[e-drug] Trial on treatment of uncomplicated falciparum malaria

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E-drug: Trial on treatment of uncomplicated falciparum malaria
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Lancet 2002; 360: 1136-43 (12 October) - Free
http://www.thelancet.com/journal/vol360/iss9340/full/llan.360.9340.original_
research.22704.1
[Copied as fair use. KM]

Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential
episodes of uncomplicated falciparum malaria in Kenya and Malawi: a
randomised clinical trial
J Sulo, P Chimpeni, J Hatcher, J G Kublin, C V Plowe, M E Molyneux, K Marsh,
T E Taylor, W M Watkins, P A Winstanley
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Centre for Geographical Medicine, Kenya Medical Research Institute (KEMRI),
Kilifi, Kenya (J Sulo MBChB, Prof K Marsh); The Malawi-Liverpool-Wellcome
Trust Programme for Tropical Medicine Research, Blantyre, Malawi (P Chimpeni
MAC, Prof M Molyneux FRCP); Division of Epidemiology, Prevention and
Screening, Alberta Cancer Board, Canada (J Hatcher PhD); Malaria Section,
Center for Vaccine Development, University of Maryland School of Medicine,
MD, USA (J G Kublin MD, Prof C V Plowe MD); Division of Tropical Medicine,
Liverpool School of Tropical Medicine, UK (Prof M E Molyneux); Nuffield
Department of Clinical Medicine, University of Oxford, John Radcliffe
Hospital, Oxford, UK (Prof K Marsh); Department of Medicine, College of
Osteopathic Medicine, Michigan State University, MI, USA (Prof T E Taylor
DO); Department of Pharmacology and Therapeutics, University of Liverpool,
Liverpool L69 3GE, UK (W M Watkins PhD, Prof P A Winstanley FRCP).
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Correspondence: Prof P A Winstanley (e-mail:peterwin@liv.ac.uk)

Summary
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.




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