Free‐Living Amoebae as Agents of Human Infection

In this issue of the Journal, Qvarnstrom et al. [1] describe the development of a species-specific real-time polymerase chain reaction (PCR) assay that identifies a freeliving amoeba of the genus Sappinia, newly discovered to be a pathogen of the human central nervous system (CNS). Previously, species from 3 genera of freeliving amoebae had been associated with human infections [2– 6]. Naegleria fowleri causes primary amoebic meningoencephalitis, a rapidly fatal hemorrhagic necrotizing infection of the CNS, which generally occurs in previously healthy children and young adults with a history of swimming and other recreational activities in warm freshwater lakes and ponds [2, 6]. Several species of Acanthamoeba cause granulomatous amoebic encephalitis (GAE), a chronic fatal disease of the CNS that is more commonly associated with immunocompromised states, particularly in patients who have undergone organ transplants, HIV-positive individuals, and individuals undergoing chemotherapy for cancer [3–5, 7]. Balamuthia mandrillaris can also cause GAE [3]. Acanthamoeba and B. mandrillaris can also infect sites other than the CNS, causing pulmonary and cutaneous lesions [3–5]. Acanthamoeba can cause sightthreatening keratitis in immunocompetent individuals and is often associated with contact lens wear [4, 8]. These freeliving amoebae feed on bacteria and other microorganisms in the environment and are widely distributed in soil and water habitats. They also have been isolated from domestic water supplies, wells, dental irrigation units, hospital water supplies, and air conditioning units [4, 9 –13]. In addition to causing serious infections, free-living amoebae also may serve as reservoirs in the environment for pathogenic bacteria such as Legionella pneumophila and Mycobacterium avium [14, 15]. Exposure to free-living amoebae appears to be common, since studies have shown that serum samples from adult humans contain antibodies to N. fowleri, Acanthamoeba species, and B. mandrillaris [16 –18]. However, it is not known why disease occurs in some individuals but not in others. The dose and strain of amoebae to which an individual is exposed may be factors involved in susceptibility. Defects in the host’s innate or acquired immunity may also play roles in susceptibility to infection [3, 5, 6]. In 2001, Gelman et al. [19] described a nonfatal case of amoebic encephalitis that was attributed to a free-living amoeba that had not previously been associated with human disease. A previously healthy, 38-year-old, immunocompetent male presented with a history of nausea, vomiting, headache, loss of consciousness, and photophobia following a sinus infection. Brain images produced by magnetic resonance imaging showed a solitary mass in the temporal lobe. Microscopic examination of the excised lesion revealed the presence of amoebic trophozoites that contained 2 apposed nuclei, a morphologic feature of the free-living amoeba Sappinia diploidea. Immunofluorescence microscopy that used antibodies to N. fowleri, Acanthamoeba species, and B. mandrillaris excluded these agents as the cause of the infection. The patient survived the infection after treatment with a combination of azithromycin, pentamidine, itraconazole, and flucytosine. Further characterization was not undertaken because live amoebae were not recovered from the patient. Neither were amoebae isolated from cerebrospinal fluid or biopsy tissue samples. Thus, on the basis of morphologic criteria, immunofluorescence assessment, and a nonfatal patient outcome, the CNS infection was attributed to S. diploidea [19, 20]. Identification of amoebae on the basis of morphological criteria is difficult and unreliable. Acanthamoeba and B. mandrillaris can be difficult to differentiate in tissues because they are similar in structure. Biochemical techniques, such as protein and isoenzyme profiles, have proven useful for distinguishing pathogenic and nonpathogenic species of some freeliving amoebae. Immunological assays that use monoclonal or polyclonal antibodies in conjunction with immunofluoReceived 16 December 2008; accepted 16 December 2008; electronically published 24 March 2009. Potential conflicts of interest: none reported. Financial support: Immunotox Foundation (grant XXX). Reprints or correspondence: Francine Marciano-Cabral, Dept. of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond VA (fmcabral@vcu.edu). The Journal of Infectious Diseases 2009; 199: 1104 – 6 © 2009 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2009/19908-0002$15.00 DOI: 10.1086/597474 E D I T O R I A L C O M M E N T A R Y