Cases Of Pneumococcal Meningitis Research Articles

Seizure prophylaxis in pneumococcal meningitis, cohort study.

Our aim was to assess seizure development as a complication of pneumococcal meningitis and its possible prevention with antiseizure medication prophylaxis. Antiseizure medication (ASM) prophylaxis has been practiced for a long time at our center. We assessed all cases of community-acquired pneumococcal meningitis admitted from January 2010 to April 2021 recorded in our prospective database and conducted further retrospective studies. Of the 86 cases recorded, 21 (24.4%) developed acute symptomatic seizures, more than half of which (11/21; 52.4%) before admission. Seizure development increased the need for orotracheal intubation and intensive care unit admission, while also lengthening hospital stays and suggesting more risk of death and disability at discharge [adjusted odds ratio (aOR), 3.13; 95% confidence interval (CI): 1-9.8]. Of the 74 patients eligible for ASM prophylaxis, 64 received it and 10 did not. ASM prophylaxis seemed effective in preventing seizure development, as only six seizure events were recorded in 64 patients with ASM prophylaxis (9.4%) compared with four in the 10 patients without prophylaxis (40%). Its preventive capacity was especially notable when administered within 4 h of admission. Differences in mortality did not reach statistical significance. Adverse effects were rare. Seizure development is a common complication in pneumococcal meningitis and is associated with increased risks of Intensive Care Unit admission, orotracheal intubation, and longer hospital stays. ASM prophylaxis may be effective in blocking seizure development in patients with preventable seizures and may be associated with better prognosis. Further studies are now warranted. Infection of the meninges (the covering of the brain) due to the common bacteria S pneumoniae, used to be a fatal disease before the introduction of antibiotics and corticoids. Thanks to these drugs, more people survive this disease but, due to the frequent complications, they may have several sequelae. Seizures are a common complication. Our study suggests that they might be prevented by using antiseizure drugs which may reduce both severity and hospital stay.

Re-evaluating the impact and cost-effectiveness of pneumococcal conjugate vaccine introduction in 112 low-income and middle-income countries in children younger than 5 years: a modelling study

Streptococcus pneumoniae has been estimated to cause 9·18 million cases of pneumococcal pneumonia, meningitis, and invasive non-pneumonia non-meningitis disease and 318 000 deaths among children younger than 5 years in 2015. We estimated the potential impact and cost-effectiveness of pneumococcal conjugate vaccine (PCV) introduction. We updated our existing pseudodynamic model to estimate the impact of 13-valent PCV (PCV13) in 112 low-income and middle-income countries by adapting our previously published pseudodynamic model with new country-specific evidence on vaccine coverage, burden, and post-introduction vaccine impact from WHO-UNICEF estimates of national immunisation coverage and a global burden study. Deaths, disability-adjusted life-years (DALYs), and cases averted were estimated for children younger than 5 years born between 2000 and 2030. We used specific PCV coverage in each country and a hypothetical scenario in which coverage increased to diphtheria-tetanus-pertussis (DTP) levels. We conducted probabilistic uncertainty analyses. Using specific vaccine coverage in countries, we estimated that PCV13 could prevent 697 000 (95% credibility interval 359 000-1 040 000) deaths, 46·0 (24·0-68·9) million DALYs, and 131 (89·0-172) million cases in 112 countries between 2000 and 2030. PCV was estimated to prevent 5·3% of pneumococcal deaths in children younger than 5 years during 2000-30. The incremental cost of vaccination would be I$851 (510-1530) per DALY averted. If PCV coverage were increased to DTP coverage in 2020, PCV13 could prevent an additional 146 000 (75 500-219 000) deaths. The inclusion of real-world evidence from lower-income settings revealed that delays in PCV roll-out globally and low PCV coverage have cost many lives. Countries with delays in vaccine introduction or low vaccine coverage have experienced many PCV-preventable deaths. These findings underscore the importance of rapidly scaling up PCV to achieve high coverage and maximise vaccine impact. Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

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.

Childhood Bacterial Meningitis Surveillance in Southern Vietnam: Trends and Vaccination Implications From 2012 to 2021.

This retrospective hospital-based surveillance aimed to assess the epidemiology, causative pathogens trend, and serotypes distribution of pneumococcal meningitis among children aged under 5 years with bacterial meningitis in Southern Vietnam after the introduction of pentavalent vaccine in the Expanded Program on Immunization (EPI). From 2012 to 2021, cerebrospinal fluid samples were collected from children aged under 5 years with suspected bacterial meningitis at Children's Hospitals 1 and 2 in Ho Chi Minh City. Probable bacterial meningitis (PBM) cases were identified using biochemistry and cytology. Real-time polymerase chain reaction was used to confirm cases of confirmed bacterial meningitis (CBM) caused by Streptococcus pneumoniae, Haemophilus influenzae, or Neisseria meningitidis. Streptococcus pneumoniae serotyping was performed. Of the 2560 PBM cases, 158 (6.2%) were laboratory-confirmed. The CBM proportion decreased during the 10-year study and was associated with age, seasonality, and permanent residence. Streptococcus pneumoniae was the most common pathogen causing bacterial meningitis (86.1%), followed by H influenzae (7.6%) and N meningitidis (6.3%). The case-fatality rate was 8.2% (95% confidence interval, 4.2%-12.2%). Pneumococcal serotypes 6A/B, 19F, 14, and 23F were the most prevalent, and the proportion of pneumococcal meningitis cases caused by the 10-valent pneumococcal conjugate vaccine (PCV) serotypes decreased from 96.2% to 57.1% during the PCV eras. Streptococcus pneumoniae is the most frequent causative agent of bacterial meningitis in children aged under 5 years in Southern Vietnam over the last decade. Policymakers may need to consider introducing PCVs into the EPI to effectively prevent and control bacterial meningitis.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Pneumococcal meningitis in Greece: A retrospective serotype surveillance study in the post-PCV13 era (2010–2020)

BackgroundAs Greece is a country which has introduced the 13-valent pneumococcal conjugate vaccine (PCV13) both in the infant and in the adult immunization programs, the aim of the study was to investigate age-specific and serotype-specific trends of pneumococcal meningitis over an 11-year period (2010–2020). Materials and MethodsData are reported from pneumococcal meningitis cases [notified to the National Public Health Organization (NPHO)], with clinical samples and bacterial isolates sent for pneumococcal identification and serotyping at the National Meningitis Reference Laboratory (NMRL). Pneumococcal identification was performed directly on clinical samples or bacterial isolates by multiplex PCR (mPCR) assay, while serotyping was carried out by application of the Capsular Sequence Typing (CST) method with the combination of single tube PCR assays. ResultsA total of 427 pneumococcal meningitis cases were notified to the NPHO between 2010 and 2020. Among those, 405 (94.8%) were microbiologically confirmed, while samples from 273 patients were sent to the NMRL for identification and/or further typing. The annual notification rate peaked at 0.47/100,000 in 2016 and since then has been decreasing. The incidence was highest in infants and in older adults. Pneumococcal serotypes were identified in 260/273 (95.2%) cases, where clinical samples were sent to the NMRL. The most prevalent serotypes (≥5%) were 3, 19A, 23B, 15B/C, 11A/D, 23A, 22F. During the study period there has been a decrease of PCV13 serotypes combined with an increase of non-PCV13 serotypes (p = 0.0045). ConclusionsThis is the first study to report serotypes for pneumococcal meningitis across all ages in the post-PCV13 era in Greece. There is a need to enhance surveillance, by close monitoring of the emerging serotypes and the impact of vaccination programs. Higher-valency PCVs may help to improve the coverage of pneumococcal disease.

Investigation of Concurrent Pneumococcal Meningitis in Two Children Attending the Same Day-Care Center

Only a few clusters of invasive pneumococcal disease have been described globally in children, and most of these cases occurred before pneumococcal vaccination implementation. Two unusual cases of pneumococcal meningitis, occurring in the same daycare center over a 3-day period, were reported. Both cerebrospinal fluid (CSF) were sent to the National reference center for pneumococci. In addition, we decided to perform a pneumococcal carriage study on all children and staff of the daycare center to analyze the pneumococcal serotypes circulating in this DCC and to discuss an antibiotic chemoprophylaxis. CSF culture was positive for pneumococcus, and serotype 25A was identified by latex agglutination. The second case had negative CSF culture, but CSF antigen test and gene amplification results were positive for Streptococcus pneumoniae. Serotype 12F was identified by using molecular biology. The absence of correlation between these strains was confirmed by multi-locus sequence typing. In the carriage study, we included 29 children (median age 1.9 years, interquartile range 1.4–2.5) and 10 adults. Among the children, 24 carried Streptococcus pneumoniae (83%). The main serotypes isolated were 23A for 6 children and 25A for 5 children; serotypes were non-typeable for 3 children. Only 1 of 10 adults tested carried Streptococcus pneumoniae (serotype 12F). Despite this temporo-spatial pattern, the cases were unrelated and not due to carriage of a particular serotype. No specific action has been taken for the other children attending this DCC, and no other case of bacterial meningitis occurred.

Clinical and Bacteriological Analysis of Pediatric Pneumococcal Meningitis after 13-Valent Pneumococcal Conjugate Vaccine Introduction in Japan.

ABSTRACTStreptococcus pneumoniae is one of the leading causes of meningitis in children. In Japan, since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), the number of pneumococcal meningitis due to non-PCV13 serotypes in children has increased. To clarify the clinical outcomes, serotype distributions, and antimicrobial susceptibility of isolated S. pneumoniae strains from pediatric pneumococcal meningitis, we clinically and bacteriologically analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the PCV13 introduction era in Japan. The median age at diagnosis was 1 year (range: 3 months–13 years). Ten (29.4%) patients had underlying diseases. Twenty-nine (85.3%) patients had received at least one dose of any pneumococcal vaccine. Of the 34 patients with pneumococcal meningitis, 6 had sequelae, and 4 died. Nine (26.5%) strains were resistant to penicillin; five (15%) strains to meropenem, with an MIC of 0.5 μg/mL. All strains were susceptible to vancomycin and linezolid. Daptomycin’s MIC50 was 0.064 μg/mL and MIC90 was 0.094 μg/mL. Among the tested strains, only four were PCV13 serotypes. Penicillin-resistant S. pneumoniae was isolated from 30.0% of the patients with sequelae and death. Particularly, the proportion of serotype 10A in the sequelae and deceased cases was significantly higher than that in the complete recovery cases. We should carefully monitor the serotype and drug susceptibility of S. pneumoniae strains isolated from patients with meningitis after the PCV13 era and reconsider the treatment strategy to prepare against further drug-resistant pneumococcal strains.IMPORTANCE We analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction era in Japan. Our study revealed that pneumococcal meningitis in children was mainly caused by non-PCV13 serotypes; all cases with sequelae and death were caused by non-PCV13 serotypes. Moreover, all serotypes of penicillin resistant Streptococcus pneumoniae strains (26.5%; 9/34) were non-PCV13 serotypes. We also analyzed antimicrobial susceptibilities of glycopeptides, linezolid (LZD), and daptomycin (DAP) of isolated S. pneumoniae strains. All tested strains were susceptible to vancomycin, teicoplanin, LZD, and DAP. Especially. DAP demonstrated the best outcome among the tested antibiotics, with MIC90 of 0.094 μg/mL. Pneumococcal meningitis in children continues to persist and is difficult to control with the current conjugate vaccines. Therefore, it is important to monitor the serotype and antimicrobial susceptibility of S. pneumoniae strains isolated from patients with meningitis and accordingly reconsider the treatment strategy.

A case of pneumococcal meningitis complicated by intervertebral discitis, spinal epidural abscess, and paravertebral abscess with splenic hypoplasia

A case of pneumococcal meningitis complicated by intervertebral discitis, spinal epidural abscess, and paravertebral abscess with splenic hypoplasia

Decline in Vaccine-Type Streptococcus pneumoniae Serotypes Following Pneumococcal Conjugate Vaccine Introduction in Madagascar.

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

Characteristics and recovery of hearing loss in 573 patients with bacterial meningitis

Objective: To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis. Methods: This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children's Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study (n=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents' evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Results: Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss (OR=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Conclusions: Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss.

Impact of 13-valent pneumococcal conjugate vaccine on laboratory-confirmed pneumococcal meningitis and purulent meningitis among children ˂5 years in Cameroon, 2011-2018.

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

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.

Performance verification of pre-PCR and real-time PCR step in the molecular diagnosis of pneumococcal meningitis cases

Isolation and determination of s.pneumoniae by culture and serological methods can be time consuming or indeterminate. Molecular diagnosis by real-time PCR is independent of the growth of the pathogen causing meningitis, and is not diminished with non-viable organisms. The aim of this study was to evaluate the performance criteria of pre-PCR-TR DNA extraction step and PCR-TR step by targeting two genes encoding s.pneumoniae. In this study we evaluated the inter-sample contamination of the pre-PCR-TR step, the intermediate fidelity and the repeatability of the DNA essay. PCR-TR verification was performed by two genes targeting s. pneumoniae the Lyt A and SP 2038 gene; sensitivity, specificity and LLD were determined. Contamination rate had a value of less than 0%, which is in agreement with an absence of inter-sample contamination; the repeatability and intermediate fidelity have a cv˂7%. The evaluation of the sensitivity and specificity of the RT-PCR assays targeted 100% the Lyt A gene and the SP 2038 gene. The standard curve generated detected less than 10copies for the Lyt A gene and less than 100copies for the SP 2038 gene. This study showed that the pre-PCR and PCR-TR assays met the performance criteria targeted in this study.

1404. Twenty-year impact of Pneumococcal Conjugate Vaccines (PCV) on the burden of invasive pneumococcal disease in US children less than 5 years of age

BackgroundClinical trials of PCV7 demonstrate significant reductions in vaccine-type (VT) invasive pneumococcal disease (IPD), clinically diagnosed pneumonia in children less than 5 years of age and VT acute otitis media in children < 2 years of age. Observational, population-based studies demonstrate a reduction in overall IPD in US children following the introduction of PCV7 and PCV13. The cumulative impact of PCV on IPD syndromes over the 20 years following introduction into the US national immunization program has not been detailed.MethodsPublished and unpublished data from the Active Bacterial Core (ABC) surveillance network were used to calculate annual incidence rates of IPD and the proportional distribution by syndrome in children < 5 years of age. Cases averted were calculated from published incidence for each IPD syndrome and population data, for the pre-PCV, PCV7, and PCV13 eras. Cases averted over 2000-2009 were assumed due to PCV7 only, and those averted from 2010-2019 were assumed due to PCV13 only. It was assumed that in the absence of PCVs, disease incidence would have remained constant.ResultsAnnual cases of overall IPD, pneumococcal meningitis, and bacteremic pneumonia each declined more than 85% between the pre PCV7 incidence and the estimated incidence for 2019 (table 1). Overall, we estimated 282,600 cases of IPD, including 30,500 cases of meningitis and 78,400 cases of bacteremic pneumonia were averted. We calculated a reduction of ~ 287,600 VT cases of IPD minimally offset by an increase of ~5,000 non-VT cases. Deaths per 100,000 children < 5 years of age attributable to IPD declined by 67% in 2009 and by 64% in 2019 compared to 1997-1999. In total, 1,628 deaths in children < 5 years were averted between 2000 and 2019.Table 1. Annual Cases of IPD by syndrome in US Children Less than 5 years of age ConclusionThe substantial public health impact of PCVs over the last two decades, as measured in cases and deaths averted in children less than 5 years, re-enforces the important role vaccines play in reducing the burden of serious disease in children.DisclosuresRotem Lapidot, MD, MSCI, Pfizer (Consultant) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Kelly Sutton, PhD, Evidera (Employee) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Shreeya Patel, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Erica Chilson, PharmD, Pfizer (Employee, Shareholder) Vincenza Snow, MD, Pfizer (Employee) Raymond Farkouh, PhD, Pfizer (Employee) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)

Recognition and Outcomes of Pneumococcal Meningitis in 2 Tertiary Pediatric Hospitals Since the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine.

The aims of the study were to analyze the demographics, presentation, laboratory findings, and complications of pediatric Streptococcus pneumoniae meningitis since the introduction of the 13-valent pneumococcal conjugate vaccine, to improve recognition, and to minimize patient morbidity and mortality. This study used a retrospective analysis of pediatric pneumococcal meningitis cases at 2 tertiary healthcare systems in the Southeastern United States from 2010 to 2018. We describe 21 cases of pneumococcal meningitis. All patients presented with fever, 95% had altered mental status by history or examination, and 48% had meningeal signs. Forty-three percent had seen another provider within 48 hours of admission. Forty-eight percent had delay in lumbar puncture (LP) of more than 6 hours after antibiotic administration, decreasing rates of positive cerebrospinal fluid cultures from 100% to 40% (P < 0.001). Decision to delay LP was due to either low suspicion for meningitis (n = 4) or clinical instability (n = 6) and was associated with lower rates of meningeal signs (P = 0.014) and higher rates of altered mental status on examination (P = 0.031). Fourteen patients (67%) were up-to-date on pneumococcal immunization. Serotypes were determined in 16 cases, with 2 patients (13%) immunized against the strain that infected them. Primary outcomes included seizures (48%), hearing loss (48%), cranial nerve palsy (33%), and death (5%). Delay in LP with low suspicion for meningitis was associated with longer hospital length of stay approaching statistical significance (P = 0.053). Pneumococcal meningitis remains a relevant and potentially fatal disease despite widespread use of 13-valent pneumococcal conjugate vaccine. Its diagnosis is often delayed during interactions with physicians, which may put patients at increased risk for poor clinical outcomes.

Evaluation of pneumococcal meningitis clusters in Burkina Faso and implications for potential reactive vaccination

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

Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010–2018

Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger.As a national reference laboratory for meningitis, Centre de Recherche Médicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010–2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010–2012) and after (2016–2018) PCV13 introduction.During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010–12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016–18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged ≥ 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged ≥ 5 years, but not among those < 5 years.VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance.

Emergence of Streptococcus pneumoniae serotype 19A (Spn19A) in the pediatric population in Bogotá, Colombia as the main cause of invasive pneumococcal disease after the introduction of PCV10

ABSTRACT Introduction: With the use of pneumococcal conjugate vaccines(PCV), the behavior of invasive pneumococcal disease(IPD) has changed relative to serotype distribution. The introduction of these vaccines in national immunization programs has reduced the incidence of IPD, with a marked decrease in the circulation of the serotypes included in the vaccine used in each country. However, the subsequent emergence of other serotypes not included in the vaccine, such 19A in case of PCV7 and PCV10, has been documented. Materials and methods: This was case series study (2008–2017) in pediatric patients admitted to 10 hospitals in Bogota who were diagnosed with IPD. It was conducted during the transitional period of implementing the PCV10 vaccine in Colombia in 2012. Cases of bacteremic pneumococcal pneumonia, meningitis, primary bacteremia and osteoarticular infection were included. A descriptive analysis of the demographic, clinical and laboratory variables of patients with IPD by Spn19A, its trend over time, profiles of antimicrobial susceptibility and clinical outcomes was performed. Results: There were 463 cases of IPD, 315(68%) with known serotypes. The prevalence of IPD by Spn19A was 17.7%(56 cases), tending to increase over time. During 2008–2011, the prevalence was 4.4%, and during 2014–2017, it was 32.4%, The most frequent diagnosis was pneumonia(80.4%). In nonmeningeal isolates, 39.6% were not susceptible to penicillin. An increase in the resistance was observed over time. Conclusion: Spn19A is a prevalent cause of IPD in the pediatric population of the analyzed cohort, with an increasing trend of this serotype during the surveillance period after the introduction of PCV10, being the most common serotype identified in recent years.

New Strategy Is Needed to Prevent Pneumococcal Meningitis.

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