Abstract :
Background
Chlorproguanil-dapsone exerts lower resistance pressure on Plasmodium falciparum than does sulfadoxine-pyrimethamine, but is rapidly eliminated. We aimed to find out whether chlorproguanil-dapsone results in a higher retreatment rate for malaria than sulfadoxine-pyrimethamine.
Methods
In a randomised trial of paediatric outpatients with uncomplicated falciparum malaria, patients received either chlorproguanil-dapsone or sulfadoxine-pyrimethamine and were followed up for up to 1 year. Sites were in Kenya (n=410) and Malawi (n=500). We used perprotocol analysis to assess the primary outcome of annual malaria incidence.
Findings
Drop-outs were 117 of 410 (28•5%) in Kenya, and 342 of 500 (68•4%) in Malawi. Follow-up was for a median of 338 days (IQR 128–360) and 342 days (152–359) in Kilifi (chlorproguanil-dapsone and sulfadoxine-pyrimethamine, respectively), and for 120 days (33–281) and 84 days (26–224) in Blantyre. Mean annual malaria incidence was 2•5 versus 2•1 in Kenya (relative risk 1•16, 95% Cl 0•98–1•37), and 2•2 versus 2•8 in Malawi (0•77, 0•63–0•94). 4•3% versus 12•8%, and 5•4% versus 20•1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively. In Kenya haemoglobin concentration of 50 g/L or less caused exit in 6•9% of chlorproguanil-dapsone patients and 1•5% of sulfadoxine-pyrimethamine patients, but most anaemia occurred before re-treatment. In Malawi only one patient exited because of anaemia.
Interpretation
Despite the rapid elimination of chlorproguanil-dapsone, children treated with this drug did not have a higher incidence of malaria episodes than those treated with sulfadoxine-pyrimethamine. Treatment failure was more common with sulfadoxine-pyrimethamine. Cause of anaemia in Kenya was probably not adverse reaction to chlorproguanil-dapsone, but this observation requires further study.
