i.e. mating assurance. During the course of a malaria infection in the
vertebrate host, the blood environment becomes increasingly deleterious
for the parasite: accompanying the increasing anaemia (caused in part by
parasite-induced haemolysis), there is a developing immune response
against the parasite. Until recently, the effect of the host’s immune
responses on parasite sexual development was thought to be restricted
to stimulation of gametocytogenesis (Carter and Graves, 1988). However,
it has been recently demonstrated that such changes in the blood
environment may also alter parasite sex determination. In animal models,
the proportion of gametocytes that were male was significantly elevated
when the vertebrate host was in a state of increased erythropoiesis
(red blood-cell production) and that the hormone responsible for
triggering erythropoiesis, erythropoietin, was implicated in this increased
allocation of male gametocytes (Paulet al., 2000). Erythropoiesis is
induced in response to increased anaemia, such as that resulting from
Plasmodiumasexual-stage proliferation. Sexual stages are produced from
these asexual stages and therefore the immune and haematological
environment within which the sexual stages occur will worsen over time,
largely due to their asexual progenitors. The immune system also
responds to the sexual stages themselves, and this response is actually
effective against the gametes once they are formed within the mosquito
blood meal (Carter et al., 1979). Essentially, an antibody response
agglutinates the gametes and slows down the ability of the male gametes
(equivalent to actively searching sperm) to find a female gamete, which
they must do within 30 min to achieve successful fertilization and hence
infection of the mosquito. Therefore both erythropoiesis (reflecting the
extent of parasite-induced anaemia) and the immune response to gameto-
cytes (produced from these asexual stages) increase simultaneously
(Fig. 10.3a). Intuitively, if males become individually less efficient, pro-
ducing more males would compensate for this. In the highly charged
blood environment during a malaria infection, fertilization is actually
very inefficient: very few gametocytes become zygotes. Can subtle
changes in sex ratio make a difference? Using a simple heuristic model
of fertilization (where two random clouds of males and females unite),
producing compensatory males can, in theory, have a dramatic effect on
zygote production. Figure 10.3b shows the mean oocyst density found in
mosquitoes over the course of an actual vertebrate infection where the sex
ratio becomes increasingly male. Using the fertilization model, a dramatic
decrease in zygotes is predicted if the sex ratio had remained female-
biased, purely as a result of the physics of fertilization (Paulet al., 1999a).
Direct evidence that sex allocation is important and probably adaptive
for mating assurance was provided by manipulating the sex ratio
experimentally. The sex ratio was increased precociously by artificially
elevating the erythropoietin levels during the host infection at a time
when asexual parasite damage and the host’s immune response were both
minimal, and this increase in sex ratio was accompanied by a drop in
mosquito infectivity rate (Paulet al., 2000). Why? Simply because theParasite Sex Determination 213