INTRODUCTION
Falciparum malaria remains a major cause of morbidity and
mortality throughout the tropical world, with as many as 500
million cases annually causing 1–3 million deaths.1 Most cases
of malaria are uncomplicated and can be treated successfully
with appropriate oral antimalarial drugs. However, in a proportion of patients, particularly in nonimmune individuals
and/or where treatment has been delayed or ineffective drugs
(chloroquine in most areas of the world) or substandard counterfeited drugs given, life-threatening severe disease can
evolve requiring hospitalization, parenteral antimalarial
therapy, and the treatment of complications. Severe malaria is
often a multisystem disorder, presenting with multiple complications, each requiring specific management. In most of the
malaria-endemic world, sophisticated intensive care facilities
are not available and treatment is necessarily resourcelimited. The mortality associated with severe malaria remains
high, ranging from 10% to 50% depending on the setting. In
this context, the main objective of the management of severe
malaria is to prevent the patient from dying. Prevention of
long-term sequelae and recrudescence (the usual primary
endpoint of antimalarial trials in uncomplicated malaria) are
secondary objectives.
The World Health Organization coordinated the production of guidelines for the management of severe and complicated malaria in 1990 and again in 2000, which also contain
strict definitions of severe malaria, useful for standardizing
clinical research.2,3 More recently, in 2006, WHO published
evidence-based guidelines for the treatment of malaria, which
include extensive advice on the management of severe malaria as well as a clinically useful distillation of the WHO
severe malaria definitions (Table 1).4
Unfortunately, the clinical evidence base on which to base
guidelines is small, as most of the clinical trials on severe