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 eitherchlorproguanil-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0.98-1.37), and 2.2 versus 2.8 in Malawi (0.77, 0.63-0.94). 4.3% versus 12.8%, and 5.4% versus 20.1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively.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.
RCT Entities:
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-dapsonepatients and 1.5% of sulfadoxine-pyrimethaminepatients, 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.
Authors: Abigael Mbaisi; Pamela Liyala; Fredrick Eyase; Rachel Achilla; Hosea Akala; Julia Wangui; Josphat Mwangi; Finnley Osuna; Uzma Alam; Bonnie L Smoak; Jon M Davis; Dennis E Kyle; Rodney L Coldren; Carl Mason; Norman C Waters Journal: Antimicrob Agents Chemother Date: 2004-09 Impact factor: 5.191
Authors: Alisa P Alker; Victor Mwapasa; Anne Purfield; Stephen J Rogerson; Malcolm E Molyneux; Deborah D Kamwendo; Eyob Tadesse; Ebbie Chaluluka; Steven R Meshnick Journal: Antimicrob Agents Chemother Date: 2005-09 Impact factor: 5.191
Authors: Ann K Miller; Nibedita Bandyopadhyay; Daniel G Wootton; Stephan Duparc; Paula L Kirby; Peter A Winstanley; Stephen A Ward Journal: Eur J Clin Pharmacol Date: 2009-06-11 Impact factor: 2.953
Authors: Frank O Odhiambo; Mary J Hamel; John Williamson; Kim Lindblade; Feiko O ter Kuile; Elizabeth Peterson; Peter Otieno; Simon Kariuki; John Vulule; Laurence Slutsker; Robert D Newman Journal: PLoS One Date: 2010-04-02 Impact factor: 3.240
Authors: David J Bell; Dan Wootton; Mavuto Mukaka; Jacqui Montgomery; Noel Kayange; Phillips Chimpeni; Dyfrig A Hughes; Malcolm E Molyneux; Steve A Ward; Peter A Winstanley; David G Lalloo Journal: Malar J Date: 2009-08-26 Impact factor: 2.979