title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Abel
authors.initials: A
authors.lastname: Nhama
authors.affiliation: Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, Mozambique. quique.bassat@cresib.cat.
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.forename: Sónia
authors.initials: S
authors.lastname: Enosse
authors.forename: Arsenio
authors.initials: A
authors.lastname: Nhacolo
authors.forename: Rosália
authors.initials: R
authors.lastname: Mutemba
authors.forename: Eva
authors.initials: E
authors.lastname: Carvalho
authors.forename: Eva
authors.initials: E
authors.lastname: Naueia
authors.forename: Esperança
authors.initials: E
authors.lastname: Sevene
authors.forename: Caterina
authors.initials: C
authors.lastname: Guinovart
authors.forename: Marian
authors.initials: M
authors.lastname: Warsame
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.forename: Abdul
authors.initials: A
authors.lastname: Mussa
authors.forename: Graça
authors.initials: G
authors.lastname: Matsinhe
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.forename: Armindo
authors.initials: A
authors.lastname: Tiago
authors.forename: Eusebio
authors.initials: E
authors.lastname: Macete
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D009073:Mozambique / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine
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