**7. Treatment**

The low degree of therapeutic success in treating amoebic encephalitis is due in part to the fact that immunocompromised individuals are most often affected, and the disease outcome

Autoimmunity in the Mediation of Granulomatous Amoebic Encephalitis: Implications for Therapy 321

In spite of high prevalence, the diseases induced by Acanthamoebae are extremely low. Although amoebic encephalitis is more commonly seen in immunocompromised individuals, the disease can occur in immunocompetent healthy individuals (Marciano-Cabral & Cabral, 2003, Schuster & Visvesvara, 2004). Our discovery that *A. castellanii* contains mimicry epitope for PLP indicates that exposure to *Acanthamoeba* can accompany autoimmunity through the generation of self-reactive T cells. Acanthamoebae are free-living organisms that are ubiquitous in the environment, leading to constant exposure. It is possible that such coexistence can help microbes acquire some of the genetic elements of their hosts as an evasive mechanism for survival. Alternatively, exposure to such organisms could lead to a break in self-tolerance as a result of antigenic mimicry in genetically susceptible individuals who potentially carry pathogenic autoreactive T cell and B cell repertoires. Further research is required to address these hypotheses, proving which creates opportunities to also target therapy toward autoimmunity in patients affected with GAE.

Aichelburg AC, Walochnik J, Assadian O, et al. (2008) Successful treatment of disseminated Acanthamoeba sp. infection with miltefosine. Emerg Infect Dis 14: 1743-1746. Akpek G, Uslu A, Huebner T*, et al.* (2011) Granulomatous amebic encephalitis: an under-

Barbeau J & Buhler T (2001) Biofilms augment the number of free-living amoebae in dental

Barker J, Scaife H & Brown MR (1995) Intraphagocytic growth induces an antibiotic-resistant phenotype of Legionella pneumophila. *Antimicrob Agents Chemother* 39: 2684-2688. Benedetto N & Auriault C (2002a) Complex network of cytokines activating murine

Benedetto N & Auriault C (2002b) Prolactin-cytokine network in the defence against

Benedetto N, Rossano F, Gorga F, Folgore A, Rao M & Romano Carratelli C (2003) Defense

Bettelli E, Oukka M & Kuchroo VK (2007) T(H)-17 cells in the circle of immunity and

Bowers B (1977) Comparison of pinocytosis and phagocytosis in Acanthamoeba castellanii.

Bowers B & Korn ED (1968) The fine structure of Acanthamoeba castellanii. I. The

Bowers B & Olszewski TE (1983) Acanthamoeba discriminates internally between digestible

Acanthamoeba castellanii infection. *Int Immunopharmacol* 3: 825-834. Berk SG, Ting RS, Turner GW & Ashburn RJ (1998) Production of respirable vesicles

recognized cause of infectious mortality after hematopoietic stem cell

microglial cell activity against Acanthamoeba castellani. *Eur Cytokine Netw* 13: 351-

Acanthamoeba castellanii in murine microglia [corrected]. *Eur Cytokine Netw* 13:

mechanisms of IFN-gamma and LPS-primed murine microglia against

containing live Legionella pneumophila cells by two Acanthamoeba spp. *Appl* 

**8. Conclusion** 

**9. References** 

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thus depends on successful treatment of underlying causes. Furthermore, *Acanthamoeba* infections tend to escape early diagnosis due to the lack of both awareness and diagnostic tools. Nonetheless, if diagnosed early, the disease can be treated successfully (Marciano-Cabral & Cabral, 2003, Schuster & Visvesvara, 2004, Khan, 2006, Khan, 2008, Matin*, et al.*, 2008, Elsheikha & Khan, 2010, Akpek*, et al.*, 2011). Various treatment regimens have been reported in the literature, but there are no reports to indicate that *Acanthamoeba* infections can be treated with a single drug; rather, a combination of multiple drugs is used (Table 1). These include ketoconazole, fluconazole, flucytosine, sulfa-trimethoprim, amphotericin B, pentamidine isothionate, azithromycin, itraconazole and rifampicin. Currently, to enhance BBB-permeability, soluble analogs of the most effective drugs are being tested (Khan, 2006). Likewise, experimental attempts also are being made to use non-viral plasmid DNAs encoding anti-sense RNA sequences for virulence factors of amoebae which can block their entry into the CNS (Elsheikha & Khan, 2010). Based on our data (Massilamany*, et al.*, 2010, Massilamany*, et al.*, 2011), we propose that amoebic encephalitis might involve mediation of autoimmunity, but this hypothesis needs to be tested experimentally in animal models and clinically in GAE patients. Proving that autoimmunity is a component of GAE provides a basis for exploring treatment modalities directed toward autoimmunity in patient subjects.


Table 1. Drugs used in the treatment of *Acanthamoeba* infections
