2. NAEGLERIA FOWLERI
• Naegleria fowleri is a free-living ameboflagellate that can cause
Primary Amoebic Meningoencephalitis (PAM) in humans.
• Of the 30+ species of Naegleria, only one demonstrated to be
pathogenic in humans.
• Number of reported cases of N. fowleri infection is small, fatality of
PAM 98%
• Amoeba and resulting meningoencephalitis are a public health
interest.
• Naegleria fowleri - kingdom Protista - Subkingdom: Protozoa
• Part of the same superclass (Rhizopodea) as other parasitic
amoebas including Entamoeba histolytica and Acanthamoeba spp
3. History of Discovery
• Dr. Fowler and Dr. Cutler first described
human disease caused by amoebo-flagellate
in Australia in 1965.
• Their work provided an example of how one
protozoa can effectively live both freely in
the environment and in a human host.
• In the years since a total of 144 cases have
been confirmed in a variety of countries.
• In 1966 Dr. Butt termed the infection
resulting from N. fowleri as Primary
Amoebic Meningoencephalitis (PAM)
4. Morphology
There are three distinct morphological stages in the life cycle of N. fowleri
1.Trophozoite
2.Flagellate
3.Cyst
TROPHOZOITE
• The trophozoite is the infective stage of the amoeba.
• They are ~10-20mm long and contain a nucleus with a
large karyosome surrounded by a halo.
• Trophozoites reproduce by binary fission
• Motile due to round processes filled with granular cytoplasm called lobopodia.
• N. fowleri is a thermophilic organism and can tolerate up to 45°C
• The ideal growth temperature for trophozoites is 42°C
6. • When free-living, trophozoites use a structure called a food-cup to ingest bacteria
and yeast.
• In a human host, ingest red blood cells, white blood cells and tissue.
• Another important structure is the contractile vacuole.
2. Bi-flagellate stage
• entered as a response to a change in pH of the amoeba’s environment.
• In just minutes to a few hours trophozoites differentiate into bi-flagellated cells.
• This change can be induced by placement of trophozoites from culture into distilled
water.
3. Cysts
• In unfavorable conditions - low nutrient, cold temperatures,
desiccation, N. fowleri form cysts.
• These cysts are ~8-15mm long and if they are introduced to the favourable
environment of the human nasal passages can revert to the trophozoite stage and
become infective.
7. LIFE CYCLE
• Occurs in a human host / freely in an aquatic/ soil environment
• In a warm, high nutrient, aquatic environment the trophozoite stage
predominates.
• This is the reproductive stage and a trophozoite that
undergoes promitosis results in two trophozoites.
• If pH changes occur surrounding the organism, the trophozoite can transition
to the more mobile bi-flagellated form.
• If the environment becomes depleted of nutrients, cold, or dry
the trophozoite can encyst to survive the unfavorable conditions.
• Cysts and trophozoites can enter the human through nasal passages, usually
related to water activities.
• Trophozoites are infective, and their penetration of the nasal mucosa and
subsequent migration to the brain results in PAM.
8.
9. Transmission/Reservoir
• Naegleria fowleri have been isolated from soil, swimming pools, cooling
towers, hospital hydrothermal pools and sewage sludge.
• Most reported infections occur after swimming in warm bodies of water.
• Introduction of trophozoites to the nasal passages of humans is the first step
in infection.
• There are no animal reservoirs of N. fowleri.
• The bodies of water and soil contaminated with N. fowleri - physical
reservoirs.
• As a free-living amoeba they can survive out of human hosts as long as the
conditions remain favourable.
10. Pathogenesis
• The period between initial contact with N. fowleri and the onset of clinical signs varies
from 2-3 days to as long as 7-15 days.
• Once symptomatic - progression of PAM is rapid and often fatal.
The portal of entry of N. fowleri into the human host is the nasal cavity.
↓
Trophozoite penetrates the nasal mucosa
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Migrates along mesaxonal spaces of unmyelinated olfactory nerves
↓
Terminating at the olfactory bulb in the subarachnoid space of the brain
↓
This space is quite vascularized - route of dissemination of trophozoites to other
areas of the CNS
11. Clinical signs/ Symptoms
• Abrupt onset of bifrontal or bitemporal headache, fever, nausea, vomiting and
encephalitis
• Sometimes early in the progression of disease changes in smell (parosmia)
and taste (ageusia) damage the olfactory system.
• Progression to coma and seizures is rapid – over a period of 3-7 days.
• PAM often resembles purulent bacterial meningitis and early in its course
differences cannot be distinguished.
• The vast majority of PAM cases end in death (98%), on average only one week
after appearance of the first symptoms.
• cerebral hemispheres are observed to be swollen and olfactory bulbs are
necrotic and hemorrhagic.
• Trophozoites can be found in olfactory nerves and in nasal mucosa.
12. Epidemiology
• Worldwide distribution and occurs most
frequently in tropical areas and during
hot summer months
• 121 cases reported from 1937-2007 in
the United States
• Most cases are diagnosed upon autopsy.
• Australia, and the Czech Republic
reported the majority.
• Major outbreaks, including one south of
Richmond in Virginia
• Tend to be the result of swimming in a
warm body of water.
13. Laboratory Diagnosis
Sample collection
• CSF – 22,000 pus cells/mm3 with counts of several hundred amoebas/ mm3
or brain tissue
• CSF examined by wet mount - Trophozoites
• Grow easily in aerobic culture on 1.5% non-nutrient agar seeded with
washed Escherichia coli – growth appears as areas of clearing on the seeded
agar after overnight incubation.
• Trophozoites are visible microscopically at the edge of the clearing.
• It is transferred to sterile distilled water – Trophozoites convert to biflagellate
in 2 to 4 hours.
• Real time PCR diagnostic methods
14. Treatment
• A few patients have survived with very high doses of Amphotericin B and
Rifampicin.
• Amphotericin B is a polyene compound that disrupts selective permeability of
plasma membranes.
• It is administered intravenously and is something of a ‘last resort’ drug as it
has high toxicity.
• Every one of the 4 documented survivors of PAM have been treated
with Amphotericin B.
• As there is no effective treatment for PAM
