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ANNEX 7. Uncomplicated Plasmodium falciparum malaria

a7.1 Question:
Are ACTs superior to AQ+SP for treating P. falciparum malaria?

Background
AQ+SP was included as a recommended antimalarial in the first edition of the WHOMalaria
treatment guidelines only as an interim measure if ACTs were unavailable.

GraDE approach

The benefits and harms of the currently recommended ACTs relative to AQ+SP were
assessed using meta-analyses of head-to-head RCTs (search date: August 2008).
1. Is DHA+PPQ superior to AQ+SP for treating uncomplicated P. falciparum malaria
in Africa? (see GRADE Table A7.1.1)
2. Is AS+MQ superior to AQ+SP for treating uncomplicated P. falciparum malaria in
Africa? (see GRADE Table A7.1.2)
3. Is AL superior to AQ+SP for treating uncomplicated P. falciparum malaria in Africa?
(see GRADE Table A7.1.3)
4. Is AS+AQ superior to AQ+SP for treating uncomplicated P. falciparum malaria in
Africa? (see GRADE Table A7.1.4)
When assessing this evidence, the WHO GRADE panel considered the following factors
to be important:
• it is a prerequisite that ACTs have a total failure rate of less than 10% (adjusted to
exclude new infections);
• the recommendation concerns ACTs as a replacement for AQ+SP; A7
• in the absence of evidence to suggest important differences in serious adverse events,
and in view of the potentially fatal consequences of inadequate treatment, the only
outcome considered to be of critical importance was the PCR-adjusted failure rate;

• the relative effects on P. vivax were not considered in this decision-making.

Other considerations
The continued availability of AQ and SP as monotherapies is likely to lead to increased
levels of resistance and shorten the useful lifespan of these drugs as partners to the
artemisinin derivatives.

Decision
On the basis of these tables, the WHO GRADE panel made a strong recommendation
that AQ+SP should no longer be recommended as a treatment for uncomplicated
P. falciparum malaria.
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