Improved Treatment of Granulomatous Amebic Encephalitis and Other Infections Caused by Balamuthia Mandrillaris and Acanthamoeba Species

BACKGROUND: Granulomatous amebic encephalitis (GAE) is a subacute to chronic central nervous system infection caused by the free-living amebae (FLA) Balamuthia mandrillaris and Acanthamoeba spp. FLA live in fresh water and soil, without the need for a host. When they do encounter a human host and GAE develops, symptoms may include personality and behavioral changes, depressed mental status, fever, photophobia, seizures, nonspecific cranial nerve dysfunction, and visual loss. Brain imaging may show single or multiple ring-enhancing lesions. B.mandrillaris and Acanthamoeba spp. also cause disseminated infections involving the skin, sinuses, lungs, liver, kidneys, or lymph nodes.  These infections are often fatal and go undiagnosed prior to death. When the diagnosis is made premortem, treatment is often ineffective. Miltefosine is an investigational drug used to treat leishmaniasis with in vitro activity against FLA. With CDC assistance, it has been given since 2009 under compassionate use for FLA infections.

METHODS: We reviewed the literature and case reports submitted to CDC to determine treatment regimens including miltefosine use and mortality for case patients with B. mandrillaris infection and non-keratitis Acanthamoeba  spp. infection. Fisher’s exact test was used to analyze proportions.

RESULTS:  We identified 62 cases of non-keratitis Acanthamoeba spp. infection for which treatment was documented between the years 1955 and 2012. Of the six cases treated with a regimen including miltefosine, 4 (67%) survived compared with 9/56 (16%) not treated with a regimen including miltefosine (P= 0.03). We also identified 57 B. mandrillaris infections from the literature and CDC case reports from 1974 to 2009 for which treatment was documented. Of the 11 treated with a miltefosine-containing regimen, five (45%) survived compared with 6/46 (13%) patients not treated with miltefosine (P= 0.05).

CONCLUSIONS: While the number of B. mandrillaris and Acanthamoeba spp. infections treated with a miltefosine-containing regimen is small, we conclude that a miltefosine-containing treatment regimen does offer a survival advantage for these often fatal infections. We recommend that CDC continue to assist clinicians with the process for obtaining miltefosine for use in treating FLA infections until it becomes commercially available in the United States.