dThe efficacy of sublingual artemether (ArTiMist) was investigated in two studies. In study 1, 31 children were randomized to sublingual artemether (n ؍ 16) or intravenous (i.v.) quinine (n ؍ 15). In study 2, 151 children were randomized to sublingual artemether (n ؍ 77) or i.v. quinine (n ؍ 74). For both studies, patients weighed between 5 and 15 kg and had either severe or complicated malaria based on WHO criteria, or they had uncomplicated malaria but were unable to tolerate oral medication as a result of nausea, vomiting, or diarrhea. Patients received either 3 mg/kg of body weight of sublingual artemether or a loading dose of 20 mg/kg of i.v. quinine followed by 10 mg/kg every 8 h i.v. thereafter. The primary endpoint was parasitological success, defined as a reduction in parasite count of >90% of that at baseline at 24 h after the first dose. Other endpoints based on parasite clearance and clinical response were evaluated. In study 1, there were parasitological success rates of 93.3% (14/15) and 66.7% M alaria remains a major health challenge in developing countries, especially in sub-Saharan Africa (SSA). Approximately 207 million cases of malaria were reported worldwide, of which 80% were in sub-Saharan Africa. Overall, 90% of the reported 627,000 deaths, of which 77% were in children under five years of age, were in SSA (1). The overwhelming majority (98%) of malaria cases in the African region are due to Plasmodium falciparum (1).In countries where the disease is highly endemic, 20% to 46% of child deaths can be attributed to malaria or febrile illness (2). In moderate-to high-transmission settings, such as is found in most SSA countries where malaria is endemic, young children are disproportionately affected by malaria (3). A child presents with an average 1.6 to 5.4 episodes of febrile malaria per year, with about 5% of malaria episodes becoming severe disease (4). Less than one-third attend clinics, and many receive malaria treatment outside the health care system. The majority of treatments are initiated on a presumptive diagnosis, with a high false-positive rate, resulting in challenges in accurate monitoring of the malaria burden in SSA (5).Despite advances in the treatment of malaria in children, "the majority of deaths from severe malaria in childhood are caused by the delayed administration of effective antimalarial treatment. There is a relentless deterioration in the clinical condition of a young child with malaria who fails to get effective treatment, with death ensuing in a matter of hours or days. Any successful attempt to reduce mortality from malaria will have to explore novel possibilities for minimizing such delays" (6).There is a clear need for a formulation of an artemisinin derivative that can be easily administered and adequately absorbed in a child who may be unconscious or uncooperative, or in whom nausea and vomiting preclude oral dosing. Artemether can be used as initial intramuscular (i.m.) monotherapy for severe malaria in children (7). It is also a recommended first...