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APPENDIX B Answers to Case Studies: Under the Microscope

CHAPTER 3

Case Study 3-1: Under the Microscope

1. The most likely cause of the infection is the

atrial ameba Naegleria fowleri.

2. Patients who contract N. fowleri resulting in

colonization of the nasal passages are usually

asymptomatic. However, in this case, the

patient developed primary amebic meningoencephalitis

(PAM). This condition occurs when

the ameboid trophozoites of N. fowleri invade

the brain, causing rapid tissue destruction.

3. N. fowleri has three morphologic forms—

ameboid trophozoite, flagellate trophozoite,

and cyst. The ameboid trophozoites of N.

fowleri are the only form known to exist in

humans. Replication of the ameboid trophozoites

occurs by simple binary fission. The

ameboid trophozoites transform into flagellate

trophozoites in vitro after being transferred

to water from a tissue or culture. The

flagellate trophozoites do not divide but lose

their flagella and convert back into the

ameboid form, in which reproduction resumes.

The cyst form is known to exist only in

the external environment. It appears that the

entire life cycle of N. fowleri occurs in the

external environment; it is primarily found in

warm bodies of water, including lakes,

streams, ponds, and swimming pools. Humans

primarily contract this ameba by swimming

in contaminated water. The ameboid trophozoites

enter the human body through the

nasal mucosa and often migrate to the brain,

causing rapid tissue destruction. Some infections

may be caused by inhaling dust infected

with N. fowleri cysts. The mechanics of how,

when, and where the transition of the cysts to

ameboid trophozoites occurs after the cysts

have been inhaled by a human have not been

described. The ameboid trophozoite is the

diagnostic stage of the infection.

4. Unfortunately, medications used to treat meningitis

and amebic infections are ineffective

against N. fowleri. There is evidence, however,

that prompt and aggressive treatment with

amphotericin B may be of benefit to patients

suffering from infections with N. fowleri,

despite its known toxicity. In rare cases,

amphotericin B in combination with rifampin

or miconazole has also proved to be an effective

treatment. Amphotericin B and miconazole

damage the cell wall of N. fowleri,

inhibiting the biosynthesis of ergosterol and

resulting in an increased membrane permeability

that causes nutrients to leak out of the

cells. Rifampicin inhibits RNA synthesis in

the ameba by binding to beta subunits of

DNA-dependent RNA polymerase, which in

turn blocks RNA transcription. A person can

survive if signs are recognized early but, if

not, PAM almost always results in death. The

survival rate is low, so prevention and early

detection are important. However, because of

the numerous bodies of water that may potentially

be infected, total eradication of N.

fowleri is highly unlikely.

5. Microscopic examination of cerebrospinal

fluid (CSF) is the method of choice for recovery

of N. fowleri ameboid trophozoites (see

Chapter 2).

6. The diagnosis of PAM is difficult because the

infection is often confused with other bacterial

or viral infections because of similarities

in clinical manifestations and laboratory

results. The peripheral white blood cell (WBC)

count is elevated with a neutrophilia in

PAM. Analysis of the spinal fluid reveals an

increased pressure, resulting in a hemorrhagic

specimen. There is also a high white blood

cell count with a neutrophilic predominance

and high red blood cell (RBC) count, as well

as an elevated protein level and a low to

normal glucose level in the spinal fluid. The

Gram stain of the spinal fluid is negative for

bacteria. A basic metabolic panel may show

abnormalities such as hyponatremia associated

with acquired hyperglycemia. PAM is

obvious when the spinal fluid is purulent,

with no bacteria present. It is best diagnosed

with a wet mount examination of the spinal

fluid for N. fowleri along with standard laboratory

tests (e.g., WBC, RBC, glucose, protein,

bacterial and fungal cultures) of the spinal

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