Developmental allometry and paediatric malaria

In 2009, an estimated 243 million cases of malaria led to approximately 863,000 deaths around the world, 80% of which WHO estimates were in infants and young children [1]. It is widely known and accepted that children are at increased risk for severe disease and death between six months and five years of age. Many studies have attempted to decipher which aspects of the parasite, host, and external environment lead malaria infection to severe disease in some, yet remain asymptomatic in others. Although acquired immunity plays a large role in protection, the host's age, apart from prior exposure, may independently influence the infection's severity. This paper considers the possibility that, for instance, in young children malaria parasites are attacking populations of erythrocytes that are intrinsically smaller, in hosts whose immune responses are intrinsically lower, slower or less durable, and that these features might have clinical correlates.The Plasmodium falciparum parasite life cycle begins when an Anopheles mosquito injects sporozoites into the human host. The parasites travel through the bloodstream into the liver, where they invade and replicate, releasing approximately 30,000 merozoites per hepatocyte [2]. The merozoites invade erythrocytes (red blood cells: RBCs). The parasite remains in the erythrocyte for about 48 h, maturing through the ring, trophozoite, and schizont stages, at which point the RBC bursts and releases 8 - 32 new merozoites that invade new RBCs. From the trophozoite stage until it bursts, the infected RBC typically adheres to endothelium and so is sequestered, out of circulation. After a few such cycles, clinical symptoms may begin to appear. A small portion of invading merozoites become gametocytes, the sexual phase of the parasite [3], which can infect a biting mosquito and continue the transmission cycle.Severe P. falciparum infections typically present two distinct clinical manifestations: severe malarial anaemia (SMA) or cerebral m