Bacterial Infections 2 Flashcards
TB meningitis is caused by
Mycobacterium tuberculosis (MTb)
MTb stanning
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
MTb is a ____ pathogen
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
Hallmark of MTb is its
very intricate and elaborated cell wall
very waxy - reason why had to diagnose and kill
layer of heavily modified lipids - cannot use gram staning
MT b Killed
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
TB meningitis is a result of
a bloodstream dissemination
- usually coming from the lung
- source site may be latent (lung granulomas)
TB meningitis First seeds the
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)
tuberculoma
(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)
TB entry into CNS
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
MTb is a ____ pathogen
NOT an opportunistic pathogen – will infect healthy individuals as well!
Risk factors for TB meningitis
- 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)
It is estimated ____ of the world has latent TB
1/4
No effective vaccine - high priority with rise in MDR [multi drug resistant] TB - treatment also involves months of antibiotics - causes other issues
Listeria monocytogenes acquired from
generally contaminated food - port of entry GI tract (mostly gastroenteritis - if healthy can contain it)
Treponema pallidum acquired from
generally sexually transmitted
Borrelia burgdorferi acquired from
tick-borne
Burkholderia pseudomallei acquired from
tropical climate, associated with water
L. monocytogenes morphology
Gram-positive bacillus
Facultative intracellular bacterium – can live both free or inside other cells
Has 12 recognized serotypes
L. monocytogenes serotypes
(based on presence of 2 antigens), three of which (1/2a, 1/2b, and 4b) cause most (95%) human illness
L. monocytogenes burden
Worldwide burden (2010) ~24,000 cases with 5,500 deaths
In US ~1,600 cases yearly with ~260 deaths
L. monocytogenes cycle food to brain
Gastroenteritis in healthy individuals
CNS infection in immunocompromised
individuals
Abortions in pregnant women
L. monocytogenes Expresses surface proteins that ____
No ___ BUT ____
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
L. monocytogenes can disseminate from cell-to-cell using
actin comets
L. monocytogenes invasive infection is a
slow process, involving an asymptomatic phase
Healthy individuals can control and clear infection
Ways L. monocytogenes enters the brain
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
Most common manifestation of L. monocytogenes
is ventriculitis, probably because ease to get in through choroid plexus - hydrocephalus
What is the/a consequence of ventriculitis?
hydrosphelus
L. monocytogenes vaccine
No vaccine – very low burden, but would be very useful for at-risk groups
At risk groups for L. monocytogenes
- Pregnant women and their newborns
- Older adults (age >65)
- People with weakened immune systems
L. monocytogenes treatment
Easily treatable with antibiotics, but needs to be diagnosed early on
- Infection is common, but disease is rare!
T. pallidum morphology
Corkscrew-shaped (spirochete) bacterium
very obvious
Spirochetes surface
is very different from other bacteria, hence aren’t classified as gram negative or positive
T. pallidum host
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
T. pallidum neurological manifestations
Can cause multiple neurological manifestations – meningitis may not be of clinical significance (just low headache)
neurosyphilis - late manifestation of the disease
T. pallidum gummas
infection can go on for a long time - resulting in gummas (if in bones) - immune system kicks in - severe inflation
Neurosyphilis incedence rate
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
Neurosyphilis is clinically
chronic meningoencephalitis (meninges & parachama) , with formation of internal gummas
sometimes also affect the spinal cord (meningoencephalomyelitis)
prior to Neurosyphilis
that infected persons may transiently develop meningitis
- mainly base of skull, affecting cranial nerves (face palsies)
- cause recurrent ischemic strokes (due to vascular inflammation)
___ allows T. pallidum to penetrate cellular barriers
___ makes T. pallidum very difficult to be
recognized by phagocytes thus ____
turning point is when ___
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
Evidence suggests T. pallidum can easily go into CNS by ____
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
T. pallidum treatment
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)
At risk groups for T. pallidum/Neurosyphilis
- Men who have sex with men
- People who are HIV positive
- Sex workers
T. pallidum incidence
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)
Myelitis is
Infection of the nerves and/or glia of the spinal cord
The parenchyma of the spinal cord
results in inflammation of the spinal cord
Types of Myelitis
acute - not side to side
transverse - all nerves from that area and down are effected
infectious diseases that cause acute myelitis
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
Burkholderia pseudomallei is the causative agent of
melioidosis, a life-threatening infection with multiple manifestations
Burkholderia pseudomallei morphology
Gram-negative environmental bacteria (soil, water, etc.)
Shows complex antimicrobial interactions - resistant and if combine antibiotics - weird interactions
Burkholderia pseudomallei location
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)
Burkholderia pseudomallei is a ___ pathogen
facultative intracellular pathogen
Large array of virulence factors (pilins, adhesins, actin-based motility, etc.)
Burkholderia pseudomallei entrance into CNS
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
Burkholderia pseudomallei Preferred way to get into the CNS
nerve hoping
nasal or throat infection - encephalomyelitis
limbs infection - myelitis
Burkholderia pseudomallei clinical manifestations
many
1 - 5% of cases affects the CNS [ Very rare - mainly cardiovascular or lungs]
Grossly underdiagnosed (lack of tools, training, etc.)
Neuromelioidosis Risk factors
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)
Commonalities between Burkholderia pseudomallei; T. pallidum; L. monocytogenes; and MTb
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!
