Abstract

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

Sulo, J. Chimpeni, P. Hatcher, J. Kublin, J. G. Plowe, C. V. Molyneux, M. E. Marsh, K. Taylor, T. E. Watkins, W. M. Winstanley, P. A.
Lancet. 2002; 3601136-43

Permanent descriptor

https://doi.org/10.1016/s0140-6736(02)11198-6

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 per-protocol 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% CI 0.98-1.37), and 2.2 versus 2.8 in Malawi (0.77, 0.63-0.94). 4.3% versus 12.8%, and 5.4% versus 20.1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively.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.