Bacterial Infections 1

Question 1

Community-acquired bacterial meningitis

Answer 1

1. H. influenza
2. S. pneumonia
3. N. meningitidis

– acquired spontaneously
from exposure to environment

Question 2

Nosocomial bacterial meningitis

Answer 2

1. E. coli
2. Other Streptococcus spp
3. Staphylococcus spp

acquired in the hospital or as a
result of an invasive medical procedure

Question 3

Epidemiology / Burden

Answer 3

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

Question 4

(H. influenzae) Common cause of

Answer 4

ear infections in children and bronchitis in adults

Question 5

(H. influenzae) non invasive infections

Answer 5

Epiglotitis (swelling of the throat)
Cellulitis (skin infection)

Question 6

(H. influenzae) Invasive infections

Answer 6

Most often pneumonia (hence namesake)
Infectious arthritis (inflammation of the joint) [inc. chances go into blood]
Bacteremia (bloodstream infection)
Meningitis - most severe

Question 7

Epiglotitis

Answer 7

swelling of the throat

Question 8

Bacteremia

Answer 8

bloodstream infection

Question 9

(H. influenzae) morphology

Answer 9

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

Question 10

Complement-mediated lysis

Answer 10

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.

Question 11

H. influenzae vaccine

Answer 11

makes it so the capsule can be eaten
antibody binds to capsule

Question 12

serotypes of H. influenzae

Answer 12

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

Question 13

gram neg vs pos

Answer 13

Question 14

comma shaped bacteria

Answer 14

Question 15

H. influenzae survives in

Answer 15

the blood stream

Question 16

Main route of entry of H. influenzae

Answer 16

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

Question 17

Once in CSF H. influenzae

Answer 17

• 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!!!

Question 18

Protection against Hib is dependent on

Answer 18

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!).

Question 19

Hib vaccine – is the

Answer 19

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!)

Question 20

H. influenzae Transmission occurs through

Answer 20

“fomites” – objects that carry the pathogen (i.e. respiratory droplets
or amniotic fluid)

Question 21

Groups at risk for H. influenzae

Answer 21

• 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

Question 22

S. pneumonia

Answer 22

Gram-positive diplococci (pairs of cocci)

Encapsulated, > 90 types of capsules

Question 23

S. pneumonia Common cause of

Answer 23

ear and sinus infections

Invasive/ when go in organs:
* Most often pneumonia
* Bacteremia (bloodstream infections)
* Meningitis (pneumococcal meningitis)

Question 24

main causative agent of bacterial meningitis in US

Answer 24

S. pneumonia

Question 25

S. pneumonia Initially colonizes ___ then ___

Answer 25

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

Question 26

Post-mortem evidence suggests preferred site of entry to CNS for S. pneumonia is

Answer 26

is the pial arterioles and venules, NOT the choroid plexus why - mabey not have specific R there

Question 27

S. pneumonia vaccine

Answer 27

Pneumococcal vaccine (PCV)

Question 28

S. pneumonia Transmission

Answer 28

by fomites between infected and uninfected, or autoinoculation if colonized

Question 29

S. pneumonia pattern

Answer 29

seasonal There is a temporal pattern – most common during winter and early Spring

Question 30

S. pneumonia risk factors

Answer 30

- 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)

Question 31

Most common cause of bacterial meningitis in children and adolescents

Answer 31

N. meningitidis everywhere - even in belt - but different strains in US vs Africa - hard to have 1 vaccine

Question 32

N. meningitidis 10% of the population has

Answer 32

it as a commensal (symbiosis relationship) most adults no longer carry it - yousto be part of flora - only in humans

Question 33

N. meningitidis Cause invasive infections known as meningococcal diseases:

Answer 33

- Meningococcemia (bloodstream infection) - Meningococcal meningitis

Question 34

N. meningitidis morphology

Answer 34

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

Question 35

Only causative agent of bacterial meningitis epidemics

Answer 35

N. meningitidis - Associated with crowding (dorms, barracks, etc.) - Epidemics happen yearly on the meningitis belt

Question 36

N. meningitidis Colonizes

Answer 36

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).

Question 37

Post-mortem evidence suggests ___ is the main entryway of N. meningitidis into the CNS

Answer 37

post-capillary venules and veins are the

Question 38

Meningococcal vaccines are avalabe for

Answer 38

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

Question 39

In collaboration with WHO, CDC leads an international consortium called MenAfriNet

Answer 39

subtype A monovalent vaccine specifically made to be affordable (targeting the main causative agent of epidemics there)

Question 40

N. meningitidis exposure through

Answer 40

Droplets or direct mechanical introduction

Question 41

N. meningitidis pattern

Answer 41

Also shows temporal pattern, but can occur throughout the year

Question 42

N. meningitidis risk factors

Answer 42

- 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)

Question 43

Common themes in N. meningitidis, S. pneumonia, H. influenzae

Answer 43

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