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

Robert Gürkov; Teferi Eshetu; Isabel Barreto Miranda; Nicole Berens-Riha; Yoseph Mamo; Tsinuel Girma; Eike Krause; Michael Schmidt; John-Martin Hempel; Thomas Löscher

doi:10.1186/1475-2875-7-179

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

Robert Gürkov, Teferi Eshetu, Isabel Barreto Miranda, Nicole Berens-Riha, Yoseph Mamo, Tsinuel Girma, Eike Krause, Michael Schmidt, John-Martin Hempel, Thomas Löscher

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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.

Original language	English
Article number	179
Journal	Malaria Journal
Volume	7
ISSN	1475-2875
DOIs	https://doi.org/10.1186/1475-2875-7-179
Publication status	Published - 2008

Keywords

Adolescent
Adult
Artemether
Artemisinins/adverse effects
Atovaquone/adverse effects
Audiometry
Child
Ethanolamines/adverse effects
Ethiopia
Female
Fluorenes/adverse effects
Hearing Loss, Sensorineural/chemically induced
Humans
Lumefantrine
Malaria, Falciparum/drug therapy
Male
Middle Aged
Proguanil/adverse effects
Quinine/adverse effects

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10.1186/1475-2875-7-179Licence: CC BY

2008mjou0179Final published version, 543 KBLicence: CC BY

Cite this

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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.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.",

keywords = "Adolescent, Adult, Artemether, Artemisinins/adverse effects, Atovaquone/adverse effects, Audiometry, Child, Ethanolamines/adverse effects, Ethiopia, Female, Fluorenes/adverse effects, Hearing Loss, Sensorineural/chemically induced, Humans, Lumefantrine, Malaria, Falciparum/drug therapy, Male, Middle Aged, Proguanil/adverse effects, Quinine/adverse effects",

author = "Robert G{\"u}rkov and Teferi Eshetu and Miranda, {Isabel Barreto} and Nicole Berens-Riha and Yoseph Mamo and Tsinuel Girma and Eike Krause and Michael Schmidt and John-Martin Hempel and Thomas L{\"o}scher",

note = "FTX; DOAJ; (CC BY 2.0)",

year = "2008",

doi = "10.1186/1475-2875-7-179",

language = "English",

volume = "7",

journal = "Malaria Journal",

issn = "1475-2875",

publisher = "BioMed Central",

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TY - JOUR

T1 - Ototoxicity of artemether/lumefantrine in the treatment of falciparum malaria: a randomized trial

AU - Gürkov, Robert

AU - Eshetu, Teferi

AU - Miranda, Isabel Barreto

AU - Berens-Riha, Nicole

AU - Mamo, Yoseph

AU - Girma, Tsinuel

AU - Krause, Eike

AU - Schmidt, Michael

AU - Hempel, John-Martin

AU - Löscher, Thomas

N1 - FTX; DOAJ; (CC BY 2.0)

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Artemether

KW - Artemisinins/adverse effects

KW - Atovaquone/adverse effects

KW - Audiometry

KW - Child

KW - Ethanolamines/adverse effects

KW - Ethiopia

KW - Female

KW - Fluorenes/adverse effects

KW - Hearing Loss, Sensorineural/chemically induced

KW - Humans

KW - Lumefantrine

KW - Malaria, Falciparum/drug therapy

KW - Male

KW - Middle Aged

KW - Proguanil/adverse effects

KW - Quinine/adverse effects

U2 - 10.1186/1475-2875-7-179

DO - 10.1186/1475-2875-7-179

M3 - A1: Web of Science-article

C2 - 18796142

SN - 1475-2875

VL - 7

JO - Malaria Journal

JF - Malaria Journal

M1 - 179

ER -

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

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