The relevance of malaria pathophysiology to strategies of clinical management.
OBJECTIVE
Malaria claims 1-2 million lives a year, mostly children in sub-Saharan Africa. The majority of hospital deaths occur within 24 h of admission despite adequate treatment with antimalarial chemotherapy. Understanding the pathophysiological disturbances of malaria should allow the development of supportive therapy to "buy time" for antimalarial chemotherapy to clear the infection. It is sobering, however, that despite many trials over the last quarter of a century all large trials of adjunctive therapy so far have resulted in either increased morbidity or mortality, or both.


RESULTS
Severe malaria may be divided broadly into neurological and metabolic complications. We review recent findings about the pathophysiology of these complications and the implications for future adjunctive therapy of malaria, including the proposed importance of fluid volume depletion and sequestration of parasitized red cells in severe malaria. We also consider other anaemia, hyperparasitaemia and renal failure, which also require urgent treatment in severe malaria.


CONCLUSIONS
We review the important pathophysiological features of severe malaria and promising adjunctive therapies such as dichloroacetate that warrant further larger trials to determine whether they improve the so-far intractable death rate of severe malaria.
Planche
Tim
T
Department of Cellular and Molecular Medicine, Centre for Infection, St. George's Hospital Medical School, London SW17 0RE, UK. tim@planche.demon.co.uk
Krishna
Sanjeev
S
D000140:Acidosis, Lactic / Q000469:parasitology; D000962:Antimalarials / Q000627:therapeutic use; D003244:Consciousness Disorders / Q000469:parasitology; D003999:Dichloroacetic Acid / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000469:parasitology; D016778:Malaria, Falciparum / Q000150:complications* / Q000188:drug therapy*
D000962:Antimalarials; D003999:Dichloroacetic Acid