Elevated plasma soluble ST2 levels are associated with neuronal injury and neurocognitive impairment in children with cerebral malaria

Authors

Elizabeth Fernander, Indiana University, USA
Pontian Adogamhe, Indiana University, USA
Dibyadyuti Datta, Indiana University, USA
Caitlin Bond, Inidana University, USA
Yi Zhao, Indiana University, USA
Paul Bangirana, Makerere University, Uganda
Andrea Conroy, Inidnana University, USA
Robert Opoka, Aga Khan UniversityFollow
Chandy John, Indiana University, USA

Document Type

Article

Department

Paediatrics and Child Health (East Africa)

Abstract

Background: Murine experimental cerebral malaria studies suggest both protective and deleterious central nervous system effects from alterations in the interleukin-33 (IL-33)/ST2 pathway.

Methods: We assessed whether soluble ST2 (sST2) was associated with neuronal injury or cognitive impairment in a cohort of Ugandan children with cerebral malaria (CM, n=224) or severe malarial anemia (SMA, n=193).

Results: Plasma concentrations of sST2 were higher in children with CM than in children with SMA or in asymptomatic community children. Cerebrospinal fluid (CSF) sST2 levels were elevated in children with CM compared with North American children. Elevated plasma and CSF ST2 levels in children with CM correlated with increased endothelial activation and increased plasma and CSF levels of tau, a marker of neuronal injury. In children with CM who were ≥5 years of age at the time of their malaria episode, but not in childrenage, elevated risk factor-adjusted plasma levels of sST2 were associated with worse scores for overall cognitive ability and attention over a 2-year follow-up.

Conclusions: The study findings suggest that sST2 may contribute to neuronal injury and long-term neurocognitive impairment in older children with CM.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Faculty at Case Western Reserve University School of Medicine

Recommended Citation

Fernander, E., Adogamhe, P., Datta, D., Bond, C., Zhao, Y., Bangirana, P., Conroy, A., Opoka, R., John, C. (2022). Elevated plasma soluble ST2 levels are associated with neuronal injury and neurocognitive impairment in children with cerebral malaria. Faculty at Case Western Reserve University School of Medicine, 7(1).
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_paediatr_child_health/277