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■Bio-mathematics, Statistics and Nano-Technologies: Mosquito Control Strategies

common antigens. This situation was suggested to be true for P. falciparum and P. malariae

in a retrospective examination made to determine parasitemia and fever episodes, since

parasitologic and clinical immunity was evident when infection with P. falciparum follows

that with P. malariae [127], [165].

5.2.7

Acquired variant-specific and variant-transcending immunity

Acquired immunity to malaria has mostly been modeled as a general phenomenon

without considering any defined variants ([43], [44], [50],[50],[109], [72], [37], [108]).

However, malaria parasite diversity is known to affect the development of parasitological

immunity since an individual may have to be exposed to the entire (or almost) diversity

of the antigenic make-ups in parasite populations in order to develop effective protection,

[165], [77], [34], [167], [86], [95]. Smith et al. [165] demonstrated this schematically us-

ing overlapping/non-overlapping blobs on two frames representing a hypothetical immune

space comprising the total repertoire of immune responses within a host. The two frames

were used to illustrate the concept of immunity acquisition by showing the dramatic differ-

ence between very young children and older people. In infants or susceptible individuals,

the mechanism which allows the persistence of chronic infections has not come into play

and the immunologic space is still sparse because the strong anti-parasitic effect of fever

itself or the cytokines released during fever [172], prevents the establishment of chronicity

(This cytokine-mediated effect is a sign of their inability to control parasite densities, thus

persistent infections do not exist). However, in older individuals residing in high transmis-

sion areas, the immunological space is already broadly occupied and new infections can

hardly be established. A similar schematic diagram as in [165] is reproduced in Figure 5.5.

The mistaken assumption by some investigators that NAI is strictly strain-specific and

lifelong (see [120], [121], [122] ) was conclusively addressed in an insightful critical ap-

praisal over 20 years ago [119]. It became clear that the basic model of lifelong strain-

specific immunity leads to impossibly dynamic predictions, which conflict with the no-

torious observed stability of malaria transmission (see [63], [173]). Considering that the

stability of a process relies on negative feedback loops, it follows that if strain-specific im-

munity which can be rapidly acquired, limits the transmission of malaria, then it must be

down-regulated equally rapidly for malaria prevalence and transmission to be as resilient

as has been proven by thousands of epidemiological studies.

A mathematical model of P. falciparum asexual parasitaemia was developed and fitted

to 35 malaria therapy cases [31]. The model included three internal mechanisms that aided

its simulation of the courses of asexual parasitaemia in human host in a more realistic way:

innate, acquired variant-specific and acquired variant-transcending immune responses, all

of which are believed to control the peaks of parasitaemia at certain levels and stages.

According to this model, the innate immune response is responsible for early control, and

thereafter becomes progressively less relevant, while the acquired variant-transcending im-

mune response is relatively inconsequential for early control but dominates in the later

stages of the infection. On the other hand, variant-specific immunity regulates the density

of a specific variant and eventually eliminates it. A general conclusion from a review of