Hoan Jong Lee

The Association of Newly Identified Respiratory Viruses with Lower Respiratory Tract Infections in Korean Children, 2000-2005

Abstract Background. This study was performed to evaluate the associations of newly recognized viruses, namely, human metapneumovirus (hMPV), human coronavirus (HCoV)–NL63, and human bocavirus (HBoV) with lower respiratory tract infections (LRTIs) in previously healthy children. Methods. To determine the prevalences of 11 viruses—respiratory syncytial virus (RSV), adenovirus, rhinovirus, parainfluenza viruses (PIVs) 1 and 3, influenza viruses A and B, hMPV, HCoV, HCoV-NL63, and HBoV—among infants or children with LRTIs, in association with their epidemiologic characteristics, we performed multiplex reverse-transcriptase polymerase chain reaction on nasopharyngeal aspirates obtained from 515 children 5 years old with LRTIs during the period 2000–2005. Results. Viruses were identified in 312 (60.6%) of the 515 patients. RSV was detected in 122 (23.7%), HBoV in 58 (11.3%), adenovirus in 35 (6.8%), PIV-3 in 32 (6.2%), rhinovirus in 30 (5.8%), hMPV in 24 (4.7%), influenza A in 24 (4.7%), PIV-1 in 9 (1.7%), influenza B in 9 (1.7%), and HCoV-NL63 in 8 (1.6%). Coinfections with 2 viruses were observed in 36 patients (11.5%). Twenty-two patients (37.9%) infected with HBoV had a coinfection. Bronchiolitis was frequently diagnosed in patients who tested positive for RSV, PIV-3, or rhinovirus, whereas influenza A, PIV-1, and HCoV-NL63 were commonly found in patients with croup. The age distributions of patients with viral infections differed; notably, RSV was responsible for 77% of LRTIs that occurred in infants 3 months old. The number of hMPV infections peaked between February and April, whereas the number of HCoV-NL63 infections peaked between April and May. Conclusions. This study describes the features of LRTIs associated with newly identified viruses in children, compared with those associated with known viruses. Additional investigations are required to define the role of HBoV in LRTI.

Bloodstream Infections by Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Children: Epidemiology and Clinical Outcome

ABSTRACT To determine the epidemiologic features and clinical outcomes of bloodstream infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, cases of bacteremia caused by these organisms in children were analyzed retrospectively. Among the 157 blood isolates recovered from 1993 to 1998 at the Seoul National University Childrens Hospital, the prevalence of ESBL production was 17.9% among the E. coli isolates and 52.9% among the K. pneumoniae isolates. The commonest ESBLs were SHV-2a and TEM-52. A novel ESBL, TEM-88, was identified. Pulsed-field gel electrophoresis analysis of the ESBL-producing organisms showed extensive diversity in clonality. The medical records of 142 episodes were reviewed. The risk factors for bloodstream infection with ESBL-producing organisms were prior hospitalization, prior use of oxyimino-cephalosporins, and admission to an intensive care unit within the previous month. There was no difference in clinical severity between patients infected with ESBL-producing strains (the ESBL group) and those infected with ESBL-nonproducing strains (the non-ESBL group) at the time of presentation. However, the overall fatality rate for the ESBL group was significantly higher than that for the non-ESBL group: 12 of 45 (26.7%) versus 5 of 87 (5.7%) (P = 0.001). In a subset analysis of patients treated with extended-spectrum cephalosporins with or without an aminoglycoside, favorable response rates were significantly higher in the non-ESBL group at the 3rd day (6 of 17 versus 33 of 51; P = 0.035), the 5th day (6 of 17 versus 36 of 50; P < 0.05), and the end of therapy (9 of 17 versus 47 of 50; P < 0.001). In conclusion, the ESBL production of the infecting organisms has a significant impact on the clinical course and survival of pediatric patients with bacteremia caused by E. coli and K. pneumoniae.

Streptococcus pneumoniae serotype 19A in children, South Korea.

A single, multidrug-resistant strain was responsible for increased incidence of this serotype before introduction of the pneumococcal 7-valent conjugate vaccine.

A Common Haplotype of Interleukin-4 Gene IL4 Is Associated with Severe Respiratory Syncytial Virus Disease in Korean Children

Respiratory syncytial virus (RSV) is a major health problem in young children, and host response to severe disease favors a Th2 immune response. To investigate the genetic basis for RSV disease severity, linked variants of 3 Th2 cytokine genes, IL4, IL13, and IL5 (which are clustered on chromosome 5q31.1) were characterized in 105 children who were hospitalized with severe RSV infection and 315 Korean control subjects in a pilot study. A common IL4 haplotype defined at 5 loci, which includes the -589T promoter variant, previously shown to be associated with increased interleukin (IL)-4 transcriptional activity and predisposition to asthma, was overrepresented in patients with severe RSV disease (odds ratio, 1.63; P=.02). These results support the hypothesis that severe RSV disease might be related to increased Th2 response, which is perhaps mediated by overexpression of IL-4, and provide preliminary evidence for a genetic link between severe RSV disease and subsequent wheezing.

Genome Type Analysis of Adenovirus Types 3 and 7 Isolated during Successive Outbreaks of Lower Respiratory Tract Infections in Children

ABSTRACT Adenovirus is an important cause of respiratory infections in infants and children. Fifty-one serotypes have been identified, and adenovirus type 3 (Ad3) and Ad7 have often been associated with outbreaks of severe respiratory tract infections. Each serotype can be further divided into genome types based on the patterns of digestion of their DNAs with restriction enzymes. DNA restriction analysis was performed with 56 strains of Ad3 and 98 strains of Ad7 by using 12 restriction enzymes recognizing 6 bp (BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). The virus strains were isolated during outbreaks of lower respiratory tract infections in children during an 11-year period from 1990 to 2000 in Seoul, Korea. Among the Ad3 strains, seven genome types were identified; Ad3a and six novel types (Ad3a13, Ad3a14, Ad3a15, Ad3a16, Ad3a17, and Ad3a18). Multiple genome types cocirculated during outbreaks, and some of these were isolated during the 11-year observation period, while others were restricted to particular outbreaks. For Ad7, two genome types, Ad7d and Ad7l, the latter of which is a novel genome type, were identified. A shift in genome types occurred from Ad7d to Ad7l during successive outbreaks. Mortality was 3.6% among children with Ad3 infections and 18% among children infected with either of the Ad7 genome types. In conclusion, the data confirm that Ad3 genome types are more diverse than those of Ad7 and suggest that shifts of genome types may occur during successive outbreaks of Ad3 and Ad7.

Genetic Diversity and Molecular Epidemiology of the G Protein of Subgroups A and B of Respiratory Syncytial Viruses Isolated over 9 Consecutive Epidemics in Korea

To study genetic variation and molecular epidemiology of the G protein of respiratory syncytial virus (RSV), 253 strains from a childrens hospital in Korea over 9 consecutive epidemics were analyzed. Restriction analysis of the entire G protein gene demonstrated 24 genotypes among 188 subgroup A and 6 among 65 subgroup B isolates. Two to 4 dominant genotypes of subgroup A cocirculated, and different genotypes predominated in each epidemic. Predominant genotypes were replaced with new genotypes during consecutive epidemics. One of 2 dominant genotypes among subgroup B predominated alternately or concurrently. Phylogenetic analysis revealed that there were multiple lineages, with clustering related to their location and time of isolation among strains from Korea and worldwide. Geographic and temporal distinction have been shown more clearly for subgroup B than subgroup A. These results suggest that the G protein of RSV is continuously evolving, with a distinct pattern presumably due to immune selection in a localized region over time.

Macrolide Resistance of Mycoplasma pneumoniae, South Korea, 2000–2011

In Korea, Mycoplasma pneumoniae was detected in 255/2,089 respiratory specimens collected during 2000–2011; 80 isolates carried 23S rRNA gene mutations, and 69/123 culture-positive samples with the mutation were resistant to 5 macrolides. During 2000–2011, prevalence of the mutation increased substantially. These findings have critical implications for the treatment of children with mycoplasma pneumonia.

The Causative Organisms of Bacterial Meningitis in Korean Children in 1996-2005

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood, despite the availability of effective vaccines against Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data on bacterial meningitis cases in Korea from 1996 through 2005. The information of all hospitalized bacteria-proven meningitis cases was obtained from 17 university hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%) cases were neonates. Streptococcus agalactiae was the most common bacteria responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumoniae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiology beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H. influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae and H. influenzae were important etiologic agents of bacterial meningitis in children in the last 10 yrs. It is required to establish the preventive strategy of the three bacteria. The nationwide epidemiologic study should be continued to evaluate immunization strategy and efficacy.

Mycoplasma pneumoniae in Korean children: the epidemiology of pneumonia over an 18-year period

OBJECTIVES Mycoplasma pneumoniae (MP) is a major cause of community-acquired pneumonia in children. The aim of this study was to investigate the long-term epidemiology of MP pneumonia in Korean children. METHODS A retrospective analysis of a database of 2405 patients with pneumonia at the Seoul National University Childrens Hospital between 1986 and 2004 was performed. Serologic diagnosis for MP infection was made based on a 4-fold rise or single titers >/=1:640, which were measured by an indirect agglutination test. RESULTS MP pneumonia was diagnosed in 568 patients over 18 years. The mean age was 5.7 years. Children younger than 5 years of age accounted for 44% of the cases. Six outbreaks were observed at intervals of 3-4 years. The earlier epidemics up until 1996 peaked in the summer, while the later epidemics peaked in the fall or early winter. Children <5 years old were more commonly affected during large epidemics compared to endemic periods. The geometric mean antibody titers were maintained >/=1:320 up to 7 months after the onset of illness. CONCLUSIONS The results of this study revealed community outbreaks of MP pneumonia at 3-4-year intervals among Korean children. A significant proportion of young Korean children were affected by MP pneumonia, especially during large epidemics.

Pulmonary Tuberculosis in Infants: Radiographic and CT Findings

OBJECTIVE As complications of tuberculosis are frequent in infancy, correct diagnosis of tuberculosis in infants is important. The purposes of this study are to summarize radiographic and CT findings of pulmonary tuberculosis in infants and to determine the radiologic features frequently seen in infants with this disease. CONCLUSION Frequent radiologic findings of pulmonary tuberculosis in infants are mediastinal or hilar lymphadenopathy with central necrosis and air-space consolidations, especially masslike consolidations with low-attenuation areas or cavities within the consolidation. Disseminated pulmonary nodules and airway complications are also frequently detected in this age group. CT is a useful diagnostic technique in infants with tuberculosis because it can show parenchymal lesions and tuberculous lymphadenopathy better than chest radiography. CT scans can also be helpful when chest radiographs are inconclusive or complications of tuberculosis are suspected.