Ototoxicity of artemether/lumefantrine in the treatment of falciparum malaria: a randomized trial

Background: Due to increasing drug resistance, artemisinin-based
combination chemotherapy (ACT) has become the first-line treatment
of falciparum malaria in many endemic countries. However,
irreversible ototoxicity associated with artemether/lumefantrine
(AL) has been reported recently and suggested to be a serious
limitation in the use of ACT. The aim of the study was to compare
ototoxicity, tolerability, and efficacy of ACT with that of quinine
and atovaquone/proguanil in the treatment of uncomplicated
falciparum malaria. Methods: Ninety-seven patients in south-west
Ethiopia with slide-confirmed malaria were randomly assigned to
receive either artemether/lumefantrine or quinine or
atovaquone/proguanil and followed-up for 90 days. Comprehensive
audiovestibular testing by pure tone audiometry (PTA), transitory
evoked (TE) and distortion product (DP) otoacoustic emissions (OAE)
and brain stem evoked response audiometry (BERA) was done before
enrolment and after seven, 28 and 90 days. Results: PTA and DP-OAE
levels revealed transient significant cochlear hearing loss in
patients treated with quinine but not in those treated with
artemether/lumefantrine or atovaquone/proguanil. TE-OAE could be
elicited in all examinations, except for three patients in the Q
group on day 7, who suffered a transient hearing loss greater than
30 dB. There was no evidence of drug-induced brain stem lesions by
BERA measurements. Conclusion: There was no detrimental effect of a
standard oral regimen of artemether/lumefantrine on peripheral
hearing or brainstem auditory pathways in patients with
uncomplicated falciparum malaria. In contrast, transient hearing
loss is common after quinine therapy and due to temporary outer
hair cell dysfunction.