AGE-DEPENDENT CHARACTERISTICS OF PROTECTION V. SUSCEPTIBILITY TO PLASMODIUM-FALCIPARUM

Naturally acquired immunity to Plasmodium falciparum may be linked to key features of the immune system that change during normal developmen t and ageing, Evidence of this was seen in non-immune Javanese transmi grants taking up residence in hyperendemic Irian Java, Indonesia. Afte r 1-2 years of residence, the adult migrants had less frequent and les s intense parasitaemias than their children. Splenomegaly and malaria- like symptoms were also less common in the adults. These age-dependent patterns of relative resistance to P. falciparum mirrored those in li felong residents. The Javanese adults acquired protective immunity aga inst chronic exposure to infection relatively quickly compared with th eir children. However, during tl;e initial exposure to infection, the incidence of emergency medical evacuation to hospital with a clinical diagnosis of malaria was 7-fold higher among the adults than in their children. The exaggerated susceptibility of adults to severe morbidity and mortality has been reported in other populations during initial e xposure to infection. Thus, whereas adults acquired protection against chronic exposure more rapidly than the children, they were initially more susceptible to severe disease. One possible explanation for these findings is the changes in the immune system that normally occur duri ng ageing. Such changes may establish differences between children and adults that profoundly affect the course of infection by P. falciparu m. The ratio of naive to memory T cells gradually diminishes during ag eing, as a result of the cumulative effect of exposure to the myriad a ntigens encountered throughout the normal course of life. Moreover, th e gradual involution of the thymus progressively limits the production of naive T cells. The likelihood of stimulating memory T cells with c ross-reactive antigens may increase with age and this may bias the imm une response to the relative benefit of the host under chronic exposur e, or to the detriment of the host under acute exposure. Intrinsic fea tures of the immune system that change with age may determine key char acteristics of the immune response to infection by P. falciparum, and whether that response is relatively harmful or beneficial may depend u pon the conditions of exposure (i.e. acute or chronic).