The majority of the clinical cases of malaria occur in sub-Saharan Africa. Nevertheless, malaria also accounts for considerable morbidity and mortality in other continents particularly South East Asia . In malaria-endemic regions (e.g. sub-Saharan Africa), where the resident population have continuous exposure to malarial parasites, most of the severe cases are seen in children . In hypoendemic regions (e.g. South East Asia), where parasite exposure is more intermittent, cases of severe malaria are also common in adults (Tab. 1).
Clinical features associated with malaria mortality vary between children and adults, but acidosis and coma are associated with malarial mortality in both populations [7, 8]. Acute renal failure (ARF) and pulmonary oedema, a marker for adult respiratory distress syndrome (ARDS), are almost exclusively reported among adults [9, 10], whereas mortality associated with hypoglycaemia is frequently reported among children .
Why malarial disease displays such age-related differences in pathophys-iology is unclear. However, these differences are not exclusive to malaria. ARDS, which is more frequently observed as a complication of trauma in adults compared with children , is believed to reflect an exaggerated pro-inflammatory response within the lung . A possible lead for future studies on these age-related differences in malaria is suggested by a report of peritoneal macrophages collected from healthy adults producing much less interleukin (IL)-10 (an anti-inflammatory cytokine), but the same levels of pro-inflammatory cytokine, than those from healthy children, giving adults a much higher pro-inflammatory status [13, 14].
The mechanism of malarial ARF pathogenesis is postulated to be multi-factorial, involving mechanical, haemodynamic, and immunological factors . The observation that ARF is more frequently observed as a complication of trauma in adults than children  suggests that age-related variations in cytokine response may again influence pathogenesis.
Hypoglycaemia is regarded as a more frequent complication of sepsis in paediatric populations compared with adults . Hypoglycaemia in children may, in part, be associated with a higher basal metabolic rate, and lower glycolytic  and gluconeogenic substrate reserves compared to adults . However, these substrates are not always limiting during acute paediatric malaria, suggesting functional impairments of glucose metabolism may also occur . Such functional impairments may, in part, be influenced by increases in inflammatory cytokines as the infection progresses.
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