Infections Caused by Free-Living Amoebae

Abstract

Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found in water and soil worldwide. Acanthamoeba spp. and B. mandrillaris cause granulomatous amoebic encephalitis (GAE), which usually presents as a mass, while N. fowleri causes primary amoebic meningoencephalitis (PAM). Acanthamoeba spp. can also cause keratitis, and both Acanthamoeba spp. and B. mandrillaris can cause lesions in skin and respiratory mucosa. These amoebae can be difficult to diagnose clinically as these infections are rare and, if not suspected, can be misdiagnosed with other more common diseases. Microscopy continues to be the key first step in diagnosis, but the amoeba can be confused with macrophages or other infectious agents if an expert in infectious disease pathology or clinical microbiology is not consulted. Although molecular methods can be helpful in establishing the diagnosis, these are only available in referral centers. Treatment requires combination of antibiotics and antifungals and, even with prompt diagnosis and treatment, the mortality for neurological disease is extremely high.

Keywords: Acanthamoeba; Balamuthia; Naegleria; clinical presentation; diagnostics; free-living amoeba; neurological disease; treatment.

FIG 1

Different diagnostic methods used for free living amoeba: (A) Free-living amoeba trophozoites observed in a culture using a non-nutrient agar and a bacterial lawn (arrows mark the trophozoites). (B) Giemsa stain of cerebrospinal fluid in a patient with Acanthamoeba spp. granulomatous amoebic encephalitis (arrows mark 2 trophozoites from the same slide but from different locations). (C) Immunofluorescence assay in brain tissue of a patient with N. fowleri (amoeba stained green). (D) Immunohistochemical assay in brain tissue of a patient with B.mandrillaris granulomatous amoebic encephalitis, red staining corresponds to the amoeba. Note that the amoeba surrounds a blood vessel. Panels A and C are from the Public Health Image Library, CDC.

FIG 2

Skin and brain Acanthamoeba spp. infections. (A) Ulcerated necrotic lesion in leg. (B) Hematoxylin and eosin stain showing thickened epidermis (*) and intense inflammatory infiltrate through the dermis. Normally, the dermis should stain mostly homogeneously pink; in this photomicrograph, the dermis appears to have multiple blue dots corresponding to the inflammatory infiltrate. (C) Hematoxylin and eosin stain showing double-walled cyst with wrinkled external wall (arrow marks the cyst). (D) Hematoxylin and eosin stain showing trophozoite (arrow marks the trophozoite) with multiple vacuoles (stained light pink inside the trophozoite) and two erythrocytes (stained dark red). Note the nuclear characteristics of the cyst and trophozoite: the karyosome is prominent and central inside the nucleus, and the nuclear chromatin is dispersed and not clumping. (E) Macroscopic photograph of brain with granulomatous amoebic encephalitis. In this case, the base of the brain was the most affected, as demonstrated by the brown/gray coloring which is distinct from the rest of the brain parenchyma. (F to H) Microscopic images of cysts and trophozoite, corresponding to the same brain. (F) Collapsed cyst (arrow marks the cyst). (G) Cyst showing the characteristic nuclear features (arrow marks the cyst). (H) Trophozoite (arrow marks the trophozoite).