Bacterial Meningitis
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Bacterial Meningitis
Meningitis is an infection and inflammation of the meninges that affects the pia, the arachnoid and the subarachnoid space. It can be caused by growth of bacteria, virus, fungi, or parasites within the subarachnoid space or by the growth of bacteria or viruses within the meningeal or ependymal cells. Bacterial meningitis affects fewer people than the viral form, but it often results in more serious health consequences. Most cases of meningitis occur when bacteria from an infection in another part of the body travel through the bloodstream to the brain and spinal cord. But bacteria can also spread directly to the brain or spine from a severe head injury or from an infection in the ear, nose or teeth (Ref.1). Almost all bacteria that are pathogenic to man have the potential to produce meningitis. For example, Group-B Streptococcus, the E. coli K12 strain and Listeria monocytogenes are the main causes of neonatal meningitis, and Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae Type b cause most cases of meningitis after the neonatal period. Infants are particularly susceptible because of their predisposition to bacterial infection, possible lower integrity of barriers, and immature defense mechanisms. Adult bacterial meningitis is predominantly due to N. meningitidis and S. pneumoniae, except in cases where there had been a penetrating wound to the skull, surgery, or immunosuppression in the host. N. meningitidis causes epidemic disease; all other forms of pyogenic meningitis are sporadic. Viral meningitis is more common than the bacterial form and generally-but not always--less serious. It can be triggered by a number of viruses, including several that can cause diarrhea. The flu virus can also lead to meningitis in rare instances. People with viral meningitis are much less likely to have permanent brain damage after the infection resolves. Fungal meningitis is much less common. Cryptococcus neoformans often causes meningitis in immunosuppressed patients, but can cause indolent meningitis in immunocompetent individuals. Coccidioides immitis and, rarely, other fungi also cause subacute meningitis (Ref.2).

Bacterial meningitis occurs when bacterial virulence factors overcome host defense mechanisms that normally protect against CNS (Central Nervous System) infection in the subarachnoid space to elicit inflammatory responses from the host, and pathophysiological alterations such as pleocytosis and BBB (Blood-Brain Barrier) disruption. Other routes of bacterial entry into the CNS, which occur less commonly, include spread from a contiguous source of infection (such as in cases of sinusitis or mastoiditis) and direct inoculation into the CSF (Cerebrospinal Fluid) in cases of skull fracture or ventricular shunts. After survival and replication in the bloodstream, the microorganisms travel through the blood and may cross the BBB and invade the subarachnoid space. In the bloodstream, infection-causing microorganisms are fought off by WBC (White Blood Cells), an important part of the immune system. However, Host defense mechanisms are unable to control infection in the CSF because of relatively low levels of local antibody and complement activity. Bacterial replication and accumulation of WBCs in the CSF enhance a local inflammatory response in the subarachnoid space because of production and release of inflammatory mediators (Ref.3). These proinflammatory and toxic compounds lead to pleocytosis and increased BBB permeability—the hallmarks of bacterial meningitis. Several mediators contribute to the migration of WBCs particularly neutrophils across the BBB and increased BBB permeability during bacterial meningitis. These include Cytokines, Chemokines, ROS (Reactive Oxygen Species), NO (Nitric Oxide), MMPs (Matrix Metalloproteinases), Arachidonic Acid metabolites, PAF (Platelet Activating Factor), proinflammatory neuropeptides, Endothelins, EAA (Excitatory Amino Acids) and Caspases. Downregulation of these mediators is recognized as a potential target for adjunctive therapy for bacterial meningitis (Ref.4).

Meningitis strikes suddenly and as the disease progresses, the brain swells and may begin to bleed. Meningitis is fatal in about 10 percent of cases. The primary clinical manifestations of meningitis are headache, fever, and nuchal rigidity (stiffness of the neck on passive forward flexion due to stretching of the inflamed meninges). Flexion of the neck may also cause reflex flexion of the legs (Brudzinski sign), and meningeal irritation may limit extension of the leg when flexed at the knee (Kernig sign). Meningeal inflammation may also cause some degree of obtundation (reduced consciousness), and seizures are common in children. If bacterial meningitis is not promptly treated, purulent material collects around the base of the brain, which may cause cranial nerve palsies and obstruct the flow of CSF, resulting in hydrocephalus. Vasculitis develops, with infarction of the brain and multifocal neurological deficits. Untreated bacterial meningitis is a uniformly fatal disease. Viral meningitis, on the other hand, is benign and self-limited (Ref.1). Seventy percent of meningitis cases occur in children under age 5, but the incidence of the disease is increasing among young people between the ages of 15 and 24. Older adults also tend to have a high incidence of meningitis. Because acute bacterial meningitis, especially when caused by N. meningitidis, can lead to death within hours or days, treatment is usually started immediately, without waiting for the results of diagnostic procedures. One or more antibiotics are given intravenously. In children, corticosteroids, such as dexamethasone, are also given. After treatment with antibiotics, inflammation develops because the antibiotics break bacteria into fragments. Corticosteroids can suppress the inflammation and reduce the resulting swelling in the brain and increased pressure within the skull (Ref.5). A vaccine can help prevent meningitis caused by N. meningitidis. The vaccine is used mainly when an epidemic occurs, when there is a threat of an epidemic in a self-contained group of people (such as those in military barracks), or when people may be repeatedly exposed to the bacteria. Children are now routinely immunized with H. influenzae Type b vaccine, which has eliminated what once was the most common cause of meningitis in children.