Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs) with hearing is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine ( ), artemether-lumefantrine ( ), or amodiaquine ( ) in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared with those of a control group of children ( ) from the same area. Findings. During the acute stage, hearing threshold levels of treated children were significantly elevated compared with controls ( ). The threshold elevations persisted up to 28 days, but no differences in hearing thresholds were evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels during the acute illness, a finding that has implications for learning and development in areas of intense transmission, as well as for evaluating potential ototoxicity of new antimalarial drugs. 1. Background Acute Plasmodium falciparum malaria is associated with varying degrees of neurological involvement, depending on the severity. Few studies have, however, investigated the effect of the disease on hearing specifically in those with uncomplicated malaria. Furthermore, several antimalarial drugs, including quinine [1, 2], chloroquine [3], and mefloquine [4], have been associated with ototoxicity, and certain artemisinin derivatives have also been associated with neuro- or ototoxicity in various animal species [5–9]. Although human studies that have evaluated possible artemisinin-related effects on hearing have, with the exception of one study [10], concluded lack of any clinically relevant ototoxicity or neurotoxicity [11–15], the majority of these studies have been done in adults, in spite of the fact that children are the subgroup of patients who, because of their still developing nervous systems, are more susceptible to such potential treatment-related effects. The lack of studies evaluating the potential effects of newly introduced antimalarial drugs on hearing in children is due to the difficulties in conducting serial audiometric measurements in childhood
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