Chi Eun Oh

Safety and immunogenicity of an inactivated split-virus influenza A/H1N1 vaccine in healthy children from 6 months to <18 years of age: a prospective, open-label, multi-center trial.

This study was conducted to determine the immunogenicity and safety of an inactivated split-virus influenza A/H1N1 vaccine in healthy Korean children from 6 months to <18 years of age. The immunization schedule consisted of two vaccinations, 21 days apart. The unadjuvanted vaccine contained 7.5microg (subjects 6 months to <3 years of age) or 15microg (subjects 3 to <18 years of age) of hemagglutinin antigen per dose. A total of 251 subjects were enrolled and 248 and 242 subjects, respectively, were included in the post-first dose and post-second dose immunogenicity evaluations conducted on a per protocol basis. By day 21, after the first dose, hemagglutination-inhibition titers of 1:40 or more were observed in 5.9% of subjects 6 months to <3 years of age, 34.9% of subjects 3 to <9 years of age and 81.4% of subjects 9-18 years of age. By day 21 after the second dose, the titer had been achieved 55.9%, 69.5% and 90.5%, respectively. No vaccination-related serious adverse events were observed. A single 15-microg dose of vaccine was highly immunogenic in subjects equal to or more than 9 years of age. However, a two-dose regimen is needed to produce potentially protective antibody titers in younger children.

Molecular characterization of methicillin-resistant Staphylococcus aureus obtained from the anterior nares of healthy Korean children attending daycare centers

OBJECTIVES This study was performed to investigate the molecular characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolated from the anterior nares of Korean children attending daycare centers. METHODS During September and October 2008, a survey of nasal carriage of MRSA was conducted among healthy children who were attending daycare centers in Seoul, Korea. Nasal swab samples were cultured to isolate S. aureus, and antimicrobial susceptibility was assessed using a disk diffusion test. All MRSA isolates were archived for subsequent molecular tests, including multilocus sequence typing, Panton-Valentine leukocidin (PVL) genes polymerase chain reaction (PCR), and staphylococcal cassette chromosome mec (SCCmec) typing. RESULTS Among 428 preschool-aged children enrolled, 9.3% (40/428) were colonized with MRSA. Among the 40 MRSA isolates, antibiotic susceptibilities to clindamycin and erythromycin were 97.5% (39/40) and 45% (18/40), respectively. All of the 21 strains susceptible to clindamycin and resistant to erythromycin had MLS(B)-inducible phenotypes. Sequence type (ST) 72-SCCmec type IV was the predominant clone (n=23; 57.5%), followed by ST72-SCCmec type II (n=6; 15%), ST1765-SCCmec type IV (n=4; 10%), ST1765-SCCmec type II (n=2; 5%), and ST1-SCCmec type IV (n=2; 5%). No clone was positive for PVL genes. CONCLUSIONS ST72 strains, which were previously found in hospital-associated MRSA, are now widely distributed in healthy Korean children. In addition, the prevalence of inducible resistance of clindamycin should be considered when selecting empirical antibiotics for community-associated MRSA infections in Korea.

Prevalence and genetic structures of Streptococcus pneumoniae serotype 6D, South Korea

To determine prevalence and genetic structures of new serotype 6D strains of pneumococci, we examined isolates from diverse clinical specimens in South Korea during 1991–2008. Fourteen serotype 6D strains accounted for 10.4% of serogroup 6 pneumococci from blood, sputum, nasopharynx, and throat samples. Serotype 6D strains consisted of 3 sequence types.

The impact of the increased use of piperacillin/tazobactam on the selection of antibiotic resistance among invasive Escherichia coli and Klebsiella pneumoniae isolates

OBJECTIVES Increasing antimicrobial resistance is related to the selective pressure exerted by antibiotic usage. This study evaluated the impact of the increased use of piperacillin/tazobactam (TZP) on the selection of antibiotic resistance. METHODS From 1999 to 2010, Escherichia coli and Klebsiella pneumoniae invasive isolates obtained from hospitalized Korean children were analyzed in antibiotic susceptibility tests and subjected to characterization of the β-lactamase types. Antibiotic consumption data were also analyzed. RESULTS Between January 1999 and December 2010, 409 invasive isolates of E. coli (n=170) and K. pneumoniae (n=239) were obtained. A rebound of extended-spectrum β-lactamase (ESBL) prevalence with an increase in total antibiotics was noted. Non-susceptibility to TZP was determined in 7.6% of E. coli isolates and 20.9% of K. pneumoniae isolates. Despite the increase in TZP usage, the overall prevalence of TZP resistance did not significantly increase over time, especially in E. coli. The mechanisms for TZP resistance included the presence of AmpC producers, possible TEM-1 hyperproducers, and multiple β-lactamases in individual organisms of a given isolate. CONCLUSIONS Replacement of only the antibiotic class appears to be insufficient to control antibiotic resistance, and continued efforts to decrease overall antibiotic pressure are needed, especially in highly endemic situations.

Clinical characteristics of children with 2009 pandemic influenza A (H1N1) admitted in a single institution

Purpose This study aims to investigate the clinical characteristics of children diagnosed with the novel influenza A (H1N1) in the winter of 2009 at a single medical institution. Methods Out of 545 confirmed cases of influenza A (H1N1) in children, using the real time RT-PCR method at Kosin University Gospel Hospital from September to December of 2009, 149 patients and their medical records were reviewed in terms of symptoms, laboratory findings, complications and transmission within a family. Results Median age of subjects was 7 years (range: 2 months-18 years). New cases increased rapidly from September to reach a peak in November, then declined rapidly. Most frequently observed symptoms were fever (96.7%), cough (73.2%), rhinorrhea (36.9%) and sore throat (31.5%). Average body temperatures on the 1st, 2nd and 3rd hospital day were 38.75±0.65℃, 38.08±0.87℃ and 37.51±0.76℃, respectively. Complete blood counts and biochemical tests performed on the first admission day showed within the reference values in most cases. Of the 82 patients with simple chest radiography, 18 (22%) had pneumonic lesions; multi-focal bronchopneumonia in eleven, single or multi-segmental lobar pneumonia in five, and diffuse interstitial pneumonia in two patients. All of the 149 patients improved from their symptoms and discharged within 9 days of admission without any late complication. Conclusion Children with 2009 pandemic influenza A (H1N1) at our single institution displayed nonspecific symptoms and laboratory findings, resembling those of common viral respiratory illnesses, and did not appear to develop more severe disease.

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults.

OBJECTIVES This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. METHODS Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. RESULTS Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. CONCLUSIONS Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine given to Korean children receiving routine pediatric vaccines

Background: The immunogenicity and safety of 13-valent and 7-valent pneumococcal conjugate vaccines (PCV13 and PCV7) were compared when administered with routine vaccines in Korea. Methods: Healthy infants (n = 180) were randomly assigned (1:1) to receive PCV13 or PCV7 at 2, 4, 6 (infant series) and 12 months (toddler dose). Immune responses 1 month after the infant series and toddler dose were measured by enzyme-linked immunosorbent assay and opsonophagocytic activity (OPA) assay. IgG antibody geometric mean concentrations and OPA functional antibody geometric mean titers were calculated. Safety was assessed. Results: After the infant series, for the 7 common serotypes, proportions of responders with IgG concentrations ≥0.35 µg/mL were comparable (≥97.6%) between groups; IgG geometric mean concentrations and OPA geometric mean titers were generally similar, but tended to be lower in the PCV13 group for some serotypes. For the 6 serotypes unique to PCV13, IgG geometric mean concentrations and OPA geometric mean titers were notably higher in the PCV13 group. Importantly, although PCV7 elicited IgG antibodies to PCV13 serotypes 5 and 19A, OPA responses were minimal, whereas serotype 6A elicited both IgG and OPA responses. These observations are consistent with at least some protection by PCV7 against 6A-mediated invasive pneumococcal disease, but no cross-protection for serotypes 5 and 19A. The toddler dose elicited higher IgG and OPA responses than postinfant series responses for most serotypes; however, for serotypes 3 and 14 only OPA responses were increased posttoddler dose. Vaccine safety profiles were similar. Conclusions: PCV13 is safe and immunogenic in Korean children. PCV13 should provide broader protection than PCV7.

Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine in healthy adolescents in Korea--A randomised trial.

BACKGROUND Neisseria meningitidis serogroup B is a significant cause of septicaemia and meningitis worldwide. This phase 3 randomised, controlled study assessed the immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in healthy Korean adolescents. METHODS 264 adolescents (11-17 years old) were randomised to receive two doses, one month apart, of 4CMenB or control vaccines [placebo followed by one dose of a quadrivalent meningococcal ACWY glycoconjugate vaccine (MenACWY-CRM)]. Immunogenicity was evaluated by serum bactericidal assay with human complement (hSBA) against three serogroup B test strains specific for individual vaccine antigens (fHbp, NadA or PorA P1.4), and by enzyme-linked immunosorbent assay (ELISA) against the NHBA antigen. Solicited reactions and adverse events (AEs) were assessed. RESULTS One month post-second vaccination, 98%, 97%, and 97% of subjects in the 4CMenB group achieved hSBA titres ≥ 4 against the fHbp, NadA and PorA test strains, respectively, while percentages in the Control group were comparable to baseline (27%, 16%, and 17%, respectively). Geometric mean ELISA concentrations (GMCs) against NHBA increased 52-fold relative to baseline in the 4CMenB group, while there was no substantial increase in GMCs in the Control group (1.05-fold). Frequencies of solicited reactions after any vaccination were higher in the 4CMenB group than in the Control group, although most reactions were of short duration and mild to moderate intensity. There were no vaccine-related serious AEs. CONCLUSIONS Two doses of 4CMenB induced robust immune responses against the vaccine antigens and were well tolerated, with no safety concerns identified, in Korean adolescents (NCT01973218).

Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea

BACKGROUND This study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs). METHODS From April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility. RESULTS A total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, P<0.001), while completion of PCV vaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P=0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one. CONCLUSION High rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea.

Safety and immunogenicity of a new trivalent inactivated split-virus influenza vaccine in healthy korean children: A randomized, double-blinded, active-controlled, Phase III study

We report results of a randomized, double-blinded, active-controlled, phase III study conducted to evaluate the immunogenicity and safety of a new trivalent inactivated split-virus influenza vaccine (GC501) manufactured by the Green Cross Corporation in Korea. A total of 283 healthy children aged 6 months to < 18 yr were randomized to receive either GC501 or control. Of the GC501 recipients, seroconversion occurred in 48.5% for A/H1N1, 67.7% for A/H3N2 and 52% for influenza B. The proportion of subjects who had post-vaccination hemagglutination-inhibition titers of 1:40 or greater was 90.7% for A/H1N1, 86.8% for A/H3N2 and 82.4% for influenza B in the GC501 recipients. No serious adverse events related to vaccination, or withdrawals because of adverse events were reported. The majority of solicited adverse events were mild in intensity. GC501 vaccine has good tolerability and favorable immunogenicity in children aged 6 months to < 18 yr. The addition of one more brand of influenza vaccine may allow for better global accessibility of vaccine for epidemics or future pandemics.