Swimming with death: Naegleria fowleri infections
in recreational waters
Travis W. Heggiea,b,*
aUniversity of North Dakota, Recreation & Tourism Studies Program, University Mail Stop #7116, Grand Forks, ND 58202,
bUniversity of North Dakota, Great Plains Injury Prevention Research Initiative, Grand Forks, ND 58202, USA
Received 12 March 2010; received in revised form 13 June 2010; accepted 17 June 2010
Available online 13 July 2010
environments such as hot springs, lakes, natural mineral water, and resort spas frequented
by tourists. N. fowleri is the etiologic agent of primary amoebic meningoencephalitis (PAM),
an acute fatal disease of the central nervous system that results in death in approximately
seven days. Previously thought to be a rare condition, the number of reported PAM cases is
increasing each year. PAM is difficult to diagnose because the clinical signs of the disease
are similar to bacterial meningitis. Thus, the key to diagnosis is physician awareness and clin-
ical suspicion. With the intent of creating awareness among travel medicine practitioners and
the tourism industry, this review focuses on the presenting features of N. fowleri and PAM and
offers insight into the prevention and treatment of the disease.
ª 2010 Elsevier Ltd. All rights reserved.
Naegleria fowleri is a free-living amoeba commonly found in warm freshwater
The relationship between good health and travel has a long
history. The use of mineral spas, pools, community baths,
and hot springs has been popular since Roman times and
eventually provided an important conceptual base leading
to the development of pleasure resorts in Europe over
two centuries ago.1,2These destinations quickly became
popular among upper, middle, and working class people as
a way to escape populated urban areas and industrial
centers.1There was also a strong belief in the curative
powers of these waters that has carried over to modern
times. For example, mineral water treatment is still used to
treat arthritis, fibrositis, neuritis, sciatica, and a range of
In 2007 the global media began reporting on a series of
deaths that threatened to change the healthy image of hot
springs, spas, and other bodies of warm freshwater.3The
reports were tied to the presence of Naegleria fowleri, an
opportunistic free-living pathogenic amoeba protist with
a human fatality rate of almost 100%. Known to exist
globally in warm bodies of water and naturally and artifi-
cially heated aquatic environments, N. fowleri is the
* University of North Dakota, Recreation & Tourism Studies
Program, University Mail Stop #7116, Grand Forks, ND, 58202, U.S.A.
Tel.: þ1 701 777 2978; fax: þ1 701 777 3845.
E-mail address: firstname.lastname@example.org
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/tmid
Travel Medicine and Infectious Disease (2010) 8, 201e206
1477-8939/$ - see front matter ª 2010 Elsevier Ltd. All rights reserved.
etiologic agent of primary amoebic meningoencephalitis
(PAM).4e7PAM is an acute, fulminant, necrotizing and
hemorrhagic meningoencephalitis that leads to death in
approximately seven days.8
The early diagnosis of PAM is crucial to survival but
making such a diagnosis is difficult because the physical
signs of PAM are similar to bacterial meningitis. There is
also little time between onset to death to mount an anti-
body response. Hence, the key to diagnosis rests on clinical
suspicion and awareness of N. fowleri as the etiologic agent
of PAM. The purpose of this study is to review the existing
literature on N. fowleri with the aim of increasing the
awareness and suspicion of N. fowleri and PAM among
physicians, the tourism industry, and practitioners of travel
medicine. This is important if the rapid diagnosis of future
incidents is to be made and the effectiveness of treatment
Origin and epidemiology
N. fowleri was first identified as a human pathogen in 1965
when it was described by Fowler and Carter in Australia.9
One year later in 1966, three more fatal cases were
reported in Florida.10In each of the Australian and Florida
cases, N. fowleri was acquired while swimming.11Since
that time N. fowleri has been found in warm, fresh or
brackish water including swimming pools, ponds, lakes,
streams, hot springs, thermally polluted water, and
sewage. Warm water does not have to be contaminated to
contain N. fowleri as the amoeba is a free-living organism.
As such, N. fowleri has been found in aquatic environments
frequented by tourists in Thailand and Japan, in swimming
areas along rivers in Italy, in swimming pools and streams in
Belgium and the former Czechoslovakia, in swimming pools
in England and New Zealand, in hot springs in California and
New Zealand, and in warm freshwater lakes throughout the
southern United States.2,11e20
N. fowleri is a free-living amoeba. Until the report from
Fowler and Carter in 1965, free-living amoeba were
considered nonpathogenic.21N. fowleri is also thermophilic
and proliferates in water when the ambient temperature
increases above 30?C.8As a result, N. fowleri will thrive
during summer months or any other time of year when the
ambient temperature is high.8The lifecycle of N. fowleri
exists as three forms.21The first form is an invasive,
reproductive trophozoite (amoebic-form) that is limax or
shoe-shaped measuring 7e20 mm.21This form is the most
common form isolated in clinical specimens. It has a clear
nucleus and a dense, prominent central nucleolus. This
trophozoite form thrives best in temperatures ranging from
35 to 46?C but transforms into a resistant cyst when the
food supply diminishes or growth conditions become
adverse.8,22The second form is a flagellate pear-shaped
form that is motile by means of two flagella attached at its
wider end.21This is a short transitory form during which the
amoeba does not divide or feed. The third form is a thick,
double-walled cyst. The cyst is usually spherical with
a thick double-walled endocyst and a closely apposed thin
ecocyst measuring approximately 9 mm in diameter.8,21The
cyst form of N. fowleri can survive much lower tempera-
tures but is always potentially infective since it can easily
convert (excyst) to the trophozoite form once it is in
a suitable environment.21
Mechanisms of pathogenisis and clinical
N. fowleri is not considered an opportunistic pathogen
because it typically presents in healthy individuals. In fact,
PAM often occurs in healthy immunologically intact children
and young adults who were exposed during recreational
activity in warm bodies of freshwater.4,21,22The organism
enters the humanhost via the nasalroute when it is splashed
or jumping into water is common but N. fowleri can become
motile even if the victim is submerged under water for any
time. Upon entering the nasal cavity, N. fowleri infects the
olfactory mucosa and ascends the olfactory nerve through
the cribiform plate until the organisms reach the olfactory
bulbs of the central nervous system.24e26Within the olfac-
tory bulbs, N. fowleri induces an intense inflammatory
response associated with lytic necrosis and hemorrhage.4
This is largely due to the amoeba developing amoebas-
tomes (sucker-like appendages) that eat and destroy tissue
cribriform plate of children and young adults places them at
higher risk to PAM.27
Patients presenting with PAM are difficult to diagnose
because there is no distinctive clinical feature that differ-
entiates PAM from other meningoencephalitides such as
awareness and the need to know the patient’s recent expo-
typically presenting with PAM and Table 2 presents case
studies illustrating the rapid nature of the disease and the
complicated nature of diagnosing the condition. The time
from initial contact to the onset of illness is approximately
5e8 days but may be as short as 24 h.8,28Some of the initial
symptoms include bifrontal or bitemporal headaches not
responsive to analgesics and fevers ranging from 38 to
41?C.21An alteration in taste or smell or even rhinitis can be
Symptoms presenting with N. fowleri infections.
? Severe headache (usually frontal or bitemporal)
? Nuchal rigidity
? Alteration in taste or smell
? Positive Kernig and Brudzinski signs
? Photophobia (in the late stages)
? Swelling and fluid buildup in the brain
? Nose bleeds
? Swollen lymph nodes
? Rapid and shallow breathing
? Cranial nerve palsies
202 T.W. Heggie
Case 1: Italy Source: Cogo et al.14
A 9-year old male was admitted to hospital with a one day history of fever and a persistent headache on the right side.
The patient had swam and played in a swimming hole along the Po River approximately 10 days prior to the onset of
his symptoms. The region was experiencing an unusually hot summer. Upon admission the patient had a temperature
of 38?C, a total leukocyte count of 13,780/mm3, a C-reactive protein level of 1.2 mg/L, and a normal cranial
computed tomographic (CT) scan without contrast. No meningeal signs were present during physical examination. The
patient was also lethargic and a neurologic evaluation determined a Glasgow Coma Scale score of 9. Treatment with
acyclovir and mannitol (0.35 g/kg every 6 h) was started. A few hours later the patient was unresponsive to painful
stimulation and was subsequently intubated and mechanically ventilated. On Day 2 the patient became progressively
sleepy and developed a stiff neck. The patient also developed arterial hypertension and tachycardia. A repeat CT
scan showed a lesion in the right frontal lobe and diffuse cerebral edema. 1 h later severe anisocoria followed by
fixed mydriasis developed. An EEG showed isoelectric activity. On Day 3 a blood analysis showed a total leukocyte
count of 19,600/mm3with 91% neutrophils and a C-reactive protein level of 10.6 mg/L. Empiric therapy with
ceftriaxone and corticosteroids was started. The patient died six days after the onset of symptoms. An autopsy found
a cerebellar tonsillar herniation and soft, easily breakable frontal lobes. Coronal sections of the cerebral hemispheres
showed diffuse and multiple foci of hemorrhagic necrosis in both grey and white matter. A preliminary
histopathologic examination identified a massive and diffuse inflammatory infiltrate, characterized by a high number
of neutrophils, few eosinophils or macrophages, and numerous large clusters of cells that resembled amebic
Case summary of Naegleria fowleri infections.
Case 2: United States (Arizona) Source: Barnett et al.21
A previously healthy 9-year old female presented with a two day history of vomiting and headaches. She was initially diagnosed
with flu-like syndromes and returned to her summer home along the Colorado River. However, two days later the patient
became obtunded and returned for medical care. The patient had injected conjunctiva and swollen tonsils. She also had
a heart rate of 128/min, respiratory rate of 26/min, a temperature of 39.9?C, cervical adenopathy, and nuchal rigidity.
Neurological evaluation revealed an imtermittently obtunded and agitated child with a Glasgow Coma Score of 10. Deep
tendon responses were normoactive and symmetric with equivocal Babinski signs. Anticonvulsant therapy and intravenous
cefuroxime, acyclovir, and steroids were initiated. A second CT scan showed cerebral edema and basilar meningeal
enhancement. Her neurologic condition deteriorated continued with deepening coma, her pupils were fixed and dilated, and
an EEG was isoelectric. She was pronounced dead four days after the onset of symptoms. A post death investigation
discovered that the patient frequently swam in a ditch near her summer home where she was known to dive and jump into
Case 3: United States (Florida) Source: Centers for Disease Control and Prevention31
An 11-year old male was admitted to hospital with suspected bacterial meningitis. The patient had a four day history of
headache, fever, nausea, confusion, and a faint rash. A cerebrospinal fluid (CSF) sample taken the day after the patient was
admitted found motile amoeba that were later identified as N. fowleri. That same day the patient was treated with
amphotericin B, epinephrine, mannitoll, fluconazole, ceftriaxone, azithromycin, and rifampin. However, the patient died
two days after admittance to hospital. The probable source of exposure was swimming and wakeboarding on a local lake
when the air temperature was 32.8?C.
Case 4: United States (Texas) Source: Centers for Disease Control and Prevention31
A 12-year old male arrived at hospital with a six day history of fever, disorientation, and acting lethargic. The patient had
been attending a summer camp in central Texas where he participated in recreational water activities in a lake bay.
Prior to hospital admission, he had visited the camp nurse three times complaining of illness. The patient’s CSF indicated
opaque appearance, bloody color, a white blood cell count of 1750 cells/mm3, a red blood cell count of 30,750 cells/
mm3, a glucose level of 92 mg/dL, and a protein level of 88 mg/dL. The admitting differential diagnosis included
meningitis, pneumonia, and bacteremia. The patient was treated with amphotericin B, rifampin, and azithromycin but
died 5 days after admission. N. fowleri was later identified in the patient’s CSF sample. The average water temperature
at the lake was 29.1?C.
Case 5: United States (Texas) Source: Centers for Disease Control and Prevention31
A 22-year old male was admitted to hospital with symptoms of photosensitivity, altered mental status, and a sudden
headache starting two days prior. The headache was frontal and described as a constant pressure sensation. A CT scan
of the head without contrast was interpreted as normal. Thus, the admission diagnosis was viral meningitis. The
patient died four days later and N. fowleri was detected in post-mortem brain specimens. The patient had fallen and
ruptured an eardrum while wakeboarding on the same lake as the victim in Case 4 one week prior to hospital
(continued on next page)
Naegleria fowleri infections203
usually present with positive Kernig and Brudzinski signs.8
Photophobia may occur later in the clinical course and be
followed by neurological abnormalities such as lethargy,
confusion, seizures, coma, diplopia, or bizarre behavior.8
Dysfunctions of the third, fourth, and sixth cranial nerves
are common with the third cranial involvement associated
with decerebrate posturing indicative of herniation.21,23
Intracranial pressure typically rises to 600 mm H2O or
higher.8Also, cardiac rhythm abnormalities and myocardial
necrosis has been associated with some cases.29Death can
usually be expected within one week.
The treating physician should request a wet mount
examination of the patient’s unrefrigerated cerebrospinal
fluid (CSF) preferably utilizing a microscope with phase-
contrast optics that will be able to detect the presence of
trophozoites. As previously noted, the ameboid tropho-
zoites will range in approximate size from 7 to 20 mm with
a large centrally placed nucleolus. Any movement of the
trophozoites will most likely be directional and rapid using
eruptive pseudopodia.8If N. fowleri is suspected, a small
drop of sedimented CSF should be mixed with 1 mL of
sterile water in a sterile tube and incubated for
a maximum of 3 h at 37?C. The tube should be examined
frequently for the presence of any pear-shaped organisms
swimming freely and possessing two flagella at its wide
end. The CSF may initially vary in color from grayish to
yellowish-white and may have a touch of red with a few
red cells in the early stage of the disease.8However, as
the disease progresses, the red blood cell count will
increase to as high as 24,600 mm?3.8Wright, Giemsa, or
Trichrome stains can be used to help visualize CSF smears.
A review of the molecular techniques developed for the
specific identification of N. fowleri (primarily done post-
mortem) has been published by Visvesvara et al.8
Pathophysiology of N. fowleri infections
In cases involving N. fowleri infections, the left and right
cerebral hemispheres of the brain tend to be soft, notice-
ably swollen with an exceptional accumulation of fluid.8
Table 2 (continued)
Case 6: United Kingdom Source: Apley et al.32
A nearly 3-year old male was admitted to hospital in early August. The patient had a week long history of a sore throat, mild
irritability, and loss of appetite. One day prior a family physician had prescribed oral penicillin. However, the patient
became progressively ill, vomited all food and liquid, and experienced intermittent pallor with peripheral cyanosis. On
admission the patient was still pale and disoriented. He had pronounced head retraction with obvious neck rigidity and
a positive Kernig’s sign. His optic fundi were normal and an examination of the nervous system showed no localizing signs.
However, the patient’s throat was inflamed with purulent exudates over both tonsils. Pyogenic meningitis was diagnosed and
treatment was started with intramuscular sulphadiazine, penicillin, and ampicillin. Six hours later the patient stopped
breathing and was placed on mechanical respiration. He remained comatose with fixed dilated pupils and no response to
stimuli. Two days later a lumbar puncture yielded a reddish brown and thick fluid with creamy deposit. It contained
amorphous debris, numerous red blood cells, and approximately 3000 white blood cells/mm3of which half were amoebae
and half were leucocytes. Treatment was changed to amphotericin B (0.25 mg/kg in one daily dose given over 3e4 h
intravenously, increasing over a week to 1 mg/kg). This treatment was continued until the death of the patient two weeks
later. Although the weather in the patient’s home area was usually temperate, over the preceding months the region had
experience elevated temperatures. The patient and two close contacts who also became ill were seen playing in muddied
puddles following a thunderstorm.
Drug information and dose recommendations for Amphotericin B.
Drug name: Amphotericin B (Amphocin, Fungizone) is a polyene antibiotic produced by a strain of
Streptomyces nodosus. It can be either fungistatic or fungicidal. It binds to sterols in the fungal cell
membrane causing intracellular components to leak with subsequent fungal cell death.
25e300 mcg IT q48e72 h and increase to 500 mcg as tolerated; alternatively, 0.25e1.5 mg/kg/d IV.
25e300 mcg IT q48e72 h and increase to 500 mcg as tolerated; alternatively, 0.5e0.7 mg/kg/d IV.
1) Antineoplastic agents may increase the chance for renal toxicity, bronchospasm, and hypotension.
2) The risk of renal toxicity is increased with cyclosporine.
3) Corticosteroids, digitalis, and thiazides may potentiate hypokalemia.
1) Monitor renal function, liver function, CBC, and hemoglobin concentrations.
2) Resume the therapy at the lowest level (0.25 mg/kg) when it is interrupted for more than 7 days.
3) Hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving
4) Fever and chills are not uncommon after the first few administrations.
5) Rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock.
204 T.W. Heggie
The leptomeninges are congested and hyperemic with
limited purulent exudates within the sulci, the base of the
brain, brainstem, and cerebellum.8The olfactory bulbs are
exudates.4,8,27,30In addition, the cerebral cortex typically
displays multiple superficial hemorrhagic regions. Most of
the lesions are found in and around the base of the orbi-
tofrontal and temporal lobes, base of the brain, hypothal-
amus, midbrain, pons, medulla oblongata, and the upper
portion of the spinal cord.8CT scans may identify the
obliteration of the cisternae bordering the midbrain and
the subarachnoid space over the left and right cerebral
Primary amoebic meningoencephalitis (PAM) is a severe,
progressive disease with a rapid onset and a high associated
mortality.33Because of the rapid onset and high mortality,
there are only a handful of known survivors. One of the
best-documented survival cases involved a nine year old
female infected while swimming in a California hot spring.
In this case the patient was successfully treated with
intravenous and intrathecal amphotericin B, intravenous
and intrathecal miconazole, and oral rifampin.34Ampho-
tericin B remains the cornerstone treatment for PAM and
has been the primary therapy in all known survival
cases.33,35e37In addition, amphotericin B can be adminis-
tered alone or in combination with other drugs such as
rifampin, azithromycin, and azole drugs such as miconazole
and ornidizole.38Table 3 displays information on the rec-
ommended doses, contraindications, interactions, and
precautions for amphotericin B. The recommended dura-
tion of treatment is 10 days.21,33
Tourist exposure and prevention
N. fowleri is widespread in the natural environment and the
rate of infection after exposure is unknown. There are even
reported cases from arid regions where N. fowleri has been
the vast majority of infections result from activity in warm
freshwater environments. An understanding of N. fowleri is
important for specialists in travel medicine due to the
potential high risk of exposure segments of the tourism
industry have to N. fowleri. PAM is a disease with a rapidly
fatal outcome and even though PAM is still considered a rare
is very possible that the incidence of N. fowleri and PAM is
underdiagnosed worldwide because most cases are diag-
nosed post-mortem and many countries have low autopsy
rates. It is also possible that global climate change is aiding
the establishment of N. fowleri in new environments and
countries it has never been recorded in. Either way, there is
little question that N. fowleri is present in environments
frequented by tourists. In the United States there are over
115 major geothermal spas and thousands of hot springs.2
The presence of N. fowleri was recently identified in high
profile hot springs frequented by tourists in Yellowstone and
Grand Teton National Parks as well as the surrounding
region.39Furthermore, spas and natural hot springs are
increasing worldwide with destinations such as Russia
reporting 3500 springs and the former Czechoslovakia region
having over 1900 mineral springs and spas.2In Thailand,
natural hot springs are a popular tourist attraction valued at
US$ 85 million per year yet visitors need to be extremely
cautious because recent studies found N. fowleri present in
35.3% of 68 sampled Thai hot springs.12
It is recognized that recreational activity in hot springs,
spas, and bodies of warm freshwater can be a serious
source of health complaints. Tourists of all ages who bathe,
swim, or dive in freshwater and untreated pools will
increase their chance of coming into contact with N.
fowleri and contracting PAM. The best method of pre-
venting this is to avoid water-based activities in warm
freshwater environments. If this cannot be avoided, risk
measures that minimize water entering the nose are rec-
ommended. For example, diving or jumping into water
where the presence of N. fowleri is likely should be
restricted or care should be taken by participating indi-
viduals to at least plug their nose or wear a nose plug. The
same caution should be taken for those who are swimming,
water skiing, and wakeboarding. Tourists should consider
not swimming in warm water, especially if it is shallow or
stagnant, as most cases of PAM have resulted from exposure
to water that is 26?C or warmer. The responsible segment
of the tourism industry should also take care to inform their
clientele of the presence of N. fowleri.
Conflict of interest
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206 T.W. Heggie