applyparastyle “fig//caption/p[1]” parastyle “FigCapt” Clinical Infectious Diseases MAJOR ARTICLE Successful Control of Streptococcus pneumoniae 19A Replacement With a Catch-up Primary Vaccination Program in Taiwan Chun-Yi Lu,1,a Chuen-Sheue Chiang,2,3,a Cheng-Hsun Chiu,4,5, En-Tzu Wang,2 Ying-Yan Chen,2 Shu-Man Yao,2 Luan-Yin Chang,1 Li-Min Huang,1 Tzou-Yien Lin,4,5,b and Jih-Haw Chou2,b 1Department of Pediatrics, National Taiwan University Children’s Hospital, 2Centers for Disease Control, Ministry of Health and Welfare, and 3School of Nursing, National Taipei University of Downloaded from https://academic.oup.com/cid/article-abstract/69/9/1581/5421736 by guest on 16 October 2019 Nursing and Health Sciences, and 4Department of Pediatrics, Chang Gung Memorial Hospital, and 5College of Medicine, Chang Gung University, Taoyuan City, Taiwan Background. Streptococcus pneumoniae infections in Taiwan mostly occur in children aged 2–4 years. Because of a significant increase in the incidence of serotype 19A-related infections, the 13-valent pneumococcal conjugate vaccine (PCV13) was initially introduced in the national immunization program for children 2–5 years of age, prior to the national programs for infants. We have assessed the impact of such vaccination programs in reducing the incidence of invasive pneumococcal disease (IPD) in Taiwanese children. Methods. We analyzed the national data on IPDs from the Taiwan Centers for Disease Control between 2008 and 2017. We cal- culated the incidence rates of IPD and incidence rate ratios (IRRs) between years for different serotypes to estimate the effectiveness of the vaccination programs. Results. The national catch-up primary vaccination schedule successfully reduced the incidence rate of IPD from 17.8/100 000 in 2012 to 5.5/100 000 in 2017 among children aged 0–5 years. The IRR (2017 over 2012) was 0.31, corresponding to a 69% reduc- tion. A modest herd effect was also observed, with a 37% reduction in the incidence of IPD in elderly people (≥70 years) from 2012 to 2017. The incidence of IPD caused by serotype 19A in children aged 0–5 years was reduced by 32.6–44.3% yearly from 2012 to 2017. In 2015, serogroup 15 outnumbered 19A, to become the leading serotypes in children 0–5 years old. Conclusions. Special catch-up vaccination programs starting from children 2–5 years of age with PCV13 have been highly effec- tive in reducing the incidence of IPD, especially as caused by serotype 19A, in Taiwanese children. Keywords. 19A; invasive pneumococcal diseases; PCV13; vaccination; Taiwan. The introduction of the 7-valent pneumococcal conjugate vac- to cope with the serotype replacement, and their use has fur- cine (PCV7) in 2000 in the United States resulted in a dramatic ther reduced the disease burden in children in many parts of and sustained decrease in the incidence of invasive pneumo- the world [4, 5]. coccal disease (IPD) in children, specifically as caused by the Taiwan introduced PCV7 in 2006. In the first few years, it was serotypes included in the PCV7. However, IPD caused by the used only in the private sectors, with low vaccination coverage. non-PCV7 serotypes increased at the same time [1], by a phe- The cumulative coverage rate of at least 1 dose of PCV7 among nomenon called serotype replacement. The predominant post- children aged <5 years increased from 0.2–0.7% in 2005 to 25.2– PCV7 serotype causing IPD in children was 19A [2]. However, 26.9% in 2008 [6, 7], and to about 45.5% in 2010 [6]. In 2009, the increase in the incidence of infections caused by 19A or the government of Taiwan implemented the first public-funded, other non-PCV7 serotypes following PCV7 varied among national PCV vaccination program, targeting high-risk children populations and was modest in absolute numbers [3]. Higher- aged <5 years. PCV10 replaced PCV7 for the high-risk groups valent PCVs—namely, PCV10 and PCV13—were introduced in 2010. During this time of partial and increasing vaccination coverage with PCV7 and PCV10, the proportion of IPDs caused by serotype 19A in children aged 2–4 years increased almost Received 17 August 2018; editorial decision 16 December 2018; accepted 15 February 2019; 4-fold, from 16.7% in 2008 to 66.7% in 2012 [8]. The magnitude published online March 28, 2019. and speed at which serotype 19A replacement occurred after a C.-Y. L. and C.-S. C. contributed equally to this manuscript. the introduction of PCV7 in Taiwan were among the highest bT.-Y. L. and J.-H. C. contributed equally to this manuscript. Correspondence: T.-Y. Lin, Department of Pediatrics, Chang Gung Memorial Hospital, No.5-7, in the world [9]. There were many children aged 2–4 years who Fu-Hsin Street, Kweishan 333, Taoyuan, Taiwan ([email protected]). suffered from severe pneumococcal pneumonia with empyema Clinical Infectious Diseases® 2019;69(9):1581–7 [10, 11]. Compared to the non-19A serotypes, IPD caused by © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]. the 19A serotype tends to result in more complicated pneu- DOI: 10.1093/cid/ciy1127 monia with empyema [12]. Such a major replacement of the PCV13 Catch-up Vaccination in Taiwan • CID 2019:69 (1 November) • 1581 invasive 19A pneumococcal infection prompted the introduc- Taiwan since October 2007 [14]. Since then, reporting of IPD tion of the PCV13 in 2011, which replaced PCV10 for high-risk cases has been required by law, including submitting the clin- groups in 2012. The history of PCV introduction in the private ical information through the National Notifiable Disease market and the implementation of vaccination programs in Surveillance System and sending S. pneumoniae isolates to Taiwan has been illustrated in Figure 1. the TCDC. Capsular serotypes of S. pneumoniae were deter- Another unique feature of the IPD epidemiology in Taiwan mined by Quellung reactions in a TCDC Central Laboratory. was the age distribution. While the incidence of IPD worldwide All IPD data collected by the TCDC were used for this anal- is highest among children aged <2 years [13], in Taiwan it is ysis. Pneumococcal diseases diagnosed by non-culture meth- highest among children aged 2–4 years [8], and the underly- ods, including polymerase chain reaction, urinary antigen ing cause for this difference is not fully understood. In many testing, Gram stain results, or clinical diagnoses, were not in- children of this age who suffered from lobar pneumonia com- cluded in this analysis. Statistics on populations of different plicated with empyema, the causative agent was Streptococcus age groups were obtained from the website of the Department Downloaded from https://academic.oup.com/cid/article-abstract/69/9/1581/5421736 by guest on 16 October 2019 pneumoniae [10]. of Household Registration, Ministry of the Interior, Taiwan To address this situation, in 2013, the Taiwan Centers for (http://www.ris.gov.tw). Disease Control (TCDC) decided to start with a vaccination program of a single-dose PCV13 for children 2 to 5 years of age, Pneumococcal Vaccination Program for Children in Taiwan without primary infant pneumococcal vaccination programs Pneumococcal conjugate vaccines have been available in Taiwan (Figure 1). The current study aims to assess the long-term since 2006, but became available through public funds in 2009. impact of the vaccination programs from 2013–2017 on the PCV7 and PCV10 were recommended by the government of prevention of IPD in children, in a country where a significant Taiwan for high-risk children in 2009 and 2010, respectively. In replacement of serotype 19A had taken place. response to the high incidence of serotype 19A–related pneu- mococcal infections, in 2013, a single dose of PCV13 was pro- vided free of charge to children 2 to 5 years of age. This was MATERIAL AND METHODS followed by an expansion of the National Program to provide National Invasive Pneumococcal Disease Surveillance Data vaccinations for children between 12 and 24 months of age in IPD, an illness during which S. pneumoniae was isolated from 2014 with 2 doses of PCV13 and the universal vaccination for at least 1 normally sterile site, became a notifiable disease in all infants in 2015. The vaccination coverage rates increased Figure 1. History of the introduction of the PCV in the private market and the implementation of national PCV vaccination programs in Taiwan. Abbreviations: IPD, invasive pneumococcal disease; NIP, national immunization program; PCV, pneumococcal conjugate vaccine. 1582 • CID 2019:69 (1 November) • Lu et al from 48.9% in 2013 to 77.9% in 2014 [5]. Since 2015, the rec- Impact of National Pneumococcal Conjugate Vaccine Immunization Program in Taiwan ommended dose of PCV13 has included 2 primary doses at 2 and 4 months of age, followed by a booster between 12 and To assess the trends in IPD incidence, especially after the 15 months of age (2 + 1 program). After 2015, the vaccination implementation of the PCV13 vaccination programs in 2013, coverage rates were 60.9% for the primary series and 80.8% for the incidence rates from 2008–2017 were analyzed in 4 groups, the catch-up series [5]. based on the years as shown in Figure 2. The overall incidence in children aged 0–5 years rose from 13.7/100 000 in 2008–2009 Statistical Analysis to 18.9/100 000 in 2010–12, then decreased continuously to Annual incidence rates based on age groups were obtained by 9.4/100 000 in 2013–2014 and 6.3/100 000 in 2015–2017.