Evaluation of the impact of 13-valent pneumococcal conjugate vaccine immunization in children by surveillance of culture-confirmed pneumococcal disease: A prospective clinical microbiological study
Introduction
Streptococcus pneumoniae is the leading cause of pneumonia, otitis media, bacteremia, and meningitis in children. S. pneumoniae causes more than 1.2 million infant deaths worldwide every year [1], [2]. Heptavalent pneumococcal conjugate vaccine (PCV7) had significantly reduced the incidence of diseases caused by these vaccine serotypes after its licensure in 2000 [3]. However, non-vaccine serotypes (NVTs) have increased in a process called “serotype replacement” [4]. The increase in non-PCV7 serotypes, most notably caused by serotype 19A, was reported in several countries [5], [6]. In Taiwan, 10-valent (PCV10) and 13-valent (PCV13) vaccines were licensed in 2009 and 2010, respectively, for broader serotype protection.
In Taiwan, different from other countries, children aged 2–4 years had the highest incidence of IPD [7], [8]. PCV13 was introduced into Taiwan initially in the private sector. In 2011, the government provided PCV13 free of charge to children aged <5 years with underlying diseases, with low socioeconomic status, and who lived in areas with poor health care resources. In 2012, this was extended to those with middle socioeconomic status and those with muscular atrophy [9]. PCV13 catch-up immunization program was implemented to children aged 2–5 years in March 2013 and extended to children aged 1–5 years in January 2014. PCV13 immunization was integrated into the national immunization program in January 2015 with a three-dose schedule for infants at 2, 4, and 12 months of age.
The overall incidence of pneumococcal diseases was underestimated as most of the surveillance systems measured the incidence of IPD. Surveillance of culture-confirmed pneumococcal disease (CCPD) may provide a more comprehensive picture on the impact of PCV13 immunization than IPD. Therefore, the present study aimed to investigate the impact of such immunization program in Taiwan by prospective surveillance of pneumococcal serotypes, sequence types, and antibiotic susceptibility of pneumococcal isolates in children.
Section snippets
Study design
This study was approved by the institutional review board in Chang Gung Memorial Hospital (CGMH) (IRB number: 201801007B0). We collected all clinical isolates of Streptococcus pneumoniae from pediatric patients <18 years of age at CGMH, Linkou, Taoyuan from 2012 to 2016. CGMH in Taoyuan is a main referral hospital for cities in northern Taiwan, including branches in Taipei, New Taipei, and Taoyuan. The population in this region is approximately 7 million. The annual incidence of CCPD was
Culture-confirmed pneumococcal disease
Initially 509 isolates of S. pneumoniae were identified from pediatric patients. Thirty-five isolates were considered as colonizing isolates as those patients had no clinical evidence of bacterial infections and hence were excluded. A total of 473 patients with CCPD, including 58 with IPD and 415 with NIPD, were further analyzed. The number of CCPD patients decreased from 152 in 2012 to 60 in 2016 (Fig. 1). The numbers of annual pediatric admissions were stable during 2012–2016. In this
Discussion
Methods to evaluate the impact of pneumococcal immunization on overall pneumococcal disease should incorporate available evidence from all pneumococcal diseases instead of focusing solely on IPD. Although IPD surveillance was still essential, NIPD was more prevalent in both inpatient and outpatient departments. Most of vaccine effectiveness studies only focused on IPD. Therefore, the overall cost-effectiveness and socioeconomic impact of pneumococcal immunization were underestimated. In this
Conclusions
A unique immunization program was effective in reducing the incidence of CCPD in Taiwan. The decrease was mainly attributed to the reduction in the incidence of NIPD caused by additional PCV13 serotypes, especially 19A. A slight increase in the incidence of NVTs was observed in patients with CCPDs but that was not considered statistically significant. Emerging NVTs, such as serotypes 15B, 15A, and 23A, constituted the second, third, and fourth most common serotypes, respectively, to cause CCPD
Author contributions
CHC, LHS, TLW, and KCK facilitated data acquisition and interpretation, drafting, and revision of the manuscript; CHC, LHS, CCH, and CHC facilitated conception and design of the study, data acquisition and interpretation, and drafting and revision of the manuscript. HCL, MHH, and CLC carried out experiments and contributed to data acquisition and interpretation. All authors provided final approval of the manuscript and agree to be accountable for the accuracy and integrity of this work.
Funding
The study was supported by grants from Chang Gung Memorial Hospital (CMRPG3H0041, CMRPG3G1971, CMRP3F1143, and CRRPG3F0083) and Ministry of Science and Technology (105-3011-F-182A-001), Taiwan.
Declaration of Competing Interest
None.
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