Madeline Nielson

PRIMARY AMOEBIC
MENINGOENCEPHALITIS
Causitive Agent
Primary amoebic meningoencephalitis (PAM)
is a fatal disease of the central nervous
system caused by the free-living
ameboflagellate Naegleria fowleri. N fowleri is
thermophilic and thrives in water that is above
30 degrees Celsius. The life cycle of the
pathogen happens in 3 stages: A reproductive
trophozoite, a flagellate pear-shape form
(during this stage it doesn’t divide or eat), and
a thick cyst that can survive at the lowest
temperature and can convert back to a
trophozoite when in higher temperatures (1,
2).

Mechanism & Infection

N. fowleri is found in warm freshwater
environments such as lakes, hot springs, and
resort spas. The organism enters the host by
the nasal route when it is inhaled or comes
https://vdsstream.wikispaces.com/file/view/
into direct contact with the nose. N. fowleri
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infects the olfactory mucosa and rises into the olfactory
nerve through the cribiform plate until the organisms reach
the olfactory bulbs of the central nervous system. The
amoeba continues to eat and destroy tissue cells within the brain and cause inflammation. Infection
is rapid once the organisms enter the brain, usually causing death within 7 days. The time from
initial contact to the appearance of illness is usually about 5-7 days and can be as short as 24
hours. The mortality rate of the organism is almost 100%(1,2). Drinking N. fowleri-containing water
has not been recorded to cause PAM(3).

Symptoms(1)
• Severe headache

• nausea

• vomiting

• fever

• change in taste and smell

• nose bleeds

• confusion

• seizures

• coma

• swollen lymph nodes

• stiff neck

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 Madeline Nielson

Virulence
The adherence to host tissues is a critical step in infection. The ability for the trophozoites to attach
to nasal mucosa and chemotactic response are important for disease progression and strong
virulence factors. N. fowleri secretes protease acid and other enzymes that degrade spingomyelin.
Trophozoites lyse and ingest erythrocytes and nerve cells. N. fowleri has developed ways to avoid
the host’s immune system. Naegleria are resistant to lysis by the host’s cytolytic molecules and the
complement system. Innate immunity is possibly more active than acquired immunity in resistance
to the N. fowleri infection. N. fowleri is not only a cause of human disease but can also be reservoirs
for pathogenic bacteria(2). The Center for Disease Control and Prevention (CDC) performed
immunoblot studies that showed IgM as the main antibody produced by the body in 4 patients who
developed PAM. 80% of hospitalized patients in the U.S. had IgG and IgM antibodies but they were
unsuccessful at neutralizing N.
fowleri(3). N. fowleri is also very fast
at causing infection in the host(2).

Risk Factors
PAM is most likely to develop in
young adults and children in good
health(3).N. fowleri has caused
infection in some animals such as
cattle. Not all hosts that are
exposed to N. fowleri accumulate a
fatal disease. Changes in
environmental climate, thermal
pollution of water and the progress
of industrialized areas with nuclear
power plants sanction for greater
growth of N. fowleri(2).

Cases
Although PAM is considered a rare
infection, the amount of cases that
are reported increases every year.
http://www.cdc.gov/parasites/naegleria/state-map.html
The incidence of N. fowleri and PAM
may be under diagnosed around the
world because most cases are
diagnosed after death and many
countries have low autopsy rates. In
the United States, most cases have
been reported in Texas and Florida.
There have been no reported cases in
Utah(1). According to the Center for
Disease Control and Prevention, of
the reported PAM infections from
1962 to 2014, 133 infections have
occurred in all age groups. However,
112 cases have happened in children.
Over 75% of the infections have been
in males.

http://www.cdc.gov/parasites/naegleria/graphs.html

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 Madeline Nielson

Diagnostic & Treatment

Because there is no distinctive features that differentiate PAM
from bacterial meningoencephalitis it is important that
clinicians collect information if the patient has had contact
with fresh water recently(3). If PAM is suspected, samples of
the CSF should be taken and immediately observed under a
microscope. Smears of CSF will need to be stained with
Giemsa or Wright stains to show the presence of
trophozoites. The CSF may be gray or yellow in color with
some red cells present. Gram stain is not useful because it is
not a bacteria(2,3). CT scans can show cerebral edema and
hemorrhaging(1).

When the disease is recognized early, the patient should be

http://x-gen.us/wp-content/uploads/2014/03/
amphotericin-e1404224233491.jpg treated with with a polyene antibiotic such as Amphotericin B
that is either fungistatic or fungicidal. The drug should be
administered by intravenous injection followed by oral
dosage. Amphotecirin B is the primary treatment for PAM and has been the main therapy for all of
the subjects that have survived. The drug attaches to the sterols in the fungal cell membrane
causing intracellular parts to leak resulting in fungal death. With the administering of Amphoticirin B,
it is important to monitor renal and liver function, and hemoglobin concentrations. Chills and fever
are not rare following the first few administrations. The most successful documented survival case
was that of a 9 year old girl infected in California by a hot spring. She was successfully treated with
intravenous Amphotecerin B, miconazole, and oral rifampin(1). Over a 4 year follow up she stayed
healthy and free of any neurological deficiency(3).

Preventative Strategies
Amoeba accumulation can be controlled by
adequate chlorination of swimming pools that are
used frequently, especially during warm times of
the year. It isn’t however, possible to chlorinate
large fresh water bodies such as lakes and ponds,
where N. fowleri may amass. In popularly visited
fresh water locations, local public health
authorities may consider monitoring and testing
the water for the free-living amoebae and posting
warnings. Not immersing your head and avoiding
diving in suspicious waters would help prevent
the microbes from entering nasal canal. The only
way to completely avoid PAM is to not enter
foreign waters or any type of water during warmer
times of the year(2). http://grade6thinkshealth.weebly.com/uploads/
4/4/3/5/44356749/8829807_orig.jpg

References
(1) Heggie, TW. 2010. Swimming With Death: Naegleria Fowleri infections in Recreational Waters. Travel Medicine and Infectious Disease.
ElSevier Ltd. 8 201-206.
(2) Marciano-Cabral, F. Cabral, GA. 2007. The immune response to Naegleria fowleri amebae and pathogenesis of infection. Federation of
European Microbiological Societies. Blackwell Publishing Ltd. Pp 243-259.
(3) Visvesvara, GS. Moura, H. Schuster, FL. 2007. Pathogenic and opportunistic free-living amoebae: acanthamoeba spp., Balamuthia
mandrillaris, Naegleria fowleria, and Sappinia diploidea. Federation of European Microbiological Societies. Blackwell Publishing
Ltd. Pp 1-26.