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greater concentrations of both pro- and anti-inflammatory cytokines than
P. falciparum
(
Yeo et al., 2010a
;
Hemmer et al., 2006
), the relationships to
disease severity are different in vivax malaria. While plasma concentrations
of the pro-inflammatory cytokines TNF and IFNg are directly related to
disease severity, plasma concentrations of IL-10 are
inversely
related to vivax
disease severity (
Andrade et al., 2010b
), suggesting a deficiency in the anti-
inflammatory response in severe vivax malaria, with an unopposed pro-
inflammatory response. Plasma concentrations of superoxide dismutase, an
enzyme produced in response to oxidative stress, have also been associated
with vivax disease severity (
Andrade et al., 2010a
), but a role in pathogenesis
has not been determined.
Another putative toxin that appears unique to
P. vivax
is a lipid found
in the cholesterol/triglyceride fraction of plasma at the time of paroxysmal
fever (
Karunaweera et al., 2003
,
2007
). This lipid has greater activity than
GPI-like phospholipids (
Karunaweera et al., 2007
), and together with host
cytokines, is known to mediate
in vitro
aggregation of leucocytes, mostly
neutrophils (
Karunaweera et al., 2003
,
2007
). This lipid may also contribute
to the greater pyrogenicity of
P. vivax
.
11.1.4. Cytoadherence and rosetting
A central mechanism in the pathophysiology of severe falciparum malaria
is the cytoadherence of late stages of
P. falciparum
to activated microvascu-
lar endothelium resulting in sequestration and microvascular obstruction
(
Marchiafava and Bignami, 1894
;
MacPherson et al., 1985
;
Pongponratn
et al., 2003
;
Turner et al., 1994
). Since all stages of
P. vivax
are visible in
peripheral blood, albeit with partial depletion of mature stages (
Field and
Shute, 1956
;
Rudolf and Ramsay, 1927
), sequestration is not thought to
occur to a significant degree in vivax malaria or cause end-organ dysfunc-
tion in the same manner as
P. falciparum
(
Anstey et al., 2009
). Recent
in vitro
data show that
P. vivax
-infected RBCs do cytoadhere to endothelial cells,
via ICAM-1 and chondroitin sulphate-A (CSA), with a similar strength but
a 10-fold lower frequency than
P. falciparum
-infected RBCs (
Carvalho et al.,
2010
). Another study showed no cytoadherence to ICAM-1 but did con-
firm cytoadherence to the glycosaminoglycans, CSA and hyaluronic acid
(
Chotivanich et al., 2012
).
Despite some cytoadherence
in vitro
, evidence for sequestration-
mediated pathology in vivax malaria
in vivo
is at best modest. Indirect
physiological studies partitioning pulmonary gas transfer in adults with
vivax malaria showed impairment of the pulmonary capillary vascular
