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.

PAM resembles acute bacterial meningitis, and these conditions may be difficult to differentiate. Unfortunately, if the CSF Gram stain is interpreted incorrectly as a false positive, the resulting antibacterial therapy has no impact on the amebae and the patient will usually die within a few days.

Clinical and laboratory data usually cannot be used to differentiate pyogenic meningitis from PAM. A high index of suspicion is often critical for early diagnosis. Most cases are associated with exposure to contaminated water through swimming or bathing. There is normally an incubation period of 1 day to 2 weeks, and then a course of 3 to 6 days, most often ending in death.

Analysis of the CSF will show decreased glucose and increased protein concentrations. The leukocyte count will range from several hundred to >20,000 cells per mm³. Although Gram stains and bacterial cultures of CSF will be negative, serious patient complications can occur as the result of incorrect therapy if false-positive Gram stains are reported.

A confirmed diagnosis is made by the identification of amebae in the CSF or in biopsy specimens. CSF should be placed on a slide, under a cover slip, and observed for motile trophozoites; smears can be stained with any of the blood stains. It is important not to mistake leukocytes for actual organisms or vice versa. This type of misidentification often occurs when using a counting chamber and the amebae sink to the bottom and round up, hence the recommendation to use just a regular slide and cover slip. Depending on the temperature and lag time between specimen collection and examination, motility may vary. Slides may be warmed slightly to improve motility. The most important differential characteristic is the spherical nucleus with a large karyosome.

Specimens should never be refrigerated before examination, and CSF should be centrifuged at a slow speed (250× g). If N. fowleri is the causative agent, only trophozoites are normally seen, whereas cysts and trophozoites can be seen with Acanthamoeba spp.

Therapy

Although many antimicrobial and antiparasitic drugs have been screened for activity against N. fowleri, only a few patients have recovered after receiving intrathecal and intravenous injections of amphotericin B or in combination with miconazole. Unfortunately, delay in diagnosis and the fulminant nature of PAM result in few survivors.

Meningoencephalitis caused by Acanthamoeba spp. may present as an acute suppurative inflammation of the brain and meninges similar to N. fowleri infection. The incubation period of GAE is unknown; several weeks or months are probably necessary to establish disease. The clinical course tends to be subacute or chronic and is usually associated with trauma or underlying disease, not as a result of swimming. GAE may present with symptoms of confusion, dizziness, drowsiness, nausea, vomiting, headache, lethargy, stiff neck, seizures, and sometimes hemiparesis. Unlike PAM caused by N. fowleri, both trophozoites and cysts are found throughout the tissue. Also, dissemination to other tissues such as the liver, kidneys, trachea, and adrenals can occur in immunocompromised individuals; or additional unusual sites also include the ear and necrotic bone from a bone graft of the mandible. Some patients, especially those with AIDS, can develop erythematous nodules, chronic ulcerative skin lesions, or abscesses.

The most effective culture approach uses non-nutrient agar plates with Page’s saline and an overlay growth of Escherichia coli on which the amebae feed. Tissue stains are also effective, and cysts isolated from cultures can be stained with Gomori’s silver methenamine, periodic acid-Schiff, and calcofluor white. Identification of Acanthamoebae in ocular samples and other tissues can be difficult, even for trained laboratory professionals; in histologic preparations, the organisms appear similar to keratoplasts, as well as neutrophils and monocytes. It has been estimated that up to 70% of clinical Acanthamoeba keratitis cases are misdiagnosed as viral keratitis. Also, the average time to diagnosis of keratitis attributable to Acanthamoeba