Pathogens of the Central Nervous System
Naegleria fowleri
What is it?
Though commonly referred to as an
amoeba, it is actually a free living
excavate form of protist.
Where does it live?
It is typically found in warm bodies of
fresh water, but can also be found in
the soil. It is found in 70% of US lakes.
What are its states?
It has three states:
•A Cyst state: found when it is exposed to unfavorable
conditions. Can help the organism evade immune detection
•A Trophozoite state: the reproductive stage, it is the state in
which the organism divides through binary fission as well as
travelling by pseudopodia, which are round processes filled with
granular cytoplasm. It is in this state that if in the human body
it will phagocytize red and white blood cells as well as tissue
•A Flagellate state: occurs when the organism is exposed to
changes in ion concentration.
cyst, trophozoite, flagellate
Rabies virus
What is it?
The virus is a negative sense ssRNA
enveloped virus with a cylindrical
morphology. It is a member of the
Rhabdoviridae family and the
Lyssavirus family and is neurotropic.
How is it transmitted?
Rabies is zoonotic and is usually
transmitted through the bite of an
infected animal.
Virulence Factors
•Has the ability to maintain neuronal
survival. Allows the host to survive and
pass on the virus
•White the mechanism is unknown, it it
known that the glycoproteins which
make up the viral membrane allow for
infection of nervous tissue
Pathogenesis
The organism enters the immune system through the
olfactory mucosa and the cribriform plate of the nasal
tissues usually from inhalation of warm water infested
with the organism. It has a unique sucking apparatus
which is uses to consume tissue. It immediately
causes necrosis and hemorrhaging of the olfactory
bulbs. It then travels by climbing along the nerve
fibers leading into the brain. Once there it consumes
brain tissue bit by bit. When it become pathogenic it
causes primary amoebic meningoencephalitis (PAM).
Less then 1% of those infected survive.
Diagram of human parthenogenesis and infection
Virulence Factors
•Sucking mechanism used to feed
•Ability to hide from immune system in cyst form
•Surface protein that allows for binding to
fibronectin
•Efficient locomotion
Life Cycle/Pathogenesis
Below is a diagram of the life cycle and pathogenesis as
expressed in dogs. The same pathway and progression of the
virus is seen in humans.
The host is bitten by an infected animal and the virus enters the
tissue. It locates its target cell using a surface receptor. Rabies
is brought into the host cell by the endosomal transport
pathway. The low pH in the endosome allows the membrane
to fuse, emptying the viral RNA into the cytosol. Once inside
the cell the virus quickly replicated eventually budding from
the cell membrane. The virus travels down the neural
pathways to the CNS (the method for this is unknown) and
other organs including the salivary glands. It continues to
replicate eventually killing the host.
How are these
organisms similar?
These organisms are varying and wide ranging
in traits and characteristics. They all enter the
body through different means (although they
all can penetrate the blood brain barrier) and
they all have a different pathogenesis. There is
however a few similarities. Almost all of these
organism go through different states in order
to survive in harsh environments and evade
the immune system after initial introduction
into the body. C. neoforms, C. tetani and N.
fowleri all have a spore-like state by which they
are able to survive the harsh conditions pre-
infection. Another similar trait and probably
one that is most important is the symptoms
that these organisms cause. All of these
organisms cause some form of encephalitis
which is acute inflammation of the brain.
Because encephalitis is an immune response it
tells a lot about why these organisms tend to
be as deadly as they are. These organism force
a strong immune response in their host which
in turn causes destruction of infected tissue.
Because this infected tissue is in the CNS, the
damage is multiplied. All of these organisms
with the exception of N. fowleri (brain-eater),
do far less damage to the CNS themselves then
the immune response that they generate. This
is one main feature that all of these organisms
share in common.
Clostridium tetani
What is it?
C. Tetani is a gram positive, spore
forming, rod shaped bacterium that
looks like a tennis racket under stain.
How is it transmitted?
The bacteria is transmitted through a
deep cut or puncture wound.
Signs and Symptoms
•Sever muscle spasms
•Risus sardonicus
•Trismus
•Seizures
•Respiratory Failure
•Death
Cryptococcus neoformans
What is it?
C. neoformans is an encapsulated yeast of the
family Tremellaceae
Where is it found?
The yeast can be found in plants and animals
and is commonly found in pigeon excrement.
Virulence Factors
•Polysaccharide Capsule- Prevents immune
response including complement,
phagocytosis and production of cytokines by
preventing recognition
•Recent data suggests that the pathogen may
be able to prevent leukocyte migration from
the bloodstream in to the inflammatory site
Life cycle/ Pathogenesis
The bacteria enters the host through a wound and begins to
establish an infection. Once an infection has been
established it produces two neural exotoxins, tetanolysin and
tetanospasmin. These two toxins are distributed to the
circulatory and lymphatic systems of the infected host. They
are taken up by the nerve axons and transported to the
synaptic junction. Once here they rapidly fix to gangliosides
on the presynaptic junction of inhibitory motor neurons.
This prevents the inhibitory motor neurons from firing.
Virulence Factors
•Tetanolysin- toxin, but it unclear how
it effects tetanus infection
•Tetanospasmin- Cause the spasms
that are typical of tetanus infection
•Spores- Allows the virus to survive in
unfavorable conditions
Vaccine
The tetanus vaccine is a toxoid, a toxin
treated with formaldehyde. The toxin
tetanospasm is taken a treated with
formaldehyde which prevents its from
breaking into two pieces (a key part of
its effectiveness). This renders the
toxin useless. It is then injected into a
person which creates an immune
response and establishes immunity.
Life Cycle/Pathogenesis
Infection by the yeast is termed Cryptococcus. Infection is rare
and usually occurs in immunocompromised individuals (usually
AIDS patients). Most infections begin in the lungs and travel to
the CNS results in fungal meningitis. The pathogen enters the
lungs in the form of a dehydrated haploid yeast or as
basidiospores. Once in the lungs the organism can be
rehydrated and gain a characteristic polysaccharide layer. The
organism then begins to reproduce by budding. The yeast soon
spread using its virulence factors to evade the already
weakened immune system. It can spread all over the body, but
seems to always travel to the CNS by unknown means. Once
there it can cause meningoencephalitis or swelling of the CNS.
Headache, confusion, dizziness and death soon occur. The yeast
is not transmissible from patient to patient.