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ANNEX 7. Uncomplicated Plasmodium falciparum malaria

a7.3 Question:
Is DHA+PPQ an alternative to the recommended ACTs for treating P. falciparum
malaria?

Background
DHA+PPQ is a relatively new antimalarial, which was not included as a recommended
ACT in the first edition of the WHO Malaria treatment guidelines.

GraDE approach
The benefits and harms of DHA+PPQ were assessed using meta-analyses of head-to-head
RCTs versus the currently recommended ACTs (search date: August 2008).
1. Is DHA+PPQ an alternative to AS+MQ for treating uncomplicated P. falciparum
malaria in Asia and South America? (See GRADE Table A7.3.1.)
2. Is DHA+PPQ an alternative to AL6 for treating uncomplicated P. falciparum malaria
worldwide? (See GRADE Table A7.3.2.)
3. Is DHA+PPQ an alternative to AS+AQ for treating uncomplicated P. falciparum
malaria worldwide? (See GRADE Table A7.3.3.)
(There were no head-to-head comparisons of DHA+PPQ versus AS+SP.)

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 DHA+PPQ as an alternative, not a replacement, as
there are benefits to having a range of available ACTs; 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
Some concerns remain that the dose of dihydroartemisinin in the co-formulated product
may be sub-optimal. At the time of publication, dihydroartemisinin plus piperaquine
was not yet available as a product produced to GMP standards.

Decision

On the basis of these tables, the WHO GRADE panel made a strong recommendation
that DHA+PPQ be added to the list of recommended ACTs for the treatment of
uncomplicated P. falciparum malaria worldwide.
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