Models of Acquired Immunity to Malaria: A Review

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munity is acquired at a rate which is dependent upon the degree of exposure and is highly

effective in adults after uninterrupted lifelong heavy exposure but can also be lost to a con-

siderable extent upon cessation of exposure. Although the rate of loss is yet unclear, it is

expected that realistic modelling should not define immunity duration beforehand as was

done by some early compartmental models. Additionally, in high transmission areas, the

prevalence of malaria infection and the risk of malaria-associated morbidity and mortality

is known to markedly decrease with age. Although immunity is age determined in such

areas, it is clear that increasing age does not in itself result in immunity acquisition since

another and major underlying determinant is not age per se but rather the accumulated in-

fection exposure risk that come with it. Hence, the need to explicitly interplay naturally

acquired immunity with age in a biologically realistic way has been emphasized. The best

evidence to date clearly indicates that NAI may be considered as the product of cumulative

exposure to multiple parasite variants over time, which gives rise to a diverse collection

of variant-specific and a general variant-transcending immune responses. This opposes the

mistaken perception of a life-long strictly variant-specific immunity. It is currently believed

that variant-specific immune response is rapidly induced, but also appears to be short-lived,

whereas the variant-transcending immune response takes time to develop and is long-lived.

In principle, the duration of variant-specific immunity can vary depending on the frequency

of antigenic variation, the polymorphic nature of the antigen, and the inoculation rate ex-

perienced by humans.

Furthermore, natural acquisition of immunity to malaria is believed to be somewhat

stage specific. However, it appears that even though the liver-stage immunity is necessary

as it protects against infection, the blood-stage immunity is the major force shaping the

observed infection dynamics. The development of clinical and parasitological immunity to

malaria is evident in the ability to control the asexual blood-stage parasite density which in

turn limits disease symptoms and pathology. Thus, the most effective part of the immune

response in clinical terms is its ability to limit parasite densities in erythrocytes, which

is the target of ant-malaria drugs. It has also been explained how the use of intervention

measures in a highly immune population which features reduction of exposure, can initially

engender rapid reductions in disease prevalence, after which the previous burden of disease

resurges as the immunity is gradually lost. The negative effect of then having small num-

ber of immune individuals in the population can only be counterbalanced by the sustained

implementation of highly-effective transmission-reducing interventions for an indefinite

period. This can also be augmented by a transmission blocking vaccine which enhances

and artificially induces immunity. The crucial role of climatic factors in the acquisition

and persistence of immunity to malaria has been emphasized. Additionally, the effect of

population dynamics, of especially the vectors, which is the major driver of malaria trans-

mission, should always be taken into account so as to engender a more ideal modeling of

transmission scenarios.

In addressing these complex factors associated with NAI to malaria, the benefits of

individual-based modelling approach are evident. The short-comings of deterministic mod-

els are not reasons for them to be rejected because they provide some quantitative under-

standing of malaria transmission. Instead, the focus is to debug some of the assumptions