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Guidelines for the treatment of malaria – 2 edition

7.2.1 Non-artemisinin based combination therapy
Non-artemisinin based combination treatments include sulfadoxine-pyrimethamine
plus chloroquine (SP+CQ) or amodiaquine (SP+AQ). The prevailing high levels of
resistance to these medicines as monotherapy have compromised their efficacy even
in combinations. There is no convincing evidence that chloroquine plus sulfadoxine-
pyrimethamine provides any additional benefit over SP, so this combination is not
recommended; amodiaquine plus sulfadoxine-pyrimethamine can be more effective than
either drug alone; but it is usually inferior to ACTs, and it is no longer recommended for
the treatment of malaria.

box 7.1
recommendation: withdrawal of non-ACTs for treatment of uncomplicated falciparum malaria

 artemisinin-based combination therapies should be used in preference to amodiaquine
plus sulfadoxine-pyrimethamine for the treatment of uncomplicated P. falciparum malaria.
Strong recommendation, moderate quality evidence

GraDE evaluation (see Annex 7, tables A7.1.1–A7.1.4)
In trials comparing AQ+SP to the recommended ACTs, the performance of AQ+SP is highly variable.
Treatment failure rates at day 28 (after polymerase chain reaction [PCR] adjustment) are as high as 16%
in Uganda and 24% in Rwanda. In addition, AQ+SP is less effective at reducing gametocyte carriage than
combinations containing an artemisinin derivative. AQ+SP performed adequately in trials from Senegal in
2003, Burkina Faso in 2005, and Madagascar in 2006.

Other considerations
The panel’s view is that the continued spread of amodiaquine and sulfadoxine-pyrimethamine resistance
is likely to reduce the effectiveness of this combination in most African countries and, thus, their use as
partners in ACT combinations.

7.2.2 Artemisinin-based combination therapy
These are combinations in which one of the components is artemisinin and its derivatives
(artesunate, artemether, dihydroartemisinin). The artemisinins produce rapid clearance
of parasitaemia and rapid resolution of symptoms, by reducing parasite numbers 100- to
1000-fold per asexual cycle of the parasite (a factor of approximately 10 000 in each 48-h
asexual cycle), which is more than the other currently available antimalarials achieve.
Because artemisinin and its derivatives are eliminated rapidly, when given alone or in
combination with rapidly eliminated compounds (tetracyclines, clindamycin), a 7-day
course of treatment with an artemisinin compound is required (see Annex 3 for details).
This long duration of treatment with the artemisinins can be reduced to 3 days when given

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