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7. Treatment of uncomplicated P. falciparum malaria

7.3.1 Deployment considerations affecting choice
Fixed-dose combination (FDC) formulations are strongly preferred and recommended
over blistered co-packaged or loose tablets combinations to promote adherence to
treatment and to reduce the potential selective use of the medicines as monotherapy.
Fixed-dose combination formulations are now available for all recommended ACTs, except
artesunate plus SP. Fixed-dose combinations may contribute to delaying artemisinin
resistance as they avoid artemisinin monotherapies being distributed (as loose tablets
or in co-packaged blisters). As formulating FDCs of ACTs is technically difficult, it is
essential that generic FDCs are shown to have satisfactory ingredient compatibility,
stability, and similar absorption rates and oral bioavailability to the separate tablets or
benchmark reference FDCs.

Resistance and tolerability to the partner medicines of artemisinins in ACTs may affect
choice. In many countries, artemether plus lumefantrine, artesunate plus mefloquine or
dihydroartemisinin plus piperaquine may give the highest cure rates. The main reason
for restricting the use of AS+MQ in African children so far has been excessive vomiting
associated with mefloquine at the recommended dose of 25 mg/kg. However, a recent
8
study found that in children weighing 10–20 kg (mean age of the study population was
4.5 ± 1.7 years) the tolerability of AS+MQ is as good as with artemether-lumefrantrine.
The low levels of resistance to AQ and SP in some parts of Africa still makes artesunate plus
amodiaquine or sulfadoxine-pyrimethamine effective options. However, amodiaquine
and sulfadoxine-pyrimethamine remain widely available as monotherapies providing
continued selection pressure, and it is likely that resistance will continue to worsen despite
the deployment of corresponding ACTs.

7.4 management of treatment failures

Recurrence of P. falciparum malaria can be the result of a re-infection, or a recrudescence
(i.e. failure). In an individual patient, it may not be possible to distinguish recrudescence
from re-infection, although if fever and parasitaemia fail to resolve or recur within two
weeks of treatment then this is considered a failure of treatment. Treatment failures
may result from drug resistance, poor adherence or inadequate drug exposure (from
under-dosing, vomiting or unusual pharmacokinetic properties in that individual) or
substandard medicines. It is important to determine from the patient’s history whether
he or she vomited the previous treatment or did not complete a full course.

Wherever possible, treatment failure must be confirmed parasitologically – preferably by
blood slide examination (as P. falciparum histidine-rich protein-2 (PfHRP2)-based tests

8 Babacar Faye et.al. A Randomized trial of artesunate mefloquine versus artemether lumefantrine for the treatment
of uncomplicated Plasmodium falciparum malaria in Senegalese children. Am. J. Trop. Med. Hyg. 82(1), 2010,
140-144.
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