Bacterial Infections 1 Flashcards
Community-acquired bacterial meningitis
- H. influenza
- S. pneumonia
- N. meningitidis
– acquired spontaneously
from exposure to environment
Nosocomial bacterial meningitis
- E. coli
- Other Streptococcus spp
- Staphylococcus spp
acquired in the hospital or as a
result of an invasive medical procedure
Epidemiology / Burden
Africa has the highest burden
* >1,100/100,000
* ~3/100,000 in developed countries
The meningitis belt
- Region of sub-Saharan Africa that experiences recurring outbreaks
- Weather-related
- Social/cultural influences
- Health infraestructure
(H. influenzae) Common cause of
ear infections in children and bronchitis in adults
(H. influenzae) non invasive infections
Epiglotitis (swelling of the throat)
Cellulitis (skin infection)
(H. influenzae) Invasive infections
Most often pneumonia (hence namesake)
Infectious arthritis (inflammation of the joint) [inc. chances go into blood]
Bacteremia (bloodstream infection)
Meningitis - most severe
Epiglotitis
swelling of the throat
Bacteremia
bloodstream infection
(H. influenzae) morphology
Gram negative coccobacilli
Encapsulated (another layer outside the cell wall) by polysaccharides
Capsule is antiphagocytic and protects against complement-mediated lysis - cells cannot eat it - does not expose antigens - cannot start adaptive immune response
Complement-mediated lysis
The complement system can cause the lysis of bacterial cells through the formation of a Membrane Attack Complex which makes holes in the targeted cell, causing its death.
H. influenzae vaccine
makes it so the capsule can be eaten
antibody binds to capsule
serotypes of H. influenzae
6 standard serotypes (a through f) - Based on the composition of its polysaccharide capsule
and Non-typeable strains lack capsule - cannot be classified - non pathogenic
gram neg vs pos
comma shaped bacteria
H. influenzae survives in
the blood stream
Main route of entry of H. influenzae
fenestrated capillaries of the choroid plexus [Also post-capillary venules and veins (lack BBB).] access CSF/SAS - restricted to minenegies.
Expresses adhesins to bind to endothelial (vesles) and epithelial (chlorid plexi) cells and metalloproteases to degrade ECM (basal membrane), as well as other virulence factors
Once in CSF H. influenzae
- Encapsulated bacteria are a challenge for APCs and macrophages
- Can’t eat them, can’t kill them, can’t activate lymphocytes!
- Depending on health condition of host, death can occur within hours!!!
Protection against Hib is dependent on
concentration of circulating serum antibodies
Adults have concentrations above the threshold [Because eventually immune system will see (ex.nose) why adults not get even if not vaccinated], but infants and young children don’t (unless they are immunized!).
Hib vaccine – is the
type B polysaccharide conjugated to a nonimmunogenic piece of the bacteria.
- Introduced in 1987 in US, now used in 192 countries
- Has resulted in a rapid and substantial decline in the incidence of Hib infection
- Rollover the meningitis belt through WHO programs – Hib no longer a major causative agent (used to be #1!)
H. influenzae Transmission occurs through
“fomites” – objects that carry the pathogen (i.e. respiratory droplets
or amniotic fluid)
Groups at risk for H. influenzae
- Children younger than 5 years; adults older than 65 years
- Unimmunized children and teenagers
- Living in a household with a person with Hib disease
- Spend time together in a room (like daycare) with a person with Hib disease
- Increased risk if any of the above plus underlying medical condition
S. pneumonia
Gram-positive diplococci (pairs of cocci)
Encapsulated, > 90 types of capsules
S. pneumonia Common cause of
ear and sinus infections
Invasive/ when go in organs:
* Most often pneumonia
* Bacteremia (bloodstream infections)
* Meningitis (pneumococcal meningitis)
main causative agent of bacterial meningitis in US
S. pneumonia
S. pneumonia Initially colonizes ___ then ___
respiratory track
After epithelial invasion it disseminates into bloodstream
Due to capsule, it can survive in bloodstream (act as a shield)
Has surface molecules that destroy complement
Binds directly to a receptor on brain endothelial cells [ binds to JAMs in BMECs - sig. cascade [Expresses metalloproteases to degrade ECM] - endocytosis]
- Triggers endocytosis and transcytosis - cross transcellularly
Post-mortem evidence suggests preferred site of entry to CNS for S. pneumonia is
is the pial arterioles and venules, NOT the choroid plexus
why - mabey not have specific R there
S. pneumonia vaccine
Pneumococcal vaccine (PCV)
S. pneumonia Transmission
by fomites between infected and uninfected, or autoinoculation if colonized
S. pneumonia pattern
seasonal
There is a temporal pattern – most common during winter and early Spring
S. pneumonia risk factors
- Unimmunized children
- Defects in immune system (not necessarily HIV)
- Attendance to childcare center
- Anatomic defects in CNS or presence of medical devices (e.g. cochlear implant)
Most common cause of bacterial meningitis in children and adolescents
N. meningitidis
everywhere - even in belt - but different strains in US vs Africa - hard to have 1 vaccine
N. meningitidis 10% of the population has
it as a commensal (symbiosis relationship)
most adults no longer carry it - yousto be part of flora - only in humans
N. meningitidis Cause invasive infections known as meningococcal diseases:
- Meningococcemia (bloodstream infection)
- Meningococcal meningitis
N. meningitidis morphology
Gram-negative diplococci
4 subtypes (A, B, C and W) main causes of epidemics
- Subtype A main causative agent in meningitis belt
has capsule
Capsule is antiphagocytic, and also inhibits complement
Only causative agent of bacterial meningitis epidemics
N. meningitidis
- Associated with crowding (dorms, barracks, etc.)
- Epidemics happen yearly on the meningitis belt
N. meningitidis Colonizes
respiratory epithelium (first)
then acesses blood stream and survives long time in blood stream
Expresses several pili (long appendages) that binds receptors on surface of brain endothelial cells
one of them triggers reorganization of the membrane [open junctions - paracellular], disrupting cellular junctions, allowing passage of Nm to the CSF by slipping between adjacent cells (paracellular route).
Post-mortem evidence suggests ___ is the main entryway of N. meningitidis into the CNS
post-capillary venules and veins are the
Meningococcal vaccines are avalabe for
5 of the 13 subtypes: A, B, C, W and Y
- in single or combination formulations
No universal recommendation – high costs
- In US a quadrivalent (A/C/W/Y) vaccine is recommended for certain groups (i.e. university students)
- In UK subtype C vaccination since 1998 and subtype B vaccination in 2015
In collaboration with WHO, CDC leads an international consortium called MenAfriNet
subtype A monovalent vaccine specifically made to be affordable (targeting the main causative agent of epidemics there)
N. meningitidis exposure through
Droplets or direct mechanical introduction
N. meningitidis pattern
Also shows temporal pattern, but can occur throughout the year
N. meningitidis risk factors
- Deficiencies in specific immune components: complement pathway, functional or anatomic asplenia, and polymorphisms in the genes for mannose-binding lectin and tumor necrosis factor
- Crowding (i.e. college or military dormitories)
- Active and passive smoking
- Race and socioeconomic factors possible - probably related to above factors
- Certain occupations (i.e. microbiologists working with N. meningitidis)
Common themes in N. meningitidis, S. pneumonia, H. influenzae
Extracellular organisms - if eaten will be destroyed
Express virulence factors that allow them to survive in bloodstream [prerequisite to be in blood]
Can target the endothelia of the brain - mostly direct interactions
Cross at areas that are considered “leaky” [chlorid plexi, post-capulary]
Can be prevented through vaccination
Similar groups at risk
