PLASMODIUM-BERGHEI INFECTION - DICHLOROACETATE IMPROVES SURVIVAL IN RATS WITH LACTIC-ACIDOSIS

The kinetics of Plasmodium berghei infection and the development of la ctic acidosis, hypoglycemia, and anemia were defined in young Wistar r ats. This model of metabolic dysfunction, which is similar to that of severe human malaria, was used to test the hypothesis that dichloroace tate, a treatment for lactic acidosis, prolonged survival in rats rece iving a single antimalarial dose of quinine (20 mg/kg). Rats with hype rlactatemia (lactate >5 mmol/liter, N = 183) were randomized to receiv e either dichloroacetate (100 mg/kg, N = 99) or saline (N = 84) and we re monitored for outcome (survival or death) for 50 hr. Logistic regre ssion modeling adjusting for baseline venous lactate concentration dem onstrated that dichloroacetate increases survival rates in rats with v enous lactate concentrations between 5 and 8.9 mmol/liter (odds ratio > 2.2, P < 0.021). This is the first demonstration that specific inter vention to treat lactic acidosis can prolong survival and suggests tha t dichloroacetate may be useful as adjunctive therapy in the managemen t of lactic acidosis complicating severe falciparum malaria. (C) 1995 Academic Press, Inc.