BACTERIAL MENINGITIS CAUSES NEUROLOGICAL DAMAGE WITH A HIGH RISK OF MORBIDITY AND MORTALITY

Lobefalo L. Bacterial meningitis causes neurological damage with a high risk of morbidity and mortality. International Journal of Infection. 2022;6(3):76-79

L. Lobefalo^*

Department of Medical and Oral Sciences and Biotechnologies, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy.

*Correspondence to:
Lucio Lobefalo, MD,
Department of Medical and Oral Sciences and Biotechnologies,
University “G. d’Annunzio” of Chieti-Pescara,
Chieti, Italy.
e-mail: lobefalo@gmail.com

Received: 12 December, 2022 Accepted: 30 December, 2022

ISSN 1972-6945 [online] Copyright 2022 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Bacterial meningitis is characterized by inflammation of the brain and has a mortality rate of approxiametly 50% in low-income countries. Meningitis can be caused by bacterial or viral agents, with the bacterium Streptococcus pneumoniae (group B) responsible for about 70% of cases. In bacterial meningitis, there is an increase in neutrophil granulocytes in the cerebrospinal fluid (CSF), increased intracranial pressure, cerebral edema, and neuronal lesions, which all contribute to neurological damage. Pneumolysin, produced by S. pneumoniae, forms pores in cell membranes, causing cell lysis and inflammation, while bacterial lipooligosaccharide (LOS) induces an immune reaction which aggravates the disease. Neuroinflammation increases the permeability of the blood-brain barrier (BBB), facilitating the entry of immune cells that produce inflammatory mediators. These reactions induce coagulation with vasculitis and the release of inflammatory mediators which are activated by bacterial toxins to induce apoptosis and necrosis, with the death of neurons and glial cells. Bacteria such as Neisseria meningitidis, S. pneumoniae, and Haemophilus influenzae use different strategies to cross the BBB.

KEYWORDS: Bacterial meningitis, neuroinflammation, neurological damage, immune, inflammation

INTRODUCTION

Bacterial meningitis is a serious disease that causes over 300,000 deaths every year across the globe with a mortality rate that can reach up to 54% in low-income countries (1). Bacterial meningitis can have high rates of complications, especially in children, the elderly, and immunocompromised individuals. In fact, in low-income countries, many survivors are left with chronic neurological sequelae, including hearing loss or focal neurological deficits.

Bacterial meningitis infection is characterized by inflammation of the protective membranes covering the brain and spinal cord, known as the meninges (2). The disease is associated with high morbidity and mortality rates if not treated promptly (3). The most common complications are cognitive deficits, hearing loss, seizures, hydrocephalus, and motor deficits.

Streptococcus pneumoniae causes over 70% of meningitis cases, while Neisseria meningitidis causes approximately 10% (4). The mortality rate due to S. pneumoniae is 10-30%, but this can vary depending on the type of pathogen, the age of the patient, and the site of infection. The bacteria first colonize the nose, pharynx, and upper respiratory tract, and then infect the bloodstream. Patients with bacterial meningitis are treated with intravenous antibiotics, often in combination with cortisone (if the pathogen is not Listeria) which inhibits inflammation and gives better results (5).

Meningitis can be caused by bacterial or viral agents that induce increased protein and leukocyte counts in the cerebrospinal fluid (CSF) (6). Bacterial meningitis increases neutrophilic granulocytes in the CSF, while viral meningitis does not (7). Pregnant women should be screened for the presence of group B streptococcus and, if positive, treated with intravenous penicillin to avoid neonatal streptococcal meningitis.

DISCUSSION

Complications of bacterial meningitis include neurological damage resulting from increased intracranial pressure, cerebral edema, and direct bacterial toxin effects, that results in serious neuronal injury, and systemic complications such as septicemia, disseminated intravascular coagulation (DIC), and multi-organ failure (8). For this, it is particularly important to control the infection rapidly (9).

Bacterial toxins include pneumolysin produced by S. pneumoniae and lipooligosaccharide (LOS), which is found in N. meningitidis (10). Pneumolysin induces pores in cell membranes, leading to cell lysis and further inflammation (11). LOS causes strong immune responses and contributes to the pathology (12) (Table I,II).

Table I. Immune Response.

Table II. Immune evasion and bacterial toxins.

In bacterial meningitis, an edematous state can occur with increased permeability of the blood-brain barrier (BBB) and inflammation that can lead to accumulation of fluid in the brain and increased intracranial pressure.

Bacteria such as N. meningitidis, S. pneumoniae, and Haemophilus influenzae can invade and survive in the bloodstream (13). They use various strategies to cross the BBB, including transcellular traversal, paracellular passage, and the “trojan horse” mechanism via infected leukocytes. Surface adhesins and pili help bacteria adhere to and invade endothelial cells. For example, N. meningitidis uses outer membrane proteins like Opc and Opa to bind to host cell receptors. Bacterial components bind to epithelial cells via adhesins and activate Toll-like receptors (TLRs) on microglia and endothelial cells.

Immune cells are activated, including neutrophils and macrophages. These cells are recruited to the infection site, where they phagocytose bacteria and release more inflammatory mediators (14). The inflammatory response increases BBB permeability, facilitating the entry of immune cells and further bacteria into the CSF.

Neuroinflammation may occur due to glial cell activation, when microglia and astrocytes in the brain become activated and produce inflammatory mediators (15). Oxidative stress is interconnected with neuroinflammation and plays a major role in the development and progression of many neurological disorders, such as Alzheimer’s, Parkinson’s, multiple sclerosis, and stroke. Inflammation-induced reactive oxygen species (ROS) can damage neurons and other cells in the brain (16). Bacteria and bacterial toxins can activate the coagulation cascade with the release of inflammatory cytokines (17), which in turn, can cause micro-thrombosis and impair blood flow. These phenomena can lead to vasculitis, which is the inflammation of the blood vessels, further contributing to brain damage (18). Damage to the meninges, neuronal death, and apoptosis are then mediated by inflammatory mediators and bacterial toxins (19).

Pro-inflammatory cytokines increase the permeability of the BBB, allowing immune cells and more bacteria to enter the central nervous system (CNS), which exacerbates inflammation. An overproduction of cytokines can lead to a “cytokine storm” that can cause severe tissue damage, edema, and increased intracranial pressure (20).

Neuroinflammation is the response of the CNS and involves the activation of glial cells such as microglia and astrocytes (21). It can be induced by infections, toxins, traumatic injuries, and neurodegeneration. Bacterial meningitis is mediated by the release of inflammatory cytokines (e.g. IL-1, TNF, IL-6, and IL-18) and chemokines (15). Activated microglia release more ROS and cytokines, creating a vicious cycle (22).  The activation of microglia and astrocytes in the CNS leads to the production of inflammatory mediators that contribute to neuronal damage and apoptosis (23). Matrix metalloproteinases (MMPs) are upregulated and break down the extracellular matrix, further disrupting the BBB (24). ROS can activate microglia and promote inflammatory signaling. However, prolonged oxidative stress supports inflammation (25).

Treatment for bacterial meningitis typically involves the prompt administration of broad-spectrum antibiotics and supportive care to manage symptoms and complications. In neuroinflammation, treatment for oxidative stress with antioxidants such as N-acetylcysteine and/or vitamin E has shown moderate therapeutic effects, suggesting that more studies should be performed investigating these (26). It is important to understand the molecular mechanisms, immune response, and inflammatory processes involved in bacterial meningitis in order to better address the disease both pathologically and therapeutically.

CONCLUSIONS

Bacterial meningitis involves complex interactions between bacterial virulence factors and host immune responses. The bacteria must evade the immune system, cross the BBB, and survive in the hostile environment of the CNS. The host’s immune response, while aimed at controlling the infection, often contributes to the pathology through inflammation and oxidative stress. Bacterial meningitis causes neurological damage due to increased intracranial pressure, cerebral edema, and direct bacterial toxin effects, and there can be significant neuronal injury, and systemic complications such as septicemia, DIC, and multi-organ failure.

Bacterial meningitis involves a complex interplay of pathogen invasion, immune response, and inflammatory processes. Understanding these mechanisms is critical for developing effective treatments and interventions to reduce the high morbidity and mortality associated with this disease.

Conflict of interest

The author declares that they have no conflict of interest.

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