The trophozoites can occur in two forms: ameboid and flagellate (Table 50-1, Figure 50-1). The size ranges from 7 to 35 µm. The diameter of the rounded forms is usually 15 µm. There is a large, central karyosome and no peripheral nuclear chromatin. The cytoplasm is somewhat granular and contains vacuoles. The ameboid form organisms change to the transient, pear-shaped flagellate form when they are transferred from culture or teased from tissue into water and maintained at a temperature of 27° to 37° C. These flagellate forms do not divide, but when the flagella are lost, the ameboid forms resume reproduction. Cysts are generally round, measuring from 7 to 15 µm with a thick double wall.

TABLE 50-1

Free-Living Amebae Causing Disease in Humans

	Acanthamoeba			Balamuthia	Naegleria
Morphology^a	Trophozoite Cyst Keratitis Acanthamoeba in brain			Trophozoite Cyst Balamuthia in brain	Trophozoite Flagellated form
Disease parameter	Granulomatous amebic encephalitis (GAE)	Acanthamoeba keratitis	Cutaneous lesions Sinusitis	GAE	Primary amebic meningoencephalitis (PAM)
General disease description	Chronic, protracted, slowly progressive CNS infection (may involve lungs); generally associated with individuals with underlying diseases	Painful, progressive, sight-threatening corneal disease; patients generally immunocompetent	Most common in patients with AIDS, with or without CNS involvement; those receiving immunosuppressive therapy for organ transplantation	Chronic, protracted, slowly progressive CNS infection (may involve lungs); generally associated with individuals with underlying diseases	Rare, but nearly always fatal infection; migration of amebae to brain through olfactory nerve; symptoms can mimic bacterial meningitis; death usually occurs 3-7 days after onset of symptoms; clinical suspicion based on history critical
Entry into body	Olfactory epithelium, respiratory tract, skin, sinuses	Corneal abrasion	Skin, sinuses, respiratory tract	Olfactory epithelium, skin, respiratory tract	Olfactory epithelium
Incubation period	Weeks to months	Days	Weeks to months	Weeks to months	Days
Clinical symptoms	Confusion, headache, stiff neck, irritability	Blurred vision, photophobia, inflammation, corneal ring, pain	Skin lesions, nodules, sinus lesions, sinusitis	Slurred speech, muscle weakness, headache, nausea, seizures	Headache, nausea, vomiting, confusion, fever, stiff neck, seizures, coma
Disease pathology	Focal necrosis, granulomas	Corneal ulceration	Granulomatous reaction in skin, inflammation	Multiple necrotic foci, inflammation, cerebral edema	Hemorrhagic necrosis
Diagnostic methods	Brain biopsy, CSF smear/wet prep, culture, indirect immunofluorescence on tissue,^b PCR^b	Corneal scrapings or biopsy, stain with calcofluor white, culture, confocal microscopy	Skin lesion biopsy, culture, indirect immunofluorescence of tissue^a	Brain biopsy, culture on mammalian cells, indirect immunofluorescence of tissue^a	Brain biopsy, CSF wet prep, culture, indirect immunofluorescence of tissue,^a PCR^a

^a Acanthamoeba in brain and Balamuthia in brain courtesy Dr. Govinda Visvesvara, Centers for Disease Control and Prevention.

^b Indirect immunofluorescence on tissue and PCR methods available from Centers for Disease Control and Prevention.

Pathogenesis and Spectrum of Disease

Primary amebic meningoencephalitis (PAM) caused by N. fowleri is an acute, suppurative infection of the brain and meninges (Figure 50-2). With extremely rare exceptions, the disease is rapidly fatal in humans. The period between organism contact and onset of symptoms such as fever, headache, and rhinitis varies from a few days to 2 weeks. Early symptoms include vague upper respiratory tract distress, headache, lethargy, and occasionally olfactory problems. The acute phase includes sore throat; a stuffy, blocked, or discharging nose; and severe headache. Progressive symptoms include pyrexia, vomiting, and stiffness of the neck. Mental confusion and coma usually occur approximately 3 to 5 days before death, which is usually caused by cardiorespiratory arrest and pulmonary edema.