Research Article

Rational deployment of antimalarial drugs in Africa: should first-line combination drugs be reserved for paediatric malaria cases?


a1 Department of Immunology & Infection, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK

a2 Biochemistry Department, Faculty of Medicine, Sultan Qaboos University, Oman

a3 School of Biological Sciences, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JZ, Edinburgh, Scotland, UK

a4 KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya and Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, CCVTM, Oxford OX3 7LJ, UK

a5 Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA

a6 Department of Epidemiology, Tropical Medicine Research Institute, National Centre for Research, Khartoum, Sudan


Artemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the ‘premier’ combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance.

(Received February 23 2011)

(Revised June 15 2011)

(Accepted June 15 2011)

(Online publication August 03 2011)


c1 Corresponding author: Dr CJ Sutherland, Department of Immunology & Infection, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK. Tel: +44 (0)20 7927 2338; E-mail: