In vivo efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated falciparum malaria in children: a multisite, open-label, two-cohort, clinical trial in Mozambique.

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.

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria at sentinel sites in Mozambique, 2015.

The resistance of Plasmodium falciparum to anti-malarial drugs continues to challenge malaria control. We assessed the therapeutic efficacy and safety of artemether-lumefantrine (AL), the first-line treatment of uncomplicated P. falciparum malaria, in children under five years of age in Mozambique. We conducted a prospective one-arm study to evaluate the clinical and parasitological efficacy of AL over 28days at four sentinel sites, using the WHO protocol for assessing the efficacy of antimalarial treatment. msp1, msp2 and glurp genes were analysed by DNA polymerase chain reaction (PCR) to differentiate recrudescence from re-infection with malaria parasites. Haemoglobin concentration was recorded at baseline and on days 7, 14 and 28. A total of 349 children with uncomplicated falciparum malaria were recruited at the four sentinel sites. Adequate clinical and parasitological response to AL on day 28 follow-up varied from 96.3% to 100% after correction by PCR. The drug was well tolerated, and no adverse event related to the drug was reported. AL, the current first-line treatment for uncomplicated falciparum malaria in Mozambique, remains highly efficacious at the study sites. Monitoring of the efficacy of the recommended antimalarial drugs should be continued in order to detect any emerging threat to their efficacy. TRIAL REGISTRATION NUMBER: ACTRN12616001680459.