Brain-derived Neurotrophic Factor Is Associated With Disease Severity and Clinical Outcome in Ugandan Children Admitted to Hospital With Severe Malaria.

01 Feb 2017
McDonald CR, Conroy AL, Hawkes M, Elphinstone RE, Gamble JL, Hayford K, Namasopo S, Opoka RO, Liles WC, Kain KC

BACKGROUND

Malaria remains a leading cause of childhood death and neurologic disability in sub-Saharan Africa. Here, we test the hypothesis that malaria-induced alterations to circulating brain-derived neurotrophic factor (BDNF) are associated with poor clinical outcomes in children with severe malaria.

METHODS

We quantified BDNF (by enzyme-linked immunosorbent assay) in plasma samples collected [at presentation (day 1), day 3 and day 14], during a prospective study of Ugandan children admitted to hospital with severe malaria (n = 179).

RESULTS

BDNF concentration at presentation (day 1) was lower in children with cerebral malaria (P < 0.01), coma (P < 0.01), Lambaréné Organ Dysfunction Score >1 (P < 0.05) and respiratory distress (P < 0.01). Higher BDNF concentration at presentation was associated with shorter time to coma recovery [hazard ratio = 1.655 (1.194-2.293); P = 0.002] and a reduced odds ratio of disability [0.50 (0.27-0.94); P = 0.047] and death [0.45 (0.22-0.92); P = 0.035]. BDNF concentration was lower on day 1 and increased in children surviving severe malaria (day 14; P < 0.0001).

CONCLUSIONS

Our findings provide the new evidence linking circulating BDNF with disease severity, coma recovery and clinical outcome in children with severe malaria.