High plasma erythropoietin levels are associated with prolonged coma duration and increased mortality in children with cerebral malaria

Estela Shabani, Robert O. Opoka, Richard Idro, Robert Schmidt, Gregory S. Park, Paul Bangirana, Gregory M. Vercellotti, James S. Hodges, John A. Widness, Chandy John

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background. Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes. Methods. A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes. Results. After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95% confidence interval, 1.09-2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors. Conclusions. High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalClinical Infectious Diseases
Volume60
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Cerebral Malaria
Child Mortality
Coma
Erythropoietin
Cerebrospinal Fluid
Mortality
Neurologic Manifestations
Nervous System
Clinical Trials
Uganda
Population Growth
Platelet Activation
Radioimmunoassay
Hemoglobins
Stroke
Confidence Intervals

Keywords

  • Cerebral malaria
  • Erythropoietin
  • Mortality
  • Neurologic deficits

ASJC Scopus subject areas

  • Medicine(all)
  • Microbiology (medical)
  • Infectious Diseases

Cite this

High plasma erythropoietin levels are associated with prolonged coma duration and increased mortality in children with cerebral malaria. / Shabani, Estela; Opoka, Robert O.; Idro, Richard; Schmidt, Robert; Park, Gregory S.; Bangirana, Paul; Vercellotti, Gregory M.; Hodges, James S.; Widness, John A.; John, Chandy.

In: Clinical Infectious Diseases, Vol. 60, No. 1, 01.01.2015, p. 27-35.

Research output: Contribution to journalArticle

Shabani, E, Opoka, RO, Idro, R, Schmidt, R, Park, GS, Bangirana, P, Vercellotti, GM, Hodges, JS, Widness, JA & John, C 2015, 'High plasma erythropoietin levels are associated with prolonged coma duration and increased mortality in children with cerebral malaria', Clinical Infectious Diseases, vol. 60, no. 1, pp. 27-35. https://doi.org/10.1093/cid/ciu735
Shabani, Estela ; Opoka, Robert O. ; Idro, Richard ; Schmidt, Robert ; Park, Gregory S. ; Bangirana, Paul ; Vercellotti, Gregory M. ; Hodges, James S. ; Widness, John A. ; John, Chandy. / High plasma erythropoietin levels are associated with prolonged coma duration and increased mortality in children with cerebral malaria. In: Clinical Infectious Diseases. 2015 ; Vol. 60, No. 1. pp. 27-35.
@article{9c23371d25604dd8bb92a3f634bfe9e8,
title = "High plasma erythropoietin levels are associated with prolonged coma duration and increased mortality in children with cerebral malaria",
abstract = "Background. Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes. Methods. A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes. Results. After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95{\%} confidence interval, 1.09-2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors. Conclusions. High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM.",
keywords = "Cerebral malaria, Erythropoietin, Mortality, Neurologic deficits",
author = "Estela Shabani and Opoka, {Robert O.} and Richard Idro and Robert Schmidt and Park, {Gregory S.} and Paul Bangirana and Vercellotti, {Gregory M.} and Hodges, {James S.} and Widness, {John A.} and Chandy John",
year = "2015",
month = "1",
day = "1",
doi = "10.1093/cid/ciu735",
language = "English (US)",
volume = "60",
pages = "27--35",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - High plasma erythropoietin levels are associated with prolonged coma duration and increased mortality in children with cerebral malaria

AU - Shabani, Estela

AU - Opoka, Robert O.

AU - Idro, Richard

AU - Schmidt, Robert

AU - Park, Gregory S.

AU - Bangirana, Paul

AU - Vercellotti, Gregory M.

AU - Hodges, James S.

AU - Widness, John A.

AU - John, Chandy

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background. Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes. Methods. A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes. Results. After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95% confidence interval, 1.09-2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors. Conclusions. High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM.

AB - Background. Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes. Methods. A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes. Results. After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95% confidence interval, 1.09-2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors. Conclusions. High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM.

KW - Cerebral malaria

KW - Erythropoietin

KW - Mortality

KW - Neurologic deficits

UR - http://www.scopus.com/inward/record.url?scp=84979857834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979857834&partnerID=8YFLogxK

U2 - 10.1093/cid/ciu735

DO - 10.1093/cid/ciu735

M3 - Article

VL - 60

SP - 27

EP - 35

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 1

ER -