Apolipoprotein-E4: risk of severe malaria and mortality and cognitive impairment in pediatric cerebral malaria

Giselle Lima-Cooper, Benson J. Ouma, Dibyadyuti Datta, Caitlin Bond, Alejandro A. Soto, Andrea L. Conroy, Gregory S. Park, Paul Bangirana, Moses L. Joloba, Robert O. Opoka, Richard Idro, Chandy C. John

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: The relationship of apolipoprotein-E4 (APOE4) to mortality and cognition after severe malaria in children is unknown. Methods: APOE genotyping was performed in children with cerebral malaria (CM, n = 261), severe malarial anemia (SMA, n = 224) and community children (CC, n = 213). Cognition was assessed over 2-year follow-up. Results: A greater proportion of children with CM or SMA than CC had APOE4 (n = 162, 31.0%; n = 142, 31.7%; n = 103, 24.2%, respectively, p = 0.02), but no difference was seen in APOE3 (n = 310, 59.4%; n = 267, 59.6%; n = 282, 66.2%, respectively, p = 0.06), or APOE2 (n = 50, 9.6%; n = 39, 8.7%; and n = 41, 9.6%, respectively, p = 0.87). APOE4 was associated with increased mortality in CM (odds ratio, 2.28; 95% CI, 1.01, 5.11). However, APOE4 was associated with better long-term cognition (ß, 0.55; 95% CI, 0.04, 1.07, p = 0.04) and attention (ß 0.78; 95% CI, 0.26, 1.30, p = 0.004) in children with CM < 5 years old, but worse attention (ß, −0.90; 95% CI, −1.69, −0.10, p = 0.03) in children with CM ≥ 5 years old. Among children with CM, risk of post-discharge malaria was increased with APOE4 and decreased with APOE3. Conclusions: APOE4 is associated with higher risk of CM or SMA and mortality in children with CM, but better long-term cognition in CM survivors <5 years of age.

Original languageEnglish
JournalPediatric Research
DOIs
Publication statusAccepted/In press - 2023
Externally publishedYes

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