Determinants of retinopathy and short-term neurological outcomes after cerebral malaria

Abstract

Neurological abnormalities are frequent after cerebral malaria (CM) resolves. The identification of survivors that should be prioritized during follow-up after CM is necessary for post-hospitalization care. We analysed social, clinical, and immune determinants of malarial retinopathy (MR) and short-term neurological outcomes after CM. Children aged 24 to 71 months with CM were prospectively followed-up until 28 days after admission at two hospitals in Benin. Direct ophthalmoscopy was performed shortly after admission. Plasma biomarkers were measured at admission. A neurocognitive deficit screener was administered at discharge and 21-28 days after admission. Of 70 children, 20 died before discharge (28.6%). Neurological deficits decreased from 100% on admission to 48.9% at discharge, and to 16.7% at 21-28 days after admission. MR was found in 58% of children. In multivariate analysis, factors associated with MR were a traditional consultation before admission and study site. In addition, neurological deficits were associated with MR (Odds Ratio 5.54 95% CI (1.30-23.54)). In univariate analysis, higher plasma levels of angiopoietin-2 were associated with neurological deficit at discharge and at days 21-28 post-admission. Therefore, MR and endothelium activation may be markers of neurological deficit, the former at hospital discharge and the latter at discharge and at D21-D28 post-admission.

Keywords: Cerebral malaria; Children; Immune markers; Neurological deficit; Retinopathy; West Africa.

Fig. 1

Flow diagram of the study participants.

Fig. 2

Fundus photograph of a paediatric patient showing white-centred retinal haemorrhages (see arrows).

Fig. 3

Association of urinary and plasma immune markers with fundoscopy status (A) and neurological deficits at discharge (B) and between 21 and 28 days post-admission (C). The heatmap presents the means of normalized values to the maximum value of each biomarker x 100. Detailed values are presented in Supplementary Tables 1 and 2. The Mann–Whitney U-test was used to test associations, * indicates p < 0.05.