TY - JOUR
T1 - Apolipoprotein-E4
T2 - risk of severe malaria and mortality and cognitive impairment in pediatric cerebral malaria
AU - Lima-Cooper, Giselle
AU - Ouma, Benson J.
AU - Datta, Dibyadyuti
AU - Bond, Caitlin
AU - Soto, Alejandro A.
AU - Conroy, Andrea L.
AU - Park, Gregory S.
AU - Bangirana, Paul
AU - Joloba, Moses L.
AU - Opoka, Robert O.
AU - Idro, Richard
AU - John, Chandy C.
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
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U2 - 10.1038/s41390-023-02912-8
DO - 10.1038/s41390-023-02912-8
M3 - Article
C2 - 38007518
AN - SCOPUS:85178111607
SN - 0031-3998
JO - Pediatric Research
JF - Pediatric Research
ER -
