he epidemiology of human malaria is exceedingly complex, with patterns of clinical disease varying from place to place, depending on levels of malaria transmission and acquired immunity. However, the relationship between the prevalence of severe malaria and transmission intensity is not linear: the lifetime risk of severe malaria may in fact be higher in areas of moderate transmission than in areas of very high transmission 1 . One potential explanation for this could be that exposure to malaria very early in childhood carries a lower risk of severe disease and serves to induce protection against subsequent severe disease. This pattern of disease has been described for viral infections such as mumps, chicken pox and polio where, in general, childhood infection is less severe than a primary infection in later life.
Of the two most common species of human malaria, Plasmodium falciparum is by far the most pathogenic, with ~1% of infections giving rise to severe (life-threatening) disease. Worldwide, this amounts to some 300 million cases, and three million lethal or life-threatening cases, per year. Severe disease encompasses a range of presentations including severe anaemia, cerebral malaria, hypoglycaemia and a systemic syndrome analagous to toxic shock. Plasmodium vivax is a major cause of morbidity but is no longer a significant cause of mortality. Unless specifically stated to the contrary, the ideas presented here apply to P. falciparum, but parallels will be drawn with P. vivax where appropriate.