CNS Infections Flashcards
What does CNS stand for?
Central Nervous System
What is the CNS comprised of?
The brain and spinal cord
What 3 layers protect the CNS?
- Hard (bone)
- Soft (Meninges)
- Liquid (Cerebro-spinal fluid)
How does the bone protect the CNS?
It protects from mechanical pressure and deformation. It is also a barrier against infection.
What are the meninges?
o Membranes covering the brain and spinal cord.
What are the 3 membranes of the meninges?
Pia Mater – innermost layer
Arachnoid – middle layer
Dura mater – outermost (toughest) layer
What is cerebro-spinal fluid and where is it found?
o Clear, colourless, odourless fluid found in the brain and spinal chord.
o Found in the subarachnoid space between the pia mater and the arachnoid.
How many ml of cerebro-spinal fluid can a personal have at any one time?
125-150ml
How many ml of cerebro-spinal fluid is produced every 24 hours?
600ml
What is cerebro-spinal fluid derived from?
Blood plasma.
Name the functions of the cerebro-spinal fluid
o Buoyancy o Protection o Prevention of brain ischaemia o Homeostasis o Clearing waste
Name the barriers which protect the CNS.
Blood-brain barrier
Blood-CSF barrier
Name the routes of invasion to infect the CNS.
- Blood-borne infections (most common)
o Microorganisms enter the blood and travels to the blood-brain barrier - Via peripheral nerves
- Local invasion from infected ears or sinuses, local injury or congenital defects
What is the most common infection caused when the blood-brain barrier is crossed by microorganisms.
Encephalitis
What is the most common infection caused when the blood-CSF barrier is crossed by microorganisms.
Meningitis
How do microorganisms transverse barrers?
- Growing across the barrier by infecting the cells that form the barrier
- Being passively transported across the barrier in intracellular vacuoles
- Being carried across by infected white cells
What barrier does Poliovirus overcome to infect the CNS?
The blood-brain barrier
How is Poliovirus transmitted?
Faecal-oral route
Describe how the Poliovirus enters the body and causes infection around the body.
- The poliovirus is ingested and infects the gut (the Gut Associated Lymphoid Tissue).
- It then travels to the Lymph and the blood and begins to infect other organs (e.g. Spleen and Liver).
- This causes a generalised infection mostly associated with the blood.
- Symptoms of fever etc occur.
- In some cases, the virus can cross the blood-brain barrier or blood-CSF barrier. If it crosses the blood-CSF barrier, Meningitis can be caused. If it crosses the blood-brain barrier, Encephalitis and often paralysis are likely.
Explain how invasion of microorganisms occurs through peripheral nerves using the examples of Herpes Simplex and Varicella-zoster.
o Both infect the skin initially.
o The infections are not fully removed by the immune system and become dormant in ganglions in the peripheral nervous system.
o They then can reoccur by travelling up the axons using retrograde transport.
What is the reoccurrence of Varicella-zoster usually called?
Shingles
How do invasions of the peripheral nerves travel up axons?
By retrograde transport
How does the body respond to invasion of the CNS by viruses?
- Increase in lymphocytes in the CSP
- Slight increase in protein
- CSF remains clear
How does the body respond to invasion of the CNS by bacteria?
- Increase in polymorpho-nuclear leukocytes
- Increase in proteins
- CSF goes cloudy
Outline some of the consequences of CNS infections.
- Can be life threatening
- Inflammation and edema
o Caused by infection in the CNS - “Closed box”
o Means that the inflammation and edema become critical. - Can take weeks to recover
- Some damage is permanent
Why do CNS infections only damage the host?
It is a closed system.
What is Encephalitis?
Inflammation of the brain resulting in brain damage.
Name some of the causes of Encephalitis.
- Infection
o Mostly by viruses (most common is Herpes Simplex – causes severe sporadic acute focal encephalitis). - Immune attack – auto-immune or post-infection
What are the symptoms of Encephalitis.
- Starts of with mild flu-like or headache
- Alterations of level of consciousness
o Mild confusion or drowsiness
o Loss of consciousness or coma - High temperature
- Aversion to light
- Seizures
- Inability to speak
- Sensory changes
- Neck stiffness
What is the mortality rate of Encephalitis?
10-30%
Name some of the sporadic causes of Encephalitis.
- Herpes simplex o Infant and adult forms - Mumps o Less common than meningitis - Varicella zoster o Associated with ophthalmic zoster - Rabies o In India 150,000 deaths per year o In USA <10 deaths per year - HIV o Sub-acute encephalitis often associated with other CNS infections
Name some of the outbreak causes of Encephalitis
- Polio and other enteroviruses o Uncommon because there is a vaccine and very few countries who have wild type polio present. o Associated with paralysis - Mosquito-born Togaviruses - Mosquito-borne Bunyaviruses
Name some of the slow viral causes of Encephalitis
- Rubella
o Infection in-utero or sub-acute sclerosing panencephalitis (SSPE) - Measles
o SSPE following uncomplicated measles - JC virus (Human polyoma virus 2)
o Usually immunocompromised, specially AIDS
Name the bacteria that cause Encephalitis and how common each are as a cause.
- Treponema pallidum (syphilis) o Rare o May affect the brain - Mycoplasma pneumoniae o Rare o Causes pneumonia originally - Borrelia burgdorferi (Lyme disease) o Uncommon
Name the protozoa and fungi that cause Encephalitis.
- Cryptococcus neoformans o Rare complication - Toxoplasma gondii o Meningoencephalitis - Plasmodium falciparum o Cerebral malaria - Trypanosoma spp. o Sleeping sickness in Africa
Name the Atypical agents of the scrapie group that cause Encephalitis.
- Prions – Creutzfeldt-Jakob and kuru in humans
- Spongiform encephalopathy
When, how and why do some post-vaccinational / post-infectious agents cause Encephalitis?
- Occurs as a rare complication 2-3 weeks after exposure to certain viruses of vaccines
- Strong autoimmune component
How does Clostridium tetani affect the CNS and what symptoms does it cause?
Blocks inhibitory neurotransmitter. Excitatory transmitter therefore cycles. No inhibition of excitation transmitter. Continuous stimulation = muscle rigidity and lockjaw.
Where are Clostridium tetani commonly found and how people are generally exposed to this microorganism.
They are found in the soil and are present in the environment. People tend to be exposed via cuts.
What toxin is present in clostridium tetani and how does this travel?
Tetanospasmin - carried in peripheral nerve axons to the CNS.
How is infection caused by Clostridium tetani treated?
Anti-tetanus immunoglobulin.
Vaccine that lasts 10 years also available.
Where is Clostridium botulinum found?
It is found in the soil and so contaminates fruit and vegetables. Frequently found when foods are canned or preserved without appropriate steralisation.
How does Clostridium botulinum affect people?
The motor and autonomic system is affected leading to weakness and paralysis followed by respiratory muscle failure.
What is the treatment for infections caused by Clostridium botulinum?
immunoglobulin and respiratory support
What is the mechanism of action for Clostridium botulinum causing infection of the CNS?
Acetyl choline containing vesicles inhibited. Acetyl Choline is not released. No stimulation in the motor end plates.
What is Meningitis?
Inflammation of the tissues that cover the brain and spinal cord.
In what people are viruses most likely to cause Meningitis?
Children
What are the most common viruses that cause MEningitis?
The most common viruses that cause Meningitis are Enterovirus, Mumps and Herpes Simplex.
What an organism must do to cause Meningitis?
- Colonise and invade mucosa
- Survive in the blood stream
- Cross the blood-brain/ blood-CSF barrier
- Survive within the CSF
Name some host defence methods against Meningitis.
- Secretory IgA antibodies
- Cellular cilia activity
- Mucosal epithelium
- Complement antibacterial activity
- Cerebral endothelium
Name some virulence factors of Pathogens to avoid host defences against Meningitis.
- IgA protease secretion
- Ciliostasis
- Adhesive pili
- Cell surface avoids stimulating complement
- Rapid bacterial replication
- Capsule to avoid phagocytosis.
- Membrane damaging toxin
o Pneumolysin
Leukotoxic
Inhibits immune cell activity
Activates compliment and contributes to inflammation - IgA Protease
o Inactivates secretory antibody
How does Pneumolysin work as a virulence factor of pathogens to avoid host defences against meningitis ?
It is Leukotoxic and so inhibits immune cell activity. It also activates compliment and contributes to inflammation.
How does IgA Protease work as a virulence factor of pathogens to avoid host defences against meningitis ?
Inactivaes secretory antibodies.
What are the host defences against colonisation and mucousal invasion of harmful bacteria?
Secretory IgA
Cellular cilia activity
Mucosal epithelium
What are the bacterial evasion mechanisms against Secretory IgA,
Cellular cilia activity and
Mucosal epithelium
IgA protease secretion
Ciliostasis
Adhesive pili
What are the host defences against harmful bacteria surviving in the blood stream?
Complement antibacterial activity
What are the bacterial evasion mechanisms against complement antibacterial activity ?
Cell surface avoids stimulating complement.
What are the host defences against harmful bacteria crossing the blood-brain barrier?
Cerebral endothelium
What are the bacterial evasion mechanisms against cerebral endothelium?
Passage through tight junctions between cells.
What are the host defences against harmful bacteria surviving within the cerebro-spinal fluid?
Poor opsonic activity
What are the bacterial evasion mechanisms against poor opsonic activity?
Rapid bacterial replication
Name some risk factors for meningitis.
Reduced Immunity: o Asplenia o Diabetes o Alcohol abuse o HIV o Hypogammaglobinaemia
What type of Meningitis does Haemophilus Influenzae cause?
b
What is different in each of the 6 different types of HAemophilus Influenzarr?
Different capsular polysaccharides
What issues/ infections can Haemophilus Influenzae cause?
Pneumonia, septic arthritis, sinusitis, otitis media, conjunctivitis, chronic bronchitis
What type of microorganism are Haemophilus influenzae?
Gram -ve coccobacilli
Are Haemophilus influenzae capsulated?
No
What do Haemophilus influenzae require for growth ?
Blood constituents
Where are Haemophilus Influenzae commensal?
The throat
What is the virulence of Haemophilus Influenzae related to and how does this work?
Virulence related to a capsule – impedes phagocytosis
Where is the reservoir for Haemophilus influenzae and how is it transmitted?
- Reservoir = humans
o Up to 80% of people are carriers - Transmission = droplet infection
Are Haemophilus influenzae catalase and oxidase +ve or -ve?
+ve
Describe how Haemophilus influenzae can be grown in the lab.
- Will only grow on chocolate agar under 4% carbon dioxide
- X (haemin) and V (NAD) factors must be provided by discs to allow growth on nutrient agar
Are Haemophilus influenzae latex agglutination +ve or -ve?
+ve
How does Neisseria meningitidis cause death?
Most deaths are caused by septicaemia, not the actual meningitidis.
What is the incubation period of Neisseria meningitidis?
1-3 days
WHat type of organisms are Neisseria meningitidis?
Gram -ve diplococci
Are Neisseria meningitidis oxidase +ve or -ve?
+ve
How do Neisseria meningitidis grow on blood agar?
As pearly looking colonies
What causes variety in Meningococcal disease?
- Varies by a number of factors; serogroup, age and prompt antibiotic treatment
Where are Streptococcus pneumoniae commensals?
The upper respiratory tract
How do Streptococcus pneumoniae grow?
As diplococci or chains
What issues do Streptococcus pneumoniae cause?
- High incidence of infection leading to pneumonia and bacteraemia – 4% of these infected sufferers will develop Meningitis.15-20% association with sequelae.
Also causes Septicaemia in splenectomised patients.
what type of organisms are Listeria monocytogenes ? Also describe the conditions required for growth.
Motile, non-sporing, Gram +ve rod bacillus.
They are aerobic and facultatively anaerobic and grow from 1-45 degress Celsius.
What type of haemolysis do Listeria monocytogenes cause?
Beta
Who does infection by Listeria monocytogenes most commony affect?
- Affects pregnant women, neonates, elderly and immunocompromised patients
What can occur if infections caused by Listeria monocytogenes arn’t treated?
- If not treated, high risk of meningitis especially in neonates
What are the symptoms of viral meningitidis?
Mild, flu-like headache
Why are the viral meningitidis reported numbers not representative?
Viral meningitis is under reported. Symptoms can be very mild and so numbers tend to report more severe cases.
How does Milliary tuberculosis cause Meningitis?
- Milliary tuberculosis subtype starts in the lungs and migrates through the lymphatic nodes to the brain.
Where does Mycobacterium tuberculosis affect mostly?
The lungs
How fast does Mycobacterium tuberculosis grow?
Slowly
Where in the body and who does Cryptococcus neoformans mostly affect?
- Primary infection of the lungs
- Found mostly in patients with depressed cell-mediated immunity
Where are Naegleria fowlerii found and how do they infect humans, leading to Meningitis?
o Free living in fresh water
o If inhaled, can reach the meninges through the olfactory tract and cribriform plate
o Rapid onset and high mortality
Who does infection by- Acanthamoebaa castellanii most frequently affect and how does it enter the body?
o More commonly affects those that are unwell or immunocompromised
o Thought to enter via the skin or respiratory tract
