Search

Objective: To test the hypothesis that international adoption of Chinese and Eastern European girls after 9 months of age results in long-term changes in the neural circuitry supporting monolingual English in later childhood. Study design: Functional magnetic resonance imaging was used to test this hypothesis by comparison with a control group of American-born English speakers (n = 13). Girls now aged 6-10 years adopted from China (n = 13) and Eastern Europe (n = 12) by English-speaking families were recruited through a pediatric hospital-based international adoption center after spending more than 6 months in an orphanage or other institution, a measure of early environmental deprivation. Functional magnetic resonance imaging scans were performed on a 3 Tesla MRI scanner using a verb generation language fluency task. Composite activation maps were computed for each group using a general linear model with random effects analysis. Results: Chinese born adoptees demonstrate atypical lateralization of language function with an apparent shift of temporal-parietal and frontal areas of brain activity toward the right hemisphere. Eastern European adoptees exhibited a rightward shift relative to controls in both frontal and temporal-parietal brain regions. Conclusions: Significant differences in lateralization between the Chinese and American-born groups in temporal-parietal language areas highlight the possible impact of early tonal Asian language exposure on neural circuitry. Findings suggest that exposure to an Asian language during infancy can leave a long-term imprint on the neural circuitry supporting English language development. [Copyright &y& Elsevier]

Abstract: To estimate the effectiveness of influenza vaccine against medical care visits for laboratory-confirmed influenza in young children we conducted a matched case–control study in children with acute respiratory illness or fever from 2005–2007. Influenza vaccine effectiveness (VE) was calculated using cases with laboratory-confirmed influenza and controls who tested negative for influenza. The effectiveness of influenza vaccine in fully vaccinated children 6–59 months of age was 56% (95% CI: 25%–74%); a significant VE was not found for partial vaccination. [Copyright &y& Elsevier]

Abstract: Definitive immunization guidelines for internationally adopted children are lacking. We examined whether these children had serologic evidence of protection against vaccine-preventable diseases. For children with ≥3 vaccine doses, overall protection was high for diphtheria (85%), tetanus (95%), polio (93%), hepatitis B (77%), and Hib (67%). For children ≥12 months of age with ≥1 dose of measles, mumps, or rubella vaccines, 95%, 72%, and 94% were immune, respectively. Children without immunization documentation had lower immunity. Serologic testing was useful in verifying the immunization status in internationally adopted children with and without documentation of immunizations. [ABSTRACT FROM AUTHOR]

The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020–March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

We sought to determine whether maternal vaccination during pregnancy was associated with a reduced risk of laboratory-confirmed influenza hospitalizations in infants <6 months old. Active population-based, laboratory-confirmed influenza surveillance was conducted in children hospitalized with fever and/or respiratory symptoms in 3 US counties from November through April during the 2002 through 2009 influenza seasons. The exposure, influenza vaccination during pregnancy, and the outcome, positive/negative influenza testing among their hospitalized infants, were compared using logistic regression analyses. Among 1510 hospitalized infants <6 months old, 151 (10%) had laboratory-confirmed influenza and 294 (19%) mothers reported receiving influenza vaccine during pregnancy. Eighteen (12%) mothers of influenza-positive infants and 276 (20%) mothers of influenza-negative infants were vaccinated (unadjusted odds ratio, 0.53; 95% confidence interval, 0.32–0.88 and adjusted odds ratio, 0.52; 95% confidence interval, 0.30–0.91). Infants of vaccinated mothers were 45-48% less likely to have influenza hospitalizations than infants of unvaccinated mothers. Our results support the current influenza vaccination recommendation for pregnant women. [Copyright &y& Elsevier]

Objective: To determine the population-based inpatient disease burden of parainfluenza virus in children <5 years of age. Study design: The New Vaccine Surveillance Network (NVSN) enrolled children <5 years of age who were hospitalized with febrile or acute respiratory illnesses. Surveillance hospitals admitted >95% of all hospitalized children from each county. Combined nasal turbinate/throat swabs were tested for parainfluenza virus (PIV), respiratory syncytial virus, and influenza virus with culture and reverse-transcription-polymerase chain reaction. Both parental interviews and medical chart reviews were conducted. Age-specific population-based hospitalization rates were calculated. Results: From October 2000 through September 2004, 2798 children were enrolled. A total of 191 PIVs were identified from 189 children (6.8% of enrolled: 73 PIV type 1, 23 PIV type 2, and 95 PIV type 3), compared with 521 respiratory syncytial viruses and 159 influenza viruses. Mean PIV hospitalization rates were 3.01, 1.73, 1.53, 0.39, and 1.02 per 1000 children per year for ages 0 to 5 months, 6 to 11 months, 12 to 23 months, 24 to 59 months, and 0 to 59 months, respectively. Conclusions: PIV accounted for 6.8% of all hospitalizations for fever, acute respiratory illnesses, or both in children <5 years of age. The pediatric PIV inpatient burden is substantial and highlights the need to find an effective vaccine candidate. [Copyright &y& Elsevier]

Background: We report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient.Patient Description: A previously healthy, eight-year-old Hispanic girl presented with subacute left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurological decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Postmortem brain autopsy remained consistent with vasculitis.Conclusion: This is the first pediatric presentation to suggest that SARS-CoV-2 can lead to a fatal, postinfectious, inflammatory small-vessel cerebral vasculitis. Our patient uniquely included supportive cerebrospinal fluid and postmortem tissue analysis. While most children recover from the neurological complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: The United States has experienced two shortages of heptavalent pneumococcal conjugate vaccine (PCV7). National guidelines called for deferring the third and fourth PCV7 doses from healthy children during these shortages. However, recommendations were not the same during the first and second shortages, and recommendations changed over time during each of the shortages as shortages worsened. Objectives: To measure PCV7 immunizing behavior for healthy children during shortage and non-shortage periods and assess the accuracy of the physicians’ reported immunizing behavior when compared to their actual immunizing behavior. Methods: We reviewed medical records in 14 randomly selected practices to measure actual immunizing behavior during shortage and non-shortage periods. We surveyed pediatricians in the Greater Cincinnati area to ascertain reported immunizing behavior. Actual and reported immunizing behaviors were compared. Results: 2888 medical records were reviewed; surveys were obtained from 51 pediatricians (65% response rate). During periods of non-shortage, 74% of healthy children received their first two doses of PCV7 on time, whereas during periods of shortage, only 66% of healthy children received their first two doses of PCV7 on time. Compared with measured immunizing behavior from chart reviews, 54–76% of the pediatricians overestimated their compliance with guidelines to defer the fourth PCV7 dose while only 5–20% underestimated their compliance. Conclusions: Physicians often overestimated the percentage of children whose vaccine doses they deferred during vaccine shortages. Despite these findings, physicians were able to maintain high coverage with the first two PCV7 doses among healthy children. [Copyright &y& Elsevier]

The COVID-19 pandemic highlighted the significance of readily available and easily performed viral testing for surveillance during future infectious pandemics. The objectives of this study were: to assess the performance of the Xpert Xpress Flu and/or RSV test, a multiplex PCR assay for detecting influenza A and B virus and respiratory syncytial virus nucleic acids in respiratory tract specimens, relative to the Quidel Lyra Influenza A+B assay and the Prodesse ProFlu+ assay, and the system's ease of use by minimally trained operators. Overall, the Xpert Xpress Flu/RSV test demonstrated a high positive and negative percent agreement with the comparator assays, and was easy to use and interpret results, based on the operators' feedback. We concluded that the Xpert Xpress Flu/RSV test is sensitive, specific, and easy to use for the diagnosis of influenza and RSV by minimally trained operators and can be a valuable tool in future infectious clusters or pandemics. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ. Objective To detect PZ resistance conferring mutations in RSV strains from children who received PZ. Study design Children aged ≤24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October–May 2001–2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods. Results Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt. Conclusions Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance. [ABSTRACT FROM AUTHOR]

Limited data are available in rural Honduran settings describing the etiology of respiratory infections, partially due to limited specimen transport. A new molecular transport media (MTM) preserves released nucleic acid at ambient temperature for later detection. Prospective surveillance was conducted in a Honduran clinic to identify 233 children less than 5 years of age presenting with respiratory symptoms. We obtained 2 nasopharyngeal samples and stored 1 in PrimeStore® MTM at room temperature and 1 in universal transport media (UTM) at −80 °C. The specimens were then transported to Cincinnati Children's Hospital and tested for 16 respiratory viruses using a multiplex PCR panel. The 2 specimen collection systems were similar for detecting the 4 most common viruses: influenza (Kappa = 0.7676, P < 0.0001), human metapneumovirus (Kappa = 0.8770, P < 0.0001), respiratory syncytial virus (Kappa = 0.6849, P < 0.0001), and parainfluenza (Kappa = 0.8796, P < 0.0001). These results suggest that clinical specimens transported via PrimeStore® MTM and UTM yield similar viral multiplex PCR results. [ABSTRACT FROM AUTHOR]

Highlights: [•] Economic burden of rotavirus medical visits has been estimated by indirect measures. [•] Indirect measures led to uncertainty of the true medical cost of rotavirus disease. [•] This study used direct methods to identify children with rotavirus medical visits. [•] This study found high medical costs prior to rotavirus vaccine licensure in the US. [•] This study found a dramatic decline in costs after introduction of rotavirus vaccines. [Copyright &y& Elsevier]

Highlights: [•] We compared study designs to find the effectiveness of pentavalent rotavirus vaccine. [•] Study designs included were the case-control design and the case-cohort design. [•] Three doses of vaccine were found to be 92% effective in each analysis. [•] Two doses of vaccine were found to be from 79% to 83% effective. [•] Both designs found the vaccine highly effective when the vaccine series is completed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Studies have documented direct medical costs of influenza-related illness in young children, however little is known about the out-of-pocket and indirect costs (e.g., missed work time) incurred by caregivers of children with medically attended influenza. Objective: To determine the indirect, out-of-pocket (OOP), and direct medical costs of laboratory-confirmed medically attended influenza illness among young children. Methods: Using a population-based surveillance network, we evaluated a representative group of children aged <5 years with laboratory-confirmed, medically attended influenza during the 2003–2004 season. Children hospitalized or seen in emergency department (ED) or outpatient settings in surveillance counties with laboratory-confirmed influenza were identified and data were collected from medical records, accounting databases, and follow-up interviews with caregivers. Outcome measures included work time missed, OOP expenses (e.g., over-the-counter medicines, travel expenses), and direct medical costs. Costs were estimated (in 2009 US Dollars) and comparisons were made among children with and without high risk conditions for influenza-related complications. Results: Data were obtained from 67 inpatients, 121 ED patients and 92 outpatients with laboratory-confirmed influenza. Caregivers of hospitalized children missed an average of 73 work hours (estimated cost $1456); caregivers of children seen in the ED and outpatient clinics missed 19 ($383) and 11 work hours ($222), respectively. Average OOP expenses were $178, $125 and $52 for inpatients, ED-patients and outpatients, respectively. OOP and indirect costs were similar between those with and without high risk conditions (p >0.10). Medical costs totaled $3990 for inpatients and $730 for ED-patients. Conclusions: Out-of-pocket and indirect costs of laboratory-confirmed and medically attended influenza in young children are substantial and support the benefits of vaccination. [Copyright &y& Elsevier]

Abstract: Background: Despite frequent use of self-reported information to determine pediatric influenza vaccination coverage, little data are available on the validity of parental reporting of their child''s influenza vaccination status and on factors affecting its accuracy. Methods: We compared parent reported influenza vaccination of children to documented reports of vaccination collected from medical records (the criterion standard) among children aged 6–59 months who presented to selected hospitals, emergency departments, and clinics in three U.S. counties with acute respiratory illness during three influenza seasons (November through May of 2004–2007). Demographic and epidemiologic data were collected from chart reviews and parental surveys. Results: Among 3072 children aged 6–59 months, 47.5% were reported by the parent to have received influenza vaccine and 39.5% of children had medical record verification of influenza vaccination. Sensitivity and specificity of parental reporting was 92.1% and 82.3%, respectively, when compared to the immunization record. However, 17.7% of children whose parents reported vaccination had no influenza vaccination documented in their medical records, and this proportion was even higher at 28.6%, among children with an underlying high-risk medical condition. Greater reporting accuracy was associated with younger age of child (6–23 months vs. 24–59 months), white non-Hispanic race/ethnicity, having health insurance, and having a mother with a college education. Conclusions: Our findings indicate that although parental report of influenza vaccination is fairly reliable (∼76–96%), over reporting by parents often occurs and immunization record review remains the preferable method for determining vaccination status in children. [Copyright &y& Elsevier]

Abstract: To determine which factors are predictive of protective antibody against vaccine-preventable diseases in internationally adopted children, we evaluated 562 children with serologic testing for at least one vaccine antigen before receiving a US vaccination. Vaccination status was defined as the number-of-doses recorded and as the presence of an up-to-date and valid record according to the American Academy of Pediatrics and the Advisory Committee on Immunization Practices guidelines. The number-of-doses recorded was the best predictor of protective antibody. These findings suggest that other options for immunization verification guidelines for internationally adopted children should be considered by policy makers. [ABSTRACT FROM AUTHOR]

Abstract: This study determined direct medical costs for influenza-associated hospitalizations and emergency department (ED) visits. For 3 influenza seasons, children <5 years of age with laboratory-confirmed influenza were identified through population-based surveillance. The mean direct cost per hospitalized child was $5402, with annual cost burden estimated at $44 to $163 million. Factors associated with high-cost hospitalizations included intensive care unit (ICU) admission and having an underlying high-risk condition. The mean medical cost per ED visit was $512, with annual ED cost burden estimated at $62 to $279 million. Implementation of the current vaccination policies will likely reduce the cost burden. [Copyright &y& Elsevier]

Abstract: Study Objective: To examine the etiology, clinical course, and outcomes of non-sexually transmitted vulvar ulcers in young females. Design: A prospective cohort study of subjects referred to a tertiary center who had active vulvar ulcers and no evidence of sexually transmitted infections were evaluated with a structured clinical and laboratory protocol and followed with visits or telephone calls. Results: Twenty eligible subjects had a mean age of 14 years (range 10–19), and five were premenarchal. Nineteen reported systemic symptoms such as fever, malaise, and headache. Most ulcers were >1cm in diameter (range 0.3–5 cm) and were located on the medial aspect of the labia minora. All viral, bacterial, and fungal cultures were negative. Serologic testing for Epstein-Barr virus (EBV) infection demonstrated 10 subjects with evidence of prior infection, two with acute infection, one indeterminate, and seven negative for infection. Two subjects had evidence of possible acute cytomegalovirus (CMV) infection. Other laboratory findings were nonspecific. The median duration of pain was 10 days (range 6–30), and 75% healed by 21 days. Follow up was available for 19 subjects (median 14 months). Seven experienced recurrent ulcers 2–16 months after the initial episode, and 10 had experienced oral aphthous ulcers. None met criteria for other etiologies of vulvar ulcers reported in the literature. Conclusions: No single infectious agent was identified as a cause of vulvar ulcers. Most cases were not temporally associated with either acute EBV or CMV infection. These ulcers are consistent with aphthous major or complex aphthosis that arise in response to acute illness. [Copyright &y& Elsevier]

Abstract: Human calicivirus was the first recognized viral agent causing gastroenteritis in humans. Norovirus (NV) and Sapovirus (SV), two genera within the Caliciviridae family, cause epidemic and endemic acute gastroenteritis in children and adults. The role of these viruses as a cause of sporadic acute gastroenteritis in young children requiring hospitalization is not well established. The aim of this study was to assess the prevalence and genetic diversity of caliciviruses among children hospitalized with symptoms of acute gastroenteritis. Stool samples were collected over 2 years from symptomatic children (N =1840) up to 5 years of age at three pediatric hospitals in the US. Overall, 156 (8.5%) samples were CV-positive, 131 (7.1%) confirmed by sequencing to be NV and 25 (1.4%) confirmed to be SV. Sequences of RT-PCR-amplified polymerase gene segments were analyzed using distance, maximum likelihood and parsimony algorithms. Phylogenetic analysis of 97 NV sequences showed that seven strains were in genogroup I, 86 strains were in genogroup II and four strains were not in genogroup I, II, or III, likely representing three new NV genogroups IV, VI and VII. Genogroup I and genogroup II strains were in 12 new genetic clusters, three in genogroup I and nine in genogroup II. Within genogroups I and II, most (98%) NV strains were in genetic clusters with no known prototype in GenBank. Phylogenetic analysis of 24 SV strains showed that half grouped with the London/92 strain in one genogroup and the remainder in three other proposed genogroups, one novel. In conclusion, NV and SV were frequent causes of hospitalization for acute gastroenteritis in young children and infecting strains were highly diverse, including newly recognized genogroups and genetic clusters within known genogroups. [Copyright &y& Elsevier]