++
Amebiasis and infections due to Entamoeba species
are discussed in Chapter 341. The ubiquitous, free-living amoebae
of the genera Naegleria, Balamuthia,Acanthamoeba,
and Sappinia are the etiologic agents of rare infections
of the central nervous system and eyes.1Naegleria
fowleri is the agent of primary amebic meningoencephalitis; Acanthamoeba and Balamuthia cause
granulomatous amebic meningoencephalitis; and Acanthamoeba also
can infect the eye, resulting in amebic keratitis.2-4 Recently, Sappinia
diploidea, another free-living amoeba that is normally
found in soil contaminated with herbivore feces, has been identified
as causing encephalitis in a healthy young man.5Naegleria,
Balamuthia,Acanthamoeba, and Sappinia have
trophozoite and cyst stages; in addition, Naegleria has
a flagellate stage. For Naegleria, only trophozoites
are found in tissues. Naegleria trophozoites are
10 to 30 μm in diameter and have a clear nucleus
with a prominent central dense nucleolus and cytoplasmic pseudopodia. Acanthamoeba and Balamuthia trophozoites
are of similar size and appearance to Naegleria, but
the cyst form of these parasites may also be observed in tissue.1,6Sappinia trophozoites
are 40 to 80 μm in diameter and have an ovoid or oblong
shape. They appear to be flattened with occasional wrinkles on the
surface, and food vacuoles are seen in cytoplasm. The mature cysts
are 15 to 30 μm in diameter and are round. They have
two adjoining nuclei.1 Unequivocal identification
of these amoebae is not routine, and specimens should be referred
to a qualified protozoologist for confirmation.
++
Almost every example of acute primary amebic meningoencephalitis
reveals a recent patient history of swimming in fresh or brackish water.
The organisms probably gain access to neural tissue via the nasal
mucosa and the cribriform plate. There have been several epidemics
in which the same swimming facility was the focus of infection.
This disease has been reported in England, the Czech Republic, Australia,
Virginia, Texas, and Florida. Naegleria fowleri has
been isolated from soil and the bottom sediment of lakes and pools
from all parts of the world. It also has been reported in thermally polluted
water, where it can reproduce at temperatures up to 46°C (114.8°F).
Seroepidemiologic studies demonstrate that most young adults in
the southern United States have agglutinating antibodies against Naegleria.7,8
++
Granulomatous amebic encephalitis caused by Acanthamoeba affects
those who are immunocompromised and debilitated, whereas Balamuthia causes
a subacute to chronic infection in both immunocompetent and immunocompromised
individuals. These infections have incubation periods that exceed
1 week, and the clinical course, which usually is fatal, can last
for weeks to months. The one known case of granulomatous amebic
encephalitis caused by Sappinia diploidea occurred
in a 38-year-old healthy white male. The patient’s prior medical
history showed a recent frontal sinus infection.5
++
Keratitis caused by Acanthamoeba is most common
in individuals who wear contact lenses. It is also seen as a complication
of other corneal injuries. Corneal infection is associated with
wearing the lenses while swimming in freshwater lakes and rivers
and with using homemade saline solutions to store the lenses.3
+++
Clinical Manifestations
++
Primary amebic meningoencephalitis has occurred in young, previously
healthy individuals between the ages of 2 and 27 years. Most patients
had swum in warm fresh water 2 to 5 days prior to the onset of symptoms.
Very early in the infection, the patient may notice changes in taste
or smell, followed by the abrupt onset of fever, headache, meningismus,
nausea, vomiting, and a rapidly deepening coma. Death follows the
onset of symptoms in approximately 1 week in most patients. Cerebrospinal
fluid usually reveals large numbers of polymorphonuclear leukocytes,
blood, hypoglycorrhachia, and elevated protein levels. Motile amoebae
can be found if the fluid is examined under high magnification on
a warm stage. Most histopathologic studies show severe lytic necrosis
and hemorrhage along the base of the brain in the regions of the
olfactory bulbs and cerebellum.2
++
Granulomatous amebic encephalitis predominantly affects those
who are immunocompromised, although Balamuthia can
cause disease in the absence of identifiable immune defects. Onset
is insidious, and presentation with focal neurological deficits
is common. Presenting signs and symptoms include mental status abnormalities
and seizures in approximately 66% of patients; fever, headache,
and meningismus in 50% of patients; and ataxia or visual
disturbances in 20% of patients. Skin ulcerations or nodules can
be observed for months before the onset of central nervous system
disease. In both subacute and chronic disease, single or multiple foci
of granulomatous inflammation have been reported that involve the
cerebellum, midbrain, and brain stem. Examination of the spinal
fluid usually reveals many mononuclear cells and is nondiagnostic.
Amoebae can be demonstrated in brain biopsies and in skin nodules
or ulcers.2
++
Nongranulomatous amebic encephalitis caused by Sappinia
diploidea occurred only in a 38-year-old previously healthy
man. Presenting signs and symptoms included loss of consciousness
for 45 minutes, bifrontal headache, photophobia, and visual disturbance
for 2 to 3 days. Magnetic resonance imaging showed a solitary 2-cm tumorlike
cerebral mass in the left temporal-parietal region of the brain.
It contained centrally located necrotic and hemorrhagic inflammation
with acute and chronic inflammatory cells but without granulomas
or eosinophils. Trophozoites with distinctive double nucleus were
visible in the mass, but no cysts were seen. Trophozoites often
contained engulfed host blood cells.1
++
Acanthamoeba keratitis is frequently misdiagnosed
as a herpes simplex virus or bacterial keratitis. Symptoms begin
with a foreign-body sensation in the eye followed by severe pain, tearing,
photophobia, and blurred vision. The disease progresses over days
to months, with periods of temporary remission common. Signs include
iritis, a distinctive corneal ring infiltrate in most patients,
and an early dendriform epithelial pattern of inflammation in some
patients. There may be marked inflammatory changes in the anterior
and posterior chambers, and uveitis also occurs. Organisms often
can be found in corneal scrapings or biopsy material.6
+++
Diagnosis and Therapy
++
Consider the diagnosis in a child with meningoencephalitis, a
recent history of freshwater exposure, and cerebrospinal fluid (CSF)
with a neutrophilic pleiocytosis and no bacteria demonstrated by
CSF cultures or Gram stain. The disease can be diagnosed by finding
motile amoebae in the unfixed purulent cerebrospinal fluid. Therapy
for Naegleria infection is not satisfactory. There is
a single well-documented report in which early diagnosis of primary
amebic meningoencephalitis was successfully treated with amphotericin
B by both the systemic and intracisternal routes. It may be necessary
to rapidly achieve therapeutic levels. Many other patients who were
treated with this drug were not helped. Although a 9-year-old girl
was treated successfully with a combination of IV and intrathecal
amphotericin B and miconazole plus oral rifampin, recent use of
this regimen in several other patients was unsatisfactory. In experimental Naegleria meningoencephalitis,
tetracycline markedly potentiated the efficacy of amphotericin B.
There is also little information to guide the treatment of granulomatous
amebic encephalitis. There are interspecies and interstrain differences
in drug susceptibility, but in general, the diamidine derivatives
(propamidine, pentamidine, dibromopropamidine), ketoconazole, paromomycin,
neomycin, 5-flucytosine, and, to a lesser extent, amphotericin B
are active against many isolates.3
++
Sappinia diploidea encephalitis can be diagnosed
by hematoxylin and eosin stains in the formalin-fixed, paraffin-embedded
brain specimens taken from a tumorlike mass. This should identify
trophozoites containing characteristic closely apposed “diploid” nuclei
(in which both nuclei may contain a dark nucleolus) and possibly
engulfed erythrocytes. Trophozoites stain brightly with Giemsa and
periodic acid Schiff (PAS). The sole patient with S diploidea infection
was successfully treated with antimicrobial therapy consisting of
azithromycin, pentamidine, itraconazole, and flucytosine.1
++
In contrast, Acanthamoeba keratitis has been
successfully treated with aggressive surgical debridement combined
with the frequent (up to nine times per day) application of topical
0.1% propamidine isethionate plus neosporin or oral itraconazole
and topical miconazole. Topical polyhexamethylene biguanide also
has been an effective treatment for this condition in a limited
number of patients.3,4