Imagine you are enjoying a nice, sunny day at a freshwater lake in the middle of July. You and your family then proceed to take a nice, relaxing, swim. You get some lake water in your nose, but you think nothing of it, for now…
Naegleria Fowleri, also known as the brain-eating amoeba, is an amoeba that has over a 97% mortality rate. It is an extremely difficult and expensive disease to diagnose, and is often misdiagnosed for other diseases. It is also extremely quick in killing hosts, most of whom die 7-10 days after the infection.
Fowleri dissection and properties:
Fowleri is concerningly common throughout most environments around the world (oh no). It is mostly found in moist, warm environments, but can survive out of water. Typical environments include hospitals, warm freshwater bodies of water, tap water, swimming pools, drinking water systems, etc. N. Fowleri can also enter your nose when you breathe in dust particles containing its cyst form, which can then transform into its trophozoite form.
It is important to note that N. Fowleri can only enter your brain through your nasal cavity, so any N. Fowleri that comes into contact with your skin, mouth, eyes, etc, will not have a harmful effect. N. Fowleri cannot be spread through people, or survive in salt water.
Fowleri has 3 forms:
- When conditions are too harsh, N. Fowleri goes into a “hibernation” mode, where it becomes dormant/inactive. When in this mode, it is extremely resistant to harsh environments and temperatures because of the thick shell it develops that allows it to survive the winter.
- When it is in non-nutritive conditions, but is in water, it becomes semi-activate. N. Fowleri gets two flagellate (wavy “tentacle-like” limbs that let it move), and adapts a pear-shaped body. This form thrives in summer months and temperatures.
- When in good conditions, it becomes a reproductively active trophozoite, adapting a long and slender structure.
Fowleri infection and pathogenesis:
Once N. Fowleri enters the nose, it penetrates the nasal mucosa (tissue that lines nasal cavity), migrates along olfactory (refers to smell in medical terms) nerves through the cribriform plate (thin bone forming nasal roof, next to brain), until it finds the olfactory bulb (involved with processing smell). N. Fowleri then can reproduce, wreak havoc, and snack on your precious neurons.
Fowleri symptoms:
- Symptoms of meningitis (Meningitis is inflammation of membranes around the brain and spine.N. Fowleri causes intense inflammatory responses. Meningitis symptoms include stiff neck and fear of light, etc)
- High fever
- Headaches
- Coma
- Mental confusion
- Trembling
- Nausea and vomiting
As you can see, N. Fowleri has many symptoms that could be mistaken for something else (i.e. Meningitis and flu). This, combined with the difficulty and cost of diagnosing it (the best way is spinal fluid tap) means patients often don’t get necessary treatment. N. Fowleri is an extremely fast disease, so when a patient is finally diagnosed with it, they are often already experiencing the last, worst symptoms of N. Fowleri, and have permanent brain damage that will kill them.
Fowleri has multiple ways to damage your brain.
1: N. Fowleri triggers a very strong inflammatory response(immune system reaction). Although balanced amounts of inflammation have certain benefits, strong inflammatory responses cause excess damage to tissues, especially the brain. The immune system will try to kill N. Fowleri by spraying toxic chemicals that kill both viruses and cells, while N. Fowleri will continue damaging neurons. Over time, this can lead to swelling and scarring in the brain, crushing tissue, and inhibiting the communication of neurons. Although some N. Fowleri are killed by the immune system, most survive.
2: N. Fowleri can also disrupt the BBB (blood brain barrier–controls what goes into the brain). The disruption of the BBB allows immune cells that are not supposed to be in the brain enter the brain. Unintended immune cells are less gentle to the brain, turning your brain into a war zone and causing excess damage to neurons.
3: N. Fowleri has sucker-like structures called “amoebastomes” that let it engulf neurons and “eat” it.
4: N. Fowleri damages mostly the frontal lobe of your brain, which includes critical parts of your brain like your prefrontal cortex (responsible for high cognitive skills), the Broca region (responsible for language), the motor cortex, etc.
Treatment:
Fowleri treatment must either reduce the excess inflammatory response caused by it, or kill N. Fowleri in the CNS (Central nervous system– includes brian and spine).
- Amphotericin B kills N. Fowleri by triggering it’s apoptosis (programmed cell death) response
- High concentrations of Fluconazole (FCZ), Azithromycin (AZM), and Rifampin (RIF) could kill N. Fowleri in early stages
- Miltefosine (MLT), usually used for breast cancer and leishmania, could be a new treatment for N. Fowleri. Combined with AmB, FCZ, AZM, RIF, and Dexamethasone (DEX), a 12 year old girl was able to make a full recovery by inducing a hypothermic state(core body temp 35 degree C), reducing excess inflammatory response which reduced brain injury.
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