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4.1 Medical Microbiology > Central Nervous System > Flashcards

Central Nervous System Flashcards

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USMLE® Step 1 flashcards Biology 101 flashcards
1
Q

What are the meninges, list the different layers?

A

Three layers of membranes that cover and protect your brain and spinal cord:
- Dura mater -> outer layer closest to the skull
- Sub-dural space
- Arachnoid mater -> middle layer
- Sub-arachnoid space and CSF channel
- Pia mater -> inner most layer closest to the brain

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2
Q

Define meningitis, how is it diagnosed?

A

Infection of the subarachnoid space with meningeal involvment

Identified by an abnormal number of white blood cells in the cerebrospinal fluid

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3
Q

What three physiological barriers does the body have in place to protect the CNS from infection?

A

Blood Brain Barrier

Blood CSF Barrier

Tight Junction of the endothelial cells (proximity to CNS) -> less permeable to antibodies and antimicrobials

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4
Q

What is the blood brain barrier, what is its structure?

A

A selective semi-permeable membrane between the blood and the interstitium of the brain

A blood vessel with a thick basement membrane and non-fenestrated enodthelium with TJ, surrounded by CNS glial cells

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5
Q

What is the Blood CSF barrier, what is its structure?
(3)

A

A physiochemical barrier that separates the blood from the CSF and permits the exchange of drugs and biomolecules

It consists of a blood vessel with fenestrated endothelium and a thin basement membrane (on the Blood vessel side)

Choroid plexus epithelium lines the CSF

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6
Q

What does the TJ of the CNS barriers do?

A

Keeps bacteria out but also keeps antibodies and antimicrobials out

Both a good thing and a bad thing

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7
Q

What are the two types of meningitis?

A

Acute: single episode, single species, uncompicated meningitis

Chronic: long duration, recurrent, complicated, unusual organisms

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8
Q

What organisms can cause meningitis?

A

Bacteria
Viruses
Fungi -> immunocompromised
Parasites

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9
Q

What are the four infections of the CNS, other than meningitis, what are they?

A

Encephalitis -> inflammation of the brain substance
Myelitis -> inflamation of spinal cord
Brain abscess -> focal, intracerebral infection, pus surrounded by a well vascularised capsule
Neuritis -> inflammation of peripheral nerves

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10
Q

What is the most common mode of entry into the CNS

A

Via the blood

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11
Q

What are the five modes of entry into the CNS?

A

Local infection -> bacteraemia -> CNS

Viral infection -> viraemia -> CNS

Defect in dura -> bacterial direct entry

Spread through cribiform plate (rare)

Spread along nerve fibres and connection (rare)

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12
Q

What are the four most common meningitis agents in 0-4 wk olds?

A

S. agalactiae (GBS)
E. Coli (think birth etc)
L. monocytogenes (think listeriosis)
K. pneumoniae (specific to neonates)

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13
Q

What are the six most common meningitis agents in 4-12wk olds?

A

S. agalactiae (GBS)
E. Coli (Birth)
L. monocytogenes (listeriosis)
H. influenzae
S. pneumoniae
N. meningitidis

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14
Q

What are the four most common meningitis agents in 3 month olds to 18yr olds?

A

N. meningitidis
S. pneumoniae
Viruses (enteroviruses)
H. influenzae

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15
Q

What are the three most common meningitis agents in 18 to 50 year olds?

A

S. pneumoniae
H. influenzae (occasionally non-group B)
S. pyogenes

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16
Q

What are the four most common meningitis agents in >50 year olds ?

A

S. pneumoniae
N. meningitidis
L. monocytogenes (occassionally)
Gram-negative bacilli (including P. aeruginosa)

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17
Q

What is the most common type of meningitis?

A

Viral meningitis

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18
Q

What viruses most commonly cause meningitis, how frequent are they?

A

Enteroviruses are the most frequent, causing 78.5% in 2015

Herpes, mumps, polio and herpes zoster can also cause meningitis but its usually as a complication of a primary infection elsewhere

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19
Q

What enteroviruses are most commonly causative of meningitis?

A

Coxsackie viruses and echoviruses

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20
Q

How frequent is viral meningitis?

A

Accounted for 78.5% of meningitis cases ni 2015

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21
Q

Is viral or bacterial meningitis more serious?

A

Bacterial meningitis is a lot more serious

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22
Q

What is the current trend in viral meningitis in Ireland?
(3)

A

Viral meningitis is on the rise

Between 2017 and 2018 there was a 29.7% rise in cases

Highest amount of cases was 435 recorded in 2014

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23
Q

What is the current trend in viral meningitis in Ireland?
(3)

A

Viral meningitis is on the rise

Between 2017 and 2018 there was a 29.7% rise in cases

Highest amount of cases was 435 recorded in 2014

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24
Q

What is the crude incidence of viral meningitis in Ireland, as last recorded in 2018, who did this effect the most?

A

Crude incidence of 7.1/100,000

Children aged between 1 and 2 accounted for 103 of the 435 cases

Children aged between 1 and 4 accounted for 69/435

=> Children <4 = 40% of cases

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25
Q

Comment on the trends in viral meningitis in Ireland (in 2018), which viruses are increasing/decreasing etc

A

PCR testing was only bought in to the NVRL in 2005, so since then there has been an overall increase in viral meningitis cases -> increase in detection

Consistently enterovirus has remained the most frequently detected pathogen (accounting for 78.5%)

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26
Q

What improvements have there been in the NVRL detection methods in recent years?
(3)

A

PCR testing introduced in 2005 for Enterovirus and human herpes virus

Parechovirus testing introduced in 2013

Enterovirus typing introduced in 2017

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27
Q

What improvements have there been in the NVRL detection methods in recent years?
(3)

A

PCR testing introduced in 2005 for Enterovirus and human herpes virus

Parechovirus testing introduced in 2013

Enterovirus typing introduced in 2017

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28
Q

How does bacterial meningitis differ from viral?
(3)

A

Bacterial is a medical emergency

Bacterial requires timely and accurate diagnosis

Targeted appropriate treatment very important -> usually have one chance to treat especially in kids

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29
Q

The WHO has introduced a Roadmap for “Defeating Meningitis by 2030”, what five areas does it intend to make improvements in?

A

Prevention and epidemic control

Diagnosis and treatment

Surveillance

Support and care for patients affected by sequelae (especially neurological symptoms)

Engagement and advocacy

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30
Q

What % of bacterial meningitis is culturable, why is this the case?

A

Only 60% of cases are culturable

If there is any clinical suspicion of meningitis bacterial meningitis antibiotics are started immediately -> if it ends up being viral the antibiotics will be stopped but its better to be over-treated then miss symptoms etc

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31
Q

In the Lab what do we usually do while waiting for blood cultures if query meningitis?

A

Run a biofire Film Array

If viral -> report and antimicrobial treatment will be stopped

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32
Q

Since the 80s how has bacterial meningitis trended in Ireland
(5)

A

From the 80s until Oct 2000 there was a steady increase in bacterial meningitis cases

MenC vaccine was introduced in Oct 2000, sharp decrease in cases ever since

From 2013 cases began to trend ever so slightly upwards again -> increase of +8 in 2014

MenB vaccine introduced in Dec 2016 -> no recent stats available to reflect this vaccine

NB: regardless of numbers or vaccines the death rate has remained high (3-15%)

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33
Q

When was the MenC vaccine introduced?

A

October 2000

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34
Q

When was MenB introduced

A

Dec 2016

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35
Q

When did bacterial meningitis cases begin to trend upwards again

A

2013 = 150
2014 = 158

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36
Q

Compare trends in meningococcal meningitis vs other bacmen

A

Since addition of MenC in 2000 Meningococcal meningitis numbers have consistantl fallen intil 2013

There hasnt been much change in numbers of other bacmen at all over the years, consistantly cause between 50 and 80 cases a year

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37
Q

What is one menbac that has trended upwards recently?

A

Cases of strep pneumo meningitis have doubled since 2000

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38
Q

What are the most common causes of bacterial pneumonia, what are there relative percentages, compare 1999 (prior to MenB) vs 2018?

A

1999:
N. meningitidis most common @ 91.3%
Streptococcus pneumonia @ 3.2%
Haemophilus influenzae @ 0.3%

2018:
N. meningitidis: 54.3% (significant reduction)
S. pneumonia: 25% (significant increase)
H. influenzae: 2.4% (increase)

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39
Q

What are three risk factors for meningitis

A

Prolonged close contact with infected patients
Travel to endemic areas
Immune deficiency, asplenia, HIV, corticosteroids etc

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40
Q

How might someone get E. Coli, Klebsiella or Pseudomonas meningitis?

A

These are much rarer meningitis bacteria in adults

Only really seen from neurological procedures

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41
Q

How does colonisation or mucosal invasion lead to meningitis, how does the body fail to defend?

A

The nasopharynx is the first to be colonised

Host defences include secretory IgA, ciliary activity and mucosal epithelium

But, pathogens utilise IgA protease, ciliostasis, adhesins and capsules to get by these

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42
Q

How does intravascular invasion lead to meningitis, how does the body fail to defend?

A

Host defences include complement activation and phagoctyic response

Pathogens evade the alternativ complement pathway by their polysaccharide capsule

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43
Q

How does the crossing the blood brain barrier lead to meningitis, how does the body fail to defend?

A

Both the BBB and the cerebral endothelium are designed to prevent noxious material getting in

Host has poor opsonic activity and thus a poor immune response

Pathogens replicate as the immune system is unable to contain them

A successful pathogen must colonise the host mucosal epithelium, invade and survive in the intravascular space, cross the BBB and survive inthe subarachnoid spacethe CSF

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44
Q

What are the five most common virulence factors of menbacs?

A

Capsule
IgA protease
pili
endotoxin
Outer membrane proteins

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45
Q

Menbacs often have virulence factors such as a capsule, IgA protease, pili, endotoxins and outer membrane proteins, which of these factors does N. meningitidis, S. pneumoniae and H. influenzae have?

A

N. meningitidis and H. influenzae have all of the above

S. pneumonia only have a capsule and IgA proteases

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46
Q

N. meningitidis, S. pneumoniae and H. influenzae all have capsules, why is this significant?

A

Capsules aid in the evasion of phagocytosis

All vaccines produced are based on capsular proteins
- they attack capsule, without capsule they loose virulence

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47
Q

Both N. meningitidis and H. influenzae have endotoxins why do we need to be concerned with these?

A

These are found in the cell walls of bacteria

We need to be careful when lysing bacterial cells as they will be released -> this can cause septic shock

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48
Q

How do bacteria get throught the tight junctions of the CNS endothelium?

A

The exact method is unknown

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49
Q

What is the most common bacteria meningitis worldwide?

A

N. meningitdis

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50
Q

How common is N. meningitidis carriage, who is it most frequent in?

A

2-25% of the population carry it in their nasopharynx
- this is uncommon in infancy and early childhood (hence not a cause in these cohorts)
- peak carriage between 15-19 (25%) (hence meningitis cases increase with this age group)

No clear relationship between rate of carriage and appearance of disease

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51
Q

How is N. meningitidis spread and when is it most frequently spread?

A

Spread through respiratory droplets (from a carrier), generated by coughing, sneezing and kissing (hence increase in teens etc)

Most cases occur in winter (January exams) and in spring in children and young adults

Diagnostic skin rash common in these cohorts, only seen in late infection

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52
Q

How frequent is Meningococcal carriage in Irish students, what were some risk factors for carriage?

A

20.6% carriage

MenW cariage = 1.9%
- Higher MenW carriage was higher in those who were vaccinated with MenC vaccine

Smoking, male gender, irish nationality were associated with colonisation

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53
Q

Where is the burden of disease, what age group most affected?

A

Incidence highest in those under 1 and really up until 4 as well as elderly with an additional peak in late teens

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54
Q

How is N. meningitidis spread

A

Respiratory and throat secretions
- coughing/sneezing
- kissing
- sharing utensils and bottles etc

Crowded settings:
- college dorms
- military barracks
- nightclubs and bars
- crowded households

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55
Q

What are the three risk factors for N. meningitidis?

A

Age:
- 0-5
- 15-24
- 65+

Living in a community setting

Immunocompromised

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56
Q

Talk about meningococcal capsular groups

A

There are 13 meningococcal capsular groups

A, B, C, W and Y are most common

The organism is associated with both assymptomatic carriage and invasive disease

> 95% of cases are sporadic but occasional outbreaks occur e.g. in families, schools, universities

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57
Q

Comment on the cell wall outer membrane proteins

A

These are responsible for the serotyping of the bacteria

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58
Q

What are meningococcal meningitis serogrouped based on?

A

Based on acidic capsular polysaccharide

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59
Q

What percentage of meningococcal meningitis is caused by Men A, B and C?

A

Men A, B and C account for 90% of all cases

Certain geographical areas have higher rates etc

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60
Q

What might predispose a person to infection with uncommon meningococcal serogroups?

A

Complement deficiency

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61
Q

Comment on the trends in some of the uncommon serogroups such as X, Y, Z and W

A

These serogroups account for very low numbers but there has been a noticable increase in these serogroups in recent years

62
Q

What are the signs and symptoms of meningococcal meningitis in adults and older children?

A

Classical symptoms and signs

Temperature, sever headache, neck stiffness, nausea and/or vomiting, dislike of bright lights, drowsiness and joint or muscle pains

Confusion, disoriented or fits

Not all of these symptoms may appear

63
Q

What is a dislike of bright lights known as?

A

Photophobia

64
Q

What are the symptoms of meningococcal meningitis in children?
(5)

A

Fever, headache and neck stiffness, these may be subtle or marked

Vomiting in 35% of cases

Sezures in 30% of cases

Cranial nerve palsies and focal cerebral signs (10-20%)

Petechiae seen in meningococcal disease with or without meningitis

65
Q

What are the signs and symptoms of meningitis in babies

A

Fever, cold hands and feet

Stiff neck

Dislike of bright lights

Convulsions/seizures

Drowsy, floppy, unresponsive

Tense, bulging fontanelle

General symptoms such as pale, blotchy skin, unusual crying, moaning, rapid breathing, fretful etc etc

66
Q

Talk about the meningococcal rash, what is it, how does it happen?

A

Can be present in both adults and babies

Happens when bacteria enter the bloodstream, they can release toxins, which can damage the walls of blood vessels causing a leakage of blood under the skin

The rash appearance can vary from tiny blood spots to bruises or blood blisters

It may be the last sign of meningitis to appear and it can spread very quickly

67
Q

What test can you carry out if you query a meningococcal rash, how do you carry out the test, how do you interpret the results?

A

The tumbler test

Press a glass tumbler against the rash to see if it disappears

If true rash it will still be visible through the glas

68
Q

What percentage of patients does the meningococcal rash appear in?

A

Only about 52% of patients

69
Q

What is probably the most telltale sign of meningococcal meningits?

A

Stiffneck accompanied by fever over 38 degrees

Fever>38 seen in 97% of patients
Neck stiffness seen in 82% of cases

70
Q

What are some sequelae that can follow meningococcal meningitis, how frequent are they?

A

In 10-20% of patients:
- Brain damage
- hearing loss
- learning disability
- amputation

Fatality in 5-10%

71
Q

What percentage of meningococcal meningtis end up fatal?

A

5-10% of cases

72
Q

Meningitis is a notifiable disease, what does this mean?

A

It must be reported to the Director of Public Health/Medical Oficer of Health by laboratories and clinicians

73
Q

Why do we report meningitis cases, what are the benefits of surveillance?
(4)

A

Identify, control and protect any case contacts

Detect and confirm any outbreaks

Monitor for trends, serogroup prevalence, antibiotic resistance etc

Monitor control strategies such as vaccination etc

74
Q

What should be done with any close contacts of a positive meningitis case?

A

Chemoprophylaxis -> theyre given antibiotics whether they are symptomatic or not

Given vaccination if theyve not been given etc

75
Q

What is the mortality rate of adult (purely) meningitis?

A

3-10% -> accounts for 85% of cases

i.e. 85% of cases were purely meningitis and out of these 3-10% resulted in death

76
Q

What is the mortality associated with meningococcal sepsis in adults?

A

15-40% but this only accounted for 15% of cases

77
Q

How many meningitis outbreaks have there been

A

Just 1 outbreak in childcare - 2 cases involved

78
Q

How does Ireland’s meningococcal rates compare to the rest of Europe, in 2017?

A

Ireland was one of the worst in Europe, only lithuania had a higher incidence rate

79
Q

Comment on meningococcal trends in Ireland, by serogroup, from 1999-2022

A

MenC vaccine introduced October 2000

MenC decreased from 2000, increasing again from 2013 on

MenB also decreased after 2000

After MenC vaccine the MenB relative % increased

From 2013/2014 the relative % of cases that were menC (as well as other serogroups) began increasing again

Numbers reached an all time low in covid years but are increasing again now

Cant really comment of efficacy of MenB vaccine yet

80
Q

Comment on meningococcal trends in Ireland, by serogroup, from 1999-2022

A

MenC vaccine introduced October 2000

MenC decreased from 2000 reaching as low as 0 percent in 2012, increasing again from 2013 on

MenB also decreased after 2000

After MenC vaccine the MenB relative % increased

From 2013/2014 the relative % of cases that were menC (as well as other serogroups) began increasing again

Numbers reached an all time low in covid years but are increasing again now

Cant really comment of efficacy of MenB vaccine yet

81
Q

Why did detection of all N. meningitidis serogroups fall in 2020 to 2021?

A

This was due to COVID 19 prevention methods
- mask wearing etc all helped reduce transmission of N.meningitidis

82
Q

What percentage of N. meningitidis cases were only PCR positive i.e. culture negative

A

37% of cases were detected only through PCR methods - i.e. 37% % of cases could have been missed

83
Q

What is meningococcaemia, what causes it?
(5)

A

Gram negative septic shock

The detection of N. meinigitidis in the bloodstream

Endotoxin in GN cell wall as well as other bacterial components come into contact with the immune system

Occurs when there is lysis of bacteria cells

This initiates a complex cascade of events beginning with the release of primary inflammatory cytokines from macrophages and other inflammatory cells

84
Q

What are the three main cytokines that are responsible for GN septic shock/meningococcaemia

A

TNF-alpha
IL-1
IL-6

85
Q

What are the four main symptoms of meningococcaemia/gram negative septic shock?

A

Purpura fulminans
Hypotension
Disseminated intravascular coagulation
Multiorgan failure
Death in 40% of cases

86
Q

What N. meningitidis vaccines are available?

A

MenC + MenC booster
Men B
Men ACWY

87
Q

What N. meningitidis vaccines are available?

A

MenC + MenC booster
Men B
Men ACWY

88
Q

When was MenC introduced, who is it for?

A

2000-2002

Introduced or infants and catchup for young adults

89
Q

When was MenC booster introduced, who is it for?

A

September 2014

Introduced for students in 1st of college

90
Q

When was MenB introduced, who is it for?

A

December 2016

Introduced for infants

91
Q

When was MenACWY introduced, who is it for?

A

Introduced in 2019? to replace MenC
- provides protection against additional serotypes

For students in 1st of secondary school

92
Q

The MenC and the MenB vaccines are conjugated, what does this mean, why are they significant?

A

Both of these vaccines targets are polysaccharides

Polysaccharides are not immunogenic enough on their own to bring about the production of antiodies and thus create immunity

We must conjugate these by connecting the polysaccharide to a protein so that we can not only detect it but produce antibodies against it

Conjugated vaccines are the only ones suitable for infants -> they can trigger T-cell dependent memory response

93
Q

Comment on trends in Men serogroups with introduction of each Men vaccine

A

Steady decrease in MenB and MenC (as well as ‘unknown’ strains) since bringing in the MenC vaccine in 2000

MenC showing increase since 2013 -> MenC booster introduced in 2014 -> too early to comment yet

Men B cases steadily decreasing, MenB introduced in 2016, too early to comment

MenACWY - too early to comment

94
Q

Talk about the MenC vaccine, when introduced, who suitable etc?
(4)

A

Introduced in October 2000

Conjugated antibody -> targets group C polysaccharide -> suitable for those 6 weeks or older

Booster available in adolescents from 2014

MenC replaced in 2019 with Men ACWY

95
Q

Talk about the Men ACWY vaccine
(3)

A

Brand name Nimenrix

Taregts group A, C, W-135 and Y pppolysaccharide

Conjugate vaccine but recommended for adolescents in first year of secondary school due to increase in nonB, nonC cases in these cohorts

96
Q

Who is the Men ACWY vaccine recommended for?

A

Adolescents

Splenectomy, haemoglobinopathies, coeliac disease

Complement or properdin deficiency

Down syndrome

Immunodeficient e.g. HSCT or SOT

97
Q

Why is there a need for Men ACWY vaccine?

A

Even though MenB and MenC show downwards trends since introduction of the vaccine

MenW and MenY are increasing -> relative percentage increase in these serotypes

98
Q

What kind of vaccine is the MenB vaccine, how and why is it different to the MenC and MenACWY?

A

MenB is developed from subcapsular antigens

MenB polysaccharide could not be used as the polysaccharide capsule is identical to that found on the surface of the human foetal neuronal cells
- this polysaccharide is poorly immunogenic and has potential to cause an autoimmune response

99
Q

the MenB polysaccharide capsule is identical to what?

A

The surface of human foetal neuronal cells

100
Q

How did we go about developing a MenB vaccine?

A

we looked for antigens which are surface-exposed, conserved and induce bactericidal activity

Through this we developed Bexsero

101
Q

What is the MenB vaccine called?

A

Bexsero

102
Q

What is reverse vaccinology

A

Reverse vaccinology

Take organism and clone it

Do an insilico search for proteins

Test protein antigenicity in mice

If mice produce antibodies are they bactericidal or do they neutralise etc

103
Q

How did we go about developing Bexsero?
(3)

A

4CMenB vaccine

OMV from the New Zealand strain was used as well as three proteins discovered through reverse vaccinology

Only the OMV was specific to MenB -> this allowed for some potential protection from other groups

104
Q

What are the four antigenic components of Bexsero?

A

fHbp -> factor binding protein

NHBA -> neisseria heparin-binding antigen

NadA -> neisseria adhesin A

NZ PorA P1.4 -> porin A

105
Q

What is fHbp?

A

Factor H binding protein

It binds factor H which enables bacterial survival in the blood

106
Q

What is NHBA?

A

Neisseria heparin-binding antigen

Binds heparin which may promote bacterial survival in the blood

Present in virtually all Men strains

107
Q

What is NadA?
(3)

A

Neisserial adhesin A

Promotes adherence to and invasion of human epithelial cells

May be important for colonisation

108
Q

What is NadA?
(3)

A

Neisserial adhesin A

Promotes adherence to and invasion of human epithelial cells

May be important for colonisation

109
Q

What is NZ PorA P1.4?

A

Porin A

An outer membrane vesicle found in NZ strain outbreak

A major outer membrane vesicle protein-induces strain specific bactericidal response

110
Q

What is NZ PorA P1.4?

A

Porin A

An outer membrane vesicle found in NZ strain outbreak

A major outer membrane vesicle protein-induces strain specific bactericidal response

111
Q

Why were four different antigens included in the MenB vaccine?

A

Combining antigens that target different steps of meningococcal pathgenisis is likely to help optimise MeB vaccine effectiveness

112
Q

Who gets the MenB vaccine?

A

All babies born afer Oct 1st

113
Q

What are your conclusions on Invasive meningococcal disease epidemiology?

A

Substantial declines in incidence since MenC in 2000

Re-emergence of MenC between 2014-2017 but may be in decline again (not enough stats to say yet)

Emergency of previously rare serogroups W and Y with small but increasing numbers

Further monitoring needed for MenB and MenACWY

114
Q

Talk about pneumococcal meningitis, when does it occur, what causes it?
(3)

A

Pnumococal meningitis caused by S. pneumoniae (one of 90 capsular types)

2/3 of invasive disease is caused by 8-10 of these serotypes

It is only really indicated where there is underlying immunological problems or foci of infection elsewhere e.g. otitis media or pneumonia which invades through lung into meningitis

115
Q

How frequent is Pneumococcal meningitis?
(2)

A

36.5 (2018) to 24.7/100,000 in 2023 in adults >65
- incidence decreasing

14/100,000 children <2 between 2022-2023

116
Q

Comment on the mortality of IPD?

A

18/100,000 adults >65
0.4/100,000 <2

Mortality significantly higher in elderly

117
Q

What is the carriage rate of pneumococcal meningitis?

A

Preschool children 60%
Primary school 35%
Secondry 25%
Adults who have children (18-29%)

118
Q

What are the requirements for diagnosis of invasive pneumococcal disease, what should be done upon diagnosis?

A

Isolation of S. pneumoniae from a normally sterile site:
- blood, CSF, joint/pleural/pericardial fluid

Its a notifiable disease

119
Q

How frequent was IPD in ireland in 2018, how do we compare to the rest of ireland?

A

514 cases

IR of 10.6/100,000

Ireland is one of the worst countried in europe for IPD, southern europe has very little IPD

120
Q

Comment on trends in IPD vs Pt Age in Ireland

A

Ignoring covid stats:
- IPD in elderly has remained roughly the same regardless of vaccinaion
- IPD in <2 year old has decreased
- IPD has remained the same for all other cohorts

*In general IPD cases have more than doubled between 1999 and 2018 despite vaccination

121
Q

What IPD vaccines are available?

A

PPV23
PCV7
PCV13
PCV15 (not in Ireland)
PCV20 (not in ireland)

122
Q

What IPD vaccines are available?

A

PPV23
PCV7
PCV13
PCV15 (not in Ireland)
PCV20 (not in ireland)

123
Q

What is the PPV23 vaccine?
(5)

A

Pneumococcal Polysaccharide Vaccine

Its on unconjugated vaccine -> not suitable for <2 yr olds

Coverage against 23 serogroups

Recommended for those >65 or immunocompromised

Uptake is really poor especially in elderly

124
Q

What are the PCV vaccines, when were they released, uptake?

A

Pneumococcal Conjugated Vaccines
-can be given to infants >6weeks of age up to 9years

PCV7 in September 2008
PCV13 in September 2010

Uptake has been really good for these vaccines

PCV15 and 20 not available in Ireland yet due to costs but available in other parts of europe

125
Q

What has been the change in burden of IPD since the introduction of the PCVs?

A

There has been a 10% increase in the burden of IPD since the introduction of the vaccines

->PCV7 serogroups decreased in all age groups (down to 0 in <5yr olds)
-> PCV13-7 i.e. the 6 strains not in 7 but in 13 decreased aswell
->non-PCV strains increased

126
Q

What has been the change in burden of IPD since the introduction of the PCVs?

A

There has been a 10% increase in the burden of IPD since the introduction of the vaccines

->PCV7 serogroups decreased in all age groups (down to 0 in <5yr olds)
-> PCV13-7 i.e. the 6 strains not in 7 but in 13 decreased aswell
->non-PCV strains increased

127
Q

Provide stats on the impact of PCV on children <5 years old from 2008 to 2018

A

100% decline in PCV 7

71% decline in PC13-7 strains

61% reduction in all serotypes

214% increase in non PCV 12 serotypes

128
Q

What strains of IPD are we concerned with?

A

PCV15 coverage: 22F + 33F

PCV20 coverage: 8, 10A, 11A, 12F, 15B, 22F + 33F

No coverage: 15A, 15C, 24F, 23B, 38

129
Q

What strains are we concerned with?

A

PCV15 coverage: 22F + 33F

PCV20 coverage: 8, 10A, 11A, 12F, 15B, 22F + 33F

No coverage: 15A, 15C, 24F, 23B, 38

130
Q

Why are we very concerned with 23B?
(3)

A

It accounted for 41% of cases between 2020 and 2021

We also see resistance in this strain

We have no vaccine coverage for it

131
Q

Talk about circulating IMP serogroups in adults >65

A

PCV7 dropped after introduction of vaccine to paediatric schedule

Some of the PCV 13-7 also dropped

6A and 7F dropped

19A and 3 were predominant in 2019 - no change

PPV23 serotype 8 was predominant -> poor uptake of vaccine

15A increased

23B accounted for 1-6% of cases

132
Q

What are the conclusions for IPD epidemiology?
(5)

A

Serotype replacement is evident

15 non PCV serotypes circulating in recent years

Some sero groups not covered in any vaccines

Paediatric vaccination increase burden of non-vaccine serotypes in both adults and children

Increase in IPD in general in adults and elderly

133
Q

What is meant by serotype replacement?

A

The global increase in the incidence of disease caused by non vaccine serotypes

Expansion of non vaccine lineages to partly fill the niche acated by the vaccine type lineages

Threatens to undermine the costly vaccination programme -> makes it pointless

134
Q

Talk about Haemophilus influenzae meningitis, how frequent is it, who does it affevt

A

Used to account for 50% of meningitis cases but now only accounts for 7% or less due to vaccination in 1992

Occurs in infants and children <6, rarely affects adults

7 distinct groups, 6 capsular types (a-f), 1 unencapsulated type NTHI

135
Q

Talk about Haemophilus influenzae meningitis, how frequent is it, who does it affevt

A

Used to account for 50% of meningitis cases but now only accounts for 7% or less due to vaccination in 1992

Occurs in infants and children <6, rarely affects adults

7 distinct groups, 6 capsular types (a-f), 1 unencapsulated type NTHI

136
Q

What Haemophilus Influenzae strains are we most concerned with?

A

Were most concerned with HIb but since conjugate vaccination in 1992 it is no longer the most common strain causing meningitis

It used to be believed that noncapsulated NTHI wasnt associated with disease but it is now our leading strain of Haemophilus influenza meningitis

137
Q

What is the frequency of each invasive Haemophilus influenza disease, how do we compare to europe?

A

NTHI 73%
Hib 9.1%
type f 10%
type e = small proportion

Ireland is again not great compare to other european countries especially southern eastern europe

138
Q

What is the frequency of each invasive Haemophilus influenza disease, how do we compare to europe?

A

NTHI 73%
Hib 9.1%
type f 10%
type e = small proportion

Ireland is again not great compare to other european countries especially southern eastern europe

139
Q

Comment on trends in invasive HI in Ireland

A

Since introduction of the Hib vaccine we have had very little HI meningitis -> <10cases per year since 1999

Even though case numbers remain low they have technically doubled from 1999 (2) to 2018(4)

Hib cases have drastically fallen since Hib vaccine
- there was whaning immunity and thus an increase in cases in the early 2000s

Hib catchup vaccine in 2005 -> Hib numbers reduced again

140
Q

Talk about Haemophilus influenzae invasive disease, how frequent is it, who does it affect, trends, mortality etc

A

58 cases in 2018, an increase of 22.9% on 2017

Children <5 and adults >65 accounted for 66% of cases

increase in the proportion of cases in over 65s -> 25% in 2004 to 50% in 2018

7 deaths with a median age of 73 all due to NTHI

There was only 1 Hib case and it was in an unvaccinated elderly patient

141
Q

In general what are the trends in HI meningitis

A

Type b rapid decrease, lull in early 2000s until booster then fall again

%non-typeable/non-capsular gradually increasing (more than double what it was)

142
Q

In general what are the conclusions on Haemophilus influenzae epidemiology

A

Substantial decline in inidence
Continued efficacy of the vaccine
NTHI now accounts for most disease in Ireland, similar trends outside ireland
Increasing diversity among capsulated strains

143
Q

Talk about S. agalactiae meningitis, what strains, vaccine etc

A

Major cause of neonatal meningitis (GBS)
- early onset <day 6 of life, late onset >day 7

10 serotypes Ia, Ib, II, III, IV, V, VI, VII, VIII, IX - based on polysaccharide capsule

Different strains predominate in different countries

Type III strain of most concern causing 80% of S. agalactiae meningitis and 60% of neonatal sepsis

Vaccine is currently in development

144
Q

Talk about S. agalactiae meningitis, what strains, vaccine etc

A

Major cause of neonatal meningitis (GBS)
- early onset <day 6 of life, late onset >day 7

10 serotypes Ia, Ib, II, III, IV, V, VI, VII, VIII, IX - based on polysaccharide capsule

Different strains predominate in different countries

Type III strain of most concern causing 80% of S. agalactiae meningitis and 60% of neonatal sepsis

Vaccine is currently in development

145
Q

How frequent is S. agalactiae meningitis?

A

Very few cases per year
-> less than 15 a year
-> trending upwards -> 4 in 1999 and 9 in 2018

146
Q

Talk about Listeria Meningitis, strains, who it affects

A

16 serotypes:
- 1a, 1b and 4b are the most common

Occurs in infants <1 month old (listeria food poisoning in mother) and in older adults (whaning immunity)

Often indicates underlying predisposing conditions

> 70yr olds have a x3 higher risk

Pregnant women have a 17x higher risk

147
Q

How frequent is Listeria Meningitis?

A

Very few cases- usually 5 or less per year

Only 17 cases between 2018 and 2022
- very broad age range from 2 weeks to 97 yrs old
- 5 cases were 4b

148
Q

Talk about tuberculous meningitis

A

Results from hematogenous spread of mycobacterium tuberculosis

Meningeall involvment most mared at the base of the brain

Concern only really in HIV patients

Very rare in Ireland with only 12 cases between 2012 and 2022

149
Q

Talk about tuberculous meningitis

A

Results from hematogenous spread of mycobacterium tuberculosis

Meningeall involvment most mared at the base of the brain

Concern only really in HIV patients

Very rare in Ireland with only 12 cases between 2012 and 2022

150
Q

Talk about fungal meningitis

A

Cryptococcus neoformans only really causative fungi

Primary site = lung, invasion

Immunocompromised individuals or those with CD4 cell dysfunction

4.1 Medical Microbiology (30 decks)

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