1. Balamuthia mandrillaris and Acanthamoeba spp. are amoebas that can cause infections in humans. 2. Both have life cycles involving cyst and trophozoite stages, and can enter the body through various means causing infections like granulomatous amebic encephalitis (GAE) or keratitis. 3. Diagnosis involves microscopic identification of cysts and trophozoites in tissue samples or fluid, and treatment involves combinations of antimicrobial drugs though outcomes are often poor.

1. Granulomatous Amebic Encephalitis
Acanthamoeba spp. Balamuthia Mandrillaris
Life Cycle:
1. Balamuthia mandrillaris has been isolated from soil and dust, and also
from autopsy specimens of infected humans and animals. B. mandrillaris
has two stages, cysts and trophozoites in its life cycle and lacks a
flagellate stage.
2. The trophozoites replicate by mitosis (nuclear membrane does not
remain intact).
3. The trophozoites are the infective forms, although both cysts and
trophozoites gain entry into the body through various means.
4. it can invade the central nervous system by hematogenous
dissemination causing granulomatous amebic encephalitis (GAE),
disseminated disease or skin lesions.
5. B. mandrillaris cysts and trophozoites are found in tissue; a few cases
have been associated with solid organ transplantation from an infected
donor.
Risk Factors:
HIV/AIDS
Diabetes
Solid organ transplant
Taking an immunosuppressive drug
Liver cirrhosis
Renal failure
Cancer
Open wounds
Life Cycle:
1. Acanthamoeba spp. are ubiquitous in the
environment and have been found in a
variety of sites, including soil; fresh,
brackish, and sea water; field-grown
vegetables; sewage; swimming pools;
contact lens supplies; medicinal pools;
dental treatment units; dialysis machines;
heating, ventilating, and air conditioning
systems; and tap water; mammalian cell
cultures; and vegetables.
2. Acanthamoeba has two stages; cysts and
trophozoites in its life cycle and lacks a
flagellate stage.
3. The trophozoites replicate by mitosis
(nuclear membrane does not remain intact)
4. The trophozoites are the infective forms,
although both cysts and trophozoites can
enter the body through various means.
5. When Acanthamoeba spp. enters the eye it
can cause severe keratitis in otherwise
healthy individuals, particularly contact lens
users.
6. When it enters the respiratory system or
through the skin, it can invade the central
nervous system by hematogenous
dissemination causing granulomatous
amebic encephalitis (GAE) or disseminated
disease.

2. Morphology
The cysts of Balamuthia
mandrillaris are highly similar
morphologically to those of
Acanthamoeba spp. and are also
typically 10—25 µm (mean 15 µm)
in diameter.
Generally these cannot be
reliably distinguished from
Acanthamoeba spp. without
either molecular confirmation or
electron microscopy. The cysts
have two walls apparent in light
microscopy, and do not have
pores: a wrinkled fibrous outer
wall (exocyst) and an inner wall
(endocyst) that may be variable in
shape. A third layer (mesocyst) is
only visible via electron
microscopy. Cysts contain only
one nucleus with a large
karyosome. Cysts may be found in
the brain, skin, lungs and other
organs.
Trophozoites of Balamuthia
mandrillaris are pleomorphic and
measure approximately 15—60
µm. They often produce long
pseudopodia (broader than those
of Acanthamoeba spp.).
Trophozoites contain a large
nucleus with a large, centrally-
located karyosome but no
peripheral chromatin. Binucleate
forms are rare. There is no
flagellated trophozoite stage in B.
mandrillaris.
Morphology
The cysts of Acanthamoeba spp. are
typically 10—25 µm in diameter. The
cysts have a two-layered wall with
pores: a wrinkled fibrous outer wall
(exocyst) and an inner wall (endocyst)
that may be hexagonal, spherical,
star-shaped or polygonal. Cysts
contain only one nucleus with a large
karyosome. Cysts may be found in
the brain, eyes, skin, lungs and other
organs
Trophozoites of Acanthamoeba
spp. are pleomorphic and measure
approximately 15—45 µm. They often
have multiple spine-like processes
called acanthapodia. Trophozoites
contain a large nucleus with a large,
centrally-located karyosome but no
peripheral chromatin. There is no
flagellated trophozoite stage in
Acanthamoeba spp.
Signs and Symptoms:
The symptoms of Balamuthia
infection can begin with a
skin wound on the face,
chest, torso, arms, or legs. If
the infection involves the
brain, the disease it causes
is called granulomatous
amebic encephalitis (GAE).
Diagnosis of Balamuthia
GAE can be difficult because
symptoms are not specific to
GAE. Early symptoms might
include:
● Fever
● Headache
● Vomiting
● Lethargy
● Nausea
Other signs of Balamuthia
GAE might include:
● Mental health
changes
● Seizures
● Weakness
● Confusion
● Partial
paralysis
● Difficulty
speaking
● Difficulty
walking
Signs and Symptoms
Acanthamoeba keratitis varies
greatly from person to person.
Affected individuals may complain
of:
● Eye pain
● Eye redness
● Blurred vision
● Sensitivity to light
● Sensation of
something in the eye
● Excessive tearing
Because there are similarities with
symptoms of other eye infections,
early diagnosis is essential for
effective treatment of Acanthamoeba
keratitis.
Disseminated infection typically
shows up as inflammation of the
lungs or sinuses, and/or skin
infections but has the potential to
spread to the brain. Skin infections
caused by Acanthamoeba can
appear as reddish nodules, skin
ulcers, or abscesses in the skin.
Symptoms of GAE include:
● Mental status changes
● Loss of coordination
● Fever
● Muscular weakness or
partial paralysis
affecting one side of
the body
● Double vision
● Sensitivity to light
● Other neurologic
problems

3. Diagnosis:
Acanthamoeba spp.: Acanthamoeba infection can be diagnosed by detection of trophozoites and cysts on microscopic
examination of stained smears of biopsy specimens (brain tissue, skin, cornea) or of corneal scrapings. Lactophenol blue,
acridine orange, silver, and calcofluor white stains have been used in the diagnosis of acanthamoebiasis on histologic
sections and environmental samples such as pelleted contact lens case contents.
In granulomatous amebic encephalitis cases, trophozoites and cysts are only rarely found in the CSF.
Acanthamoeba can be cultured from clinical and environmental samples in the laboratory on non-nutrient agar with a
Page’s saline and Escherichia coli overlay.
Balamuthia mandrillaris infection is generally diagnosed post-mortem. Outside of molecular detection via PCR and
recently, metagenomic deep sequencing, B. mandrillaris is most reliably detected via immunofluorescence or
immunoperoxidase staining of tissue samples.
Management:
Although there have been more than 200 cases of Balamuthia infection worldwide, few patients are known to have survived
as a result of successful drug treatment. Early diagnosis and treatment might increase the chances for survival.
Drugs used in treating granulomatous amebic encephalitis (GAE) caused by Balamuthia have included a combination of
flucytosine, pentamidine, fluconazole, sulfadiazine and either azithromycin or clarithromycin. Recently, miltefosine in
combination with some of these other drugs has shown some promise. Much more information is needed in treating patients
with GAE due to Balamuthia.
Acanthamoeba keratitis
Medical treatment consists of topical antimicrobial agents, which can achieve high concentrations at the site of the infection.
Because the cyst form may be highly resistant to therapy, a combination of agents generally is used.
Treatment is not standardized, and data is limited. Among the successfully treated
patients with GAE and disseminated disease, all but 2 were given a combination of
antimicrobials. The 2 patients treated with single agent therapy received
sulfamethazine or trimethoprim-sulfamethoxazole (TMP-SMX). If possible,
immunosuppression should be reversed. A combination of pentamidine, an azole
(fluconazole or itraconazole), a sulfadiazine, and flucytosine can be considered.
Combination regimens used include:
● TMP-SMX, flucytosine, and sulfadiazine
● Penicillin G and chloramphenicol (chloramphenicol is no
longer available in the United States)
● Sulfadiazine, pyrimethamine, and fluconazole
● Pentamidine, levofloxacin, amphotericin B, flucytosine,
rifampin, and itraconazole
● Pentamidine, flucytosine, itraconazole, topical chlorhexidine,
and ketoconazole
● Pentamidine and itraconazole
● Fluconazole, sulfadiazine, and surgical debulking
● Ketoconazole, rifampin, and TMP-SMX
● TMP-SMX, rifampin, and surgical debulking
● Oral and topical miltefosine with intrathecal and systemic
amikacin