lumefantrine and Hearing-Loss

An association between artemether-lumefantrine treatment of uncomplicated falciparum malaria and decreases in audiometrically determined hearing thresholds has been reported. Questions arising from this report were whether the effect described is attributable to drug or disease, the effects of subject weight and age on audiometric changes, and whether the changes are reversible. Spearman's correlation coefficients were calculated to look for relationships between audiometric changes and: (1) the interval spanning artemether-lumefantrine exposure and study exit audiogram; (2) subject age; (3) subject weight. The study utilised prospectively collected data from an occupational health clinic in Mozambique (N = 150). The exposure-exit audiogram interval ranged from 3 to 392 days (mean 163.8 days, SD 91.91 days). Spearman's correlation coefficients were effectively zero for analyses (1) and (2), and too weak to contribute significantly to variances for analysis (3). Previous audiometric studies in malaria patients and healthy volunteers point away from malaria as causing irreversible audiometric changes. The audiometric changes associated with the artemether-lumefantrine treatment of malaria appear irreversible. Ototoxicity is common to many antimalarials and the elucidation of a common antiparasitic and ototoxic pathway will assist in the design of safer new antimalarials.

Topics: Adult; Age Factors; Aged; Antimalarials; Artemether; Artemisinins; Audiometry; Body Weight; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Hearing Loss; Humans; Lumefantrine; Malaria, Falciparum; Male; Middle Aged; Mozambique; Time Factors; Treatment Outcome

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.

Topics: Acoustic Impedance Tests; Adolescent; Adult; Aged; Antimalarials; Artemether; Artemisinins; Audiometry; Case-Control Studies; Child; Drug Therapy, Combination; Ethanolamines; Evoked Potentials, Auditory, Brain Stem; Female; Fluorenes; Hearing Loss; Humans; Lumefantrine; Malaria; Male; Middle Aged; Treatment Outcome

Topics: Anti-Infective Agents; Artemisinins; Audiometry; Auditory Threshold; Case-Control Studies; Ethanolamines; Fluorenes; Hearing Loss; Humans; Lumefantrine; Malaria; Research; Sesquiterpenes; Time Factors