Swimming with Deadly Amoebas

UPDATE: I posted this article on Mini Amedeo but thought it should be added here, as well.  The article discusses a possible link between N. fowleri infection with the use of Neti Pots.  The article reminds you to only use boiled, distilled or sterilized water with them!  LINKY

This week’s news highlighted the deaths of three young Americans who were infected with the dangerous Naegleria fowleri amoeba.  Apparently, this amoeba rears its ugly head each summer and results in a few deaths among children who enjoy swimming in natural freshwater areas.  Infection is incredibly rare, however.  According to an article by Madison Park on CNN.com, only 2 – 3 cases are seen each year in the United States and the median age of patients is 12.  This means that in the past ten years, there have only been 32 reported cases.  Ms. Park dramatically compares this with the number of reported drowning deaths each year: 36,000.

                The Central for Disease Control (CDC) offers a few tips for preventing infection by the amoeba:

           Don't swim in high temperature, low water level and poorly treated areas

           Use nose clips or hold your nose while swimming

                      Don’t disturb the sediments of shallow water areas

      On the incredibly rare chance that someone becomes infected by this amoeba, symptoms resemble meningitis: high fever, vomiting, headache, neck stiffness.  In fact, when admitted to the hospital, the patient is normally treated as such until a spinal tap reveals the presence of N. fowleri.  

      What then?  Well… 95% of the time, the patient dies approximately 3 – 7 days following infection.  In 1978, one person survived and he is the only one recorded.  

                “The incidence of this disease is very very small, but when it happens it’s tragic.”

-          Francine Cabral, Microbiology professor, Virginia Commonwealth University School of Medicine

So what happens?  In short, while swimming, the amoeba becomes stuck inside the swimmer’s nose.  Unlike a parasite, N. fowleri is not hunting for a human to live inside; its final resting place is purely accidental.  However, once there, the amoeba needs food so it travels to the brain where it begins to eat neurons (brain cells).  A perfect storm of reactions happen then: brain damage due to traumatic neuronal death, reproduction of amoebas, immune system response.  These all cause the brain to swell and eventually choke it and the patient of life.

On this tragic note, one has to ask what types of interventions are available.  Currently, doctors inject amphotericin B (antifungal) into the brain and veins.  Given the extremely high lethality rate, it is not surprising that a few scientists are searching for something better.  

A recent paper from the journal Parasite Immunology discusses how N. fowleri actually brings about the death of individual brain cells.  Doctors say “The brain cells died.”  Scientists want to know how.  

Think about when a building is knocked down.  It’s easy to say “Yup, they tore that building,” but how the building came to be torn down is another matter.  Did they set up strategic explosives?  Did they use a wrecking ball?  

The how is extremely important because if we understand it, we might be able to stop it.  If we know that in order to successfully tear down the building, explosives must be set in exactly five places to weaken the structure, then we can exploit that information if we want to stop the building’s destruction.  The same is true of cells.  If know exactly how the amoeba brings about cell death, we can potentially block the amoeba’s action, which will starve it of nutrients and eventually lead to its death instead of the patient’s.

Okay… let’s discuss a little bit about cell death.

Cells kill themselves all the time.  It’s common, necessary, and very much a part of life.  The most well understood mechanism of cell death is called apoptosis.  The term comes from the Greek words apo (from) and ptosis (falling).  

Signals outside the cell can tell it that it’s time to die.  For example, during development, surrounding cells will tell other cells to die.  We aren’t born with webs between our fingers but they do exist for a time inside the womb.  Signals within the cell can also say it’s time to move on.  The sun damages our skin cells’ DNA or nutrients become too low, the cell will assess the situation and, at some point, finally conclude it’s time to pack it in and kill itself.

Cells are tightly regulated (post HPV: The Cell (cont’d Henrietta)) and if anything goes wrong, it knows to kill itself to protect the surrounding cells from its problems.  Cells are very thoughtful that way.

Anyway, apoptosis is a very logical process.  Following initiation signals (whether those stem from inside the cell or outside the cell), certain proteins are told its time to kill the cell.  These proteins talk to other proteins, which then perform all sorts of functions.  Scientists have worked out the communication signals and know which signals lead to which proteins and who those proteins talk to.  

We know how apoptosis works.  Because we know, we can exploit the predetermined steps that follow once apoptosis has started to potentially stop cell death.  In fact, this is one mechanism that HPV uses to keep diseased cells around.  Normally, infected cells would die upon infection by HPV, but the virus comes with proteins that disrupt the known signals involved in apoptosis and those cells stick around instead of dying.  Tricky virus, huh?  (If you want to read more about HPV, I direct you to the Series: Henrietta Lacks posts)

So, is N. fowleri inducing apoptosis in cells?  Is that how it is causing neuronal cell death?

The answer is no, but we are surprisingly close.

Many other kinds of cell death also exist that are equally organized and somewhat understood.  The authors considered authophagic cell death and necroptosis, as well.  

                They incubated T lymphocytes (a type of white blood cell) with N. fowleri and studied the morphology of the cells before and after.  The cells showed signs of necroptosis: swelling of intracellular organelles, plasma membrane lysis, and condensation of DNA (Figure 29.1).  They also studied various proteins in the cell and found that key proteins involved in apoptosis were not activated.  

In some final experiments, they pre-treated cells with a known necroptosis inhibitor and found that cell death was greatly diminished as compared to untreated cells.

More work needs to be done and large avenue of research will still follow this work, but understanding the how is half the battle to discovering ways to treat infection.  Perhaps one day, we’ll no longer have to read stories about these three dead children.  I want to say to their families that my sympathies are with them – no child should die in such a tragic and innocent way.

Neurons: an electrically excitable cell and that can process and transmit information (from Wikipedia.com)

Apoptosis: programmed cell death

REFERENCES

Park, Madison. “Brain-eating amoebas blamed in three deaths.” www.CNN.com (2011).

Link:  http://www.cnn.com/2011/HEALTH/08/17/amoeba.kids.deaths/index.html?iref=allsearch

Quigley, Rachel. “Brain-eating amoeba claims third victim as man dies after using tap water to clear his sinuses.” www.dailymail.co.uk (2011).

Link:  http://www.dailymail.co.uk/news/article-2027012/Brain-eating-amoeba-claims-victim.html

Song, K. J. et al. “Reactive oxygen species-dependent necroptosis in Jurkat T cells induced by pathogenic free-living Naegleria fowleri.” Parasite Immunology  (2011) 33, pgs 390 – 400.