Pathogens IV - CNS infections Flashcards
What are the microbiological features of Streptococcus Pneumoniae? (=Pneumococcus)
- Catalase negative, Gram positive diplococci = streptococci
- Alpha hemolysis > optochin sensitive , encapsulated
What are the microbiological features of Neisseria?
- Gram negative diplococci,
- Non-enteric
- Non-fermenting - aerobic
What are the microbiological features of Haemophilus?
*Gram-negative, pleomorphic, coccobacilli
* Non- enteric
* Non-fermenting - aerobic
* Fastidous
Are Neisseria + Haemophilus Oxidase +/- ?
- Oxidase +
> Non-fermeting organisms
Where are non-fermenting organisms found?
What temperature do they usually grow?
What is a common linking factor of these organisms?
e.g. Neisseria + Haemophilus (Gram negative organisms)
- Upper respiratory tract, oropharynx + nares
- 35-37degrees
- Luxuriant capsules
If you are immune competent, what organisms are more likely to be found in the following samples?
- Urethritis/Cervicitis
-CSF
- Respiratory
- Blood
*Haemophilus depends on vaccination status
If you are immune compromised, what organisms are more likely to be found in the following samples ASWELLLL?
- CSF
- Respiratory
- CSF: + Pseudomonas
- Respiratory: + Pseudomonas, Burkholderia, Acinetobacter, Stenotrophomonas
What samples are cultured in GC agar and what samples cultured in Blood agar and Chocolate agar?
GC > Urethritis/cervicitis + CSF
Blood+ chocolate > CSF, respiratory, blood
Despite being aerobic, How else can the bacteria grow?
- Despite aerobic, can use nitrates as proton acceptor and grow best in CO2 (5%).
How do we narrow in to determine EACH ORGANISM… not members of genus?
Define
- meningitis
- encephalitis
- Bacterial meningitis
- Viral meningitis
- Septic meningitis
- Aseptic meningitis
- meningitis > inflammation of meninges.. subarachnoid space
- encephalitis > inflammation of brain parenchyma
- Bacterial meningitis > V.severe acute medical emergency , organism isolated
- Viral meningitis > Less severe, organism detected but not cultured
- Septic meningitis > organism can be cultured
- Aseptic meningitis > organism not cultured… does not mean its not present
- What is the brain parenchyma separated from the CSF + blood by?
- Where is the bbb found?
- Are the CNS and brain parenchyma immune privileged?
- Pia mater and bbb
- Arachnoid mater, layer that containing blood vessels
- Yes, but has microglia. Derived from myeloid lineage. > Migrate in before bbb seals the CNS off. > self replicate and are not derived from bone marrow.
- Great numbers in brain parenchyma limited in CSF
What is the bbb composed of? How does this help with its function?
How does bbb affect CSF composition
- Tightly joined modified epithelial cells
> Prevents entry of blood cells and nutrients + pharmaceutical agents - Limited composition.. high glucose and low protein levels when healthy
How can potential pathogens gain entry to CNS?
1- BBB, this route is hard thooo
2- Via afferent neurons :
-Neurons that provide afferent signals to the CNS are constantly shuttling biomolecules along the length of their axons:
- carry material from cell body to synapse via anterograde transport and return to cell body by retrograde transport
> If a pathogen gains entry to the presynaptic terminal of a neuron, they can hijack this transport system and head towards the CNS
Name the most common causative organisms in community-acquired meningitis.
True/False, Viral organisms often cause encephalitis than true meningitis.
- True
Age is a predictor of what is causing the problem. What is the epidemiology of causative organisms in community acquired disease:
> Neonatal - less than 3 months
> Paediatric - less than 16
> Young adult - less than 25
> Adult - less than 60
> Older patient - more than 60
1- What are the primary colonisation routes for each bacteria?
2- After colonisation how do they get to CSF?
1- Image..
2- Initial colonisation > Spread to bloodstream from primary site > Spread to CSF from bloodstream:
- Meningococcus = paracellular
- Pneumococcus = transcellular
Neisseria meningitidis also known as menigococci colonises where?
What does prevention of infection depend on?
What happens to non-pathogenic Neisseria?
- Meningococci colonise the nasal epithelium of humans
> Prevention of infection relies on either failure to invade the nasal epithelium or rapid clearance from the blood. (ability to cause invasive disease depends on the ability of the organism to reach higher levels in the blood)
- Without a capsule they rapidly accumulate complement and will either be phagocytosed or active lysed.
What happens when we don’t use antibodies specifically derived against these virulence factors?
- Lipooligosacharide
- Factor H binding protein
- Polysacharide capsule
No clearance → Results in sepsis, Meningitis or both = Meningococcal disease
How does meningococcus infect CSF? i.e cross the blood brain barrier?
- Adhesion > meningococci attach to the endothelial cells of the blood brain barrier.
- Porin A adhesions of meningococcus bind to laminin receptors (LR) on endothelial cells of BBB
> Binding leads to a confirmation change of LR that recruits CD147 on endothelial cells and ß2 adrenergic receptors - This complex of receptors causes formation of cortical plaque, a microtubules array, within the endothelial cells, below the meningococcus
> Cortical plaque causes disruption of tight junctions and moves the meningococcus paracellularly through the blood brain barrier
- Entry of meningococcus → colonisation of CSF
Invasion of CSF lead to…
- Inflammation and disruption of BBB
> Bacteria are not immediately detected by microglia as they are sparse in meninges
- Microglia encounter replicating organisms > phagocytosis limited due to capsules and lack of opsonins > pro inflammatory cytokine release to recruit cells to CSF
- BBB disruption due to inflammation > Neutrophils extravasate into CSF > acute phase protein and tissue fluid fill CSF.
= no innate clearance just ongoing cycle of inflammation + cell recruitment as no antibodies to virulence factors = intracranial pressure + sepsis
As clinicians what should we look for?
- Lethargy and drowsiness are key features. Pressure in the CNS causes this…
- Increased CSF > increases pressure on optic nerve … looking at bright lights painful
- Increased pressure on spinal nerves increases muscle tone “my neck feels stiff”
Non- blanching rash is part of sepsis marker of meningitis. How does it occur?
What is petechiae and purpurae ?
- Disturbances causes by release of lipooligosaccharide (LOS)
-> Petechial rash = less than 3mm
-> Purpurae = 3mm or greater
- Meningococci have LOS in outer membrane > die/replicate membrane shed as blebs covered in LOS > LOS binds to platelets very efficiently.
-In combination with release of tissue factor from endothelial cells that occurs when bacteria are in bloodstream > platelets begin to drive fibrin deposition + micro clots > clotting in small capillaries i.e skin, retina, renal tissue, conjunctiva of eye
-Haemorrages lead to bleeding form petechiae becomes visible and into larger patches > purpurae. = blister
In systemic circulation what does:
- TNFalpha do
- TF
- NO
What KEY test do we do to identify causative organism?
When is PCR required?
What should normal CSF sample look like compared to one that shows infection?
We also need to manage for sepsis so what else must else must be sent for microbiology?
1- Lumbar puncture > L3/4 : Contraindicated in patients with high inter cranial pressure … brainstem herniation… CT sca.. delay
2-
3-
4- Gram-staining will show infiltration of polymorphonuclear cells and the presence of your pathogen (Gram-negative diplococci, if it is meningococcal)
- Blood cultures - check for markers of organ function
