Monday, January 2, 2012

Naegleria fowleri: Thanksgiving in Your Brain

Picture this scenario.  It is a hot summer day and you are hanging out with your friends at the local Walmart causing nothing but trouble trying on clothes you are not going to buy, cruising around on the handicap carts, and playing freeze tag.  Being such a sweltering day you decide to give the Walmart employees a break by heading over to the lake to cool off and take a dip.  Arriving at the beach you shut the car off, swing open the door, and race to the water.  Showing off for your friends you take a giant leap at the edge of the water, go airborne, super-man, and then finish by gracefully diving into the water.  Unfortunately for you, you were not graceful enough and receive a nice sinus flushing.  Other than a minor lingering headache that hangs around the rest of the day, you are fine, for now.  Normally they say what you do not know does not hurt you, but in this case it will kill you.  Funny how a day full of fun and pranks can turn in to one of unbearable pain, vomiting, and death, all thanks to the water-borne amoeba Naegleria fowleri.
N. fowleri life stages
            Unbeknownst to you, the water that flushed your sinuses contained the free-living amoeba N. fowleri.  To make matters worse, it has begun burrowing its way through your skull towards your brain, where it will feast.  N. fowleri was first cultured and documented by the medical scientists M. Fowler and R. F. Carter in Southern Australia 1965 (1).  They, as is common practice today, extracted the amoeba from the dead body of a N. fowleri victim.  The problem with this practice is the patient is all ready dead, so they cannot be helped.  Interestingly N. fowleri exists in three diverse morphological states: the classic amoebic trophozoite, the flagellate, and the cyst.  Trophozoites are the actively breeding, feeding, and infecting morphology of N. fowleri.  In this form it is motile via active sinusoidal/limacine (oscillating) locomotion and reproduces strictly by binary fission (2).  Trophozoites transform into the flagellate form when ionic concentrations are changed, but this has only been observed under laboratory conditions.  Common in nature however is the highly resilient cyst form of N. fowleri, which Trophozoites transform to under nutrient starvation or harsh conditions (1).  Understanding the variant morphological forms and how they lead to a N. fowleri infection may help shed light on possible treatments.
Food-cup shown by red arrow (1).    
            Upon arriving in your nose, and if conditions are right, the amoeba will find itself at the olfactory neuroepithelium, the thin tissue loaded with nerve endings that connects your nasal passageway to your brain.  At this point it is believed that your own cells phagocytose, or engulf, N. fowleri cells, bringing them inside your own cells possibly to generate an immune response (2).  Depending upon the virulence of the N. fowleri strain inoculated in your nose, the amoeba will begin burrowing its way towards your brain, evading an immune response.  It literally follows the nerves directly to the brain, eating tissue as it goes.  In culture N. fowleri has indistinguishable surface structures called “food-cups” that are believed to act as a mouth for the organism, nibbling away at tissue and engulfing it piece by piece in a process called trogocytosis (3).  Within a few days of burrowing N. fowleri will reach your brain, upon which it will kill you.  Reaching the brain is like thanksgiving for the amoeba, as it literally goes on a feeding frenzy gorging on your neural flesh.  N. fowleri also begins reproducing at this point, increasing the number of trophozoites in your skull, amplifying the effects of the infection.
            Upon reaching the cranial cavity and reproducing the infection is now considered primary amebic meningoencephalitis (PAM).  PAM is described as a rapidly fatal disease of the central nervous system (1).  The problem with a N. fowleri infection, PAM, and for you is that detecting the infection early enough is difficult as the symptoms associated with PAM are extremely vague.  With PAM you may experience an intense headache, fever, nausea, vomiting, stiff neck, and potentially a few seizures, all of which would not lead you to the idea that a microbe is slowly burrowing into your brain killing you.  Adding to the confusing symptoms is the fact that you are a healthy, immune-competent young adult; this distinguishes N. fowleri from other free-living amoeba in that it is not an opportunistic infector, but a direct pathogen (2).  In the end you will die a brutally painful death as your brain hemorrhages and you slowly bleed to death
            Depending upon the virulence of the N. fowleri strain eating its way into your brain, your body may or may not develop an effective immune response on its own.  Your first defense is going to be the complement system.  If you are lucky complement will bind to N. fowleri cells, opsonize it (cover the cell surface), and potentially destroy it.  If you are not lucky N. fowleri will simply absorb the complement proteins, negating its immunological effect, or it will express regulatory surface markers that avoid the attention of complement all together.  Next in line are your phagocytic leukocytes, macrophages and neutrophils.  Depending upon the virulence of the amoeba your leukocytes will either destroy the N. fowleri, or be destroyed.  Your body does generate plenty of antibodies against N. fowleri, but without competent cells to react to the antibodies effects they are useless (1).  If your body fails to eliminate the N. fowleri infection on its own you are out of luck.  Currently there are no clinically used drugs that affectively treat a N. fowleri infection.  Doctors have tried using various combinations of Amphotericin B and fluconazole, potent anti-fungal drugs that both target the membrane bound molecule ergosterol, along with rifampin, a drug that prohibits DNA transcription.  The combination has shown promise in the laboratory, but has seen little effect in patients (1).
            While N. fowleri is found in just about every warm body of water possible, the frequency of infection is relatively low with about one case per year (2).  The only way to avoid a possible infection is to stay out of contaminated water all together.  While that is not entirely feasible for some people, I would say you can play the odds, enjoy the water and pray that you are not the one person a year who is brutally killed by the brain eating amoeba, Naegleria fowleri.

Submitted by KH


1.              Cabral, Guy A. "The Immune Response to Naegleria fowleri Amebae and Pathogenesis of Infection." FEMS Immunology & Medical Microbiology. 51.2 (2007): 243-259.
2.              Visvesvara, Govinda S. "Pathogenic and Opportunistic Free-living Amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea." FEMS Immunology & Medical Microbiology. 50.1 (2007): 1-26.
3.              Marciano-Cabral F.  “Cytopathology of pathogenic and nonpathogenic Naegleria species for cultured rat neuroblastoma cells.”  Applied Environmental Microbiology.  51. (1986): 1133-1137.