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Aim: A low Glasgow Coma Scale Score (GCS) on admission is a known predictor of poor outcome from childhood bacterial meningitis. In turn, the factors associated with the admission GCS are less known. Our aim was to identify them, both for clinical alerts of reserved prognosis and to find potential targets for intervention. Methods: This study is a secondary analysis of data collected prospectively in Angola and in Latin America between 1996 and 2007. Children with bacterial meningitis were examined on hospital admission and their GCS was assessed using the age‐adjusted scale. Associations between on‐admission GCS and host clinical factors were examined. Results: A total of 1376 patients with confirmed bacterial meningitis were included in the analysis (609 from Latin America and 767 from Angola). The median GCS was 13 for all patients (12 in Angola and 13 in Latin America). In the multivariate analysis, in the areas combined, seizures, focal neurological signs, and pneumococcal aetiology associated with GCS <13, as did treatment delay in Latin America. Conclusion: Besides pneumococcal aetiology, we identified characteristics, easily registrable on admission, which are associated with a low GCS in childhood bacterial meningitis. Of these, expanding pneumococcal vaccinations and treatment delays could be modified. [ABSTRACT FROM AUTHOR]

Background: Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy. Methods: Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL). Results: Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM. Conclusions: This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5). Bacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51–68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103–1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9–105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0–2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6–2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4–3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6–3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6–3.9; p < 0.001). High CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial Meningitis (BM) is a serious health problem worldwide with high mortality and permanent longterm neurological sequelae. Cerebrospinal Fluid (CSF) analysis is the cornerstone for diagnosing BM, but the lack of specificity creates a difficult clinical scenario for initiating proper treatment. Empiric antibiotic use in patients with suspected meningitis at primary care settings decreases the yield of CSF culture and alters CSF cytological and biochemical findings, making it further difficult to diagnose BM. To overcome this difficulty, there is a need for other biochemical markers with higher sensitivity and specificity. Aim: To determine the diagnostic sensitivity and specificity of Procalcitonin (PCT) in serum and CSF in patients with BM and compare its diagnostic accuracy in both sample types. Materials and Methods: A cross-sectional study was conducted in the Department of Internal Medicine at a tertiary care centre in eastern India from September 2018 to August 2020. A total of 82 adult patients with meningitis were recruited as per the protocol, and CSF analysis was done along with estimation of PCT in serum and CSF. Receiver Operating Characteristics (ROC) curve analysis of serum and CSF PCT was used to determine sensitivity and specificity with a 95% confidence interval. Results: Out of the 82 patients recruited, 30 (36.6%) had BM. CSF PCT with a cut-off value of >0.45 ng/mL had a sensitivity of 86.7% and specificity of 92.3%. The sensitivity of serum PCT with a cut-off value of >0.6 ng/mL was 83.3%, and specificity was 86.5%. There was no statistically significant difference in sensitivity and specificity between CSF and serum PCT in patients with BM (p-value=0.7988). Conclusion: Both serum and CSF PCT were found to have high sensitivity and specificity as markers for diagnosing BM without any statistically significant difference between them. [ABSTRACT FROM AUTHOR]

Objective: Fabry disease is caused by enzymatic defects in alpha‐galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features. Methods: We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases. Results: Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis. Interpretation: Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro‐inflammatory signaling pathways. [ABSTRACT FROM AUTHOR]

Introduction: Most current treatment strategies and investigations on cryptococcal meningitis (CM) focus primarily on the central nervous system (CNS), often overlooking the complex interplay between the CNS and the peripheral system. This study aims to explore the characteristics of central and peripheral metabolism in patients with CM. Methods: Patients diagnosed with CM as per the hospital records of the Fourth People's Hospital of Nanning were retrospectively analyzed. Patients were divided into two groups, non-structural damage of the brain (NSDB) and structural damage of the brain (SDB), according to the presence of brain lesions as detected with imaging. Based on the presence of enlarged cerebral ventricles, the cases in the SDB group were classified into non-ventriculomegaly (NVM) and ventriculomegaly (VM). Various parameters of cerebrospinal fluid (CSF) and peripheral blood (PB) were analyzed. Results: A significant correlation was detected between CSF and PB parameters. The levels of CSF-adenosine dehydrogenase (ADA), CSF-protein, CSF-glucose, and CSF-chloride ions were significantly correlated with the levels of PB-aminotransferase, PB-bilirubin, PB-creatinine (Cr), PB-urea nitrogen, PB-electrolyte, PB-protein, and PB-lipid. Compared with NSDB, the levels of CSF-glucose were significantly decreased in the SDB group, while the levels of CSF-lactate dehydrogenase (LDH) and CSF-protein were significantly increased in the SDB group. In the SDB group, the levels of PB-potassium, PB-hemoglobin(Hb), and PB-albumin were significantly decreased in the patients with VM, while the level of PB-urea nitrogen was significantly increased in these patients. Conclusion: Metabolic and structural alterations in the brain may be associated with peripheral metabolic changes. [ABSTRACT FROM AUTHOR]

Streptococcus suis is a pathogen of emerging zoonotic diseases and meningoencephalitis is the most frequent clinical symptom of S. suis infection in humans. Rapid diagnosis of S. suis meningoencephalitis is critical for the treatment of the disease. While the current routine microbiological tests including bacterial culture and gram staining are poorly sensitive, diagnosis of S. suis meningoencephalitis by metagenomic next-generation sequencing (mNGS) has been rarely reported. Here, we report a 52-year-old female pork food producer with a broken finger developed S. suis meningoencephalitis. After her admission, no pathogenic bacteria were detected through bacterial culture and Gram staining microscopy in the cerebrospinal fluid obtained via lumbar puncture. However, mNGS identified the presence of S. suis in the sample. mNGS is a promising diagnostic tool for rapid diagnosis of rare infectious diseases in the central nervous system. [ABSTRACT FROM AUTHOR]

La vaccination pneumococcique conjuguée (7- puis 13-valente) a considérablement modifié le profil des méningites à pneumocoque en faisant disparaître les souches virulentes les plus résistantes aux bêtalactamines en France. L'observatoire national des méningites bactériennes de l'enfant du Groupe de pathologie infectieuse pédiatrique (GPIP) de la Société française de pédiatrie ainsi que le Centre national de référence des pneumocoques n'ont pas répertorié de cas de méningite due à des pneumocoques résistants aux céphalosporines de troisième génération (C3G), même si des souches de profil moins favorable (sérotype 15) ont semblé émerger en 2021. Ces données récentes justifient de reconduire les recommandations de 2016 et à limiter l'usage de la vancomycine à la phase secondaire de traitement des méningites à pneumocoque lorsque la CMI de la souche isolée vis-à-vis des C3G injectables est > 0,5 mg/L. La seule modification notable proposée par le GPIP dans cette actualisation 2023 de ses recommandations porte sur la suppression de l'association de la ciprofloxacine au céfotaxime dans les méningites à Escherichia coli du nouveau-né et du jeune nourrisson. L'observatoire national des méningites de l'enfant est un outil précieux en raison de sa bonne exhaustivité et de sa pérennité depuis 15 ans. Le maintien de la surveillance épidémiologique permettra d'adapter si nécessaire, les nouveaux schémas thérapeutiques à l'évolution des profils de sensibilité des pneumocoques et aux changements sérotypiques éventuels à venir. Les abcès cérébraux communautaires sont des maladies rares, mais leur prise en charge nécessite une approche rigoureuse : une imagerie de qualité, un prélèvement bactériologique avant l'antibiothérapie dans la mesure du possible, et un traitement antibiotique incluant le métronidazole en plus du céfotaxime. Ces abcès cérébraux nécessitent toujours une collaboration multidisciplinaire, incluant les professionnels des maladies infectieuses et un avis neurochirurgical. In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to beta-lactams. Over recent years, the nationwide pediatric meningitis network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have not recorded any cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (C3G), even though in 2021, strains with a less favorable profile appeared to emerge. These recent data justify renewal of the 2016 recommendations and limitation of vancomycin to the secondary phase of treatment of pneumococcal meningitis when the MIC of the isolated strain against injectable C3Gs is > 0.5 mg/L. The only major change proposed by the GPIP in this 2023 update of its recommendations is discontinuation of the recommendation of a combination of ciprofloxacin and cefotaxime in Escherichia coli meningitis in newborns and young infants. The nationwide observatory of meningitis in children is a valuable tool because of its completeness and its continuity over the past 15 years. The maintenance of epidemiological surveillance will allow us to adapt new therapeutic regimens to the evolution of pneumococcal susceptibility profiles and to future serotype-specific changes. Community-acquired cerebral abscesses are rare diseases, of which the management requires a rigorous approach: high-quality imaging, bacteriological sampling prior to antibiotic therapy whenever possible, and antibiotic treatment including metronidazole in addition to cefotaxime. Multidisciplinary collaboration, including infectious disease and neurosurgical advice, is always called for. [ABSTRACT FROM AUTHOR]

Background and objectives: Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. Methods: This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. Results: We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. Conclusion: The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition. [ABSTRACT FROM AUTHOR]

Background: In 2012, Botswana introduced 13-valent pneumococcal conjugate vaccine (PCV-13) to its childhood immunization program in a 3+0 schedule, achieving coverage rates of above 90% by 2014. In other settings, PCV introduction has been followed by an increase in carriage or disease caused by non-vaccine serotypes, including some serotypes with a high prevalence of antibiotic resistance. Methods: We characterized the serotype epidemiology and antibiotic resistance of pneumococcal isolates cultured from nasopharyngeal samples collected from infants (≤12 months) in southeastern Botswana between 2016 and 2019. Capsular serotyping was performed using the Quellung reaction. E-tests were used to determine minimum inhibitory concentrations for common antibiotics. Results: We cultured 264 pneumococcal isolates from samples collected from 150 infants. At the time of sample collection, 81% of infants had received at least one dose of PCV-13 and 53% had completed the three-dose series. PCV-13 serotypes accounted for 27% of isolates, with the most prevalent vaccine serotypes being 19F (n = 20, 8%), 19A (n = 16, 6%), and 6A (n = 10, 4%). The most frequently identified non-vaccine serotypes were 23B (n = 29, 11%), 21 (n = 12, 5%), and 16F (n = 11, 4%). Only three (1%) pneumococcal isolates were resistant to amoxicillin; however, we observed an increasing prevalence of penicillin resistance using the meningitis breakpoint (2016: 41%, 2019: 71%; Cochran-Armitage test for trend, p = 0.0003) and non-susceptibility to trimethoprim-sulfamethoxazole (2016: 55%, 2019: 79%; p = 0.04). Three (1%) isolates were multi-drug resistant. Conclusions: PCV-13 serotypes accounted for a substantial proportion of isolates colonizing infants in Botswana during a four-year period starting four years after vaccine introduction. A low prevalence of amoxicillin resistance supports its continued use as the first-line agent for non-meningeal pneumococcal infections. The observed increase in penicillin resistance at the meningitis breakpoint and the low prevalence of resistance to ceftriaxone supports use of third-generation cephalosporins for empirical treatment of suspected bacterial meningitis. [ABSTRACT FROM AUTHOR]

We introduce a model to describe the evolution of bacterial meningitis epidemics in a non-constant population. We derive the value of the basic reproduction number of our model. We analyze the local and global stability of the disease-free and endemic equilibria. We confirm the results by a numerical analysis of the model. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To analyze the performance of commonly used blood tests in febrile infants ≤90 days of age to identify patients at low risk for invasive bacterial infection (bacterial pathogen in blood or cerebrospinal fluid) by duration of fever. METHODS: We conducted a secondary analysis of a prospective single-center registry that includes all consecutive infants #90 days of age with fever without a source evaluated at 1 pediatric emergency department between 2008 and 2021. We defined 3 groups based on caregiver-reported hours of fever (<2, 2-12, and ≥12) and analyzed the performance of the biomarkers and Pediatric Emergency Care Applied Research Network, American Academy of Pediatrics, and Step-by-Step clinical decision rules. RESULTS: We included 2411 infants; 76 (3.0%) were diagnosed with an invasive bacterial infection. The median duration of fever was 4 (interquartile range, 2-12) hours, with 633 (26.3%) patients with fever of <2 hours. The area under the curve was significantly lower in patients with <2 hours for absolute neutrophil count (0.562 vs 0.609 and 0.728) and C-reactive protein (0.568 vs 0.760 and 0.812), but not for procalcitonin (0.749 vs 0.780 and 0.773). Among well-appearing infants older than 21 days and negative urine dipstick with <2 hours of fever, procalcitonin ≥0.14 ng/mL showed a better sensitivity (100% with specificity 53.8%) than that of the combination of biomarkers of Step-by-Step (50.0% and 82.2%), and of the American Academy of Pediatrics and Pediatric Emergency Care Applied Research Network rules (83.3% and 58.3%), respectively. CONCLUSIONS: The performance of blood biomarkers, except for procalcitonin, in febrile young infants is lower in fever of very short duration, decreasing the accuracy of the clinical decision rules. [ABSTRACT FROM AUTHOR]

Introduction: Febrile young infants are at risk of serious bacterial infections (SBIs), which are potentially life-threatening. This study aims to investigate the association between delayed presentation and the risk of SBIs among febrile infants. Method: We performed a prospective cohort study on febrile infants ≤90 days old presenting to a Singapore paediatric emergency department (ED) between November 2017 and July 2022. We defined delayed presentation as presentation to the ED >24 hours from fever onset. We compared the proportion of SBIs in infants who had delayed presentation compared to those without, and their clinical outcomes. We also performed a multivariable logistic regression to study if delayed presentation was independently associated with the presence of SBIs. Results: Among 1911 febrile infants analysed, 198 infants (10%) had delayed presentation. Febrile infants with delayed presentation were more likely to have SBIs (28.8% versus [vs] 16.3%, P<0.001). A higher proportion of infants with delayed presentation required intravenous antibiotics (64.1% vs 51.9%, P=0.001). After adjusting for age, sex and severity index score, delayed presentation was independently associated with the presence of SBI (adjusted odds ratio [AOR] 1.78, 95% confidence interval 1.26–2.52, P<0.001). Conclusion: Febrile infants with delayed presentation are at higher risk of SBI. Frontline clinicians should take this into account when assessing febrile infants. [ABSTRACT FROM AUTHOR]

Background: Tuberculous meningitis (TBM) accounts for about 1% of all tuberculosis cases and about 5% of extrapulmonary tuberculosis cases. However, it poses major importance because approximately half of those affected die or become severely disabled. Herein, the successful treatment of an 11-month-old boy with progressive limb weakness, fever, developmental retardation, and loss of consciousness due to tuberculosis, was reported. Case presentation: An 11-month-old (Iranian Turk) boy was referred to Loghman Hakim hospital for progressive limb weakness and loss of previously attained developmental milestones for the past 2 months. He also had persistent fever and loss of consciousness for about 14 to 21 days. Before being referred to our center, the patient had been diagnosed with hydrocephalus at another center due to possible acute bacterial meningitis based on a CT scan and MRI imaging. On physical examination, anterior fontanel bulging and neck stiffness were observed on the admission. His body temperature and heart rate were 38.1 C and 86 beats per minute (bpm), respectively. He had left 6 cranial nerve palsy and spastic quadriparesis with a power of grade 3/5. Other systemic examinations were normal. Endoscopic third ventriculostomy (ETV) (and leptomeningeal biopsy) revealed diffuse thickening of the floor and lateral walls of the 3rd ventricle and also a cobblestone appearance in the form of multiple white patchy lesions was detected on the floor of the 3rd ventricle. CSF analysis and polymerase chain reaction confirmed the TB meningitis. During hospitalization, a temporary EVD (external ventricular drain) was initially inserted. Eventually, defervescence was denoted 5–6 days after initiation of anti-TB medications, and a permanent ventriculoperitoneal shunt was inserted due to hydrocephalus. Gradually his truncal and limb tone and motor function improved, as did his emotional responses to his parents and ability to eat. The patient can walk without help in the 15th month following the operation and resolved hydrocephalus demonstrated on follow-up imaging. Conclusion: Over half of treated TB meningitis patients die or suffer severe neurological sequelae, mainly due to late diagnosis. Hence, early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome. [ABSTRACT FROM AUTHOR]

Obejective: To investigate the impact of curcumin (Cur) regulating the brain-derived neurotrophic factor (BDNF) /tropomyosin related kinase B receptor (TrkB) signaling pathway on neuronal apoptosis in neonatal rat with bacterial meningitis (BM). Methods: 15 rats were randomly selected as non-infected group (NF group), other rats injected streptococcus pneumoniae ATCC49619 suspension into frontal subarachnoid space to construct BM rat model, the successful BM model was randomly divided into BM group, L-Cur group (1.25 mg/kg), M-Cur group (2.5 mg/kg), H-Cur group (5 mg/kg), H-Cur+K252a group (5 mg/kg Cur+2.5 +g/kg K252a), 15 rats in each group, once a day, the injections were given continuously for 3 weeks. The rats were weighed and clinical scored, HE staining and Nissl staining were used to observe the damage of nerve cells; TUNEL staining was used to evaluate neuronal apoptosis. The levels of glial fibrillary acid protein (GFAP) and spinal cord calcium ion adaptor protein-1 (IBA-1) were detected by immunofluorescence staining. The levels of inflammatory factors and chemokines in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Western blot was used to detect the expression of apoptosis protein and BDNF/TrkB pathway protein in brain tissue. Results: The brain tissue structure of the NF group was normal, large area of blue Nissl bodies appeared in the cytoplasm of neurons. In the BM group, a large amount of inflammatory exudate and inflammatory cell infiltration appeared in the subarachnoid space, the cell bodies were enlarged, the processes contracted, and the morphology was irregular; the number of Nissl bodies, weight, the levels of Bcl-2, BDNF, and p-TrkB/TrkB protein decreased obviously (P<0.05), the clinical score, the relative fluorescence intensity values of IBA-1 and GFAP, the relative expression of chemokine ligand-2 (CCL-2), chemokine ligand-3 (CCL-3), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the rate of neuronal apoptosis, and the level of BCL2-Associated X protein (Bax) protein increased obviously (P<0.05). The inflammatory exudate and cell infiltration of brain tissue were reduced, the number of Nissl bodies, weight, the levels of B-lymphoblastoma-2 gene (Bcl-2), BDNF, and p-TrkB/TrkB protein increased obviously in each group after Cur treatment (P<0.05), the clinical score, the relative fluorescence intensity values of IBA-1 and GFAP, the relative expression of CCL-2, CCL-3, TNF-α, and IL-6, the rate of neuronal apoptosis, and the level of Bax protein decreased obviously (P<0.05), the higher the addition dose of Cur, the more obvious the change; the effect of H-Cur+K252a group was similar to that of BM group, K252a reversed the improvement effects of Cur on neuron apoptosis and damage in BM rat. Conclusion: Cur might reduced neuronal apoptosis in BM rat by activating BDNF/TrkB signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Healthcare-associated Gram-negative bacterial meningitis is a substantial clinical issue with poor outcomes, especially for neurosurgical patients. Here, we aimed to study the characteristics and treatment options of patients with healthcare-associated carbapenem-non-susceptible (Carba-NS) Gram-negative bacterial meningitis. Methods: This observational cohort study was conducted at a teaching hospital from 2004 to 2019. The clinical characteristics of patients with meningitis with Carba-NS and carbapenem-susceptible (Carba-S) bacilli were compared, and the antimicrobial chemotherapy regimens and outcomes for Carba-NS Gram-negative bacterial meningitis were analyzed. Results: A total of 505 patients were included, of whom 83.8% were post-neurosurgical patients. The most common isolates were Acinetobacter spp. and Klebsiella spp., which had meropenem-resistance rates of 50.6% and 42.5%, respectively, and showed a markedly growing carbapenem-resistance trend. Kaplan–Meier curve analysis revealed that Carba-NS Gram-negative bacilli were associated with a significantly higher in-hospital mortality rate (18.8%, 35/186) compared to the Carba-S group (7.4%, 9/122; P = 0.001). For Carba-NS Enterobacterales meningitis, aminoglycoside-based and trimethoprim-sulfamethoxazole-based regimens yielded significantly higher clinical efficacy rates than non-aminoglycoside-based and non-trimethoprim-sulfamethoxazole-based regimens (69.0% vs. 38.7%, P = 0.019 and 81.8% vs. 46.9%, P = 0.036, respectively). For Carba-NS A. baumannii complex meningitis, tetracycline-based (including doxycycline, minocycline, or tigecycline) therapy achieved a significantly higher clinical efficacy rate (62.9%, 22/35) than the non-tetracycline-based therapy group (40.4%, 19/47; P = 0.044). Conclusions: Our findings revealed that Carba-NS Gram-negative bacilli are associated with higher in-hospital mortality in patients with healthcare-associated meningitis. The combination therapies involving particular old antibiotics may improve patients' outcome. Trial registration: This study was registered on the Chinese Clinical Trial Register under ChiCTR2000036572 (08/2020). [ABSTRACT FROM AUTHOR]

Aim: The pneumococcal conjugate vaccine, which covered seven serotypes of Streptococcus pneumoniae (PCV7), was introduced in Stockholm, Sweden, in 2007. It was replaced by a 13‐valent vaccine (PCV13) in 2011. We previously reported a decreased incidence of pneumonia and sinusitis among young children 4 years after the introduction of the PCV7. This study followed the incidence of pneumonia, sinusitis, mastoiditis and meningitis for four more years. Methods: We studied validated hospital registry data covering children up to 17 years of age, who were hospitalised in the Stockholm region from 2003 to 2016, when the child population peaked at 485 687. All 11 115 cases diagnosed with pneumonia, coded as bacterial pneumonia, sinusitis, mastoiditis, bacterial meningitis or empyema, were identified. The controls had viral pneumonia or pyelonephritis. Results: The incidence rates for children under 2 years of age hospitalised for sinusitis, mastoiditis and meningitis decreased significantly by 61%–79% during the eight‐year post‐vaccination period. Hospitalisations for bacterial pneumonia decreased by 19%–25% in the same age group. These changes were probably due to both the vaccines and changes in diagnosis routines. Conclusion: The effect of vaccination on children under 2 years of age was sustained 8 years after the introduction of the pneumococcal conjugate vaccines. [ABSTRACT FROM AUTHOR]

The resection of the jugum (planum) sphenoidale meningioma (JSM) is challenging, and there is a scarcity of available data in the literature. This study aimed to describe the surgical management and long-term outcome of jugum sphenoidale meningioma. This was a retrospective, single-center, cohort study of 91 JSM patients treated in our department from 2005 to 2022. All the included patients have undergone surgical treatment. Clinical, radiologic, and surgical data were extracted with specific attention to the age at onset, family history, duration from symptoms to diagnosis, clinical presentation, quality of excision, recurrence, and treatment outcome. WHO grade I and grade II meningioma were 83.5% (n = 76) and 16.5% (n = 15) respectively. Fronto-lateral 42.9% (n = 39) and pterional approaches 57.1% (n = 52) were the 2 major surgical approaches used for the management of planum sphenoidale meningioma. Twelve patients needed emergency surgical treatment at admission: 4 (4.4%) External CSF Shunt and 8 (8.8%) VP-Shunt. We have found a statistically significant (P = 0.032) association between the quality of excision and the risk of recurrence. The GTR (Hazard ratio = 1) of the planum meningioma protects the patient from recurrence within 60 months of follow-up. Postoperative complications encountered were CSF-Leak in 2.2%, Meningitis 4.4%, surgical site infection 2.2%, and surgical site hematoma 3.3%. The overall postoperative favorable outcome was 68.1% (n = 62). The pterional approach has allowed the achievement of GTR for jugum sphenoidale meningioma with protective odds from recurrence risk. [ABSTRACT FROM AUTHOR]

Purpose: Clinical presentations encompass respiratory, feeding issues, nasopharyngeal mass, meningitis, CSF leakage, craniofacial anomalies, and endocrine problems. Surgery is the primary treatment, transitioning from frontal craniotomy to endoscopic methods, offering improved outcomes. Yet, more studies are needed. A comprehensive review on trans-sellar trans-sphenoidal encephalocele (TSTSE) is missing. Our study aims to fill this gap, offering a comprehensive perspective for physicians. Methods: This review adhered to the PRISMA guideline. Eligible studies focused on human subjects, specifically trans-sellar encephaloceles, and provided comprehensive treatment details. English language articles published up to April 11th, 2023, were considered. Two trained researchers conducted article screening using consistent criteria. Data extraction covered various aspects, including clinical presentation, surgical methods, and outcomes, with results presented descriptively in two tables. Due to the rarity of this congenital anomaly, meta-analysis and publication bias assessment were not feasible. Data extraction was independently conducted by two reviewers, with subsequent cross-verification. Results: A total of 36 patients were identified from 14 studies, the most frequently observed clinical presentation was dyspnea (41.67%) and the most frequently observed accompanying anomaly was cleft lip/palate (55.56%). CT and MRI were adopted in nearly all the cases, and trans-nasal approach was the most often used surgical approach (57.14%) with the 'soft material combination' the most commonly used method for cranial base repairment (35.71%). A total of two deaths occurred and diabetes insipidus was the most common perioperative complication which occurred in six surgery patients (21.43%). Conclusion: TSTSE predominantly affects males and presents with dyspnea, visual deficits, pituitary insufficiency, and cranial base-related symptoms. Early diagnosis is critical, with advanced imaging playing a key role. Endocrine assessment is vital for hormone management. Surgery offers symptom relief but entails risks, including reported fatalities and complications. The choice between surgery and conservative management requires careful deliberation. The trans-nasal approach is favored for its reduced trauma, yet further research is necessary to validate this preference. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to compare the effect of text and video formats of an online theory-based Meningitis B (MenB) health message intervention on college students. Participants: College freshmen and transfer students admitted at a Southern U.S. University. Methods: In a 2-arm randomized study, knowledge, perceptions, and intention to receive the vaccine were compared pre- and post-intervention. Results: Post intervention, participants in both the written and video interventions had significantly higher scores of knowledge, perceptions, and intentions. Upon comparing the change in scores pre- to post-intervention between both text and video groups, no significant differences were found between both groups. Conclusions: This study, a first in using a theory-based MenB online education intervention and questionnaire to compare text and video formats, suggests that both text and video formats are equally effective in raising young adults' awareness about the MenB vaccine. [ABSTRACT FROM AUTHOR]

The article offers information on neonatal meningitis, a rare but serious disease affecting newborns, with acute inflammation of the brain tissue. Topics include the categorization of neonatal meningitis into early and late onset, common pathogens like Group B Streptococcus and Escherichia coli, and risk factors such as prematurity and maternal colonization.

Introduction: Although concomitant pneumonia is sometimes diagnosed in childhood bacterial meningitis, its role in the illness course and prognosis is not known. We examined these associations using prospectively collected data from Finland, Latin America and Angola. Methods: This was a secondary descriptive analysis of prospectively collected data (clinical and laboratory findings at admission, during hospitalisation and outcome) from five clinical bacterial meningitis trials. We included children aged 2 months to 15 years from sites with confirmed bacterial meningitis and potential concomitant pneumonia (diagnosed clinically with or without a chest radiograph). Results: Pneumonia was not observed in the 341 children included in Finland. Pneumonia was observed in 8% (51/606) of children in Latin America and in 46% (377/819) in Angola (p < 0.0001). In multivariate analyses, predisposing factors for pneumonia in Latin America were age <1 year, seizures and severe anaemia; the corresponding factors for Angola were preadmission duration of illness >3 days and non‐meningococcal meningitis. Concomitant pneumonia increased the severity of the disease and disabling sequelae. Conclusion: Bacterial meningitis with pneumonia is a major, previously undescribed entity of severe bacterial meningitis, especially in Angola. [ABSTRACT FROM AUTHOR]

The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults. This study aims to investigate the association between eCRPv and bacterial etiologies among pediatric patients with very elevated CRP levels. We conducted a retrospective analysis of patients under 18 years of age who had been admitted to our Pediatric Emergency Department from 2018 to 2020 with a fever and CRP levels ≥ 150 mg/L. Bacterial and non-bacterial etiologies were determined from hospital discharge diagnoses, which were monitored independently by three physicians from the research team. The records of 495 suitable patients (51.2% males, median age 3.2 years) were retrieved of whom 444 (89.7%) were eventually diagnosed with bacterial infections. The mean CRP levels were significantly higher for bacterial etiologies compared with other causes (209.2 ± 59.8 mg/L vs. 185.6 ± 35.8 mg/L, respectively, p <.001), while the mean eCRPv values did not differ significantly (p =.15). In a time course analysis, we found that specifically in patients presenting ≥ 72 h after symptom onset, only a eCRPv1 level > 1.08 mg/L/h was an independent predictor of bacterial infection (aOR = 5.5 [95% CI 1.7–17.8], p =.004). Conclusion: Pediatric patients with very high CRP levels and fever mostly have bacterial infections. eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset, warranting further prospective investigations into CRP kinetics in pediatric patients. What is Known: • The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. • Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults, but data on CRP kinetics in pediatric patients is sparse. What is New: • eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset in pediatric patients with remarkably elevated CRP levels. [ABSTRACT FROM AUTHOR]

Background: Pediatric coronavirus disease 2019 infection usually presents with respiratory and gastrointestinal symptoms. In this report we present fulminant meningitis as the main presentation of coronavirus disease 2019 without major signs and symptoms of other organs' involvement in 3 infants. Cases: The first case was a 4 months Iranian male infant with fulminant meningitis as the main presentation of coronavirus disease 2019 without other organ involvement. He was treated as suspected bacterial meningitis but CSF PCR and CSF culture were negative for common meningeal pathogens. On 3rd day, his coronavirus disease 2019 PCR test became positive, while it was negative on 1st day. The second case was a 13 months Iranian male infant with fever, irritability, and photophobia for 24 h before poorly controlled status epilepticus. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. Seizures were controlled with multiple anti-seizure medications. The third case was a 14 months Iranian female infant with fever and seizure1 hour before admission, leading to poorly controlled status epilepticus despite anti-epileptic therapy 10 h after admission. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. He was controlled with multiple anti-seizure medications. Conclusion: Meningitis of coronavirus disease 2019 should be considered in severely ill pediatric cases with poorly controlled seizures and RBC in CSF smear. Also, pediatricians can consider corticosteroids, remdesivir, and IVIG therapy in these cases. [ABSTRACT FROM AUTHOR]

Background: Neisseria meningitides, Streptococcus pneumonia, and hemophilic influenza type B are frequently linked to bacterial meningitis (BM) in children. It's an infectious sickness that kills and severely mobilizes children. For a variety of reasons, bacterial meningitis remains a global public health concern; most cases and deaths are found in Sub-Saharan Africa, particularly in Ethiopia. Even though vaccination has made BM more preventable, children worldwide are still severely harmed by this serious illness. Age, sex, and co-morbidity are among the risk variables for BM that have been found. Therefore, the main objective of this study was to identify the variables influencing the time to recovery for children with bacterial meningitis at Jigjiga University referral hospital in the Somali regional state of Ethiopia. Method: A retrospective cohort of 535 children with bacterial meningitis who received antibiotic treatment was the subject of this study. Parametric Shared Frailty ty and the AFT model were employed with log likelihood, BIC, and AIC methods of model selection. The frailty models all employed the patients' kebele as a clustering factor. Results: The number of cases of BM declined in young children during the duration of the 2 year, 11 month study period, but not in the elderly. Streptococcus pneumonia (50%), hemophilic influenza (30.5%), and Neisseria meningitides (15%) were the most frequent causes of BM. The time to recovery of patients from bacteria was significantly influenced by the covariates male patients (ϕ = 0.927; 95% CI (0.866, 0.984); p-value = 0.014), patients without a vaccination history (ϕ = 0.898; 95% CI (0.834, 0.965); P value = 0.0037), and patients who were not breastfeeding (ϕ = 0.616; 95% CI (0.404, 0.039); P-value = 0.024). The recovery times for male, non-breastfed children with bacterial patients are 7.9 and 48.4% shorter, respectively. In contrast to children with comorbidity, the recovery time for children without comorbidity increased by 8.7%. Conclusion: Age group, sex, vaccination status, co-morbidity, breastfeeding, and medication regimen were the main determinant factors for the time to recovery of patients with bacterial meningitis. Patients with co-morbidities require the doctor at Jigjiga University Referral Hospital to pay close attention to them. [ABSTRACT FROM AUTHOR]

Steroid-induced neuropsychiatric sequelae are common, and pose significant risks to people usually receiving glucocorticoids in the context of physical illness. Steroid-induced mania and hypomania are the most common of the acute complications, yet despite great progress in understandings in neurophysiology there are no recent studies which review the factors which might predict who will experience this severe complication, nor are there consensus guidelines on management. We report the unusual case of a woman in her 50s admitted to a psychiatric unit with steroid-induced mania despite compliance with two mood stabilisers, several days after the administration of a Dexamethasone and Docetaxel chemotherapy regime adjunctive to lumpectomy for breast cancer. She had previously been diagnosed with an organic affective disorder (with classical bipolar 1 pattern) following severe ventriculitis related to ventricular drain insertion for obstructive hydrocephalus secondary to a colloid cyst. She had no psychiatric illness before this brain injury, but has a maternal history of idiopathic bipolar 1 affective disorder. Her episode of steroid-induced mania resolved following use of sedative medications, continuation of her existing mood stabilisers, and reductions of the steroid dosing in collaboration with her oncology team, which also protected her from further manic relapses during continued chemotherapy. Established mental illness, a family history, and acquired brain injury may reflect risk factors for steroid-induced mania through currently unclear pathways. Future epidemiological studies could better confirm these observations, and basic neuroscience may look to further explore the role of extrinsic glucocorticoids in the pathophysiology of affective disorders. [ABSTRACT FROM AUTHOR]

This study aims to audit the adherence of Jordanian medical care staff to the guidelines provided by the Infectious Disease Society of America (IDSA) for managing pediatric patients admitted with suspected cases of meningitis. A retrospective observational study was conducted at Jordan University Hospital (JUH). All pediatric patients admitted to JUH with suspected meningitis between January 1, 2019, and September 30, 2022, who underwent Cerebrospinal Fluid (CSF) and blood culture tests were recruited in this study unless there was a reason for exclusion. The study collected data on the empiric antibiotics prescribed prior to diagnostic cultures and susceptibility results. Additionally, the length of hospital stay and all-cause mortality were observed. The appropriateness of antibiotics prescription before culture results was compared to IDSA guidelines, and an overall adherence rate was calculated. A total of 332 pediatric patients were included in this study, of whom 12.3% (n = 41) were diagnosed with bacterial meningitis. Among the enrolled pediatric patients, only 27 patients (8.1%) received appropriate treatment adhering to the IDSA guidelines. The remaining 91.9% (n = 305) showed various forms of non-adherence to recommendations. The highest adherence rate was observed for performing CSF culture (n = 330, 99.4%), while the lowest adherence rate was found in selecting the appropriate dose and duration for empiric antibiotics (n = 107, 41.3% and n = 133, 51.0%, respectively). This study revealed a low overall adherence in the management of pediatric patients with meningitis in Jordan. Establishing an antimicrobial stewardship program may improve the outcomes of meningitis infections found in Jordan, and prevent dangerous adverse effects and bacterial resistance. [ABSTRACT FROM AUTHOR]

Bacterial meningitis is a severe infection with a high fatality rate, and affects children in particular. Three vaccines against the most common bacterial causatives of meningitis, Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitides, exist. Monitoring the type and incidence of bacterial meningitis is important for making future prevention and control plans. In this study, we retrospectively analyzed data regarding bacterial meningitis recovered in the Italian Hospital of Desio from 2000 to 2019. Samples from a total of 128 patients were included. Streptococcus pneumoniae was the most common microorganism, isolated in 45 cases, followed by Neisseria meningitidis (14), Listeria monocytogenes (8), Streptococcus agalactiae (group B) (4), and Haemophilus influenzae type b (2). The implementation of vaccination schedules decreased the number of bacterial meningitis cases caused by H. influenzae type b, S. pneumoniae, and N. meningitidis. Considering the bacterial meningitis cases in subjects aged 0–12 years, no H. influenzae type b strain was isolated, five cases of N. meningitidis were identified before the introduction of vaccination, and seven S. pneumoniae strains were isolated before the introduction of the PCV13 vaccination. Surveillance studies allowed us to monitor changes in bacteria distribution and to guide vaccination strategies. [ABSTRACT FROM AUTHOR]

The recent outbreak of the influenza virus has grown to be a significant issue and a matter of great concern in terms of controlling the impending influenza pandemic. The influenza virus poses a serious threat as it directly infects and impairs the immune system reaction and the respiratory tract. The virus effectively produces infectious viral particles when haemagglutinin molecules are properly cleaved at the respiratory epithelium. The mode of transmission is via droplets from an affected case. The lungs, responsible for the vital exchange of gases, can fail due to various mechanisms, including the destruction of epithelial cells, significant degradation of the extracellular matrix, and airway obstruction. Influenza is a primary cause of severe pneumonia, but it can be accompanied by further bacterial infections, commonly involving bacteria such as Streptococcus pneumoniae and S. aureus. Influenza infection increases the susceptibility to developing Acute Respiratory Distress Syndrome (ARDS) and bacterial sepsis. Both adults and children have a 30-50% chance of experiencing viral infections along with bacterial pneumonia. Notably, Influenza A virus (H3N2) influenza has been associated with a significant increase in admissions to intensive care units. Among the factors contributing to the development of ARDS, individuals between the ages of 36 and 55 years, pregnant women, and obese individuals are at a higher risk. However, infection with influenza viruses A (H3N2) or B, female sex, and influenza vaccination have been identified as protective factors against ARDS. Influenza infection increases the susceptibility to developing ARDS and bacterial sepsis. Disease progression can be limited by spreading awareness among the people about the factors responsible for transmission, clinical manifestations, and preventive methodologies. [ABSTRACT FROM AUTHOR]

Introduction: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a rapidly progressing, rare disease that often presents as meningitis or sepsis. It mostly affects infants and adolescents, with high fatality rates or long-term sequelae. In the Netherlands, serogroup B (MenB) is most prevalent. We aimed to estimate the economic burden of MenB-related IMD between 2015 and 2019, including direct and indirect medical costs from short- and long-term sequelae, from a societal perspective. Methods: IMD incidence was based on laboratory-based case numbers from the Netherlands Reference Laboratory for Bacterial Meningitis (Amsterdam UMC, Amsterdam, the Netherlands); there were 74 MenB cases on average per year in the study period 2015–2019. Case-fatality rate (3.8%) and percentage of patients discharged with sequelae (46%) were derived from literature. Direct costs included treatment costs of the acute phase, long-term sequelae, and public health response. Indirect costs were calculated using the human capital (HCA) and friction costs (FCA) approaches, in which productivity losses were estimated for patients and parents during the acute and sequelae phases. Costs were discounted by 4% yearly. Results: Estimated costs due to MenB IMD in an annual cohort were €3,094,199 with FCA and €9,480,764 with HCA. Direct costs amounted to €2,974,996, of which 75.2% were related to sequelae. Indirect costs related to sequelae were €52,532 with FCA and €5,220,398 with HCA. Conclusion: Our analysis reflects the high economic burden of MenB-related IMD in the Netherlands. Sequelae costs represent a high proportion of the total costs. Societal costs were dependent on the applied approach (FCA or HCA). Graphical Plain Language Summary: [ABSTRACT FROM AUTHOR]

Introduction: Neonatal bacterial meningitis (NBM) is the most devastating complication of late‑onset sepsis with incidence ranging from 12.5% to 61.11% with a mortality rate of 16‑45.5% and disability rate of 25-50%. Objectives: To estimate the clinical and laboratory predictors of mortality in outborn neonates with NBM. Methods: A prospective observational study was carried out on 150 outborn neonates with late‑onset sepsis and with clinically diagnosed meningitis; and CSF biochemical abnormalities with or without CSF culture positivity at a tertiary care teaching hospital in central India over a period of 2 years. Data on demographic, maternal, neonatal, and socio‑cultural factors were recorded and analyzed using a univariate and multiple regression model. Results: Distance travelled more than 150 km (OR 1.01, CI 1.0‑1.02, P = 0.04), transport duration >3 hrs (OR 4.58, CI 2.07‑10.11, P < 0.0001), premature rupture of membrane >24 hours (OR 9.68, CI 2.14‑43.70, P < 0.0001), transaminitis (SGPT >40IU/L) (OR 0.93, CI 0.88‑0.97, P < 0.003), CSF turbidity (OR 16.70, CI 4.45‑62.70, P < 0.0001), raised CSF protein (OR 8.81, CI 1.45‑53.34, P = 0.018), and low CSF sugar (OR 20.48, CI 4.18‑100.26, P < 0.0001) were independent predictors of mortality in neonatal meningitis on multivariate analysis. Conclusion: Anticipation, early recognition, and prompt treatment of maternal, neonatal, socio‑cultural, and laboratory risk factors are important to reduce the mortality of devastating complication of late‑onset sepsis. [ABSTRACT FROM AUTHOR]

The article focuses on Streptococcus suis, a zoonotic bacterial pathogen transmitted through swine, causing severe infections in humans, especially meningitis and sepsis. Topics include the prevalence and transmission routes of S. suis infections, the molecular epidemiology and population structure of zoonotic S. suis clades, and efforts to enhance surveillance and understanding of this underreported pathogen, particularly in Europe.

Background: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. Methods: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age. Results: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. Conclusions: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis in children. Methods: The peripheral blood of five bacterial meningitis patients, five viral meningitis samples, and five healthy individuals were collected for RNA sequencing. Then, the differentially expressed lncRNA and mRNA were detected in bacterial meningitis vs. controls, viral meningitis vs. healthy samples, and bacterial vs. viral meningitis patients. Besides, co-expression and the competing endogenous RNA (ceRNA) networks were constructed. Receiver operating characteristic curve (ROC) analysis was performed. Results: Compared with the control group, 2 lncRNAs and 32 mRNAs were identified in bacterial meningitis patients, and 115 lncRNAs and 54 mRNAs were detected in viral meningitis. Compared with bacterial meningitis, 165 lncRNAs and 765 mRNAs were identified in viral meningitis. 2 lncRNAs and 31 mRNAs were specific to bacterial meningitis, and 115 lncRNAs and 53 mRNAs were specific to viral meningitis. The function enrichment results indicated that these mRNAs were involved in innate immune response, inflammatory response, and immune system process. A total of 8 and 1401 co-expression relationships were respectively found in bacterial and viral meningitis groups. The ceRNA networks contained 1 lncRNA-mRNA pair and 4 miRNA-mRNA pairs in viral meningitis group. GPR68 and KIF5C, identified in bacterial meningitis co-expression analysis, had an area under the curve (AUC) of 1.00, while the AUC of OR52K2 and CCR5 is 0.883 and 0.698, respectively. Conclusions: Our research is the first to profile the lncRNAs in bacterial and viral meningitis in children and may provide new insight into understanding meningitis regulatory mechanisms. [ABSTRACT FROM AUTHOR]

Aim: This study examined the predisposing factors, clinical picture, bacterial aetiology and clinical outcomes of infants and children with bacterial meningitis (BM). Methods: The medical records of patients under 16 years of age, treated by Turku University Hospital, Finland, from 2011 to 2018, were screened for meningitis using the International Classification of Diseases, Tenth Revision codes. Patients were included if bacteria were detected in cerebrospinal fluid (CSF) or other predefined laboratory variables indicated BM, despite CSF testing negative for bacteria. The Glasgow Outcome Scale (GOS) was used to determine outcomes. Results: We identified 37 children with BM: 22 infants aged 0–89 days and 15 children aged 90 days to 15 years. The overall incidence was approximately 5.7/100 000/year. Nosocomial meningitis was documented in 51%. Bacterial growth was detected in the CSF or blood cultures of the majority of patients (57%). Escherichia coli (14%), group B streptococcus (11%) and Streptococcus pneumoniae (8%) were the most common pathogens. There were 14% of patients with unfavourable outcomes, namely GOS scores of 1–4, but no deaths. Conclusion: The incidence of paediatric BM was low during the study period, but the proportion of nosocomial meningitis was substantial. The frequency of unfavourable long‐term outcomes was relatively low. [ABSTRACT FROM AUTHOR]

The evaluation and management of young infants presenting with fever remains an area of significant practice variation. While most well-appearing febrile young infants have a viral illness, identifying those at risk for invasive bacterial infections, specifically bacteremia and bacterial meningitis, is critical. This statement considers infants aged ≤90 days who present with a rectal temperature ≥38.0°C but appear well otherwise. Applying recent risk-stratification criteria to guide management and incorporating diagnostic testing with procalcitonin are advised. Management decisions for infants meeting low-risk criteria should reflect the probability of disease, consider the balance of risks and potential harm, and include parents/caregivers in shared decision-making when options exist. Optimal management may also be influenced by pragmatic considerations, such as access to diagnostic investigations, observation units, tertiary care, and follow-up. Special considerations such as temperature measurement, risk for invasive herpes simplex infection, and post-immunization fever are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Buffalo farming has become economically important in Brazil given the highly rustic nature of the species and the better nutritional characteristics of buffalo meat and milk. However, the sector has been impacted by the occurrence of different diseases in buffaloes that have been poorly described in the international literature to date. This study reports and describes the clinically observed neurological signs and the macroscopic and microscopic lesions of bacterial meningitis in adult buffaloes raised in the Amazon biome. These lesions are associated with fractures of the base of the horn and exposure of the frontal sinus. Meningitis is the inflammation of the membranes surrounding the central nervous system and is poorly described in water buffaloes. Five cases of meningitis in adults buffaloes of the Murrah and Mediterranean breads were studied. All buffaloes came from a farm located in the municipality of Castanhal, Pará, Brazil at different times. Clinical examination showed neurological clinical signs, such as apathy, reluctance to move, spastic paresis especially of the pelvic limbs, hypermetria, difficulty getting up, pressing of the head into obstacles and convulsion. In three buffaloes, a large part of the horn had been lost, exposing the corresponding frontal sinus, through which a bloody to purulent exudate flowed. The hemogram revealed neutrophilic leukocytosis. At necropsy, adherence of the dura mater to the periosteum and a purulent to fibrinopurulent exudate were observed in the sulci of the cerebral cortex and on the pia mater over almost the entire surface of the brain and throughout the spinal cord. The cerebrospinal fluid had a cloudy aspect with fibrin filaments. The histopathology of buffaloes confirmed the diagnosis of bacterial fibrinopurulent meningitis. Buffaloes are susceptible to bacterial inflammation of the meninges due to fractures of the base of the horn and mostly present with neurological manifestations. [ABSTRACT FROM AUTHOR]

What Is Known? and Objective. Ceftriaxone has been widely used to treat bacterial meningitis in pediatric patients. Ceftriaxone dosing regimens of 80–120 mg/kg/day have been recommended for bacterial meningitis in pediatric patients, and the usual duration of therapy is 7–14 days. Although the target site for meningitis is cerebrospinal fluid (CSF), a CSF pharmacokinetic (PK) model in pediatric patients has not been reported. We aimed to develop a CSF PK model of ceftriaxone, using not only serum but also CSF concentration data, and to evaluate the appropriateness of dosing regimens for pediatric patients with bacterial meningitis. Methods. The population PK model was developed by simultaneously fitting serum and CSF data from pediatric patients described in nine published articles. Probabilities of attaining a pharmacodynamic target (100% T > MIC, 100% of time that drug concentrations above the minimum inhibitory concentration) in CSF were estimated for some dosing regimens. Results and Discussion. Twenty-four pediatric patients with meningitis were the subjects for PK modeling (0.52–13 years old, and 3.5–50 kg of body weight). Sixty-eight serum concentrations and 98 CSF samples were used to develop the CSF PK model. The CSF/serum concentration ratio at the same sampling time was 0.0628 ± 0.0689. Age was not a statistically significant covariate in the PK parameter. In the CSF PK model, 40–60 mg/kg q12 h achieved a target attainment probability >90% against causative bacteria for bacterial meningitis. However, 4-h infusion (rather than 0.5-h infusion) dosing regimens were required for efficacy against antimicrobial-resistant bacteria with high MICs. What Is New? and Conclusion. Ceftriaxone-dosing regimens with prolonged infusion times might be reasonably effective for treating antimicrobial-resistant pathogens in empiric therapy. [ABSTRACT FROM AUTHOR]

The article describes the case of a previously healthy and fully immunized three-year-old female child with high fever, vomiting, lethargy and occipital headache for the past 12 hours. Topics discussed include an initial diagnosis of bacterial meningitis, ways Listeria infection is usually acquired, and reason that diagnosis of Listeria monocytogenes meningitis might often be delayed.

Background: Bacterial infections are considered a leading cause of hospitalization and death globally. There is still a need for a rapid and feasible biomarker for bacterial infections. Heparin-binding protein (HBP) was shown to be related to bacterial infections. The objective of the study is to investigate the diagnostic accuracy of HBP in bacterial infections. Methods: Articles were screened in PubMed, SCOPUS, Web of Science, and Cochrane to recognize eligible studies. We included studies investigating the diagnostic accuracy of HBP and reported the necessary data to construct 2 × 2 tables. A univariate analysis was conducted to determine the pooled sensitivity and specificity, and a bivariate diagnostic random-effects model was used to calculate the optimal cut-off point. Results: The analysis comprised sixteen studies in total. Plasma HBP showed a sensitivity of 0.90 (95% CI: [0.79, 0.96]) and a specificity of 0.87 (95% CI: [0.66, 0.96]) in diagnosing bacterial infections using blood samples. Pooling data from seven studies revealed that HBP in cerebrospinal fluid (CSF) has sensitivity and specificity of 96% (95% CI: [0.85, 0.99]), and 95% (95% CI: [0.89, 0.97]), respectively, for the diagnosis of bacterial meningitis. In urinary tract infections (UTI), urine-HBP was revealed to have a high diagnostic value in discriminating bacterial from non-bacterial UTI infection at a cut-off value of 32.868 ng/ml with sensitivity and specificity of 87%. Conclusion: HBP has shown a high diagnostic accuracy of bacterial infections, including UTI and meningitis. Further studies are needed to determine its prognostic value and whether it could guide antibiotic therapy. [ABSTRACT FROM AUTHOR]

Bacterial meningitis remains a leading cause of infection-related mortality worldwide. Although Escherichia coli (E. coli) is the most common etiology of neonatal meningitis, the underlying mechanisms governing bacterial blood-brain barrier (BBB) disruption during infection remain elusive. We observed that infection of human brain microvascular endothelial cells with meningitic E. coli triggers the activation of early growth response 1 (Egr-1), a host transcriptional activator. Through integrated chromatin immunoprecipitation sequencing and transcriptome analysis, we identified Egr-1 as a crucial regulator for maintaining BBB integrity. Mechanistically, Egr-1 induced cytoskeletal changes and downregulated tight junction protein expression by directly targeting VEGFA, PDGFB, and ANGPTL4, resulting in increased BBB permeability. Meanwhile, Egr-1 also served as a master regulator in the initiation of neuroinflammatory response during meningitic E. coli infection. Our findings support an Egr-1-dependent mechanism of BBB disruption by meningitic E. coli, highlighting a promising therapeutic target for bacterial meningitis. [ABSTRACT FROM AUTHOR]

Cryptococcal meningitis is a rare disease caused by Cryptococcus neoformans or Cryptococcus gatii as the fungal pathogen in humans. The disease is highly prevalent in people living with human immunodeficiency virus (HIV) and is the major cause of mortality in an immunocompromised individual. This life-threatening disease does not often occur with specific signs and symptoms. We reported a case of an early adulthood HIV-infected patient with a mild headache and low-grade fever. There was no altered mental status or other significant specific manifestations. Blood examination, chest radiography, and computed tomography scan revealed no significant results. C. neoformans were isolated from a culture of the cerebrospinal fluid specimen as the conventional gold standard examination for cryptococcal meningitis. A positive result was confirmed in the India ink staining preparation. The patient was treated with fluconazole monotherapy for the induction and consolidation phase and showed a positive disease progression during observations. [ABSTRACT FROM AUTHOR]

Neonatal bacterial infections have long been recognized as an important cause of acute morbidity and mortality, but long-term neurodevelopmental consequences have not been comprehensively described and discussed. We aimed to summarize evidence on the pathogenesis, diagnosis, and epidemiology of long-term sequelae after neonatal bacterial sepsis and meningitis. We also discuss approaches for future studies to quantify the public health impact of neonatal infection-associated neurodevelopmental impairment. We identified studies, both research articles and reviews, which provide mechanistic information on the long-term disease, as well as epidemiological studies that describe the frequency of neurodevelopmental impairment in children with and, for comparison, without a history of neonatal bacterial infection. Tools currently used in clinical practice and research settings to assess neurodevelopmental impairment were also reviewed. We first enumerate potential direct and indirect mechanisms that can lead to brain injury following neonatal infections. We then discuss summary data, either frequencies or measures of association, from epidemiological studies. Risk factors that predict long-term outcomes are also described. Finally, we describe clinical approaches for identifying children with neurodevelopmental impairment and provide an overview of common diagnostic tools. The limited number of studies that describe the long-term consequences of neonatal infections, often undertaken in high-income settings and using variable designs and diagnostic tools, are not sufficient to inform clinical practice and policy prioritization. Multi-country studies with follow-up into adolescence, standardized diagnostic approaches, and local comparator groups are needed, especially in low and middle-income countries where the incidence of neonatal sepsis is high. [ABSTRACT FROM AUTHOR]

Introduction: Understanding the epidemiology and cost implications of acute bacterial meningitis is crucial for effective health planning, timely treatment implementation, and comprehensive patient support measures, as well as for determining appropriate hospital expenses. Therefore, we conducted an analysis of hospitalization cases for bacterial meningitis in Brazil from January 2008 to December 2019. Methods: This is a descriptive ecological study that utilized the Hospital Information System of Brazil's National Unified Health System (SIH/SUS) database. The variables included sex, region, age group, hospitalizations, deaths, lethality rate, and hospital service expenses. The data were tabulated to focus specifically on the epidemiological aspect of bacterial meningitis. Results: During the study period, there were 20,207 hospitalizations for bacterial meningitis in Brazil. Men accounted for a higher number of cases, with 11,690 (57.67%), while women had a higher lethality rate of 10.64%. The Southeast region had the highest percentage of both hospitalizations (45.78%) and deaths (46.42%). Bacterial meningitis remains an important cause of morbidity and mortality, particularly in children under 5 years of age. Notably, the elderly and the Northeast region showed higher rates of lethality. The total expenditure on hospital services exceeded 43 million in Brazilian real, with the highest expenditure observed in 2019 and the lowest in 2011. Conclusion: A higher prevalence of the disease was observed in males, in children under 1-year-old and in the southeast region. Hospital expenditures were found to be substantial and increasing over time, underscoring the significance of early diagnosis and the promotion of vaccination campaigns. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is a Gram-positive, opportunistic bacterium capable of causing serious diseases such as meningitis. The main risk factor is the susceptible host with cancer or human immunodeficiency virus infection, with hematopoietic progenitor cell transplantation, pregnant women, newborns, and older adults. Ubiquitous, whose source of contagion is contaminated food such as cold meats, sausages, cheeses, and smoked fish. Despite the fact that its incidence is low, reporting between 0.1 and 10 cases per million people infected per year; the impact on morbidity and mortality is high and its diagnosis is complex. We present the case of a 16-year-old female patient, immunologically competent, with no significant history and a complete vaccination schedule for her age; that she went to an emergency department with an infection in the central nervous system and a fatal evolution. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate diagnostic accuracy of serum and cerebrospinal fluid (CSF) procalcitonin for diagnosing CNS bacterial infections. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and International Web of Science databases from January 1, 2016, to September 30, 2022. STUDY SELECTION: Randomized controlled trials and observational studies, either prospective or retrospective, focusing on procalcitonin as a biomarker for CNS infections. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. Data for diagnostic sensitivity and specificity were pooled using the bivariate or hierarchical model, as appropriate. DATA SYNTHESIS: Of 5,347 citations identified, 23 studies were included. Overall, CSF procalcitonin showed slightly higher pooled sensitivity, specificity, and positive likelihood ratio compared with serum procalcitonin. In adults, pooled sensitivity of CSF procalcitonin was 0.89 (95% CI, 0.71–0.96), specificity 0.81 (95% CI, 0.66–0.91); pooled sensitivity of serum procalcitonin was 0.82 (95% CI, 0.58–0.94), specificity 0.77 (95% CI, 0.60–0.89). In children, pooled sensitivity of CSF procalcitonin was 0.96 (95% CI, 0.88–0.99), specificity 0.91 (95% CI, 0.72–0.97); pooled sensitivity of serum procalcitonin was 0.90 (95% CI, 0.75–0.97), specificity 0.83 (95% CI, 0.67–0.92). In post-neurosurgical patients, pooled sensitivity of CSF procalcitonin was 0.82 (95% CI, 0.53–0.95), specificity 0.81 (95% CI, 0.63–0.91); pooled sensitivity of serum procalcitonin was 0.65 (95% CI, 0.33–0.88), specificity 0.61 (95% CI, 0.41–0.78). Logistic regression revealed between-study heterogeneity higher for serum than CSF procalcitonin. For the latter, threshold variability was found as source of heterogeneity. CONCLUSIONS: In children and critical post-neurosurgical patients, CSF procalcitonin gains superior sensitivity and specificity compared with serum procalcitonin. Overall, CSF procalcitonin appears to have a higher pooled positive likelihood ratio compared with serum procalcitonin. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcal meningoencephalitis (SME) is a rare, and frequently lethal, acute infection, and inflammation of the central nervous system parenchyma, with associated meningeal involvement. Bacterial meningoencephalitis is generally associated with high rates of morbidity and mortality, despite available antimicrobial and corticosteroid treatments. While Streptococcus pneumoniae is well recognised to cause bacterial meningitis, direct extension into the central nervous system parenchyma is rare. Case Presentation: A previously well 49-year-old man presented with sudden onset severe headache, fevers, neck stiffness, and reduced consciousness. The manifestations of SME in this patient were bilateral pupil-involving third-nerve palsies, wall-eyed bilateral internuclear ophthalmoplegia (WEBINO), bilateral blindness, bilateral deafness, a right lower motor neuron facial palsy, and upper motor neuron signs in his limbs. Initially, a partial response to high dose intravenous antibiotics occurred, but with administration of intravenous corticosteroids, further substantial resolution of the patient's neurological and neuro-ophthalmological deficits occurred. Conclusion: This case highlights the benefit of multidisciplinary diagnostic and therapeutic interventions in a case of SME complicated by bilateral pupil-involving third-nerve palsies, WEBINO, bilateral blindness, bilateral deafness, a right lower motor neuron facial palsy, and upper motor neuron signs. It appears to be the first reported case of SME with this rare collection of neuro-ophthalmological abnormalities. [ABSTRACT FROM AUTHOR]

Introduction: In this case report, we present a rare case of bilateral cryptococcal choroiditis following a diagnosis of meningitis in a 38-year-old woman with HIV. Case Presentation: A Colombian woman, newly diagnosed with HIV, presented with respiratory distress followed by meningeal syndrome. Further evaluation revealed cryptococcal meningitis caused by Cryptococcus neoformans, confirmed through cerebrospinal fluid analysis and brain magnetic resonance imaging. The patient reported mild blurred vision, prompting an ophthalmic examination that included indocyanine green angiography. The findings revealed signs of HIV retinopathy and multifocal choroidal lesions in both eyes, suggestive of choroidal cryptococcosis. Treatment involved intravenous administration of amphotericin B and flucytosine, followed by oral fluconazole. Subsequently, the choroidal lesions gradually regressed, and regular monitoring demonstrated no signs of recurrence. Conclusion: Cryptococcal choroiditis, though exceptionally rare, can occur in HIV-positive patients with disseminated cryptococcosis. Ophthalmologists should maintain a high index of suspicion for opportunistic infections, even in the absence of pronounced ocular symptoms, particularly in immunocompromised individuals. Early diagnosis and appropriate treatment are crucial for achieving favorable outcomes in such cases. [ABSTRACT FROM AUTHOR]

Invasive bacterial disease is associated with significant morbidity and mortality. In winter 2022, there was an apparent increased rate of invasive bacterial disease compared to preceding years. Cross-site retrospective analysis of the three Children's Health Ireland (CHI) hospitals looking at children admitted between 1st October 2022–31st December 2022 (Q4) with community-acquired invasive bacterial disease, defined as an abscess in a normally sterile site in the head, neck and chest or isolation or PCR detection of Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus pyogenes (Group A streptococcus) or Haemophilus influenzae from a normally sterile site. Case numbers were compared to Q4 in each of 2018–2021. Eighty-two children met the case definition in Q4 2022 vs 97 (Q4 2018–2021). In 2022, 42/82 (51%) were female, median age 3.75 years (1.5–8.25 years). Only 2 (2%) were immunosuppressed and 2 others (2%) had underlying neurodisability. Fifty (61%) were admitted on second or subsequent presentation to a healthcare setting. Fifty-six (68%) had an abscess in a sterile site. Bloodstream infection (positive blood culture or PCR: 24 (29%)) was the most common site of infection, followed by neck 22 (27%) and intracranial 12 (15%). Group A streptococcus (GAS) 27 (33%) was the most common organism isolated. Seven cases (9%) died in 2022 compared to 2 patients (2%) from 2018 to 2021 (p < 0.05). More children had Paediatric Overall Performance Category (POPC) scores > 1 in 2022 than 2018–2021 (p = 0.003). Conclusion: Invasive bacterial diseases increased in Q4 2022 with higher morbidity and mortality than in the preceding 4 years. Group A streptococcal infection was the most significant organism in 2022. What is known: • Invasive bacterial disease is the leading cause of childhood mortality globally. • There was an increase in cases of invasive Group A streptococcus infections reported in many countries (including Ireland) during the winter of 2022/23. What is new: • Head, neck and chest abscesses increased in Q4 of 2022 compared to the previous 4 years combined. • Invasive bacterial infections in Q4 of 2022 were associated with higher rates of mortality (9%), paediatric intensive care unit (PICU) admission (24%) and requirement for surgical drainage or intervention (67%) than in the preceding years. [ABSTRACT FROM AUTHOR]