Models of Acquired Immunity to Malaria: A Review

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nism seem to benefit both the host and the incumbent parasite by keeping parasite density

at levels that are not severe before the role of NAI activates. A similar study by Portugal

[81], [82] who explored the possibility of the liver-stage of infection to be modulated by

the presence of an ongoing blood-stage infection and contribute to acquisition of immu-

nity, explains that this mechanism arises as Plasmodium in the blood strives to protects its

niche, perhaps ensuring transmission on the basis of first-come, first-served. This appears

to enable the host immune system to fight one circulating parasite at a time, consequently

raising the host’s chances of survival. In addition, the number of scenarios of liver-stage in-

fections would be more than that of blood-stage infections, boosting the immune response

to the liver stage without exposing the host to blood-stage infection. This action seems to

contribute to the more rapid acquisition of immunity to severe disease (see also [111]).

On the other hand, some deterministic models which consider malaria infection as

binary, assume that an individual can be completely protected from superinfection after

attaining a certain threshold of parasite density [108], [106]. In [108], individuals whose

parasite density are below a defined threshold are described as primary infectious and are

prone to superinfection, whereas secondary infectious individuals are assumed to be com-

pletely protected from superinfection [81], [82]. These theories and studies try to explain

the how the impact of superinfection and can be suppressed; and how NAI to severe dis-

eases can be boosted in non-naive individuals even during the occurrence of superinfection,

but the underlying mechanisms seems either unclear or unrealistic.

In general, the idea that already present chronic infections can protect against super-

infection dates from the work in [168] where the concept of premunition was brought up,

and was used by Cohen and Deans [169] to refer NAI which frequently controls parasite

densities, but does not eliminate infection. However, in [165], the concept of premunition

is used as the limitation of superinfection. Thus, the outcome of superinfection is con-

trolled by limiting the rate of newly infecting homologous and even heterologous (Table

5.2) haplotypes that could get established in the host. This implies that parasites which have

similar antigenic properties with those already existing would be suppressed or controlled

based on the extent of overlap of their antigenic haplotypes i.e the degree of relatedness of

the antigenic repertoire of the incoming infection, with prior experienced antigens [192],

[173], [165], [166], [190], [70]. However, it should be noted that the maximum number

of superinfection decreases with age due to the acquisition of immunity (See also [80],

[165]). This is because chronic malaria infection is known to occur in older individuals

who have mounted immune response which controls parasite densities sufficient enough to

avert clinical attacks but allows the infection to remain at low density [171], [169], [168],

[173]. On the other hand, in non-immune individuals, superinfection poses a high risk of

hyperparasitemia and mortality [82].

5.2.9

Other factors influencing the acquisition of immunity

5.2.9.1

Effect of intervention measures on immunity acquisition and malaria prevalence

Populations utilizing intervention strategies which reduce malaria transmission and

subsequently immunity, such as insecticidal-nets and drug treatment, may also be prone to