• Journal of Yeungnam Medical Science
• /
• v.29 no.1
• /
• pp.1-8
• /
• 2012

Streptococcus pneumonia is a very important pathogen for children and elderly people. Two types of pneumococcal vaccines are available in the market: pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV). PPSVs have been used for more than 30 years, and PCVs for about 10 years. There have been many reports concerning the evaluation of the vaccines' efficacies in preventing pneumococcal diseases such as meningitis, pneumonia, and otitis media and bacteremia, but the clinical trials had been performed with different conditions, such as diverse vaccine valencies, age groups, races, target outcomes, immunological cut-off values, and follow-up periods. PPSV is recommended for elderly people and chronic disease patients such as asthma, diabetes mellitus, chronic renal failure, and hyposplenic patients. According to the data from several systemic reviews and population-based surveillances, PPSV is effective for pneumococcal pneumonia and vaccine-type bacteremia among healthy adults. Until now, however, there is insufficient evidence of the effectiveness of PPSV among high-risk adults. PCV is very effective in preventing vaccine-type invasive pneumococcal disease (IPD) among children, but its efficacy for pneumonia is very low among children. The incidence of vaccine-related or non-vaccine-type IPDs is increasing after the introduction of 7-valent PCV (PCV7) as a routine immunization for children. Recently, 10- and 13-valent PCVs have been used for children, instead of PCV7. Therefore, continuous surveillance for serotype change among pneumococcal diseases is necessary to evaluate the vaccines' efficacy.

• Clinical and Experimental Pediatrics
• /
• v.55 no.11
• /
• pp.424-429
• /
• 2012

Purpose: Methods for quick and reliable detection of Streptococcus pneumoniae are needed for the diagnosis of pneumococcal disease and vaccine studies. This study aimed to show that sequential multiplex polymerase chain reaction (PCR) is more efficient than conventional culture in achieving S. pneumoniae -positive results. Methods: Nasopharyngeal (NP) secretions were obtained from 842 pediatric patients admitted with lower respiratory infections at Severance Children's Hospital in Korea between March 2009 and June 2010. For identification and serotype determination of pneumococci from the NP secretions, the secretions were evaluated via multiplex PCR technique with 35 serotype-specific primers arranged in 8 multiplex PCR sets and conventional bacteriological culture technique. Results: Among the results for 793 samples that underwent both bacterial culture and PCR analysis for pneumococcal detection, 153 (19.3%) results obtained by PCR and 81 (10.2%) results obtained by conventional culture technique were positive for S. pneumoniae. The predominant serotypes observed, in order of decreasing frequency, were 19A (23%), 6A/B (16%), 19F (11%), 15B/C (5%), 15A (5%), and 11A (4%); further, 26% of the isolates were non-typeable. Conclusion: As opposed to conventional bacteriological tests, PCR analysis can accurately and rapidly identify pneumococcal serotypes.

• Clinical and Experimental Pediatrics
• /
• v.54 no.4
• /
• pp.163-168
• /
• 2011

Purpose: The purpose of this study was to evaluate the immune response to serotype 19A in children aged 12-23 months after immunization of the 19F containing 7-valent pneumococcal conjugate vaccine (PCV7). Methods: Blood samples from a total of 45 subjects (age 12-23 months) were included in the study. Subjects were categorized according to immunization status into three groups as follows: 18 subjects with 3 primary doses and 1 booster dose of PCV7 (booster group), 21 subjects with 3 primary doses before 12 months of age (primary group), and 6 subjects with no vaccination history of PCV7 (control group). An ELISA and opsonophagocytic killing assay (OPKA) was done to evaluate the immune responses against serotypes 19F and 19A. Results: According to the ELISA, all subjects had antibody titers ${\geq}0.35{\mu}g/mL$ for serotypes 19F and 19A in the booster and primary group and 83.0% and 66.7% in the control group, respectively. According to the OPKA, subjects with opsonic activity (${\geq}20$) against serotypes 19F and 19A were 100% and 61.1% of the subjects in the booster group and 66.7% and 19.0% in the primary group, respectively. No subjects in the control group had opsonic antibodies against both serotypes. Conclusion: In conclusion, in children 12-23 months age who were previously vaccinated with PCV7, a cross-reactive immune response is elicited against serotype 19A after a primary series of 3 doses in a small proportion of subjects, and this response is amplified after booster vaccination.

• Pediatric Infection and Vaccine
• /
• v.13 no.2
• /
• pp.89-98
• /
• 2006

Purpose : The prevalence of serotypes can be changed with respect to age of the patients, regions and times of the surveillance. The aim of this study is to analyze changes in serotype distribution of pneumococcal isolates from Korean pediatric patients. Methods : Four hundred and sixty five strains of S. pneumoniae were isolated from various clinical specimens at the Seoul National University Children's Hospital during a 15 year-period, from 1991 to 2005, were subjected to serotype and penicillin susceptibility. The study period was divided into three 5 year-periods, 1991~1995(period I), 1996~2000(period II), and 2001~2005(period III). Results : Common serotypes were 19F, 23F, 19A, 6B, 14, 6A and 9V in decreasing orders of frequency, and these 7 serotypes accounted for 79% of total 465 strains. In the serotype distribution of invasive infection isolates from children <60 months of age, similar serotypes accounted for 70% of 101 strains. In total strains, the proportion of serotype 19A and 6A increased, while that of serotype 19F and 14 decreased. The majority(75~92%) of vaccine types and cross-reactive types from invasive infection isolates was penicillin-resistant, whereas 34.4% of non-vaccine types was penicillin-resistant. Conclusion : Distribution of serotypes of S. pneuomoniae isolated from Korean children has changed significantly over the last 15 years. The surveillance for pneumococcal serotypes should be continued to monitor changes in serotype distribution which are essential for the establishment of pneumococcal vaccine policy.

• Clinical and Experimental Pediatrics
• /
• v.51 no.6
• /
• pp.622-628
• /
• 2008

Purpose : The purpose of this study was to evaluate the immunogenicity of the booster immunization with pneumococcal conjugate vaccine in Korean children. Methods : Thirty-nine children aged 12-23 months who visited Kangnam CHA Hospital between September 2006 and December 2006 were enrolled. The children were divided into primary and booster groups depending on their vaccination status for the 7-valent pneumococcal conjugate vaccine. The anti-pneumococcal antibody levels of each serotype included in the vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) were determined by third-generation ELISA. Results : The geometric mean titer (GMT) of antibodies to each pneumococcal serotype in the booster group was higher than in the primary group (P<.05). The percentage of subjects with pneumococcal antibodies ${\geq}0.35{\mu}g/mL$ was 90.5-100% for all serotypes in both the primary and booster groups. The percentage of subjects with pneumococcal antibodies ${\geq}1.0g/mL$ in the booster group was 94.4-100%, which was higher than the primary group except for serotypes 6B and 14 (P<.05). The percentage of subjects with pneumococcal antibodies ${\geq}5.0{\mu}g/mL$ in the booster group was 50.0-94.4% which was higher than the primary group for all serotypes (P<0.05). Conclusion : The immunogenicity of a booster dose of the pneumococcal conjugate vaccine in Korean children was high and the immunogenicity of a primary series was also relatively high. To determine the feasibility of the introduction of the pneumococcal conjugate vaccine and the appropriate schedule for Korean children, further prospective investigation of the immunogenicity of the booster immunization is needed.

• Pediatric Infection and Vaccine
• /
• v.10 no.2
• /
• pp.159-166
• /
• 2003

Purpose : Streptococcus pneumoniae is part of the normal flora but is also responsible for causing many invasive diseases such as pneumonia, meningitis, and sepsis in addition to noninvasive diseases such as otitis in children. Multi-drug resistant strains has raised a lot of concern worldwide and thus the importance of prevention has been emphasized. We have analyzed the current serotypes and antibiotic sensitivity of each serotype as a baseline study to estimate the efficacy of the pneumococcal vaccine in Korean children. Methods : One hundred sixteen cases of pneumococcus cultured at Yonsei Medical Center from September 2001 to January 2003 were analyzed. The serotyping was done with the Quellung reaction and penicillin resistance was tested using the oxacillin disc diffusion method. Results : Pneumococcus were cultured from the sputum in 76 cases(65.5%), from the blood in 13 cases(11.2%), from the ear discharge in 12 cases(10.3%), from the throat in 7 cases(6.0%), from the nasal cavity in 2 cases(1.7%), and one case(0.9%) each from the cerebrospinal fluid, eye discharge, peritoneal fluid, post-operational wound, brain abscess, and catheter tip. Serotyping was possible with 98 cases and the following serotypes were found; 15 cases of type 19F(15.3%), 11 cases of 19A(11.2%), 8 cases of 11A(8.2%), 7 cases each of 6A, 14 and 3(7.1%), 6 cases each of 35, 6B and 23F(6.1%). Eighty two cases(70.7%) out of 116 cases were penicillin resistant and serotypes 19F, 19A, 11A, 23F, 6A, 9V constituted the majority, 48 cases(59.8%). These serotypes showed resistance to cotrimoxazole (74.4%), tetracycline(69.5%), and erythromycin(90.3%) as well. In the 22 cases cultured from children, 19A and 19F were found in 25.0%, 6A, 6B, and 23F in 10.0%, 11A, 14, 19, and 29 in 5.0%. Fifty percent(10/20) of the clinical isolates were represented in the current 7-valent pneumococcal protein conjugate vaccine, and 85%(17/20) when the cross-reacting serotypes were included. Penicillin resistance was found in 86.4%(19/22). Conclusion : The percentage of serotypes included in the 7 valent pneumococcal protein conjugate vaccine found in our study was 40.8% which was less than other prior studies. In anticipation of a change of pneumococcal serotypes, a nationwide multicenter study is needed before the initiation of pneumococcal vaccines in Korea.

• Clinical and Experimental Pediatrics
• /
• v.50 no.2
• /
• pp.151-156
• /
• 2007

Purpose : Streptococcus pneumoniae is a major etiologic agent for pneumonia, meningitis, otitis media, and sepsis among young children. Multi-drug resistant strains have raised great concern worldwide, thus the importance of prevention with vaccines has been emphasized. However, vaccines may force the appearance of pneumococcal infections by nonvaccine serotypes. Thus, distribution of pneumococcal serotypes should be monitored to estimate vaccine efficacy. We used a new and efficient multibead assay in determining pnemococcal serotypes. Methods : From January to February 2005, 643 children were recruited from ten day care centers to isolate pneumococci from their oropharynx. Pneumococcal serotyping was performed on 62 pneumococcal isolates from 60 children by multibead assay. This immunoassay required two sets of latex particles coated with pneumococcal polysaccharides and serotype-specific antibodies. Twenty four newly developed monoclonal antibodies specific for common serotypes and a pool of polyclonal rabbit sera for some of the less common serotypes were used. Results : The most prevalent pneumococcal serotypes were serotype 6A, 19A, 19F, 23F, and 11A/D/F which accounted more than 50 precent of all the 62 pneumococcal isolates. We found that multibead assay can be performed very rapidly and objectively. Conclusion : This multibead immunoassay was very useful in serotyping clinical isolates of S. pneumoniae because it was simple, reliable and fast.

• Pediatric Infection and Vaccine
• /
• v.13 no.2
• /
• pp.115-123
• /
• 2006

Purpose : We investigated whether there had been any change in the epidemiology of Streptococcus pneumoniae in Korea before and after introduction of heptavalent pneumococcal conjugate vaccine(PCV7). Methods : Between September 2001 and August 2006, clinical isolates were collected from patients with pneumococcal infection in Severance Hospital, Seoul, Korea. We analyzed trends in serotype distribution and antibiotic resistance before and after the introduction of PCV7. Results : There were 363 strains of Streptococcus pneumoniae isolated from clinical specimens; 143 before and 220 after PCV7 introduction. The predominant serotypes, in order of decreasing frequency, were 19F, 19A, 23F, 6B, 6A, 3, 9V, 14, 11A, 4, 29, and 18C; 152 isolates(41.9%) belonged to types included in PCV7. The proportion of clinical isolates that were nonsusceptible to penicillin increased from 58.8% in 2001 to 83.6% in 2006(P=0.046). There was no significant diminution in pneumococcal infection caused by vaccine serotypes after the introduction of PCV7. In children younger than age 2 years, the proportion of clinical isolates that were vaccine serotypes was higher than in persons older than age 15 years (59.3% vs 37.8%, P=0.004). Conclusions : There was no significant diminution in pneumococcal infection caused by vaccine serotypes after the introduction of PCV7, therefore more universal pneumococcal immunization program is recommended especially for children younger than age 2 years.

• Journal of Environmental Health Sciences
• /
• v.30 no.1
• /
• pp.15-21
• /
• 2004

In an attempt to analyze the characteristics of domestic pathogenic strains of S. pneumoniae, the basic epidemiological charactristics of pathogenic strains such as their serotypes and frequency of penicillin resistance, and pattern of chromosomal DNA from PFGE(pulsed-field gel electrophoresis) were observed. For this study,56 strains of S. pneumoniae isolated from inpatients and outpatients in the four domestic university hospitals were collected from January to December in 1998. Among those strains, a total of 56 pathogenic strains from blood(39 isolates), cerebrospinal fluid(8 isolates) and other specimen(9 isolates) were selected and isolated. The penicillin resistance frequency of those 56 strains was identified with disk diffusion method with 66.1％. From the invasive strains, predominant serotypes were isolated in the order of 19F(12.5％), 23F(10.7%), 14(10.7%) and 9V(10.7％), totalling 45 percent. This experiment also used PFGE patterns to compare the correlations among genetic subtypes in several serotypes. The DNA fragments digested with Sma I and Apa I were resolved by PFGE. The PFGE patterns digested with Sma I were better than Apa I for analysis. In the DNA fragments digested with Sma 1, PFGE analysis of 56 S. pneumoniae isolates showed 25 different patterns. As a result, serotype was on the whole correlated to PFGE pattern on the ground that each different PFGE pattern by serotype was observed. This study can be utilized not only fur the study of incidence trend of domestic pneumococcal diseases but also as a useful basic data for the development of identification tool and treatment.

• Pediatric Infection and Vaccine
• /
• v.22 no.2
• /
• pp.97-105
• /
• 2015

Purpose: Serotyping pneumococcal isolates is important to monitor efficacy of pneumococcal vaccines. Because of difficulties of typing pnueumocci, a multiplex bead-based (multibead) serotyping assay was recently introduced. The aim of this study is to establish a new multibead serotyping assay and to apply this method to analyze clinical isolates of pneumococci in Korea. Methods: To establish the multibead serotyping assay, six key reagents were transferred from University of Alabama at Birmingham (UAB) to Ewha Center for Vaccine Evaluation and Study (ECVES): bead set coated with polysaccharide and monoclonal antibody pool were used in one multiplex inhibition-type immunoassay and 2 bead sets coated DNA probe and 2 primer pools were used in two multiplex PCR-based assays. After multibead serotyping assay was set up, 75 test samples of pneumococci were analyzed whether ECVES is able to identify serotype correctly. After confirming the performance, serotyping assay was applied to identify serotypes of 528 clinical isolates of pneumococci collected from 3 different hospitals. Results: After establishment of the multibead pneumococcal serotyping assay system at ECVES, 75 test samples were analyzed. There was no discrepancy of serotypes of 75 test samples between the results assigned at UAB and those at ECVES. The serotypes of 528 pneumococci isolated from patients or healthy subjects were determined in 94.3% of isolates (498/528). Conclusions: The multibead pneumococcal serotyping assay can be successfully established in Korea. With this method, surveillance of serotypes of pneumococci isolated from patients as well as healthy subjects could be studied.