Microbiology of meningitis Flashcards

1
Q

What is meningitis?

A

Inflammation of the meninges around the brain and spinal cord.
Can be caused by infections from bacteria, viruses and protozoa. Other causes include cancer, inflammatory disease and drugs.

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2
Q

What is encephalitis?

A

Inflammation of the brain parenchymal tissue.
Most common cause is viral HSV and parasites
Other causes include autoimmune disease and certain medications.

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3
Q

Where can cerebral spinal fluid be found?

A

In the subarachnoid space and the ventricular system.

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4
Q

What are the two infection routes associated with infections in the brain?

A

Bacteraemia - infection in the blood stream crosses the blood-brain barrier
Severe trauma - breaks the barriers in the head and spine, makes it easier for pathogens to enter.

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5
Q

What is the normal immune status of the CSF?

A

The CSF typically has a very low level of leukocytes, with a poorer immune system protection is relies on the bones providing the physical protection.

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6
Q

What makes up the blood brain barrier?

A

Continous capillaries, endothelial cells with tight junctions and a basement membrane, often surrounded by pericytes. Astrocytes have astrocytic end feet that wrap around the basement membrane.
Some areas of the brain lack a blood brain barrier these are known as circumventricular organs.

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7
Q

How do the risks of meningitis change with treatment?

A

Without antibiotics their is a very high mortality rate.
Even with antibiotics 5-10% of people die, and this a risk of serious neurological damage.

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8
Q

What pathogens are most common in neonatal meningitis?

A

Group B Streptococcus
Streptococcus pneumonia
Listeria monocytogenes
E.coli

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9
Q

What is the most common cause of menigitis in older adults?

A

S. pneumonia
N. menigitidis
H. influenza
Group B streptococcus
L. monocytogenes

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10
Q

What is the most common cause of meningitis in young adults and teenagers?

A

Neisseria menigitidis
Streptococcus pneumonia

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11
Q

What are the common meningitis pathogens in babies and young children?

A

Streptococcus penumonia
Neisseria menigitidis
h. Influenza
Group B streptococcus
M tuberculosis

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12
Q

What are the common meningitis pathogens in immunosuppressed individual?

A

Cryptococcus neoformans.
Listeria Monocytogenes
‘Protozoal parasites’

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13
Q

What is menigococcal septicaemia?

A

Term used when sepsis accompanies meningitis due to Neisseria meningitidis entering the blood stream.

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14
Q

What are the symptoms of meningitis?

A

Fever higher than 38 degrees
Mental status reduction - often reduced consciousnes
Headaches
Photophobia
Nausea and vomiting
Non-blanching rash.

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15
Q

What is nuchal rigidity?

A

A stiff neck, neck resists passive flexion is a pathgnomonic sign of meningeal irritation.

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16
Q

What is kernigs sign?

A

Patient is in the supine position, thigh is flexed on the abdomen and the knee is flexed. Attemps to passively extend the knee cause knee pain.
Sign of meningeal irritation.

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17
Q

What is Brudzinski sign?

A

Patients in the supine position, passive flexion of the neck results in spontaneous flexion of the hip and knees.
Patient does this to avoid pain from the damaged meningis

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18
Q

What is a purpuric rash?

A

Purple-coloured spots and patches on the skin and mucus membranes, including the lining of the mouth.

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19
Q

What does a rash in meningitis indicate?

A

Commonly indicates septicaemia alongside meningitis.

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20
Q

What is the gram stain and shape of streptococcus pneumoniae?

A

Chains of round bacteria
gram positive - stains blue or purple

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21
Q

What is the gram stain and shape of group B streptococcus?

A

Purples chains of round bacteria

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22
Q

What is the gram stain and shape of neisseria meningitidis?

A

Gram negative or pink
Diploccoci - two circles

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23
Q

What gram stain and shap is the haemophilius influenzae?

A

Gram negative - pink
Rods- bacillus
Coccobacillus - intermedius between cocci and a baccilus, may appear oval shaped

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24
Q

What is the gram stain and shape of listeria monocytogenes?

A

Gram positive - blue/purple
Rods - bacillus

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25
Q

What is the gram stain and shape of escherichia coli?

A

gram negative - pink
bacillus - rod

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26
Q

What meningitis pathogens are common in older adults?

A

S.pneumoniae
N. meningitidis
H. influenzae
Group B stertococcus
L. monocytogenes

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27
Q

What causes meningitis patterns to vary regionally and temporaly?

A

Vaccination programmes
Genetic differences in host septibility.

28
Q

What are the three different ways a meningitis pathogen may cross the blood brain barrier?

A

Pathogen degrades tight junction proteins and crosses in the newly formed gap between endothelial cells.
Trojan horse startergy - contained within a vesicle in a neutrophil, neutrophil migrates into the area attracked by chemokines.
Passess directly through the endothelial cells, is engulfed within the endothelial cell then is exocytosed on the other side.

29
Q

What damage can meningitis pathogens cause in the bloodstream?

A

Complement activation
Intravascular thrombosis - liver secretes more thrombonin
DAMPS and PAMP release can trigger the innate immune response.

30
Q

What are some of the immediate consequences of inflammation in the meningis?

A

Increased intracranial pressure
Cerebral oedema.
Thrombosis - leading to ischemia and vaspasam (due to reduced blood flow to brain) can result in tissue death.

31
Q

What is the effect of cytokines on the blood brain barrier permeability?

A

Causes an increase in MMP release which break down proteins in the tight juncton
Causes an increase in NO, vasodilator

32
Q

What effects do cytokines have in meningitis?

A

Increase BBB permeability
Alter the cerebral blood flow - decrease perfusion pressure causing ischemia
Increase binding protein expression on endothelial cells so more leukocyte adherence + migration
Increases the number of reactive oxygen species - damage tissue

33
Q

What happens as a result of changes in CSF flow and composition in menigitis?

A

Obstructions to CSF absoprtion and flow
Obstructive and communicating hydrocephalus.

34
Q

What causes neuronal damage in meningitis?

A

Increases cranial presssure and cerebral oedema
Cytotoxic metabolites, ischemia and bacterial toxins result in damage

35
Q

What tissue in the brain in particularly vulnerable to damage during meningitis?

A

Hippocampus
Role in sensory functions, behaviour and gait.

36
Q

Give an overview of neisseria meningitidis?

A

Also called meningococcus
Humans are the only reservoir
High levels of asymptomatic carriage in the throat
Becomes pathogenic when crosses the nasopharangeal mucosa to enter the blood stream.
There are 13 serotypes world wide, 6 of which are responsible for the largest disease burden

37
Q

What contributes to the pathogenicity of neisseria meningitidis?

A

Polysaccharide capsule resists phagocytosis
Type 4 pilus attach to the mucosa, causes adhesion factors to develop act as microvilli
Triggers bacterial internalization, by pili induced signalling causes actin rearrangement to form membrane intrusion egulfing the pathogen
Lipo-oligosaccharide endotoxin causes damage to host, aids invasion of bloodstream, colonsiation of nasopharynx, and high death rates
IgA proteases: facilitiates growth on mucosal surfaces

38
Q

What is a serotype?

A

A distinct variatoin within a species or virus or bacteria.

39
Q

What is NMEC?

A

Neontal Meningitis E.Coli
Extraintestinal E.Coli
Also frequently found within the gut, transfered from mother.
Most frequent cause of gram negative meningitis in neonates
Fatality rates up to 40%

40
Q

How common is neonatal bacterial meningitis?

A

250 to 300 cases a year in the UK

41
Q

What is the ventricular system?

A

A set of hollow structures filled with CSF continous with the central canal of the spinal cord.

42
Q

Explain how NMEC is pathogenic.

A

Bacteria acquired perinatally from the mother, enter the blood stream.
Type 1 pilli bind to CD48, in closer proximity to the target endothelial cells adhesion molecules form
OmpA binds to ECGP96
S-fimbriae to sialic acid
CNF1 toxin binds to 67LR
IbeA invasion factor binds to receptor
This triggers actin rearrangment so that the pathogen is internalised.
The K1 capsule protects from lysomal fusion (phagocytosis, good for trojan horse startergy)

43
Q

What is ent(erobactin)?

A

Associated with gram negative bacteria mainly NMEC,
collects Iron for the microbe

44
Q

What is the diagnostic protocol for meningitis?

A

Diagnosing meningitis is a medical emergency.
Samples and results must be processes immediatly in order to inform antimicrobial treatment choices such as what specific antibiotic should be used
Broad spectrum antibiotics are often given before the exact bacteria has been identified is meningitis suspected.

45
Q

How is the CSF sampled?

A

Lumbar puncture
Into the dural sac into the subarachnoid space, between L3 and L4.
Patient lies on their side with the neck and hips/knees flexed to creat a maximum distance between the two vertebrae.
Hollow needle is used, this should not be painful but may feel uncomfortable.

46
Q

How is a CSF sample processed?

A
  1. Appearance - should be colourless, turgidity =wbc, red = blood, yellow = pus?, signs of infection stroke and hemorrhage
  2. Cell count
    3.Centrifugation
    4.Gram stain
  3. Culture identification
  4. Further tests if needed
47
Q

In a CSF cell count what is often considered?

A

Bacterial meningitis recruits leukocytes into the CSF
Consider: total number, types and ratios of bc
In children and adults wbc are normally below 5mm3
In neonates wbc numbers are normally below 20mm3
In bacterial meningitis often above 1000m3
In viral and tuberculosis meningitis WBC count is often lower but still higher than normal..

48
Q

What needs to be considered when testing to identify a microbe in meningitis?

A

Most pathogens are capsulated - capsule staining
In some cases when antibiotics are given early or meningitis is still in the early stage the pathogen is not identified in the CSF
In this case antigen detection is often used
PCR tests are often requested for more rapid and specific diagnosis, based on presumed pathogens given patients age.

49
Q

What are the guidelines when treating meningitis?

A

If suspected begin treatment before CSF sample
High dose intravenous benzylpenicillin given early as possible in under 16s
Treat children and young people with high dose intravenous 3rd gen cephlasporins and if under 3 months old penicillin.
Antibiotic suspectibility testing may alter choice
Tuberculosis or cryptococcal meningitis may require longer term anti-tubercular and anti-fungal treatments.

50
Q

How should close contacts of people with meningitis be managed?

A

Given prophylactic antibiotics.

51
Q

What are the different meningitis vaccines?

A

-6 in 1 vaccine - protection against diptheria, tetanus, whooping cough, hepatitis B, polio and Hemophilus Influenzae B
-meningitis B vaccine
-pneumococcal vaccine
- Hib/Men C vaccine
-Meningitis ACWY vaccine

52
Q

What are the common pathogens causing viral meningitis?

A

Enteroviruses
HSV-2
LCMV
Arbovirus
Mumps

53
Q

What are the less common pathogen causing viral meningitis?

A

HSV-1
CMV
EBV
VZV
Adenovirus
Measels
Rubella

54
Q

What pathogens cause rare cases of viral meningitis?

A

Influenza
Parainfluenza
Rotavirus
Vaccinia
Encephalomyocarditis

55
Q

How do you treat viral meningitis?

A

Data on the treatment of viral meningitis is very limited
Treatment is often symptomatic including anaglesics, antipyretics and antiemetics.
Acyclovir may be given in severe cases.

56
Q

How is group B streptococcus and E.coli commonly spread?

A

From mother to baby by birth

57
Q

How are h.influenza, s.pneumonia and m,tuberculosis often spread?

A

By coughing, cloxe proximity allows droplet transmission

58
Q

What are the most common serogroups of N.menigitidis in the UK?

A

C and B

59
Q

How is neisseria menigitidis often spread?

A

By sharing salvia by close contact such as kissing or prolonged contact such as living together

60
Q

How do people often get sick with e.coli and l.monocytogenes menigitis?

A

Eating contaminated food

61
Q

How is E.coli identified as the cause of menigitis?

A

Gram negative bacillia (pink)
Catalase positive
Oxidase negative

62
Q

How is maeophilius influenza identified as the cause of menigitis?

A

Gram negative coccobacillia (pink)
Cataslas positive
Oxidase positive

63
Q

How is listeria monocytogenes identified as the cause of menigitis?

A

Gram positive bacillus (purple)
Catalase positive
Oxidase negative

64
Q

How is neisseria menigitidis identified as the cause of menigitis?

A

Gram negative diplococci
Catalase positive
oxidase positive

65
Q

How is group B streptococcus identified as the cause of menigitis?

A

Gram positive diplococci or chains (purple)
Catalse positive
Oxidase negative

Most common in neonates

66
Q

How is streptococcus pneumonia identified as the cause of menigitis?

A

Gram positive lancet shaped (positive)
Catalase negative
Oxidase negative

Common in infant, children and adults

67
Q

What are the key diagnosit steps in a menigitis case?

A

Lumbar puncture
Complete cell count
Differenteiral leuocyte count
Gram stain smear
Culture
Determine glucose and protein concentrations
PCR where appropriate
Antigen testsing
MALDI if available