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Objective: The objective of this study was to investigate the cytological features and diagnostic significance of cerebrospinal fluid (CSF) in bacterial meningitis (BM). Material and Methods: Patients diagnosed with BM at the First Affiliated Hospital of Nanchang University Hospital between August 2021 and April 2022 were enrolled. Clinical, cranial imaging, CSF-next-generation sequencing, CSF examination, and CSF cytology data were retrospectively analyzed. CSF cytology samples were prepared using a CSF cell pelletizer (precipitation method) and stained using the May-Grunwald-Glemsa (MGG) method. The χ2 test was employed to compare the positive rate of routine CSF count and CSF cytology. Results: Eight patients (four males and four females), aged 41-67 years, were included. Among them, two patients had undergone brain surgery within the past 4 months, one patient had an 8-year history of otitis media, and two patients had a history of sudden toothache. Clinical manifestations included fever, headache, sudden disturbance of consciousness, and neck stiffness. CSF cytology revealed abnormal inflammatory changes dominated by neutrophils in seven patients. Routine CSF cell counts exceeded 100/uL in only four cases, indicating a higher positive rate of CSF cytology for detecting CSF inflammatory reactions compared to routine cell count. Conclusion: Comparative detection of bacteria through the observation of CSF cytology inflammatory status in BM patients are more useful for diagnosing BM than routine CSF counts.
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Bacterial meningitis is a serious central nervous system (CNS) infection, claiming millions of human lives annually around the globe. The deadly infection involves severe inflammation of the protective sheath of the brain, i.e., meninges, and sometimes also consists of the brain tissue, called meningoencephalitis. Several inflammatory pathways involved in the pathogenesis of meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus suis, etc. are mentioned in the scientific literature. Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs), Nucleotide oligomerization domain (NOD)-like receptor-mediated signaling, pneumolysin related signaling, NF-κB signaling and many other pathways that lead to pro-inflammatory cascade and subsequent cytokine release including interleukine (IL)-1ß, tumor necrosis factor(TNF)-α, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) along with other mediators, leading to neuroinflammation. The activation of another protein complex, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, also takes place resulting in the maturation and release of IL-1ß and IL-18, hence potentiating neuroinflammation. This review aims to outline the inflammatory signaling pathways associated with the pathogenesis of bacterial meningitis leading to extensive pathological changes in neurons, astrocytes, oligodendrocytes, and other central nervous system cells.
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Quimiocinas , Citocinas , Inflamação , Meningites Bacterianas , Transdução de Sinais , Humanos , Transdução de Sinais/imunologia , Meningites Bacterianas/imunologia , Meningites Bacterianas/microbiologia , Meningites Bacterianas/metabolismo , Citocinas/metabolismo , Citocinas/imunologia , Animais , Quimiocinas/metabolismo , Quimiocinas/imunologia , Inflamação/imunologia , Barreira Hematoencefálica/imunologia , Inflamassomos/imunologia , Inflamassomos/metabolismoRESUMO
BACKGROUND: Post-neurosurgical meningitis (PNM) constitutes a grave complication associated with substantial morbidity and mortality. This study aimed to determine the risk factors predisposing patients to PNM following surgery for low- and high-grade gliomas. METHODS: We conducted a retrospective analysis encompassing all patients who underwent glioma surgery involving craniotomy at Turku University Hospital, Turku, Finland, between 2011 and 2018. Inclusion criteria for PNM were defined as follows: (1) Positive cerebrospinal fluid (CSF) culture, (2) CSF leukocyte count ≥ 250 × 106/L with granulocyte percentage ≥ 50%, or (3) CSF lactate concentration ≥ 4 mmol/L, detected after glioma surgery. Glioma grades 3-4 were classified as high-grade (n = 261), while grades 1-2 were designated as low-grade (n = 84). RESULTS: Among the 345 patients included in this study, PNM developed in 7% (n = 25) of cases. The median time interval between glioma surgery and diagnosis of PNM was 12 days. Positive CSF cultures were observed in 7 (28%) PNM cases, with identified pathogens encompassing Staphylococcus epidermidis (3), Staphylococcus aureus (2), Enterobacter cloacae (1), and Pseudomonas aeruginosa (1). The PNM group exhibited a higher incidence of reoperations (52% vs. 18%, p < 0.001) and revision surgery (40% vs. 6%, p < 0.001) in comparison to patients without PNM. Multivariable analysis revealed that reoperation (OR 2.63, 95% CI 1.04-6.67) and revision surgery (OR 7.08, 95% CI 2.55-19.70) were significantly associated with PNM, while glioma grade (high-grade vs. low-grade glioma, OR 0.81, 95% CI 0.30-2.22) showed no significant association. CONCLUSIONS: The PNM rate following glioma surgery was 7%. Patients requiring reoperation and revision surgery were at elevated risk for PNM. Glioma grade did not exhibit a direct link with PNM; however, the presence of low-grade gliomas may indirectly heighten the PNM risk through an increased likelihood of future reoperations. These findings underscore the importance of meticulous post-operative care and infection prevention measures in glioma surgeries.
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Neoplasias Encefálicas , Glioma , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias , Humanos , Glioma/cirurgia , Glioma/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Neoplasias Encefálicas/cirurgia , Adulto , Idoso , Fatores de Risco , Procedimentos Neurocirúrgicos/efeitos adversos , Gradação de Tumores , Reoperação , Adulto Jovem , Meningite/etiologia , Craniotomia/efeitos adversosRESUMO
Purpose of Review: Despite the availability of effective vaccines against the three primary pathogens (Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis) that cause bacterial meningitis, this condition remains a significant cause of morbidity, neurologic sequelae, and mortality among children and adults living in low-income and middle-income countries. Recent Findings: Bacterial meningitis represents a significant public health challenge for national and global health systems. Since vaccine-preventable meningitis remains highly prevalent in low-income and middle-income countries, the World Health Organization (WHO) recently developed a global roadmap to defeating meningitis by 2030 and ameliorating its associated neurological sequelae. Summary: There is a need for a global approach to surveillance and prevention of bacterial meningitis. Increasing vaccination coverage with conjugate vaccines against pneumococcus and meningococcus with optimal immunization schedules are high-value healthcare interventions. Additionally, overcoming diagnostic challenges and the early institution of empirical antibiotic therapy and, when feasible, adjunctive steroid therapy constitutes the pillars of reducing the disease burden of bacterial meningitis in resource-limited settings.
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BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.
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Meningites Bacterianas , Infecções Estreptocócicas , Streptococcus pyogenes , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antibacterianos/uso terapêutico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Meningites Bacterianas/mortalidade , Fatores de Risco , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/mortalidadeRESUMO
Capnocytophaga canimorsus is a bacterium commonly found in the oral cavities of cats and dogs. Infections are particularly common in immunocompromised patients who have been exposed to bites or come in contact with saliva from these animals. The manifestations of infection include bacteremia, fever, and, rarely, meningitis. Diagnosis is challenging given the bacteria has slow growth on culture media. The organism is susceptible to beta-lactam antibiotics, with higher-generation cephalosporins recommended for treating meningitis. We present a case of a 74-year-old woman with altered mental status and no signs of immunosuppression. She was diagnosed with meningitis caused by Capnocytophaga, with an intriguing finding of pneumocephalus, which is a rare occurrence as per literature review.
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PURPOSE: To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic. METHODS: In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model. RESULTS: We included 1,699 patients in 2006-2020, 50 patients in 2020-2021, and 182 patients in 2021-2023. After March 2020 relatively more alcoholism was reported (2006-2020, 6.1%; 2020-2021, 18%; 2021-2023, 9.7%; P = 0.002) and otitis-sinusitis was less frequently reported (2006-2020, 45%; 2020-2021, 22%; 2021-2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006-2020, 89%; 2020-2021, 74%; 2021-2022, 86%; P = 0.002) and outcomes were worse ('good recovery', 2020-2021, OR 0.5, 95% CI 0.3-0.8). CONCLUSION: During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality.
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Chronic inflammatory diseases are caused due to prolonged inflammation at a specific site of the body. Among other inflammatory diseases, bacterial meningitis, chronic obstructive pulmonary disease (COPD), atherosclerosis and inflammatory bowel diseases (IBD) are primarily focused on because of their adverse effects and fatality rates around the globe in recent times. In order to come up with novel strategies to eradicate these diseases, a clear understanding of the mechanisms of the diseases is needed. Similarly, detailed insight into the mechanisms of commercially available drugs and potent lead compounds from natural sources are also important to establish efficient therapeutic effects. Zebrafish is widely accepted as a model to study drug toxicity and the pharmacokinetic effects of the drug. Moreover, researchers use various inducers to trigger inflammatory cascades and stimulate physiological changes in zebrafish. The effect of these inducers contrasts with the type of zebrafish used in the investigation. Hence, a thorough analysis is required to study the current advancements in the zebrafish model for chronic inflammatory disease suppression. This review presents the most common inflammatory diseases, commercially available drugs, novel therapeutics, and their mechanisms of action for disease suppression. The review also provides a detailed description of various zebrafish models for these diseases. Finally, the future prospects and challenges for the same are described, which can help the researchers understand the potency of the zebrafish model and its further exploration for disease attenuation.
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We present a rare case of Moraxella catarrhalis meningitis in a 51-year-old immunocompetent woman after surgical resection of a fourth ventricle ganglioma. Notably, the patient had no history of sinusitis or otitis media, which are typical predisposing factors for Moraxella infection. She developed symptoms including headache, altered mental status, and neurological deficits three days post discharge, leading to her diagnosis confirmed by cerebrospinal fluid culture. This case highlights the diagnostic challenges and management complexities of atypical meningitis post neurosurgery. The occurrence emphasizes the necessity of considering Moraxella catarrhalis in differential diagnoses, particularly following neurosurgical procedures. This instance contributes to the scarce documentation of such infections in immunocompetent adults, underscoring the importance of vigilant microbiological evaluation and tailored antimicrobial therapy in postoperative settings.
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The incidence of incomplete partition Type I inner ear malformation is very low; therefore, bacterial meningitis caused by this malformation is also rare. Here, we report a case of such a patient. This case is a young female patient, who is 7 years old, began to have recurrent headaches, and after 5 years, also began to have chest and back pain. The doctor diagnosed meningitis, and the anti-infection treatment was effective. She was followed up annually and continued to have outbreaks repeatedly for 17 years, but the cause of repeated infection was not found. After a detailed diagnosis and treatment in our hospital, the patient was finally diagnosed with incomplete partition Type I inner ear malformation, resulting in repeated bacterial meningitis. The patient recovered well after surgical treatment, and the symptoms did not recur after 1-year follow-up.
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A 43-year-old man was admitted to our department due to fever and headache. The cerebrospinal fluid analysis confirmed bacterial meningitis. Campylobacter species were isolated from blood cultures on the third day of admission. The patient was treated with meropenem (MEPM) and discharged on the 17th day. However, he experienced a recurrence of meningitis and was readmitted on the 68th day, initiating MEPM therapy. Campylobacter fetus was isolated from cerebrospinal fluid cultures on the 74th day. MEPM was continued until the 81st day, followed by one month of minocycline (MINO) therapy. The patient had an uneventful recovery without further recurrence. This case highlights the potential for recurrence of Campylobacter fetus meningitis approximately two months after the resolution of the initial infection. In addition to carbapenem therapy for at least two weeks, the adjunctive administration of MINO may be beneficial.
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Antibacterianos , Infecções por Campylobacter , Campylobacter fetus , Meningites Bacterianas , Meropeném , Minociclina , Recidiva , Humanos , Masculino , Adulto , Campylobacter fetus/isolamento & purificação , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/complicações , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/microbiologia , Meropeném/administração & dosagem , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Meningites Bacterianas/diagnóstico , Antibacterianos/administração & dosagem , Fatores de Tempo , Minociclina/administração & dosagem , Resultado do Tratamento , Tienamicinas/administração & dosagem , Quimioterapia CombinadaRESUMO
Background This study aimed to determine if the cerebrospinal fluid (CSF) cell count is useful for predicting the infection severity or prognosis in Japanese adults with community-acquired bacterial meningitis. Methodology This study retrospectively evaluated the prognosis of patients diagnosed with community-acquired bacterial meningitis at our hospital from January 2004 to December 2021 using the modified Rankin scale (mRs) (Showa General Hospital; N = 39). Patients were classified into the following two groups: (i) favorable (mRs: 0-3) and (ii) unfavorable (mRs: 4-6). Eight factors were selected and compared with outcomes, and then two factors were evaluated from those, and a multivariate logistic regression was used to determine the significant variables. Results CSF cell count was observed to be associated with poor prognoses (odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.99995-0.99999, p = 0.0012). Glasgow coma scale (GCS) score on admission was also observed to be associated with poor prognoses (OR = 0.93, 95% CI = 0.89145-0.97290, p = 0.0029). Conclusions Low CSF cell count and low GCS on admission were observed as risk factors for poor prognoses in patients with bacterial meningitis.
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OBJECTIVE: This study investigated executive functions (EFs) in young adult survivors of childhood bacterial meningitis (BM). These skills are important for normal development, and their potential vulnerability in early years suggests that childhood BM could affect executive functions in the longer term. METHOD: The adult self-report Behavior Rating Inventory of Executive Function was administered to 474 young adult survivors of childhood BM who participated in the 20|30 Dutch Postmeningitis study. Average scores were compared to population-norm group scores. Subgroup scores were compared according to causative pathogen and age at onset. RESULTS: Young adult survivors of childhood BM scored lower on overall metacognition than the age-matched population norm group. Young adult survivors of childhood BM caused by Streptococcus pneumoniae, S. agalactiae, or Escherichia coli had lower scores than cases caused by Neisseria meningitidis. Survivors with age-at-onset below 12 months had a higher (worse) overall EF score than survivors with age-at-onset above 12 months. CONCLUSIONS: Young adult survivors of childhood BM experience difficulties in EF. However, most of the self-reported EF scores were within the norm. Future studies need to additionally assess EF in adult survivors of childhood BM using performance-based tests.
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Pathogen identification is essential for the treatment of bacterial meningitis. However, cerebrospinal fluid (CSF) culture tests are often negative when antimicrobial agents are administered before CSF is collected. Therefore, it is necessary to improve the culturing process for such samples. Here, we report a case of bacterial meningitis where the causative bacteria were detected by inoculating that patient's CSF samples into blood culture bottles. A 52-year-old man developed a fever and headache after undergoing transnasal transsphenoidal surgery for a nonfunctioning pituitary neuroendocrine tumor. He was suspected of having a wound infection, for which he was treated with cefozopran and vancomycin. A CSF test was also performed, owing to persistent fever, and bacterial meningitis was suspected. Although conventional CSF culture tests were negative, CSF cultures using blood culture bottles detected Enterococcus faecalis. The antimicrobial agents were therefore changed to ampicillin and gentamicin, after which the patient's meningitis improved. The blood culture bottles used contained adsorbed polymer beads with antimicrobial neutralizing properties, which likely contributed to the isolation of the bacteria. In addition to conventional cultures, ones done in blood culture bottles may be useful for diagnosing bacterial meningitis via CSF samples-particularly in cases where antimicrobial agents have already been administered.
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The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of our study was to evaluate the epidemiological and bacteriological profile of paediatric bacterial meningitis (BM) in Tunisian children, during the period 2003-2019, following the implementation of Haemophilus influenzae type b (Hib) vaccine (April 2011) and before 10-valent pneumoccocal conjugate vaccine (PCV10) introduction to the childhood immunization program.All bacteriologically confirmed cases of BM admitted to children's hospital of Tunis were recorded (January 2003 to April 2019). Serogroups of Neisseria meningitidis (Nm) and serotypes of Streptococcus pneumoniae (Sp) and H. influenzae (Hi) and antibiotic resistance were determined using conventional and molecular methods.Among 388 cases, the most frequent species were Sp (51.3%), followed by Nm (27.5%) and Hi (16.8%). We observed a significant decrease in Hi BM rate during the conjugated Hib vaccine use period (P < 0.0001). The main pneumococcal serotypes were 14, 19F, 6B, 23F and 19A and the serotype coverage of PCV10, PCV13, PCV15 and PCV20 was 71.3 and 78.8%, 79.4 and 81.9% respectively. The most frequent Nm serogroup was B (83.1%). Most Hi strains were of serotype b (86.9%). High levels of resistance were found: Sp and Nm to penicillin (respectively 60.1 and 80%) and Hi to ampicillin (42.6%). All meningococcal and Hi isolates were susceptible to third-generation cephalosporins and 7.2% of pneumococcal strains had decreased susceptibility to these antibiotics.The Hib conjugate vaccine decreased the rate of BM. Sp dominated the aetiology of BM in children in Tunisia. Conjugate vaccines introducing decreases not only BM cases but also antimicrobial resistance.
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Antibacterianos , Meningites Bacterianas , Neisseria meningitidis , Vacinas Pneumocócicas , Streptococcus pneumoniae , Humanos , Tunísia/epidemiologia , Pré-Escolar , Lactente , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/efeitos dos fármacos , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Neisseria meningitidis/classificação , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis/efeitos dos fármacos , Masculino , Feminino , Criança , Vacinas Pneumocócicas/administração & dosagem , Antibacterianos/farmacologia , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/classificação , Haemophilus influenzae/efeitos dos fármacos , Vacinas Anti-Haemophilus/administração & dosagem , Sorogrupo , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Recém-Nascido , Adolescente , Cápsulas BacterianasRESUMO
Meningitis is the inflammation of meninges either septic or aseptic depending on the source of infection. Typical signs and symptoms of meningitis in children include fever, headache, neck stiffness, nuchal rigidity represented by positive Kernig and Brudzinski signs, photophobia, nausea, vomiting, confusion, lethargy, and irritability. Bacterial meningitis is commonly caused by Streptococcus pneumoniae in children over the age of three months. Although there has been a decline in infections due to the introduction of the pneumococcal conjugate and pneumococcal polysaccharide vaccines, there are still reported cases of invasive pneumococcal infections mostly with non-vaccine serotypes. We report a fully immunized six-year-old male patient with a presentation of classic meningitis signs and symptoms who developed rapid progression of disease including sudden and dramatic change in physical exam and subsequent respiratory depression within 12 hours of admission. Our patient had a history of extensive traumatic facial bone fractures six months prior. Our case demonstrates a unique presentation of rapidly progressing pneumococcal meningitis due to a suspected complication of septic thrombophlebitis and subsequent brain herniation in a fully immunized patient six months after a severe traumatic facial injury.
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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-1ß, 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-1ß, 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.
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Meningites Bacterianas , Neutrófilos , Humanos , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/diagnóstico , Estudos Retrospectivos , Prognóstico , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos de Casos e Controles , Peroxidase/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Adulto JovemRESUMO
BACKGROUND: Inflammation is a key pathological process in bacterial meningitis, and the transforming growth factor-beta-activated kinase 1 (TAK1)/nuclear factor-kappa B (NF-κB) pathway is implicated in the activation of microglia and the production of inflammatory factors. Interleukin (IL)-10 is an anti-inflammatory cytokine acting in an autocrine fashion in macrophages to limit inflammatory responses by decreasing the production of pro-inflammatory cytokines. This paper investigates how IL-10 can inhibit microglia activation and reduce the inflammatory response of nervous system diseases. METHODS: This study used a pneumococcal-induced in Pneumococcal meningitis (PM) C57BL/6 mice and BV-2 cells model of microglial activation, assessing the effects of IL-10 on the TAK1/NF-κB pathway. The impact of IL-10 on microglial autophagy was investigated through western blot and immunofluorescence. The effects of IL-10 were evaluated by examining cellular activation markers and the activity of molecular signaling pathways (such as phosphorylation levels of TAK1 and NF-κB). RESULTS: Pneumococcus induced the activation of microglia and reduced IL-10. IL-10 inhibited the TAK1/NF-κB pathway, reducing the pneumococcal-induced inflammatory response in microglia. IL-10 ameliorated pneumococcal infection-induced microglial injury by inhibiting autophagy. Animal experiment results also showed that IL-10 inhibited inflammation and autophagy during Pneumococcal meningitis in mice. CONCLUSION: Our study demonstrates that IL-10 reduces the inflammatory response of microglia by inhibiting the TAK1/NF-κB pathway. Additionally, IL-10 ameliorates pneumococcal infection-induced microglial injury by inhibiting the process of autophagy. These results provide a new theoretical basis and offer new insights for developing strategies to treat bacterial meningitis.
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Interleucina-10 , MAP Quinase Quinase Quinases , Meningite Pneumocócica , Camundongos Endogâmicos C57BL , Microglia , NF-kappa B , Animais , Interleucina-10/metabolismo , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Camundongos , Meningite Pneumocócica/tratamento farmacológico , Meningite Pneumocócica/imunologia , Meningite Pneumocócica/patologia , NF-kappa B/metabolismo , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Inflamação/patologia , Autofagia/efeitos dos fármacos , Modelos Animais de Doenças , Linhagem Celular , Streptococcus pneumoniaeRESUMO
Bacterial meningitis is an acute infection which requires rapid diagnosis and treatment due to the high mortality and serious consequences of the disease. The purpose of this study was to design a homemade multiplex PCR and a novel fluorescence biosensor on chip (FBC) to detect three important agents of meningitis including Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), and Haemophilus influenzae (H. influenzae). The homemade multiplex PCR can diagnose three bacterial species simultaneously. Fabrication of FBC was carried out based on the deposition of lead nanoparticles on a quartz slide using the thermal evaporation method. Then, the SH-Cap Probe/Target ssDNA /FAM-Rep probe was loaded on lead film. The evaluation of the fluorescence reaction when the probes bind to the target ssDNA was assessed by a Cytation 5 Cell Imaging Multimode Reader Bio-Tek. The limit of detections (LOD) in homemade PCR and FBC to identify S. pneumoniae were 119 × 102 CFU/mL (0.27 ng/µL) and 380 CFU/mL (9 pg/µL), respectively. The LODs of homemade PCR and FBC for detection of N. meningitidis were 4.49 CFU/mL (1.1 pg/µL) and 13 × 103 CFU/mL (30 pg/µL), respectively. Our results confirmed the LODs of homemade PCR and FBC in detection of H. influenzae were 15.1 CFU/mL (30 fg/µL) and 41 × 102 CFU/mL (90 pg/ µL), respectively. Both techniques had appropriate sensitivity and specificity in detection of S. pneumoniae, N. meningitidis and H. influenzae.