Central Nervous System 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
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
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
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
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
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
7
Q
What are the two types of meningitis?
A
Acute: single episode, single species, uncompicated meningitis
Chronic: long duration, recurrent, complicated, unusual organisms
8
Q
What organisms can cause meningitis?
A
Bacteria
Viruses
Fungi -> immunocompromised
Parasites
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
10
Q
What is the most common mode of entry into the CNS
A
Via the blood
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)
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)
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
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
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
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)
17
Q
What is the most common type of meningitis?
A
Viral meningitis
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
19
Q
What enteroviruses are most commonly causative of meningitis?
A
Coxsackie viruses and echoviruses
20
Q
How frequent is viral meningitis?
A
Accounted for 78.5% of meningitis cases ni 2015
21
Q
Is viral or bacterial meningitis more serious?
A
Bacterial meningitis is a lot more serious
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
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
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
25
Comment on the trends in viral meningitis in Ireland (in 2018), which viruses are increasing/decreasing etc
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%)
26
What improvements have there been in the NVRL detection methods in recent years?
(3)
PCR testing introduced in 2005 for Enterovirus and human herpes virus
Parechovirus testing introduced in 2013
Enterovirus typing introduced in 2017
27
What improvements have there been in the NVRL detection methods in recent years?
(3)
PCR testing introduced in 2005 for Enterovirus and human herpes virus
Parechovirus testing introduced in 2013
Enterovirus typing introduced in 2017
28
How does bacterial meningitis differ from viral?
(3)
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
29
The WHO has introduced a Roadmap for "Defeating Meningitis by 2030", what five areas does it intend to make improvements in?
Prevention and epidemic control
Diagnosis and treatment
Surveillance
Support and care for patients affected by sequelae (especially neurological symptoms)
Engagement and advocacy
30
What % of bacterial meningitis is culturable, why is this the case?
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
31
In the Lab what do we usually do while waiting for blood cultures if query meningitis?
Run a biofire Film Array
If viral -> report and antimicrobial treatment will be stopped
32
Since the 80s how has bacterial meningitis trended in Ireland
(5)
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%)
33
When was the MenC vaccine introduced?
October 2000
34
When was MenB introduced
Dec 2016
35
When did bacterial meningitis cases begin to trend upwards again
2013 = 150
2014 = 158
36
Compare trends in meningococcal meningitis vs other bacmen
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
37
What is one menbac that has trended upwards recently?
Cases of strep pneumo meningitis have doubled since 2000
38
What are the most common causes of bacterial pneumonia, what are there relative percentages, compare 1999 (prior to MenB) vs 2018?
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)
39
What are three risk factors for meningitis
Prolonged close contact with infected patients
Travel to endemic areas
Immune deficiency, asplenia, HIV, corticosteroids etc
40
How might someone get E. Coli, Klebsiella or Pseudomonas meningitis?
These are much rarer meningitis bacteria in adults
Only really seen from neurological procedures
41
How does colonisation or mucosal invasion lead to meningitis, how does the body fail to defend?
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
42
How does intravascular invasion lead to meningitis, how does the body fail to defend?
Host defences include complement activation and phagoctyic response
Pathogens evade the alternativ complement pathway by their polysaccharide capsule
43
How does the crossing the blood brain barrier lead to meningitis, how does the body fail to defend?
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
44
What are the five most common virulence factors of menbacs?
Capsule
IgA protease
pili
endotoxin
Outer membrane proteins
45
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?
N. meningitidis and H. influenzae have all of the above
S. pneumonia only have a capsule and IgA proteases
46
N. meningitidis, S. pneumoniae and H. influenzae all have capsules, why is this significant?
Capsules aid in the evasion of phagocytosis
All vaccines produced are based on capsular proteins
- they attack capsule, without capsule they loose virulence
47
Both N. meningitidis and H. influenzae have endotoxins why do we need to be concerned with these?
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
48
How do bacteria get throught the tight junctions of the CNS endothelium?
The exact method is unknown
49
What is the most common bacteria meningitis worldwide?
N. meningitdis
50
How common is N. meningitidis carriage, who is it most frequent in?
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
51
How is N. meningitidis spread and when is it most frequently spread?
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
52
How frequent is Meningococcal carriage in Irish students, what were some risk factors for carriage?
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
53
Where is the burden of disease, what age group most affected?
Incidence highest in those under 1 and really up until 4 as well as elderly with an additional peak in late teens
54
How is N. meningitidis spread
Respiratory and throat secretions
- coughing/sneezing
- kissing
- sharing utensils and bottles etc
Crowded settings:
- college dorms
- military barracks
- nightclubs and bars
- crowded households
55
What are the three risk factors for N. meningitidis?
Age:
- 0-5
- 15-24
- 65+
Living in a community setting
Immunocompromised
56
Talk about meningococcal capsular groups
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
57
Comment on the cell wall outer membrane proteins
These are responsible for the serotyping of the bacteria
58
What are meningococcal meningitis serogrouped based on?
Based on acidic capsular polysaccharide
59
What percentage of meningococcal meningitis is caused by Men A, B and C?
Men A, B and C account for 90% of all cases
Certain geographical areas have higher rates etc
60
What might predispose a person to infection with uncommon meningococcal serogroups?
Complement deficiency
61
Comment on the trends in some of the uncommon serogroups such as X, Y, Z and W
These serogroups account for very low numbers but there has been a noticable increase in these serogroups in recent years
62
What are the signs and symptoms of meningococcal meningitis in adults and older children?
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
What is a dislike of bright lights known as?
Photophobia
64
What are the symptoms of meningococcal meningitis in children?
(5)
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
What are the signs and symptoms of meningitis in babies
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
Talk about the meningococcal rash, what is it, how does it happen?
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
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?
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
What percentage of patients does the meningococcal rash appear in?
Only about 52% of patients
69
What is probably the most telltale sign of meningococcal meningits?
Stiffneck accompanied by fever over 38 degrees
Fever>38 seen in 97% of patients
Neck stiffness seen in 82% of cases
70
What are some sequelae that can follow meningococcal meningitis, how frequent are they?
In 10-20% of patients:
- Brain damage
- hearing loss
- learning disability
- amputation
Fatality in 5-10%
71
What percentage of meningococcal meningtis end up fatal?
5-10% of cases
72
Meningitis is a notifiable disease, what does this mean?
It must be reported to the Director of Public Health/Medical Oficer of Health by laboratories and clinicians
73
Why do we report meningitis cases, what are the benefits of surveillance?
(4)
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
What should be done with any close contacts of a positive meningitis case?
Chemoprophylaxis -> theyre given antibiotics whether they are symptomatic or not
Given vaccination if theyve not been given etc
75
What is the mortality rate of adult (purely) meningitis?
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
What is the mortality associated with meningococcal sepsis in adults?
15-40% but this only accounted for 15% of cases
77
How many meningitis outbreaks have there been
Just 1 outbreak in childcare - 2 cases involved
78
How does Ireland's meningococcal rates compare to the rest of Europe, in 2017?
Ireland was one of the worst in Europe, only lithuania had a higher incidence rate
79
Comment on meningococcal trends in Ireland, by serogroup, from 1999-2022
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
Comment on meningococcal trends in Ireland, by serogroup, from 1999-2022
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
Why did detection of all N. meningitidis serogroups fall in 2020 to 2021?
This was due to COVID 19 prevention methods
- mask wearing etc all helped reduce transmission of N.meningitidis
82
What percentage of N. meningitidis cases were only PCR positive i.e. culture negative
37% of cases were detected only through PCR methods - i.e. 37% % of cases could have been missed
83
What is meningococcaemia, what causes it?
(5)
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
What are the three main cytokines that are responsible for GN septic shock/meningococcaemia
TNF-alpha
IL-1
IL-6
85
What are the four main symptoms of meningococcaemia/gram negative septic shock?
Purpura fulminans
Hypotension
Disseminated intravascular coagulation
Multiorgan failure
Death in 40% of cases
86
What N. meningitidis vaccines are available?
MenC + MenC booster
Men B
Men ACWY
87
What N. meningitidis vaccines are available?
MenC + MenC booster
Men B
Men ACWY
88
When was MenC introduced, who is it for?
2000-2002
Introduced or infants and catchup for young adults
89
When was MenC booster introduced, who is it for?
September 2014
Introduced for students in 1st of college
90
When was MenB introduced, who is it for?
December 2016
Introduced for infants
91
When was MenACWY introduced, who is it for?
Introduced in 2019? to replace MenC
- provides protection against additional serotypes
For students in 1st of secondary school
92
The MenC and the MenB vaccines are conjugated, what does this mean, why are they significant?
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
Comment on trends in Men serogroups with introduction of each Men vaccine
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
Talk about the MenC vaccine, when introduced, who suitable etc?
(4)
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
Talk about the Men ACWY vaccine
(3)
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
Who is the Men ACWY vaccine recommended for?
Adolescents
Splenectomy, haemoglobinopathies, coeliac disease
Complement or properdin deficiency
Down syndrome
Immunodeficient e.g. HSCT or SOT
97
Why is there a need for Men ACWY vaccine?
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
What kind of vaccine is the MenB vaccine, how and why is it different to the MenC and MenACWY?
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
the MenB polysaccharide capsule is identical to what?
The surface of human foetal neuronal cells
100
How did we go about developing a MenB vaccine?
we looked for antigens which are surface-exposed, conserved and induce bactericidal activity
Through this we developed Bexsero
101
What is the MenB vaccine called?
Bexsero
102
What is reverse vaccinology
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
How did we go about developing Bexsero?
(3)
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
What are the four antigenic components of Bexsero?
fHbp -> factor binding protein
NHBA -> neisseria heparin-binding antigen
NadA -> neisseria adhesin A
NZ PorA P1.4 -> porin A
105
What is fHbp?
Factor H binding protein
It binds factor H which enables bacterial survival in the blood
106
What is NHBA?
Neisseria heparin-binding antigen
Binds heparin which may promote bacterial survival in the blood
Present in virtually all Men strains
107
What is NadA?
(3)
Neisserial adhesin A
Promotes adherence to and invasion of human epithelial cells
May be important for colonisation
108
What is NadA?
(3)
Neisserial adhesin A
Promotes adherence to and invasion of human epithelial cells
May be important for colonisation
109
What is NZ PorA P1.4?
Porin A
An outer membrane vesicle found in NZ strain outbreak
A major outer membrane vesicle protein-induces strain specific bactericidal response
110
What is NZ PorA P1.4?
Porin A
An outer membrane vesicle found in NZ strain outbreak
A major outer membrane vesicle protein-induces strain specific bactericidal response
111
Why were four different antigens included in the MenB vaccine?
Combining antigens that target different steps of meningococcal pathgenisis is likely to help optimise MeB vaccine effectiveness
112
Who gets the MenB vaccine?
All babies born afer Oct 1st
113
What are your conclusions on Invasive meningococcal disease epidemiology?
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
Talk about pneumococcal meningitis, when does it occur, what causes it?
(3)
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
How frequent is Pneumococcal meningitis?
(2)
36.5 (2018) to 24.7/100,000 in 2023 in adults >65
- incidence decreasing
14/100,000 children <2 between 2022-2023
116
Comment on the mortality of IPD?
18/100,000 adults >65
0.4/100,000 <2
Mortality significantly higher in elderly
117
What is the carriage rate of pneumococcal meningitis?
Preschool children 60%
Primary school 35%
Secondry 25%
Adults who have children (18-29%)
118
What are the requirements for diagnosis of invasive pneumococcal disease, what should be done upon diagnosis?
Isolation of S. pneumoniae from a normally sterile site:
- blood, CSF, joint/pleural/pericardial fluid
Its a notifiable disease
119
How frequent was IPD in ireland in 2018, how do we compare to the rest of ireland?
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
Comment on trends in IPD vs Pt Age in Ireland
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
What IPD vaccines are available?
PPV23
PCV7
PCV13
PCV15 (not in Ireland)
PCV20 (not in ireland)
122
What IPD vaccines are available?
PPV23
PCV7
PCV13
PCV15 (not in Ireland)
PCV20 (not in ireland)
123
What is the PPV23 vaccine?
(5)
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
What are the PCV vaccines, when were they released, uptake?
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
What has been the change in burden of IPD since the introduction of the PCVs?
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
What has been the change in burden of IPD since the introduction of the PCVs?
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
Provide stats on the impact of PCV on children <5 years old from 2008 to 2018
100% decline in PCV 7
71% decline in PC13-7 strains
61% reduction in all serotypes
214% increase in non PCV 12 serotypes
128
What strains of IPD are we concerned with?
PCV15 coverage: 22F + 33F
PCV20 coverage: 8, 10A, 11A, 12F, 15B, 22F + 33F
No coverage: 15A, 15C, 24F, 23B, 38
129
What strains are we concerned with?
PCV15 coverage: 22F + 33F
PCV20 coverage: 8, 10A, 11A, 12F, 15B, 22F + 33F
No coverage: 15A, 15C, 24F, 23B, 38
130
Why are we very concerned with 23B?
(3)
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
Talk about circulating IMP serogroups in adults >65
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
What are the conclusions for IPD epidemiology?
(5)
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
What is meant by serotype replacement?
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
Talk about Haemophilus influenzae meningitis, how frequent is it, who does it affevt
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
Talk about Haemophilus influenzae meningitis, how frequent is it, who does it affevt
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
What Haemophilus Influenzae strains are we most concerned with?
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
What is the frequency of each invasive Haemophilus influenza disease, how do we compare to europe?
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
What is the frequency of each invasive Haemophilus influenza disease, how do we compare to europe?
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
Comment on trends in invasive HI in Ireland
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
Talk about Haemophilus influenzae invasive disease, how frequent is it, who does it affect, trends, mortality etc
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
In general what are the trends in HI meningitis
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
In general what are the conclusions on Haemophilus influenzae epidemiology
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
Talk about S. agalactiae meningitis, what strains, vaccine etc
Major cause of neonatal meningitis (GBS)
- early 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
Talk about S. agalactiae meningitis, what strains, vaccine etc
Major cause of neonatal meningitis (GBS)
- early 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
How frequent is S. agalactiae meningitis?
Very few cases per year
-> less than 15 a year
-> trending upwards -> 4 in 1999 and 9 in 2018
146
Talk about Listeria Meningitis, strains, who it affects
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
How frequent is Listeria Meningitis?
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
Talk about tuberculous meningitis
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
Talk about tuberculous meningitis
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
Talk about fungal meningitis
Cryptococcus neoformans only really causative fungi
Primary site = lung, invasion
Immunocompromised individuals or those with CD4 cell dysfunction
