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44548
Bacterial Meningitis
Beschreibung
Microbiology Mindmap am Bacterial Meningitis, erstellt von maisie_oj am 12/04/2013.
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microbiology
microbiology
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Zusammenfassung der Ressource
Bacterial Meningitis
Pathogenic agents causing meningitis in persons >60 y.o. in the USA
49% - Streptococcus pneumomiae
14% - Listeria monocytogenes
4% - Neisseria meningitidis
3% - Group B Streptococcus
4% - Haemophilus influenzae
26% - Others
Streptococcus pneumoniae
Gram +ve bacteria
More than 90 known serotypes
Major virulence factor - polysaccharide capsule
Cheap and easy to do epidemiological tests
Capsular type-specific antibody is protective
Fastidious - grows best in 5% carbon dioxide
Nearly 20% of fresh clinical isolates require fully anaerobic conditions
Growth requires catalase (e.g. blood) to neutralise the hydrogen peroxide produced by the bacteria
Has a doubling time of 20-30 minutes in complex blood media at 37'C
Culture
Grown on blood agar
Alpha haemolytic
Zone of inhibition around optochin disk
1mm glistening colonies
Phase Variation
Two serotypes - types 3 and 37 are mucoid
Serotyping
The Quellung reaction (swelling reaction) is used
Bacterial capsule swells with binding of a homologous antibody
Mix a loopful of colony with equal quantity of specific antiserum and examine under a microscope at x1000
Cross-reactivity has been observed between capsular types 2 and 5/3and 8/7 and 18/13 and 30
Cross-reactivity has also be observed with E. coli, Klebsiella, H. influenza type b and some viridans Streptococci
viridans = alpha haemolytic
Spontaneously undergo a genetically determined phase variation
Colonies change from opaque to transparent at a rate of 1 in 10^5
Transparent colony type is adapted to colonization of nasopharynx
Opaque colony type is adapted to survival in the blood
Significant difference in surface protein expression between two serotypes
Nasopharangeal carriage may occur in 60% of healthy pre-school children and 30% of healthy children and adults
S. pneumoniae Cell Wall
6 layers thick
Comprised of peptidoglycan with teichioic acids attached to every 3rd N-acetylmuramic acid
Leipoteichioic acids and Teichioic acids
Lipoteichioic acid is chemically identical to teichioic acid but binds to a lipid moiety
Teichioic acid and lipoteichioic acid contain phosphorylcholine - 2 choline residues can covalently bind to each carboyhrate repeat
Choline binds to choline-binding receptors found on almost all human cells
Linked via a C-terminal fatty acyl group
Carbohydrate phosphate polymers, rich in choline
Linked via a phosphodiester linkage
Pili
Hair-like structures which extend from the surface
Contribute to colonization of upper respiratory tract
Increase the formation of large amounts of TNF during invasive infection
Surface Proteins
More than 500
Some are membrane-associated lipoproteins, some are physically associated with the cell wall
Cell-wall proteins include 5 penicillin binding proteins (PBPs), 2 neuraminidases, 1 IgA protease and Choline-binding proteins (CBPs)
Pneumococcal surface antigen (PsaA)
Located underneath the peptidoglycan layer
Attached to cell membrane via an LXXC motif
Penicillin binding proteins (PBPs)
Located in the periplasmic space
Interact with the peptidoglycan
Display a single, N-terminal transmembrane helix
Hyaluronate lyase (Hyl)
Tethered to the peptidoglycan via an LPXTG motif
Choline binding proteins (CBPs)
12 CBPs non-covalently bind to the choline moiety and 'snap' different functional elements onto the bacterial surface
All share a common C-terminal CB domain with different N-terminals
Include PspA (protective antigen), Lyt A/B/C (autolysins) and CbpA (adhesin)
Colonization
ECM Interaction
1st mechanical barrier
Colonization is facilitated by cleavage of bound IgA1 by the IgA1 protease and removal of terminal sialic acids by NanA
Glycolytic enzymes enolase and GAPDH bind human plasminogen (PLG)
Converted to the protease plasmin (PA) and promotes ECM compound degredation
ZmpC activates MMP-9 which has collagenase activity - degrades the ECM
Non-classical surface-associated protein PavA binds to immobilized fibronectin (Fn) and modulates pneumococcal adherence
Cellular Receptors
ECM degradation could be a prerequisite for pneumococci-receptor interactions
Major adhesion of pneumococci is PspC
Interacts with the ectodomain of the human polymeric immunoglobulin receptor (plgR)
PCho mediates pneumococcal adherence to stimulated cells via interaction with upregulated PAFr
The lipoprotein PsaA may act as an adhesin
Pathogenesis
Disease usually caused by spread from the site of colonization
Middle ear = otitis media (non-invasive)
Alveoli = pneumonia (non-invasive)
Blood = bacteraemia (invasive)
Most common in children under 2
Mucocillary escalator - mucus is coughed up and swallowed
CSF = meningitis (invasive)
Most common cause of bacterial meningitis in US - mostly <2 y.o.
Risk Factors
Sickle cell anaemia
HIV intection
Race/Ethnicity
Out-of-home group care
Functional/Anatomic asplenia
Investigation
Surveillance
Measure the burden of invasive pneumococcal disease among all ages
Track emerging antibiotic resistance
Study the impact of pneumococcal vaccines
Reporting
Isolates causing invasive pneumococcal disease (IPD) in children <5 y.o. and are drug resistant are reported as DRSP
Isolates susceptible to antibiotics (or unknown susceptibility) are reported as IPD (not drug resistant)
Critical Data
Demographic
Clinical
Risk Factors
Vaccination History
Compare state rates to other states
Compare among populations within state
Epidemiologic investigation if rates of invasive disease are elevated
Serotyping no longer routinely available
Vaccine
Must contain antigens from multiple serotypes - large amount of diversity
Serotypes are grouped according to antigenic similarities in Danish numbering classification system
Cross-reactivity within serotypes increases vaccine serotypic coverage by 80%
~90% of penicillin-resistant isolates and in serotypes found in 23-valent vaccine (in 1990)
Immune response
Poor correlation between immunological response and protection
Antigens change
23-valent vaccine doesn't elicit a satisfactory immune response in children <2 y.o.
In HIV-positive patients, immune response is decreased in those with a CD4+ count <500 cells/ul
Given to elderly people
79% clinical effectiveness against pneumonia/bacteremia
M Protein Gene Typing
emm gene (Streptococcus pyogenes gene)
Amplified with primers 1 and 2
Encodes the cell surface M virulence protein
Responsible for at least 100 known M serospecificities of S. pyogenes
htrA
S. pneumonia gene
Regulated by the CiaRH 2-component system
Involved in nasopharangeal colonization
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