Bacterial Meningitis Notes.docx

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Western University
Microbiology and Immunology
Microbiology and Immunology 2500A/B
John Mc Cormick

Bacterial Meningitis Meningitis Meningitis is an infection of the meninges. Meningitis is usually due to viral (less severe; can be resolved without specific treatment) or bacteria Infection (very severe). The meninges are membranes that envelop the CNS (brain and spinal cord), and it includes the dura mater, arachnoid mater, and pia mater. Cerebrospinal fluid is located between the arachnoid and pia maters (subarachnoid space). The BBB is a protective cellular structure that restricts the passage of chemicals, toxins, and microorganisms from the blood to the CNS  not the same as the meninges. If you inject a die into the CSF, the brain turns blue while the rest of the body’s compartments did not, showing that there is a barrier that compartmentalizes these two structures (BBB). The BBB Due to the BBB, the CNS is an “immune privileged” site, meaning that if you put something exogenous in, you wont get any infection. Astrocytes are located in the brain and provide support for other cells of the CNS including the BBB. Endothelial cells and associated astrocytes are stitched together by structures called “tight junctions”, preventing things from entering the brain. Since white blood cells are not present in the CNS, you wont have antibodies present in the CNS either. Note: Microglia cells are the “tissue macrophages” of the CNS. The disease: bacterial meningitis The major pathogens that cause bacterial meningitis live in our nasopharynx. 1. Nasopharynx colonization 2. Invasion into the blood 3. Multiplication in the blood 4. Crossing of the BBB 5. Invasion of the meninges and the CNS 6. Increased permeability of the BBB 7. Increased inflammation 8. Edema, increased cranial pressure, leukocyte migration 9. Pro-inflammatory cytokines from WBC 10.Neuronal damage Note: once the bacteria enters the CNS, there is no immune system to control them The disease: bacterial meningitis Is rare, but a very dangerous disease (can kill in days). Early signs may be non- specific. In an outbreak, the first people to develop disease are the most likely to die, but once the outbreak is known, people are more wary of the initial symptoms. People who survive the disease may have irreversible neurological damage (especially children), such as brain damage, blindness, hearing loss, and learning disabilities. The main symptoms in children and adults vary, but 95% of people infected will have at least two of the following symptoms:  High fever  Severe headache  Confusion  Stiff neck Symptoms in infants involve excessive crying as well as a bulge in the soft spot on top of a baby’s head (fontanel). There are also many risk factors that contribute to bacterial meningitis. These include a lack of vaccination, being 15 months to 25 years, and living in a community setting. Immunocompromised individuals are also at risk due to disease, chemotherapy, or surgery (such as cranial). Diagnosis of bacterial meningitis involves looking at the history and symptoms of the individual, blood tests for inflammatory markers, CT/MRI imaging, and the most important  spirdl tapthlumbar puncture): spinal needle is inserted usually between the 3 and 4 lumbar vertebrae. CSF is withdrawn and subject to gram stain and culture. If there is white cells and low glucose (due to organisms using it up), then you can confirm the disease. Other methods involve: Nucal rigidity: inability to flex the head forward Brudzinski’s sign: severe neck stiffness causes patients knees to flex when the head is flexed Kernig’s sign: sever stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees But, LUMBAR PUNCTURE IS THE MAIN TOOL FOR DIAGNOSIS Treatment must be sought immediately:  IV antibiotics (prior to culture analysis)  Corticosteroids (dexamethasone) to redice swelling in the meninges  Supportive therapies (monitoring, oxygen, fluids, etc…) Major causes of bacterial meningitis Almost all bacteria has the potential to cause bacterial meningitis, The major causes of bacterial meningitis are:  Neisseria meningitides  Streptococcus pneumonia  (Haemophilus influenza) – not influenze flu  Listeria monocytogenes In infants (0-2 months):  Streptococcus agalactiae  E. coli KI Note: These diverse pathogens (except Listeria) produce a capsule as a major virulence factor. Capsule A capsule is a loose, relatively unstructured network of polymers that cover the surface of some bacteria. Most are composed of polysaccharides, and the main role in meningitis is to protect bacteria from inflammatory responses (major way is by preventing complement activation and phagocytic killing). Encapsulated bacteria are less likely to be opsonized by C3b using the alternative complement cascade. C3b is deposited on the bacterial surface, but what the capsule does it block the complement receptors (of the phagocytic WBC) from getting access to C3b.
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