Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

Assessment of potential drug-related problems (PDRP) and clinical outcomes in bacterial meningitis patients admitted to tertiary care hospitals.

Meningitis is an important cause of morbidity and mortality in children and adults. Its treatment strategy varies with age and gender. To assess potential drug-related problems (PDRP) and clinical outcomes in bacterial meningitis patients, a multicenter, clinical, descriptive, cross-sectional prospective observational study in 120 patients admitted to different tertiary care hospitals in Karachi was conducted. It includes both males 48% and females 52% belonging from all age groups i.e. peadiatrics (01 to 12 years), adults (18 to 65 years), and geriatrics (66 to 75 years). Out of these 72 patients were admitted in the public sector and 48 patients were admitted in private sector hospitals. Nosocomial infections were developed in 41% of patients during their stay at the hospital. Potentially nephrotoxic drugs were administered to all BM patients, these drugs should be administered carefully. Majorly Ceftriaxone was administered to 86% of patients, Vancomycin 71%, and meropenem 73% whereas 68% of patients were administered piperacillin-tazobactam. Organisms involved as causative agents in the majority of patients are Neisseria meningitides, Pseudomonas aeruginosa and, Streptococcus pneumoniae. DRPs impacted patient clinical outcomes in presence of many other factors like comorbidities, DDIs, Nis, administration of potentially nephrotoxic drugs, and administration of watch group and reserve group antibiotics without having culture sensitivity test, even after having CST no principles of de-escalation for antibiotics were done, which is a very important factor for hospitalized patients having IV antibiotics. The mortality rate among BM patients was 66%. The majority of patients (87%) stay at the hospital was 1-10 days. The present study helped in the identification of DRPs along with some other factors affecting the clinical outcomes in patients suffering from bacterial meningitis. Healthcare professionals should receive awareness and education on the importance of CST before initiating antibiotic therapy. Pharmacist-led medication review is necessary and should be followed to avoid negative outcomes and serious consequences related to DRPs.

Clinical variation in the early assessment and management of suspected community-acquired meningitis: a multicentre retrospective study.

BACKGROUND: Bacterial meningitis is a medical emergency and timely management has been shown to improve outcomes. The aim of this study was to compare the early assessment and management of adults with suspected community-onset meningitis between hospitals and identify opportunities for clinical practice improvement. METHODS: This retrospective cohort study was conducted at three principal referral hospitals in Sydney, Australia. Adult patients with suspected meningitis undergoing cerebrospinal fluid sampling between 1 July 2018 and 31 June 2019 were included. Relevant clinical and laboratory data were extracted from the medical record. Differences between sites were analysed and factors associated with time to antimicrobial therapy were assessed by Cox regression. RESULTS: In 260 patients, the median time from triage to antibiotic administration was 332 min with a difference of up to 147 min between hospitals. Median time from triage to lumbar puncture (LP) was 366 min with an inter-hospital difference of up to 198 min. Seventy per cent of patients had neuroimaging prior to LP, and this group had a significantly longer median time to antibiotic administration (367 vs 231 min; P = 0.001). Guideline concordant antibiotics were administered in 84% of patients, with only 39% of those administered adjunctive corticosteroids. Seven (3%) patients had confirmed bacterial meningitis. Modifiable factors associated with earlier antimicrobial administration included infectious diseases involvement (adjusted hazard ratio [aHR], 1.50 [95% confidence interval (CI), 1.01-2.24]) and computed tomography (CT) scanning (aHR, 0.67 [95% CI, 0.46-0.98]). CONCLUSION: Opportunities for improvement include reducing the time to LP and antibiotic administration, improving coadministration of corticosteroids and avoiding potentially unnecessary CT scanning.

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.

Accurate, fast and cost-effective simultaneous detection of bacterial meningitis by qualitative PCR with high-resolution melting.

Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are leading causes of meningitis and acute invasive infections. PCR-based methods are widely used for the diagnosis and surveillance of bacterial pathogens because of their high sensitivity, specificity and high-throughput capabilities compared with conventional laboratory methods. This study evaluated a high-resolution melting qualitative PCR analysis method for the simultaneous detection of these three pathogens. The assay has been optimized to detect three species-specific genes of each organism isolated from clinical samples, enabling accurate identification of the etiological agent. The method proved to be highly sensitive and cheaper than the real-time PCR TaqMan® system because it is probe-free; it could be used for the diagnosis of invasive diseases in public health laboratories of developing countries.

The Cost of Suspected and Confirmed Bacterial Meningitis Cases Treated at Jimma University Medical Center, Ethiopia.

Background: Infections of the central nervous system (CNS) such as meningitis or encephalitis can be caused by myriad of microorganisms and may be life-threatening. In Ethiopia, it is an important cause of premature death and disability, being the 9th most common cause of years of life lost and loss of disability-adjusted life years.The objective of this study was to estimate the cost of suspected and confirmed bacterial meningitis among inpatient managed patients at JUMC. Methods: A facility-based cross-sectional study was conducted from July 28 to September 12, 2018. A semi-structured questionnaire was used in this study. Checklists were used to collect the types of laboratory tests performed and prescribed medications. This cost of illness study was conducted from the patient perspectives. We employed a micro-costing bottom-up approach to estimate the direct cost of meningitis. The human capital approach was used for estimating wages lost. Result: Among total patients admitted and treated in JUMC, higher proportions (69.8%) were suspected bacterial meningitis but have been treated as confirmed cases. Total median costs for both suspected and confirmed bacterial meningitis patients were estimated to be ETB 98,812.32 (US $ 3,593.2; IQR 1,303.0 to 5,734.0). Total median direct cost was ETB 79,248.02 (US $ 2,881.75; IQR 890.7 to 3,576.7). Moreover, 45.3% of the patients reported that they were either admitted or given medication at JUMC or nearby health facility before their current admissions. Conclusion: These findings indicate that most cases of bacterial meningitis were treated only empirically, and the cost of the treatment was high, especially for resource-limited countries like Ethiopia. To minimize the burden of meningitis and avoid unnecessary hospitalizations, the availability of diagnostic techniques is vitally important.

Risk-stratification in febrile infants 29 to 60 days old: a cost-effectiveness analysis.

BACKGROUND: Multiple clinical prediction rules have been published to risk-stratify febrile infants ≤60 days of age for serious bacterial infections (SBI), which is present in 8-13% of infants. We evaluate the cost-effectiveness of strategies to identify infants with SBI in the emergency department. METHODS: We developed a Markov decision model to estimate outcomes in well-appearing, febrile term infants, using the following strategies: Boston, Rochester, Philadelphia, Modified Philadelphia, Pediatric Emergency Care Applied Research Network (PECARN), Step-by-Step, Aronson, and clinical suspicion. Infants were categorized as low risk or not low risk using each strategy. Simulated cohorts were followed for 1 year from a healthcare perspective. Our primary model focused on bacteremia, with secondary models for urinary tract infection and bacterial meningitis. One-way, structural, and probabilistic sensitivity analyses were performed. The main outcomes were SBI correctly diagnosed and incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: In the bacteremia model, the PECARN strategy was the least expensive strategy ($3671, 0.779 QALYs). The Boston strategy was the most cost-effective strategy and cost $9799/QALY gained. All other strategies were less effective and more costly. Despite low initial costs, clinical suspicion was among the most expensive and least effective strategies. Results were sensitive to the specificity of selected strategies. In probabilistic sensitivity analyses, the Boston strategy was most likely to be favored at a willingness-to-pay threshold of $100,000/QALY. In the urinary tract infection model, PECARN was preferred compared to other strategies and the Boston strategy was preferred in the bacterial meningitis model. CONCLUSIONS: The Boston clinical prediction rule offers an economically reasonable strategy compared to alternatives for identification of SBI.

Trends in Management of Simple Febrile Seizures at US Children's Hospitals.

OBJECTIVE: We sought to measure trends in evaluation and management of children with simple febrile seizures (SFSs) before and after the American Academy of Pediatrics updated guidelines published in 2011. METHODS: In this retrospective, cross-sectional analysis, we used the Pediatric Health Information System database comprising 49 tertiary care pediatric hospitals in the United States from 2005 to 2019. We included children aged 6 to 60 months with an emergency department visit for first SFS identified using codes from the International Classification of Diseases, Ninth Revision, and International Classification of Diseases 10th Revision. RESULTS: We identified 142 121 children (median age 21 months, 42.4% female) with an emergency department visit for SFS. A total of 49 668 (35.0%) children presented before and 92 453 (65.1%) after the guideline. The rate of lumbar puncture for all ages declined from 11.6% (95% confidence interval [CI], 10.8% to 12.4%) in 2005 to 0.6% (95% CI, 0.5% to 0.8%) in 2019 (P < .001). Similar reductions were noted in rates of head computed tomography (10.6% to 1.6%; P < .001), complete blood cell count (38.8% to 10.9%; P < .001), hospital admission (19.2% to 5.2%; P < .001), and mean costs ($1523 to $601; P < .001). Reductions in all outcomes began before, and continued after, the publication of the American Academy of Pediatrics guideline. There was no significant change in delayed diagnosis of bacterial meningitis (preperiod 2 of 49 668 [0.0040%; 95% CI, 0.00049% to 0.015%], postperiod 3 of 92 453 [0.0032%; 95% CI, 0.00066% to 0.0094%]; P = .99). CONCLUSIONS: Diagnostic testing, hospital admission, and costs decreased over the study period, without a concomitant increase in delayed diagnosis of bacterial meningitis. These data suggest most children with SFSs can be safely managed without lumber puncture or other diagnostic testing.

Ability of Procalcitonin and C-Reactive Protein for Discriminating between Bacterial and Enteroviral Meningitis in Children Using Decision Tree.

Bacterial meningitis (BM) is a public health burden in developing countries, including Central Asia. This disease is characterized by a high mortality rate and serious neurological complications. Delay with the start of adequate therapy is associated with an increase in mortality for patients with acute bacterial meningitis. Cerebrospinal fluid culture, as a gold standard in bacterial meningitis diagnosis, is time-consuming with modest sensitivity, and this is unsuitable for timely decision-making. It has been shown that bacterial meningitis differentiation from viral meningitis could be done through different parameters such as clinical signs and symptoms, laboratory values, such as PCR, including blood and cerebrospinal fluid (CSF) analysis. In this study, we proposed the method for distinguishing the bacterial form of meningitis from enteroviral one. The method is based on the machine learning process deriving making decision rules. The proposed fast-and-frugal trees (FFTree) decision tree approach showed an ability to determine procalcitonin and C-reactive protein (CRP) with cut-off values for distinguishing between bacterial and enteroviral meningitis (EVM) in children. Such a method demonstrated 100% sensitivity, 96% specificity, and 98% accuracy in the differentiation of all cases of bacterial meningitis in this study. These findings and proposed method may be useful for clinicians to facilitate the decision-making process and optimize the diagnostics of meningitis.

Variation in Target Attainment of Beta-Lactam Antibiotic Dosing Between International Pediatric Formularies.

As antimicrobial susceptibility of common bacterial pathogens decreases, ensuring optimal dosing may preserve the use of older antibiotics in order to limit the spread of resistance to newer agents. Beta-lactams represent the most widely prescribed antibiotic class, yet most were licensed prior to legislation changes mandating their study in children. As a result, significant heterogeneity persists in the pediatric doses used globally, along with quality of evidence used to inform dosing. This review summarizes dosing recommendations from the major pediatric reference sources and tries to answer the questions: Does beta-lactam dose heterogeneity matter? Does it impact pharmacodynamic target attainment? For three important severe clinical infections-pneumonia, sepsis, and meningitis-pharmacokinetic models were identified for common for beta-lactam antibiotics. Real-world demographics were derived from three multicenter point prevalence surveys. Simulation results were compared with minimum inhibitory concentration distributions to inform appropriateness of recommended doses in targeted and empiric treatment. While cephalosporin dosing regimens are largely adequate for target attainment, they also pose the most risk of neurotoxicity. Our review highlights aminopenicillin, piperacillin, and meropenem doses as potentially requiring review/optimization in order to preserve the use of these agents in future.

Paediatric bacterial meningitis in the USA: outcomes and healthcare resource utilization of nosocomial versus community-acquired infection.

Introduction. Paediatric bacterial meningitis remains a costly disease, both financially and clinically.Hypothesis/Gap Statement. Previous epidemiological and cost studies of bacterial meningitis (BM) have largely focused on adult populations or single pathogens. There have been few recent, large-scale studies of pediatric BM in the USA.Aim. We examined healthcare resource utilization (HCRU) and associated morbidity and mortality of community-acquired versus nosocomial bacterial infections in children across the USA.Methodology. The IBM MarketScan Research databases were used to identify patients <18 years old admitted to USA hospitals from 2008 to 2015 with a primary diagnosis of BM. Cases were categorized as either community-acquired or nosocomial. HCRU, post-diagnosis neurosurgical procedures, 30-day in-hospital mortality, and complications were compared between groups. Multivariable regression adjusted for sex, age and Gram staining was used to compare costs of nosocomial versus community-acquired infections over time.Results. We identified 1928 cases of paediatric BM without prior head trauma or neurological/systemic complications. Of these, 15.4 % were nosocomial and 84.6 % were community-acquired infections. After diagnostic lumbar puncture (37.1 %), the most common neurosurgical procedure was placement of ventricular catheter (12.6 %). The 30-day complication rates for nosocomial and community-acquired infections were 40.5 and 45.9 %, respectively. The most common complications were hydrocephalus (20.8 %), intracranial abscess (8.8 %) and cerebral oedema (8.1 %). The 30-day in-hospital mortality rates for nosocomial and community-acquired infections were 2.7 and 2.8 %, respectively.Median length of admission was 14.0 days (Q1: 7 days, Q3: 26 days). Median 90-day cost was $40 861 (Q1: $11 988, Q3: $114,499) for the nosocomial group and $56 569 (Q1: $26 127, Q3: $142 780) for the community-acquired group. In multivariable regression, the 90-day post-diagnosis total costs were comparable between groups (cost ratio: 0.89; 95 % CI: 0.70 to 1.13), but at 2 years post-diagnosis, the nosocomial group was associated with 137 % higher costs (CR: 2.37, 95 % CI: 1.51 to 3.70).Conclusion. In multivariable analysis, nosocomial infections were associated with significantly higher long-term costs up to 2 years post-infection. Hydrocephalus, intracranial epidural abscess and cerebral oedema were the most common complications, and lumbar punctures and ventricular catheter placement were the most common neurosurgical procedures. This study represents the first nation-wide, longitudinal comparison of the outcomes and considerable HCRU of nosocomial versus community-acquired paediatric BM, including characterization of complications and procedures contributing to the high costs of these infections.

Accuracy of clinical scoring systems for the diagnosis of tuberculosis meningitis in a case mix of meningitides a retrospective cohort study.

BACKGROUND: Tuberculosis meningitis (TBM) is elusive to diagnosis. Two widely used clinical scores are the Thwaites diagnostic score (TDS) and The Lancet Consensus score (LCS). We aim to evaluate the accuracy of these scores in a retrospective cohort of meningitis patients. METHODS: A retrospective review of all meningitis cases admitted to a tertiary center in a 7-year period. The primary outcome was the sensitivity and the specificity of a preset cutoff on the TDS and the LCS and finding the best cutoff value with optimum sensitivity and specificity using Receiver operating characteristic (ROC) curve analysis. RESULTS: We included 156 cases of meningitis; 80 TBM and 76 controls (other meningitides). Seventy-eight (97.5%) of TB cases were suggestive of TBM compared to 45(59.2%) of controls (p < .001) using the TDS. Sensitivity was 97.5% and specificity was 40.8%. The PPV was 63.4% and the NPV was 93.9%. The area under the ROC curve (AUC) was 0.80 (0.73-0.87 at 95% CI). When calculated for bacterial meningitis vs TBM a cutoff of 4 showed excellent sensitivity (93%) and specificity (96%). AUC =0.96 (0.89-1.00 at 95% CI). While for the LCS, 67 (83.3%) were suggestive of TBM vs. 11 controls (14.5%) (p < .001). Sensitivity was 83.8%, specificity was 85.5%, and PPV and NPV were 85.9% and 83.3% respectfully. The AUC was 0.93 (95% CI 0.89-0.97). CONCLUSION: The TDS performs best in differentiating bacterial meningitis from TBM and has a good negative predictive value. The LCS has good sensitivity and specificity in differentiating TBM from others forms of meningitides.

Otoacoustic emissions in patients with bacterial meningitis.

Objective: Systematic evaluation of studies using otoacoustic emissions (OAEs) to monitor cochlear damage in patients with bacterial meningitis.Design: Systematic review. This includes articles retrieved from PUBMED and EMBASE. The search-strategy was based on the PICO-model. Data processing involved Cochrane Public Health Data Extraction template in addition to assessment of risk of bias and applicability with the Second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.Study samples: Thirty-eight articles were identified with 6 studies comprising 391 children and 17 adult patients eligible for full assessment.Results: Studies were heterogenic and the timing of OAE was incomparable between studies. The frequency of severe loss of hearing was reported to occur between 1.6 and 21% of the patients with culture-proven meningitis. The included studies, albeit heterogenic, found OAE-screening feasible and sensitive in children recovering from bacterial meningitis.Conclusion: No children with hearing loss were reported to pass an OAE screening in any of the included studies. The timing, sensitivity and extent of sensorineural hearing loss determined by OAE could not be assessed from the included studies. Levels of risk of bias were inconsistent and the clinical feasibility for routine inclusion of patients with bacterial meningitis was uncertain. The technological development within this field implies the need for further research.

Análise epidemiológica da meningite bacteriana no Estado do Amapá nos anos de 2013 a 2018 / Epidemiological analysis of bacterial meningitis in the State of Amapáin the years 2013 to 2018

A meningite é uma doença infectocontagiosa caracterizada pelo processo inflamatório das meninges aracnoide e pia-máter e do líquido cefalorraquidiano. Seus principais agentes etiológicos bacterianos são Neisseria meningitidis, Streptococcus pneumoniae e Haemophilus influenzae. O presente trabalho teve como objetivo realizar uma análise epidemiológica da meningite bacteriana no Estado do Amapá, nos anos de 2013 a 2018. Trata-se de um estudo documental descritivo, de caráter transversal, com dados obtidos através do Sistema de Informações de Agravos de Notificação (SINAN). Os resultados demostram que ocorreram, no período estudado, 26 casos de meningite bacteriana. Os agentes Streptococcus pneumoniae e Neisseria meningitidis foram responsáveis por 38% e 35% das ocorrências, respectivamente, enquanto 27% dos casos foram classificados somente como meningite bacteriana. A capital do estado, Macapá, foi responsável pelo maior número de casos confirmados (81%) e, quanto à sazonalidade, o mês de julho apresentou maior ocorrência (23%). Do total de casos avaliados 54% ocorreram em pessoas do sexo masculino, e 46% em pessoas do sexo feminino, e a principal faixa etária acometida foi de crianças menores de um ano (38%). Quanto à evolução da doença, 65% das pessoas receberam alta, enquanto 27% foram à óbito por meningite. Conclui-se que apesar de a maior parte dos casos evoluírem para alta, a porcentagem de pacientes que foram à óbito por meningite ressalta a necessidade de ações em saúde voltadas tanto para a faixa etária mais acometida quanto para as demais, em função da rápida evolução que a doença apresenta.(AU)

Meningitis is an infectious disease characterized by the inflammatory process of the arachnoid and pia mater meninges.and cerebrospinal fluid. Its main bacterial etiologic agents are Neisseria meningitidis, Streptococcuspneumoniae and Haemophilus influenzae. This study aimed to carry out an epidemiological analysisof bacterial meningitis in the State of Amapá, from 2013 to 2018. This is a descriptive documentary study,transversal, with data obtained through the Notifiable Diseases Information System (SINAN). YouResults show that, during the study period, there were 26 cases of bacterial meningitis. Streptococcus agentspneumoniae and Neisseria meningitidis were responsible for 38% and 35% of the occurrences, respectively, while27% of the cases were classified as bacterial meningitis only. The state capital, Macapá, was responsibleby the highest number of confirmed cases (81%) and, regarding seasonality, the month of July had the highest occurrence(23%). Of the total number of cases evaluated, 54% occurred in males, and 46% in females,and the main age group affected was children under one year old (38%). As for the evolution of the disease, 65% ofpeople were discharged, while 27% died of meningitis. It is concluded that although most casesprogress to discharge, the percentage of patients who died from meningitis highlights the need for actions inhealth care aimed at both the most affected age group and the others, due to the rapid evolution that thedisease presents.(AU)

Hospital-based Surveillance for Pediatric Bacterial Meningitis in the Era of the 13-Valent Pneumococcal Conjugate Vaccine in Ghana.

BACKGROUND: Global surveillance for vaccine preventable invasive bacterial diseases has been set up by the World Health Organization to provide disease burden data to support decisions on introducing pneumococcal conjugate vaccine (PCV). We present data from 2010 to 2016 collected at the 2 sentinel sites in Ghana. METHODS: Data were collected from children <5 years of age presenting at the 2 major teaching hospitals with clinical signs of meningitis. Cerebrospinal fluid specimens were collected and tested first at the sentinel site laboratory with conventional microbiology methods and subsequently with molecular analysis, at the World Health Organization Regional Reference Laboratory housed at the Medical Research Council Unit The Gambia, for identification of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, the 3 most common bacteria causing meningitis. RESULTS: There were 4008 suspected cases of meningitis during the surveillance period, of which 31 (0.8%) were laboratory confirmed. Suspected meningitis cases decreased from 923 in 2010 to 219 in 2016. Of 3817 patients with available outcome data, 226 (5.9%) died. S. pneumoniae was the most common bacterial pathogen, accounting for 68.5% of confirmed cases (50 of 73). H. influenzae and N. meningitidis accounted for 6.8% (5 of 73) and 21.9% (16 of 73), respectively. The proportion of pneumococcal vaccine serotypes causing meningitis decreased from 81.3% (13 of 16) before the introduction of 13-valent PCV (2010-2012) to 40.0% (8 of 20) after its introduction (2013-2016). CONCLUSIONS: Cases of suspected meningitis decreased among children <5 years of age between 2010 and 2016, with declines in the proportion of vaccine-type pneumococcal meningitis after the introduction of 13-valent PCV in Ghana.

Pediatric Bacterial Meningitis Surveillance in Nigeria From 2010 to 2016, Prior to and During the Phased Introduction of the 10-Valent Pneumococcal Conjugate Vaccine.

BACKGROUND: Historically, Nigeria has experienced large bacterial meningitis outbreaks with high mortality in children. Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae are major causes of this invasive disease. In collaboration with the World Health Organization, we conducted longitudinal surveillance in sentinel hospitals within Nigeria to establish the burden of pediatric bacterial meningitis (PBM). METHODS: From 2010 to 2016, cerebrospinal fluid was collected from children <5 years of age, admitted to 5 sentinel hospitals in 5 Nigerian states. Microbiological and latex agglutination techniques were performed to detect the presence of pneumococcus, meningococcus, and H. influenzae. Species-specific polymerase chain reaction and serotyping/grouping were conducted to determine specific causative agents of PBM. RESULTS: A total of 5134 children with suspected meningitis were enrolled at the participating hospitals; of these 153 (2.9%) were confirmed PBM cases. The mortality rate for those infected was 15.0% (23/153). The dominant pathogen was pneumococcus (46.4%: 71/153) followed by meningococcus (34.6%: 53/153) and H. influenzae (19.0%: 29/153). Nearly half the pneumococcal meningitis cases successfully serotyped (46.4%: 13/28) were caused by serotypes that are included in the 10-valent pneumococcal conjugate vaccine. The most prevalent meningococcal and H. influenzae strains were serogroup W and serotype b, respectively. CONCLUSIONS: Vaccine-type bacterial meningitis continues to be common among children <5 years in Nigeria. Challenges with vaccine introduction and coverage may explain some of these finding. Continued surveillance is needed to determine the distribution of serotypes/groups of meningeal pathogens across Nigeria and help inform and sustain vaccination policies in the country.