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During the coronavirus disease 2019 (COVID-19) pandemic, a novel multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide since the first cases were reported in Europe in April 2020. MIS-C is temporally associated with severe acute respiratory syndrome coronavirus 2 infection and shows Kawasaki disease (KD)-like features. The epidemiological and clinical characteristics in COVID-19, KD, and MIS-C differ, but severe cases of each disease share similar clinical and laboratory findings such as a protracted clinical course, multiorgan involvement, and similar activated biomarkers. These findings suggest that a common control system of the host may act against severe disease insult. To solve the enigmas, we proposed the protein-homeostasis-system hypothesis in that every disease involves etiological substances and the host’s immune system controls them by their size and biochemical properties. Also, it is proposed that the etiological agents of KD and MIS-C might be certain strains in the microbiota of human species and etiological substances in severe COVID-19, KD, and MIS-C originate from pathogen-infected cells. Since disease severity depends on the amounts of inflammation-inducing substances and corresponding immune activation in the early stage of the disease, an early proper dose of corticosteroids and/or intravenous immunoglobulin (IVIG) may help reduce morbidity and possibly mortality among patients with these diseases. Corticosteroids are low cost and an analogue of host-origin cortisol among immune modulators. This study’s findings will help clinicians treating severe COVID-19, KD, and MIS-C, especially in developing countries, where IVIG and biologics supplies are insufficient.

The human microbiome, which consists of a collective cluster of commensal, symbiotic, and pathogenic microorganisms living in the human body, plays a key role in host health and immunity. The human nasal cavity harbors commensal bacteria that suppress the colonization of opportunistic pathogens. However, dysbiosis of the nasal microbial community is associated with many diseases, such as acute respiratory infections including otitis media, sinusitis and bronchitis and allergic respiratory diseases including asthma. The nasopharyngeal acquisition of pneumococcus, which exists as a pathobiont in the nasal cavity, is the initial step in virtually all pneumococcal diseases. Although the factors influencing nasal colonization and elimination are not fully understood, the adhesion of opportunistic pathogens to nasopharyngeal mucosa receptors and the eliciting of immune responses in the host are implicated in addition to bacterial microbiota properties and colonization resistance dynamics. Probiotics or synbiotic interventions may show promising and effective roles in the adjunctive treatment of dysbiosis; however, more studies are needed to characterize how these interventions can be applied in clinical practice in the future.

Background Mycoplasma pneumoniae (MP) is one of the most common causes of bacterial pneumonia in children. In the recent decade, macrolide-resistant MP (MRMP) has been increasing in proportion, leading to children unresponsive to initial macrolide therapy. The purpose of this study was to evaluate the outcomes of children with lobar or segmental MP pneumonia unresponsive to initial macrolide therapy, who received non-macrolide (NM), macrolide plus steroids (M+S), and non-macrolide plus steroids (NM+S) according to the 2019 guideline during the 2019-2020 Mycoplasma epidemic in South Korea. Methods This was a retrospective cohort study of children below 18 years old, admitted during the 2019-2020 MP outbreak for lobar or segmental MP pneumonia. The inclusion criteria were as follows: 1) sputum or nasopharyngeal swab MP PCR positive, 2) no history of pneumonia within one month of positive MP PCR, 3) lobar or segmental pneumonia on chest x-ray, and 4) initial treatment with macrolide monotherapy. Children that were unresponsive to the initial 3-5-day macrolide monotherapy were divided into 3 groups depending on the next regimen: NM, M+S, and NM+S group. Their outcomes were assessed. Results During May 2019 to March 2020 MP epidemic, a total 190 patients that fit all of the inclusion criteria were included as study participants. Of these, 16.8% (n=32/190) were responsive to initial macrolide monotherapy and 83.2% (158/190) were unresponsive. Of the 158 patients unresponsive during the initial 5-day macrolide therapy, 8.2% (n=13) were switched to a NM, 75.9% (n=120) were added steroids (M+S), and 15.8% (25/158) were switched to a non-macrolide plus steroids (NM+S). Treatment success rates were 46%, 81%, and 100% in the NM, M+S, and NM+S groups, respectively (P=0.001). Compared to patients in the NM+S group, those in the M+S group were 8.0 (Confidence interval [CI], 1.3-61.7; P=0.046) times more likely to have prolonged fever ≥4 days after the switch in treatment regimen compared to patients with NM+S, and 10.7 (CI, 1.5-108.7; P=0.046) times more likely in the NM group. Conclusion In patients with severe mycoplasma pneumonia with failure of response to initial macrolide therapy, a non-macrolide antibiotic plus steroid combination had the highest treatment success rate and shorter duration of fever. Disclosures All Authors: No reported disclosures.

The inactivated trivalent influenza vaccine (TIV) offers limited protection when two influenza B lineages co-circulate or when there is a vaccine mismatch (i.e., discordance in the predominant circulating B strain and WHO-recommended B strain). Inactivated quadrivalent influenza vaccine (QIV) may reduce the burden of influenza. Here, we report the results of a phase 3 clinical trial that evaluated the immunogenicity and safety of a novel QIV, GC3110A, in Korean children aged 6–35 months, which has been approved and is currently in use in Korea. The study involved two parts. In Part 1, the safety of GC3110A was evaluated in 10 subjects. After none of the subjects reported grade 3 adverse events (AEs), we proceeded to Part 2. Part 2 was a randomized, double-blind, multicenter phase 3 trial wherein we compared the immunogenicity and safety of GC3110A with those of a licensed control TIV. Immunogenicity was evaluated by measuring hemagglutination inhibition titers. The 200 participants enrolled in Part 2 were randomized in a 4:1 ratio to receive GC3110A or control TIV. The study vaccine group met both primary (i.e., the lower limit of 95% confidence interval [CI] of the seroconversion rate exceeds 40% for four strains) and secondary (i.e., the lower limit of 95% CI of the seroprotection rate exceeds 70% for four strains) immunogenicity endpoints. There was no significant between-group difference in the seroconversion rate, seroprotection rate, and geometric mean titer for the shared strains. However, the study vaccine group demonstrated significantly higher immunity for the additional strain B/Yamagata. In the safety analysis, there was no significant between-group difference in the proportion of participants with solicited local AEs, solicited systemic AEs, and unsolicited AEs. In conclusion, the results indicate that GC3110A has comparable immunogenicity and safety to those of TIV. Clinical Trial Registry Number: NCT03285997.

Introduction: Although prolonged fever in patients with neutropenic fever (NF) during empirical antibiotic therapy could be caused by dysregulated immune responses, its association with cytokine concentrations has rarely been investigated. This study determined the kinetics of cytokine concentrations in pediatric patients with NF and bacteremia and evaluated the impact of cytokine concentration kinetics on prolonged fever. Methods: Concentrations of 13 cytokines were measured on the initial day of NF (Day 1) and 3 days (Day 4) and 7 days (Day 8) later in 10 patients with NF with bacteremia, and their kinetics was determined. The results for each cytokine concentration on each sampling day were compared for patients with fever that lasted ⩾3 days and those with fever that lasted

Infections with Haemophilus influenzae type b have been decreasing due to widespread use of conjugate vaccines thereto, and there has been an increasing trend in the relative proportion of invasive infections by non-typeable H. influenzae (NTHi). NTHi commonly colonizes the upper respiratory tract and causes recurrent infections of the adjacent organs. There is a rapid development of antibiotic resistance in NTHi strains, and therefore it is important to select appropriate antibiotics for treatment. We report a case of recurrent NTHi meningitis in a 5-year-old girl with a previous history of recurrent otitis media. The patient presented with fever accompanying recurrent vomiting, and β-lactamase-positive amoxicillin/clavulanate-resistant NTHi was isolated in cerebrospinal fluid culture. Antibiotic resistance testing revealed penicillin-binding protein 3 mutation, which is an important emerging mechanism of antibiotic resistance of NTHi. Cystic cochleovestibular malformation was also identified, which may be the predisposing condition for recurrent otitis media, and invasive NTHi infection. Acute symptoms resolved with antibiotic therapy (cefotaxime, 200 mg/kg per day). After surgical revision, the patient has been in good health without recurrence. In children with recurrent respiratory tract infections, or invasive NTHi infection, it is important to consider the presence of underlying diseases and infections due to antibiotic resistant pathogens, in order to select an appropriate antibiotic agent for treatment.

The novel coronavirus disease 2019 (COVID-19) is spreading globally. Although its etiologic agent is discovered as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), there are many unsolved issues in COVID-19 and other infectious diseases. The causes of different clinical phenotypes and incubation periods among individuals, species specificity, and cytokine storm with lymphopenia as well as the mechanism of damage to organ cells are unknown. It has been suggested that in viral pneumonia, virus itself is not a direct cause of acute lung injury; rather, aberrant immune reactions of the host to the insults from viral infection are responsible. According to its epidemiological and clinical characteristics, SARS-CoV-2 may be a virus with low virulence in nature that has adapted to the human species. Current immunological concepts have limited ability to explain such unsolved issues, and a presumed immunopathogenesis of COVID-19 is presented under the proteinhomeostasis-system hypothesis. Every disease, including COVID-19, has etiological substances controlled by the host immune system according to size and biochemical properties. Patients with severe pneumonia caused by SARS-CoV-2 show more severe hypercytokinemia with corresponding lymphocytopenia than patients with mild pneumonia; thus, early immunomodulator treatment, including corticosteroids, has been considered. However, current guidelines recommend their use only for patients with advanced pneumonia or acute respiratory distress syndrome. Since the immunopathogenesis of pneumonia may be the same for all patients regardless of age or severity and the critical immune-mediated lung injury may begin in the early stage of the disease, early immunomodulator treatment, including corticosteroids and intravenous immunoglobulin, can help reduce morbidity and possibly mortality rates of older patients with underlying conditions.

This study was conducted to assess the nasopharyngeal (NP) carriage and acute otitis media (AOM) occurrence in Korean children who received pneumococcal conjugate vaccines (PCVs). The longitudinal study was conducted through four consecutive visits. At each visit, NP aspirates were obtained and subjects were asked to visit if AOM occurred. A total of 305 subjects were enrolled and received PCV13 (n = 182) or PCV10 (n = 123). In the PCV13 group, the NP carriage of Streptococcus pneumoniae at each visit was 2.7%, 14.8%, 18.7%, and 15.9%, respectively. Non-typeable Haemophilus influenzae (NTHi) was 3.3%, 2.7%, 2.7%, and 5.5%, and that of Moraxella catarrhalis was 1.1%, 9.3%, 4.9%, and 0.5%. In the PCV10 group, the NP carriage of S. pneumoniae at each visit was 3.3%, 7.3%, 6.5%, and 4.1%, respectively. That of NTHi was 2.4%, 4.1%, 1.6%, and 0.8%, and that of M. catarrhalis was 4.1%, 0.8%, 0.8%, and 0.0%. AOM occurrence in the PCV13 group observed after the primary dose and before booster dose was 20.9%, occurrence after booster dose was 11.0%, and the incidence of two or more AOM was 11.0%. In the PCV10 group, AOM occurrence was 9.8%, 7.3%, respectively, and the incidence of two or more AOM was 2.4%. The predominant S. pneumoniae isolated were non-vaccine type (10A, 15A, and 15B). In this study, AOM occurrence was lower in the PCV10 group than in the PCV13 group. This seems to be related to ecological changes that lead to differences in NP carriage, especially S. pneumoniae and NTHi.

Objectives. Deep neck infections (DNIs) can cause life-threatening complications, and prompt diagnosis and management are necessary. Kawasaki disease (KD) may be accompanied by deep neck inflammation; making it difficult to distinguish from DNIs. This study was performed to evaluate clinical features and outcomes of children with parapharyngeal and retropharyngeal inflammation.Methods. Medical records of the children diagnosed with parapharyngeal and retropharyngeal cellulitis or abscess using cervical computed tomography (CT) between 2013 and 2017 were retrospectively reviewed.Results. A total of 47 children were diagnosed with parapharyngeal and retropharyngeal inflammation. Eleven (23.4%) of them were eventually diagnosed with KD, and 36 (76.6%) were diagnosed with DNIs. There were no significantly different clinical and laboratory characteristics on admission between children diagnosed with KD and DNIs; however, significantly more children with KD were febrile for ≥3 days after admission compared to those with DNIs (P=0.009). Deep neck abscesses on CT were observed in 16 children with DNIs (44.4%) and in no child with KD (P=0.009). Among the 36 children with DNIs, 30 (83.3%) were cured with antibiotic therapy only.Conclusion. A quarter of children presenting with deep neck inflammation were diagnosed with KD. KD should be considered in children showing deep neck inflammation unresponsive to empirical antibiotic therapy after 3 days, especially in those presenting with deep neck cellulitis rather than deep neck abscess.

Replacement with nonvaccine serotypes (NVTs) among invasive pneumococcal diseases (IPDs) after the introduction of extended-valency pneumococcal conjugate vaccines varies in predominant serotypes across countries. This study analyzed changes in serotype distribution through serotyping, multilocus sequence typing, and antimicrobial susceptibility testing of 168 pediatric IPD isolates obtained from a multihospital-based surveillance system during 2014-2019 in South Korea. Vaccine serotypes (VTs) accounted for 16.1% (19A, 10.1%; 6A, 1.8%; and 19F 1.8%), 82.1% were NVTs (10A, 23.8%; 15A, 8.3%; 12F, 6.5%; 15C, 6.5%; and 15B, 6.0%), and three (1.8%) were nontypeable. Serotype 10A was the most common serotype, with a significant increase from 11.5% in 2014 to 33.3% in 2019 (p < 0.05 for the trend). Other NVTs decreased from 70.4% to 41.7% between 2015 and 2019, most notably in serotype 12F (from 14.8% to 0%). Almost all (95.0%) serotype 10A isolates were ST11189, which were multidrug resistant.

Purpose There are limited population-based data regarding herpes zoster in children. Thus we conducted a multi-institutional epidemiological analysis of herpes zoster in children and comparative analysis according to their immune status. Materials and Methods The study included 126 children under the age of 18 years who were hospitalized for herpes zoster at 8 hospitals in South Korea, between July 2009 and June 2015. The subjects were divided into 2 groups according to their immune status, and medical records were reviewed. Results There were 61 cases (48.4%) in the immunocompetent group and 65 cases (51.6%) in the immunocompromised group. Median age was older in immunocompromised group (11.4 vs. 8.6) (p

Background: In South Korea, the one-dose varicella vaccine was included in the National Immunization Program for children aged 12–15 months in 2005, and the vaccine coverage reached >95%. The impact of varicella vaccination on varicella and herpes zoster (HZ) was investigated, accounting for demographic changes over time. Methods: We calculated the crude and age-sex standardized incidence rates (IRs) and age-specific IRs of varicella and HZ from 2003 to 2015, using the National Health Information Database including approximately 50 million Koreans. The annual incidence rate ratios (IRRs) were calculated using a negative binomial regression analysis, adjusting for age and sex. Results: The crude varicella IR steadily declined by 67%, from 5.70/1000 to 1.87/1000 person years (IRR per year: 0.91; 95% CI 0.89–0.93), but the adjusted IRs showed a significant decline only during 2010–2015 (adjusted IRR per year: 0.90; 95% CI 0.88–0.93). The greatest decline was found in children ≤4 years of age, whereas the IR increased until 2011 and then declined afterward in children aged 5–9 years, who represented the highest incidence age group in 2013–2015. The crude HZ IR increased from 2.67/1000 to 9.80/1000 person years (IRR per year: 1.12; 95% CI 1.10–1.15), and the adjusted IR also followed the same trend. A similar increasing trend was observed before and after universal vaccination. Conclusions: One-dose varicella vaccination was moderately effective in preventing varicella, but this strategy was insufficient to interrupt varicella transmission in children. Furthermore, the HZ incidence dramatically increased over this decade. The current vaccination strategy against varicella-zoster disease should be reconsidered.

BACKGROUND: Recently, four influenza viruses are circulating worldwide: A(H1N1)pdm09, A(H3N2), B/Victoria, and B/Yamagata. However, information on the clinical differences among pediatric patients infected with four recently circulating influenza viruses is sparse. METHODS: Medical records of pediatric patients (

Monitoring regional antibiotic resistance patterns of uropathogens are important for deciding suitable empirical antibiotics for urinary tract infections (UTIs) in children. This study aimed to investigate regional differences in antimicrobial susceptibility patterns of E. coli and Klebsiella spp. in children below 24 months old, diagnosed with their first episode of UTI, and to find factors associated with an increased risk for UTI caused by extended-spectrum &beta, lactamase (ESBL)-producing uropathogens. This was a retrospective cohort study of children diagnosed between 2011 and 2017 in four different hospitals located in four different regions of South Korea, regions A, B, C, and D. The government&rsquo, s big data repository was used to acquire data on regional antibiotic prescriptions. The pooled antimicrobial susceptibilities of E. coli and Klebsiella spp. (n = 2044) were as follows: ampicillin&ndash, sulbactam (61.0%), 3rd generation cephalosporin (3C) (82.8%), and trimethoprim&ndash, sulfamethoxazole (72.0%). Multivariate analysis showed that children diagnosed at hospital A (OR, 1.8, 95% confidence interval [CI], 1.2&ndash, 2.6, P = 0.002) and every year that increased in the study period (OR, 1.1, 95% CI, 1.1&ndash, 1.2, P &lt, 0.001) were factors associated with an increased risk for UTIs with ESBL-producers. Regions A and B had significantly higher amounts of oral 3Cs prescribed compared to regions C and D (P = 0.009), which correlate with hospitals in the regions that had higher proportions of UTIs with ESBL-producing uropathogens (A and B vs. C and D, P &lt, 0.001). Therefore, children in certain regions are at a higher risk for UTIs caused by ESBL-producers compared to other regions, which correlate with regions that had higher amounts of oral 3Cs prescribed.

Background The necessity of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine in adolescence and adults has been emphasized since the resurgence of small-scale pertussis in Korea and worldwide due to the waning effect of the vaccine and variant pathogenic stains in the late 1990s. GreenCross Pharma (GC Pharma), a Korean company, developed the Tdap vaccine GC3111 in 2010. Recently, they enhanced the vaccine, GC3111, produced previously in 2010 to reinforce the antibody response against filamentous hemagglutinin (FHA). In this study, immunogenicity and efficacy of the enhanced Tdap vaccine compared and evaluated with two Tdap vaccines, GC3111 vaccine produced in 2010 previously and commercially available Tdap vaccine in a murine model. Methods Two tests groups and positive control group of Balb/c mice were primed with two doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine followed by a single booster Tdap vaccine at 9 week using the commercially available Tdap vaccine or 2 Tdap vaccines from GC Pharma (GC3111, enhanced GC3111). Humoral response was assessed 1 week before and 2 and 4 weeks after Tdap booster vaccination. The enhanced GC3111 generated similar humoral response compare to the commercial vaccine for filamentous hemagglutinin (FHA). The interferon gamma (IFN-γ) (Th1), interleukin 5 (IL-5) (Th2) and interleukin 17 (IL-17) (Th17) cytokines were assessed 4 weeks after booster vaccination by stimulation with three simulators: heat inactivated Bordetella pertussis (hBp), vaccine antigens, and hBp mixed with antigens (hBp + antigen). A bacterial challenge test was performed 4 weeks after booster vaccination. Results Regarding cell-mediated immunity, cytokine secretion differed among the three simulators. However, no difference was found between two test groups and positive control group. All the vaccinated groups indicated a Th1 or Th1/Th2 response. On Day 5 post-bacterial challenge, B. pertussis colonies were absent in the lungs in two test groups and positive control group. Conclusions Our results confirmed the immunogenicity of GC Pharma’s Tdap vaccine; enhanced GC3111 was equivalent to the presently used commercial vaccine in terms of humoral response as well as cell-mediated cytokine expression.

Hand, foot, and mouth disease (HFMD) is a pediatric public health concern in Asia. Surveillance data on the circulating serotypes of HFMD suggest that

Since the 2000s, two lineages of the influenza B virus (influenza B/Victoria and influenza B/Yamagata) have been co-circulating. Information on the age distribution of patients infected by each influenza B virus lineage may be helpful for establishing differentiated influenza prevention and control strategies for each age group. Age distributions were compared between patients infected by influenza A and B viruses and between those infected by the influenza B virus when B/Victoria and B/Yamagata lineages circulated dominantly. Between the 2014–2015 and 2018–2019 influenza seasons, 2,718 and 1,397 patients were diagnosed with influenza A and B virus infections, respectively. The median age of patients infected by the influenza B virus was lower than that of patients infected by the influenza A virus (8 vs 12 years, p p = 0.732); however, in the Victoria season, the median age of patients infected by the influenza B virus was lower than that of patients infected by the influenza A virus (6 vs 10 years, p p The age distribution of patients infected by the influenza virus was different between the Yamagata and Victoria seasons. Different influenza prevention and control strategies should be considered on the basis of the predominantly circulating virus and the affected age group.

Immunization is the most effective preventive strategy against varicella. While the Oka strain is commonly used for varicella vaccination worldwide, Korea widely uses the MAV/06 strain. A new live attenuated MAV/06 strain varicella vaccine (MG1111), which uses the new cell line Medical Research Council-5 for better viral propagation, was developed. MG1111 was approved by Korean health authorities. Here, we report the results of phase III, randomized, double–blind, multicenter study conducted in Korea and Thailand, which compared the immunogenicity and safety profiles of MG1111 versus the control vaccine, VarivaxTM. In total, 515 healthy children (12 month–12 years) were randomized 1:1 to receive either the MG1111 or control vaccine (MG1111: 258, Control: 257). The seroconversion rate (SCR) and geometric mean titer (GMT) were measured using the fluorescent antibody to membrane antigen (FAMA) test. The MG1111 group achieved a SCR of 97.9% (95% CI: 95.2–99.3) after vaccination. The lower limit of 95% CI for SCR difference (MG1111-VarivaxTM) was –4.0%, which was higher than the specified non-inferiority margin of –10%. Further, the GMT of the MG1111 increased from 2.0 to 74.2 (95% CI: 65.0–84.8) and the lower limits of the 95% CI for post–vaccination GMT ratios (MG1111/VarivaxTM) were 0.55 higher than the specified parameter of 0.5. Therefore, the MG1111 group was not statistically inferior to the control vaccine group in terms of SCR and GMT. Furthermore, the MG1111 and control vaccine groups were not significantly different in the percentage of participants showing adverse events—solicited, local, or systemic during 43-day period of observation and serious adverse events during 6 month of observation. The present results indicate that MG1111was not immunologically inferior to VarivaxTM, and safety profiles of MG1111 are similar to those of VarivaxTM.

Background/Purpose: Although assessing the immunogenicity and protective efficacy of acellular pertussis (aP) vaccines via murine model studies faces limitations, preliminary assessments have been achieved by evaluating respiratory challenge and humoral and cellular immunity. Methods: We performed a long-term intranasal respiratory challenge with reference and clinically isolated strains of Bordetella pertussis. Simultaneously, we assessed humoral and cellular immunity for evaluating the immunogenicity of a newly developed tri-component diphtheria-tetanus-aP (DTaP) vaccine. Moreover, comparative assessment was made by performing the same evaluations with a commercially available tri-component DTaP vaccine as the positive control. Results: Both groups showed significantly increased levels of antibodies against pertussis toxin, filamentous hemagglutinin and pertactin, and the levels of interferon-γ and interleukin-10 were significantly increased after two doses of vaccination. Furthermore, since cross cell-mediated immune reactivity between the two vaccines was detected, the possibility of interchangeability was indirectly suggested. Although the positive control group showed significantly higher titers in antibody responses for filamentous hemagglutinin and pertactin compared to the experimental group, anti-pertussis toxin antibody titers of the two groups were not significantly different and the protective efficacy against the clinical and reference strains was maintained in both groups for 18 weeks. Conclusion: The results showed inferior immunogenicity of the new DTaP vaccine compared to a commercial vaccine despite comparable cellular immunity and protective efficacy. Some efforts are necessary for improving immunogenicity against filamentous hemagglutinin and pertactin before conducting human clinical trials. Keywords: Diphtheria-tetanus-acellular pertussis vaccine, Immunogenicity, Efficacy, Mice

Background Understanding the population genetics of pneumococci will allow detection of changes in the prevalence of circulating genotypes and evidence for capsular switching. We aimed to analyze the genetic structure of invasive pneumococcal isolates obtained from children before and after the use of pneumococcal conjugate vaccines (PCVs) in Korea. Methods A total of 285 invasive pneumococcal isolates were analyzed using serotyping, multilocus sequence typing, and antimicrobial susceptibility testing. We classified the isolation year to pre-PCV7 (1995–2003; n = 70), post-PCV7 (2004–2010; n = 142), and post-PCV13 (2011–2013; n = 73) periods. Results Of the 10 clonal complexes (CCs), antibiotic-resistant international clones, CC320 (31.6%), CC81 (14.7%), and CC166 (6.7%) were the main complexes. Serotype 19A was the main serotype of CC320 throughout the periods. Serotypes of CC81 mainly comprised of 23F (53.3%) in pre-PCV7 period and replaced by non-vaccine types (NVTs; 6C [10%], 13 [30%], 15A [40%], and 15B/C [20%]) in post-PCV13 period. The main serotype responsible for CC166 also changed from 9 V (80%) in pre-PCV7 to NVT 11A (50%) in post-PCV13 periods. Non-susceptibility to penicillin (42.3%) was the highest in CC320, increasing from 0 to 76%. Conclusion The genetic structures of invasive pneumococcal isolates in Korean children have changed concomitantly with serotype after the implementation of PCVs.

BACKGROUND Although Escherichia coli is a common cause of bacterial enteritis in Korea, reports on community-acquired E. coli enteritis in Korean children are scarce. This study aimed to determine the clinical characteristics and pathotype distribution of community-acquired E. coli enteritis diagnosed by a multiplex polymerase chain reaction (PCR) assay in Korean children. MATERIALS AND METHODS The medical records of children aged 18 years or less who were diagnosed with acute gastroenteritis by the attending physician between 2013 and 2016 were retrospectively reviewed. The clinical characteristics of children diagnosed with E. coli enteritis were investigated and compared with those diagnosed with Salmonella enteritis. E. coli and Salmonella infections were diagnosed by a stool PCR assay. RESULTS Among 279 children, in whom PCR assays for E. coli and Salmonella spp. were performed, Salmonella enteritis and E. coli enteritis were diagnosed in 43 (15.4%) and 39 (14.0%) children, respectively. Among the 39 children with E. coli enteritis, enteropathogenic E. coli (n=21, 53.8%) and enteroaggregative E. coli (n=15, 38.4%) were the most common causative agents. Empirical antibiotics were administered to 33 (84.6%) children. A total of 31 (79.5%) children developed fever, and 25 (80.6%) of them had the fever for 3 days or less, which resolved a median of 1 day (range 0-3 days) after hospitalization. The most frequent gastrointestinal symptom was diarrhea (n=36, 92.3%). Significantly more children with E. coli enteritis were aged 2 years or less as compared with those with Salmonella enteritis (41.0% vs. 21.9%, P = 0.021). Children with Salmonella enteritis more frequently complained of fever (97.7% vs. 79.5%, P = 0.012), abdominal pain (90.7% vs. 64.1%, P = 0.004), and hematochezia (46.5% vs. 10.3%, P

Although aseptic meningitis associated with echovirus type 30 has emerged as a global public health concern, no data have been reported on Children’s immune status against echovirus type 30. The current study aimed to investigate the seropositivity among Korean children for antibodies against echovirus 30. Two hundred and fifty residual serum samples were collected at St. Paul’s Hospital. Individuals were categorized by age into four groups: group 1 (3 months–2 years), group 2 (3–6 years), group 3 (7–10 years) and group 4 (11–15 years). Neutralizing antibodies against echovirus 30 were measured. Seroprotective neutralizing antibodies against echovirus 30 were detected in 129 (49%) individuals. Seropositivity rates were 23%, 48%, 55% and 73% in groups 1–4, respectively. For antibody titers, 1:256–1:512 was the highest neutralizing antibody titer range in group 2, while 1:1024–1:2048 in group 3 and 4. Among the seropositive individuals in group 3 and 4, 6% and 12% had neutralizing antibody titers of 1:2048, respectively. The seropositivity rate increased significantly with age. The distribution of neutralizing antibody titers varied by age group, and higher ranges of neutralizing antibody titers were observed in higher age groups. These findings suggest high susceptibility to echovirus 30 infection in children younger than 2 years old. Echovirus 30 infection in childhood may have contributed to increased neutralizing antibody titers with age.

Background Tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccination during adolescence was introduced in response to the resurgence of pertussis in various countries. A new Tdap vaccine was manufactured in Korea as a countermeasure against a predicted Tdap vaccine shortage. This study was performed to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model. Methods Four-week-old BABL/c mice were used for assessment of immunogenicity and protection efficacy. A single dose of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered, followed by a single dose of Tdap booster vaccine after a 12-week interval. Anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG titers were measured before primary vaccination, and before and after booster vaccination. An intranasal challenge test was performed after booster vaccination to determine protection efficacy. To assess safety, mouse weight gain test and leukocytosis promotion test were performed using 4-week-old ddY female mice. Results Anti-PT and anti-FHA IgG titers after booster vaccination were significantly higher than those before booster vaccination with either the new vaccine or a commercially available Tdap vaccine (P = 0.01 for all occasions). After booster vaccination, no significant difference was observed between the two vaccines in antibody titers against pertussis antigens (P = 0.53 for anti-PT IgG, P = 0.91 for anti-FHA IgG, P = 0.39 for anti-PRN IgG). In the intranasal challenge test, inoculated B. pertussis was eradicated 7 days after infection. On days 4 and 7 after infection, colony counts of B. pertussis were not significantly different between the new and positive control vaccine groups (P = 1.00). Mean body weight changes and leukocyte counts of the new vaccine, positive control, and negative control groups were not significantly different 7 days after vaccination (P = 0.87 and P = 0.37, respectively). All leukocyte counts in the new vaccine group were within a mean ± 3 standard deviations range. Conclusions A murine model involving a single dose primary DTaP vaccination followed by a single dose Tdap booster vaccination can be used for non-clinical studies of Tdap vaccines. The new Tdap vaccine manufactured in Korea exhibited comparable immunogenicity, protection efficacy, and safety with a commercially available Tdap vaccine.

Background This prospective study was performed to evaluate serotype distribution, multilocus sequence typing, and antibiotic susceptibility of Streptococcus pneumoniae identified in Korean children with acute otitis media (AOM) after the introduction of a 7-valent pneumococcal conjugate vaccine (PCV7). Methods Nasopharyngeal aspirates were collected from children diagnosed with AOM in seven hospitals in Korea. The bacteria identified in these samples and the serotypes, sequence types (STs), and antibiotic susceptibilities of S. pneumoniae isolates were evaluated. Results A total of 390 children were enrolled, and bacteria were identified in 376 (96.4%) children. S. pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were identified in 155 (39.7%), 127 (32.6%) and 86 (22.1%) children, respectively. Serotype 19A (22.4%) was the most common S. pneumoniae serotype, with serogroups 11 (14.7%) and 15 (13.5%) following. ST320 (23.5%) was the most common ST; ST166 (17.0%) and ST83 (8.5%) followed. The overall susceptibility rates of S. pneumoniae to oral penicillin V and amoxicillin/clavulanate were 2.6% and 53.2%, respectively. The susceptibility rate to cefditoren was 91.0%; however, the rates for other cephalosporins were less than 10.0%. Compared with other serogroups, S. pneumoniae serogroups 19, 11, and 15 showed significantly lower susceptibility rates to all the antibiotics tested. Conclusion S. pneumoniae serotype 19A, serogroups 11 and 15 were the major nasopharyngeal-colonizing bacteria in Korean children with AOM after the introduction of PCV7. These relatively prevalent serotype/serogroups showed lower antibiotic susceptibility rates.

Background: Vaccination for hepatitis B virus (HBV) after chemotherapy among pediatric patients with acute leukemia is still a debated issue. We investigated HBV immunity before and after chemotherapy and assessed immune response to re-vaccination after chemotherapy. Methods: We retrospectively analyzed data of children and adolescents aged

Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015-2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24-36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP) (1-2 mg/kg) was administered for mild pneumonia patients, and IVMP (5 -10 mg/kg/day) for severe pneumonia patients. If patients showed persistent fever for 36-48 hours or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Eighty-five patients received only a broad-spectrum antibiotic without macrolide. The mean age and the male:female ratio were 5.6 ± 3.1 years, respectively. Seventy-four percent of patients (190/257) showed immediate defervescence within 24 h, and 95.7% (246/257) of patients showed defervescence within 72 h with improvements in clinical symptoms. Eight patients who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.

Antibiotics&rsquo, effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015&ndash, 2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24&ndash, 36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP, 1&ndash, 2 mg/kg) was administered for mild pneumonia patients, and IVMP (5&ndash, 10 mg/kg/day) for severe pneumonia patients. If patients showed a persistent fever for 36&ndash, 48 h or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Thirty-three percent of patients received only a broad-spectrum antibiotic without a macrolide. The mean age and the male-to-female ratio was 5.6 &plusmn, 3.1 years and 1:1, respectively. Seventy-four percent of patients showed immediate defervescence within 24 h, and 96% of patients showed defervescence within 72 h with improvements in clinical symptoms. Three percent of patients (8/257) who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.

Background This study was conducted to assess the immunogenicity and safety of GC1107 (adult tetanus diphtheria [Td] vaccine). The primary goal was to evaluate the non-inferiority of the immunogenicity of GC1107 compared to the control vaccine. Additionally, the safety profiles of GC1107 and the control vaccine were compared. Methods The subjects were adults ≥ 18 years old who were not injected with Td or adult tetanus-diphtheria-pertussis (TdaP) vaccine within the recent 5 years. A total of 253 subjects were enrolled and randomized to either the GC1107 group or the control group. For immunogenicity assessment, blood samples were collected at baseline and 28 days after vaccination and antibody titer of diphtheria and tetanus were assessed. Results The seroprotection rates of diphtheria and tetanus were 89.76% and 91.34%, respectively, in the GC1107 group, and 87.80% and 86.99% in the control group. The geometric mean titer (GMT) of the anti-diphtheria antibody increased after vaccination in both groups, showing no significant difference between the groups (P = 0.139). The anti-tetanus GMTs after vaccination also showed comparable increases in both groups, and showed no significant difference (P = 0.860). In the safety evaluation, solicited local adverse reactions occurred in 81.2% of the subjects in the GC1107 group and in 86.4% of the subjects in the control group. Solicited systemic adverse events occurred in 33.2% of the subjects in the GC1107 group and in 47.2% of the subjects in the control group, which did not reach statistical significance. Conclusion This phase III study demonstrated non-inferiority in immunogenicity and comparable safety of GC1107 compared with the control Td vaccine. Trial Registration ClinicalTrials.gov Identifier: NCT02361866, Graphical Abstract