Advances in the pathogenesis and treatment of pneumococcal meningitis.
Ontology highlight
ABSTRACT:
SUBMITTER: Xu Y
PROVIDER: S-EPMC11364070 | biostudies-literature | 2024 Dec
REPOSITORIES: biostudies-literature
Publications
Advances in the pathogenesis and treatment of pneumococcal meningitis.
Xu Yiyun Y Wang Ji J Qin Xiaosong X Liu Jianhua J
Virulence 20240827 1
<i>Streptococcus pneumoniae</i> is a common pathogen associated with community-acquired bacterial meningitis, characterized by high morbidity and mortality rates. While vaccination reduces the incidence of meningitis, many survivors experience severe brain damage and corresponding sequelae. The pathogenesis of pneumococcal meningitis has not been fully elucidated. Currently, meningitis requires bacterial disruption of the blood - brain barrier, a process that involves the interaction of bacteria ...[more]
Similar Datasets
Project description:BackgroundInvasive pneumococcal disease declined among children and adults after the introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, but its effect on pneumococcal meningitis is unclear.MethodsWe examined trends in pneumococcal meningitis from 1998 through 2005 using active, population-based surveillance data from eight sites in the United States. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others). Changes in the incidence of pneumococcal meningitis were assessed against baseline values from 1998-1999.ResultsWe identified 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998-1999 and 2004-2005 (a 30.1% decline, P<0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P<0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P<0.001) among patients of all ages. Although rates of PCV7-related-serotype disease decreased by 32.1% (P=0.08), rates of non-PCV7-serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P<0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P=0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P=0.03).ConclusionsRates of pneumococcal meningitis have decreased among children and adults since PCV7 was introduced. Although the overall effect of the vaccine remains substantial, a recent increase in meningitis caused by non-PCV7 serotypes, including strains nonsusceptible to antibiotics, is a concern.
| S-EPMC4663990 | biostudies-literature
Project description:This article presents a comprehensive review on migraine, a prevalent neurological disorder characterized by chronic headaches, by focusing on their pathogenesis and treatment advances. By examining molecular markers and leveraging imaging techniques, the research identifies key mechanisms and triggers in migraine pathology, thereby improving our understanding of its pathophysiology. Special emphasis is given to the role of calcitonin gene-related peptide (CGRP) in migraine development. CGRP not only contributes to symptoms but also represents a promising therapeutic target, with inhibitors showing effectiveness in migraine management. The article further explores traditional medical treatments, scrutinizing the mechanisms, benefits, and limitations of commonly prescribed medications. This provides a segue into an analysis of emerging therapeutic strategies and their potential to enhance migraine management. Finally, the paper delves into neuromodulation as an innovative treatment modality. Clinical studies indicating its effectiveness in migraine management are reviewed, and the advantages and limitations of this technique are discussed. In summary, the article aims to enhance the understanding of migraine pathogenesis and present novel therapeutic possibilities that could revolutionize patient care.
| S-EPMC10535528 | biostudies-literature
Project description:Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases and the leading cause of premature death worldwide. However, the pathogenesis of the hypertension, especially essential hypertension, is complex and requires in-depth studies. Recently, new findings about essential hypertension have emerged, and these may provide important theoretical bases and therapeutic tools to break through the existing bottleneck of essential hypertension. In this review, we demonstrated important advances in the different pathogenesis areas of essential hypertension, and highlighted new treatments proposed in these areas, hoping to provide insight for the prevention and treatment of the essential hypertension.
| S-EPMC9616110 | biostudies-literature
Project description:BackgroundThe leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis.Methods and analysisThe AddaMAP trial is a phase II, open-label, Simon's two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required.Ethics and disseminationThe study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03480191.
| S-EPMC10373719 | biostudies-literature
Project description:ObjectiveOur aim was to assess seizure development as a complication of pneumococcal meningitis and its possible prevention with antiseizure medication prophylaxis.MethodsAntiseizure medication (ASM) prophylaxis has been practiced for a long time at our center. We assessed all cases of community-acquired pneumococcal meningitis admitted from January 2010 to April 2021 recorded in our prospective database and conducted further retrospective studies.ResultsOf the 86 cases recorded, 21 (24.4%) developed acute symptomatic seizures, more than half of which (11/21; 52.4%) before admission. Seizure development increased the need for orotracheal intubation and intensive care unit admission, while also lengthening hospital stays and suggesting more risk of death and disability at discharge [adjusted odds ratio (aOR), 3.13; 95% confidence interval (CI): 1-9.8]. Of the 74 patients eligible for ASM prophylaxis, 64 received it and 10 did not. ASM prophylaxis seemed effective in preventing seizure development, as only six seizure events were recorded in 64 patients with ASM prophylaxis (9.4%) compared with four in the 10 patients without prophylaxis (40%). Its preventive capacity was especially notable when administered within 4 h of admission. Differences in mortality did not reach statistical significance. Adverse effects were rare.SignificanceSeizure development is a common complication in pneumococcal meningitis and is associated with increased risks of Intensive Care Unit admission, orotracheal intubation, and longer hospital stays. ASM prophylaxis may be effective in blocking seizure development in patients with preventable seizures and may be associated with better prognosis. Further studies are now warranted.Plain language summaryInfection of the meninges (the covering of the brain) due to the common bacteria S pneumoniae, used to be a fatal disease before the introduction of antibiotics and corticoids. Thanks to these drugs, more people survive this disease but, due to the frequent complications, they may have several sequelae. Seizures are a common complication. Our study suggests that they might be prevented by using antiseizure drugs which may reduce both severity and hospital stay.
| S-EPMC11633693 | biostudies-literature
Project description:Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by eosinophil-rich granulomatous inflammation and necrotizing vasculitis, pre-dominantly affecting small-to-medium-sized vessels. It is categorized as a primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) but also shares features of hypereosinophilic syndrome (HES); therefore, both vessel inflammation and eosinophilic infiltration are suggested to cause organ damage. This dual nature of the disease causes variable clinical presentation. As a result, careful differentiation from mimicking conditions is needed, especially from HES, given the overlapping clinical, radiologic, and histologic features, and biomarker profile. EGPA also remains a diagnostic challenge, in part because of asthma, which may pre-dominate for years, and often requires chronic corticosteroids (CS), which can mask other disease features. The pathogenesis is still not fully understood, however, the interaction between eosinophils and lymphocytes B and T seems to play an important role. Furthermore, the role of ANCA is not clear, and only up to 40% of patients are ANCA-positive. Moreover, two ANCA-dependent clinically and genetically distinct subgroups have been identified. However, a gold standard test for establishing a diagnosis is not available. In practice, the disease is mainly diagnosed based on the clinical symptoms and results of non-invasive tests. The unmet needs include uniform diagnostic criteria and biomarkers to help distinguish EGPA from HESs. Despite its rarity, notable progress has been made in understanding the disease and in its management. A better understanding of the pathophysiology has provided new insights into the pathogenesis and therapeutic targets, which are reflected in novel biological agents. However, there remains an ongoing reliance on corticosteroid therapy. Therefore, there is a significant need for more effective and better-tolerated steroid-sparing treatment schemes.
| S-EPMC10193253 | biostudies-literature
Project description:Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury. Here we review the steps from primary infection to cerebral disease, factors that contribute to the virulence of the organism and the vulnerability of the host and discuss the immune response and the clinical manifestations arising. Priorities for future research directions are suggested.
| S-EPMC6355360 | biostudies-literature
Project description:Hippocampal apoptosis is a characteristic feature of penumococcal meningitis associated with learning and memory deficitis as a sequel of the disease. We investigated the effect of vitamin B6 using an established infant rat model of experimental pneumococcal meningitis by histomorphology, transcriptomics and measurement of cellular nicotine amide adenine dinucleotide content. The data provides evidence that vitamin B6 is neuroprotecitve in terms of reduced hippocampal apoptosis involving reduction of the inflammatory response, preservation of cellular energy stores and up-regulated brain-derived neurotrophic factor levels.
2012-02-20 | E-MEXP-3555 | biostudies-arrayexpress
Project description:Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10(-7)). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10(-6); G allele OR 3.21 [95% CI 2.05-5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10(-5); G allele OR 0.66 [95% CI 0.54-0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10(-7)). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis.
| S-EPMC4937363 | biostudies-literature
Project description:Behcet's disease (BD) is a chronic multi-systemic disease characterized by relapsing-remitting oral ulcers, genital ulcers, ocular inflammatory involvements, and numerous other systemic features. Ocular involvements are quite common in BD and may cause severe tissue damage and potentially blindness. Even though the pathogenesis of BD remains ambiguous, growing evidences have shown that genetic factors, environmental triggers and immunological abnormalities play significant roles in its development and progression. Novel biotherapies targeting IFN-γ, TNF-α and interleukins have been used in recent years. In this review, we mainly pay attention to the ocular involvement of BD, and discuss the current understanding of mechanisms and advances in therapeutic approaches, especially novel biologics. Finally, we discuss the management in patients with pregnancy.
| S-EPMC10570607 | biostudies-literature