Vaccine-preventable Pediatric Acute Bacterial Meningitis in France: A Time Series Analysis of a 19-Year Prospective National Surveillance Network.

BACKGROUND: In France, vaccination has been implemented against Hi serotype b (Hib), pneumococcus with pneumococcal conjugate vaccines (PCV), and Neisseria meningitidis serogroup C (MenC). These interventions with different coverage and uptake have disrupted the epidemiology of vaccine-preventable acute bacterial meningitis (ABM). METHODS: We analyzed data from a French prospective surveillance network of ABM in children ≤15 years old enrolled by 259 pediatric wards (estimated national coverage: 61%). From 2001 to 2020, the effect of vaccine implementation was estimated with segmented linear regression. RESULTS: We analyzed 7,186 cases, mainly due to meningococcus (35.0%), pneumococcus (29.8%), and Hi (3.7%). MenC ABM incidence decreased (-0.12%/month, 95% CI: -0.17 to -0.07, P < 0.001) with no change for the overall meningococcal ABM when comparing the pre-MenC vaccination and the post-MenC vaccination trends. Despite a decreasing MenB ABM incidence without a vaccination program (-0.43%/month, 95% CI: -0.53 to -0.34, P < 0.001), 68.3% of meningococcal ABM involved MenB. No change in pneumococcal ABM incidence was observed after the PCV7 recommendation. By contrast, this incidence significantly decreased after the switch to PCV13 (-0.9%/month, 95% CI: -1.6 to -0.2%, P = 0.01). After May 2014, a rebound occurred (0.5%/month, 95% CI: 0.3-0.8%, P < 0.001), with 89.5% of non-PCV13 vaccine serotypes. Hib ABM incidence increased after June 2017. CONCLUSIONS: PCV7 and MenC vaccine introduction in France, with slow vaccine uptake and low coverage, had no to little impact as compared to the switch from PCV7 to PCV13, which occurred when coverage was optimal. Our data suggest that MenB and next-generation PCVs could prevent a large part of the ABM incidence in France.

Prevalence, aetiology, vaccination coverage and spatio-temporal pattern among patients admitted with acute bacterial meningitis to the sentinel hospital surveillance network in Yemen, 2014-20, before and during the civil war.

BACKGROUND: Acute bacterial meningitis (ABM) is a serious health issue in Yemen where civil war, which continues unabated, has crippled the healthcare system. We conducted a nationwide retrospective observational study in Yemeni sentinel hospitals to identify the prevalence, aetiology, vaccination coverage and spatio-temporal pattern of ABM in children aged <5 years before and during the civil war, 2014-20. METHODS: Cerebrospinal fluid samples were collected from hospitalized children and were analysed macroscopically for appearance and microscopically by Gram stain and white blood cell count. Culture and latex agglutination tests were performed. Data on the prevalence of and vaccination coverage for ABM were obtained from the Ministry of Health. Joinpoint regression was used to assess the annual percent change (APC) of ABM prevalence and vaccination coverage. Pearson's correlation was used to evaluate the association between ABM prevalence and vaccination coverage. RESULTS: In total, 11 339 hospitalized children had suspected cases of ABM (prevalence, 40.07/100 000 of the whole Yemeni population) and 2.6% (293/11 339) of suspected ABM cases were confirmed (prevalence, 1.04/100 000 of the whole Yemeni population). The dominant pathogens were Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). The civil war reduced the Hib and pneumococcal vaccination coverage (APC = -1.92), reaching its lowest (79.5%) in 2018. The prevalence of suspected ABM increased (APC = 3.46), reaching its maximum (6.08/100 000 of the whole Yemeni population) in 2019. The conflict inversely correlated with the ABM prevalence and vaccination coverage (Pearson correlation coefficient (r), -0.69 to -0.53). Ta'izz region, which was severely affected by the civil war, had the highest prevalence of suspected ABM (120.90/100 000 of the whole Yemeni population) and lowest vaccination coverage (60%). CONCLUSIONS: The civil war had a negative impact on vaccination coverage and coincided with increasing prevalence of ABM in Yemen. Streptococcus pneumoniae is the dominant causative pathogen.

Evaluation of the World Health Organization Global Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network's Laboratory External Quality Assessment Programme, 2014-2019.

Introduction. In 2009, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine Preventable Disease (IB-VPD) Surveillance Network (GISN) to monitor the global burden and aetiology of bacterial meningitis, pneumonia and sepsis caused by Haemophilus influenzae (Hi), Neisseria meningitidis (Nm) and Streptococcus pneumoniae (Sp).Hypothesis/Gap Statement. The GISN established an external quality assessment (EQA) programme for the characterization of Hi, Nm and Sp by culture and diagnostic PCR.Aim. To assess the performance of sentinel site laboratories (SSLs), national laboratories (NLs) and regional reference laboratories (RRLs) between 2014 and 2019 in the EQA programme.Methodology. Test samples consisted of bacterial smears for Gram-staining, viable isolates for identification and serotyping or serogrouping (ST/SG), plus simulated cerebrospinal fluid (CSF) samples for species detection and ST/SG by PCR. SSLs and NLs were only required to analyse the slides for Gram staining and identify the species of the live isolates. RRLs, and any SLs and NLs that had the additional laboratory capacity, were also required to ST/SG the viable isolates and analyse the simulated CSF samples.Results. Across the period, 69-112 SS/NL labs and eight or nine RRLs participated in the EQA exercise. Most participants correctly identified Nm and Sp in Gram-stained smears but were less successful with Hi and other species. SSLs/NLs identified the Hi, Nm and Sp cultures well and also submitted up to 56 % of Hi, 62 % of Nm and 33 % of Sp optional ST/SG results each year. There was an increasing trend in the proportion of correct results submitted over the 6 years for Nm and Sp. Some SSLs/NLs also performed the optional detection and ST/SG of the three organisms by PCR in simulated CSF from 2015 onwards; 89-100 % of the CSF samples were correctly identified and 76-93 % of Hi-, 90-100 % of Nm- and 75-100 % of Sp-positive samples were also correctly ST/SG across the distributions. The RRLs performed all parts of the EQA to a very high standard, with very few errors across all aspects of the EQA.Conclusion. The EQA has been an important tool in maintaining high standards of laboratory testing and building of laboratory capacity in the GISN.

Meningitis and encephalitis in Poland in 2021.

Introduction: Meningitis meningitis and/or encephalitis regardless of etiology are subject to monitoring in Poland as part of routine epidemiological surveillance. In this paper, meningitis and/or encephalitis in 2021 caused by Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae and tick-borne encephalitis virus are discussed in detail. In Poland, immunoprophylaxis in the form of mandatory or recommended vaccinations is used to prevent diseases caused by the aforementioned etiological agents. Aim of the study: The aim of this study was to assess the epidemiological incidence of meningoencephalitis and encephalitis in Poland, in 2021 including analysis of the impact of the COVID-19 pandemic. Material and methods: To analyse the epidemiological situation of neuroinfections in Poland, we used data sent to NIPH NIH - NRI by Voivodeship Sanitary and Epidemiological Stations and published in the annual bulletin: "Infectious diseases and poisonings in Poland in 2021" and "Protective vaccination in Poland in 2021" as well as individual epidemiological interviews recorded in the EpiBase system. Results: In 2021, a total of 973 cases of meningitis and/or encephalitis were registered in Poland. This is a 16.1% increase in the number of cases compared to 2020, but still a 57% decrease in the number of cases compared to 2019 when 2,249 cases were recorded. For infections of bacterial etiology, including cases of neuroborreliosis, the number of cases increased by 38.3% (from 376 to 520, incidence from 0.96 to 1.76 per 100,000). Compared to 2020 and 2019, the incidence of meningitis and/or encephalitis of N. meningitidis decreased by 10.7% (from 0.13 to 0.15) and 47.4% (from 0.25 to 0.13), respectively, and for H. influenzae by 75% (from 0.01 to 0.03) and 70% (from 0.01 to 0.03). For S. pneumoniae, we can speak of an increase in incidence against 2020 of 57.1% (121 vs 77 cases, incidence 0.32 vs 0.20) and a decrease against 2019. (121 vs 190, incidence 0.32 vs 0.47). Infections of viral etiology accounted for 47% of all registered cases. There was a slight decrease in their number, by 2% (from 462 to 453 cases). In addition, there was an increase in cases of tick-borne encephalitis, from 158 in 2020 to 210 in 2021 (an increase of 32.9%), and a decrease in cases from 265 in 2019 (a decrease of 20.8%). Summary and conclusions: 2021 showed an overall upward trend in the number of recorded cases of bacterial meningitis and/or encephalitis, and a slight decrease in the number of viral meningitis and/or encephalitis cases compared to 2020. Still, the observed number of meningitis and/or encephalitis cases in 2021, both bacterial and viral incidences, remains below the levels observed in the pre-pandemic COVID-19 period (2019). As a result of the SARS-CoV-2 outbreak, the introduction of measures to limit the transmission of the SARS-CoV-2 virus has been observed to reduce the spread of other droplet- and airborne pathogens, thus also pathogens such as S. pneumoniae, H.influenzae and N. menningitidis.

[Interpretation of defeating meningitis by 2030: a global road map].

Meningitis is a life-threatening disease. In order to reduce its threat to public health, the World Health Assembly indorsed a resolution in 2020 for urgent global action to prevent and control meningitis. Defeating Meningitis by 2030: a Global Roadmap was officially launched by the World Health Organization in 2021. We interpreted some key information of the roadmap from the aspects of coverage, objectives and pillar strategies, providing ideas for further strengthening the prevention and control of bacterial meningitis in China.

Bacterial meningitis: Aetiology, risk factors, disease trends and severe sequelae during 50 years in Sweden.

BACKGROUND: Bacterial meningitis (BM) is a rare but severe infection. Few population-based studies have characterised BM episodes and sequelae over long periods. METHODS: This was a population-based observational cohort study with national coverage, using data on aetiological pathogens, sex, premorbid conditions, steroid pretreatment, severe sequelae and birth, death and diagnosis dates collected from 10,339 patients with BM reported to the National Board of Health and Welfare in Sweden between 1964 and 2014. RESULTS: During the 50-year study period, the incidence of BM decreased in young children, but not in the elderly. The most common cause of BM was pneumococci (34%), followed by Haemophilus influenzae (26%), and meningococci (18%), mainly community acquired. Premorbid conditions were found in 20%. After the H. influenzae type b vaccine was introduced in 1993, the BM incidence decreased by 36%. Following pneumococcal conjugated vaccine introduction in 2009, the incidence and 30-day mortality from pneumococcal meningitis decreased by 64% and 100%, respectively, in previously healthy children, and the 30-day mortality decreased by 64% among comorbid adults. The BM incidence in immunosuppressed patients increased by 3% annually post vaccine introduction. The 30-day mortality was 3% in children and 14% in adults, and the rate of severe sequelae was 44%. On average, patients lost 11 years of healthy life due to BM. CONCLUSION: The introduction of conjugated vaccines into the childhood vaccination program has reduced the incidence of BM in young children, but not in adults. Post vaccine introduction, patients present with more premorbid conditions and other bacterial causes of BM, emphasising the need for a correct diagnosis when treating these infections.

Current status and challenges in the care of patients with bacterial meningitis in the Philippines: A scoping review.

OBJECTIVE: Bacterial meningitis is associated with high morbidity and mortality if not treated early. Due to the high disease burden, there are barriers in the provision of healthcare services for these patients, especially in low- to middle-income countries, such as the Philippines. We aimed to give an overview of healthcare services delivery and identify gaps in the provision of care for patients with bacterial meningitis in the Philippines. METHOD: We conducted a scoping review on the available literature on the epidemiology, research, health services delivery, diagnostics and management of Filipino patients with bacterial meningitis. A qualitative summary of the results was conducted to provide an overview of the findings. RESULTS: There is a paucity of epidemiological data and research on bacterial meningitis. Healthcare expenditure remains out-of-pocket, with limited coverage from the national health insurance programme. There is an inadequate number of neurologists as well as inequities in the distribution of manpower and facilities due to the devolution of the healthcare system. Diagnosis remains a challenge due to the inaccessibility of tests for CSF analysis. Costs of antibiotics, adjunctive treatment, neurosurgical interventions and rehabilitation are also prohibitive. Outbreaks can be prevented by strengthening existing surveillance systems and improving vaccination coverage against the most common causative organisms. CONCLUSION: Enormous challenges still exist with regards to health services delivery in patients with bacterial meningitis in the Philippines in terms of epidemiologic data and research, access to healthcare facilities and diagnostic tools, healthcare costs, surveillance systems and immunisation against causative pathogens.

The Burden of Invasive Bacterial Disease and the Impact of 10-Valent Pneumococcal Conjugate Vaccine in Children <5 years hospitalized for Meningitis in Lusaka, Zambia, 2010-2019.

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 Global Landscape of Pediatric Bacterial Meningitis Data Reported to the World Health Organization-Coordinated Invasive Bacterial Vaccine-Preventable Disease Surveillance Network, 2014-2019.

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.

Toward Establishing Integrated, Comprehensive, and Sustainable Meningitis Surveillance in Africa to Better Inform Vaccination Strategies.

Large populations across sub-Saharan Africa remain at risk of devastating acute bacterial meningitis epidemics and endemic disease. Meningitis surveillance is a cornerstone of disease control, essential for describing temporal changes in disease epidemiology, the rapid detection of outbreaks, guiding vaccine introduction and monitoring vaccine impact. However, meningitis surveillance in most African countries is weak, undermined by parallel surveillance systems with little to no synergy and limited laboratory capacity. African countries need to implement comprehensive meningitis surveillance systems to adapt to the rapidly changing disease trends and vaccine landscapes. The World Health Organization and partners have developed a new investment case to restructure vaccine-preventable disease surveillance. With this new structure, countries will establish comprehensive and sustainable meningitis surveillance systems integrated with greater harmonization between population-based and sentinel surveillance systems. There will also be stronger linkage with existing surveillance systems for vaccine-preventable diseases, such as polio, measles, yellow fever, and rotavirus, as well as with other epidemic-prone diseases to leverage their infrastructure, transport systems, equipment, human resources and funding. The implementation of these concepts is currently being piloted in a few countries in sub-Saharan Africa with support from the World Health Organization and other partners. African countries need to take urgent action to improve synergies and coordination between different surveillance systems to set joint priorities that will inform action to control devastating acute bacterial meningitis effectively.

Defeating meningitis by 2030 - an ambitious target.

Acute bacterial meningitis remains a major cause of mortality and morbidity, especially in lower-income countries. Thus, in 2017, a group of people concerned with this continuing problem came together to plan a way forward. A task force was established, a baseline situation analysis undertaken and a road map for a new initiative 'Defeating Meningitis by 2030' prepared. This road map will be launched officially in September 2021. Additional finances for meningitis control will be needed, together with the support of many different institutions and people with different skills, if the 'Defeating Meningitis by 2030' initiative is to achieve its ambitious goals.

Community-acquired bacterial meningitis.

Progress has been made in the prevention and treatment of community-acquired bacterial meningitis during the past three decades but the burden of the disease remains high globally. Conjugate vaccines against the three most common causative pathogens (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae) have reduced the incidence of disease, but with the replacement by non-vaccine pneumococcal serotypes and the emergence of bacterial strains with reduced susceptibility to antimicrobial treatment, meningitis continues to pose a major health challenge worldwide. In patients presenting with bacterial meningitis, typical clinical characteristics (such as the classic triad of neck stiffness, fever, and an altered mental status) might be absent and cerebrospinal fluid examination for biochemistry, microscopy, culture, and PCR to identify bacterial DNA are essential for the diagnosis. Multiplex PCR point-of-care panels in cerebrospinal fluid show promise in accelerating the diagnosis, but diagnostic accuracy studies to justify routine implementation are scarce and randomised, controlled studies are absent. Early administration of antimicrobial treatment (within 1 hour of presentation) improves outcomes and needs to be adjusted according to local emergence of drug resistance. Adjunctive dexamethasone treatment has proven efficacy beyond the neonatal age but only in patients from high-income countries. Further progress can be expected from implementing preventive measures, especially the development of new vaccines, implementation of hospital protocols aimed at early treatment, and new treatments targeting checkpoints of the inflammatory cascade.

Knowledge, beliefs and practices regarding prevention of bacterial meningitis in Burkina Faso, 5 years after MenAfriVac mass campaigns.

BACKGROUND: To adapt communications concerning vaccine prevention, we studied knowledge, beliefs and practices around meningitis risk and prevention in a young adult population in Burkina Faso in 2016, 5 years after the MenAfriVac® mass campaign and one year before the vaccine's inclusion in the infant immunization schedule. METHODS: In a representative sample of the population aged 15 to 33 years (N = 220) in Bobo-Dioulasso, Burkina Faso, study nurses administered a standardized paper questionnaire consisting of predominantly open questions, collecting information on meningitis risk factors and prevention, and on exposure to dry air and kitchen fire smoke. We identified themes and analyzed their frequency. We created a meningitis knowledge score (range 0 to 4) based on pre-defined best responses and analyzed the determinants of knowledge score levels ≥2 (basic score) and ≥3 (high score) using multivariate logistic regression. RESULTS: Biomedically supported facts and good practices were known by the majority of participants (eg vaccine prevention, 84.5%). Younger women aged 15-20 years had a higher frequency of low scores <2 (17.0%) compared to older women aged 21-33 years (6.3%) and men of both age groups (3.8%). Junior secondary School attendance explained the differences between the two groups of women, the gender gap for the older, but not the young women, and explained score differences among young women. Local understandings and practices for risk and prevention were commonly reported and used (risk from unripe mango consumption and prevention through nasal application of shea nut butter). DISCUSSION: This study shows a gender gap in knowledge of meningitis risk and prevention, largely due to education-level inequalities. Women below 21 years had particularly low levels of knowledge and may need interventions outside schools and perinatal care. Our study suggests a strong adherence to local understandings of and practices around meningitis risk and prevention, which should be taken into account by vaccination promotion.

The Potentials of Melatonin in the Prevention and Treatment of Bacterial Meningitis Disease.

Bacterial meningitis (BM) is an acute infectious central nervous system (CNS) disease worldwide, occurring with 50% of the survivors left with a long-term serious sequela. Acute bacterial meningitis is more prevalent in resource-poor than resource-rich areas. The pathogenesis of BM involves complex mechanisms that are related to bacterial survival and multiplication in the bloodstream, increased permeability of blood-brain barrier (BBB), oxidative stress, and excessive inflammatory response in CNS. Considering drug-resistant bacteria increases the difficulty of meningitis treatment and the vaccine also has been limited to several serotypes, and the morbidity rate of BM still is very high. With recent development in neurology, there is promising progress for drug supplements of effectively preventing and treating BM. Several in vivo and in vitro studies have elaborated on understanding the significant mechanism of melatonin on BM. Melatonin is mainly secreted in the pineal gland and can cross the BBB. Melatonin and its metabolite have been reported as effective antioxidants and anti-inflammation, which are potentially useful as prevention and treatment therapy of BM. In bacterial meningitis, melatonin can play multiple protection effects in BM through various mechanisms, including immune response, antibacterial ability, the protection of BBB integrity, free radical scavenging, anti-inflammation, signaling pathways, and gut microbiome. This manuscript summarizes the major neuroprotective mechanisms of melatonin and explores the potential prevention and treatment approaches aimed at reducing morbidity and alleviating nerve injury of BM.

Changing Epidemiology of Bacterial Meningitis Since Introduction of Conjugate Vaccines: 3 Decades of National Meningitis Surveillance in The Netherlands.

BACKGROUND: The epidemiology of acute bacterial meningitis has changed substantially since the introduction of conjugate vaccines. METHODS: We analyzed nationwide surveillance data of all cerebrospinal fluid isolates received by the Netherlands Reference Laboratory for Bacterial Meningitis in the Netherlands. We assessed the impact of conjugate vaccines on incidence (defined as episodes per 100 000 population per year) and for different age groups using incidence rate ratios (IRRs), comparing incidence before and after conjugate vaccine introduction. RESULTS: We analyzed 17 393 episodes, of which 5960 episodes (34%) occurred in preschool children (aged 3 months to 4 years). Overall, bacterial meningitis incidence decreased from 6.37 to 1.58 between 1989-1993 and 2014-2019 (IRR, 0.25 [95% confidence interval {CI}, .23-.26]; P < .001). This decrease was most pronounced in preschool and school-aged children (5-15 years); IRR, 0.10 [95% CI, .09-.12] and 0.08 [95% CI, .06-.10]; both P < .001. The incidence was highest in young infants (<90 days) due to a high incidence of group B Streptococcus and Escherichia coli meningitis (42.48 and 19.49, respectively). Conjugate vaccines effectively reduced the incidence of Haemophilus influenzae type b, Neisseria meningitidis serogroup C, and 10 pneumococcal serotypes (IRRs, .02-.04; P < .001). At the end of the observed period, Streptococcus pneumoniae caused the majority of meningitis cases (829/1616 [51%]), mostly in older adults (aged 45-64 years) and elderly adults (aged ≥65 years; incidence of 1.06 and 1.54, respectively). CONCLUSIONS: Conjugate vaccines reduced the burden of bacterial meningitis, especially in children. The efforts for new measures to prevent bacterial meningitis should be focused on neonates and elderly, as the residual rate of disease is still high in these age groups.

Local complications of adjunct intrathecal antibiotics for nosocomial meningitis associated with gram-negative pathogens: a meta-analysis.

Direct delivery of antibiotics to the ventricular system offers an alternative for the management of nosocomial meningitis. However, the available literature frequently results in controversial findings regarding its safety. The present meta-analysis aimed at summarizing the risk of local complications after the administration of intraventricular/intrathecal (IVT/IT) antibiotics for the treatment of ventriculitis/meningitis (VM) associated with gram-negative pathogens. We systematically searched the medical literature from 1964 until July 2018, for clinical studies reporting on complications after the index treatment. The quality of the eligible studies was classified as "high," "moderated," and "low" for randomized controlled trials, observational studies, and case series, respectively. The results were summarized as pooled frequencies, estimated by the random- or fixed-effects models, according to the inter-study heterogeneity. The publication bias was visualized in trim-and-fill funnel plots. Τhe analysis included twenty-three primary studies with 229 patients. The overall complication rate was as high as 0.13 (95% CI 0.08; 0.19, I2 = 9%); chemical meningitis and seizures represented the majority of the complications, with an occurrence rate of 0.11 (95% CI 0.07; 0.17, I2 = 0%) and 0.07 (95% CI 0.04; 0.12; I2 = 0%), respectively. The meta-analysis was based on studies of "moderate" and "low" reporting quality, while the publication bias after inspecting of the funnel plots revealed significant asymmetry. The present review denotes the absence of large, high-quality studies in the field. Nevertheless, IVT/IT was associated with moderate morbidity, mainly attributed to chemical meningitis and seizures. Further high-quality studies are still required before this therapeutic modality becomes broadly established.

Conjugate vaccines dramatically reshaped the epidemiology of bacterial meningitis in a well-defined child population.

AIM: We explored the impact of vaccination on bacterial meningitis in a well-defined population of children on the island of Crete, Greece, over a 27-y period. METHODS: This was a retrospective observational study of all mandatory notifications of bacterial meningitis in patients aged 1 mo-14 y from 1991 to 2017. RESULTS: There were 245 patients with proven (n = 227) or suspected (n = 18) bacterial meningitis, and eight deaths were recorded, giving a case fatality rate of 3.3%. The mean annual incidence rate (IR) per 100 000 children was 4.9 for Neisseria meningitidis, 2.2 for Streptococcus pneumoniae and 0.4 for Haemophilus influenzae type b (Hib). Cases of meningitis C dropped significantly after the conjugate meningitis C vaccine was licensed for routine vaccination in Greece in 2000 (IR of 1.5 vs 0.3, P < 0.028) while the Streptococcus pneumoniae cases showed a threefold decrease after the PCV13 vaccine was licensed in Greece in 2009 (IR 2.7 vs 1.0, P < 0.03). Vaccination had already eliminated Hib in Greece in the 1990s. CONCLUSION: Bacterial meningitis cases decreased in children following the introduction of the meningitis C and PCV13 vaccines in Greece. Hib had already disappeared and significant reductions in meningitis C and Streptococcus pneumoniae were observed.