Anti-malaria Drug Combination Could Help Address Treatment Cri-
sis in Africa
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The Lancet
24 April 2005
Using a combination of two drugs - artemether and lumefantrine -
is the most effective way to treat malaria in the areas of Af-
rica where resistance to commonly used malaria drugs is high,
concludes a randomised trial published in this week's issue of
The Lancet.
Cheap and effective treatment for malaria with one drug is no
longer an option for most countries in Africa because of the
rapid emergence of drug resistance. The parasite that causes the
most severe form of malaria, Plasmodium falciparum, is resistant
to the antimalaria drug chloroquine in nearly all the areas
where the disease is rife. This, along with the fact that resis-
tance to sulfadoxine-pyrimethamine is spreading rapidly, has led
to strong calls for the introduction of combination treatments.
However, there is little data on the effectiveness of these com-
binations when used in routine practice.
Theonest Mutabingwa (London School of Hygiene and Tropical Medi-
cine, UK) and colleagues compared the effectiveness of three
drug combinations that are available in Africa, can be used in
children, and stand a realistic chance of being deployed. Around
1800 children in Tanzania aged 4-59 months with malaria were re-
cruited onto the trial between September 2002 and October 2004.
They were randomly assigned to amodiaquine alone (270), amo-
diaquine and sulfadoxine-pyrimethamine (507), amodiaquine and
artesunate (515), or artemether-lumefantrine (519). The drugs
were taken orally at home to test their use under real-life con-
ditions. Around 1700 children were followed-up 14 days after the
start of treatment. Failure to clear malaria parasites from the
blood was found in 42% of patients on amodiaquine, 20% on amo-
diaquine and sulfadoxine-pyrimethamine, 11% on amo-
diaquineartesunate, and 1% on artemether-lumefantrine. Recruit-
ment to the amodiaquine group was stopped early because of the
high failure rate. 28 days after treatment, failure rates were
higher in all groups but the failure rate was only 3% in the
children who received artemetherlumefantrine. The investigators
conclude that six doses of arthemether-lumefantrine, packaged by
the World Health Organisation, was highly effective when taken
at home in an area where the levels of resistance to sulfadox-
ine-pyrimethamine and amodiaquine is high.
Dr Mutabingwa concludes: We found that the artemether-
lumefantrine combination is effective taken unsupervised. The
cost of the drug means that it is likely to reach only a frac-
tion of those who need it, unless the price is substantially re-
duced either through market mechanisms or, more realistically,
through subsidy.
Further evidence to show drug combination works in realistic Af-
rican setting
Also this week's issue of The Lancetan article by Patrice Piola
(Epicentre, Paris France) and colleagues describes the results
of a randomised trial, which found that the effectiveness of the
artemether-lumefantrine drug combination was very high, exceed-
ing 96%, whether given supervised or unsupervised. Adherence to
the complicated, twice-daily, three-day regimen might be sub op-
timal and could reduce the effectiveness of the drug combina-
tion. The investigators compared the effectiveness and safety of
the drug combination in patients who had all their doses super-
vised with fatty food intake and in patients who only had their
first dose supervised and were given nutritional advice. The
trial involved around 960 patients, of all ages, with uncompli-
cated falciparum malaria in Mbarara, Uganda.
Dr Piola concludes: We believe that the six-dose regimen of ar-
temether-lumefantrine is a very promising option for the replac-
ing failing antimalarial therapies in Uganda and other African
countries. Our experience suggests that providing systematically
a short explanation on drug intake to patients at the point of
prescription is a simple but important intervention to enhance
adherence.
In an accompanying CommentPeter Gottfried Kremsner (Institute of
Tropical Medicine, Tubingen, Germany) states: Together these two
papers convincingly show that the effectiveness of arthemether-
lumefantrine is excellent in the artificial real-world condition
in a research trial. How effectively such trials can show the
effectiveness of antimalarial drugs in Africa is still an open
question.
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