Biology Reference
In-Depth Information
pathogenesis of malaria infection, particularly when produced by CD4
þ
Tcells.
52,53
Thus in an Ascaris-infected individual, protective effects may
be observed if the Ascaris infection pre-empts or supplements the
production of immunoregulatory cytokines generated by the malaria
infection. However, the role of Ascaris co-infection in modulating
malarial anaemia is less clear (Abanyie et al., unpublished observa-
tions).
54
e
56
In situations where the immunoregulatory immune
responses generated by malaria infection are sufficiently robust, it may
be that additional Ascaris-mediated immune regulation has no effect on
modulating the pathogenesis of malaria infection.
An alternative mechanism has been proposed to explain the protec-
tive effects of Ascaris co-infection on cerebral malaria and involves the
effects of IgE complexes induced by Ascaris infection. IgE complexes
may stimulate the production of parasiticidal nitric oxide from endo-
thelial cells by ligating the IgE receptor Fc
RII reducing localized pRBC
sequestration by downregulating the expression of intercellular adhe-
sion molecule-1 (ICAM-1), an adhesin for RBCs infected with Plasmo-
dium falcaiprum.
57
To support this hypothesis it has been observed that
Ascaris/malaria-co-infected individuals have higher levels of reactive
nitrogen intermediates (the end products of nitric oxide) and a lower
number of circulating schizonts when compared with those infected
with malaria alone.
7
In addition during malaria infection one study
showed a positive correlation between circulating IgE levels and reactive
nitrogen intermediates.
58
Although some evidence from experiments
carried out on lung endothelial cells in vitro lends weight to the validity
of this hypothesis,
59
no correlation between total IgE levels and pro-
tection from cerebral malaria has been found
60
and it has not yet been
formally shown that IgE complexes induced in Ascaris infection lessen
the sequestration of pRBCs in malaria infection. However, with the
development of luciferase-expressing parasite lines in rodent models of
malaria
61
it will now be possible to assess the effect of IgE complexes on
the sequestration of pRBCs using whole body scanning of malaria-
infected mice co-infected with model GI helminth infections or artifi-
cially injected with IgE complexes.
While preliminary evidence suggests that de-worming programs may
in some situations adversely affect the pathogenesis of malaria infections
as observed in the late 1970s by Murray et al.
62,63
reduced transmission
of malaria within a malaria-endemic area may be a benefit of de-worming
Ascaris-infected individuals. Co-infection has been associated with
increased carriage of gametocytes, the transmissible form of malaria in the
blood stream.
64
Mixed infections with P. falciparum and P. vivax were
also elevated in co-infected individuals in this same study area com-
pared to individuals with just malaria infection.
65
It is possible that
Ascaris-generated immunoregulatory responses may impact on the
ε
