{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T01:57:20Z","timestamp":1762999040089},"reference-count":48,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,2]]},"abstract":"<jats:p>Although artemisinin-based combination therapies (ACTs) are widely viewed as safe drugs with a wide therapeutic dose range, concerns about neuroauditory safety of artemisinins arose during their development. A decade ago, reviews of human data suggested a potential neuro-ototoxic effect, but the validity of these findings was questioned. With 5\u201310 years of programmatic use, emerging artemisinin-tolerant falciparum malaria in southeast Asia, and the first calls to consider an increased dose of artemisinins, we review neuroauditory safety data on ACTs to treat uncomplicated falciparum malaria. Fifteen studies reported a neurological or auditory assessment. The large heterogeneity of neuro-ototoxic end points and assessment methodologies and the descriptive nature of assessments hampered a formal meta-analysis and definitive conclusions, but they highlight the persistent lack of data from young children. This subgroup is potentially most vulnerable to any neuroauditory toxicity because of their development stage, increased malaria susceptibility, and repeated ACT exposure in settings lacking robust safety monitoring.<\/jats:p>","DOI":"10.4269\/ajtmh.13-0702","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T06:49:05Z","timestamp":1401259745000},"page":"62-73","source":"Crossref","is-referenced-by-count":24,"title":["Neuroauditory Toxicity of Artemisinin Combination Therapies\u2014Have Safety Concerns Been Addressed?"],"prefix":"10.4269","volume":"91","author":[{"given":"Virginia","family":"Ramos-Mart\u00edn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Gonz\u00e1lez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Mackenzie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Schmutzhard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Pace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Lalloo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianne J.","family":"Terlouw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"year":"2012","series-title":"Novartis Malaria Initiative","author":"Novartis","key":"R1"},{"issue":"(Suppl 1)","key":"R2","series-title":"Trans R Soc Trop Med Hyg","first-page":"S33","article-title":"Neurotoxicity in animals due to arteether and artemether","volume":"88","author":"Brewer","year":"1994"},{"key":"R3","series-title":"Brain Res Bull","first-page":"199","article-title":"Dose-dependent brainstem neuropathology following repeated arteether administration in rats","volume":"45","author":"Genovese","year":"1998"},{"key":"R4","series-title":"Pharmacol Biochem Behav","first-page":"449","article-title":"Behavioral and neural toxicity of arteether in rats","volume":"60","author":"Genovese","year":"1998"},{"key":"R5","series-title":"Am J Trop Med Hyg","first-page":"423","article-title":"Neuropathologic toxicity of artemisinin derivatives in a mouse model","volume":"67","author":"Nontprasert","year":"2002"},{"key":"R6","series-title":"Trans R Soc Trop Med Hyg","first-page":"99","article-title":"Assessment of the neurotoxicity of oral dihydroartemisinin in mice","volume":"96","author":"Nontprasert","year":"2002"},{"key":"R7","series-title":"Am J Trop Med Hyg","first-page":"390","article-title":"Arteether: risks of two-week administration in Macaca mulatta","volume":"56","author":"Petras","year":"1997"},{"key":"R8","series-title":"Anat Embryol (Berl)","first-page":"383","article-title":"Arteether-induced brain injury in Macaca mulatta. 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