Models of Acquired Immunity to Malaria: A Review

■73

agent-based models (ABMs) of human and mosquito populations, and populations of par-

asites within individual human hosts, addressed previously unresolved inconsistencies be-

tween models and empirical knowledge. We close by explaining how these modeling ap-

proaches were merged to provide the kinds of advanced, quite realistic models we rely

on today, especially those included in the OpenMalaria ensemble. The materials for the

discussion of the review were found by a systematic literature search and through expert

knowledge (see Appendix 5.A for more details).

5.2

COMPLEX FACTORS OF ACQUIRED IMMUNITY AND THEIR MODEL-

ING APPROACHES

Various kinds of NAI against plasmodium parasites in humans have been defined: anti-

disease immunity, anti-parasite immunity, and premunition (see Table 5.1). Thus, protec-

tion is defined as objective evidence of a lower risk of clinical diseases resulting from

lower densities of parasitemia. Moreso, NAI to malaria in humans comprises two stages:

liver-stage and blood-stage immunity (see Figure 5.1). The pre-erythrocytic (liver-stage)

immunity can be responsible for lowering the probability of developing a blood-stage in-

fection upon receiving a bite from an infected mosquito, implying that it can lower the

proportion of infected bites that lead to blood-stage infection. This it does by reducing the

number of infected liver cells that successfully mature to release merozoites and initiate the

blood-stage infection. The liver-stage immunity can provide a window of opportunity to

ultimately abort infection [136], [135]. This is because parasites are relatively few in num-

ber and confined within a single organ during liver stage development, while blood stage

parasites develop in billions and spread allover the body. Upon initiating the blood stage

infection, parasites grow at a rate dependent on how many merozoites successfully invade

new RBCs, and this increase in parasitemia is considered as the parasite multiplication rate

(PMR) [6]. Thus, the blood-stage immunity is responsible for reducing the probability of

a mosquito contacting infection upon biting an infectious human, by lowering the number

of merozoites that develop into gametocytes [34], [136], [160]. With constant exposure,

the blood-stage immunity which is expressed by reduction in PMR, can suppress infection

by either limiting the parasites from attaining a density sufficient to produce more than a

slight clinical attack or constituting a greater delay until infection is detected [6], [159].

Thus, the most efficient role of the immune response is the ability to impede the growth of

parasites in erythrocytes [78]. Hence, it is evident that antigenic functions are split between

liver- and blood-stage parasites [197].

Acquired immunity to malaria is thought to be influenced by many complex factors

such as climate, use of intervention measures, population (both host and vector) variation,

parasite diversity, age and intensity of exposure. It is also believed to constitute some as-

pects of protections in humans which can wane after sometime, if not duly sustained . All

of these concepts have been perceived in different ways by different researchers, some of

which are either correct, questionable, or yet unclear. These complex factors associated

to NAI to malaria have been included “in parts” in malaria models in somewhat different

ways. Some modellers have made some artificial assumptions for simplicity. Thus, this

review seeks to reevaluate these perceptions about NAI to malaria.