86

■Bio-mathematics, Statistics and Nano-Technologies: Mosquito Control Strategies

of immunity. The study in [45] is just illustrative without any field data and it handles a

single undifferenciated form of immunity. There is limited quantitative data from which to

estimate rates of decay of immune protection against malaria.

5.2.6

Malaria parasite variants

Malaria parasite diversity and transmission intensity affect the acquisition of parasito-

logical immunity (Table 5.1) [104]. The time needed to develop this immunity is thought

to be directly proportional to parasite diversity (i.e., genetic diversity of Plasmodium in-

fection) and inversely proportional to transmission intensity [90], [164]. As earlier men-

tioned, there are five species known to cause malaria in humans, each of which comprises

multitudes of variants. The strain theory by Gupta and Day [123] assumed that malaria

comprised of discrete, independently transmitted, immutable strains [121], [122]. This def-

inition entails that a strain retains its identity in a locality where other strains occur such

that the gametocytes of one strain should be resistant to fertilization by another. The the-

ory has been considered inappropriate since Plasmodium, just like other protozoan and

bacterial pathogens, has the ability to modify surface protein expression, and thereby alter

the profile of antigens that are exposed to the immune system of a host [138], [180]. This

results in the amplification of extensive repertoires of multi-copy, hyper-variable gene fam-

ilies that encode infected erythrocyte or merozoite surface proteins. Thus, a single parasite

genotype can express numerous and diverse antigenic and functional phenotypes upon re-

infection [180].

Additionally, when mosquitos acquire gametocytes of two different clones in a blood

meal, crossing generates recombinant clones differing from their parental genotypes [176],

[177], [178]. The high level of antigenic diversity is believed to be sustained by both gene

conversion and recombination events [105], [139], [138]. This mechanism of antigenic

variation enables malaria parasites to succeed in bypassing the immune response of a host,

to establish long-term, persistent infections, thereby increasing the efficiency by which

they are transmitted to mosquito vector [173]. This genetic diversity of the parasites is one

of the major causes of the slow acquisition of immunity to malaria [167]. Thus, the more

individuals are exposed to diverse circulating parasites, the more they develop effective

anti- malarial immunity [77], [34], [86], [95]. On the other hand, increasing the number of

locally circulating variants can prolong the time needed to develop broad immunity [192].

Thus, the term strain can be used for a freely mixing unstructured population of par-

asites, recovered from a source in a given geographical area, that possesses confirmed or

suspected distinctive characteristics that may be the results of the pressure of natural se-

lection [164]. This idea of freely mixing strains implies that the control of malaria may

be far more difficult than previously assumed. Strains of a given species of Plasmodium

can be viewed in this context as different races of the same Plasmodium species which

apparently share common antigens [141], [88]. This suggests that if a definite immunity is

built against a strain of P. falciparum for instance, it extends to the strain of same species in

several hundred miles away. In the experiment conducted in [141], the different response to

infection appeared to be much more dependent on the quantitative degree of immunity of