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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, Malcolm E, Marsh, Kevin, Taylor, T. E., Watkins, W. M. and Winstanley, P. A. (2002) 'Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial'. Lancet, Vol 360, Issue 9340, pp. 1136-1143.

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0.98-1.37), and 2.2 versus 2.8 in Malawi (0.77, 0.63-0.94). 4.3% versus 12.8%, and 5.4% versus 20.1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively.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

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs
QX Parasitology > Protozoa > QX 135 Plasmodia
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 770 Therapy
Digital Object Identifer (DOI): https://doi.org/10.1016/s0140-6736(02)11198-6
Depositing User: Martin Chapman
Date Deposited: 03 Jun 2013 13:07
Last Modified: 21 Nov 2024 12:07
URI: https://archive.lstmed.ac.uk/id/eprint/2989

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