Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial

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. 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. 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0·98–1·37), and 2·2 versus 2·8 in Malawi (0·77, 0·63–0·94). 4·3% versus 12·8%, and 5·4% versus 20·1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively.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. 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.