Biology Reference
In-Depth Information
11.1.5. Deformability and fragility of parasitized erythrocytes
In
P. falciparum
, deformability of both infected and non-infected RBCs
is reduced and is thought to contribute to impaired organ perfusion
(
Dondorp et al., 1999
). In contrast, the deformability of vivax-infected
RBCs is increased (
Suwanarusk et al., 2004
;
Handayani et al., 2009
). This
may enable
P. vivax
to pass through the narrow interendothelial slits of
the splenic sinusoids (mean dimensions 1.89 × 0.65 µm) (
Handayani
et al., 2009
;
Deplaine et al., 2011
) and makes it an unlikely mechanism
for impaired organ perfusion in severe vivax malaria. Such deformability
may, however, be accompanied by increased fragility of both
P. vivax
-
infected and -non-infected RBCs (
Handayani et al., 2009
), though the
extent to which this is an artefact of the
ex vivo
microfluidic system used
is unknown.
11.1.6. Endothelial activation and altered thrombostasis
Concentrations of circulating endothelial activation markers are as high
(ICAM-1 and E-selectin) or higher (angiopoietin-2) in uncomplicated vivax
malaria than in falciparum malaria (
Yeo et al., 2010a
;
Jakobsen et al., 1994
).
Endothelial dysfunction and impaired NO bioavailability are significant
contributors to severe falciparum malaria (
Yeo et al., 2007
,
2009
,
2010b
),
but their importance in severe vivax malaria is not known. Autopsies in fatal
cases of
P. vivax
malariotherapy of neurosyphilis demonstrated endothelial
'stimulation'(
Bruetsch, 1932a
;
Clark and Tomlinson, 1949
), and endothelial
activation and damage has been described in fatal vivax-associated ARDS
(
Valecha et al., 2009
). With the reduced ability of
P. vivax
to cytoadhere,
pathogenic consequences of endothelial activation in promoting seques-
tration of parasitized red cells will be much less in vivax malaria than in
falciparum malaria.
However, other consequences of endothelial activation and altered
thrombostasis may be more important in
P. vivax
infection. Elevated von
Willebrand factor (VWF) and reduced ADAMTS-13 have been associ-
ated with disease severity in falciparum malaria (
Larkin et al., 2009
;
Lowenberg et al., 2010
). Increased procoagulant activity (
Hemmer
et al., 2006
), VWF (
de Mast et al., 2008
) and ADAMTS-13 deficiency
(
de Mast et al., 2008
) have now been reported in uncomplicated vivax
malaria. The role of altered haemostatic pathways, intravascular coag-
ulation and endothelial inflammation through increased formation of
ultra-large VWF and platelet aggregates in severe vivax malaria is not
