Common Cause Of Bacterial Meningitis Research Articles

Hydrogen peroxide is responsible for the cytotoxic effects of Streptococcus pneumoniae on primary microglia in the absence of pneumolysin.

Streptococcus pneumoniae is the most common cause of bacterial meningitis and meningoencephalitis in humans. The bacterium produces numerous virulence determinants, among them hydrogen peroxide (H2O2) and pneumolysin (Ply), which contribute to bacterial cytotoxicity. Microglia, the resident phagocytes in the brain, are distinct from other macrophages, and we thus compared their susceptibility to pneumococcal toxicity and their ability to phagocytose pneumococci with those of bone marrow-derived macrophages (BMDM). Microglia and BMDM were co-incubated with S. pneumoniae D39 to analyze survival of phagocytes by fluorescence microscopy, bacterial growth by quantitative plating, and phagocytosis by an antibiotic protection assay. Ply was detected by hemolysis assay and Western blot analysis. We found that microglia were killed during pneumococcal infection with a wild-type and an isogenic ply-deficient mutant, whereas viability of BMDM was not affected by pneumococci. Treatment with recombinant Ply showed a dose-dependent cytotoxic effect on microglia and BMDM. However, high concentrations of recombinant Ply were required and under the chosen experimental conditions, Ply was not detectable in the supernatant during infection of microglia. Inactivation of H2O2 by exogenously added catalase abolished its cytotoxic effect. Consequently, infection of microglia with pneumococci deficient for the pyruvate oxidase SpxB, primarily producing H2O2, resulted in reduced killing of microglia. Taken together, in the absence of Ply, H2O2 caused cell death in primary phagocytes in concentrations produced by pneumococci.

Hemophilus meningitis – Current Aspects of Epidemiology and Prevention: a Descriptive Review

Relevance. H. influenzae is a common cause of bacterial meningitis in children worldwide. Significant data have been accumulated worldwide on the use of H. influenzae type b conjugate vaccines over the past three decades. In the Russian Federation, constant monitoring of hemophilic meningitis is carried out, but data on the incidence of hemophilic infection are limited.Target. To consider global changes in the epidemiology of invasive forms of H. influenzae in the world and in the Russian Federation.Conclusions. The use of conjugate vaccines has resulted in a steady decline in invasive Hib infections. However, there has been a significant increase in invasive infections with non-typeable H. influenzae and non-b serotypes. In the Russian Federation, the incidence of meningitis caused by H. influenzae does not tend to increase or decrease; the majority of cases occur in children under 5 years of age.

Pneumococcal Meningitis with Serotype 7 Who Develops 12. Nerve Paralysis

Meningitis is an inflammatory disease of the leptomeninges surrounding the spinal cord and brain. Streptococcus pneumoniae (S. pneumoniae) is the most common cause of bacterial meningitis in infants and children older than one month. In this report, we present a 13-month-old infant who, after receiving three doses of the 13-valent conjugated pneumococcal vaccine, had nervus hypoglossus paralysis as a result of serotype 7 S. pneumoniae meningitis. She was admitted into our center with complaints of high fever for 2 days, apathy that started in the last 24 hours, and a tendency for sleeping. Penicillin and ceftriaxone susceptible S. pneumoniae grew in cerebrospinal fluid culture. Antibiotic treatment was completed in six weeks as she had a millimetric abscess in MR imaging. Considering common variable immunodeficiency in the patient who was examined for immunodeficiency, intravenous immunoglobulin treatment was started. The physical examination results of the patient were entirely improved. In conclusion, meningitis is a pediatric emergency with a high mortality and complication rate. If meningitis is managed on time and correctly it can heal without sequelae. Vaccination is crucial for prevention. Despite vaccination, although rare, infection with vaccine strains may occur. Patients infected with vaccine strains may require evaluation in terms of immunodeficiency.

Secondary Cases of Invasive Disease Caused by Encapsulated and Nontypeable Haemophilus influenzae - 10 U.S. Jurisdictions, 2011-2018.

Haemophilus influenzae (Hi) can cause meningitis and other serious invasive disease. Encapsulated Hi is classified into six serotypes (a-f) based on chemical composition of the polysaccharide capsule; unencapsulated strains are termed nontypeable Hi (NTHi). Hi serotype b (Hib) was the most common cause of bacterial meningitis in children in the pre-Hib vaccine era, and secondary transmission of Hi among children (e.g., to household contacts and in child care facilities) (1,2) led to the Advisory Committee on Immunization Practices (ACIP) recommendation for antibiotic chemoprophylaxis to prevent Hib disease in certain circumstances.* High Hib vaccination coverage since the 1990s has substantially reduced Hib disease, and other serotypes now account for most Hi-associated invasive disease in the United States (3). Nevertheless, CDC does not currently recommend chemoprophylaxis for contacts of persons with invasive disease caused by serotypes other than Hib and by NTHi (non-b Hi). Given this changing epidemiology, U.S. surveillance data were reviewed to investigate secondary cases of invasive disease caused by Hi. The estimated prevalence of secondary transmission was 0.32% among persons with encapsulated Hi disease (≤60 days of one another) and 0.12% among persons with NTHi disease (≤14 days of one another). Isolates from all Hi case pairs were genetically closely related, and all patients with potential secondary infection had underlying medical conditions. These results strongly suggest that secondary transmission of non-b Hi occurs. Expansion of Hi chemoprophylaxis recommendations might be warranted to control invasive Hi disease in certain populations in the United States, but further analysis is needed to evaluate the potential benefits against the risks, such as increased antibiotic use.

DNase Treatment Prevents Cerebrospinal Fluid Block in Early Experimental Pneumococcal Meningitis.

Streptococcus pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with high mortality and morbidity worldwide. Diffuse brain swelling is a leading cause of morbidity in S pneumoniae meningitis. We hypothesized that neutrophil extracellular traps (NETs) disrupt cerebrospinal fluid (CSF) transport by the glymphatic system and contribute to edema formation in S pneumoniae meningitis. We used DNase I treatment to disrupt NETs and then assessed glymphatic function by cisterna magna injections of CSF tracers in a rat model of S pneumoniae meningitis. Our analysis showed that CSF influx into the brain parenchyma, as well as CSF drainage to the cervical lymph nodes, was significantly reduced in the rat model of S pneumoniae meningitis. Degrading NETs by DNase treatment restored glymphatic transport and eliminated the increase in brain weight in the rats. In contrast, first-line antibiotic treatment had no such effect on restoring fluid dynamics. This study suggests that CSF accumulation is responsible for cerebral edema formation and identifies the glymphatic system and NETs as possible new treatment targets in S pneumoniae meningitis. ANN NEUROL 2021;90:653-669.

Extended Spectrum Beta Lactamase (ESBL) Producing Neisseria meningitidis – Isolated from a Case of Pneumonia

Neisseria meningitidis (meningococci) is the most common cause of bacterial meningitis in all age groups. Invasive meningococcal disease manifesting as meningococcal pneumonia is a very rare clinical condition. Here we have a 72 year old male who presented with meningococcal pneumonia and sepsis following a flu like illness. It is notable that he did not develop the syndrome of meningococcemia or its associated complications. This patient was treated with injections of Piperacillin-Tazobactum and Azithromycin because of the unusual antibiotic resistance pattern of the organism. He recovered completely without any sequelae. The meningococci isolated was an ESBL (extended spectrum beta lactamase) producing strain, hence it was resistant to Penicillin and third generation Cephalosporins which are usually used for the treatment of meningococcal infections .This strain was also resistant to Ciprofloxacin .This poses a threat to the community as well, especially because Ciprofloxacin is used as a chemo prophylactic drug by the contacts of the patient and the laboratory workers dealing with the patient’s clinical samples.

Invasive Haemophilus influenzae Infections after 3 Decades of Hib Protein Conjugate Vaccine Use.

Haemophilus influenzae serotype b (Hib) was previously the most common cause of bacterial meningitis and an important etiologic agent of pneumonia in children aged <5 years. Its major virulence factor is the polyribosyl ribitol phosphate (PRP) polysaccharide capsule. In the 1980s, PRP-protein conjugate Hib vaccines were developed and are now included in almost all national immunization programs, achieving a sustained decline in invasive Hib infections. However, invasive Hib disease has not yet been eliminated in countries with low vaccine coverage, and sporadic outbreaks of Hib infection still occur occasionally in countries with high vaccine coverage. Over the past 2 decades, other capsulated serotypes have been recognized increasingly as causing invasive infections. H. influenzae serotype a (Hia) is now a major cause of invasive infection in Indigenous communities of North America, prompting a possible requirement for an Hia conjugate vaccine. H. influenzae serotypes e and f are now more common than serotype b in Europe. Significant year-to-year increases in nontypeable H. influenzae invasive infections have occurred in many regions of the world. Invasive H. influenzae infections are now seen predominantly in patients at the extremes of life and those with underlying comorbidities. This review provides a comprehensive and critical overview of the current global epidemiology of invasive H. influenzae infections in different geographic regions of the world. It discusses those now at risk of invasive Hib disease, describes the emergence of other severe invasive H. influenzae infections, and emphasizes the importance of long-term, comprehensive, clinical and microbiologic surveillance to monitor a vaccine's impact.

Long Term Impact of Conjugate Vaccines on Haemophilus influenzae Meningitis: Narrative Review.

H. influenzae serotype b (Hib) used to be the commonest cause of bacterial meningitis in young children. The widespread use of Hib conjugate vaccine has profoundly altered the epidemiology of H. influenzae meningitis. This short review reports on the spectrum of H. influenzae meningitis thirty years after Hib conjugate vaccine was first introduced into a National Immunization Program (NIP). Hib meningitis is now uncommon, but meningitis caused by other capsulated serotypes of H. influenzae and non-typeable strains (NTHi) should be considered. H. influenzae serotype a (Hia) has emerged as a significant cause of meningitis in Indigenous children in North America, which may necessitate a Hia conjugate vaccine. Cases of Hie, Hif, and NTHi meningitis are predominantly seen in young children and less common in older age groups. This short review reports on the spectrum of H. influenzae meningitis thirty years after Hib conjugate vaccine was first introduced into a NIP.

The Epidemiology of Meningitis in Infants under 90 Days of Age in a Large Pediatric Hospital.

Background: Meningitis is associated with substantial morbidity and mortality, particularly in the first three months of life. Methods: We conducted a retrospective review of patients <90 days of age with meningitis at Texas Children’s Hospital from 2010–2017. Cases were confirmed using the National Healthcare Safety Network (NHSN) definition of meningitis. Results: Among 694 infants with meningitis, the most common etiology was viral (n = 351; 51%), primarily caused by enterovirus (n = 332; 95%). A quarter of cases were caused by bacterial infections (n = 190; 27%). The most common cause of bacterial meningitis was group B Streptococcus (GBS, n = 60; 32%), followed by Gram-negative rods other than E. coli (n = 40; 21%), and E. coli (n = 37; 19%). The majority of Gram-negative organisms (63%) were resistant to ampicillin, and nearly one-fourth of Gram-negative rods (23%) other than E. coli and 2 (6%) E. coli isolates were resistant to third-generation cephalosporins. Significant risk factors for bacterial meningitis were early preterm birth and the Black race. Conclusions: Enteroviruses most commonly caused viral meningitis in infants; GBS was the most common bacterial cause despite universal screening and intrapartum prophylaxis. The emergence of MRSA and resistance to third-generation cephalosporins in Gram-negative bacterial meningitis challenges the options for empirical antimicrobial therapy.

Pneumococcal Meningitis and Its Sequelae - A Devastating CNS Disease.

IntroductionIn countries where Haemophilus influenzae type B vaccine is used, Streptococcus pneumoniae is the most common cause of bacterial meningitis in young children and notable cause of morbidity/mortality. The authors present material of magnetic resonance imaging (MRI) of patients with pneumococcal meningitis from archive of Department of Diagnostic Imaging of Institute of Mother and Child in Warsaw.Materials and methodsWe performed 27 brain MRI scans and 1 follow-up computed tomography (CT) in 10 children (2 girls and 8 boys) aged from neonate to 5 years at disease onset with proven pneumococcal infection.ResultsFollow-up period range was 0–12 years. Two children underwent only one MRI, one of them died before follow-up and the other was lost from further observation. There was one case of relatively benign disease course with mild changes on MRI. In another seemingly benign case, acute transient hydrocephalus was observed. Six children developed hydrocephalus, and two required ventriculoperitoneal shunting complicated by neuroinfection, shunt malfunction and revisions. Two patients developed epilepsy. In six children, spastic paresis of various severity was diagnosed, up to quadriplegia in one who is under the longest observation (>12 years) and survived in vegetative state. Three other children suffer from delayed psychomotor development to severe intellectual disability.ConclusionsMRI shows perfectly the degree of central nervous system (CNS) damage during and after pneumococcal invasion. Despite appropriate treatment, disease course may be unpredictably serious. Attempts to eliminate the obligation to vaccinate are extremely irresponsible taking into account potential danger of death, vegetative state or another form of severe damage to CNS. Social and financial costs of care of survivors are very high with shunts placements and changes, (neuro)infections, rehabilitation, families breakdown, etc.

Recent trends in pediatric bacterial meningitis in Japan, 2016–2018 – S. agalactiae has been the most common pathogen

BackgroundHaemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan. The overall incidence of bacterial meningitis decreased thereafter. Streptococcus agalactiae has become the main organism. ObjectivesThe purpose of the present study was to investigate the incidence rate per 1000 admissions of bacterial meningitis and the change in causative organisms in subsequent years. MethodsA cross-sectional, multicenter, non-interventional retrospective study regarding pediatric bacterial meningitis was conducted in Japan in 2019. We analyzed the epidemiological and clinical data for 2016–2018, and compared the information obtained in our previous nationwide survey database. We also investigated the risk factors for disease outcome. ResultsIn the 2016–2018 surveys, 197 patients from 153 hospitals from all prefectures were evaluated. S. agalactiae (0–3 months, 39%), Streptococcus pneumoniae (2–112 months, 20%), and E. coli (0–136 months, 13%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.00 to 1.68 in 2000–2010 to 0.38 in 2013–2015, bu remained stable thereafter (0.35–0.40 in 2016–2018). Only one case with Neisseria meningitidis was reported. Nine cases with death were reported, including four cases with S. agalactiae. Risk factors for death and sequelae were consciousness disturbance, duration of convulsion, low CSF glucose levels, and disuse of dexamethasone (p < 0.05). ConclusionsThe incidence in pediatric bacterial meningitis remained low, and S. agalactiae remains the most common cause of bacterial meningitis in Japan since 2012. S. pneumoniae is the most common cause after 3 months of age.

Antibiotics &amp; adjuvant corticosteroids in management of pneumococcal meningitis: a retrospective case-notes audit

Background Pneumococcus remains the most common cause of bacterial meningitis with high morbidity and mortality. Adjuvant corticosteroids with early antibiotics have been shown to reduce the neurological morbidity and mortality respectively and this is reflected in British Infection Society (BIS) guidance. Aim To assess how closely BIS guidelines were followed regarding antibiotic and adjuvant corticosteroid administration in management of pneumococcal meningitis. Methods Newcastle Upon Tyne Hospital case-notes of pneumococcal meningitis from a 7-year-period(2012-2019) were audited. Patients were identified using microbiological records and case-notes. Data was collected on intervals from initial-assessment to commencing antibiotics and corticosteroids. Results Eighteen cases were identified of whom three(17%) presented with the classic triad (fever, meningism, reduced GCS). All patients received appropriate antibiotics: 3/18(17%) within first hour of assessment. The median time to antibiotics was 5h 8mins (range:21-7129min). Eight patients(44%) received antibiotics &gt;6h after assessment. Twelve patients(67%) received corticosteroids; only six(33%) at the recommended dose and duration. Mean time from antibiotics to corticosteroids was 6h1min. Five deaths occurred in the cohort with three attributable to pneumococcal sepsis (all had late presentations). 6/18 had significant neurological sequelae, irrespective of whether they received corticosteroids. Discussion The significant morbidity and mortality of pneumococcal meningitis demands a high index of suspicion. BIS guideline targets are repeatedly not met; long delays exist between assessment and antibiotic and corticosteroid administration. Integrated electronic prescribing and clinical Early Warning Systems have potential to ameliorate this with meningitis-tailored order sets to prompt consideration of meningitis and guide correct prescribing.

The Frequency of Meningitis Cases in Zagazig Fever Hospital: A Cross-sectional Study

Background and study aim: Meningitis is the inflammation of meninges and can be life-threatening in some cases. The study aimed to determine the frequency and clinical presentations of the meningitis cases in ZagazigFeverHospital to put recommendations to assist in improving the preventive and management measure-ments for meningitis. Patients and Methods: A cross-section study included all of 70 meningitis patients in ZagazigFeverHospital, who fulfilled the selection criteria, over a period of one year from September 2016 to September 2017. The data collection sheet included demographic, clinical assessments, diagnostic lumbar puncture with CSF analysis. Results: The majority of meningitis cases were males (57.1%), from urban areas (67.1%), aged less than ten years or more than forty years, and diagnosed in winter (42.9%), especially in February. According to the CSF culture results, patients were classified into two groups; 87.1% as aseptic meningitis (group A) and 12.8% as bacterial meningitis (group B). Neisseria meningitides was the common cause of bacterial meningitis. The death rate was (11.4%), and the old age was a significant risk factor for mortality (P= 0.02). Conclusion: Meningitis is a real health problem in Al Sharkia Governorate; Neisseria meningitides was the common cause of septic meningitis. Health authorities in Al Sharkia governorate should focus their preventive efforts on the age group 40 years.

Characterization of a Listeria monocytogenes meningitis mouse model

BackgroundListeria monocytogenes is a common cause of bacterial meningitis. We developed an animal model of listerial meningitis.MethodsIn survival studies, C57BL/6 mice received intracisternal injections with different L. monocytogenes sequence type 1 (ST1) colony forming units per milliliter (CFU; n = 48, 105, 106, 107, 108, and 109 CFU/ml). Second, mice were inoculated with 108 CFU/ml ST1 and sacrificed at 6 h and 24 h (n = 12/group). Outcome parameters were clinical score, CFUs, cyto- and chemokine levels, and brain histopathology. Third, 84 mice were inoculated (109 CFU/ml ST1) to determine optimal antibiotic treatment with different doses of amoxicillin and gentamicin. Fourth, mice were inoculated with 109 CFU/ml ST1, treated with amoxicillin, and sacrificed at 16 h and 24 h (n = 12/group) for outcome assessment. Finally, time point experiments were repeated with ST6 (n = 24/group).ResultsMedian survival time for inoculation with 108 and 109 CFU/ml ST1 was 46 h and 40 h; lower doses of bacteria led to minimal clinical signs of disease. Brain levels of IL-6, IL-17A, and IFN-γ were elevated at 24 h, and IL-1β, IL-6, IL-10, IFN-γ, and TNF-α were elevated in blood at 6 h and 24 h. Histopathology showed increased meningeal infiltration, vascular inflammation of meningeal vessels, hemorrhages, and ventriculitis. In the treatment model, brain levels of IL-6 and IL-17A and blood levels of IL-6 and IFN-γ were elevated. Compared to ST6, infection with ST1 led initially to higher levels of IL-1β and TNF-α in blood and more profound neuropathological damage. At 16 h post inoculation, IL-1β, IL-10, and TNF-α in blood and IL-6, IL17A, TNF-α, and IFN-γ levels in brain were higher in ST1 compared to ST6 without differences in CFUs between STs. At 24 h, neuropathology score was higher in ST1 compared to ST6 (p = 0.002) infected mice.ConclusionsWe developed and validated a murine model of listerial meningitis. ST1-infected mice had a more severe inflammatory response and brain damage as compared to ST6-infected mice.

Histopathology of Listeria Meningitis

Listeria monocytogenes meningitis is the third most common cause of bacterial meningitis in adults and has high mortality and morbidity rates. We describe the clinical course and score brain pathology of 5 patients who died of listeria meningitis. All patients were immunocompromised and ages ranged between 48 and 76 years. Three cases were confirmed by cerebrospinal fluid culture; one was confirmed by brain culture; and one diagnosis was based on a positive blood culture and neuropathological findings. Mild inflammation of meningeal arteries was found in 3 of 5 cases (60%). Moderate/severe ventriculitis was seen in 4 of 4 cases (100%), abscesses in 3 of 4 cases (75%), mild vascular inflammation in 4 of 5 cases (80%), mild/moderate hemorrhage in 2 of 4 cases (50%), mild/moderate thrombosis of meningeal artery in 3 of 5 cases (60%), and 1 case (25%) showed a moderate infarct. The inflammatory cells present in the meninges were characterized by a mix of monocytes, macrophages, and neutrophils and removal of apoptotic inflammatory cells by macrophages (efferocytosis). Gram stain showed intra- and extracellular presence of rod-shaped bacteria in 3 cases. Pathological examination was characterized by moderate to severe ventriculitis, abscesses and abundant efferocytosis which has been suggested to be exploited by L. monocytogenes for cell-to-cell spread.

Potential Coverage of the 4CMenB Vaccine against Invasive Serogroup B Neisseria meningitidis Isolated from 2009 to 2013 in the Republic of Ireland.

Neisseria meningitidis is a common cause of bacterial meningitis in children and young adults worldwide. The 4CMenB vaccine (Bexsero), developed to combat meningococcal serogroup B (MenB) disease, contains subcapsular antigens that may induce immunity against strains of N.meningitidis, regardless of serogroup. Owing to differential levels of expression and peptide diversity in vaccine antigens across meningococcal strains, the meningococcal antigen typing system (MATS) was developed to estimate the potential MenB strain coverage of 4CMenB. Prior to introducing the 4CMenB vaccine into routine use, we sought to estimate the potential 4CMenB coverage against invasive MenB strains isolated in the Republic of Ireland (RoI) over four consecutive epidemiological years. MATS was applied to a panel of 105 invasive MenB strains isolated during July 2009 to June 2013. Sequence data characterizing the multilocus sequence typing (MLST) alleles and the major 4CMenB target peptides were extracted from isolate genome sequence data, hosted in the Bacterial Isolate Sequencing database (BIGSdb). MATS data indicated that 4CMenB may induce protective immunity against 69.5% (95% confidence interval [CI95%], 64.8% to 84.8%) of circulating MenB strains. Estimated coverage was highest against the most prevalent disease-causing lineage, cc41/44, where the most frequently observed sequence types, ST-154 and ST-41 (21% of isolates, collectively), were typically covered by three antigens. No significant temporal trends were observed. Overall, these data provide a baseline of strain coverage prior to the introduction of 4CMenB and indicate that a decrease in invasive meningococcal disease (IMD) is predicted following the introduction of 4CMenB into the routine infant immunization schedule in the RoI.IMPORTANCE The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA) that measures both the levels of expression and the immune reactivity of the three recombinant 4CMenB antigens. Together with PorA variable-region sequence data, this system provides an estimation of how susceptible MenB isolates are to killing by 4CMenB vaccine-induced antibodies. Assays based on subcapsular antigen phenotype analyses, such as MATS, are important in situations where conventional vaccine coverage estimations are not possible. Subcapsular antigens are typically highly diverse across strains, and vaccine coverage estimations would require unfeasibly large efficacy trials and screening of an exhaustive strain panel for antibody functional activity. Here, MATS was applied to all invasive meningococcal serogroup B (MenB) strains isolated over four consecutive epidemiological years (n = 105) and predicted reasonably high 4CMenB vaccine coverage in the Republic of Ireland.

Global etiology of bacterial meningitis: A systematic review and meta-analysis.

Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this systematic review and meta-analysis was to assess the etiology of bacterial meningitis in different age groups across global regions. PubMed and EMBASE were systematically searched for English language studies on bacterial meningitis, limited to articles published in the last five years. The methodological quality of the studies was assessed using a customized scoring system. Meta-analyses were conducted to determine the frequency (percentages) of seven bacterial types known to cause meningitis: Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, with results being stratified by six geographical regions as determined by the World Health Organization, and seven age groups.Of the 3227 studies retrieved, 56 were eligible for the final analysis. In all age groups, S. pneumoniae and N. meningitidis were the predominant pathogens in all regions, accounting for 25.1–41.2% and 9.1–36.2% of bacterial meningitis cases, respectively. S. pneumoniae infection was the most common cause of bacterial meningitis in the ‘all children’ group, ranging from 22.5% (Europe) to 41.1% (Africa), and in all adults ranging from 9.6% (Western Pacific) to 75.2% (Africa). E. coli and S. pneumoniae were the most common pathogens that caused bacterial meningitis in neonates in Africa (17.7% and 20.4%, respectively). N. meningitidis was the most common in children aged ±1–5 years in Europe (47.0%). Due to paucity of data, meta-analyses could not be performed in all age groups for all regions.A clear difference in the weighted frequency of bacterial meningitis cases caused by the different etiological agents was observed between age groups and between geographic regions. These findings may facilitate bacterial meningitis prevention and treatment strategies.

Neuroborreliosis in Swedish Children: A Population-based Study on Incidence and Clinical Characteristics

Borrelia burgdorferi is a common cause of bacterial meningitis, but there are very few studies on incidence in Europe. The aim of this study was to report the incidence and symptoms of neuroborreliosis in Swedish children. Medical records of children (< 15 years) treated for neuroborreliosis 2002-2014 were studied retrospectively. The patients were identified in the computerized registers of discharge diagnoses at the Departments of Pediatrics and Infectious Diseases in Gothenburg, Borås, Trollhättan and Halmstad using International Classification of Diseases 10 diagnosis codes G51.0, G01.9 and/or A69.1. Of those, patients with symptoms compatible with neuroborreliosis and a white blood cell count in cerebrospinal fluid ≥ 7 cells/mm with ≥ 80% mononuclear cells were included. Only children living in the city of Gothenburg and 10 surrounding municipalities were included. Five hundred forty-eight children were included. The median age was 7 (1-14) years. The total incidence for the 13-year-period was 2.8/10,000 and remained unchanged during the period. The incidence was significantly higher in rural (4.0/10,000) than in urban municipalities (2.1/10,000). The most common presenting symptoms were headache (n = 335), fatigue (n = 330) and cranial nerve palsies (n = 329). The median duration of symptoms before admittance was 4.0 days for facial palsy and 14.0 days for other symptoms (P < 0.001). The median white blood cell count in cerebrospinal fluid was 129 (7-1069) cells/mm. This study is the largest so far in a pediatric population. The incidence of neuroborreliosis was higher than in previous European reports. This might be explained by increased Borrelia awareness, the distribution of tick population in Sweden, and the possibility that Swedish children more frequently play outdoors.

Magnesium therapy improves outcome in Streptococcus pneumoniae meningitis by altering pneumolysin pore formation.

Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults and is characterized by high lethality and substantial cognitive disabilities in survivors. Here, we have studied the capacity of an established therapeutic agent, magnesium, to improve survival in pneumococcal meningitis by modulating the neurological effects of the major pneumococcal pathogenic factor, pneumolysin. We used mixed primary glial and acute brain slice cultures, pneumolysin injection in infant rats, a mouse meningitis model and complementary approaches such as Western blot, a black lipid bilayer conductance assay and live imaging of primary glial cells. Treatment with therapeutic concentrations of magnesium chloride (500mg·kg-1 in animals and 2mM in cultures) prevented pneumolysin-induced brain swelling and tissue remodelling both in brain slices and in animal models. In contrast to other divalent ions, which diminish the membrane binding of pneumolysin in non-therapeutic concentrations, magnesium delayed toxin-driven pore formation without affecting its membrane binding or the conductance profile of its pores. Finally, magnesium prolonged the survival and improved clinical condition of mice with pneumococcal meningitis, in the absence of antibiotic treatment. Magnesium is a well-established and safe therapeutic agent that has demonstrated capacity for attenuating pneumolysin-triggered pathogenic effects on the brain. The improved animal survival and clinical condition in the meningitis model identifies magnesium as a promising candidate for adjunctive treatment of pneumococcal meningitis, together with antibiotic therapy.

Characterization of a listeria monocytogenes meningitis mouse model

L. monocytogenes is the third most common cause of bacterial meningitis in adults. Further understanding of the pathophysiology of listeria meningitis is needed to improve the prognosis.