Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether

Animal studies have demonstrated artemisinin brain stem toxicity with auditory centres being especially affected; there has, to date, been no evidence of such toxicity with oral artemisinins in humans. Subjects working at a construction site in Mozambique had audiometric assessments taken on joining and leaving the project. Subjects with uncomplicated malarias received co-artemether (artemether-lumefantrine) (n = 150) while age-, gender-, weight- and race-matched controls (n = 150) neither suffered malaria nor received antimalarial. therapy. Hearing thresholds were measured at predefined frequencies in treated subjects and controls. Subjects receiving co-artemether had a significantly greater hearing loss than controls at all frequencies except 250 Hz and 500 Hz (P values ranging from <0.001 to 0.04, Mann-Whitney U). Mean changes at the different frequencies in subjects ranged from -6.50 dB (95% Cl -8.19 to -4.81) [at 1 kHz frequency] to -0.07 dB (95% Cl -2.19 to 2.05) [at 6 kHz frequency]. Mean changes in the control group ranged from -4.20 dB (95% Cl -5.97 to -2.43) [at 1 kHz frequency] to +2.7dB (95% Cl -0.93 to 4.47) [at 6 kHz frequency]. Treatment of uncomplicated malaria with co-artemether is associated with hearing loss, possibly from synergy between potentially ototoxic agents in combination. The safety and neurotoxicity of artemesinins and other endoperoxides needs to be more fully evaluated. (C) 2004 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.