Extract

Background and study aims Malaria is a serious tropical disease caused by a parasite that is spread by mosquitoes. Antimalarial medication is used to prevent and treat malaria. However, resistance to antimalarial drugs can develop when genetic mutations allow the parasite to survive in the presence of the drug. The development of resistance is of huge public health concern. In Malawi, sulphadoxine-pyrimethamine (SDX-PYM) replaced chloroquine (CQ) in 1993 as the first-line treatment for uncomplicated malaria because of high levels of CQ resistance. However, SDX-PYM resistance is increasing. Combination treatment with two or more drugs working by different mechanisms is proposed as a means to delay the development of resistance. Combination treatments containing artemisinin (ART) are proposed as ideal for this purpose because they kill malaria parasites very rapidly and no resistance had been reported at the time of this study. There is also evidence supporting the possible use of a non-ART combination treatment as a possible alternative. Since CQ was withdrawn in 1993 there has been evidence suggesting a possible return of CQ sensitivity. Amodiaquine (AQ) in combination with SDX-PYM has been shown to be effective and well tolerated in Uganda in an area of high-level CQ resistance. This issue is of huge public health importance as combinations of CQ or AQ plus SDX-PYM would be considerably more affordable compared to ART combination treatment. The aims of this study are: 1. To compare the effectiveness of different antimalarial combination treatments 2. To compare the development of resistance when using these different treatments 3. To investigate what happens to the drugs after they are taken – their absorption and how fast they are eliminated from the body Who can participate? Children aged between 1 and 5 with uncomplicated malaria What does the study involve? Participants are randomly allocated to receive one of four treatment combinations: 1. SDX-PYM (single oral dose) and placebo (dummy drug) 2. SDX-PYM (single oral dose) + CQ (once daily for 3 days) 3. SDX-PYM (single oral dose) + Artesunate (once daily for 3 days) 4. SDX-PYM (single oral dose) + AQ (once daily for 3 days) Participants are followed up for 42 days to assess their response to treatment and the development of resistance or side effects. What are the possible benefits and risks of participating? The treatments offered all contain SDX-PYM, the standard treatment for malaria in Malawi, plus an additional medicine – placebo, CQ, AQ or ART. Apart from the placebo, all of these treatments are expected to improve the cure rates for the children. Participation in the study involves additional blood tests for all the children and additional visits to the clinic. These may be an inconvenience for the children and mothers, but do provide a higher level of care than is otherwise available. Where is the study run from? Chileka Health Centre (Malawi) When is the study starting and how long is it expected to run for? September 2003 to March 2006 Who is funding the study? Wellcome Trust (UK) Who is the main contact? Dr David Bell [email protected]

Inclusion criteria

• Uncomplicated Malaria

Links

• ictrp
• isrctn