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Estimation of the sequestered parasite load in severe malaria patients using both host and parasite markers

Published online by Cambridge University Press:  28 June 2005

L. B. OCHOLA ,
K. MARSH ,
B. LOWE ,
S. GAL ,
G. PLUSCHKE  and
T. SMITH
L. B. OCHOLA
Affiliation:
Swiss Tropical Institute, Socinstrasse 57, Postfach, CH-4002, Basel, Switzerland Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Research Coast, P.O. Box 230, Kilifi, Kenya
K. MARSH
Affiliation:
Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Research Coast, P.O. Box 230, Kilifi, Kenya Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK
B. LOWE
Affiliation:
Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Research Coast, P.O. Box 230, Kilifi, Kenya
S. GAL
Affiliation:
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK
G. PLUSCHKE
Affiliation:
Swiss Tropical Institute, Socinstrasse 57, Postfach, CH-4002, Basel, Switzerland
T. SMITH
Affiliation:
Swiss Tropical Institute, Socinstrasse 57, Postfach, CH-4002, Basel, Switzerland
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Abstract

The virulence of the malaria parasite Plasmodium falciparum is due, in part, to its ability to cytoadhere in deep vascular beds. Our inability to quantify the load of sequestered parasites hampers our understanding of the pathophysiological mechanisms involved in disease progression and complicates diagnosis. In this study we evaluate potential biochemical markers of sequestered load by comparing them with estimates of the sequestered load from a statistical model fitted to longitudinal patterns of peripheral parasite densities in a series of 22 patients with severe Plasmodium falciparum malaria. The markers comprised the host factors: haematocrit, circulating host DNA, sTNF-R75 and parasite derived products HRP2, pLDH, pigments and circulating parasite DNA. We investigated the suitability of these markers in determining sequestered loads in patients on quinine treatment. Observed peripheral parasitaemia, plasma levels of sTNF-R75 and circulating parasite DNA were most strongly correlated with estimates of sequestered loads on admission. However the dynamics of both sTNF-R75 and circulating parasite DNA during follow-up were very different from those of the estimated sequestered mass. These analyses suggest that none of the markers gave reliable estimates of the current sequestered load, though they may reflect the history of infection. Longitudinal analyses are needed that allow for the clearance rates of the marker molecules and for variations between hosts in the history of parasitaemia.

Keywords

Plasmodium falciparumsequestrationbiochemical and parasitological markersstatistical models
Type
Research Article
Information
Parasitology , Volume 131 , Issue 4 , October 2005 , pp. 449 - 458
Copyright
© 2005 Cambridge University Press

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