardised Kawasaki disease case definition would increase confidence in the findings and add value to future studies of pre- or post-licensure vaccine safety studies.

We report a case of a 22-month old girl who presented with a ventriculoperitoneal shunt (VPS) infection, secondary to herniation of a perforated Meckel's diverticulum through a ventral abdominal wall defect from a previous VPS revision. This is the first description of the kind in the pediatric or surgical literature.

We present three cases ofVLBW infants with Candida albicans fungemia who had brainmicroabscesses (

BACKGROUND AND OBJECTIVES: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone. METHODS: Randomized, multicenter, open-label study. Healthy infants (6-14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving only the monovalent rotavirus vaccine received 2 doses of vaccine and the other 4 groups received 3 doses of vaccine. Serum for immunogenicity testing was obtained 1 month after the last vaccine dose and the proportion of seropositive children (rotavirus immunoglobulin A >20 U/mL) were compared in all the vaccine groups. RESULTS: Between March 2011 and September 2013, 1393 children were enrolled and randomized. Immune responses to all the sequential mixed vaccine schedules were shown to be noninferior when compared with the 2 single vaccine reference groups. The proportion of children seropositive to at least 1 vaccine antigen at 1 month after vaccination ranged from 77% to 96%, and was not significantly different among all the study groups. All schedules were well tolerated. CONCLUSIONS: Mixed schedules are safe and induced comparable immune responses when compared with the licensed rotavirus vaccines given alone. Fil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos Fil: McNeal, Monica. Cincinnati Children's Hospital Medical Center; Estados Unidos Fil: Walter, Emmanuel B.. Duke University School Of Medicine; Estados Unidos Fil: Shane, Andi L.. University of Emory; Estados Unidos Fil: Winokur, Patricia. University of Iowa; Estados Unidos Fil: Cress, Gretchen. University of Iowa; Estados Unidos Fil: Berry, Andrea A.. University of Maryland; Estados Unidos Fil: Kotloff, Karen L.. University of Maryland; Estados Unidos Fil: Sarpong, Kwabena. University of Texas Medical Branch; Estados Unidos Fil: Turley, Christine B.. University of Texas Medical Branch; Estados Unidos Fil: Harrison, Christopher J.. Children's Mercy Hospital; Estados Unidos Fil: Pahud, Barbara A.. Children's Mercy Hospital; Estados Unidos Fil: Marbin, Jyothi. Benioff Children's Hospital Oakland; Estados Unidos Fil: Dunn, John. Group Health Cooperative; Estados Unidos Fil: El-Khorazaty, Jill. Emmes Corporation; Estados Unidos Fil: Barret, Jill. Emmes Corporation; Estados Unidos Fil: Edwards, Kathryn M. Vanderbilt University; Estados Unidos

This report defines the role of Apophysomyces as an aggressive fungal pathogen seen after a tornado injury. Clinical and laboratory manifestations of infections after environmentally contaminated wounds incurred during a tornado are outlined, emphasizing mechanism of injury, comorbidities, and diagnostic and treatment challenges. Therapy with systemic antifungal therapy and aggressive serial tissue debridement was successful in achieving cure.

We describe a case of immune thrombocytopenic purpura (ITP) occurring 15 days after the first dose of a 4-dose rabies vaccination series. ITP is thought to be an immune-mediated process triggered by an infection or toxin. There is little evidence in the literature beyond case reports of an association of ITP with vaccines other than with the measles, mumps, and rubella vaccine. This is the third reported case of ITP associated with rabies vaccination. Because of the rare occurrence of this adverse event relative to the severity of rabies infection, the benefits of rabies vaccination, when indicated, outweigh the low and possible risk of ITP.

Monovalent 2009 H1N1 influenza vaccines were licensed and administered in the United States during the H1N1 influenza pandemic between 2009 and 2013.Vaccine Adverse Event Reporting System received reports of adverse events following immunization (AEFI) after H1N1 vaccination. Selected reports were referred to the Centers for Disease Control and Prevention's Clinical Immunization Safety Assessment network for additional review. We assessed causality using modified World Health Organization criteria.There were 3,928 reports of AEFI in children younger than age 18 years after 2009 H1N1 vaccination received by January 31, 2010. Of these, 214 (5.4%) were classified as serious nonfatal and 109 were referred to Clinical Immunization Safety Assessment for further evaluation. Ninety-nine (91%) had sufficient initial information to begin investigation and are described here. The mean age was 8 years (range, 6 months-17 years) and 38% were female. Median number of days between vaccination and symptom onset was 2 (range, -11 days to +41 days). Receipt of inactivated, live attenuated, or unknown type of 2009 H1N1 vaccines was reported by 68, 26 and 5 cases, respectively. Serious AEFI were categorized as neurologic events in 47 cases, as hypersensitivity in 15 cases and as respiratory events in 10 cases. At the time of evaluation, recovery was described as complete (61), partial (16), no improvement (1), or unknown (21). Causality assessment yielded the following likelihood of association with 2009 H1N1 vaccination: 8 definitely; 8 probably; 21 possibly; 43 unlikely; 17 unrelated; and 2 unclassifiable.Most AEFI in children evaluated were not causally related to vaccine and resolved without sequelae. Detailed clinical assessment of individual serious AEFI can provide reassurance of vaccine safety.

Background Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. Methods Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. Results 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barre Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as "possibly" related (33%), 108 as "unlikely" related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were classified as "probable" or "definite" and 12 were unclassifiable (6%). Conclusion The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment.