A randomized trial of vitamin D supplementation to prevent seasonal influenza and enterovirus infection in children.

PURPOSE: This study aimed to evaluate whether vitamin D supplementation can reduce the incidence of influenza and enterovirus infection in Taiwanese children. METHODS: This randomized, double-blind, controlled trial included children aged two to five years between April 2018 and October 2019 from daycare centers. All the participants were randomly assigned to a vitamin D supplementation group (2000 IU/day) or placebo group for one month. The primary outcome was the incidence of influenza and enterovirus infection in the following six months, and the secondary outcome was the incidence of influenza and enterovirus infection in the children's household members. RESULTS: Two hundred and forty-eight children participated. The vitamin D group showed a relative risk reduction of 84% against influenza compared to the placebo group but did not reach statistical significance. Kaplan-Meier curves revealed that the placebo group had a higher probability of influenza infection than the vitamin D group (log-rank test, p = 0.055), but the incidence of enterovirus infection was similar between the two groups (p = 0.946) among children. Among children's household members, the incidence of influenza (p = 0.586) and enterovirus infection (p = 0.528) were both similar between the two groups. All children who were tested for serum 25(OH)D levels after vitamin D intervention had 25(OH)D levels above 30 ng/ml CONCLUSION: Vitamin D supplementation may have a small preventative effect against influenza infection but does not affect enterovirus infection among preschool children. A high-dose short-term vitamin D intervention might be a way to elevate children's serum vitamin D levels in the first month of starting kindergarten.

Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6-35 Months of Age: Results From a Phase 2, Randomized, Observer-blind, Multicenter, Dose-ranging Study.

BACKGROUND: This phase 2 observer-blind, randomized, multicenter, dose-ranging study evaluated immunogenicity and safety of different formulations of an AS03-adjuvanted H5N1 influenza vaccine in children 6-35 months of age. METHODS: One hundred eighty-five children randomized into 5 groups [1.9 µg hemagglutinin (HA)/AS03B, 0.9 µg HA/AS03C, 1.9 µg HA/AS03C, 3.75 µg HA/AS03C or 3.75 µg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03B the highest amount. One year later, all subjects were to receive unadjuvanted 3.75 µg HA as antigen challenge. Immunogenicity was assessed 21 days after primary vaccination (day 42) and 7 days after antigen challenge (day 392). Immunogenicity-fever index, based on hemagglutination inhibition and microneutralization antibody titers at day 42 and fever 7 days after each vaccination, was used to guide the selection of an acceptable formulation. RESULTS: After primary vaccination, formulations elicited strong homologous immune responses with all subjects' hemagglutination inhibition titers ≥1:40 post-vaccination. Immunogenicity-fever index based on hemagglutination inhibition and microneutralization assays showed that 1.9 µg HA/AS03B ranked the highest. Antibody levels persisted >4 times above baseline 12 months after primary vaccination with all formulations (day 385). Antibodies increased >4-fold after antigen challenge (day 392/day 385) with 1.9 µg HA/AS03B, 0.9 µg HA/AS03C and 1.9 µg HA/AS03C formulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 µg HA/AS03D) to 60.5% (1.9 µg HA/AS03B). CONCLUSIONS: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 µg HA/AS03B providing the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age.

Effects of influenza vaccine and sun exposure time against laboratory-confirmed influenza hospitalizations among young children during the 2012-13 to 2015-16 influenza seasons.

BACKGROUND: Influenza is a major cause of acute respiratory infection burden worldwide, leading to many hospitalizations. An annual influenza vaccine is believed to be the best way to prevent influenza-related illnesses. We focused on the efficacies of other possible preventive measures such as increasing sun exposure time and dietary supplements to prevent these illnesses. METHODS: We conducted a matched-pair case-control study along with the Taiwan Pediatric Infectious Disease Alliance. We included influenza-related hospitalized patients with age ranging from 6 months to 5 years during the 2012-2013, 2013-2014, 2014-2015, and 2015-2016 influenza seasons. The controls were comparable to cases in age, sex, and residential area and had no influenza-related hospitalization records in the same season. We extracted data from vaccination histories and got the patients' guardians to complete questionnaires. Data were analyzed using conditional logistic regression. RESULTS: We enrolled 1514 children (421 influenza-infected cases and 1093 controls) in the study. We found seasonal influenza vaccination to be an independent protective factor against hospitalizations owing to influenza [p < 0.01; odds ratio (OR), 0.427; 95% confidence interval (CI), 0.306-0.594]. Children with mean sun exposure time of >7 h/week had a significantly lower risk of influenza-related hospitalizations than those with the mean sun exposure time of ≤7 h/week (p < 0.05; OR, 0.667; 95% CI, 0.491-0.906). CONCLUSIONS: Seasonal influenza vaccination effectively prevents influenza-related hospitalizations in children aged ≤5 years. Besides, >7 h of sun exposure/week may also be associated with lower risk of influenza-related hospitalizations in children.

Influence of Latitude on the Prevalence of Kawasaki Disease: A Retrospective Cohort Study from the Taiwan National Health Insurance Database and Review of the Literature.

Background: Countries at higher latitudes have higher incidence rates of Kawasaki disease (KD) than do countries at lower latitudes in the Asian and West Pacific area. However, the precise influence of latitude on KD incidence rates requires further clarification. Methods: We searched the Longitudinal Health Insurance Database 2005 to retrieve patients’ medical records from 1996 to 2009. The patients with KD were categorized as living in northern, middle, and southern Taiwan; the period prevalence of KD for each area was determined. Climate variables, including temperature, sunshine duration, precipitation, and relative humidity, were collected from the Taiwan Central Weather Bureau. The effect of latitude on the period KD prevalence and the correlation between climate variables and KD prevalence were calculated. Results: After patients without complete data excluded, a total of 61,830 children up to 10 years old were retrieved, from which 404 patients with KD were recognized. The period prevalence of KD increased significantly with latitude (p = 0.0004). Climate variables associated with high temperature demonstrated a connection with KD prevalence; however, this correlation was not statistically significant. Conclusions: Our study demonstrated that higher latitude is associated with a higher KD prevalence in Taiwan.

Does Vitamin D Deficiency Affect the Immunogenic Responses to Influenza Vaccination? A Systematic Review and Meta-Analysis.

Influenza virus infection is a major global public health problem, and the efficacy of influenza vaccination is not satisfactory. Vitamin D is involved in many immune-mediated inflammatory processes. The impact of vitamin D levels on the immunogenic response to influenza vaccination is not clear. We performed a comprehensive literature search and systematic review of studies that investigated vitamin D and influenza vaccination. Data pertaining to study population, vaccine components, vitamin D levels, and immunogenic response were analyzed. Nine studies, with a combined study population of 2367 patients, were included in the systematic review. Four studies were included in the meta-analysis to investigate the influence of vitamin D deficiency (VDD) on the seroprotection (SP) rates and seroconversion (SC) rates following influenza vaccination. We found no significant association between vitamin D level and the immunogenic response to influenza vaccination. However, strain-specific differences may exist. We observed lower SP rates of influenza A virus subtype H3N2 (A/H3N2) and B strain in VDD patients than patients with normal vitamin D levels (A/H3N2: 71.8% vs. 80.1%, odds ratio (OR): 0.63, 95% confidence interval (CI): 0.43-0.91, p = 0.01; B strain: 69.6% vs. 76.4%, OR: 0.68, 95% CI: 0.5-0.93, p = 0.01). However, the SP rates of A/H1N1 and SC rates of all three strains were not significantly different in VDD and control groups. In conclusion, no association was observed between VDD and immunogenic response to influenza vaccination.

Increase the risk of intellectual disability in children with scabies: A nationwide population-based cohort study.

Scabies is a common and distressing disease caused by the mite Sarcoptes scabiei var. hominis. Psychiatric disorder in childhood is an important disease and easily neglected. There are several similarities in scabies and psychiatric disorders in childhood (PDC). Both of them may present with pruritus. They are relatively common in patients with lower socioeconomic status and crowded environment. Furthermore, immune-mediated inflammatory processes play a role in the pathophysiology in both diseases. An association between scabies and psychiatric disorders may exist. This nationwide population-based cohort study utilized data from the National Health Insurance Research Database to investigate the relationship between scabies and PDC. A total of 2137 children with scabies were identified as the study group and 8548 age- and sex-matched children were selected as the control group. A total of 607 (5.68%) children developed PDC during the 7-year follow-up period. The overall incidences of PDC are similar but patients with scabies had a higher risk of developing intellectual disability (ID) (scabies group vs control group: 1.3% vs 0.6%, adjusted hazard ratio: 2.04 and 95% confidence interval: 1.25-3.32). The immune-mediated inflammatory processes of both diseases were reviewed and may contribute to the 104% increased risk of interleukin in patients with scabies. We suggest a more comprehensive management in treating patients with scabies or ID. Early and comprehensive treatment of scabies and other risk factors may decrease the risk of subsequent ID. When we approach patients with ID, concurrent evaluation of scabies and other risk factors may contribute to successful management.

A Truncating De Novo Point Mutation in a Young Infant with Severe Menkes Disease.

Menkes disease is a rare neurodegenerative disorder caused by mutations in ATP7A gene. Deficiency in copper-dependent enzymes results in the unique kinky hair appearance, neurodegeneration, developmental delay, seizures, failure to thrive and other connective tissue or organ abnormalities. Other than biochemical tests, DNA-based diagnosis is now playing an important role. More than two hundred mutations in ATP7A gene were identified. Early copper supplementation can help improve neurological symptoms, but not non-neurological problems. Further molecular studies are needed to identify additional mutation types and to understand the mechanism of pathogenesis. This may help in discovering the possible treatment measures to cure the disease. We present a case with the clinical features and biochemical findings, abnormal brain magnetic resonance imaging as well as the effects of treatment with copper-histidine. Direct sequencing of ATP7A gene revealed a de novo point mutation which resulted in an early stop codon with truncated protein.

The Reversible Corpus Callosum Splenium Lesion in A Neonate with Hypoglycemia and Seizure.

PURPOSE: Reversible splenial lesion syndrome is a distinct clinicoradiological syndrome with diverse etiologies. Hypoglycemia induced reversible splenial lesion syndrome has been documented in adults and children, but rare in neonates. We demonstrate a neonate with hypoglycemia presenting with a typical reversible splenial syndrome. CASE REPORT: Patient A four-day-old male neonate had hypoglycemia and seizure, whose symptoms improved soon after glucose supplementation. Magnetic resonance imaging examination showed restricted diffusion of the splenium of the corpus callosum. Proton MR spectroscopy revealed a decreased N-acetylaspartate peak. The lesion resolved in subsequent MRI images. The patient is free from clinical symptoms and has normal development currently. CONCLUSION: The patient presented typical clinical course and radiological features of reversible splenial lesion syndrome. Through timely and proper treatment, the outcome could be favorable.

Serial sonographic findings of lenticulostriate vasculopathy.

The vessels supplying basal ganglia and thalami are not usually detectable on the neurosonogram in the neonates. In recent studies, bright linear echogenesitis in these regions have been well decribed and were defined as lentriculostriate vasculopathy (LSV). These lesions suggested as a marker of a previous insult to the fetal or neonatal brain and the hemodynamics in the immature brain play an important role in its pathogenesis. In a period of 2 year and 5 months, we collected 39 cases of neonates and prematurities with LSV. These include 16 cases of premature babies, 16 cases of normal full-term neonates and 7 cases with perinatal insults. LSV was detected incidentally in most cases, distinctly different from the previous reports that LSV are linked with congenital anomaly, chromosomal anomaly, prematurity, perinatal insult or congenital infection, etc. There are early onset (< or = 7 days) LSV in 23 cases (59%) and late onset (>7 days) in 16 cases (41%). 16 cases (41%) had total remission, 7 cases (18%) had partial remission, and 16 cases (41%) remained persistantly. Rare reports remined of the long term effect of LSV including tics, attention deficit hyperactive disorder and developmental delay. An isolated LSV generally has a good long term prognosis and a grave neurologic deficit may be mainly due to its associated brain damage.