A CASE-CONTROL AUDITORY EVALUATION OF PATIENTS TREATED WITH ARTEMETHER-LUMEFANTRINE

ROBERT HUTAGALUNG Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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HSAR HTOO Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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PAW NWEE Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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JARUWAN ARUNKAMOMKIRI Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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JULIEN ZWANG Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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VERENA I. CARRARA Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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ELIZABETH ASHLEY Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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PRATAP SINGHASIVANON Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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NICHOLAS J. WHITE Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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FRANÇOIS NOSTEN Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Artemether-lumefantrine is the first registered, fixed, artemisinin-based combination treatment. Artemisinin derivatives are highly effective antimalarials with a favorable safety profile. Concerns remain over their potential neurotoxicity, although there has been no clinical evidence of this in humans. In animals (rats, dogs, and monkeys) artemether, a derivative of artemisinin is associated with an unusual toxicity pattern in specific brain nuclei involving the auditory and vestibular pathways. A recent report from Mozambique described a small but significant and irreversible hearing loss in patients exposed to artemether-lumefantrine. To explore this issue, we conducted a case-control study using tympanometry, audiometry and auditory brain-stem responses. We assessed 68 subjects who had been treated with artemether-lumefantrine within the previous five years and 68 age- and sex-matched controls living in the malarious region along the Thailand-Myanmar border. There were no differences in the test results between cases and controls. There was no neurophysiologic evidence of auditory brainstem toxicity that could be attributed to artemether-lumefantrine in this study population.

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