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Free-Living Amebas

By Richard D. Pearson, MD, Emeritus Professor of Medicine, University of Virginia School of Medicine

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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 (amebiasis). Pathogenic free-living amebas are of the genera Naegleria, Acanthamoeba, Balamuthia, and Sappinia.

Three major syndromes occur:

  • Primary amebic meningoencephalitis

  • Granulomatous amebic encephalitis

  • Amebic keratitis

Acanthamoeba and Balamuthia can also cause skin lesions or disseminated disease in immunocompromised people; Acanthamoeba can also cause infection of the sinuses or lungs.

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 and Signs

Symptoms of primary amebic meningoencephalitis 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

  • CSF examination

Primary amebic meningoencephalitis 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 can be seen in Giemsa-stained specimens but are destroyed by Gram stain techniques).

Immunohistochemistry, amebic culture, PCR of CSF, and/or brain biopsy are available in specialized reference laboratories.

Treatment

  • Various treatment regimens

  • Multiple drugs, including miltefosine plus antifungal drugs and antibiotics

Optimal treatment is unclear.

A reasonable regimen would include miltefosine, an antileishmanial drug, which has been used to successfully treat granulomatous amebic encephalitis. Miltefosine is available through consultation from the 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)

  • Azithromycin

Anticonvulsants and dexamethasone are often needed to control seizures and cerebral edema.

Key Points

  • Primary amebic meningoencephalitis is usually fatal.

  • The infection is acquired when swimming in contaminated fresh water; Naegleria fowleri enters the CNS via olfactory neuroepithelium and the cribriform plate.

  • Diagnostic tests should include a wet mount and Giemsa-stained specimen of CSF.

  • Treat the infection with appropriate antimicrobial drugs; if needed, treat seizures and cerebral edema with anticonvulsants and dexamethasone.

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. Sappinia pedata was implicated in one case of amebic encephalitis in Texas.

The life cycle of Acanthamoeba involves only 2 stages: cysts and trophozoites (the infective form). The trophozoites form double-walled cysts, which resist eradication. The entry portal is thought to be the skin or lower respiratory tract, with subsequent hematogenous dissemination to the CNS. In infected patients, cysts and trophozoites may be found in tissues.

Symptoms

Onset is insidious, often with focal neurologic manifestations. Mental status change, seizures, and headache are common.

Acanthamoeba sp and B. mandrillaris may also cause skin lesions; patients can present with ulcerative skin lesions and later develop neurologic symptoms and signs. In a few patients with AIDS, disseminated Acanthamoeba infection affects only the skin.

Survival is uncommon; death usually occurs between 7 and 120 days after onset.

Diagnosis

  • CT with contrast and MRI

  • CSF analysis

  • Biopsy of skin lesions

Diagnosis of granulomatous amebic encephalitis is often postmortem.

Diagnosis of Acanthamoeba infections

In patients with Acanthamoeba infections, CT with contrast 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. These tests help exclude other possible causes but usually cannot confirm the diagnosis.

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.

Diagnosis of B. mandrillaris infections

In patients with B. mandrillaris infection, CT and MRI typically show multiple nodular, ring-enhancing lesions. Intralesional hemorrhage is an important radiologic clue.

Treatment

  • A combination of drugs, usually including miltefosine

  • Consultation with the CDC

Optimal treatment of Acanthamoeba encephalitis is unclear. Multiple drugs (often > 5) are typically used in combination. 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 Acanthamoeba encephalitis include pentamidine, sulfadiazine or trimethoprim/sulfamethoxazole, flucytosine, an azole (fluconazole, itraconazole, or voriconazole), rifampin and amphotericin B.

For B. mandrillaris encephalitis, miltefosine in combination with other drugs such as flucytosine, pentamidine, fluconazole, and/or sulfadiazine plus either azithromycin or clarithromycin plus surgical resection have been used.

A case of Sappinia pedata encephalitis was successfully treated with a combination of azithromycin, pentamidine, itraconazole, and flucytosine plus surgical resection of the CNS lesion. Adding miltefosine to this regimen should be considered.

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. mandrillaris are usually treated with the same drugs plus surgical debridement.

Key Points

  • Granulomatous amebic encephalitis is a rare, usually fatal CNS infection.

  • Acanthamoeba encephalitis occurs almost entirely in immunocompromised or otherwise debilitated patients, but B. mandrillaris may infect healthy hosts.

  • Do CT with contrast, MRI, and CSF tests to exclude other causes, and biopsy any skin lesions to check for amebas.

  • Consult with the CDC about optimal treatment.

  • Treat with miltefosine plus other drugs (eg, pentamidine, sulfadiazine, flucytosine, an azole).

Amebic Keratitis

Amebic keratitis is corneal infection with Acanthamoebasp, typically occurring in contact lens wearers.

Acanthamoeba spp 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.

Acanthamoeba are present worldwide in water, soil, and dust. The life cycle of Acanthamoeba involves only 2 stages: cysts and trophozoites (the infective form). The trophozoites form double-walled cysts, which resist eradication. Both forms can enter the body through various means (eg, eyes, nasal mucous membranes, broken skin). When Acanthamoeba enter the eye, they can cause severe keratitis. In infected patients, cysts and trophozoites may be found in tissues.

Symptoms and Signs

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

  • Examination and culture of corneal scrapings

Consultation with an ophthalmologist is important for diagnosis and treatment.

Diagnosis of amebic keratitis 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.

Treatment

  • Corneal debridement

  • Topical chlorhexidine, polyhexamethylene biguanide, or both

  • In severe cases, systemic itraconazole or ketoconazole

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. The initial choice is

  • Topical chlorhexidine 0.02%

  • Topical polyhexamethylene biguanide 0.02%

  • Both drugs

For the first 3 days, drugs are given every 1 to 2 h. Other topical drugs used as adjunct therapy include propamidine and hexamidine diisethionate.

Systemic treatment with itraconazole or ketoconazole has been used in conjunction with topical therapy, particularly in patients with anterior uveitis or involvement of the sclera. Systemic ketoconazole can cause severe liver injury and adrenal gland problems and should be used only when alternative antifungal drugs are not available or not tolerated (see FDA Drug Safety Communication: Ketoconazole).

Early recognition and treatment have eliminated the need for therapeutic keratoplasty in most instances, but keratoplasty 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.

Prevention

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.

Key Points

  • Acanthamoeba spp can cause chronic and progressively destructive keratitis in otherwise healthy hosts, mainly in contact lens users.

  • Consult with an ophthalmologist about management.

  • Diagnose by examining Giemsa- or trichrome-stained corneal scrapings and by culturing the sample using special media.

  • Herpes simplex keratitis can cause similar lesions; if it seems a possible diagnosis, do viral culture.

  • Debride corneal lesions, and treat with topical chlorhexidine, polyhexamethylene biguanide, or both.

  • For severe infections, consider treatment with systemic itraconazole, or if itraconazole is ineffective or not tolerated, consider ketoconazole.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • OZURDEX
  • DIFLUCAN
  • No US brand name
  • BIAXIN
  • ZITHROMAX
  • NIZORAL
  • VFEND
  • RIFADIN, RIMACTANE
  • SPORANOX
  • ANCOBON
  • NEBUPENT