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A - Neuroinfectious Diseases 2 > Bacterial Infections 1 > Flashcards

Bacterial Infections 1 Flashcards

1
Q

Community-acquired bacterial meningitis

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

– acquired spontaneously
from exposure to environment

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2
Q

Nosocomial bacterial meningitis

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

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

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3
Q

Epidemiology / Burden

A

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
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4
Q

(H. influenzae) Common cause of

A

ear infections in children and bronchitis in adults

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5
Q

(H. influenzae) non invasive infections

A

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

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6
Q

(H. influenzae) Invasive infections

A

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

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7
Q

Epiglotitis

A

swelling of the throat

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8
Q

Bacteremia

A

bloodstream infection

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9
Q

(H. influenzae) morphology

A

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

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10
Q

Complement-mediated lysis

A

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.

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11
Q

H. influenzae vaccine

A

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

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12
Q

serotypes of H. influenzae

A

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

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13
Q

gram neg vs pos

A
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14
Q

comma shaped bacteria

A
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15
Q

H. influenzae survives in

A

the blood stream

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16
Q

Main route of entry of H. influenzae

A

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

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17
Q

Once in CSF H. influenzae

A
  • 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!!!
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18
Q

Protection against Hib is dependent on

A

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!).

19
Q

Hib vaccine – is the

A

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!)
20
Q

H. influenzae Transmission occurs through

A

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

21
Q

Groups at risk for H. influenzae

A
  • 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
22
Q

S. pneumonia

A

Gram-positive diplococci (pairs of cocci)

Encapsulated, > 90 types of capsules

23
Q

S. pneumonia Common cause of

A

ear and sinus infections

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

24
Q

main causative agent of bacterial meningitis in US

A

S. pneumonia

25
Q

S. pneumonia Initially colonizes ___ then ___

A

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

26
Q

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

A

is the pial arterioles and venules, NOT the choroid plexus

why - mabey not have specific R there

27
Q

S. pneumonia vaccine

A

Pneumococcal vaccine (PCV)

28
Q

S. pneumonia Transmission

A

by fomites between infected and uninfected, or autoinoculation if colonized

29
Q

S. pneumonia pattern

A

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

30
Q

S. pneumonia risk factors

A
  • 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)
31
Q

Most common cause of bacterial meningitis in children and adolescents

A

N. meningitidis

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

32
Q

N. meningitidis 10% of the population has

A

it as a commensal (symbiosis relationship)

most adults no longer carry it - yousto be part of flora - only in humans

33
Q

N. meningitidis Cause invasive infections known as meningococcal diseases:

A
  • Meningococcemia (bloodstream infection)
  • Meningococcal meningitis
34
Q

N. meningitidis morphology

A

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

35
Q

Only causative agent of bacterial meningitis epidemics

A

N. meningitidis

  • Associated with crowding (dorms, barracks, etc.)
  • Epidemics happen yearly on the meningitis belt
36
Q

N. meningitidis Colonizes

A

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).

37
Q

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

A

post-capillary venules and veins are the

38
Q

Meningococcal vaccines are avalabe for

A

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

39
Q

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

A

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

40
Q

N. meningitidis exposure through

A

Droplets or direct mechanical introduction

41
Q

N. meningitidis pattern

A

Also shows temporal pattern, but can occur throughout the year

42
Q

N. meningitidis risk factors

A
  • 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)
43
Q

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

A

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

A - Neuroinfectious Diseases 2 (9 decks)

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