Bacterial Infections 2

Question 1

TB meningitis is caused by

Answer 1

Mycobacterium tuberculosis (MTb)

Question 2

MTb stanning

Answer 2

can’t be gram stained (b/c of nusual, waxy coating on its cell surface primarily due to the presence of mycolic acid)

test used - Acid-fast bacilli

Question 3

MTb is a ____ pathogen

Answer 3

Facultative intracellular pathogen - lives inside and outside cells

Considered one of the most successful pathogens in history - only lives in humans - have been unable to find a resevar

Question 4

Hallmark of MTb is its

Answer 4

very intricate and elaborated cell wall

very waxy - reason why had to diagnose and kill

layer of heavily modified lipids - cannot use gram staning

Question 5

MT b Killed

Answer 5

1.6 million people in 2017
- mostly due to pneumonia and its complications
- ~5% of TB patients develop TB meningitis
- Mostly children, elderly, or HIV+ patients

Question 6

TB meningitis is a result of

Answer 6

a bloodstream dissemination
- usually coming from the lung
- source site may be latent (lung granulomas)

Question 7

TB meningitis First seeds the

Answer 7

meninges, usually around the base of the skull
- classic triad: headache/fever, malaise, and neck pain

May produce hydrocephalus and cranial nerve palsies

As disease progresses, the parenchyma can be seeded
- forms brain abscesses (can be known as tuberculomas- can be latent for years)

Question 8

tuberculoma

Answer 8

(in brain) immune response - try to wall of to contain infection - but not clear it - later in life can break open

(granuloma - can also be in lungs)

Question 8

TB entry into CNS

Answer 8

Multiple routes of entry

Expresses virulence factors that enable invasion of BMECs
- cross transcellularly [into SAS APCs in - pro inflammatory cytokines - activate endothelial (makes BBB more loose) - also attract immune to control infection into turbucluomas - immune can also already be infected (constant infltration of immune can also cause BBB breakdown)]

Can also survive inside phagocytes
- cross using Trojan horse

Once in parenchyma, recognition induces immune response - BBB breakdown

Question 9

MTb is a ____ pathogen

Answer 9

NOT an opportunistic pathogen – will infect healthy individuals as well!

Question 10

Risk factors for TB meningitis

Answer 10

• Close contacts of a person with infectious TB disease
• Persons who have immigrated from areas of the world with high rates of TB
• Persons who work or reside with people who are at high risk for TB (i.e. hospitals, jails, nursing homes, etc.)
• Immunocompromised individuals (i.e. HIV)

Question 11

It is estimated ____ of the world has latent TB

Answer 11

1/4

No effective vaccine - high priority with rise in MDR [multi drug resistant] TB - treatment also involves months of antibiotics - causes other issues

Question 12

Listeria monocytogenes acquired from

Answer 12

generally contaminated food - port of entry GI tract (mostly gastroenteritis - if healthy can contain it)

Question 13

Treponema pallidum acquired from

Answer 13

generally sexually transmitted

Question 14

Borrelia burgdorferi acquired from

Answer 14

tick-borne

Question 15

Burkholderia pseudomallei acquired from

Answer 15

tropical climate, associated with water

Question 16

L. monocytogenes morphology

Answer 16

Gram-positive bacillus

Facultative intracellular bacterium – can live both free or inside other cells

Has 12 recognized serotypes

Question 17

L. monocytogenes serotypes

Answer 17

(based on presence of 2 antigens), three of which (1/2a, 1/2b, and 4b) cause most (95%) human illness

Question 18

L. monocytogenes burden

Answer 18

Worldwide burden (2010) ~24,000 cases with 5,500 deaths

In US ~1,600 cases yearly with ~260 deaths

Question 19

L. monocytogenes cycle food to brain

Answer 19

Gastroenteritis in healthy individuals

CNS infection in immunocompromised
individuals

Abortions in pregnant women

Question 20

L. monocytogenes Expresses surface proteins that ____

No ___ BUT ____

Answer 20

promote invasion of non-phagocytic (end/epithelial) cells

No capsule, easily internalized by phagocytes

BUT Once intracellular, it escapes the vacuole (phagosome - into cytoplasm) and replicates in the cytosol

Question 21

L. monocytogenes can disseminate from cell-to-cell using

Answer 21

actin comets

Question 22

L. monocytogenes invasive infection is a

Answer 22

slow process, involving an asymptomatic phase

Healthy individuals can control and clear infection

Question 23

Ways L. monocytogenes enters the brain

Answer 23

1) from the bloodstream – it can induce its own phagocytocis by BMECs, and once inside it induces immune signals and activation of BMECs

2) from infected contiguous tissue – once inside a cell, it can disseminate through actin comets that propel the bacterium from one cell into the neighboring cell

3) Trojan horse – not only can use phagocytes [survives inside phagocites] to move between organs and spread, but it can use them to cross as a passenger into the brain parenchyma

Question 24

Most common manifestation of L. monocytogenes

Answer 24

is ventriculitis, probably because ease to get in through choroid plexus - hydrocephalus

Question 25

What is the/a consequence of ventriculitis?

Answer 25

hydrosphelus

Question 26

L. monocytogenes vaccine

Answer 26

No vaccine – very low burden, but would be very useful for at-risk groups

Question 27

At risk groups for L. monocytogenes

Answer 27

- Pregnant women and their newborns - Older adults (age >65) - People with weakened immune systems

Question 28

L. monocytogenes treatment

Answer 28

Easily treatable with antibiotics, but needs to be diagnosed early on - Infection is common, but disease is rare!

Question 29

T. pallidum morphology

Answer 29

Corkscrew-shaped (spirochete) bacterium very obvious

Question 30

Spirochetes surface

Answer 30

is very different from other bacteria, hence aren’t classified as gram negative or positive

Question 31

T. pallidum host

Answer 31

only known hose - humans (only recently found way to culture) Can’t be cultured on lab – hindered research into pathogenesis and in turn, into vaccine development

Question 32

T. pallidum neurological manifestations

Answer 32

Can cause multiple neurological manifestations – meningitis may not be of clinical significance (just low headache) neurosyphilis - late manifestation of the disease

Question 33

T. pallidum gummas

Answer 33

infection can go on for a long time - resulting in gummas (if in bones) - immune system kicks in - severe inflation

Question 34

Neurosyphilis incedence rate

Answer 34

Usually very late manifestation of the disease May occurs in 10% of infected and untreated individuals after 10 – 15 years can ocour at any time - symptoms appear much later

Question 35

Neurosyphilis is clinically

Answer 35

chronic meningoencephalitis (meninges & parachama) , with formation of internal gummas sometimes also affect the spinal cord (meningoencephalomyelitis)

Question 36

prior to Neurosyphilis

Answer 36

that infected persons may transiently develop meningitis - mainly base of skull, affecting cranial nerves (face palsies) - cause recurrent ischemic strokes (due to vascular inflammation)

Question 37

___ allows T. pallidum to penetrate cellular barriers ___ makes T. pallidum very difficult to be recognized by phagocytes thus ____ turning point is when ___

Answer 37

Corkscrew-shape and movement Lacks antigenic proteins (PAMPs) on the surface thus Can move around the body without detection - little inflammation when phagocytes ingest it: It remains extracellular, as phagocytes are able to kill it if they can ingest it – turning point when antibodies are develop - inflammation goes overboard - gummas

Question 38

Evidence suggests T. pallidum can easily go into CNS by ____

Answer 38

disrupting cellular junctions, crossing between the endothelial cells (paracellular route) Depending on the area it crosses (pia arterioles/venules vs BBB) it can reach different areas of the CNS Once on the CSF, if it finds its way down the central canal, it can cross into the spinal cord

Question 39

T. pallidum treatment

Answer 39

Easily treatable with penicillin G (if diagnosed early on), and no cases of resistance have ever been reported Ethics of the Tuskegee Study (not given penicillin - wanted to develop late stages to see late manifestations if the disease)

Question 40

At risk groups for T. pallidum/Neurosyphilis

Answer 40

- Men who have sex with men - People who are HIV positive - Sex workers

Question 41

T. pallidum incidence

Answer 41

in US has increased in the last decade - <3 cases/100,000 in 2000 - ~7 cases/100,000 in 2016 - inc. 4x in recent years sence pandemic Pregnancy testing now routine (some states also require it for marriage certificates)

Question 42

Myelitis is

Answer 42

Infection of the nerves and/or glia of the spinal cord The parenchyma of the spinal cord results in inflammation of the spinal cord

Question 43

Types of Myelitis

Answer 43

acute - not side to side transverse - all nerves from that area and down are effected

Question 44

infectious diseases that cause acute myelitis

Answer 44

bacteria - rare (B. burgdorferi, S. aureus, B. pseudomallei, M. leprae) mainly viruses (Polio or Herpes) most of the time cause is not known - is Idiopathic

Question 45

Burkholderia pseudomallei is the causative agent of

Answer 45

melioidosis, a life-threatening infection with multiple manifestations

Question 46

Burkholderia pseudomallei morphology

Answer 46

Gram-negative environmental bacteria (soil, water, etc.) Shows complex antimicrobial interactions - resistant and if combine antibiotics - weird interactions

Question 47

Burkholderia pseudomallei location

Answer 47

A disease of tropical climates, especially in Southeast Asia and northern Australia [yousto be restricted of oceanea] Research interest due to potential as a bioweapon Incidence in Western Hemisphere unknown – recent cases identified in parts of the Caribbean, Central America, and South America, usually associated with extreme weather events (tropical storms or heavy rainfall)

Question 48

Burkholderia pseudomallei is a ___ pathogen

Answer 48

facultative intracellular pathogen Large array of virulence factors (pilins, adhesins, actin-based motility, etc.)

Question 49

Burkholderia pseudomallei entrance into CNS

Answer 49

Enters and replicates in epithelial cells - Trigeminal Nerve (into CNS) Once inside (also Can multiply within phagocytes), can lyse the cell and infect the next cell down, but can also propagate between adjacent cells through actin comets prefered way - nerve hopping

Question 50

Burkholderia pseudomallei Preferred way to get into the CNS

Answer 50

nerve hoping nasal or throat infection - encephalomyelitis limbs infection - myelitis

Question 51

Burkholderia pseudomallei clinical manifestations

Answer 51

many 1 - 5% of cases affects the CNS [ Very rare - mainly cardiovascular or lungs] Grossly underdiagnosed (lack of tools, training, etc.)

Question 52

Neuromelioidosis Risk factors

Answer 52

Exposure to soil or water in endemic areas (especially during the rainy season) Diabetes mellitus Liver disease, chronic lung disease, chronic kidney disease and thalassaemia (all of which would affect your immune system)

Question 53

Commonalities between Burkholderia pseudomallei; T. pallidum; L. monocytogenes; and MTb

Answer 53

They all have specialized surfaces Can use multiple or unique ways to cross the CNS barriers - L. monocytogenes can invade BMECs directly, then infect contiguous tissue, or use Trojan horse. - The spirochetes use unique shape and motility to “drill” a hole between cellular barriers, including BBB - B. pseudomallei can invade nerves peripherally and spread cell-to-cell back into the CNS. Big challenge, diagnosis!