• The infection within the subarachnoid space or throughout the leptomeninges is called meningitis.
• Meningitis is divided into two major categories based on the host’s response to the invading microorganism. They are:
  • purulent meningitis
  • aseptic meningitis.

 1. Purulent meningitis

• A patient with purulent meningitis typically has a marked, acute inflammatory exudative cerebral spinal fluid containing large numbers of polymorphonuclear cells (PMNs).
• The underlying CNS tissue, in particular the ventricles, may be involved.
• Ventriculitis means the involvement of ventricles.
• The cause of these infections is bacterial organisms.

Pathogenesis of purulent meningitis:

• Within the Central Nervous System, the blood-brain barrier is the important host defense mechanism.
• This barrier involves the choroid plexus, arachnoid membrane, and the cerebral microvascular endothelium.
• Vascular endothelium has got the unique structural properties.
• There is the presence of continuous intercellular tight junctions.
• It minimizes the passage of infectious agents into the CSF and acts as a barrier.
• The vascular endothelium helps in regulating the transport of nutrients in and out of the CSF.
• It includes low-molecular-weight plasma proteins, glucose, and electrolytes.
• Different underlying conditions and the host’s age may be responsible for the development of infectious meningitis.
• The highest rate of infection of meningitis is in neonates.
• It is because of the:
  • the immature neonatal immune system
  • the increased permeability of the blood-brain barrier in newborns
• The presence of colonizing bacteria in the female vaginal tract
• The most common bacterial pathogens responsible for meningitis in newborns are:
  • Group B streptococci
  • Escherichia coli
  • Listeria monocytogenes
• Before the development of the vaccine i.e Hib vaccine, the common cause of meningitis is Haemophilus influenza type b.
• It occurred in children of 4 months to 5 years of age.
• There is a decline in the Hib disease because of this childhood immunization program.
• Neisseria meningitidis causes meningitis in young adults.

Two meningococcal vaccines (vaccines for N. meningitidis) are available:

• The meningococcal polysaccharide vaccine (MPSV4): for older than 55 years of age
• The meningococcal conjugate vaccine (MCV4): for adolescents.
• The cause of meningitis in young children and elderly people is Streptococcus pneumonia.
• This meningitis develops from bacteremia or infection of the sinuses or middle ear.

Two pneumococcal vaccines (vaccines for S. pneumoniae) are:

• The pneumococcal conjugate vaccine (PCV13):
• protects against infection from 13 different serotypes of pneumonia
• used for vaccination of children and adults.
• Pneumococcal polysaccharide vaccine (PPSV):
  • protects from 23 serotypes of pneumonia
  • recommended vaccine for adults 65 years of age and older
  • recommended vaccine for anyone over the age of 2 who has long-term health problems or is immunocompromised.
• The primary portal of entry for causative agents of meningitis is the respiratory tract.
• Predisposing factors of meningitis to the adults are usually the same factors that cause pneumonia or other respiratory tract colonization or infection.
• Increased risk in:
  • Alcoholism
  • Splenectomy
  • diabetes mellitus
  • prosthetic devices
  • immunosuppression
• Patients with prosthetic devices, particularly CNS and ventriculoperitoneal shunts, are at increased risk for developing meningitis.
• Host defense mechanisms must be overcome by the organism to reach the CNS (primarily by the blood-borne route).
• The pathogen should colonize and cross the host mucosal epithelium.
• Then it should enter and thrive within the bloodstream.
• Pathogen should be able to evade the host defenses at each level.
• By breaking the blood-brain barrier at the level of microvascular endothelium, helps the organism to enter the CNS.

Virulence factors of Streptococcus pneumoniae:

• IgA protease: It is secreted by the Streptococcus pneumoniae and meningitidis. It can destroy the host’s secretory IgA and helps in bacterial attachment to the epithelium.
• Capsule: It is antiphagocytic and helps to evade destruction by the host immune system.
• Pili
• polysaccharide capsules
• lipoteichoic acids
• Organisms can enter by
  • disrupting tight junctions of the blood-brain barrier
  • transport within circulating phagocytic cells
  • crossing the endothelial cell lining within endothelial cell vacuoles.
• Then multiplication occurs within the CSF.

Clinical Manifestation of purulent meningitis:

i). Acute meningitis

• Symptoms of acute meningitis include:
  • Fever
  • stiff neck
  • headache
  • nausea and vomiting
  • neurologic abnormalities
  • change in mental status.
  • Presence of large numbers of inflammatory cells (>1000/mm3), primarily polymorphonuclear cells (PMNs) in the CSF.
• In CSF there is:
  • decreased glucose level relative to the serum glucose level
  • an increase in protein concentration.
  • In Normal condition:
    • The normal CSF glucose level is 0.6 of the serum glucose level and ranges from 45 to 100 mg/dL
    • The CSF protein range in an adult is 15 to 50 mg/dL; newborn CSF protein ranges run as high as 170 mg/dL with an average of 90 mg/dL.
• The sequelae of acute bacterial meningitis in children are frequent and serious. It includes:

• • Seizures
  • cerebral edema
  • hydrocephalus
  • cerebral herniation
  • focal neurologic changes.
• In about 10% of children recovering from bacterial meningitis, permanent deafness can occur.

ii). Chronic Meningitis

• May occur in immunocompromised patients.
• Symptoms:
  • Fever
  • Headache
  • stiff neck
  • nausea and vomiting,
  • Lethargy
  • Confusion
  • mental deterioration.
• Symptoms may persist for a month or longer before treatment is sought.
• Manifestation in CSF:
  • an abnormal number of white blood cells (usually lymphocytic)
  • elevated protein
  • decrease in glucose content

The pathogenesis of chronic meningitis is similar to that of acute disease.

Etiologic agents of Chronic Meningitis:

• HIV cytomegalovirus
• Enterovirus
• HSV
• Mycobacterium tuberculosis
• Cryptococcus neoformans
• Coccidioides immitis
• Histoplasma capsulatum
• Blastomyces dermatitidis
• Candida
• Aspergillosis
• Mucormycosis
• Miscellaneous other fungi
• Nocardia
• Actinomyces
• Treponema pallidum
• Brucella
• Borrelia burgdorferi
• Sporothrix schenckii
• Rare parasites—Toxoplasma gondii, cysticercus, Paragonimus westermani, Trichinella spiralis, Schistosoma , Acanthamoeba

2. Aseptic meningitis:

• It is usually viral and characterized by an increase of lymphocytes and other mononuclear cells (pleocytosis) in the CSF
• Bacterial and fungal cultures are negative.
• It is usually self-limiting.
• Symptoms:
  • Fever
  • Headache
  • Stiff neck
  • nausea, and vomiting
• Increase of lymphocytes and other mononuclear cells in the CSF
• Normal glucose level
• Normal or slightly elevated protein CSF level.
• Aseptic meningitis can also be a symptom for syphilis and some other spirochete diseases (e.g., leptospirosis and Lyme borreliosis).
• Stiff neck and CSF pleocytosis may also be associated with other disease processes, such as malignancy.

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