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Western University
Microbiology and Immunology
Microbiology and Immunology 2500A/B

Meningitis – Feb. 25, 2013  Ending with ‘itis’ usually refers to inflammation  Meningitis is an inflammation/infection of the meninges  It is usually due to a viral or a bacterial infection  Viral meningitis tends to be less severe than bacterial meningitis and can usually be resolved with a specific treatment  While on the other hand, bacterial meningitis can be extremely severe (very dangerous)  Meninges  they are the membranes that envelop the central nervous system (CNS) which includes the brain and the spinal cord  This includes: dura mater, arachnoid mater & pia mater  Dura mater  Closest to the skull (thicker layer)  Arachnoid mater  between dura mater & pia mater  Pia mater  Closest to the brain (thin, delicate membrane)  Between the arachnoid and pia maters contains a little space which is filled by the cerebral spinal fluid  Blood Brain Barrier (BBB)  it is a protective cellular structure that restricts the passage of chemicals, toxins and microorganisms from the blood to the CNS  Blue dye is injected to an animal  The animal is sacrificed to see the organs (liver, pancreas, kidneys) turn blue; however the brain did not turn blue  So the blue dye was then injected into the cerebral spinal fluid causing the brain to turn blue, but the rest of the organs did not  This is due to the blood brain barrier Astrocyte  Provides the support for the blood vessel Endothelial cells  It forms tight junctions to prevent foreign substances from getting through  Due to the BBB, the CNS is known to be an “immune privileged” site (Ex. Testicles, eyes, placenta)  There is no inflammation at these sites because it would simple damage its own tissue  As mentioned before, the astrocytes provide support for other cells of the CNS including the BBB  The endothelial cells are bounded together by structures called the “tight junctions”  There are no white blood cells or antibodies present in the CNS, but it does contain microglia cells, which are the ‘tissue macrophages’ of the CNS The Disease: Bacterial Meningitis (Steps) 1) Bacterial meningitis live in the nasopharynx (nasopharyngeal colonization) 2) An event occurs where the bacteria invades epithelial layer and gains access to the blood 3) The bacteria multiplies in the blood (counter our immune system) 4) It then crosses the BBB 5) By crossing the BBB, it is able to invade the meninges and CNS 6) It also increases the permeability of the BBB causing more bacteria to crossover and invade 7) This will lead to severe inflammation 8) Results in edema, increased cranial pressure and leukocyte migration 9) Proinflammatory cytokines are produced from the white blood cells 10) All these processes cause neuronal damage  This disease is rare but also dangerous; capable to killing in days  Early signs may be non-specific  Generally in an outbreak, the people who are infected by the disease first are most likely to die  People are generally more wary of the initial symptoms if the outbreak is known to be occurring  Mortality rate is still around (10-25%)  Even the individuals who have survived have irreversible neurological damage resulting in permanent brain damage, blindness, hearing loss and learning disabilities Symptoms in Children & Adults  High Fever**  Severe Headache**  Vomiting or Nausea  Confusion or Difficulty concentrating**  in the very young, this may appear is inability to maintain eye contact  Seizures  Sleepiness or difficulty waking up  Stiff Neck**  Sensitivity to light (photophobia)  Lack of interest in drinking and eating  Skin rashes in cases of meningococcal meningitis **95% of the patients will have atleast two of these symptoms; major symptoms Symptoms in Infants  Constant crying  Excessive sleepiness or irritability  Poor feeding  A bulge in the soft spot on top of the baby’s head (fontanel)  Stiffness in the baby’s body and neck  Skin rash in the cases of meningococcal meningitis Risk Factors o Lack of vaccination o People who are in the age of 15 months to 25 years old o Living in a community setting (Crammed settings)  University students living in dormitories  Military personnel  Boarding schools  Childcare facilities  Prisons o Disease can also result in immunocompromised individuals due to disease or chemotherapy o Also in individuals who have gone through cranial surgery Diagnosis  There are blood tests done to locate inflammatory markers  But the major diagnostic tool is the lumbar puncture (spinal tap) rd th  A needle is inserted in between the 3 & 4 lumbar vertebrae to extract fluid from there  That fluid is then examined: gram stain & culture, presence of white cells and low glucose  Then there is also imaging (CT or MRI)  Nucal Rigidity  The individual is unable to flex their head forward  Brudzinski’s sign  The neck stiffness is so severe that it causes the patient’s knees to flex up when the neck is flexed  Kernig’s sign  When the hip is flexed to a 90 degrees, the patient is unable to straighten their leg due to severe stiffness of the hamstrings Treatment  It should be treated immediately  The patient must begin intravenous antibiotics before the cerebral spinal fluid can be examined for culture analysis  Corticosteroids (dexamethasone) are used to reduce the swelling (inflammation) in the meninges  There are also supportive therapies for monitoring, oxygen levels, fluids & etc.  Even with all these possible treatments, the mortality rate is still very high Bacterial Pathogen  Almost any bacterial pathogen has the potential to cause meningitis but very few account for most cases  Major causes of bacterial meningitis:  Neisseria meningitides  Streptococcus pneumonia  Haemophilus influenza  Listeria monocytogenes (this one is different from the ones above)  The major cause for infants (0-2 months)  Streptococcus agalactiae (Group B Streptococcus)  Escherichia coli K1  All these pathogens are very diverse, except for Listeria, and they are capable of producing a capsule as a major virulence factor Capsule  They are a loose, relatively unstructured network of polymers that surround/cover the surface of the bacterial cells  They are mostly composed of polysaccharides  Its main role in meningitis is to protect the bacteria from
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