**2.2 Host distribution and susceptibility**

The amoeba has a two-stage life-cycle: trophozoites (infective and invasive) and cysts (dormant). The life cycle can be completed in either the environment or infected hosts (Chagla & Griffiths, 1974, Marciano-Cabral & Cabral, 2003). Under unfavorable conditions, such as extremes of pH and temperature, trophozoites become cysts that are highly resistant to commonly used disinfectants containing chlorine and the cysts can survive environmental temperatures even upto 80o C (De Jonckheere & van de Voorde, 1976, Khunkitti*, et al.*, 1998, Storey*, et al.*, 2004). *Balamuthia* spp. (e.g., *B. mandrillaris*) can cause GAE in a wide range of species such as horses, baboons, sheeps, dogs, and humans (Martinez & Visvesvara, 2001), but development of clinical disease takes months to years. Likewise, *Acanthamoeba* infections are also reported in humans including domestic and nondomestic species such as dogs, monkeys, kangaroos and buffaloes (Schuster & Visvesvara, 2004). Found ubiquitously, Acanthamoebae have been isolated from a variety of sources such as soil; drinking, natural and sea water; hospitals, eye wash stations, and dental irrigation systems; swimming pools; and heating and cooling ducts (Jahnes & Fullmer, 1957, Kingston & Warhurst, 1969, Casemore, 1977, De Jonckheere, 1991, Barbeau & Buhler, 2001, Marciano-Cabral & Cabral, 2003, da Rocha-Azevedo*, et al.*, 2009) and the amoebae generally feed on bacteria, algae, and yeast (Bowers, 1977, Bowers & Olszewski, 1983, Marciano-Cabral & Cabral, 2003, da Rocha-Azevedo*, et al.*, 2009).

Generally, GAE is regarded as a disease of immunocompromised individuals. HIV patients, individuals undergoing immunosuppressive and steroid therapies, and those who have received organ or stem cell transplants are at great risk of developing the disease (Marciano-Cabral*, et al.*, 2000, Seijo Martinez*, et al.*, 2000, Marciano-Cabral & Cabral, 2003, Schuster & Visvesvara, 2004, Khan, 2006, da Rocha-Azevedo*, et al.*, 2009). Other predisposing factors include malignancies and debilitated conditions such as diabetes, chronic alcoholism and malnutrition (Martinez & Janitschke, 1985, Sell*, et al.*, 1997, Marciano-Cabral & Cabral, 2003, Khan, 2006). Exacerbation of GAE lesions was reported in one patient undergoing treatment for cryoglobulinemia with a monoclonal antibody directed against CD20 which selectively depletes mature B cells (Meersseman*, et al.*, 2007). Likewise, GAE can occur in patients with systemic lupus erythematosus, further emphasizing the importance of a compromised immune system for disease-predisposition (Koide*, et al.*, 1998, Uschuplich*, et al.*, 2004, Cha*, et al.*, 2006). Since amoebic encephalitis is not a reportable disease, and diagnosis is often made postmortem, the number of cases documented in the literature does not reflect actual disease-incidence. One study has reported to have documented upto 500 cases of amoebic encephalitis worldwide (Sarica*, et al.*, 2009). However, the recent availability of PCR-based detection of *Acanthamoeba* is greatly facilitating diagnosis (Schroeder*, et al.*, 2001, Khan, 2006, da Rocha-Azevedo*, et al.*, 2009, Maritschnegg*, et al.*, 2011) and as a result, the number of cases reported in recent years show an increasing trend.
