1180. Comparing Changes in Pneumococcal Meningitis Incidence to all Invasive Pneumococcal Disease Following Introduction of PCV10 and PCV13: The PSERENADE Project

Background The introduction of higher valency pneumococcal conjugate vaccines (PCV10 and PCV13) has reduced invasive pneumococcal disease (IPD) incidence. It is unknown whether the degree of reduction differs for pneumococcal meningitis, a small subset of pneumococcal disease but a major cause of severe childhood morbidity and mortality globally. We compared the impact of PCV10/13 on pneumococcal meningitis and all IPD by estimating the changes in incidence following the introduction of PCV10/13 among children < 5 years of age. Methods Data on confirmed positive cases for pneumococcus in cerebrospinal fluid (CSF) were obtained directly from surveillance sites. PCV10/13 impact on all-serotype pneumococcal meningitis and all IPD were estimated using site-specific incidence rate ratios (IRRs) at each post-PCV10/13 year relative to the pre-PCV period, using Bayesian multi-level, mixed effects Poisson regression. All-site weighted average IRRs were estimated using linear mixed-effects regression. Results were stratified by product (PCV10 vs. PCV13) and amount of prior PCV7 use (none; some (1-3 years or 4-5 years with < 70% uptake); or many (≥ 4 years with ≥ 70% uptake). Results 40 surveillance sites (9 PCV10, 31 PCV13) in 28 countries, primarily high-income (82%) that had both CSF and IPD data were included in analyses. CSF+ accounted for 9.0% of IPD cases (IQR across sites: 6.2%-15.6%). The rate and amount of decline was generally similar between meningitis and IPD across all strata. At 5 years after PCV10/13 introduction, the IRRs across PCV7-use strata were 0.28-0.32 for pneumococcal meningitis and 0.22-0.43 for all IPD at PCV10-using sites, and 0.27-0.41 and 0.21-0.32, respectively, for PCV13-using sites. Only one site from the African meningitis belt contributed eligible data, which lacked pre-PCV data to estimate IRRs, but incidence rate of both IPD and meningitis decreased following PCV introduction. Figure 1. All-Site Weighted Average Incidence Rate Ratios, Children < 5 years * Total sites indicate the number of sites with incidence rate data included and pre/post sites indicate the number of sites with both pre− and post−PCV data to estimate site−specific IRRs for each outcome. The size of point estimates is relative to the number of sites with both pre− and post− data. ** Year 0 indicates the year of PCV10/13 introduction and year −1 indicates the last year of PCV7 use prior to PCV10/13 introduction. Conclusion Net declines in all-serotype IPD and CSF+ meningitis in children < 5 years were similar on average for both PCV10 and PCV13. Data from low-income, high-burden, and meningitis-belt regions were limited. Disclosures Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Clinical Features and Outcomes of Streptococcus pneumoniae Meningitis in Children: A Retrospective Analysis of 26 Cases in China

Background Streptococcus pneumoniae is an important cause of pediatric meningitis. Objective The aim of this study was to analyze the clinical features and outcomes of children with pneumococcal meningitis at our hospital in China, so as to provide basis for improving the clinical treatment effect. Methods This retrospective analysis included patients aged <16 years treated for pneumococcal meningitis at the Department of Neurology, Children's Hospital of Shanxi (January 2014–February 2016). Clinical data were extracted from the medical records. Patients were followed up for 6 months after discharge. Results The analysis included 26 children aged 2 months to 13 years, with 17 (65.4%) aged <3 years. Presenting symptoms included fever (100%), lethargy (100%), impaired consciousness (88.5%), neck stiffness (69.2%), seizures (53.8%), and headache (50.0%). All patients had positive cerebrospinal fluid (CSF) cultures. The final treatment was vancomycin combined with a third-generation cephalosporin or other antibiotics in 25 patients. Eleven patients (42.3%) were recovered, 3 (11.5%) had neurological sequelae, and 12 (46.2%) died. Impaired consciousness (p = 0.035), cerebral hernia (p = 0.037), respiratory failure (p = 0.004), heart failure (p = 0.044), septic shock (p = 0.037), low CSF white blood cell count (p = 0.036), high CSF protein levels (p = 0.028), low white blood cell count (p = 0.036), and low blood neutrophil ratio (p = 0.016) are associated with a poor prognosis to pneumococcal meningitis. Conclusion Pneumococcal meningitis is associated with a poor prognosis in many children. Poor prognosis might be related to early ineffective antibiotic therapy, a combination of systemic failure, neurological problems, and changed inflammatory response. It is important to rapid initiation of appropriate antibiotic therapy if meningitis is suspected.

Pneumococcal Meningitis in Adults in 2014-2018 After Introduction of Pediatric 13-valent Pneumococcal Conjugate Vaccine in Japan

We assessed the impact of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014-2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n=222) and without (n=1,258) meningitis. Pneumococcal meningitis annual incidence in 2016-2018 was 0.20–0.26 cases/100,000 population. Age (p<0.001) and case fatality rate (p=0.003) were significantly lower in patients with meningitis than in those without meningitis. Meningitis risk was higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27–4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10–5.06) or 23A (aOR 3.91, 95% CI 2.47–6.19), but lower for those aged ³65 years (aOR 0.59, 95% CI 0.44–0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- and ceftriaxone-resistant. We also confirmed association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51–5.65).

Silent Mastoiditis Associated with Pneumococcal Meningitis

Streptococcus pneumoniae (S pneumoniae) can cause a wide spectrum of diseases which includes upper respiratory tract infection as well as more severe invasive disease such as meningitis. Meningitis may be caused by invasion of the organism through the blood brain barrier, either via haematological spread or from an adjacent focus of infection such as the ears. We describe two infants with pneumococcal meningitis and silent mastoiditis. They both presented with a classical history to suggest meningitis with no apparent focus of infection. A brain imaging was done in the first infant to look for the underlying cause of his focal seizure and in the second infant, to assess for complications of meningitis, as he had a slow recovery. While they did not have any clinical signs to point towards the diagnosis, they were both diagnosed to have acute mastoiditis from brain imaging. We would like to highlight the importance of brain imaging in excluding silent mastoiditis in infants with meningitis, particularly in those whose clinical course appears atypical.