Efficacy of artesunate for emergency malaria treatment.(Safety and Efficacy Issues)

Plasmodium falciparum malaria causes hundreds of thousands of deaths annually, especially in children in sub-Saharan Africa. Many of those living in malaria-endemic areas do not have ready access to health facilities and for patients too ill to take oral medication, delay in access to prompt injectable therapy can be fatal. Rural health workers and even parents can be taught to identify the symptoms and signs of severe, life-threatening malaria (1) and rectal artesunate makes for a rapidly acting and effective drug for patients with acute malaria.

The UNDP, World Bank, and WHO Special Programme for Tropical Diseases Research (TDR) selected artesunate on the basis of its rapid antimalarial activity (2, 3), favourable bioavailability (4), and reassuring safety (5) and efficacy profiles (6) compared with other available treatments. Despite isolated case reports of failed supervised treatment (7, 8), no evidence exists of stable parasite resistance developing during lengthy clinical use with artemisinins (9). A thermostable suppository formulation of artesunate was developed for reasons of easy storage and administration in difficult settings.

A study recently reported in the Lancet (10) has assessed the reliability, absorption and initial therapeutic efficacy of rectal artesunate. The Trial involved 109 children in Malawi and a smaller number of 35 adults in KwaZulu Natal, South Africa. Patients with moderately severe malaria were randomly assigned to a single dose of 10 mg/kg rectal artesunate or parenteral quinine. Since artemisinin derivatives are the most rapidly acting antimalarials known (4), the study aimed to determine whether early administration of rectal artesunate would provide beneficial initial antimalarial cover, indicated by a rapid fall in the density of parasitaemia (less than 60% of baseline after 12 hours), and clinical improvement without serious adverse reactions. In both study groups, treatment was completed with the administration of sulfadoxine-pyrimethamine according to prevailing national policy.

Clinical outcome

Rectal artesunate, given as a single dose of 10 mg/kg, showed rapid antimalarial efficacy within 24 hours of administration in moderately severe falciparum malaria in children and adults (Table 1). All patients had either pharmacodynamic or pharmacokinetic evidence of absorption of …