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

Abstract 

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 250Hz and 500Hz (P values ranging from <0.001 to 0.04, Mann–Whitney U). Mean changes at the different frequencies in subjects ranged from −6.50dB (95% CI −8.19 to −4.81) [at 1kHz frequency] to −0.07dB (95% CI −2.19 to 2.05) [at 6kHz frequency]. Mean changes in the control group ranged from −4.20dB (95% CI −5.97 to −2.43) [at 1kHz frequency] to +2.7dB (95% CI −0.93 to 4.47) [at 6kHz 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.

Keywords:  Falciparum malaria, Ototoxicity, Neurotoxicity, Artemesinins, Endoperoxides, Co-artemether