Incidence Of Pneumococcal Meningitis Research Articles

Effect of 10-valent pneumococcal conjugate vaccine on trends of pneumococcal meningitis in children under five years, Uganda, 2003-2022.

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. 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. 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. 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.

Characteristics of children with invasive pneumococcal disease eligible for the 1+1 compared with the 2+1 PCV13 infant immunisation schedule in England: a prospective national observational surveillance study

On Jan 1, 2020, the UK transitioned from a 2+1 to a 1+1 national infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13). We assessed whether the 1+1 PCV13 schedule had any impact on incidence, disease characteristics, or outcomes after invasive pneumococcal disease (IPD) in eligible children aged 0-3 years. The UK Health Security Agency conducts IPD surveillance and serotyping of invasive pneumococcal isolates via whole-genome sequencing in England. IPD was defined as identification of Streptococcus pneumoniae in a sterile site. We compared IPD incidence, demographics, clinical presentation, comorbidity prevalence, serotype distribution, and case-fatality rates (CFRs) in children from a single birth cohort eligible for the 1+1 schedule (born between Jan 1, 2020, and Dec 31, 2022) who developed IPD in the 2022-23 financial year (April to March) with children from three equivalent historical birth cohorts (born between Jan 1, 2015, and Dec 31, 2019) eligible for the 2+1 schedule who developed IPD during three respective pre-pandemic financial years: 2017-18, 2018-19, and 2019-20. There were a total of 702 IPD episodes in 697 children, including 158 (incidence 8·99 per 100 000 person-years) in the single 1+1 birth cohort and 544 (incidence 9·39 per 100 000 person-years) in the 2+1 birth cohorts, with no significant difference in the incidence of overall IPD (incidence rate ratio 0·96, 95% CI 0·80-1·14, p=0·63), PCV13-type IPD (1·21, 0·71-2·00, p=0·45), or pneumococcal meningitis (0·97, 0·66-1·40, p=0·88). Comorbidity prevalence, clinical presentation, and CFRs were also similar between the two cohorts, as was the percentage of cases in infants too young to be vaccinated (<2 months old) and infants aged 5-11 months who received one or two PCV13 priming doses, in the 1+1 and 2+1 cohorts respectively. After 3 years, the 1+1 schedule continues to provide direct and indirect protection against PCV13-type IPD in children, with no significant change in overall IPD incidence, serotype distribution, clinical presentation, or CFRs in children eligible for the 1+1 compared with the 2+1 schedule. Ongoing surveillance will be important to assess longer-term direct and indirect population protection. None.

How common is otogenic meningitis? A retrospective study in southern Sweden over 18years.

Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children < 2years, compared to 1% post-PCV. The average incidence in the adult population, on the other hand, increased post-PCV, though there were large annual variations. S. pneumoniae was the most commonly identified pathogen in everyone but teenagers, in whom N. meningitidis was predominant. AOM is an important cause of meningitis in children and adults. Though bacterial meningitis almost disappeared in children < 2years after the introduction of PCV, the incidence of pneumococcal meningitis in adults seems to have increased.

1722. Impact of Universal Conjugate Pneumococcal Vaccination in Infants on the Incidence and Mortality of Pneumococcal Meningitis in the General Population in Uruguay, South America (2005 – 2022).

Abstract Background Universal vaccination of children with conjugate vaccines was introduced using the 7 – valent pneumococcal conjugate vaccine (PCV7), which was changed to PCV13 (2 + 1 schedule, years 2008 to 2010), with nationwide coverage of 95 %. The objective of this study is to analyze the impact of universal children vaccination with PCV7 and PCV13 on the incidence and mortality of pneumococcal meningitis (PM) in the general population in Uruguay. Methods This is a descriptive, retrospective study that includes all cases (children and adults) reported to the Department of Health Surveillance of the Ministry of Public Health with a diagnosis of PM between January 1, 2005, and December 31, 2022. Variables: cases per year, sex, age (≤ 15 years and &amp;gt; 15 years), identified serotype, and deaths by year. The average rates of cases per 100,000 inhabitants are described in two periods: Period 1 or pre – universal vaccination (P1) from 2005 to 2007 and Period 2 or post – universal vaccination (P2) from 2011 to 2022, with their respective confidence intervals. Statistical analysis were established based on frequency distribution and statistical significance tests as appropriate, considering a value of p equal to or less than 0.05 as statistically significant. The research was approved by the institutional Ethics Committee. Results The total number of cases (N) is 555, 56.5% are men. 102 cases from the vaccine introduction period (2008 to 2010) were excluded. The N for P1 is 149 (3 years), while for P2 it is 304 (12 years). The main results of incidence and mortality are shown in Table 1 and in the attached graphs. Lethality remains high (26.5% average for the total period). The vaccine serotypes (VS) decrease from 28.2% (95% CI: 20 to 35) in P1 to 12.2% (95% CI: 8.4 to 15) in P2, p: 0.00006. The non – VS increase from 18.1% (95% CI: 11 to 24) in P1 to 44.7% (95% CI: 39.1 to 50.3) in P2, p: 0.00000001. The predominant VS in P1 is 14 (26.2%, 95% CI: 13-39); in P2 there are 8.1%, 95% CI: 0.7-16.9), p: 0.071. The predominant VS in P2 is 3 (46%, 95% CI: 30-62); in P1 9.5% (95% CI: 0.6-18), p: 0.0003. The non – VS predominant in both periods is 12F. Evolution of incidence rates of PM in the general population and in people under and over 15 years of age as a function of time (in years). Mortality rates Conclusion The incidence and mortality of PM statistically decreased in children under 15 years old and in the general population, which can be attributed to herd immunity. Disclosures Marcos Delfino, Pediatrician, Pediatric Infectious Diseases, Pfizer: Finna María Catalina Pírez, Pediatrician, Pediatric infectologist, microbiologist Professor of pediatric, Degree V, Merck, Pfizer: Expert Testimony|Merck, Pfizer: Honoraria

Disease Burden of Meningitis Caused by Streptococcus pneumoniae Among Under-Fives in China: A Systematic Review and Meta-analysis.

Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China. A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I2 and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates. A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine. Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.

Epidemiological Features of Purulent Bacterial Meningitis in the Russian Federation at the Present Stage

Relevance. The decrease in the number of cases of invasive diseases caused by N. meningitidis, S. pneumoniae, H. influenzae and in the world has been associated with measures against the spread of the 2019 coronavirus disease (COVID-19).Aim. Presentation of the epidemiological features of purulent bacterial meningitis (PBM) in the Russian Federation at the present stage.Materials and methods. On the basis of the Russian Reference Center for Monitoring Bacterial Meningitis (RCMC), an in-depth personalized system for recording PBM cases has been established. Since 2010, all territories of the Russian Federation have been included in the monitoring system. In 2022, the RCMC received information on 1596 cases of PBM. The descriptive-evaluative epidemiological method was used in the work: a retrospective analysis.Results. The increase in the incidence of a generalized form of meningococcal infection (GFMI), which began in 2017, was recorded in 2018 and 2019, but in 2020–2021 growth was interrupted: the indicator dropped sharply, amounting to 0.26–0.21 per 100 thousand of the population, which is most likely due to the disunity of the population as a result of measures aimed at combating the new coronavirus infection. Measures to combat COVID-19 were canceled in 2021, and already in 2022 the incidence rate of GBM increased by 1.4 times, while the GFMI by 2 times, amounting to 0.44 per 100 thousand of the population. A sharp decrease in the incidence of PBM caused by S. pneumoniae and H. influenzae in 2020-2021 was replaced in 2022 by an increase in the incidence of pneumococcal meningitis, however, the incidence of meningitis caused by H. influenzae remained at the same level.Conclusion. Continued monitoring of the incidence of PBM and the properties of the pathogen are extremely important tasks in order to identify risk groups and areas for the timely optimization of vaccination measures, given that the three infections that cause bacterial meningitis are vaccine-controlled, and vaccination is recognized as the most effective measure to combat meningococcal, pneumococcal and hemophilic infections.

Trends in laboratory-confirmed bacterial meningitis (2012-2019): national observational study, England.

Bacterial meningitis is associated with significant morbidity and mortality worldwide. We aimed to describe the epidemiology, aetiology, trends over time and outcomes of laboratory-confirmed bacterial meningitis in England during 2012-2019. UK Health Security Agency routinely receives electronic notifications of confirmed infections from National Health Service hospital laboratories in England. Data were extracted for positive bacterial cultures, PCR-positive results for Neisseria meningitidis or Streptococcus pneumoniae from cerebrospinal fluid and positive blood cultures in patients with clinical meningitis. During 2012-19, there were 6554 laboratory-confirmed cases. Mean annual incidence was 1.49/100,000, which remained stable throughout the surveillance period (p=0.745). There were 155 different bacterial species identified, including 68.4% (106/1550) Gram-negative and 31.6% (49/155) Gram-positive bacteria. After excluding coagulase-negative staphylococci (2481/6554, 37.9%), the main pathogens causing meningitis were Streptococcus pneumoniae (811/4073, 19.9%), Neisseria meningitidis (497/4073, 12.2%), Staphylococcus aureus (467/4073, 11.5%), Escherichia coli (314/4073, 7.7%) and group B streptococcus (268/4073, 6.6%). Pneumococcal meningitis incidence increased significantly during 2012-9, while meningococcal, group A streptococcal and tuberculous meningitis declined. Infants aged <3 months had the highest mean incidence (55.6/100,000; 95% CI, 47.7-63.5) driven mainly by group B streptococci, followed by 3-11 month-olds (8.1/100,000; 95% CI 7.1-9.0), where pneumococcal and meningitis predominated. The 30-day case-fatality rate (CFR) was 10.0% (71/6554). Group A streptococcal meningitis had the highest CFR (47/85, 55.3%). The probability of surviving at 30 days was 95.3% (95% CI, 93.4-97.3%) for infants and 80.0% for older adults (77-84%). The incidence of bacterial meningitis has remained stable. The high CFR highlights a need for prevention through vaccination. PHE.

Trends in Pneumococcal and Bacterial Meningitis in Brazil from 2007 to 2019.

The pneumococcal conjugate vaccination (PCV) was introduced into the Brazilian Childhood National Immunization Program in 2010; however, universal pneumococcal vaccination for older adults has not been implemented yet. Our aim is to evaluate the trends in pneumococcal meningitis incidence and case fatality rate (CFR) across all age groups from 2007 to 2019 using data from the National Surveillance System. The pre-PCV (2007-2009) and post-PCV (2011-2019) periods were compared; changes in incidence and CFR were assessed by joinpoint regression. Additional analyses of bacterial meningitis were performed to compare the patterns and trends. Over the 13-year period, 81,203 and 13,837 cases were classified as bacterial and pneumococcal meningitis, respectively. S. pneumoniae was the main etiological agent of bacterial meningitis in adults aged ≥50 years and the most lethal in all age groups. In the post-PCV period, a 56.5% reduction in the average incidence was seen in pneumococcal meningitis in the pediatric population. In contrast, there was an increasing trend among adults. The CFR for pneumococcal and bacterial meningitis remained stable in most age groups during the study period. These findings highlight the value of expanding pneumococcal vaccination policies, including vaccines that provide better indirect protection from children to adults and broadening vaccination to older adults.

206. Using Genome-Wide Association Analysis of Pneumococcal Isolates to Identify Novel Gene Variants in Central Nervous System Infection

Abstract Background Streptococcus pneumoniae is the leading cause of meningitis in children and is associated with significant morbidity and mortality. Despite conjugate pneumococcal vaccines that have otherwise been successful in reducing invasive disease caused by vaccine serotypes, the incidence of pneumococcal meningitis remains relatively unchanged. Using genome-wide association, we identified sequence elements associated with pneumococcal central nervous system (CNS) infection. Methods From 1996 to 2018, 366 clinical pneumococcal isolates were collected from pediatric patients and paired with clinical metadata. All isolates underwent whole-genome sequencing and in silico serotyping. Fifty-four clinical isolates were from children with CNS infection. Sequence element enrichment analysis was performed using elastic net and linear mixed modeling statistical methods to find genetic variants associated with CNS infection. We identified associated genes by mapping statistically associated variants to a serotype 19F reference S. pneumoniae genome. Results CNS isolates spanned 22 unique serotypes; the most common were 22F (n = 6), 7F (n = 5), 18C (n = 4), and 35B (n = 4). We identified two intergenic sequence variants and one intragenic sequence variant significantly associated with CNS infection (p &amp;lt; 1.48 × 10-7). The top intragenic candidate in our analysis was located within cpsC, a gene involved in regulation of capsule synthesis. The CNS infection-associated cpsC variant was found in serotypes 22F (n = 1), 18C (n = 4), and 14 (n = 2). Conclusion The diversity of pneumococcal isolates associated with CNS infection suggests the importance of genetic determinants beyond capsular serotype. We identified a number of novel microbial genetic variants significantly associated with pneumococcal CNS infection across serotypes, including a coding mutation in cpsC. Functional characterization of cpsC variants is needed to inform mechanisms contributing to pneumococcal CNS virulence. Disclosures Anne J. Blaschke, MD, PhD, BioFire Diagnostics/Biomerieux: Advisor/Consultant|BioFire Diagnostics/Biomerieux: Grant/Research Support|BioFire Diagnostics/Biomerieux: IP licensed to BioFire Diagnostics through the University of Utah and royalties received through the University of Utah related to the FilmArray|Merck: Advisor/Consultant.

Purulent Bacterial Meningitis in the Russian Federation: Epidemiology and Immunization

Relevance: Purulent bacterial meningitis and invasive meningococcal disease remain relevant throughout the world and are of particular concern due to high mortality and disability rates, as well as regular outbreaks of meningococcal infections. Objective: To establish epidemiological features of purulent bacterial meningitis and meningococcal disease in the Russian Federation and to highlight the problem of immunization. Materials and methods: Data were collected at the Russian Reference Center for Bacterial Meningitis Monitoring of the Central Research Institute of Epidemiology in the personified system for registering cases of purulent bacterial meningitis, including meningococcal disease, meningitis of non-meningococcal and unknown etiology. We examined 28,440 registered cases. Results: We established that three pathogens, that is, meningococcus, pneumococcus and Haemophilus influenzae, accounted for 84 % of all cases of bacterial meningitis, the most vulnerable age group being children under 5 years of age. Despite a general decrease in the incidence of purulent bacterial meningitis in the Russian Federation in 2010–2019, we noted an increasing incidence of pneumococcal meningitis and invasive meningococcal disease by the end of the study period. In terms of age, the 10-year observation period demonstrated a decrease in the incidence of invasive meningococcal disease in children and its rise among adolescents and young adults; an increase in the incidence of pneumococcal meningitis in adults and a null decrease in children; and the absence of a downward trend in the incidence of Haemophilus meningitis in children. Discussion: Organization of epidemiological monitoring of bacterial meningitis within the system of epidemiological surveillance in the Russian Federation in 2010, its testing and 12-year implementation has enabled us to trace changes in the incidence, mortality, and fatality of the disease and to establish age groups at risk. To reduce the burden of the disease, it is expedient to further improve the existing immunization programs in the Russian Federation.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Pneumococcal meningitis in adults in 2014\u20132018 after introduction of pediatric 13-valent pneumococcal conjugate vaccine in Japan

We assessed the impact of the 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 = 1258) meningitis. The annual incidence of pneumococcal meningitis 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. The odds of developing meningitis were 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 ≥ 65 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- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51–5.65).

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

BackgroundThe 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.MethodsData 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).Results40 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.ConclusionNet 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)

Pneumococcal Meningitis in Adults: A Prospective Nationwide Cohort Study Over a 20-year Period.

BackgroundThe epidemiology and treatment of pneumococcal meningitis has changed with the implementation of conjugate vaccines and the introduction of adjunctive dexamethasone therapy.MethodsWe 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.ResultsThere 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.ConclusionImplementation 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.

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5–7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.

Impact of 10-valent pneumococcal conjugate (PCV 10) vaccination on incidence and mortality rates of pneumococcal meningitis in children under 5 in Brazil

The objective of this study was to assess the impact of 10-valent pneumococcal conjugate (PCV10) vaccination on the incidence and mortality of pneumococcal meningitis in children under 5 in Brazil. A descriptive ecological, population-based quantitative study of secondary data from SINAN records for 2003-2009 and 2011-2017 and on vaccine coverage for 2011-2017 was conducted. The study was approved under permit CAAE 23629719.6.0000.5181. After PCV10 vaccine introduction, a substantial consistent reduction in incidence of and mortality rates of pneumococcal meningitis (70.33% Northeast, 69.49% Southeast) was observed across all regions of Brazil. Although the Human Development Index (HDI) improved during the study period, lethality rates remained high (North = 34.45% pre versus 40.08% post-vaccination), with no clear pattern of reduction associated with improved HDI in Brazil. In the final years of the study, a concerning decline in vaccination coverage rates was evident. Only the South (96.52%) and Mid-West (96.17%) regions attained the ≥ 95% vaccine coverage recommended by the Ministry of Health. This situation highlights the need for urgent measures to restore coverage rates and prevent recrudescence in cases and deaths associated with potentially preventable diseases.

Hospital incidence, in-hospital mortality and medical costs of pneumococcal disease in Spain (2008–2017): a retrospective multicentre study

Objective The aim of this study was to analyze the characteristics of the patients attended with a pneumococcal disease in Spanish hospitals, to evaluate trends in hospital incidence and in-hospital mortality and to quantify patients’ use of resources and medical costs. Methods Medical admission records of patients admitted due to pneumococcal disease between 1 January 2008 and 31 December 2017 were obtained from a Spanish hospital discharge database. Records were identified with the International Statistical Classification of Diseases and Related Health Problems, 9th and 10th version codes corresponding to pneumococcal pneumonia, bacteraemia, pyogenic arthritis, endocarditis, meningitis, peritonitis and unspecified pneumococcal infections. Results Admissions of 168,074 patients were analyzed, with a mean age of 63.5 years (median = 72; interquartile range = 28). Pneumococcal pneumonia was responsible for 64.1% of all admissions, with a hospital incidence of 31.1 per 10,000 patients that decreased significantly over the study period (p = .002). Hospital incidence of meningitis also displayed a decreasing trend over the study period (p = .003), whereas incidence of bacteraemia and pyogenic arthritis increased significantly (p = .001; p = .004). Mean Charlson Comorbidity Index was 3.3 (standard deviation = 2.2). In-hospital mortality was 7.0% over the study period, being the highest in patients admitted with endocarditis (17.2%). Sepsis, acute renal failure, disorders of fluid electrolyte and acid-base balance, heart failure and acute respiratory failure were strongly associated with in-hospital mortality. Mean length of hospital stay was of 11.1 days (median = 22; interquartile range = 26) and there was a majority of urgent admissions (95.0%); the most extended stays were registered in patients with endocarditis, meningitis and pyogenic arthritis. The mean hospital admission cost was €5676, €104.2 million annually for all registered patients; 50.3% of all costs were associated with pneumonia, whereas the highest admission costs were registered in patients with endocarditis (€15,991) and meningitis (€11,934). Mean admission costs increased significantly over the study period for pneumonia and bacteraemia and decreased for endocarditis. Conclusions The incidence of pneumococcal pneumonia and meningitis decreased over the study period after the introduction of vaccination in Spain. The advanced age of patients and presence of chronic comorbid conditions that are associated to in-hospital mortality must be taken into account when improving care protocols and upcoming vaccination plans.

PIN12 THE COST-EFFECTIVENESS OF THE 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN CHINESE CITIES

The 13-valent pneumococcal conjugate vaccine (PCV13) offers protection against 13 pneumococcal serotypes, reducing the incidence of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM). This study estimates the cost-effectiveness of immunization of PCV13 in select Chinese cities. We localized a previously published cost-effectiveness model comparing PCV13 to no vaccination to Beijing, Shanghai, Suzhou, Chengdu, Karamay, Qingdao, and Shenzhen. A systematic literature review (SLR) through 10/11/2019 was undertaken to identify previously published PCV cost-effectiveness models in China. The SLR was utilized to identify sources for estimating the age-specific incidence of pneumococcal bacteremia, pneumococcal meningitis, pneumonia, and OM. Sources identified in the literature review were combined with data from the CHIRA database (2013-2015) to estimate incidence rates. Age-specific direct healthcare costs for each health state were sourced directly from the CHIRA database (2013-2015) and available for Tier 1 cities and nationally. The base case analysis considered a vaccination rate of 85%, herd effect, a 5% discount rate, and took a payer perspective. The number of IPD, pneumonia, and OM cases avoided due to PCV13 vaccination in each city ranged from 13 to 581, 1,039 to 43,769, and 174 to 7,112, respectively. Deaths avoided ranged 18 to 1,061 (1 to 29 for IPD and 17 to 1,032 for pneumonia), which resulted in 275 to 15,134 additional quality-adjusted life-years for PCV13 vaccination compared to no vaccination. The incremental total direct costs of the PCV13 vaccination program ranged between ¥5,462,884 and ¥156,224,157 in the included cities. The incremental cost-effectiveness ratio for PCV13 compared to no vaccination for each city was between ¥1,300 and ¥19,684 per QALY gained, below 1xGDP per capita of each city. PCV13 can be considered highly cost-effective when compared to no vaccination at a vaccination rate of 85% in Beijing, Shanghai, Suzhou, Chengdu, Karamay, Qingdao, and Shenzhen.

Molecular serotype-specific identification of Streptococcus pneumoniae using loop-mediated isothermal amplification

In children, the incidence of pneumococcal meningitis has decreased since the introduction of pneumococcal conjugate vaccine (PCV7 and PCV13). However, since the introduction of the vaccine, developed countries have seen the emergence of non-PCV13 serotypes. However, invasive pneumococcal disease (IPD) caused by PCV13-targeted serotypes still represents an important public health problem in resource-limited countries. To develop a rapid, simple, and cost-effective assay to detect serotypes of Streptococcus pneumoniae, we developed a novel loop-mediated isothermal amplification (LAMP) assay based on the sequences available for the 13 capsular types that are included in PCV13: 1, 3, 4, 5, 6 A, 6B, 7 F, 9 V, 14, 18 C, 19 A, 19 F, and 23 F. We evaluated test reactivity, specificity, sensitivity and performance, and compared the results between established LAMP and conventional PCR assays. To support its clinical use, the detection limits of the LAMP assay were evaluated using bacterial genomic DNA-spiked cerebrospinal fluid (CSF) and blood specimens. We confirmed the specificity of the LAMP assay using 41 serotypes of pneumococcal strains. The sensitivity of the LAMP assay was 10 to 100 copies per reaction, compared to 10 to 104 copies per reaction for PCR assays. The detection limits of the LAMP assay were comparable when using DNA-spiked CSF and blood specimens, as compared to using purified DNA as the template. In conclusion, a rapid and simple LAMP-based pneumococcal serotyping method has been developed. This is the first report of a LAMP method for a PCV13 serotype-specific identification assay, which could be a promising step to facilitate epidemiological studies of pneumococcal serotyping.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis, Burkina Faso, 2016-2017.

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. 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. 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. 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.