Primary amoebic meningoencephalitis: amoebicidal effects of clinically approved drugs against Naegleria fowleri
Abstract
Naegleria fowleri is a protist pathogen known to produce fulminating primary amoebic meningoencephalitis (PAM) ( Marciano-Cabral & Cabral, 2007 ; Visvesvara et al., 2007 ). Although rare, PAM is a serious human disease with a fatality rate of >95 %. It is generally associated with swimming in contaminated freshwater and possibly through nasal irrigation for cleansing ( Marciano-Cabral & Cabral, 2007 ; Visvesvara et al., 2007 ). PAM cases have recently been observed in Muslims who routinely perform ritual ablution, which involves repeated water exposure to the nostrils for cleansing ( Siddiqui & Khan, 2011 ). These so-called ‘brain-eating amoebae’ invade the nervous system via the nose when contaminated water is deeply inhaled into the nose, and migrate to the brain tissue where severe haemorrhaging and inflammation are caused, resulting in widespread brain tissue destruction ( Marciano-Cabral & Cabral, 2007 ; Visvesvara et al., 2007 ). As well studied as this protist is, we still do not know of any effective chemotherapeutic interventions. The current treatment regimen involves a mixture of drugs ranging from antimicrobial compounds to experimental anti-cancer drugs ( Marciano-Cabral & Cabral, 2007 ; Visvesvara et al., 2007 ), to provide additive or synergistic effects, but even then the mortality remains very high (~98 %) ( Marciano-Cabral & Cabral, 2007 ; Visvesvara et al., 2007 ). This is probably due to difficulties in early diagnosis, resulting in delayed initiation of effective chemotherapy, and/or poor penetration of antimicrobial compounds across the blood–brain barrier. With the devastating nature of this disease and the problems associated with its chemotherapy, the overall aim of the present study was to test anti- N. fowleri effects of clinically available drugs in vitro.