ORIGINAL ARTICLE Pediatrics http://dx.doi.org/10.3346/jkms.2016.31.7.1082 • J Korean Med Sci 2016; 31: 1082-1088 Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013 Eun Young Cho,1,2 Eun Hwa Choi,1 This study was performed to measure early changes in the serotype distribution of 3 4 Jin Han Kang, Kyung-Hyo Kim, pneumococci isolated from children with invasive disease during the 3-year period Dong Soo Kim,5 Yae-Jean Kim,6 Young Min Ahn,7 Byung Wook Eun,7 following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) Sung Hee Oh,8 Sung-Ho Cha,9 in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, 10 11 Hye-Kyung Cho, Young Jin Hong, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Kwang Nam Kim,12 Nam Hee Kim,13 Yun-Kyung Kim,14 Jong-Hyun Kim,3 Serotypes were determined using the Quellung reaction, and the change in serotype Hyunju Lee,15 Taekjin Lee,16 distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of 17 18 Hwang Min Kim, Kun Song Lee, patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of Chun Soo Kim,19 Su Eun Park,20 Young Mi Kim,20 Chi Eun Oh,21 pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and Sang Hyuk Ma,22 Dae Sun Jo,23 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 24 25 Young Youn Choi, Jina Lee, 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F, and 19A) Geun-Ryang Bae,26 Ok Park,26 Young-Joon Park,26 Eun Seong Kim,26 accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the and Hoan Jong Lee1 PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency 1Seoul National University College of Medicine, Seoul, from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 Korea; 2Chungnam National University Hospital, types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Daejeon, Korea; 3College of Medicine, the Catholic Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued University of Korea, Seoul, Korea; 4School of Medicine, Ewha Womans University, Seoul, Korea; 5Yonsei to be the most common serotype causing IPD in children. Subsequently, the proportion of University College of Medicine, Seoul, Korea; 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The 6Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea; 7Eulji University impact of extended-valent vaccines must be continuously monitored. School of Medicine, Daejeon, Korea; 8Hanyang University, College of Medicine, Seoul, Korea; 9Kyung Hee Keywords: Streptococcus pneumoniae; Serotype; Pneumococcal Vaccines University School of Medicine, Seoul, Korea; 10Graduate School of Medicine, Gachon University, Incheon, Korea; 11Inha University School of Medicine, Incheon, Korea; 12Hallym University College of Medicine, Chuncheon, Korea; 13Inje University College of Medicine, Seoul, Korea; 14Korea University College of Medicine, Seoul, INTRODUCTION Korea; 15Seoul National University Bundang Hospital, Seoul, Korea; 16CHA Bundang Medical Center, CHA University, Seoul, Korea; 17Yonsei University Wonju Streptococcus pneumoniae is a leading cause of invasive bacterial infection in children. College of Medicine, Wonju, Korea; 18College of Medicine, The invasiveness and antibiotic resistance pattern of pneumococcus vary according to Dankook University, Cheonan, Korea; 19Keimyung University School of Medicine, Daegu, Korea; 20Pusan serotype (1). After the introduction of the 7-valent pneumococcal conjugate vaccine National University School of Medicine, Busan, Korea; (PCV7, Prevnar, Wyeth, Collegeville, PA, USA), the annual incidence of invasive pneu- 21Kosin University College of Medicine, Busan, Korea; 22Changwon Fatima Hospital, Changwon, Korea; mococcal disease (IPD) caused by the PCV7 serotypes decreased. However, replace- 23Chonbuk National University Medical School, Jeonju, ment by non-PCV7 serotypes has been observed, and pneumococcus has caused sig- Korea; 24Chonnam National University Medical School, Gwangju, Korea; 25University of Ulsan College of nificant morbidity despite the reduction of PCV7-type IPD. In 2010, a 13-valent conju- Medicine, Seoul, Korea; 26Korea Centers for Disease gate vaccine (PCV13, Prevnar-13, Pfizer, New York, NY, USA) replaced PCV7 for use Control and Prevention, Cheongju, Korea during routine immunization in children (2), and by June 2013, the incidence of IPD, Received: 2 October 2015 especially that caused by the PCV13 minus PCV7 serotypes, was further reduced across Accepted: 7 April 2016 all age groups in the USA (3). Address for Correspondence: In Korea, S. pneumoniae is the most common cause of invasive bacterial infections Hoan Jong Lee, MD Seoul National University College of Medicine, 101 Daehak-ro, in immunocompetent children aged 3 months to 5 years (4). PCV7 was first introduced Jongno-gu, Seoul 03080, Korea in Korea in November 2003 for optional use in the private sector, and the estimated E-mail: [email protected] PCV7 coverage rates among children aged 7-83 months increased from 44.8% to 73.8% Funding: This research was supported by a fund from the Research of Korea Centers for Disease Control and Prevention (Grant numbers; for the 3-dose infant series and from 31.3% to 50.8% for the toddler dose from 2006 to 2011E3200400, 2012E32004, and 2013E3200200). © 2016 The Korean Academy of Medical Sciences. pISSN 1011-8934 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. eISSN 1598-6357 Cho EY, et al. • Serotype Changes of Invasive Pneumococcal Isolates in Children 2010 (5). Although PCV7 was available as an optional immuni- additional serotypes: 1, 3, 5, 7F, and 19A. The non-PCV13 types zation, a multicenter study between 2006 and 2010 revealed a included all other serotypes (3,10). significant reduction in the proportion of PCV7 serotypes and a The serotype distribution was analyzed according to age, the significant increase in non-PCV7 serotypes (especially 19A) presence of comorbid disorders, clinical diagnosis, and outcome. isolated from children with IPD (6). In June 2010, the 10-valent Trend analysis was performed by year. pneumococcal conjugate vaccine (PCV10, Synflorix®; GlaxoS- mithKline, Brentford, London, UK) and PCV13 replaced PCV7 Statistical analysis in Korea. In May 2014, both PCV10 and PCV13 were included The statistical analyses were performed using SPSS software in the national immunization program for children under 60 version 22.0 (IBM, Armonk, NY, USA). The rates and propor- months of age. tions were appropriately compared using either the χ2 test or The purpose of this study was to analyze the early changes in Fisher’s exact test. For trend analysis, a linear-by-linear associa- the serotype distribution of pneumococcus isolated from Kore- tion model was used in addition to the Pearson χ2 test. A P value an children with invasive disease during the 3-year period fol- < 0.05 was considered statistically significant. lowing the introduction of the 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. Ethics statement This study protocol was approved by the institutional review MATERIALS AND METHODS board of Seoul National University Hospital (IRB No. 1106-015- 364) as well as each participating hospital. Informed consent Study design was confirmed by the IRB and was obtained from the patient From January 2011 to December 2013, twenty-five hospitals lo- and/or the guardian of the child. cated throughout Korea participated in this study. Children un- der 18 years of age with IPD were included in this study. IPD RESULTS was defined as the isolation of S. pneumoniae from a normally sterile body fluid (e.g., blood, cerebrospinal fluid, pleural fluid, Patient characteristics joint fluid, or ascites). A standardized case report form was used A total of 105 episodes of invasive pneumococcal infections was to collect information. The demographic data, comorbid disor- identified during the study period. Among these cases, 75 iso- ders, clinical diagnoses, and outcomes were collected. The co- lates (71.4% of the total) were collected from consenting partici- morbid disorders were classified according to the recommen- pants for inclusion in the study. The breakdown according to dations of the Advisory Committee on Immunization Practices year was as follows: 24 cases in 2011, 33 cases in 2012, and 18 (ACIP). In the current study, the following conditions were con- cases in 2013. sidered risk factors for pneumococcal infection: chronic heart The male-female ratio in the current study was 1.08:1 (39:36). disease, chronic lung disease, cerebrospinal fluid leaks, cochle- The percentage of patients separated by age group was 40.0% ar implants, functional or anatomic asplenia, and weakened (30 cases) aged 0-23 months, 42.7% (32 cases) aged 24-59 months, immunity secondary to chronic renal failure and nephrotic syn- and 17.3% (13 cases) aged ≥ 60 months. Twenty-four patients drome, the administration of immunosuppressive drugs, or con- (32%) were at increased risk of pneumococcal infection (10 pa- genital immunodeficiency (2). tients received immunosuppressive drugs, 4 had chronic heart disease, 3 had chronic renal failure or nephrotic syndrome, 2 Serotype determination had congenital immunodeficiency, 2 had cerebrospinal fluid A total of 75 pneumococcal isolates obtained from IPD patients leak, 2 had cochlear implants, and 1 had chronic lung disease). were prospectively collected and subjected to serotype deter- The clinical diagnoses were pneumonia (i.e., bacteremic pneu- mination.