Abstract:
Background: Mozambique adopted artemisinin-based combination therapy (ACT) for the treatment of uncomplicated
Plasmodium falciparum malaria in the year 2006, and since 2009 artemether-lumefantrine (AL) and artesunate-
amodiaquine (ASAQ) have been proposed as alternative first-line treatments. A multicentre study was conducted in five
sites across the country to assess the in vivo efficacy and tolerability of these two drugs.
Methods: Children aged six to 59 months with uncomplicated malaria were recruited between June 2011 and January
2012 in five sites across Mozambique (Montepuez, Dondo, Tete, Chokwe, and Manhiça), and treated with AL or ASAQ
in a non-randomized study. Follow-up was organized following standard WHO recommendations for in vivo studies,
and included daily visits during the three-day-long supervised treatment course, followed by weekly visits up to day 28.
The study primary outcome was the day 28 PCR-corrected early treatment failure (ETF), late clinical failure (LCF), late
parasitological failure (LPF), and adequate clinical and parasitological response (ACPR). PCR was performed centrally for
all cases of recurrent parasitaemia from day 7 onwards to distinguish recrudescence from re-infection.
Results: Four-hundred and thirty-nine (AL cohort; five sites) and 261 (ASAQ cohort, three sites) children were recruited
to the study. Day 28 PCR-corrected efficacy for AL was 96.0% (335/339; 95% CI: 93.4-97.8), while for ASAQ it was 99.6%
(232/233; 95% CI: 97.6-99.9). The majority of recurring parasitaemia cases throughout follow-up were shown to be
re-infections by PCR. Both drugs were well tolerated, with the most frequent adverse event being vomiting (AL 4.5%
[20/439]; ASAQ 9.6% [25/261]) and no significant events deemed related to the study drugs.
Conclusion: This study confirms that both AL and ASAQ remain highly efficacious and well tolerated for the treatment
of uncomplicated malaria in Mozambican children. Studies such as these should be replicated regularly in the selected
surveillance sentinel sites to continuously monitor the efficacy of these drugs and to rapidly detect any potential signs
of declining efficacy to ACT, the mainstay of malaria treatment.
