title: Ototoxicity of artemether/lumefantrine in the treatment of falciparum malaria: a randomized trial.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Ludwig Maximilians University, Munich, Germany. robert.guerkov@med.uni-muenchen.de
authors.forename: Robert
authors.initials: R
authors.lastname: Gürkov
authors.forename: Teferi
authors.initials: T
authors.lastname: Eshetu
authors.forename: Isabel Barreto
authors.initials: IB
authors.lastname: Miranda
authors.forename: Nicole
authors.initials: N
authors.lastname: Berens-Riha
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Mamo
authors.forename: Tsinuel
authors.initials: T
authors.lastname: Girma
authors.forename: Eike
authors.initials: E
authors.lastname: Krause
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.forename: John-Martin
authors.initials: JM
authors.lastname: Hempel
authors.forename: Thomas
authors.initials: T
authors.lastname: Löscher
mesh_terms: D000293:Adolescent; D000328:Adult; D000077549:Artemether; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use; D053626:Atovaquone / Q000009:adverse effects / Q000627:therapeutic use; D001299:Audiometry; D002648:Child; D004983:Ethanolamines / Q000009:adverse effects* / Q000627:therapeutic use; D005002:Ethiopia; D005260:Female; D005449:Fluorenes / Q000009:adverse effects* / Q000627:therapeutic use; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D002727:Proguanil / Q000009:adverse effects / Q000627:therapeutic use; D011803:Quinine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D011803:Quinine; D000077549:Artemether; D000078102:Lumefantrine; D002727:Proguanil; D053626:Atovaquone
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