Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum

Abstract

Naturally acquired immunity to Plasmodium falciparum may be linked to key features of the immune system that change during normal development and ageing. Evidence of this was seen in non-immune Javanese transmigrants taking up residence in hyperendemic Irian Jaya, Indonesia. After 1-2 years of residence, the adult migrants had less frequent and less 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 lifelong residents. The Javanese adults acquired protective immunity against chronic exposure to infection relatively quickly compared with their children. However, during the 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 exposure 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 during ageing. Such changes may establish differences between children and adults that profoundly affect the course of infection by P. falciparum. The ratio of naive to memory T cells gradually diminishes during ageing, as a result of the cumulative effect of exposure to the myriad antigens encountered throughout the normal course of life. Moreover, the gradual involution of the thymus progressively limits the production of naive T cells. The likelihood of stimulating memory T cells with cross-reactive antigens may increase with age and this may bias the immune response to the relative benefits of the host under chronic exposure, or to the detriment of the host under acute exposure. Intrinsic features of the immune system that change with age may determine key characteristics of the immune response to infection by P. falciparum, and whether that response is relatively harmful or beneficial may depend upon the conditions of exposure (i.e. acute or chronic).