Models of Acquired Immunity to Malaria: A Review

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older infants 1 - 4 years, after-which the recovery rate increased by a factor of more than

10 in older individuals. The study suggested that the fall in recovery rate in those aged 1 -

4 years could be either because of loss of maternal immunity or because of superinfection

and that the subsequent rise in recovery rate in older people is due to increasing immunity

(see also [189]).

On the other hand, Smith et al. [188] found in their study that the average multiplicity

of infections increases at the same time as children acquire immunity. This was interpreted

to be mainly because the average duration of infection increases even though children are

becoming more immune (see also [191], [193]). The suggested reason is that lower par-

asite densities reduce the effective variant introduction rate, thereby slowing parasite and

immune dynamics. Slower switching rate exhausts variants at a slower pace, prolonging in-

fection duration until further slowing fails to subdue adaptive immunity (see [192]). They

also argued that the short durations of infection in adults estimated by microscopy data

[41], [189] could be due to diminished sensitivity of microscopy at low parasite densi-

ties. However, recent studies of infection duration with age (since cumulative exposure

and acquired immunity increase with age) [124], [125] found no general age trend [213],

[192]. An involvement of NAI would entail that short infection durations should become

repeatedly common in older age groups, which has not yet been reported by any study.

5.2.4

Age and acquired immunity

The burden of malaria in humans residing in endemic areas is strongly age-determined

[68]. A simplistic demonstration can be seen in the simulated solution plot of the

age-specific SIRS model in [44] (given in Figure 5.2). It reveals how prevalence changes

with respect to age for different values of force of infection. With a higher rate of infection

(h = 5/yr), typical for endemic areas, malaria prevalence rises speedily at young age up

to a peak, from where it gradually declines to a low level in adulthood, as a result of the

increase in immunity. Contrarily, prevalence is shown to have an insignificant dependence

on age for low force of infection (h = 0.05/yr). This model predicts that in highly endemic

areas, the prevalence rapidly rises in early childhood and gradually wanes into adulthood

as a result of slow acquisition of immunity with age and time. Also, it can be seen that the

prevalence in adults is highest at intermediate infection rates. This is consistent with the

infection pattern summarized by Boyd for tropical Africa [60] and also with the specula-

tions of some epidemiologist that partial control, which leads to a moderate reduction of

transmission from initially high levels, could increase adult prevalence [148], [63]. While

immunity to malaria generally rises with age, especially in places with the highest forces

of infection and stabilizes at adulthood, this increase with respect to age is not noticeable

at low force of infection. In areas where the disease is not endemic and exposure is only

occasional (i.e. once every few years), the burden posed by malaria extends into adulthood

and similar infection levels is seen among various age groups since protective immunity is

not consistently maintained [71]. See Appendix 5.B for more explanation of this model.

In high transmission areas, children below the age of five are most vulnerable to se-

vere malaria attacks [29]. This is related to the fact that these children with the least prior