Biology Reference
In-Depth Information
11.1.2. Relapse
A fundamental difference between
P. falciparum
and
P. vivax
is the ability of
P. vivax
to relapse from dormant hypnozoites and cause repeated episodes of
clinical and subclinical infections. Differences in relapse patterns may be a
major contributor to the geographic variation in vivax morbidity and dis-
ease severity. In tropical regions,
P. vivax
is characterized by frequent relapses
3-6 weeks apart (
Goller et al., 2007
and reviewed by
Coatney et al., 1971
),
resulting in recurrent infections often with heterologous strains to which
there is little cross-immunity (
Imwong et al., 2007
;
Chen et al., 2007
). Fre-
quent recurrent infections prevent adequate time for the patient to achieve
haematological recovery from each bout of haemolysis. In contrast, in tem-
perate areas, relapses are fewer and delayed, and the associated impact of
each recurrence is less (see
Price et al., 2009
;
Goller et al., 2007
;
Song et al.,
2003
for review).
11.1.3. Greater inflammatory response in
P. vivax
than
P. falciparum
Plasmodium vivax
has a lower pyrogenic threshold than
P. falciparum
(
Ross
and Thomson, 1911
;
Kitchen, 1949a
). Cytokine production (
Hemmer et al.,
2006
;
Karunaweera et al., 1992
;
Yeo et al., 2010a
), endothelial activation
(
Yeo et al., 2010a
) and pulmonary inflammatory responses (
Anstey et al.,
2007
) are higher during and after
P. vivax
infections than in
P. falciparum
infections of similar parasite biomass. Although the inflammatory corre-
lates of the lower pyrogenic threshold have been reported, the underlying
mechanism(s) have not. Hypothesised reasons include differences between
the two species in candidate 'malaria toxin(s)', including glycosylphosphati-
dylinositol (GPI) (
Boutlis et al., 2005
) and
Plasmodium
DNA associated with
haemozoin (
Parroche et al., 2007
). Because
P. vivax
has a greater GC con-
tent, approximately twice that of
P. falciparum
(
Carlton et al., 2008
), greater
concentrations of TLR9-stimulating CpG motifs within
P. vivax
haemozoin
may account for greater inflammatory responses (
Anstey et al., 2009
). It is
possible that
Plasmodium
spp. priming of the innate immune response to
bacterial products (
Franklin et al., 2009
) may be greater in
P. vivax
than
that shown in
P. falciparum
, though this remains to be demonstrated. If so,
this may explain the septic shock-like presentations increasingly reported in
severe vivax disease (
Leoratti et al., 2012
) (Section
11.1.6
).
In falciparum malaria, plasma concentrations of the pro-inflammatory
cytokine TNF (
Kern et al., 1989
;
Grau et al., 1989
;
Day et al., 1999
) and the
anti-inflammatory cytokine IL-10 (
Anstey et al., 1996
;
Day et al., 1999
) are
directly related to disease severity. Although
P. vivax
is capable of eliciting
