Opsonophagocytic Antibodies of Intravenous Immunoglobulin Preparations against Seven Streptococcus agalactiae Serotypes

Purpose@#Group B streptococcus (GBS) is a causative organism of invasive infections in neonates and pregnant women as well as in non-pregnant adults. Among 10 known serotypes of GBS, uncommon serotypes, such as IV and VI to IX, can cause invasive infections in immunocompromised patients. However, opsonophagocytic antibodies against these serotypes in human sera and intravenous immunoglobulin (IVIG) have not yet been studied.IVIG therapy is used to treat or prevent invasive infections in patients with primary antibody deficiencies. Here, we analyzed the activity of opsonophagocytic antibodies against GBS in IVIG preparations. @*Methods@#Opsonophagocytic antibody activity (opsonic index [OI]) against seven GBS serotypes (II and IV to IX) was evaluated in 16 commercially available IVIG preparations using the opsonophagocytic assay (OPA) in HL-60 cells and baby rabbit complement assay during 2015–2016 in South Korea (UAB GBS OPA, at http://www.vaccine.uab.edu). @*Results@#The estimated serum trough levels of OIs against GBS exceeded the limit of detection (≥4) in all IVIG preparations. For serotype VII, the serum levels of OIs were 6–136, the lowest among all serotypes. An IVIG dose of 400 mg/kg was found to be appropriate for immunocompromised individuals to prevent invasive GBS infections. @*Conclusions@#Most immunoglobulin products displayed high levels of opsonophagocytic activity against GBS, except for serotype VII. IVIG preparations could serve as a therapeutic or immunomodulatory agent for immunocompromised individuals.

Opsonophagocytic Antibodies of Intravenous Immunoglobulin Preparations against Seven Streptococcus agalactiae Serotypes

Purpose@#Group B streptococcus (GBS) is a causative organism of invasive infections in neonates and pregnant women as well as in non-pregnant adults. Among 10 known serotypes of GBS, uncommon serotypes, such as IV and VI to IX, can cause invasive infections in immunocompromised patients. However, opsonophagocytic antibodies against these serotypes in human sera and intravenous immunoglobulin (IVIG) have not yet been studied.IVIG therapy is used to treat or prevent invasive infections in patients with primary antibody deficiencies. Here, we analyzed the activity of opsonophagocytic antibodies against GBS in IVIG preparations. @*Methods@#Opsonophagocytic antibody activity (opsonic index [OI]) against seven GBS serotypes (II and IV to IX) was evaluated in 16 commercially available IVIG preparations using the opsonophagocytic assay (OPA) in HL-60 cells and baby rabbit complement assay during 2015–2016 in South Korea (UAB GBS OPA, at http://www.vaccine.uab.edu). @*Results@#The estimated serum trough levels of OIs against GBS exceeded the limit of detection (≥4) in all IVIG preparations. For serotype VII, the serum levels of OIs were 6–136, the lowest among all serotypes. An IVIG dose of 400 mg/kg was found to be appropriate for immunocompromised individuals to prevent invasive GBS infections. @*Conclusions@#Most immunoglobulin products displayed high levels of opsonophagocytic activity against GBS, except for serotype VII. IVIG preparations could serve as a therapeutic or immunomodulatory agent for immunocompromised individuals.

Validation of a Multiplexed Opsonophagocytic Assay for 11 Additional Pneumococcal Serotypes and Its Application to Functional Antibody Evaluation Induced by Pneumococcal Polysaccharide Vaccine

BACKGROUND: Various pneumococcal vaccines have been evaluated for immunogenicity by opsonophagocytic assay (OPA). A multiplexed OPA (MOPA) for 13 pneumococcal serotypes was developed by Nahm and Burton, and expanded to 26 serotypes in 2012. The development of new conjugate vaccines with increased valence has necessitated expanded MOPAs to include these additional serotypes. In this study, we validated this expanded MOPA platform and applied to measure antibodies against 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F) in human sera. METHODS: All materials, including serum, complement, bacterial master stocks, and HL-60 cells, were evaluated for assay optimization. Following optimization, the assay was validated for accuracy, specificity, and intra- and inter-assay precision with sera from adult donors following standard protocols. The assay was applied to evaluate functional antibodies of 42 sera immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23). RESULTS: The expanded MOPA platform was specific for all serotypes, with the exception of serotype 20. The assay results were highly correlated with those obtained from single-serotype OPA, indicating acceptable accuracy. The coefficients of variation were 7%–24% and 13%–39% in tests of intra- and inter-assay precision, respectively, using three quality-control samples. A MOPA that included 11 additional serotypes in the PPV23 was established and validated with respect to accuracy, specificity, and precision. The opsonic indices of immune sera were obtained using this validated assay. CONCLUSION: The expanded MOPA will be useful for evaluation of the immunogenicity of PPV23 and future conjugate vaccine formulations.

Current Clinical Features of Febrile Seizures in a Pediatric Emergency Room / 이화의대지

OBJECTIVES: To expand current knowledge on febrile seizures (FSs), the most common childhood seizure disorder, we investigated clinical features and risk factors of FS in the pediatric emergency department of a center in western Seoul. METHODS: Children with FS that visited the pediatric emergency room of the Ewha Womans University Medical Center from January to December 2014 were included in this study. A retrospective medical record review was conducted for a total of 404 seizure events relative to 265 patients. RESULTS: A total of 150 boys and 115 girls were enrolled. Children presenting their first FSs were 70.9% (n=188). Average age of FS onset was 28.9 months. Family history was reported in 95 children (36.8%) with higher relevance of paternal inheritance (44.2%, n=42/95). More than half of the seizures (56.4%, n=228/404) occurred on the first day of fever. The most common cause of fever was upper respiratory tract infection (65.8%, n=266/404). Children attending a daycare center had higher incidence of multiple FS compared to those cared for at home. Approximately one third of seizure events (31.7%, n=128/404) were admission cases, mainly because of prolonged fever. CONCLUSION: FS is a common neurologic disorder with relatively high admission rate among pediatric emergency department visits. Daycare attendance is associated with current increased incidence of multiple FS. Further study with long-term follow up is necessary to expand knowledge on improving clinical care strategy in FS.

Characterization of Oropharyngeal Carriage Isolates of Neisseria meningitidis in Healthy Korean Adolescents in 2015

The meningococcus carriage rate is age-dependent, with a high prevalence in adolescents and young adults. This cross-sectional study aimed to estimate the oropharyngeal carriage rate of meningococcus among healthy Korean adolescents and its relationship with several population characteristics. The survey was conducted from April to May 2015 among 1,460 first-year high-school students in 9 high schools located in Gyeonggi province, Korea. Each student answered a short questionnaire assessing risk factors for carriage, and posterior pharyngeal wall swab samples were obtained. These samples were cultured on meningococcus-selective media, with colonies resembling meningococci identified using the Vitek® MS system (bioMérieux, Marcy l'Etoile, France). All isolates were characterized by molecular serogrouping and multilocus sequence typing (MLST). Meningococci were identified from 3.4% (49/1,460) swabs. Current smokers had significantly higher carriage rates than non-smokers (8.2% vs. 2.9%, P = 0.002), and boys had significantly higher carriage rates than girls (4.4% vs. 1.6%, P = 0.004). Serogroup B was the most common serogroup, followed by serogroup C, then 29E and Y. Twenty-seven different sequence types (STs) were identified; the most common were ST-3091, ST-11278, and ST-44. These belonged to clonal complexes (CCs) 269, 32, and 41/44, respectively, known as the hypervirulent clones. Evaluating meningococcal carriage is important to understand the epidemiology of meningococcal disease; however, little data exist in Korea. Similar to western countries, meningococcal serogroup B has emerged in Korea, and hypervirulent clones were identified. It is necessary to monitor the genetic and serologic characteristics of circulating meningococci and to assess the potential strain coverage of meningococcal vaccines.

Vaccine Evaluation Studies Performed in Korea from 2000 to 2014

PURPOSE: Vaccine evaluation studies were initiated from 2000 by the Ministry of Food and Drug Safety to produce proper data about the safety and immunogenicity of vaccines. The purpose of this study was to review studies and reports on evaluation of vaccine such as immunogenicity, efficacy, effectiveness, safety and other related topics in order to find and analyze the data on the usefulness of each vaccine. METHODS: From 2000 to 2014, the project "The vaccine evaluation" had been performed by several researchers, and studies and reports of vaccine evaluation. We reviewed the results and outcomes of studies regarding the evaluation of vaccine's usefulness and analyzed the possibilities of applying these data for establishing vaccine policies. For each vaccine, data analysis and organization were done according to evaluation fields. RESULTS: A total of 83 studies were performed on vaccines from 2000 to 2014. For each vaccine, 8 studies were performed on BCG, 14 on DTaP/Td, 1 on poliovirus, 5 on Hib, 3 on pneumococcus, 11 on influenza, 3 on hepatitis A, 11 on MMR, 11 on varicella, and 16 on Japanese encephalitis. All studies were analyzed by the following evaluation area, such as safety, immunogenicity, seroprevalence, persistence of immunity, efficacy, effectiveness, vaccine evaluation methods, quality control product for vaccine, and others. CONCLUSIONS: Vaccine evaluation studies performed in Korea may be useful as references for establishing vaccination strategy and policy and could be used as baseline data for future studies on vaccine evaluation, vaccine policy establishment, and public/expert vaccine education in Korea.

High Spontaneous Resolution Rates of Severe Primary Vesicoureteral Reflux and Minimal Development of New Renal Scars

PURPOSE: The previous reports regarding VUR resolution were not precise due to early frequent surgical intervention. We evaluated the spontaneous resolution (SR) rate and the incidence of new renal scars in primary VUR, focusing on severe reflux. METHODS: Medical records of 334 patients with primary VUR who were on medical prophylaxis without surgery for 1 to 9 years, were retrospectively reviewed. Medical prophylaxis was initiated with low-dose antibiotic prophylaxis or probiotics. Radioisotope cystourethrography was performed every 1 to 3 years until SR of reflux. New renal scar was evaluated with follow-up 99mTc DMSA renal scan. RESULTS: The SR rates decreased as VUR grades were getting higher (P=0.00). The overall and annual SR were 58.4% and 14.9%/yr in grade IV reflux and 37.5% and 9.3%/yr in grade V reflux. The median times of SR were 38 months in grade IV reflux and 66 months in grade V reflux. The probable SR rates in grade IV and V reflux were 7.8% and 8.9% in the 1st year, 46.0% and 30.8% in the 3rd year and 74.4% and 64.4% in the 5th year. The incidences of new renal scars between low to moderate reflux and severe reflux showed no significant difference (P=0.32). CONCLUSION: The SR rates of severe primary VUR were higher than previously reported and most new renal scars were focal and mild.

The relationship between eosinophilia and bronchopulmonary dysplasia in premature infants at less than 34 weeks' gestation / 소아과

PURPOSE: Eosinophilia is common in premature infants, and its incidence increases with a shorter gestation period. We investigated the clinical significance of eosinophilia in premature infants born at 3% of the total leukocytes. Perinatal parameters and clinical parameters were also analyzed. RESULTS: Of the 261 infants born at <34 weeks gestation, 22.4% demonstrated eosinophilia at birth. The eosinophil percentage peaked in the fourth postnatal week at 7.5%. The incidence of severe eosinophilia increased after birth up to the fourth postnatal week when 8.8% of all patients had severe eosinophilia. Severity of eosinophilia was positively correlated with a lower gestational age, birth weight, and Apgar score. Respiratory distress syndrome, bronchopulmonary dysplasia, nephrocalcinosis, intraventricular hemorrhage, and sepsis were associated with a higher eosinophil percentage. The eosinophil percentage was significantly higher in infants with bronchopulmonary dysplasia from the first postnatal week and the percentage was the highest in the fourth postnatal week, with the maximal difference being 4.1% (P<0.001). CONCLUSION: Eosinophilia is common in premature infants and reaches peak incidence and severity in the fourth postnatal week. The eosinophil percentage was significantly higher in bronchopulmonary dysplasia patients from the first postnatal week. Severe eosinophilia was significantly associated with the incidence of bronchopulmonary dysplasia even after adjusting for other variables.