Blood‒Brain Barrier Pathology and CNS Outcomes in Streptococcus pneumoniae Meningitis

Yau, Belinda; Hunt, Nicholas H.; Mitchell, Andrew J.; Too, Lay Khoon

doi:10.3390/ijms19113555

Cited by 52 publications

(41 citation statements)

References 179 publications

(208 reference statements)

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“…Furthermore, the duration of hospitalization in the ICU was significantly longer in the S. pneumoniae group. This correlates with the course of pneumococcal meningitis as a risk for severe CNS complications along with hydrocephalus, brain edema, intracranial hemorrhage, cerebral venous and arterial complications and seizures, contributing to mortality and long-term disabilities and the need for a longer duration of hospitalization in the ICU [40].…”

Section: Discussionmentioning

confidence: 97%

Retrospective analysis of the etiology, clinical characteristics and outcomes of community-acquired bacterial meningitis in the University Infectious Diseases Centre in Lithuania

et al. 2020

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Background The morbidity and mortality in community-acquired bacterial meningitis (CABM) remain substantial, and the etiology, clinical characteristics, treatment outcomes and predictors of poor prognosis must be assessed regularly. The aim of this study was to identify the distribution of etiological agents and their relationship with clinical characteristics, treatment and outcomes in this cohort of patients with CABM. Methods Our retrospective chart review analyzed the causative microorganisms, clinical characteristics, laboratory findings, treatment and outcomes of 159 adults with CABM hospitalized in the Infectious Diseases Centre of Vilnius University Hospital from January 1, 2009 to December 31, 2016. A Glasgow Outcome Scale (GOS) score ≤ 3 was defined as unfavorable outcome. Predictors of an unfavorable outcome were identified through logistic regression analysis. Results The median patient age was 36 (IQR 24–56), and 51.6% were male. Microbiologically confirmed causative agents were identified in 80 (50.3%) patients: N. meningitidis in 55 (34.6%) patients with serotype B accounting for 85% of cases, S. pneumoniae in 15 (9.4%), L. monocytogenes in 5 (3.1%) and other in 5 (3.1%). The clinical triad of fever, neck stiffness and a change in mental status was present in 59.1% of patients. Coexisting conditions and comorbidities were similar in all groups stratified by etiology. Initial antimicrobial treatment consisted of penicillin in 78 patients (49.1%) and ceftriaxone in 72 patients (45.3%). The median time in which antibiotic treatment was started was 40 min (IQR 30.0–90.0). The outcome was unfavorable in 15.7% of episodes and death occurred in 5.7% of cases and did not differ according to the causative agent. Risk factors for an unfavorable outcome were age > 65 years, coexisting pneumonia and a platelet count <150x10e9/l. Conclusions The most common causative agent of CABM was N. meningitidis, with serotype B clearly dominant. Causative agents did not influence the disease outcome. The strongest risk factors for an unfavorable outcome were older age, pneumonia and a low platelet count. Since the introduction of routine vaccination against meningococcus B for infants in Lithuania in 2018, the national vaccination policy may hopefully contribute to a decrease in the incidence of serogroup B meningococcal disease in the Lithuanian population.

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Section: Discussionmentioning

confidence: 97%

Retrospective analysis of the etiology, clinical characteristics and outcomes of community-acquired bacterial meningitis in the University Infectious Diseases Centre in Lithuania

et al. 2020

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“…Impaired or insufficient inflammatory response can result in prolonged and/or recurrent infections. In contrast, excessive hyper-inflammation is associated with fatal outcome (82,83).…”

Section: Role Of Nlrp3 Inflammasome In Pneumococcal Infectionsmentioning

confidence: 99%

The Role of NLRP3 Inflammasome in Pneumococcal Infections

et al. 2020

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Inflammasomes are innate immune sensors that regulate caspase-1 mediated inflammation in response to environmental, host- and pathogen-derived factors. The NLRP3 inflammasome is highly versatile as it is activated by a diverse range of stimuli. However, excessive or chronic inflammasome activation and subsequent interleukin-1β (IL-1β) release are implicated in the pathogenesis of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and diabetes. Accordingly, inflammasome inhibitor therapy has a therapeutic benefit in these diseases. In contrast, NLRP3 inflammasome is an important defense mechanism against microbial infections. IL-1β antagonizes bacterial invasion and dissemination. Unfortunately, patients receiving IL-1β or inflammasome inhibitors are reported to be at a disproportionate risk to experience invasive bacterial infections including pneumococcal infections. Pneumococci are typical colonizers of immunocompromised individuals and a leading cause of community-acquired pneumonia worldwide. Here, we summarize the current limited knowledge of inflammasome activation in pneumococcal infections of the respiratory tract and how inflammasome inhibition may benefit these infections in immunocompromised patients.

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“…The BBB is a physical barrier consisting of specialized endothelial cells, tight junctions, pericytes and the end-feet of astrocytes [ 85 ]. Microbial pathogens have evolved a multitude of mechanisms through which they can cross the BBB and lead to numerous neurological sequelae that are often secondary to an initial infection within the periphery [ 86 , 87 ]. Once inside the CNS, immunopathological damage from the pathogen is often irreversible, leading to neuronal cell death and subsequent motor and/or cognitive impairment.…”

Section: Clinical Implications Of Il-27 and Its Role In Infectious Disementioning

confidence: 99%

IL-27 Regulation of Innate Immunity and Control of Microbial Growth

Povroznik

Robinson

2020

Future Sci. OA

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IL-27 is a pleiotropic cytokine capable of influencing both innate and adaptive immune responses. With anti- and pro-inflammatory activity, IL-27 exerts its opposing effects in a cell-dependent and infectious context-specific manner. Upon pathogenic stimuli, IL-27 regulates innate immune cells, such as monocytes, dendritic cells, macrophages and neutrophils. Immune responses involving these innate cells that are negatively regulated by IL-27 signaling include inflammatory cytokine production, phagolysosomal acidification following phagocytosis, oxidative burst and autophagy. IL-27 signaling is crucial in maintaining the subtle balance between Th1 and Th2 immunity, in which protective inflammation is upregulated within the early stages of infection and subsequently downregulated once microbial growth is controlled. The immunomodulatory effects of IL-27 provide promising therapeutic targets for multiple disease types.

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Blood‒Brain Barrier Pathology and CNS Outcomes in Streptococcus pneumoniae Meningitis

Cited by 52 publications

References 179 publications

Retrospective analysis of the etiology, clinical characteristics and outcomes of community-acquired bacterial meningitis in the University Infectious Diseases Centre in Lithuania

Retrospective analysis of the etiology, clinical characteristics and outcomes of community-acquired bacterial meningitis in the University Infectious Diseases Centre in Lithuania

The Role of NLRP3 Inflammasome in Pneumococcal Infections

IL-27 Regulation of Innate Immunity and Control of Microbial Growth

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