Biology Reference
In-Depth Information
11.2. Pathophysiology of Specific Syndromes of Severe
Vivax Malaria
11.2.1. Severe vivax anaemia
The aetiology of vivax-associated anaemia is complex and confounded by
intercurrent infection with
P. falciparum
. Likely mechanisms include loss
of both vivax-infected and uninfected red cells from the circulation and
impaired RBC production (see
Anstey et al., 2009
;
Douglas et al., 2012
for reviews). Malariotherapy data show that removal of red cells from the
circulation is particularly pronounced during acute infection (
Collins et al.,
2003
;
Kitchen, 1938
), over and above the rate modelled from reticulocyte
loss and impaired supply of mature red cells (
McQueen and McKenzie,
2004
;
Antia et al., 2008
). The removal of red cells occurs from both extra-
vascular loss in the spleen and from intravascular red cell loss (
Douglas et al.,
2012
). Despite the lower parasite biomass of
P. vivax
relative to
P. falciparum
,
red-cell removal is comparable because of the greater proportional removal
of uninfected red cells following
P. vivax
infection. In vivax malaria, approx-
imately 34 uninfected red cells are removed for every infected red cell
(
Collins et al., 2003
;
Douglas et al., 2012
) compared to approximately eight
uninfected red cells for every infected red cell in falciparum malaria (
Price
et al., 2001
;
Jakeman et al., 1999
). Mechanisms for this difference are not
clear, but may relate to the greater proportionate inflammatory response in
vivax relative to falciparum malaria (
Hemmer et al., 2006
;
Yeo et al., 2010a
),
both systemically and possibly in the spleen where the majority of extravas-
cular haemolysis occurs (
Douglas et al., 2012
). Littman showed the impor-
tance of the spleen as a site of extravascular RBC removal when he found
that a relapsed
P. vivax
infection in a splenectomised patient did not cause
anaemia, whereas
P. vivax
infection in the same patient before splenectomy
caused severe anaemia (
Littman, 1974
). The greater proportionate inflam-
matory response to
P. vivax
has been hypothesized to be paraleled by greater
red-cell oxidative stress (
Douglas et al., 2012
;
Bhattacharya and Swarup-
Mitra, 1987
;
Meera et al., 1999
;
Erel et al., 1997
). Although removal of both
infected and uninfected erythrocytes is greatest during the early stages of
infection, enhanced removal of uninfected RBCs has been shown to persist
for at least 5 weeks after antimalarial treatment (
Looareesuwan et al, 1987
;
Woodruff et al., 1979
).
An additive factor in the anaemia of
P. vivax
is relapse. In equatorial
latitudes, over 80% of
P. vivax
infections relapse at 3-4-week intervals and
progressive anaemia is associated with recurrent episodes of haemolysis and
dyserythropoiesis prior to haematological recovery from the preceding
