Artemisinin-based combination therapy for ... - The Cochrane Library

Main results
Fifty studies met the inclusion criteria. All five ACTs achieved PCR adjusted failure rates of < 10%, in line with WHO recommendations,
at most study sites.
Dihydroartemisinin-piperaquine performed well compared to the ACTs in current use (PCR adjusted treatment failure versus artesunate
plus mefloquine in Asia; RR 0.39, 95% CI 0.19 to 0.79; three trials, 1062 participants; versus artemether-lumefantrine in Africa; RR
0.39, 95% CI 0.24 to 0.64; three trials, 1136 participants).
ACTs were superior to amodiaquine plus sulfadoxine-pyrimethamine in East Africa (PCR adjusted treatment failure versus artemetherlumefantrine;
RR 0.12, 95% CI 0.06 to 0.24; two trials, 618 participants; versus AS+AQ; RR 0.44, 95% CI 0.22 to 0.89; three trials,
1515 participants).
Dihydroartemisinin-piperaquine (RR 0.32, 95% CI 0.24 to 0.43; four trials, 1442 participants) and artesunate plus mefloquine (RR
0.30, 95% CI 0.21 to 0.41; four trials, 1003 participants) were more effective than artemether-lumefantrine at reducing the incidence
of P.vivax over 42 days follow up.
Authors’ conclusions
Dihydroartemisinin-piperaquine is another effective first-line treatment for P. falciparum malaria.
The performance of the non-ACT (amodiaquine plus sulfadoxine-pyrimethamine) falls below WHO recommendations for first-line
therapy in parts of Africa.
In areas where primaquine is not being used for radical cure of P. vivax, ACTs with long half-lives may provide some benefit.
P L A I N L A N G U A G E S U M M A R Y
Artemisinin-based combination treatments for uncomplicated malaria
Malaria is a major cause of illness and death in many of the world’s poorest countries. It is spread from person to person by the bite
of mosquitoes infected with a microorganism called Plasmodium. The Plasmodium species P. falciparum is the most common cause of
malaria worldwide and causes the majority of deaths. Uncomplicated malaria is the mild form of the disease which, if left untreated,
can progress rapidly to become life threatening. The drugs traditionally used to treat uncomplicated malaria have become ineffective
in many parts of the world due to the development of drug resistance.
The World Health Organization now recommends Artemisinin-based Combination Therapy (ACTs) for treating uncomplicated
malaria. The ACTs combine an artemisinin-derivative (a relatively new group of drugs which are very effective) with another longerlasting
drug to try and reduce the risk of further resistance developing.
This review summarizes the relative benefits and harms of the four ACTs in common use, one relatively new ACT (dihydroartemisinin
plus piperaquine), and one combination which does not contain an artemisinin derivative but remains in use in some African countries
(amodiaquine plus sulfadoxine-pyrimethamine).
All five ACTs were shown to be highly effective at treating P. falciparum in most places where they have been studied. However, there
were several trials where ACTs had high levels of treatment failure, which emphasises the need to continue to monitor their performance.
The new ACT, dihydroartemisinin plus piperaquine, was shown to be at least as effective as the ACTs currently in widespread use in
Asia and Africa, and represents another option for malaria treatment.
ACTs were shown to be more effective than amodiaquine plus sulfadoxine-pyrimethamine in countries from East Africa which probably
represents high levels of resistance, to both drugs in this combination, in this region.
The second most common form of malaria, P. vivax, can also be treated with ACTs but requires additional treatment to cure the patient
completely. This is because the P. vivax parasite can lie dormant in the liver for months or years before becoming active again. ACTs
where the partner drug has a long duration of action may help to delay these relapses.
The ACTs seem to be relatively safe with few serious side effects. Minor side effects are more common but can be difficult to distinguish
from the symptoms of malaria itself. Fifty trials were included in this review but did not include the most vulnerable populations;
pregnant women and young infants (age < six months).
Artemisinin-based combination therapy for treating uncomplicated malaria (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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