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Title: Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria
Authors: Josh Hanson
Sophia W.K. Lam
Kishore Chandra Mahanta
Rajayabardhan Pattnaik
Shamsul Alam
Sanjib Mohanty
Mahatab Uddin Hasan
Amir Hossain
Prakaykaew Charunwatthana
Kesinee Chotivanich
Richard J. Maude
Hugh Kingston
Nicholas P. Day
Saroj Mishra
Nicholas J. White
Arjen M. Dondorp
Cairns Base Hospital
Mahidol University
Ispat General Hospital
Chittagong Medical College Hospital
Nuffield Department of Clinical Medicine
Keywords: Medicine
Issue Date: 15-Aug-2012
Citation: Journal of Infectious Diseases. Vol.206, No.4 (2012), 571-579
Abstract: Background. Sequestration of parasitized erythrocytes in the microcirculation is considered the central pathophysiological process in severe falciparum malaria. Hypovolemia with reduced oxygen delivery and microvascular obstruction have different implications for patient management; however, their relative contributions to disease severity are uncertain. Methods. Adult patients (n = 28) with severe Plasmodium falciparum malaria were enrolled in a prospective hemodynamic study. Volume status and oxygen delivery were assessed using transpulmonary thermodilution. Microvascular sequestration was measured using orthogonal polarized spectroscopy. Findings. Duration of therapy before study enrollment was correlated with the amount of directly visualized and quantitated microvascular sequestration (P = .03). The amount of sequestration correlated with plasma lactate (r s = 0.55; P = .003) and disease severity (r s = 0.41; P = .04). In patients who had received artesunate for < 10 hours, sequestration was higher in fatal cases than in survivors: median (range) 45% (32-50) vs 15% (0-40); P = .03). Parasite biomass estimated from plasma P. falciparum histidine-rich protein 2 correlated positively with disease severity (r s = 0.48; P = .01) and was significantly higher in patients who died (P = .046). There was no relationship between oxygen delivery and disease severity (P = .64) or outcome (P = .74). Interpretation. Vital organ dysfunction in severe malaria results primaril y from sequestration of parasitized erythrocytes in the microvasculature rather than reduction in circulating blood volume and oxygen delivery. © The Author 2012.
ISSN: 00221899
Appears in Collections:Scopus 2011-2015

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