It's difficult to cure people of malaria because the parasite has developed resistance to many of the drugs in current use. There is a new group of anti-malarial drugs developed from a Chinese herb which are powerful, but when used alone need a long course of treatment, but may be better when used in combination with existing compounds. The International Artemisinin Study Group combined data from 16 randomised trials to see whether adding artesunate to other anti-malarials could improve cure rates, reduce spread of the disease and slow the development of drug resistance.

Artesunate has several attractive features as an anti-malarial drug, as it:

• acts quickly
• kills malaria parasites that are resistant to other drugs
• reduces blood levels of gametocytes – the parasite stage that is taken up by mosquitoes and allows spread to other people.

The researchers used data from 12 studies in Africa, three in Thailand and one in Peru. In these trials, artesunate was combined with chloroquine (three trials), amodiaquine (three), sulfadoxine-pyrimethamine (SP – seven) or mefloquine (three). The results showed that, compared with standard treatment alone, adding three days of artesunate:

• reduces the risk of treatment failure after 14 days (by 73%) and 28 days
• doubles the rate of parasite clearance from the blood
• shortens the duration of fever
• lowers gametocyte counts on day 7, with larger effects at days 14 and 28
• has similar numbers of serious side effects.

The effects of adding artesunate for only one day are similar but less striking.

Policy-makers are looking for malaria treatments that are cost-effective and minimise development of drug resistance. Combination treatments including artesunate could help to achieve both aims. But decisions to change national anti-malarial treatment policies have major health, implementation and cost implications. Combination treatments are costly. A blister pack of artesunate and SP or artesunate and amodiaquine costs US$ 1.2-1.8, compared with US$ 0.15 for chloroquine and US$ 0.25 for SP.

To get the most benefit from artemisinin-based combinations, the background drug needs to be highly effective. But high levels of drug resistance in Africa mean that, even in combination with artesunate, cure rates are often unsatisfactory. Policy change is recommended when failure rates exceed 25%, but by this stage resistance is already well advanced. In many countries, failure rates already exceed this level. If resistance to the partner drug is low, then the immediate benefit of adding artesunate will be small, reducing its appeal to policy-makers. But this is the best way to introduce such combinations, to slow resistance and ensure long-lasting effectiveness.

The researchers recommend that national malaria control programmes aiming to maximise treatment success and minimise drug resistance should:

• combine artemisinin derivatives with drugs that are clinically effective rather than relying on them to rescue drugs that are failing due to high levels of resistance
• attempt to reduce malaria transmission as well as improving individual treatment outcomes
• campaign for international help to buy the new, more effective drug combinations.

Source(s):
‘Artesunate combinations for treatment of malaria: meta-analysis’, The Lancet 363: 9-17, by the International Artemisinin Study Group, 2004

Funded by: WHO/TDR; Italian Ministry of Foreign Affairs; Portuguese Ministry of Foreign Affairs; MSF/Epicentre; Peruvian Ministry of Health; USA CDC; Wellcome Trust; UK Department for International Development; UK Medical Research Council; British Heart Foundation

id21 Research Highlight: 20 May 2004

Further Information:
Paul Garner
International Health Research Group
Liverpool School of Tropical Medicine
Liverpool
UK

Contact the contributor: pgarner@liv.ac.uk

International Artemisinin Study Group

Other related links:
'Artemether-lumefantrine: is it effective for treating uncomplicated malaria?'

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

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

'Resisting change? Tackling drug-resistant malaria'

See id21's collection of links relevant to infectious diseases.