Infections of the CNS Flashcards
Describe clinical features of Meningitis.
- Headache, sore throat, drowsiness
- Rapid onset fever, photophobia, neck stiffness
- Level of consciousness progressively falls
- Petechial or purpuric rash
- Intravascular coagulation, endotoxaemia, shock, multi-organ failure, raised intracranial pressure.
- Gangrene
- Life-threatening emergency!
Identify a test to ensure whether or not a rash is from meningitis.
GLASS TEST
“Press a clear drinking glass against the rash. If the rash and marks are visible even while pressing down on the glass (non-blanching rash), seek medical help immediately.
This is a sign that the rash is petechial. Petechial rashes can result from meningitis or other serious illnesses that cause bleeding.”
Identify possible complications of meningitis.
- Gangrene
- Purpura fulminans (of acute meningitis)- thrombotic disorder
Describe diagnosis of meningitis.
• Initial diagnosis based on symptoms (listed above)
• Other symptoms in babies:
– Tense or bulging soft spot on their head
– Refusing to feed
– Irritable when picked up, with
a high pitched or moaning cry
– A stiff body with jerky movements, or else floppy and lifeless
• To confirm, “spinal tap to collect cerebrospinal fluid (CSF)”
Define meningitis, encephalitis, and sepsis.
• Meningitis – Inflammation of the meninges • Encephalitis – Inflammation of the brain • Sepsis – Whole-body inflammation
Identify ways through which infectious agents from outwith the brain can cause infection in the brain.
• Blood-brain barrier (BBB)
– Breach by infectious agents causes encephalitis.
• Blood- cerebrospinal spinal fluid (CSF) barrier
– Breach by infectious agents causes meningitis.
• Direct Spread
– Sinuses
– Otitis media
– Skull fracture
What forms the BBB ?
– Created by tightly packed endothelial cells lining the blood
vessels in the brain.
– Endothelial cells mechanically supported by thin basement membrane
What forms the blood-CSF barrier ?
– Similar barrier as BBB at arachnoid membrane and in ventricles.
How can pathogens cross barriers protecting the brain ?
– Growing across and infecting cells comprising barrier
– Passive transfer in intracellular vacuoles
– Carriage across in infected white blood cells
What laboratory investigations
would be carried out to confirm diagnosis of meningitis ?
• Blood – culture – NAAT – glucose – FBC – UandE – clotting
• CSF (through lumbar puncture): – white cell count – Gram stain – Ziehl-Neelsen stain – India ink – NAAT
When is a lumbar puncture contra-indicated ?
- Skin infection near the site of the lumbar puncture
- Suspicion of increased intracranial pressure due to a cerebral mass
Identify possible causative pathogens of meningitis.
BACTERIA
- Neisseria meningitidis
- Haemophilus influenzae
- Streptococcus pneumoniae
- Myobacterium tuberculosis
VIRUSES
- Enteroviruses (echovirus, coxsackie viruses A and B, poliovirus)
- Herpes viruses (Herpes simplex 1 and 2)
- Paramyxovirus (complication of mumps)
FUNGI
-Cryptococcus neoformans
PROTOZOA
- Amoebae
- Naegleria
- Acantoamoeba
NEISSERIA MENINGITIDIS
- Condition caused
- Classification
- Transmission
- Strains
NEISSERIA MENINGITIDIS
- Condition caused: meningococcal disease
- Classification: Gram negative, intracellular diplococcus, humans only, (exists as) normal microbiota of nasopharynx
- Transmission: by droplet spread or direct contact from carriers
- Strains: 5 (A, B, C, W135, Y)
(Also, distinct pathogenic serogroups)
HAEMOPHILUS INFLUENZAE
- Classification
- Strain
HAEMOPHILUS INFLUENZAE
- Classification: Gram-negative, coccobacilli
- Strain: Six capsular serotypes (a-f) known to cause disease, most virulant strain is H. influenzae type B (Hib)
STREPTOCOCCUS PNEUMONIAE
- Classification
- Conditions caused
STREPTOCOCCUS PNEUMONIAE
- Classification: Gram positive, chains of cocci, (exists as) normal microbiota in nasopharynx
- Conditions caused: Meningitis, pneumococcal disease, pneumonia, otitis media
Identify virulence factors of bacterial meningitis.
- Anti-phagocytic polysaccharide capsule
- Endotoxin
- IgA protease
- Outer membrane proteins (OMPs)
- Pili (fimbriae)
- All play an important role in pathogenesis
BACTERIAL MENINGITIS
- Appearance
- Cells
- Protein
- Glucose
- Gram Stain
- White Cell Count
BACTERIAL MENINGITIS
- Appearance: turbid
- Cells: polymorphs (100-2000/ul)
- Protein: Increased (50-300 mg/dL)
- Glucose: Reduced (0-5 mg/dL)
- Gram Stain: Perform (result is usually Gram negative)
- White Cell Count: Neutrophilia
VIRAL MENINGITIS
- Appearance
- Cells
- Protein
- Glucose
- Gram Stain
- White Cell Count
VIRAL MENINGITIS
- Appearance: Clear
- Cells: Lymphocytes (15-200/ul)
- Protein: Slight increase (50-100)
- Glucose: Normal
- Gram Stain: N/A
- White Cell Count: Normal
TUBERCULOUS MENINGITIS
- Appearance
- Cells
- Protein
- Glucose
- Gram Stain
- White Cell Count
TUBERCULOUS MENINGITIS
- Appearance: Clear (may cobweb)
- Cells: Lymphocytes (15-500/ul)
- Protein: Increased (100-600 mg/dL)
- Glucose: Reduced (0-5 mg/dL)
- Gram Stain: Do Ziehl- Neelsen stain
- White Cell Count: Normal
Which age groups are particularly at risk of pneumococcal meningitis ?
0 to 4 years make up majority
What are common causative pathogens of bacterial meningitis in:
- Neonates
- <5 years old
- Young adults
- Older
- Immunosuppressed
Neonates:
Escherichia coli
Group B Streptococcus
Listeria monocytogenes
<5 years old:
Neisseria meningitidis Haemophilus influenzae
Young adults:
Neisseria meningitidis
Older:
Strep pneumoniae
Listeria monocytogenes
Immunosuppressed:
- Myobacterium tuberculosis
- Cryptococcus neoformans
Distinguish between early, and late onset neonatal meningitis.
EARLY ONSET • Occurs <7 days • Infected by heavily colonised mother • Premature rupture of membranes • Pretermdelivery • 60% fatality rate
LATE ONSET • Occurs <3 months • Lack of maternal antibody • Poor hygiene in nursery • 20% fatality rate
Identify possible complications of bacterial meningitis.
- Sepsis
- Intellectual deficit
- Deafness
- Arthritis
- Skin necrosis
Describe treatment for bacterial meningitis, especially:
- Suspected meningococcal infection
- Suspected meningococcal infection <3 months old
- N. Meningitidis
- H. influenzae
- Strep. pneumoniae
- Group B Strep
- Gram negative bacilli
- L. monocytogenes
Suspected meningococcal infection:
IV/IM Penicillin (by GP on pre-admission)
IV Ceftriaxone (on admission)
Suspected meningococcal infection <3 months old
IV Cefotaxime + amoxicillin
N. meningitidis
IV Ceftriaxone 7d
H. influenzae
IV Ceftriaxone 10d
Strep. pneumoniae
IV Ceftriaxone 14d
Group B Streptococcus
IV Cefotaxime 14d
Gram negative bacilli
IV Cefotaxime 21d
L. monocytogenes
IV Amoxicillin 21d + IV Gentamicin first 7d
Describe prevention of bacterial meningitis.
VACCINES • MenC (meningococcal group C) • Hib (Haemophilus influenzae type B) • BCG (Mycobacterium tuberculosis) • Strep. Pneumoniae (pneumonococcal) • MenB (meningococcal group B) • Men ACWY (quadrivalent)
Does anyone need to be notified about this diagnosis, in bacterial meningitis ?
Meningococcal disease is a notifiable disease under the Public Health etc. (Scotland) Act 2008:
1) Reference Laboratories:
• Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory (SHLMPRL)
2) Public Health Action:
• Public Health will identify the close contacts and arrange antibiotics. Vaccination may also be required.
• If the patient is a child at school information letters and MRF info leaflets for all school parents are arranged.
3) Public Awareness:
• The public should be aware of the key signs and symptoms and to seek urgent medical advice if concerned.
What is a notifiable diseases ?
- Any disease that is required by law to be reported to government authorities
- Allows the authorities to monitor the disease
- Provides early warning of possible outbreaks
E.g. acute meningitis
How many cases, and deaths due to meningococcal meningitis worldwide ? Which environments is it most prevalent in ?
- Approx. 500,000 cases (50,000 deaths) worldwide
* Endemic in temperate climates. Endemic and epidemic in sub-Saharan Africa
Define meningitis belt.
4 African countries reported 88, 000 suspected cases
Which meninigitis serogroup has been responsible for most infectionsin Scotland ?
Group B (Group C also used to be responsible for a large amount of infections, but Group C vaccine was introduced in 2000)
VIRAL v BACTERIAL MENINGITIS
- More severe form
- More common form
VIRAL v BACTERIAL MENINGITIS
- More severe form: bacterial
- More common form: viral
Describe diagnosis of viral meningitis.
- NAAT is a valuable diagnostic tool
* Identify in faeces, urine, CSF, serology
Describe treatment for viral meningitis.
- No specific treatment
- Aciclovir (if herpes virus)
- Use of vaccination (if poliovirus)
Describe clinical features, diagnosis, and treatment of Tuberculous Meningitis.
TUBERCULOUS MENINGITIS
-Clinical: Usually develops when Rich focus discharges contents in sub-arachnoid space
-Diagnosis:
• Acid-fast bacilli in CSF smear
• NAAT and culture from CSF
-Treatment:
• Treated with rifampicin, isonazid, pyrazinamide, ethambutol
• Vaccination with BCG
Which other condition is tuberculous meningitis often associated with ?
Frequently associated with miliary TB
Which group of pathogens usually cause encephalitis ? How do these pathogens gain access to the CNS ?
Usually viral in origin
• Viruses gain access to CNS via blood or neurons
Identify the main kinds of encephalitis.
• Primary encephalitis
– First exposure to virus results in virus directly affecting brain / spinal cord
• Secondary encephalitis
– Virus first infects another part of body, then affects CNS when reactivated
Identify common causative pathogens of encephalitis.
- Cerebral malaria (Plasmodium sp.)
- Toxoplasma gondii
- Rabies
- Lyme disease (Borrelia burgdorferi)
- Herpes simplex virus
Identify signs of cerebral dysfunction, and an example of condition which may cause these.
ENCEPHALITIS – Abnormal behaviour – Seizures – Altered consciousness – Nausea – Vomiting – Fever
Identify a possible complication of encephalitis.
Brain Abscess
Describe formation of brain abscesses as a result of encephalitis.
- Begin as diffuse inflammation of brain matter progressing to focal lesion
- Arise from pia mater suppuration
How is brain abscess diagnosed ?
- Visualised by MRI or CT scans
* Diagnosed by culture from aspirated pus
Identify predisposing factors to brain abscess.
• Predisposing factors
– Otitis media
– Mastoiditis
– Sinusitis
Identify pathogens associated with brain abscesses.
• Oral-nasopharyngeal microbiota
– Aerobic (S. aureus, Strep. milleri)
– Anaerobic (Bacteroides sp., Fusobacterium sp.)
• Immunocompromised (eg. HIV, transplantation)
– Protozoa (Toxoplasma gondii)
– Fungi (Candida sp., Nocardia sp., Aspergillus sp.)
What are Transmissible Spongiform Encephalopathies ?
Prion diseases
Which living beings do TSEs affect ?
• Affects humans…
– Creutzfeldt-Jakob disease (CJD)
– New variant Creutzfeldt-Jakob disease (nvCJD)
• …and animals
– Bovine Spongiform Encephalopathy (BSE)
– Kuru
– Scrapie
What is the mechanism of action of rabies for infection of the CNS ?
Interference with function of infected nerve cells
What is the mechanism of action of poliomyelitis for infection of the CNS ?
Direct damage to nerve cells
What is the mechanism of action of botulism, tetanus for infection of the CNS ?
Release of neurotoxins released at a distant site
