Abstract
Previous analyses have suggested that immunity to non-cerebral severe malaria due to Plasmodium falciparum is acquired after only a few infections, whereas longitudinal studies show that some children experience multiple episodes of severe disease, suggesting that immunity may not be acquired so quickly. We fitted a mathematical model for the acquisition and loss of immunity to severe disease to the age distribution of severe malaria cases stratified by symptoms from a range of transmission settings in Tanzania, combined with data from several African countries on the age distribution and overall incidence of severe malaria. We found that immunity to severe disease was acquired more gradually with exposure than previously thought. The model also suggests that physiological changes, rather than exposure, may alter the symptoms of disease with increasing age, suggesting that a later age at infection would be associated with a higher proportion of cases presenting with cerebral malaria regardless of exposure. This has consequences for the expected pattern of severe disease as transmission changes. Careful monitoring of the decline in immunity associated with reduced transmission will therefore be needed to ensure rebound epidemics of severe and fatal malaria are avoided.
Highlights
A small minority of Plasmodium falciparum infections result in severe malaria, requiring admission to hospital [1]
In the highest transmission area (Tanga, altitude below 600 m), the majority of admissions were in the youngest age groups (43% aged below 1 year), the most common manifestation was severe malarial anaemia (47% of cases) and 3% of cases presented with cerebral malaria
Our analysis demonstrates that variations in patterns of severe malaria with age and transmission intensity can be explained by exposure- and age-driven acquisition of immunity, which determine the incidence of severe malaria, coupled with age-dependent physiological changes, which determine the dominant clinical syndrome of severe malaria
Summary
A small minority of Plasmodium falciparum infections result in severe malaria, requiring admission to hospital [1]. In 1999, Gupta et al used a mathematical model fitted to the age distribution of cerebral and non-cerebral malaria incidence across different transmission settings in Kenya and Gambia to estimate the rate of acquisition of immunity to these syndromes [11,31] This model assumed that infections were acquired at a constant rate from birth, but that in young infants the proportion of cases with severe disease was reduced by passive immunity from maternal antibodies and that the proportion of cases with severe disease varied with exposure. Further details of the model-fitting methodology and the parameter estimates are given in the electronic supplementary material, text S1
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