Abstract:
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.
