Free-living amebas are protozoa that live independently in soil or water and do not require a human or animal host. They rarely cause disease, in contrast to the parasitic ameba Entamoeba histolytica, which is a common cause of intestinal infection (see Amebiasis). Pathogenic free-living amebas are of the genera Naegleria, Acanthamoeba, Balamuthia, and Sappinia (S. pedata was implicated in one case of amebic encephalitis in Texas).
Three major syndromes occur:
Acanthamoeba and Balamuthia can also cause skin lesions or disseminated disease in immunocompromised people; Acanthamoeba can cause infection of the sinuses or lungs.
The case of S. pedata encephalitis was successfully treated with a combination of azithromycin, pentamidine, itraconazole, and flucytosine plus surgical resection of the CNS lesion. Adding miltefosine could be considered.
Primary Amebic Meningoencephalitis
Primary amebic meningoencephalitis is a generally fatal, acute CNS infection caused by Naegleria fowleri.
Naegleria fowleri inhabit bodies of warm fresh water worldwide. Swimming in contaminated water exposes nasal mucosa to the organism, which can enter the CNS via olfactory neuroepithelium and the cribriform plate. Most patients are healthy children or young adults.
Symptoms begin within 1 to 2 wk of exposure, sometimes with alteration of smell and taste. Fulminant meningoencephalitis ensues, with headache, meningismus, and mental status change, progressing to death within 10 days, usually due to cerebral herniation. Only a few patients have survived.
Diagnosis is suspected based on history of swimming in fresh water, but confirmation is difficult because CT and routine CSF tests, although necessary to exclude other causes, are nonspecific. Wet mount of CSF should be done; it may demonstrate motile amebic trophozoites (which are destroyed by Gram stain techniques). Immunohistochemistry, amebic culture and PCR of CSF and/or brain biopsy are available in specialized laboratories.
Optimal treatment is unclear. A reasonable regimen would include miltefosine, an experimental antileishmanial drug, which has been used to successfully treat granulomatous amebic encephalitis. Miltefosine is available through consultation from the Centers for Disease Control and Prevention (CDC—see CDC information on Naegleria). Other drugs that have been used in combination treatment regimens for Naegleria include amphotericin B, rifampin, an azole (fluconazole, voriconazole, or ketoconazole), and azithromycin.
Granulomatous Amebic Encephalitis
Granulomatous amebic encephalitis is a generally fatal subacute CNS infection caused by Acanthamoeba sp in immunocompromised or debilitated hosts or by Balamuthia mandrillaris.
Acanthamoeba sp and Balamuthia mandrillaris are present worldwide in water, soil, and dust. Human exposure is common, but infection is rare. Acanthamoeba infection of the CNS occurs almost entirely in immunocompromised or otherwise debilitated patients, but B. mandrillaris may also infect healthy hosts. The entry portal is thought to be the skin or lower respiratory tract, with subsequent hematogenous dissemination to the CNS.
Onset is insidious, often with focal neurologic manifestations. Mental status change, seizures, and headache are common. B. mandrillaris may also cause skin lesions; patients with B. mandrillaris infection can present with skin lesions and later develop neurologic symptoms and signs. Survival is highly unlikely (and only in immunocompetent patients); death occurs between 7 and 120 days after onset.
Diagnosis is often postmortem. In patients with Acanthamoeba infections, CT and MRI may show single or multiple space-occupying lesions with ring enhancement, most commonly in the temporal and parietal lobes. In CSF, WBC count (predominantly lymphocytes) is elevated, but trophozoites are rarely seen. Visible skin lesions often contain amebas and should be biopsied; if detected, amebas may be cultured and tested for drug sensitivity. Brain biopsy is often positive. PCR-based assays are available in specialized reference laboratories. In patients with B. mandrillaris infection, CT and MRI typically show multiple nodular, ring-enhancing lesions. Intralesional hemorrhage is an important radiologic clue.
Optimal treatment of granulomatous amebic encephalitis is unclear. Some cases of granulomatous encephalitis respond to combinations of drugs. Although the number of patients treated with a regimen containing miltefosine is small, miltefosine appears to offer a survival advantage. Miltefosine is available directly from the CDC. Other drugs that have been used in combination to treat this syndrome include pentamidine, sulfadiazine or trimethoprim/sulfamethoxazole, flucytosine, an azole (fluconazole, itraconazole, or voriconazole), and amphotericin B. Albendazole has been used with miltefosine and other drugs to treat B. mandrillaris encephalitis. For all cases of amebic encephalitis, immediate consultation with the CDC is recommended (call the CDC Emergency Operations Center at 770-488-7100).
Skin infections caused by Acanthamoeba sp or B. mandrillarisare usually treated with the same drugs plus surgical debridement.
Amebic keratitis is corneal infection with Acanthamoeba sp, typically occurring in contact lens wearers.
Acanthamoeba sp can cause chronic and progressively destructive keratitis in normal hosts. The main risk factor (85% of cases) is contact lens use, particularly if lenses are worn while swimming or if unsterile lens cleaning solution is used. Some infections follow corneal abrasion.
Lesions are typically very painful and produce a foreign body sensation. Initially, lesions have a dendriform appearance resembling herpes simplex keratitis. Later, there are patchy stromal infiltrates and sometimes a characteristic ring-shaped lesion. Anterior uveitis is usually also present. Vision is diminished.
Diagnosis is confirmed by examination of Giemsa- or trichrome-stained corneal scrapings and by culture on special media. Viral culture is done if herpes is considered.
Early, superficial infection responds better to treatment. The encysted stage of the life cycle appears to cause most problems.
Epithelial lesions are debrided, and intensive drug therapy is applied. Topical propamidine isethionate 0.1% plus either polyhexamethylene biguanide or biguanide chlorhexidine drops is frequently the initial choice; for the first 3 days, drugs are given every 1 to 2 h. Other topical drugs that can be used include aminoglycosides, hexamidine diisethionate, miconazole, and neosporin.
Systemic treatment with fluconazole or itraconazole has also been used, particularly in patients with anterior uveitis or involvement of the sclera. Early recognition and treatment have eliminated the need for therapeutic keratoplasty in most instances, but it remains an option when pharmacologic therapy fails. Intensive treatment is required for the first month; it is tapered per clinical response but often continued for 6 to 12 mo. Recurrence is common if treatment is stopped prematurely.
Contact lens solution should be kept clean. Nonsterile homemade contact lens solutions should not be used. Wearing contact lenses while swimming or showering should be avoided.
Last full review/revision January 2014 by Richard D. Pearson, MD
Content last modified January 2014