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 heating 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% CI -8.19 to -4.81) [at 1kHz frequency] to -0.07 dB (95% CI -2.19 to 2.05) [at 6 kHz frequency]. Mean changes in the control group ranged from -4.20 dB (95% CI -5.97 to -2.43) [at 1 kHz frequency] to +2.7 dB (95% CI -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.