Impact of Oxidative Stress on Risk of Death and Readmission in African Children With Severe Malaria: A Prospective Observational Study

Daniel B. Blatt, Benjamin Hanisch, Katrina Co, Dibyadyuti Datta, Caitlin Bond, Robert O. Opoka, Sarah E. Cusick, Ian C. Michelow, Chandy C. John

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

BACKGROUND: We hypothesized that oxidative stress in Ugandan children with severe malaria is associated with mortality.

METHODS: We evaluated biomarkers of oxidative stress in children with cerebral malaria (CM, n = 77) or severe malarial anemia (SMA, n = 79), who were enrolled in a randomized clinical trial of immediate vs delayed iron therapy, compared with community children (CC, n = 83). Associations between admission biomarkers and risk of death during hospitalization or risk of readmission within 6 months were analyzed.

RESULTS: Nine children with CM and none with SMA died during hospitalization. Children with CM or SMA had higher levels of heme oxygenase-1 (HO-1) (P < .001) and lower superoxide dismutase (SOD) activity than CC (P < .02). Children with CM had a higher risk of death with increasing HO-1 concentration (odds ratio [OR], 6.07 [95% confidence interval {CI}, 1.17-31.31]; P = .03) but a lower risk of death with increasing SOD activity (OR, 0.02 [95% CI, .001-.70]; P = .03). There were no associations between oxidative stress biomarkers on admission and risk of readmission within 6 months of enrollment.

CONCLUSIONS: Children with CM or SMA develop oxidative stress in response to severe malaria. Oxidative stress is associated with higher mortality in children with CM but not with SMA.

CLINICAL TRIALS REGISTRATION: NCT01093989.

Original languageEnglish (US)
Pages (from-to)714-722
Number of pages9
JournalJournal of Infectious Diseases
Volume226
Issue number4
DOIs
StatePublished - Aug 15 2022

Bibliographical note

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Keywords

  • Plasmodium falciparum
  • cerebral malaria
  • child
  • heme oxygenase-1
  • malaria
  • malondialdehyde
  • oxidative stress
  • severe malarial anemia
  • superoxide dismutase
  • Superoxide Dismutase/blood
  • Prospective Studies
  • Malaria, Falciparum/complications
  • Oxidative Stress
  • Patient Readmission
  • Anemia/physiopathology
  • Humans
  • Uganda/epidemiology
  • Infant
  • Randomized Controlled Trials as Topic
  • Malaria, Cerebral/complications
  • Biomarkers/blood
  • Heme Oxygenase-1/blood
  • Child

PubMed: MeSH publication types

  • Observational Study
  • Journal Article
  • Research Support, N.I.H., Extramural

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