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Objectives: This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis., Methods: Data have been prospectively collected for the period1977-2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5-1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin., Results: In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone ( p  = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone ( p  = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone ( p  = 0.000)., Conclusions: A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.

Objective: To characterize the institutional utilization of pneumococcal vaccination during an index hospital admission for acute cerebrospinal fluid (CSF) leakage and associated infectious and clinical outcomes., Methods: This retrospective cohort study included patients hospitalized and treated for an acute CSF leak from January 2017 to June 2022. The primary outcome evaluated the incidence of pneumococcal vaccination during the index admission in patients without prior vaccination. Secondary outcomes evaluated the incidence of meningitis, time from CSF leak identification to meningitis, and mortality within 1 year of the index admission., Results: A total of 94 patients were included. Nineteen (20.2%) patients received pneumococcal vaccination prior to admission. Of the 75 patients without prior vaccination, 4 (5.3%) patients received vaccination during the admission. Meningitis occurred in 5/94 (5.3%) patients and occurred 4-24 days from CSF leak identification. Mortality was observed in 9/94 (9.6%) patients. None of the meningitis cases were attributed to culture-positive findings of pneumococcal disease., Conclusions: The results of this study demonstrate an overall low institutional utilization of pneumococcal vaccination in patients with an acute CSF leak. Infectious and clinical outcomes reflected comparable to previous reported literature. Further evaluation into the risk-benefit relationship of vaccination omission is warranted in this patient population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pneumococcal meningitis, a vaccine-preventable disease caused by Streptococcus pneumoniae (Spn) is the leading bacterial meningitis in under five children. In April 2014, Uganda introduced routine immunization with 10-valent Pneumococcal Conjugate Vaccine (PCV10) for infants. The target coverage for herd immunity is ≥ 90% with three doses (PCV10-dose 3). We assessed the effect of PCV10 introduction and coverage on the trends of pneumococcal meningitis in under five children., Methods: We analyzed laboratory-confirmed pediatric bacterial meningitis (PBM) data at two high-volume WHO-accredited sentinel surveillance hospitals in Kampala City and Gulu District, from 2003 to 2022. We used confirmed cases to estimate the minimum incidence of pneumococcal meningitis in the host districts and calculated annual incidence of pneumococcal meningitis per one million populations, and the proportion of confirmed PBM attributable to Spn. We divided the study period into 2003-2013 (pre-PCV10) and 2014-2022 (post-PCV10), and conducted interrupted time series analysis using autoregressive integrated moving average models for the effect of PCV10 on trends of pneumococcal meningitis and PBM attributable to Spn. We analyzed reported PCV10 data in DHIS2 from 2014 to 2022 for annual PCV10-dose 3 coverage., Results: Among the 534 confirmed PBM cases, 331(62%) were pneumococcal meningitis; 227(69%) from Gulu District and 104(31%) from Kampala City. The majority (95%) of the isolates were not serotyped. The majority (57%) were male and unimmunized (98%); median age = 14(IQR = 6-27) months with most (55%) aged ≥ 12 months. The case-fatality rate was 9%. During Pre-PCV10 period, the overall incidence of pneumococcal meningitis in the host districts increased; slope change = 1.0 (95%CI = 0.99999, 1.00001) but declined in post-PCV10 period (2014-2022) by 92% from 86 cases /1,000,000 in 2014 to 7/1,000,000 in 2022, slope change= -1.00006 (95%CI=-1.00033, -0.99979). Whereas there was an immediate decline in the proportion of confirmed PBM attributable to Spn in the host districts, level change=-1.84611(95%CI=-1.98365,-1.70856), an upward trend was recorded from 2016 to 2022, slope change = 1.0 (95%CI = 0.99997, 1.00003). During 2015-2022, PCV10-dose 3 coverage was largely > 90% for Gulu District and 52-72% for Kampala City., Conclusion: The PCV10 routine immunization program reduced the incidence of pneumococcal meningitis in Kampala City and Gulu District. There was no effect on the confirmed PBM proportionately attributable to Spn. Kampala City persistently recorded PCV10-dose3 coverage < 90%. We recommend enhancing serotyping and periodic nasopharyngeal carriage surveys to ascertain the maximum vaccine effectiveness and monitor Spn serotypes, and strengthening routine immunization in Kampala City., (© 2024. The Author(s).)

Introduction: Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal but not pneumococcal meningitis. Mathematical modelling is a useful tool for assessing the potential impact of different pneumococcal control strategies. This work aimed to estimate the impact of reactive vaccination with pneumococcal conjugate vaccine (PCV) had it been implemented in past African meningitis belt outbreaks and assess their efficiency relative to existing routine infant immunisation with PCV., Methods & Results: Using recent pneumococcal meningitis outbreaks in Burkina Faso, Chad, and Ghana as case studies, we investigated the potential impact of reactive vaccination. We calculated the number needed to vaccinate to avert one case (NNV) in each outbreak setting and over all outbreaks and compared this to the NNV for existing routine infant vaccination. We extended previous analyses of reactive vaccination by considering longer-term protection in vaccinees over five years, incorporating a proxy for indirect effects. We found that implementing reactive vaccination in previous pneumococcal meningitis outbreaks could have averted up to 10-20 % of outbreak cases, with the biggest potential impact in Brong Ahafo, Ghana (2015-2016) and Goundi, Chad (2009). The NNV, and hence the value of reactive vaccination, varied greatly. 'Large' (80 + cumulative modelled cases per 100,000 population) and/or 'prolonged' (exceeding a response threshold of 10 suspected cases per 100,000 per week for four weeks or more) outbreaks had NNV estimates under 10,000. For routine infant vaccination with PCV, the estimated NNV ranged from 3,100-5,600 in Burkina Faso and 1,500-2,600 in Ghana., Implications: This analysis provides evidence to inform the design of pneumococcal meningitis outbreak response guidelines. Countries should consider reactive vaccination in each outbreak event, together with maintaining routine infant vaccination as the primary intervention to reduce pneumococcal disease burden and outbreak risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic., Objective: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden., Methods: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis., Results: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025., Conclusions: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide., Trial Registration: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m., International Registered Report Identifier (irrid): DERR1-10.2196/50678., (©Jay J Park, Jakov Tiefenbach, Mohammed Ma'arij Anwar, Sandhya Narayanan, Beatrice Ope, Selene Seo Bin Han, Boni Maxime Ale, Davies Adeloye, Igor Rudan. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 16.07.2024.)

Introduction: Streptococcus pneumoniae, is associated with the highest incidence of post-meningitic SNHL. The exact impact of 13-valent pneumococcal conjugate vaccine (PCV) on pediatric SNHL from pneumococcal meningitis is unknown. We aimed to identify clinical factors associated with post-meningitic SNHL (pmSNHL) from pneumococcal meningitis and describe its rates based on three time periods: pre-PCV, PCV-7 and PCV13 eras., Methods: A retrospective case-control study was performed for patients 18 years and younger diagnosed with pneumococcal meningitis from January 1, 2010 to December 31, 2020 at Children's Hospital Colorado. Demographic and clinical risk factors between those with or without SNHL were compared. Detailed hearing outcomes of those with resulting SNHL are described., Results: 23 patients with CSF cultures or Meningitis/Encephalitis Panel positive for pneumococcal meningitis were identified. Twenty patients both survived the infection and had audiologic evaluation. Six patients had pmSNHL, with 50 % affected bilaterally. The rate of pmSNHL from S. pneumoniae in the PCV-13 era at our institution was similar to historical rates from the pre-PCV and PCV-7 eras. Similar proportions of patients with pmSNHL completed PCV vaccination (66.7 %) compared to those without (71.4 %). Non-PCV-13 serotypes were responsible 83 % of patients with pmSNHL versus 57 % of patients without pmSNHL., Conclusions: Despite high rates of PCV-13 uptake in our cohort, pmSNHL was still common, severe, and commonly associated with non-PCV-13 serotypes. Non-PCV-13 serotypes may be contributing to the persistently high rate of post-meningitic SNHL and the severity of SNHL. Newer pneumococcal conjugate vaccines with expanded serotypes may help mitigate the SNHL associated with pneumococcal meningitis., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: As Greece is a country which has introduced the 13-valent pneumococcal conjugate vaccine (PCV13) both in the infant and in the adult immunization programs, the aim of the study was to investigate age-specific and serotype-specific trends of pneumococcal meningitis over an 11-year period (2010-2020)., Materials and Methods: Data are reported from pneumococcal meningitis cases [notified to the National Public Health Organization (NPHO)], with clinical samples and bacterial isolates sent for pneumococcal identification and serotyping at the National Meningitis Reference Laboratory (NMRL). Pneumococcal identification was performed directly on clinical samples or bacterial isolates by multiplex PCR (mPCR) assay, while serotyping was carried out by application of the Capsular Sequence Typing (CST) method with the combination of single tube PCR assays., Results: A total of 427 pneumococcal meningitis cases were notified to the NPHO between 2010 and 2020. Among those, 405 (94.8%) were microbiologically confirmed, while samples from 273 patients were sent to the NMRL for identification and/or further typing. The annual notification rate peaked at 0.47/100,000 in 2016 and since then has been decreasing. The incidence was highest in infants and in older adults. Pneumococcal serotypes were identified in 260/273 (95.2%) cases, where clinical samples were sent to the NMRL. The most prevalent serotypes (≥5%) were 3, 19A, 23B, 15B/C, 11A/D, 23A, 22F. During the study period there has been a decrease of PCV13 serotypes combined with an increase of non-PCV13 serotypes (p = 0.0045)., Conclusions: This is the first study to report serotypes for pneumococcal meningitis across all ages in the post-PCV13 era in Greece. There is a need to enhance surveillance, by close monitoring of the emerging serotypes and the impact of vaccination programs. Higher-valency PCVs may help to improve the coverage of pneumococcal disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Streptococcus pneumoniae is one of the leading causes of meningitis in children. In Japan, since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), the number of pneumococcal meningitis due to non-PCV13 serotypes in children has increased. To clarify the clinical outcomes, serotype distributions, and antimicrobial susceptibility of isolated S. pneumoniae strains from pediatric pneumococcal meningitis, we clinically and bacteriologically analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the PCV13 introduction era in Japan. The median age at diagnosis was 1 year (range: 3 months-13 years). Ten (29.4%) patients had underlying diseases. Twenty-nine (85.3%) patients had received at least one dose of any pneumococcal vaccine. Of the 34 patients with pneumococcal meningitis, 6 had sequelae, and 4 died. Nine (26.5%) strains were resistant to penicillin; five (15%) strains to meropenem, with an MIC of 0.5 μg/mL. All strains were susceptible to vancomycin and linezolid. Daptomycin's MIC 50 was 0.064 μg/mL and MIC 90 was 0.094 μg/mL. Among the tested strains, only four were PCV13 serotypes. Penicillin-resistant S. pneumoniae was isolated from 30.0% of the patients with sequelae and death. Particularly, the proportion of serotype 10A in the sequelae and deceased cases was significantly higher than that in the complete recovery cases. We should carefully monitor the serotype and drug susceptibility of S. pneumoniae strains isolated from patients with meningitis after the PCV13 era and reconsider the treatment strategy to prepare against further drug-resistant pneumococcal strains. IMPORTANCE We analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction era in Japan. Our study revealed that pneumococcal meningitis in children was mainly caused by non-PCV13 serotypes; all cases with sequelae and death were caused by non-PCV13 serotypes. Moreover, all serotypes of penicillin resistant Streptococcus pneumoniae strains (26.5%; 9/34) were non-PCV13 serotypes. We also analyzed antimicrobial susceptibilities of glycopeptides, linezolid (LZD), and daptomycin (DAP) of isolated S. pneumoniae strains. All tested strains were susceptible to vancomycin, teicoplanin, LZD, and DAP. Especially. DAP demonstrated the best outcome among the tested antibiotics, with MIC 90 of 0.094 μg/mL. Pneumococcal meningitis in children continues to persist and is difficult to control with the current conjugate vaccines. Therefore, it is important to monitor the serotype and antimicrobial susceptibility of S. pneumoniae strains isolated from patients with meningitis and accordingly reconsider the treatment strategy.

Background: The epidemiology and treatment of pneumococcal meningitis has changed with the implementation of conjugate vaccines and the introduction of adjunctive dexamethasone therapy., Methods: We analyzed episodes of community-acquired pneumococcal meningitis in adults (≥16 years) in the Netherlands, identified by the National Reference Laboratory for Bacterial Meningitis or treating physician between October 1, 1998, and April 1, 2002, and between January 1, 2006, and July 1, 2018. We studied incidence, pneumococcal serotypes, and clinical features. Predictors for unfavorable outcome (Glasgow Outcome Scale score 1-4) were identified in a multivariable logistic regression model. Two physicians independently categorized causes of death as neurological or systemic., Results: There were 1816 episodes in 1783 patients. The incidence of 7- and 10-7-valent pneumococcal conjugate vaccine serotypes decreased (from 0.42 to 0.06, P = .001; from 0.12 to 0.03 episodes per 100 000 population per year, P = .014). Incidence of nonvaccine serotypes increased (from 0.45 to 0.68, P = .005). The use of adjunctive treatment with dexamethasone increased and was administered in 85% of patients in 2018. In-hospital death occurred in 363 episodes (20%) and unfavorable outcome in 772 episodes (43%). Delayed cerebral thrombosis occurred in 29 patients (2%), of whom 15 patients (52%) died. Adjunctive dexamethasone therapy was associated with favorable outcome (adjusted odds ratio 2.27, P < .001), individual pneumococcal serotypes were not., Conclusion: Implementation of conjugate vaccines and adjunctive dexamethasone therapy have changed the incidence and outcome of pneumococcal meningitis in adults over the last two decades. Despite recent advances pneumococcal meningitis remains associated with a residual high rate of mortality and morbidity., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: The aims of the study were to analyze the demographics, presentation, laboratory findings, and complications of pediatric Streptococcus pneumoniae meningitis since the introduction of the 13-valent pneumococcal conjugate vaccine, to improve recognition, and to minimize patient morbidity and mortality., Methods: This study used a retrospective analysis of pediatric pneumococcal meningitis cases at 2 tertiary healthcare systems in the Southeastern United States from 2010 to 2018., Results: We describe 21 cases of pneumococcal meningitis. All patients presented with fever, 95% had altered mental status by history or examination, and 48% had meningeal signs. Forty-three percent had seen another provider within 48 hours of admission. Forty-eight percent had delay in lumbar puncture (LP) of more than 6 hours after antibiotic administration, decreasing rates of positive cerebrospinal fluid cultures from 100% to 40% (P < 0.001). Decision to delay LP was due to either low suspicion for meningitis (n = 4) or clinical instability (n = 6) and was associated with lower rates of meningeal signs (P = 0.014) and higher rates of altered mental status on examination (P = 0.031). Fourteen patients (67%) were up-to-date on pneumococcal immunization. Serotypes were determined in 16 cases, with 2 patients (13%) immunized against the strain that infected them. Primary outcomes included seizures (48%), hearing loss (48%), cranial nerve palsy (33%), and death (5%). Delay in LP with low suspicion for meningitis was associated with longer hospital length of stay approaching statistical significance (P = 0.053)., Conclusions: Pneumococcal meningitis remains a relevant and potentially fatal disease despite widespread use of 13-valent pneumococcal conjugate vaccine. Its diagnosis is often delayed during interactions with physicians, which may put patients at increased risk for poor clinical outcomes., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The 10-valent conjugate vaccine (PCV10) was introduced into the Extended Program on Immunization in Madagascar. We assessed the impact of PCV10 on the targeted pneumococcal serotypes among children < 5 years of age at Centre Hospitalier Universitaire Mère Enfant Tsaralalàna., Method: Between 2012 and December 2018, cerebrospinal fluid (CSF) samples were collected and tested for S. pneumoniae by culture, and antigen tests. The Sentinel Site Laboratory (SSL) referred available CSF samples to the Regional Reference Laboratory (RRL) for real-time polymerase chain reaction confirmatory testing and serotyping., Results: In total, 3616 CSF specimens were collected. The SSL referred 2716 to the RRL; 125 were positive for S. pneumoniae. At the RRL, 115 samples that tested positive for S. pneumoniae were serotyped; PCV10 serotypes accounted for 20%. Compared to the pre-PCV period, the proportion of S. pneumoniae detected declined from 22% to 6.6%, (P < .05), the proportion of PCV10 serotypes as the cause of pneumococcal meningitis cases declined by 26% following vaccine introduction., Conclusions: In our findings, PCV10 introduction resulted in a decline of meningitis caused by S. pneumoniae and PCV10 vaccine serotypes., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Despite the availability of vaccines, invasive bacterial diseases remain a public health concern and cause childhood morbidity and mortality. We investigated the characteristics of etiological agents causing bacterial meningitis in children <5 years in the years pre- (2010-2012) and post- (2014-2019) 10-valent pneumococcal conjugate vaccine (PCV10) introduction in Zambia., Methods: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hi), and Neisseria meningitidis (Nm) from cerebrospinal fluid (CSF) were identified by microbiological culture and/or real-time polymerase chain reaction., Results: During the surveillance period, a total of 3811 children were admitted with suspected meningitis, 16% (598 of 3811) of which were probable cases. Bacterial meningitis was confirmed in 37% (221 of 598) of the probable cases. Spn pneumoniae, Hi, and Nm accounted for 67% (148 of 221), 14% (31 of 221), and 19% (42 of 221) of confirmed cases, respectively. Thirty-six percent of pneumococcal meningitis was caused by 10-valent pneumococcal conjugate vaccine (PCV10) serotypes, 16% 13-valent pneumococcal conjugate vaccine and 39% by nonvaccine serotype (NVS). There was an association between the introduction of PCV10 vaccination and a decrease in both Spn meningitis and the proportion of PVC10 serotypes in the postvaccination period. Antimicrobial susceptibility of 47 Spn isolates revealed 34% (16 of 47) penicillin resistance. The 31 serotyped Hi accounted for 74% type b (Hib) and 10% type a (Hia). All 42 serogrouped Nm belonged to serogroup W., Conclusions: There was a decline in pneumococcal meningitis and proportion of PCV10 serotypes in the postvaccination period. However, the serotype replacement with non-PCV10 serotypes and penicillin resistance warrant continued surveillance to inform policy., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis., Methods: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies., Results: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region., Conclusions: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Streptococcus pneumoniae is an important pathogen responsible for severe pneumococcal diseases, including pneumonia, bacteraemia/sepsis, and meningitis. Inflammatory bowel disease [IBD] patients have an increased risk for infections due to an altered immune system and treatment with immunosuppressive medications. The aim of this study was to assess the prevalence of severe pneumococcal disease [SPD] and evaluate the impact of pneumococcal vaccination on the risk of SPD in Veterans with IBD., Methods: Subjects with IBD and SPD were identified from the VA Health Administration database using ICD9/10 codes. Pneumococcal vaccination and use of immunosuppressant medications were collected. Risk of SPD was evaluated using an adjusted Cox proportional hazards model controlling for demographics, medications, vaccination, and comorbidities., Results: A total of 1798 cases of SPD were identified [283 pneumonia, 1513 bacteraemia, and two meningitis]. SPD patients were older [60.9 years vs 59.4 years; p <0.001], had more comorbidities [Charlson Comorbidity Index of 2.11 vs 0.96; p <0.001], and had increased mortality [4.6% vs 1.5%, p <0.001]. The risk of SPD was increased in Crohn's disease (hazard ratio [HR] 1.15; 95% confidence interval [CI] 1.05-1.27) and with more comorbidities [HR 1.45; 95% CI 1.42-1.48]. Use of immunosuppressive medications increased the risk of SPD. Receipt of PCV13 either alone or in combination with PPSV23 predicted a 5-fold decreased risk of SPD compared with no vaccination., Conclusions: Risk factors for severe pneumococcal disease include having Crohn's disease, more comorbidities, and exposure to combination immunosuppression. Vaccination with PCV13 alone or in combination with PPSV23 and revaccination with PPSV23, was protective against SPD. All IBD patients should be evaluated for pneumococcal vaccination, particularly those receiving or expected to receive immunosuppressive therapies., (Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation (ECCO) 2021.)

Background: Ghana introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunization program in 2012, using a three-dose primary series without a booster. Despite ≥ 88% reported three-dose vaccination coverage since 2013, PCV13-type pneumococcal meningitis outbreaks have occurred. We estimated the ongoing economic burden of PCV13-type pneumococcal meningitis and pneumonia in northern Ghana, an area within the African meningitis belt with seasonal increases of pneumococcal meningitis post-PCV13 introduction, to inform PCV13 vaccination policy., Methods: We performed a cross-sectional survey among patients with pneumonia or meningitis at three hospitals in northern Ghana to determine patient-level costs (direct medical and nonmedical, indirect patient and caregiver costs) incurred in household, outpatient, and inpatient settings. Pneumonia burden was estimated using 2017-2018 administrative records. Pneumococcal meningitis burden was estimated using 2017-2018 case-based surveillance data. Economic burden was reported in 2019 U.S. dollars ($) from the societal perspective., Results: For an area with a total population of 5,068,521, our model estimated 6,441 PCV13-type pneumonia cases and 286 PCV13-type meningitis cases occurred in a typical year post-PCV13. In the base case scenario, the total economic burden was $5,230,035 per year ($777 per case). By age group, cost per PCV13-type pneumonia case was $423 (<5 years), $911 (5-14 years), and $784 (≥15 years); cost per PCV13-type meningitis case was $2,128 (<5 years), $3,247 (5-14 years), and $2,883 (≥15 years). Most (78.0-93.4%) of the total societal cost was due to indirect costs related to deaths from PCV13-type diseases., Conclusions: The estimated economic burden of PCV13-type disease in northern Ghana remains substantial, especially in older children and adults who were expected to have benefited from indirect effects from infant immunization. Additional interventions such as changes in the infant immunization schedule, reactive vaccination, or catch-up PCV13 vaccination may be needed to control remaining vaccine-type disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185  S . pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % ( n =6) in the post-PCV introduction period compared to 21.9 % ( n =14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % ( n =17), compared to the pre-PCV period in neighbouring Senegal, 51 % ( n =27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.

Background: No previous studies have reported long-term follow-up of ten-valent pneumococcal conjugate vaccine (PCV10) program impact on pneumococcal meningitis (PM). We assessed the effects of infant PCV10 program on PM incidence, mortality and serotype distribution in children and adults during 7 years after introduction., Methods: We conducted a population-based observational study. A case of PM was defined as isolation of Streptococcus pneumoniae from cerebrospinal fluid or, a patient with S. pneumoniae isolated from blood and an ICD-10 hospital discharge diagnosis of bacterial meningitis within 30 days before or after positive culture date.We compared age- and serotype-specific incidence and associated 30-day mortality rates in 2011-2017 (PCV10 period) with those in 2004-2010 (pre-PCV10 baseline) by using Poisson regression models. Absolute rate differences and 95% confidence intervals (CIs) were calculated from the parameter estimates by using delta method., Results: During the PCV10 period, the overall incidence of PCV10 serotype meningitis decreased by 68% (95%CI 57%-77%), and the overall PM incidence by 27% (95%CI: 12%-39%). In age groups 0-4, 50-64, and ≥ 18 years, the overall PM incidence was reduced by 64%, 34% and 19%, respectively. In adults ≥ 65 years of age, a 69% reduction in PCV10 serotypes was offset by 157% (56%-342%) increase in non-PCV10 serotypes. The overall PM-related mortality rate decreased by 42% (95%CI 4%-65%). Overall case fatality proportion (CFP) was 16% in pre-PCV10 period and 12% in PCV10 period (p = 0.41); among persons 50-64 years the CFP decreased from 25% to 10% (p = 0.04)., Conclusions: We observed substantial impact and herd protection for vaccine-serotype PM and associated mortality after infant PCV10 introduction. However, in older adults ≥ 65 years of age, PM burden remains unchanged due to serotype replacement., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The Finnish Institute for Health and Welfare has received research funding from GlaxoSmithKline Vaccines for the conduct of a nationwide effectiveness trial of the 10-valent pneumococcal conjugate vaccine, and from Pfizer, Inc. and Sanofi Pasteur, Inc. for non-pneumococcal research. Hanna Rinta-Kokko, Arto A. Palmu and Maija Toropainen are co-investigators in these studies. The other authors have no conflicts to disclose. The current study was entirely publicly funded.]., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) entered Cameroon's childhood national immunization programme (NIP) in July 2011 under a 3-dose schedule (6, 10, 14 weeks of age) without any catch-up. We described the impact of PCV13 onserotype distribution among pneumococcal meningitis cases over time., Methods: We used laboratory-based sentinel surveillance data to identify meningitis cases among 2- to 59-month-old children with clinically-suspected bacterial meningitis (CSBM) admitted to hospitals in Yaoundé (August 2011-December 2018). Purulent meningitis cases had a cerebrospinal fluid (CSF) white blood cell (WBC) count ≥20 per mm3. Pneumococcal meningitis cases had S. pneumoniae identified from CSF, with serotyping by polymerase chain reaction. Years 2011-2014 were described as early PCV13 era (EPE) and years 2015-2018 as late PCV13 era (LPE) impact periods., Results: Among children hospitalized with CSBM who had a lumbar puncture obtained, there was no significant change from the EPE versus the LPE in the percentage identified with purulent meningitis: 7.5% (112/1486) versus 9.4% (154/1645), p = 0.0846. The percentage of pneumococcal meningitis cases due to PCV13 vaccine-serotype (VST) decreased from 62.0% (31/50) during the EPE to 35.8% (19/53) in the LPE, p = 0.0081. The most frequent pneumococcal meningitis VSTs during the EPE were 6A/6B (30%) and 5 (6%), and during the LPE were 14 (13.2%), 3 (7.6%), 4 (5.6%) and 18C (5.6%)., Conclusion: Four to seven years after PCV13 introduction, the proportion of pneumococcal meningitis due to vaccine serotypes has declined, mainly due to reductions of serotypes 6A/6B, 1, 19A, and 23F; nevertheless, PCV13 VSTs remain common. Because the analyzed surveillance system was not consistent or population based, we could not estimate incidence or overall impact; this emphasizes the need for improved surveillance to document further the utility of PCV13 immunization in Cameroon., Competing Interests: Some of the co-authors (MA, BB, JS, MAF, RB and BG) are employed by Pfizer, Inc and may own stock or stock options. The authors adhere to PLOS ONE policies on sharing data and materials.

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 × 10 3 /μL), low platelet count (<28.1 × 10 4 /μL), 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., Competing Interests: Declaration of competing interest S. Iwata has received grant support from Sumitomo Dainippon Pharma Co., Ltd., Pfizer Japan Inc., Taisho Toyama Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., and MSD K. K. K. Ubukata has received payment for lectures from Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., and HORIBA, Ltd. I. Miyairi has received payments for lectures from Sumitomo Dainippon Pharma Co., Ltd., bioMelieux Japan Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Japan Vaccine Co., Ltd., Sanofi, Tanabe Mitsubishi Pharma Co., Ltd., Abbvie Inc. and Abbott diagnostics. The other authors declare that they have no conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae , Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis , S. pneumoniae , and H. influenzae used in routine meningitis surveillance . A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium . Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Background: To better understand how to prevent and respond to pneumococcal meningitis outbreaks in the meningitis belt, we retrospectively examined Burkina Faso's case-based meningitis surveillance data for pneumococcal meningitis clusters and assessed potential usefulness of response strategies., Methods: Demographic and clinical information, and cerebrospinal fluid laboratory results for meningitis cases were collected through nationwide surveillance. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We reviewed data from 2011 to 2017 to identify and describe clusters of ≥ 5 confirmed pneumococcal meningitis cases per week in a single district. We assessed whether identified clusters met the 2016 WHO provisional pneumococcal meningitis outbreak definition: a district with a weekly incidence of >5 suspected meningitis cases/100,000 persons, >60% of confirmed meningitis cases caused by Streptococcus pneumoniae, and >10 confirmed pneumococcal meningitis cases., Results: Twenty pneumococcal meningitis clusters were identified, with a maximum weekly incidence of 7 cases and a maximum duration of 4 weeks. Most identified clusters (15/20; 75%) occurred before nationwide introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013. Most cases were due to serotype 1 (74%), 10% were due to PCV13 serotypes besides serotype 1, and 8 clusters had >1 serotype. While 6 identified clusters had a weekly incidence of >5 suspected cases/100,000 and all 20 clusters had >60% of confirmed meningitis cases due to S. pneumoniae, no cluster had >10 confirmed pneumococcal meningitis cases in a single week., Conclusions: Following PCV13 introduction, pneumococcal meningitis clusters were rarely detected, and none met the WHO provisional pneumococcal outbreak definition. Due to the limited cluster size and duration, there were no clear instances where reactive vaccination could have been useful. More data are needed to inform potential response strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger. As a national reference laboratory for meningitis, Centre de Recherche Médicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010-2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010-2012) and after (2016-2018) PCV13 introduction. During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010-12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016-18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged ≥ 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged ≥ 5 years, but not among those < 5 years. VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Polysaccharide conjugate vaccines (PCVs) target the pneumococcal capsular types that most commonly cause fatal pneumonia and sepsis. Because these types were eliminated by the vaccines, it became apparent that in immunized populations, most invasive pneumococcal diseases, including bacteremia, sepsis and complicated pneumonia, were greatly reduced. However, the protective effects of PCVs against another invasive disease, meningitis, has shown much less or no decrease in disease incidence., Methods: References were identified through searches of PubMed for articles published from January 1930 to the present by use of specific search terms. Relevant articles were also identified through searches in Google and Google Scholar. Relevant references cited in those articles were also reviewed., Results: Even in the presence of the PCVs, meningitis rates in children have been reported globally to be as high as 13 per 100,000 annually. Widespread use of vaccines resulted in the emergence of a broad diversity of replacement non-PCV type strains. These strains generally failed to cause sepsis, but caused meningitis of comparable severity and levels similar to, or in excess of, prior pneumococcal meningitis rates. This is probably because these non-PCV type strains do not survive well in the blood, therefore possibly entering the brain through nonhematogenous routes., Conclusions: Because virtually all cases of pneumococcal meningitis lead to either permanent neurologic sequelae or death, it would be well worth the effort to develop a new vaccine capable of preventing pneumococcal meningitis regardless of capsular type. Such a vaccine would need to protect against colonization with most, if not all, pneumococci.

Aim: To investigate if adult cochlear implant (CI) recipients have received the recommended immunisations as compared to current guidelines and to report instances of meningitis within this population., Methods: Telephone interview of CI recipient's general practitioner (GP) surgeries for details regarding immunisations received. Subsequent reporting of immunisation rates of adult patients, under the care of the Northern Cochlear Implant Programme (NCIP) in New Zealand, when compared to the recommended guidelines from the Immunisation Advisory Centre (IMAC) and rates of meningitis of CI recipients are presented., Results: It is recommended to immunise against the most common organisms causing meningitis, Streptococcus pneumoniae and Haemophilus influenzae type b (HiB), as well as influenza. Data for 135 CI recipients over the last five years was complete. 14.8% of patients had received a full pneumococcal immunisation schedule. 11.9% had received a HiB immunisation and 62.2% an influenza vaccination. No patient had developed meningitis following CI insertion., Conclusion: This paper highlights clear issues with the immunisation of adult CI recipients., Competing Interests: Dr Neeff is the chairperson of the Northern Cochlear Implant Programme Advisory Group. The Northern Cochlear Implant Programme (NCIP) is a publicly funded programme for profoundly deaf children and adults in the northern region of New Zealand.

Background: Studies on the impact of pneumococcal conjugate vaccines (PCV) on mortality, especially among preschoolers are scarce. We aimed to assess time trend mortality from lower respiratory infections (LRI), taken as a proxy of pneumonia, from 1990 to 2017., Methods: This ecological study assessed the mortality rate among Brazilians under-five before and after the national PCV-10 implementation in 2010. Pneumococcal meningitis (PM) and diarrheal diseases (DD) were included as a "positive and negative controls", respectively. Trend analysis was performed through Global Burden of Disease estimates. Joinpoint regression modeling was used to describe trends in mortality and to identify time points of its statistically significant decreases throughout the study period., Results: There was a sustainable reduction in mortality rates for these three diseases, with no relevant changes in the secular trends for LRI and PM after the PCV-10 implementation. For LRI, PM, and DD the higher and statistically significant (p < 0.05) annual percent change reduction occurred between 2000 and 2003, (-8.3%), 1997-2000 (-11.9%), and 1990-1994. (-13.8%), respectively, i.e., several years before the nationwide implementation of PCV-10. Moreover, for LRI the annual percent change (from -5.9 to -8.8) verified from 1990 to 2009, i.e., 20 years before countrywide vaccination, was comparable to that observed during the PCV era, that is, from minus 5.8 to minus 7.8, between 2010 and 2017., Conclusion: Mortality from LRI, PM, and DD decreased over time, irrespective of national PCV-10 implementation in Brazil. Other factors such as healthcare delivery, socioeconomic status improvement, and health interventions may have impacted this secular trend., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Streptococcus pneumoniae is the most common pathogen causing bacterial meningitis. The routine use of multivalent conjugate pneumococcal vaccines has led to a decline of invasive pneumococcal disease caused by serotypes included in the vaccine serotypes. Recently, several reports have described a concomitant rise in the incidence of non-vaccine serotypes, suggesting serotype replacement., Objective: We aim to review the effect of pneumococcal vaccination on the incidence of pneumococcal meningitis in Europe and northern America with a particular interest in serotype replacement., Sources: Articles that include data on invasive pneumococcal disease incidence before and after the introduction of vaccination, or on invasive pneumococcal serotype, are discussed, with a focus on pneumococcal meningitis., Content: The introduction of pneumococcal conjugate vaccines has universally resulted in a decline in vaccine-serotype pneumococcal meningitis incidence throughout Europe and northern America. Serotype replacement by non-vaccine serotypes has however been reported following the introduction of the 7-, 10- and 13-valent pneumococcal conjugate vaccines, which in several regions abolished the overall effect of vaccination on pneumococcal meningitis incidence., Implications: The promising decline in the incidence of pneumococcal meningitis following the introduction of vaccination seems to have been temporary. Replacement by non-vaccine serotypes illustrates that pneumococcal meningitis continues to pose a major challenge. We need new approaches to prevention, new vaccines and continued efforts to improve treatment for patients with pneumococcal meningitis., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Since the widespread introduction of the conjugate pneumococcal vaccine and subsequent decline of invasive pneumococcal disease in children, a significant proportion of children with pneumococcal meningitis are identified as having an underlying immunodeficiency or predisposing anatomic abnormality. We present 3 cases of recurrent pneumococcal meningitis where detailed neuro-imaging revealed subtle anterior base of skull defects not detected on initial investigations.

Toll-like receptor (TLR) 2 and 4 signalling pathways are central to the body's defence against invading pathogens during pneumococcal meningitis. Whereas several studies support their importance in innate immunity, thereby preventing host mortality, any role in protecting neurological function during meningeal infection is ill-understood. Here we investigated both the acute immunological reaction and the long-term neurobehavioural consequences of experimental pneumococcal meningitis in mice lacking both TLR2 and TLR4. The absence of these TLRs significantly impaired survival in mice inoculated intracerebroventricularly with Streptococcus pneumoniae. During the acute phase of infection, TLR2/4-deficient mice had lower cerebrospinal fluid concentrations of interleukin-1β, and higher interferon-γ, than their wild-type counterparts. After antibiotic cure, TLR2/4 double deficiency was associated with aggravation of behavioural impairment in mice, as shown by diurnal hypolocomotion throughout the adaptation phases in the Intellicage of TLR-deficient mice compared to their wild-type counterparts. While TLR2/4 double deficiency did not affect the cognitive ability of mice in a patrolling task, it aggravated the impairment of cognitive flexibility. We conclude that TLR2 and TLR4 are central to regulating the host inflammatory response in pneumococcal meningitis, which may mediate diverse compensatory mechanisms that protect the host not only against mortality but also long-term neurological complications.

Background: In 2013, Burkina Faso introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization program, to be administered to children at 8, 12, and 16 weeks of age. We evaluated the impact of PCV13 on pneumococcal meningitis., Methods: Using nationwide surveillance, we gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We compared annual incidence (cases per 100 000) 4 years after PCV13's introduction (2017) to average pre-PCV13 incidence (2011-2013). We adjusted incidence for age and proportion of cases with CSF tested at national laboratories., Results: In 2017, pneumococcal meningitis incidence was 2.7 overall and 10.5 (<1 year), 3.8 (1-4 years), 3.5 (5-14 years), and 1.4 (≥15 years) by age group. Compared to 2011-2013, PCV13-serotype incidence was significantly lower among all age groups, with the greatest decline among children aged <1 year (77%; 95% confidence interval [CI], 65%-84%). Among all ages, the drop in incidence was larger for PCV13 serotypes excluding serotype 1 (79%; 95% CI, 72%-84%) than for serotype 1 (52%; 95% CI, 44%-59%); incidence of non-PCV13 serotypes also declined (53%; 95% CI, 37%-65%). In 2017, 45% of serotyped cases among all ages were serotype 1 and 12% were other PCV13 serotypes., Conclusions: In Burkina Faso, meningitis caused by PCV13 serotypes continues to decrease, especially among young children. However, the concurrent decline in non-PCV13 serotypes and short pre-PCV13 observation period complicate evaluation of PCV13's impact. Efforts to improve control of serotype 1, such as switching from a 3 + 0 schedule to a 2 + 1 schedule, may improve overall control of pneumococcal meningitis in this setting., (Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Streptococcus suis is an emerging zoonotic agent. Its natural habitat is the tonsils, which are the main portals of S. suis entry into the bloodstream of pigs. The remarkable variability of the bacteria and complex pathogenic mechanisms make the development of a vaccine a difficult task., Method: Five conserved virulence factors involved in critical events of S. suis pathogenesis were combined and used as an intranasal vaccine (V5). The effect of V5 was investigated with intranasal and systemic challenge models., Results: V5 induced antibody and T-cell responses at the mucosal site and systemically. The immunity promoted clearance of S. suis from the nasopharynx independent of S. suis serotypes and reduced lethality after systemic challenge with S. suis serotype 2. Moreover, mice that survived sepsis from intravenous infection developed meningitis, whereas none of these mice showed neuropathological symptoms after V5 receipt., Conclusion: Intranasal immunization with multiple conserved virulence factors decreases S. suis colonization at the nasopharynx across serotypes and inhibits the dissemination of the bacteria in the host. The protective mucosal immunity effects would potentially reduce the S. suis reservoir and prevent S. suis disease in pigs., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: South Africa introduced seven-valent pneumococcal conjugate vaccine (PCV7) in 2009 and PCV13 in 2011. We aimed to compare the estimated impact of PCV on pneumococcal meningitis (PM) to impact of PCV on total invasive pneumococcal disease (tIPD) based on risk reduction after PCV introduction., Methods: We conducted national, laboratory-based surveillance for tIPD during 2005-2016. We estimated and compared rates of PCV13 and non-PCV13 serotype disease among tIPD and PM in individuals aged <5 years and ≥5 years, and compared these rates between the 2005-2008 pre-PCV introduction period and two time points after PCV introduction, 2012 and 2016., Results: We enrolled 45,853 tIPD cases; 17,251 (38%) were PM. By 2016, IPD caused by all serotypes decreased 55% (95%CI -57% to -53%) for tIPD, and 54% for PM (95%CI -58% to -51%), 0.7% difference between estimates (p = 0.7). No significant differences were observed between PCV7-serotype disease reduction in tIPD and PM in both age groups or the additional 6 serotypes included in PCV13 in <5 year olds in 2012 and 2016. In 2012 there was a significant difference between increases in non-PCV13 serotype disease in those ≥5 years for tIPD and PM (32% greater increase in PM, p < 0.001), but this difference was absent by 2016. There was a significant difference between the estimated decrease in additional PCV13 type disease in 2016 between tIPD and PM for those aged ≥5 years (28% greater reduction in PM, p = 0.008)., Conclusion: PM showed similar reductions to tIPD seven years after PCV introduction in vaccine serotype disease in those <5 years, and increases in non-vaccine serotype disease in all ages., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Streptococcus pneumoniae is a leading cause of pneumonia and meningitis in children aged <5 years. Zimbabwe introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2012 using a 3-dose infant schedule with no booster dose or catch-up campaign. We evaluated the impact of PCV13 on pediatric pneumonia and meningitis., Methods: We examined annual changes in the proportion of hospitalizations due to pneumonia and meningitis among children aged <5 years at Harare Central Hospital (HCH) pre-PCV13 (January 2010-June 2012) and post-PCV13 (July 2013-December 2016) using a negative binomial regression model, adjusting for seasonality. We also evaluated post-PCV13 changes in serotype distribution among children with confirmed pneumococcal meningitis at HCH and acute respiratory infection (ARI) trends using Ministry of Health outpatient data., Results: Pneumonia hospitalizations among children aged <5 years steadily declined pre-PCV13; no significant change in annual decline was observed post-PCV13. Post-PCV13 introduction, meningitis hospitalization decreased 30% annually (95% confidence interval [CI], -42, -14) among children aged 12-59 months, and no change was observed among children aged 0-11 months. Pneumococcal meningitis caused by PCV13 serotypes decreased from 100% in 2011 to 50% in 2016. Annual severe and moderate outpatient ARI decreased by 30% (95% CI, -33, -26) and 7% (95% CI, -11, -2), respectively, post-PCV13 introduction., Conclusions: We observed declines in pediatric meningitis hospitalizations, PCV13-type pneumococcal meningitis, and severe and moderate ARI outpatient visits post-PCV13 introduction. Low specificity of discharge codes, changes in referral patterns, and improvements in human immunodeficiency virus care may have contributed to the lack of additional declines in pneumonia hospitalizations post-PCV13 introduction., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Acute bacterial meningitis remains a major cause of childhood mortality in sub-Saharan Africa. We document findings from hospital-based sentinel surveillance of bacterial meningitis among children <5 years of age in The Gambia, from 2010 to 2016., Methods: Cerebrospinal fluid (CSF) was collected from children admitted to the Edward Francis Small Teaching Hospital with suspected meningitis. Identification of Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae was performed by microbiological culture and/or polymerase chain reaction where possible. Whole genome sequencing was performed on pneumococcal isolates., Results: A total of 438 children were admitted with suspected meningitis during the surveillance period. The median age of the patients was 13 (interquartile range, 3-30) months. Bacterial meningitis was confirmed in 21.4% (69/323) of all CSF samples analyzed. Pneumococcus, meningococcus, and H. influenzae accounted for 52.2%, 31.9%, and 16.0% of confirmed cases, respectively. There was a significant reduction of pneumococcal conjugate vaccine (PCV) serotypes, from 44.4% in 2011 to 0.0% in 2014, 5 years after PCV implementation. The majority of serotyped meningococcus and H. influenzae belonged to meningococcus serogroup W (45.5%) and H. influenzae type b (54.5%), respectively. Meningitis pathogens were more frequently isolated during the dry dusty season of the year. Reduced susceptibility to tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol was observed. No resistance to penicillin was found., Conclusions: The proportion of meningitis cases due to pneumococcus declined in the post-PCV era. However, the persistence of vaccine-preventable meningitis in children aged <5 years is a major concern and demonstrates the need for sustained high-quality surveillance., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Streptococcus pneumoniae is increasingly recognised as an important cause of bacterial meningitis in the African meningitis belt. The World Health Organization sets guidelines for response to outbreaks of meningococcal meningitis, but there are no current guidelines for outbreaks where S. pneumoniae is implicated. We aimed to evaluate the impact of using a similar response to target outbreaks of vaccine-preventable pneumococcal meningitis in the meningitis belt. Here, we adapt a previous model of reactive vaccination for meningococcal outbreaks to estimate the potential impact of reactive vaccination in a recent pneumococcal meningitis outbreak in the Brong-Ahafo region of central Ghana using weekly line list data on all suspected cases over a period of five months. We determine the sensitivity and specificity of various epidemic thresholds and model the cases and deaths averted by reactive vaccination. An epidemic threshold of 10 suspected cases per 100,000 population per week performed the best, predicting large outbreaks with 100% sensitivity and more than 85% specificity. In this outbreak, reactive vaccination would have prevented a lower number of cases per individual vaccinated (approximately 15,300 doses per case averted) than previously estimated for meningococcal outbreaks. Since the burden of death and disability from pneumococcal meningitis is higher than that from meningococcal meningitis, there may still be merit in considering reactive vaccination for outbreaks of pneumococcal meningitis. More outbreak data are needed to refine our model estimates. Whatever policy is followed, we emphasize the importance of timely laboratory confirmation of suspected cases to enable appropriate decisions about outbreak response., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We describe the effects of the 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines on pneumococcal meningitis in England and Wales during July 1, 2000-June 30, 2016. Overall, 84,473 laboratory-confirmed invasive pneumococcal disease cases, including 4,160 (4.9%) cases with meningitis, occurred. PCV7 implementation in 2006 did not lower overall pneumococcal meningitis incidence because of replacement with non-PCV7-type meningitis incidence. Replacement with PCV13 in 2010, however, led to a 48% reduction in pneumococcal meningitis incidence by 2015-16. The overall case-fatality rate was 17.5%: 10.7% among patients <5 years of age, 17.3% among patients 5-64 years of age, and 31.9% among patients >65 years of age. Serotype 8 was associated with increased odds of death (adjusted odds ratio 2.9, 95% CI 1.8-4.7). In England and Wales, an effect on pneumococcal meningitis was observed only after PCV13 implementation. Further studies are needed to assess pneumococcal meningitis caused by the replacing serotypes.

Geographic variations of invasive pneumococcal disease incidence and serotype distributions were observed after pneumococcal conjugate vaccine introduction at regional levels and among French administrative areas. The variations could be related to regional vaccine coverage (VC) variations that might have direct consequences for vaccination-policy impact on invasive pneumococcal disease, particularly pneumococcal meningitis (PM) incidence. We assessed vaccine impact from 2001 to 2016 in France by estimating the contribution of regional VC differences to variations of annual local PM incidence. Using a mixed-effect Poisson model, we showed that, despite some variations of VC among administrative areas, vaccine impact on vaccine-serotype PM was homogeneously confirmed among administrative areas. Compared with the prevaccine era, the cumulative VC impact on vaccine serotypes led, in 2016, to PM reductions ranging among regions from 87% (25th percentile) to 91% (75th percentile) for 7-valent pneumococcal conjugate vaccine serotypes and from 58% to 63% for the 6 additional 13-valent pneumococcal conjugate vaccine serotypes. Nonvaccine-serotype PM increases from the prevaccine era ranged among areas from 98% to 127%. By taking into account the cumulative impact of growing VC and VC differences, our analyses confirmed high vaccine impact on vaccine-serotype PM case rates and suggest that VC variations cannot explain PM administrative area differences., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objective: To analyze the pneumococcal meningitis incidence rates in the State of São Paulo, Brazil, by age group, municipalities and micro-regions, as well as the spatial distribution of pneumococcal meningitis incidence rates among children under 5 years old in the pre- (2005-2009) and post-vaccination (2011-2013) periods and its associations with socioeconomic variables and vaccination coverage., Methods: The data source was the Brazilian Notifiable Diseases Information System. For the pre- and post-vaccination periods, thematic maps were built for pneumococcal meningitis incidence in under-5 children, by São Paulo state micro-regions, vaccination coverage and socioeconomic variables, using QGIS 2.6.1 software. Scan statistics performed by the SatScan 9.2 software were used to analyze spatial and spatiotemporal clusters in São Paulo municipalities and micro-regions. A Bayesian inference for latent Gaussian model with zero-inflated Poisson model through the integrated nested Laplace approximation was used in the spatial analysis to evaluate associations between pneumococcal meningitis incidence rates and socioeconomic variables of interest in São Paulo micro-regions., Results: From 2005 to 2013, 3,963 pneumococcal meningitis cases were reported in São Paulo. Under-5 children were the most affected in the whole period. In the post-vaccination period, pneumococcal meningitis incidence rates decreased among this population, particularly among infants (from 4.17/100,000 in 2005 to 2.54/100,000 in 2013). Two clusters were found in pre-vaccination - one of low risk for pneumococcal meningitis, in the northwest of the state (OR = 0.45, p = 0.0003); and another of high risk in the southeast (OR = 1.62, p = 0.0000). In the post-vaccination period, only a high-risk cluster remained, in the southeast (RR = 1.97, p = 0.0570). In Bayesian analysis, wealth was the only variable positively associated to pneumococcal meningitis (RR = 1.026, 95%CI 1.002-1.052)., Conclusions: Pneumococcal meningitis is probably underdiagnosed and underreported in São Paulo. Differentiated rates of pneumococcal meningitis diagnosis and reporting in each microregion, according to the São Paulo Index of Social Responsibility, might explain our results.

In a case-control study within the Kaiser Permanente Northern California adult population, prior head or spine surgery was associated with increased Streptococcus pneumoniae meningitis outside of the postoperative period (no prior head or spine surgery; odds ratio, 6.0 [95% confidence interval, 1.9-18.6]). Among the cases, only 33.3% had received any prior pneumococcal vaccinations., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Estimation of the magnitude of the herd effect on invasive pneumococcal disease (IPD) is important when evaluating health benefits and cost-effectiveness of paediatric pneumococcal conjugate vaccine (PCV) programmes and may influence policy makers' decisions on PCV use. Several epidemiological, programmatic, and immunological factors can affect the magnitude of the PCV herd effect. We investigated to what extent the choice of analytical methodology may also influence herd effect estimates., Methods: To estimate the magnitude of the herd effect from paediatric PCV programmes, we examined overall IPD incidence rates in ≥65-year-olds from Finland, Australia, England/Wales, and the United States under different analytical scenarios. We used two different statistical methods: before/after comparison of average IPD incidence rates and interrupted time series (ITS) analysis accounting for underlying time trends. We also investigated how varying the length of the pre- and post-PCV analysis periods influenced the outcomes., Results: The estimated impact of paediatric PCV programmes on IPD incidence rates in adults ≥65 years varied substantially across the different scenarios within each country. The choice of statistical method and analysis periods contributed to this variation, and their influence varied by setting. For the datasets from England/Wales and the United States, the different scenarios produced relatively minor variation in estimated impact. For the Australian and Finnish datasets, differences were more prominent. In particular, for Finland, opposite conclusions could be drawn depending on the methodology: while no estimated herd effect was seen with the before/after method, a herd effect was evident with the ITS method., Conclusions: The choice of statistical method and analysis periods can substantially influence the magnitude of estimated herd effects from paediatric PCV programmes. It is important to consider the reliability and presence of pre-PCV patterns in the IPD surveillance data used for analysis, the methodology and associated assumptions used to estimate herd effects., (Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.)

Background: The introduction of the pneumococcal conjugated vaccines (PCVs) resulted in a substantial reduction of invasive pneumococcal disease (IPD) rates. However, impact on nonsevere IPD (mostly occult bacteremia) has not yet been fully elucidated. We assessed severe and nonsevere IPD (SIPD and NSIPD, respectively) rate dynamics in children < 5 years in Israel before and after PCV7/PCV13 implementation., Methods: A prospective, population-based, nationwide surveillance. All IPD episodes recorded from 1999 through 2015 were included. NSIPD was defined as IPD episodes without meningitis, pneumonia or mastoiditis in a child with a favorable outcome (not hospitalized or hospitalized in a nonintensive care unit < 5 days, without mortality). Three subperiods were defined: pre-PCV (1999-2008), PCV7 (2010-2011) and PCV13 (2013-2015). Incidence rate ratios (IRRs) were calculated., Results: Overall, 4,457 IPD episodes were identified; 3,398 (76.2%) SIPD, 1,022 (22.9%) NSIPD and 37 (0.8%) unknown. In 90% of NSIPD episodes, no focus was identified. In the PCV7 period, NSIPD rates significantly declined by 52%, while SIPD rates declined less prominently by 24%. Following PCV13 introduction, compared with the PCV7 period, NSIPD rates declined nonsignificantly by 17% while SIPD rates declined significantly further by an additional 53%. These trends resulted in overall reductions (comparing PCV13 and pre-PCV periods) of NSIPD and SIPD of 60% (IRR = 0.4; 0.32-0.51) and 64% (IRR = 0.36; 0.32-0.42), respectively., Conclusions: Following PCV7/PCV13 introduction, SIPD and NSIPD rates substantially declined, with differences in rate-dynamics, alluding to differences in serotype distribution between the 2 groups. Future surveillance is warranted when considering modification in treatment protocols for suspected occult bacteremia/NSIPD cases.

Background: Bacterial meningitis is a significant cause of morbidity and mortality worldwide among children aged 1-59 months. We aimed to describe its burden in South Asia, focusing on vaccine-preventable aetiologies., Methods: We searched five databases for studies published from January 1, 1990, to April 25, 2017. We estimated incidence and aetiology-specific proportions using random-effects meta-analysis. In secondary analyses, we described vaccine impact and pneumococcal meningitis serotypes., Results: We included 48 articles cumulatively reporting 20,707 cases from 1987 to 2013. Mean annual incidence was 105 (95% confidence interval [CI], 53-173) cases per 100,000 children. On average, Haemophilus influenzae type b (Hib) accounted for 13% (95% CI, 8-19%) of cases, pneumococcus for 10% (95% CI, 6-15%), and meningococcus for 1% (95% CI, 0-2%). These meta-analyses had substantial between-study heterogeneity (I 2  > 78%, P < 0.0001). Among studies reporting only confirmed cases, these three bacteria caused a median of 78% cases (IQR, 50-87%). Hib meningitis incidence declined by 72-83% at sentinel hospitals in Pakistan and Bangladesh, respectively, within two years of implementing nationwide vaccination. On average, PCV10 covered 49% (95% CI, 39-58%), PCV13 covered 51% (95% CI, 40-61%), and PPSV23 covered 74% (95% CI, 67-80%) of pneumococcal meningitis serotypes. Lower PCV10 and PCV13 serotype coverage in Bangladesh was associated with higher prevalence of serotype 2, compared to India and Pakistan., Conclusions: South Asia has relatively high incidence of bacterial meningitis among children aged 1-59 months, with vaccine-preventable bacteria causing a substantial proportion. These estimates are likely underestimates due to multiple epidemiological and microbiological factors. Further research on vaccine impact and distribution of pneumococcal serotypes will inform vaccine policymaking and implementation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Children immunization with pneumococcal conjugate vaccine (PCV) had profound public health effects across the globe. Colombian adopted PCV10 universal vaccination, but PCV incremental impact need to be revalued. The objective of this analysis was to estimate the cost-effectiveness of switch to PCV13 versus continue PCV10 in Colombian children., Methods: A complete economic analysis was carried-out assessing potential epidemiological and economic impact of switching from PCV10 to PCV13. Epidemiological information on PCV10 impact was obtained from lab-based epidemiological surveillance on pneumococcal isolates at the Colombian National Institute of Health. Economic inputs were extracted from the literature. Incremental PCV13 effectiveness was based in additional serotypes included. Comparisons among alternatives were evaluated with the Incremental Cost-Effectiveness Ratio (ICER) at a willingness to pay of one GDP per capita (USD$ 6631) per Year of Live Saved (YLS). All costs were reported in 2014USD. Deterministic and probabilistic sensitivity analyses were performed, and 95% confidence interval reported., Results: After four years using PCV10 for universal vaccination on children the Colombian health surveillance system showed a relative increment on non PCV10 isolates. To change from PCV10 to PCV13 would avoid 587 (CI95% -49-1008) ambulatory Rx community-acquired pneumoniae (CAP), 1622 (CI95% 591-2343) Inpatient RxCAP, 10 (CI 95% 6-11) pneumococcal meningitis, and 79 (CI95% 76-98) deaths. ICER per YLS was USD$ 2319 (CI95% Dominated - USD$ 4225) for Keep-PCV10 and USD$ 1771 (CI95% USD$ 1285-9884) for Switch-to PCV13. In spite of its cost-effectiveness Keep-PCV10 is an extended dominated alternative and Switch-to PCV13 would be preferred. Results are robust to parameters changes in the sensitivity analyses., Conclusion: A national immunization strategy based in Switch-to PCV13 was found to be good value for money and prevent additional burden of pneumococcal disease saving additional treatment costs, when compared with to Keep-PCV10 in Colombia, however additional criteria to decision making must be taken into account., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Increases in pneumococcal meningitis were reported from Ghanaian regions that lie in the meningitis belt in 2016-2017, despite introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in 2012 using a 3-dose schedule (6, 10, and 14 weeks). We describe pneumococcal meningitis epidemiology in the Ghanaian Northern and Upper West regions across two meningitis seasons., Methods: Suspected meningitis cases were identified using World Health Organization standard definitions. Pneumococcal meningitis was confirmed if pneumococcus was the sole pathogen detected by polymerase chain reaction, culture, or latex agglutination in cerebrospinal fluid collected from a person with suspected meningitis during December 2015-March 2017. Pneumococcal serotyping was done using PCR. Annual age-specific pneumococcal meningitis incidence (cases per 100,000 population) was calculated, adjusting for suspected meningitis cases lacking confirmatory testing., Findings: Among 153 pneumococcal meningitis cases, 137 (89.5%) were serotyped; 100 (73.0%) were PCV13-type, including 85 (62.0%) that were serotype 1, a PCV13-targeted serotype. Persons aged ≥5 years accounted for 96.7% (148/153) of cases. Comparing 2015-2016 and 2016-2017 seasons, the proportion of non-serotype 1 PCV13-type cases decreased from 20.0% (9/45) to 4.1% (3/74) (p = 0.008), whereas the proportion that was serotype 1 was stable (71.1% (32/45) vs. 58.1% (43/74); p = 0.16). Estimated adjusted pneumococcal meningitis incidence was 1.8 in children aged <5 years and ranged from 6.8-10.5 in older children and adults., Conclusions: High pneumococcal meningitis incidence with a large proportion of serotype 1 disease in older children and adults suggests infant PCV13 vaccination has not induced herd protection with this schedule in this high-transmission setting., Competing Interests: The authors have declared that no competing interests exist.

We report a pneumococcal meningitis outbreak in the Central African Republic (251 suspected cases; 60 confirmed by latex agglutination test) in 2016-2017. Case-fatality rates (10% for confirmed case-patients) were low. In areas where a recent pneumococcal conjugate vaccine campaign was conducted, a smaller proportion of cases was seen in youngest children.

Introduction: Widespread introduction of pneumococcal conjugated vaccines (PCVs) impacted on invasive pneumococcal disease (IPD). However, IPD reduction may not be similar in all outcomes within IPD. We assessed PCV7/PCV13 impact on pneumococcal meningitis, bacteremic pneumonia (BP) and other (non-meningitis, non-pneumonia) IPD episodes in children <5years in Israel., Methods: A prospective, population-based, active nationwide surveillance. All pneumococcal invasive episodes with positive blood/CSF cultures, July 2000 through June 2016, were included. Three sub-periods were defined: pre-PCV (2000-2008), PCV7 (2009-2011) and PCV13 (2014-2016). Incidence rate ratios (IRRs) were calculated., Results: Overall, 4321 episodes were recorded; 456 (10.6%) meningitis, 1478 (34.2%) pneumonia and 2387 (55.2%) other-IPD. In the pre-PCV period, proportion of serotypes in PCV13, but not in PCV7 (mainly serotypes 1, 5 and 19A) was higher in BP (43.3%) compared with other-IPD episodes (32.8%, p<0.001) and similar to that of meningitis (37.6%, p=0.1). The proportion of episodes in children <12months was higher in meningitis (52.1%) compared with pneumonia (23.2%) and other-IPD episodes (39.5%; p<0.001 for both). The declines of the 3 entities were not similar; Meningitis rate non-significantly declined by 24% (IRR=0.76; 95% CI 0.57-1.01), while BP and other-IPD rates significantly declined by 57% and 70%, respectively. In contrast to other entities, BP did not decline significantly after PCV7 introduction but started to decline only after PCV13 introduction. Rates of meningitis, pneumonia and other-IPD caused by PCV13-serotypes (VT13) substantially declined by 88%, 95% and 97%, respectively, comparing PCV13 and the pre-PCV periods. However, diseases caused by non-VT13 increased by 256%, 302% in meningitis and pneumonia, respectively, but only 116% in other-IPD., Conclusions: Following PCV7/PCV13 introduction, rates of episodes caused by VT13 were substantially reduced in all 3 groups. However, differences in age distribution, serotype replacement and specific serotype decrease suggest different pathogenesis and host susceptibility between the 3 entities., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The indirect effect of pneumococcal conjugate vaccine on adult pneumococcal meningitis has not been thoroughly investigated. We present data from active surveillance on pneumococcal meningitis in adults in Israel occurring during July 2009-June 2015. Pneumococcal meningitis was diagnosed for 221 patients, 9.4% of all invasive pneumococcal disease (IPD) cases. Although overall IPD incidence decreased during the study period, meningitis increased nonsignificantly from 0.66 to 0.85 cases/100,000 population. Incidence of vaccine type (VT) pneumococcal meningitis (VT13) decreased by 70%, but non-VT13 pneumococcal meningitis increased from 0.32 to 0.75 cases/100,000 population (incident rate ratio 2.35, 95% CI 1.27-4.35). Pneumococcal meningitis patients were younger and healthier than nonmeningitis IPD patients, and 20.2% had a history of previous head surgery or cerebrospinal fluid leak compared with <2.0% of nonmeningitis patients (p<0.0001). Non-VT13 types that rarely cause IPD (15B/C, 6C, 23A, 23B, 24F) seem to be emerging as common causes of meningitis.

Colombia introduced mass pneumococcal conjugate vaccination at the end of 2011. Using 2005-2015 surveillance data, we conducted a retrospective interrupted time-series analysis. A significant trend towards reduced monthly was observed in the post-vaccination period (2012-2015) compared with the expected rate, reaching in 2015 a reduction of 90.5% of pneumococcal meningitis. This trend was not observed for control diseases.