All in the mix: combining malaria drugs to beat resistance in sub-Saharan Africa

Malaria control in Africa depends on the availability of effective, safe and cheap drugs. Rapid spread of drug resistance is a major problem. Researchers at Kilifi District Hospital, Kenya, and Ndirande Health Centre, Blantyre, Malawi, compared the current first-line treatment, sulfadoxine-pyrimethamine (SP), with a new combination, chlorproguanil-dapsone (CD), that is less likely to induce resistance.

Resistance has wiped out the effectiveness of the old drug, chloroquine, throughout sub-Saharan Africa. Nine countries have switched to SP as their first-line treatment and others will follow. Malawi changed in 1993, but use of SP became routine only recently in Kenya.

SP stays in the body for a long time and this allows malaria parasites to build resistance rapidly. So we need to find effective, safe, practicable and affordable drugs that are less likely to produce resistance. CD is under development as a low-cost tablet to treat uncomplicated malaria in areas where SP resistance is growing. It requires three days of treatment. But because it is cleared rapidly from the body, CD does not protect against re-infection after successful treatment. Will this cause greater numbers of infections and increase the workload of overstretched health facilities?

Researchers gave one of the two drug combinations to children coming to outpatients with uncomplicated malaria. In Kilifi, 188 received CD and 195 took SP. In Blantyre, the numbers were 222 and 224 respectively. The study showed that:

• Children taking CD are not more susceptible to malaria than those treated with SP.
• Unsuccessful treatment is more common with SP than with CD.
• Use of CD has little effect on annual malaria rates currently seen with SP.
• Anaemia is more common in patients treated with CD than those receiving SP.

CD was submitted to the Regulatory Authorities (in African countries and the UK) in 2002; in the UK it comes before the Committee on Safety of Medicines in March 2003. The researchers point out that adding a drug from the artemisinin (extracted from the leaves of the sweet wormwood plant) class of antimalarials to other agents may slow the development of drug resistance. A triple combination of CD-artesunate is under development and may prolong the useful life of these drugs.

Source(s):
‘Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial’, The Lancet 360: 1136-1143, by J. Sulo, et al., 2002 Full document.

Funded by: WHO Special Programme for Research and Training in Tropical Diseases (TDR); SmithKline Beecham; Wellcome Trust

id21 Research Highlight: 20 February 2003

Further Information:
Peter Winstanley
Department of Pharmacology and Therapeutics
University of Liverpool
Liverpool
L69 3GE
UK

Contact the contributor: peterwin@liv.ac.uk

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'A winning alliance: researchers and policy-makers tackle malaria drug resistance'

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'Future prospects: long-term effects of severe malaria in childhood'

'Seeking treatment with caution – anti-malarial treatment in the Gambia'

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