A THEORETICAL FRAMEWORK FOR THE IMMUNOEPIDEMIOLOGY OF PLASMODIUM-FALCIPARUM MALARIA

Molecular genetic analyses of P. falciparum have led to the cloning an d sequencing of a number of antigens that are potential candidates for vaccination against malaria. Seroepidemiological studies in endemic a reas have attempted to assess the relative importance of these antigen s in protection against malaria. In this paper, we attempt to evaluate the relative contributions of conserved and strain-specific immune re sponses by modelling their influence of age-specific patterns of infec tion and disease. The modelling exercises in this paper clearly demons trate that the observed patterns ns of age-prevalence are best explain ed by proposing that the accumulation to a threshold of an immune resp onse against a conserved determinant is required for protection agains t infection, while 'antidisease' immunity develops more linearly with exposure. This is compatible with the conjecture that the parasite pop ulation is structured into several independently, transmitted strains, that each confers some degree of 'antidisease' immunity, but does not protect against further infection by the same strain. Within this fra mework, the average duration of parasitaemia increases with age, as pr eviously encountered strains endure for longer periods at a subclinica l level. Indirect evidence for the increase in duration of parasitaemi a with age may be obtained from a comparison of age-prevalence curves between dry and rainy seasons. By using mathematical methods to struct ure epidemiological and immunological information, we provide a cohere nt theoretical framework for the dissection of the important component s of naturally acquired immunity to malaria.