Models of Acquired Immunity to Malaria: A Review

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of life, so maternal protection is unimportant. However, in a case where transmission is

frequent, then all mothers will probably have similar immune level. An exception to the

age-dependence of NAI in endemic areas is seen in pregnant women. The risk of disease is

much higher, even with prior immunity, because pregnant women are immuno-suppressed,

so that they can carry the baby without reacting to it [142]. An additional reason is due to

preferential sequestration of infected erythrocytes in the placenta [129], often referred to

as “placental malaria”.

Although NAI results from uninterrupted heavy exposure to infection, it appears that

no amount of heavy exposure in children can induce an adult-like protective immunity for

individuals in a given area [205]. Baird [170] demonstrated an approach to assess the ef-

fects of cumulative exposure and age by studying NAI among people of all ages who are

shortly exposed to intense infection pressure. After a year of residing in a hyperendemic

area of Irian Jaya, the frequency and density of parasitemia among newcomers from Java,

decreases with increasing age. Adult newcomers manifested evidence of naturally acquired

protection relatively rapidly, whereas their children remained susceptible. It is wondered

why adults are resistant to infection, while children remain susceptible after a brief pe-

riod of apparently uniform intense exposure among all age groups (see also [179]). This

is presumed to be as a result of the difference in the structure of the immune system of

a child and that of an adult [35] and age-dependent pathophysiological mechanism [99],

which accounts for an immune system in children that is less capable of mounting protec-

tive response against parasites. In [102], this concept of immune maturation as humans age

was accounted for by allowing a slow change of the immune stimulation parameter from

a relatively low value at infant ages to relatively higher values as age increases. It allowed

for more efficient “adult response” to an identical exposure, compared to that of a child. As

such, the rate and duration of severe episodes decline with age due to immune maturation.

Smith et al. [118], evaluated immunity to P. falciparum infection in African children by

comparing SIS to SIRS models, allowing for heterogeneous infection rates and superinfec-

tions. In this study, the model that fitted best to the malaria data of African children was the

SIS model with no immunity to reinfection. This was suggested to be because children do

not acquire protection to new infections after recovering from a single infection, but pro-

tective immunity requires repeated exposure or perhaps some change in immune function

with with respect to age (see [52]). However, in some models such as in [72], immunity

was modelled as a function of individual exposure history only, without taking age into

account; moreso in most compartmental models, time is represented through age with the

assumption that the population has reached its equilibrium pattern of infection, which is

erroneous. Recent stochastic models have incoporated both age and exposure history in a

more practical way [114], [205].

On the other hand, the growth in body surface area with the age of a host, entails more

exposure of adults to mosquito bite [7] and perhaps explain why they seem to acquire im-

munity faster than children when exposed to heavy malaria transmission for the first time

[205]. Smith et al. [205] proposed a model for the relationship between the EIR and the

force of infection in endemic areas. The model considered the effects of increased exposure

to mosquito bites resulting from the growth in body surface area with the age of the host,