**8. Conclusion**

320 Non-Flavivirus Encephalitis

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.

Species Disease Drugs Outcome Reference

Died Gardner*, et al.*, 1991

Died Gordon*, et al.*, 1992

Died Murakawa*, et al.*, 1995

Survived Petry*, et al.*, 2006

Died Cha*, et al.*, 2006

Survived Gupta*, et al.*, 2008

Survived Lackner*, et al.*, 2010

Survived Maritschnegg*, et al.*, 2011

Survived Seijo Martinez*, et al.*, 2000

*Acanthamoeba* spp. GAE Pyrimethamine and

*Acanthamoeba* spp. GAE Pyrimethamine and

amoebiasis and GAE

*Acanthamoeba* spp. GAE Sulfadiazine, pyrimethamine,

*Acanthamoeba* T1 GAE Fluoxetine, pantoprazole and

*Acanthamoeba* spp. GAE Ketoconazole, trimethoprim,

*Acanthamoeba* T4 GAE Fluconazole, rifampicin,

*Acanthamoeba* spp. Cutaneous

*Acanthamoeba lenticulata* T3

*Acanthamoeba* group II T4

fluconazole

sulfadiazine

Fluorocytosine and pentamidine

Metronidazole and sulfadiazine

and cotrimoxazole

prednisolone.

GAE Meropenem, linezolid,

GAE Trimethoprim-

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

fluconazole and sulfadiazine

sulfamethoxazole, rifampicin

moxifloxacin and fluconazole

sulfamethoxazole, fluconazole, pentamidine and miltefosine

*Acanthamoeba* T2 GAE Miltefosine and amikacin. Survived Walochnik*, et al.*, 2008 *Acanthamoeba* spp. GAE Miltefosine and amikacin Survived Aichelburg*, et al.*, 2008 *Acanthamoeba* spp. GAE Rifampicin and co-trimoxazole Survived Fung*, et al.*, 2008

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.
