Alanine Metabolism in Acute Falciparum Malaria

We investigated the integrity of the gluconeogenic pathway in severe malaria using alanine metabolism as a measure. Alanine disposition and liver blood flow, assessed by indocyanine green (ICG) clearance, were measured simultaneously in 10 patients with falciparum malaria (six severe and four moderately severe malaria). After intravenous infusion of alanine (0.3 g/kg), glucose increments (AUC0-55 min) were lower in patients with severe malaria than in those with moderately severe malaria (median = 508 vs. 808 mmol/min/l; P = 0.055). There were no significant differences in the other metabolite increments (alanine, lactate and pyruvate; P >/= 0.27). The two fatal cases had markedly delayed alanine removal (larger AUC0-55 min), prolonged T(1/2) and slower clearance (P </= 0.007). Overall the increments in blood alanine correlated directly with lactate increments (rs = 0.84; P = 0.002) and inversely with glucose (rs = -0.70; P = 0.025). Between acute and convalescent studies, the increments (AUC0-55 min) of alanine and glucose were not significantly different (P >/= 0.07) but the increments of lactate and pyruvate were lower in convalescence. Thus, the ratio of the increments of alanine to those of lactate and pyruvate were significantly higher in the convalescent study (P </= 0.017). The mean (SD) ICG clearance during acute malaria was not significantly different to that in convalescence (21.6 +/- 9.3 vs. 34.1 +/- 15.5 ml/min/kg; P = 0.25). During the acute study, there was a significant inverse correlation between ICG clearance and the post-infusion increments of lactate (rs = -0.63, P = 0.049) and pyruvate (rs = -0.74, P = 0.014). These data indicate that alanine clearance is impaired in acute falciparum malaria in proportion to the severity of illness and suggest an important role for anaerobic glycolysis in the pathogenesis of hypoglycaemia in severe malaria.