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7. Treatment of uncomplicated P. falciparum malaria

in combination with slowly eliminated antimalarials. With this shorter 3-day course, the
complete clearance of all parasites is dependent on the partner medicine being effective and
persisting at parasiticidal concentrations until all the infecting parasites have been killed.
Thus, the partner compounds need to be relatively slowly eliminated. This also results in
the artemisinin component being protected from resistance by the partner medicine, while
the partner medicine is also partly protected by the artemisinin derivative.
An additional advantage from a public health perspective is the ability of the artemisinins
to reduce gametocyte carriage and, thus, the transmissibility of malaria. This contributes
to malaria control, particularly in areas of low-to-moderate endemicity.
To eliminate at least 90% of the parasitaemia, a 3-day course of the artemisinin is required
to cover up to three post-treatment asexual cycles of the parasite. This ensures that only
about 10% of the parasitamia is present for clearance by the partner medicine, thus reducing
the potential for development of resistance. Shorter courses of 1–2 days of the artemisinin
component of the ACTs would lead to a larger proportion of parasitaemia for clearance by
the partner medicine; this is not recommended for the following additional reasons:
■ they are less efficacious (except when the partner drug is highly effective),
■ they have less of an effect on gametocyte carriage,
■ they provide less protection of the slowly eliminated partner antimalarial.

box 7.2
recommendation: duration of artemisinin component in combination treatment of uncomplicated
P. falciparum malaria

 acts should include at least 3 days of treatment with an artemisinin derivative.
Strong recommendation, high quality evidence
GraDE evaluation (see Annex 7, Table A7.2.1)
In trials comparing the addition of 3 days of artesunate to sulfadoxine-pyrimethamine with adding 1 day
of artesunate, there was a significant reduction in treatment failure at day 28 with the 3-day combination
(5 trials, 1634 participants; relative risk [RR] 0.62, 95% confidence interval [CI] 0.55–0.69).

7.3 act options

Although there are some minor differences in oral absorption and bioavailability
between the different artemisinin derivatives, there is no evidence that these differences
are clinically significant in currently available formulations. It is the properties of the
partner medicine that determine the efficacy and choice of combination. Resistance to
the artemisinins’ partner medicines compromises the efficacy of the ACT.

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