Drastic reduction in pneumococcal meningitis in children owing to the introduction of pneumococcal conjugate vaccines: Longitudinal analysis from 2002 to 2016 in Japan

Introduction: The characteristics of pneumococcal isolates and their associations with outcomes in pediatric meningitis are unclear. This study aimed to clarify serotypes and resistance genotypes of Streptococcus pneumoniae from children with meningitis and evaluate the patient prognoses and backgrounds.Methods: Large-scale surveillance was conducted from 2002 to 2016 through periods I-V. Serotypes and penicillin (PEN) resistance genotypes were analyzed for pneumococcal isolates (n = 459) and cerebrospinal fluid (CSF) samples (n = 25). Furthermore, underlying diseases (n = 251), prognoses (n = 202), and laboratory data were evaluated.Results: The number of meningitis cases decreased drastically after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) to -53.6% and after switching to PCV13 to -70.2%. In particular, this reduction was apparent at <= 3 years of age. The proportion of the PCV7 serotype decreased sharply from 70.1% before introduction to 2.6% during period V; however, the non-vaccine type increased from 17.5% to 87.2%. The PEN resistance rate (gPRSP) was decreased from approximately 49% to 12.2% during period V. Among cases revealed prognosis, sequelae and mortality rates were 16.3% and 5.4%, respectively. The rate of the patients with underlying diseases was 26.3% and relatively high in >= 6 years. Laboratory data associated with a poor prognosis were low white blood cell count (<12.7 x 10(3)/mu L), low platelet count (<28.1 x 10(4)/mu L), low CSF-glucose (<36 mg/dL), and high CSF-protein (>= 142 mg/dL).Conclusions: Changes in serotype prevalence warrant continuous monitoring to observe future trends of pneumococcal meningitis, and further developments in multivalent conjugate vaccines are required. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.