Charles Darwin University

CDU eSpace
Institutional Repository

 
CDU Staff and Student only
 

Microvascular obstruction and endothelial activation are independently associated with the clinical manifestations of severe falciparum malaria in adults: an observational study

Hanson, Josh, Lee, Sue J., Hossain, Amir, Anstey, Nicholas M., Charunwatthana, Prakaykaew, Maude, Richard J., Kingston, Hugh W. F., Mishra, Saroj K., Mohanty, Sanjib, Plewes, Katherine, Piera, Kim A., Hassan, Mahtab U., Ghose, Aniruddha, Faiz, M. Abdul, White, Nicholas J., Day, Nicholas P. J. and Dondorp, Arjen M. (2015). Microvascular obstruction and endothelial activation are independently associated with the clinical manifestations of severe falciparum malaria in adults: an observational study. BMC Medicine,13(Article No. 122).

Document type: Journal Article
Citation counts: Altmetric Score Altmetric Score is 9
Google Scholar Search Google Scholar
Attached Files (Some files may be inaccessible until you login with your CDU eSpace credentials)
Name Description MIMEType Size Downloads
Download this reading Hanson_59268.pdf Published version application/pdf 913.96KB 5
Reading the attached file works best in Firefox, Chrome and IE 9 or later.

IRMA ID 75039815xPUB866
Title Microvascular obstruction and endothelial activation are independently associated with the clinical manifestations of severe falciparum malaria in adults: an observational study
Author Hanson, Josh
Lee, Sue J.
Hossain, Amir
Anstey, Nicholas M.
Charunwatthana, Prakaykaew
Maude, Richard J.
Kingston, Hugh W. F.
Mishra, Saroj K.
Mohanty, Sanjib
Plewes, Katherine
Piera, Kim A.
Hassan, Mahtab U.
Ghose, Aniruddha
Faiz, M. Abdul
White, Nicholas J.
Day, Nicholas P. J.
Dondorp, Arjen M.
Journal Name BMC Medicine
Publication Date 2015
Volume Number 13
Issue Number Article No. 122
ISSN 1741-7015   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84930163225
Total Pages 11
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DIISR)
Abstract Background
Microvascular obstruction and endothelial dysfunction have both been linked to tissue hypoperfusion in falciparum malaria, but their relative contributions to the disease’s pathogenesis and outcome are unknown.

Methods
Microvascular blood flow was quantified in adults with severe falciparum malaria on their admission to hospital; plasma biomarkers of endothelial function were measured simultaneously. The relationship between these indices and the patients’ clinical findings and in-hospital course was examined.

Results
Microvascular obstruction was observed in 119/142 (84 %) patients; a median (interquartile range (IQR)) of 14.9 % (6.6–34.9 %) of capillaries were obstructed in patients that died versus 8.3 % (1.7–26.6 %) in survivors (P = 0.039). The proportion of obstructed capillaries correlated with the estimated parasite biomass (rs = 0.25, P = 0.004) and with plasma lactate (rs = 0.38, P <0.0001), the strongest predictor of death in the series. Plasma angiopoietin-2 (Ang-2) concentrations were markedly elevated suggesting widespread endothelial activation; the median (IQR) Ang-2 concentration was 21.9 ng/mL (13.4–29.4 ng/mL) in patients that died versus 14.9 ng/mL (9.8–29.3 ng/mL) in survivors (P = 0.035). Ang-2 concentrations correlated with estimated parasite biomass (rs = 0.35, P <0.001) and plasma lactate (rs = 0.37, P <0.0001). Microvascular obstruction and Ang-2 concentrations were not significantly correlated with each other (rs = 0.17, P = 0.06), but were independently associated with plasma lactate (P <0.001 and P = 0.002, respectively).

Conclusions

Microvascular obstruction and systemic endothelial activation are independently associated with plasma lactate, the strongest predictor of death in adults with falciparum malaria. This supports the hypothesis that the two processes make an independent contribution to the pathogenesis and clinical manifestations of the disease.
Keywords Falciparum malaria
Microcirculation
Pathophysiology
Endothelial dysfunction
DOI http://dx.doi.org/10.1186/s12916-015-0365-9   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 4.0 License
URL https://creativecommons.org/licenses/by/4.0/au


© copyright

Every reasonable effort has been made to ensure that permission has been obtained for items included in CDU eSpace. If you believe that your rights have been infringed by this repository, please contact digitisation@cdu.edu.au.

 
Versions
Version Filter Type
Access Statistics: 25 Abstract Views, 5 File Downloads  -  Detailed Statistics
Created: Tue, 26 Jul 2016, 12:53:38 CST