Severe malaria in children leads to a significant impairment of transitory otoacoustic emissions--a prospective multicenter cohort study.

BACKGROUND: Severe malaria may influence inner ear function, although this possibility has not been examined prospectively. In a retrospective analysis, hearing impairment was found in 9 of 23 patients with cerebral malaria. An objective method to quickly evaluate the function of the inner ear are the otoacoustic emissions. Negative transient otoacoustic emissions are associated with a threshold shift of 20 dB and above. METHODS: This prospective multicenter study analyses otoacoustic emissions in patients with severe malaria up to the age of 10 years. In three study sites (Ghana, Gabon, Kenya) 144 patients with severe malaria and 108 control children were included. All malaria patients were treated with parental artesunate. RESULTS: In the control group, 92.6 % (n = 108, 95 % confidence interval 86.19-6.2 %) passed otoacoustic emission screening. In malaria patients, 58.5 % (n = 94, malaria vs controls p < 0.001, 95 % confidence interval 48.4-67.9 %) passed otoacoustic emission screening at the baseline measurement. The value increased to 65.2 % (n = 66, p < 0.001, 95 % confidence interval 53.1-75.5 %) at follow up 14-28 days after diagnosis of malaria. The study population was divided into severe non-cerebral malaria and severe malaria with neurological symptoms (cerebral malaria). Whereas otoacoustic emissions in severe malaria improved to a passing percentage of 72.9 % (n = 48, 95 % confidence interval 59-83.4 %) at follow-up, the patients with cerebral malaria showed a drop in the passing percentage to 33 % (n = 18) 3-7 days after diagnosis. This shows a significant impairment in the cerebral malaria group (p = 0.012 at days 3-7, 95 % confidence interval 16.3-56.3 %; p = 0.031 at day 14-28, 95 % confidence interval 24.5-66.3 %). CONCLUSION: The presented data show that 40 % of children have involvement of the inner ear early in severe malaria. In children, audiological screening after severe malaria infection is not currently recommended, but is worth investigating in larger studies

Results of Experiment 6 presented in a form that is relevant for interpreting the interaction of change type (CA vs. CD) and gap (continuous, vs. silence gap, vs. noise gap).

<p>The introduction of gaps adversely affected performance on CA but not CD changes. Error bars are 1 SE.</p

Results of the main change detection task (

<p> <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#s4" target="_blank"><b>Experiment 2</b></a><b>). Error bars are 1 SE.</b></p

Results of Experiment 5, change detection as a function of time of change (early vs. late) for CA and CD.

<p>Error bars are 1 SE.</p

Results of

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#s3" target="_blank"><b>Experiment 1</b></a><b> which tested listener's ability to judge whether a probe (a single AM tone) is present within a NC scene.</b> Plotted are sensitivity scores as a function of scene size. Dark blue: probe presented before the scene; light blue: probe presented after the scene. Error bars are 1 standard error (SE).</p

Results of

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#s5" target="_blank"><b>Experiment 3</b></a><b>.</b> A loudness change in the form of a single upwards or downwards step in amplitude was introduced in all stimuli, at the nominal change time. A, B show results from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#s5" target="_blank">Experiment 3</a>A (randomized presentation). C shows d′ data obtained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#s5" target="_blank">Experiment 3</a>B where the same stimuli were presented in blocks according to change type (CA or CD). Error bars are 1 SE.</p

Results of Experiment 4 which tested listeners' ability to identify the component that appeared or disappeared in CA and CD scenes.

<p>In <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#s6" target="_blank">Experiment 4</a>A (left) the probe was identical to the changed component (frequency+AM). In <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#s6" target="_blank">Experiment 4</a>B (right) the probe carrier frequency was fixed at 500 Hz and only the AM varied. Error bars are 1 SE.</p

Results of Experiment 6, comparing performance on continuous scenes (A) and those where a silence (B) or noise-filled (C) gap was inserted at the time of change.

<p>Error bars are 1 SE.</p

Example of the ‘splash’ stimuli.

<p>‘Splashes’ are chords of four concurrently presented 200 ms tones, amplitude modulated at 100 Hz. They occur at the time of change but do not mask any scene components (‘Splash’ frequencies were chosen such that they were separated by at least 2 ERB from each scene component). A: ‘no-change’ (NC) stimulus with six components. B and C show the ‘change-disappear’ (CD) and ‘change-appear’ (CA) variations. Dashed lines show the nominal change time. The plots represent ‘auditory’ spectrograms, generated with a filter bank of 1/ERB wide channels <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#pone.0046167-Moore3" target="_blank">[17]</a> equally spaced on a scale of ERB-rate. Channels are smoothed to obtain a temporal resolution similar to the Equivalent Rectangular Duration <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046167#pone.0046167-Plack1" target="_blank">[41]</a>.</p

Results of Experiment 7, comparing performance on non-interrupted scenes and those where a brief acoustic ‘splash’ occurred at the time of change.

<p>Error bars are 1 SE. Note that the scenes sizes used here are different from the previous experiments. Reducing the maximum scene size to 10 (rather than 14) was necessary because ‘splash’ components and scene elements shared the same frequency pool.</p