title: 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 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.
authors.affiliation: SAA-Netcare Travel Clinics, South Africa and Mozambique, P.O. Box 786692, Sandton, 2146, South Africa. toovey@travelclinic.co.az
authors.forename: Stephen
authors.initials: S
authors.lastname: Toovey
authors.forename: Andrew
authors.initials: A
authors.lastname: Jamieson
mesh_terms: D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000009:adverse effects*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects*; D001299:Audiometry; D004338:Drug Combinations; D004983:Ethanolamines; D005260:Female; D005449:Fluorenes / Q000009:adverse effects*; D006311:Hearing Disorders / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012717:Sesquiterpenes / Q000009:adverse effects*
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes