Malaria infections induce multiple humoral and cellular responses, most of which are probably not protective. This discussion of the epidemiology of acquired immunity to malaria will concentrate on two main areas: first, the relationship between parasitism and disease in endemic settings and the contraints placed on determining which responses are important in acquired protective immunity; second, the central importance ofantigenic diversity in the host-parasite relationship. The emphasis throughout, unless otherwise stated, will be on the major human pathogen Plasmodium falciparum.
Infection with P. falciparum in naive subjects of any age invariably leads to clinical disease which, if untreated, carries a high mortality rate. In endemic areas this picture is modified by acquired immunity since not only does the point prevalence of blood-stage parasites decline with age in a characteristic way in the face of continuing challenge but also significant clinical disease and death owing to malaria no longer occur with advancing age. It would be convenient if these two observations could be taken to represent the same underlying phenomenon, but this is not necessarily the case. Parasite rates in many areas continue to rise beyond the point at which malaria deaths cease. Furthermore, for an individual the presence and density of I'. fufciparum parasitaemia at any one