title: Therapeutic efficacy and effects of artesunate-amodiaquine and artemether-lumefantrine on malaria-associated anaemia in Nigerian children aged two years and under.
abstract: BACKGROUND
  Artemisinin-based combination therapies are recommended as first-line treatments for uncomplicated falciparum malaria, but there is little evaluation of their efficacy and effects on uncomplicated malaria-associated anaemia in children aged 2 years and under.
  
  
  METHODS
  Parasitological efficacy and effects on malaria-associated anaemia were evaluated in 250 malarious children aged 2 years and under, and efficacy was evaluated in 603 malarious children older than two but younger than 5 years of age following treatment with artesunate-amodiaquine (AA) or artemether-lumefantrine (AL). Kinetics of the disposition of parasitaemia following treatment were evaluated using a non-compartment model. Late-appearing anaemia (LAA) was diagnosed using the following criteria: clearance of parasitaemia, fever and other symptoms occurring within 7 days of starting treatment, adequate clinical and parasitological response on days 28-42, haematocrit (HCT) ≥ 30 % at 1 and/or 2 weeks, a fall in HCT to < 30 % occurring at 3-6 weeks, absence of concomitant illness at 1-6 weeks, and absence of asexual parasitaemia detected using both microscopy and polymerase chain reaction (PCR) at 1-6 weeks.
  
  
  RESULTS
  Overall, in children aged 2 years and under, the PCR-corrected parasitological efficacy was 97.2 % (95 % CI 92.8-101.6), which was similar for both treatments. In children older than 2 years, parasitological efficacy was also similar for both treatments, but parasite prevalence 1 day after treatment began was significantly higher, and fever and parasite clearance times were significantly faster in the AA-treated children compared with the AL-treated children. Declines in parasitaemia were monoexponential with an estimated elimination half-time of 1 h. Elimination half-times were similar for both treatments. In children aged 2 years and under who were anaemic at presentation, the mean anaemia recovery time was 12.1 days (95 % CI 10.6-13.6, n = 127), which was similar for both treatments. Relatively asymptomatic LAA occurred in 11 children (4.4 %) aged 2 years and under, the recovery from which was uneventful.
  
  
  CONCLUSIONS
  This study showed that AA and AL are efficacious treatments for uncomplicated falciparum malaria in Nigerian children aged 2 years and under, and that AA clears parasitaemia and fever significantly faster than AL in children older than 2 years. Both treatments may cause a relatively asymptomatic LAA with uneventful recovery in a small proportion of children aged 2 years and under.
  
  
  BACKGROUND
  Pan African Clinical Trial Registry PACTR201508001188143, 3 July 2015; PACTR201510001189370, 3 July 2015; PACTR201508001191898, 7 July 2015 and PACTR201508001193368, 8 July 2015  http://www.pactr.org .
authors.affiliation: Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria. akinsowunmi@hotmail.com.|Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria. akinsowunmi@hotmail.com.
authors.forename: Akintunde
authors.initials: A
authors.lastname: Sowunmi
authors.affiliation: Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.
authors.forename: Kazeem
authors.initials: K
authors.lastname: Akano
authors.affiliation: Department of Paediatrics, University of Ibadan, Ibadan, Nigeria.
authors.forename: Adejumoke I
authors.initials: AI
authors.lastname: Ayede
authors.affiliation: Malaria Elimination Programme, Federal Ministry of Health, Abuja, Nigeria.
authors.forename: Godwin
authors.initials: G
authors.lastname: Ntadom
authors.affiliation: Department of Physiology, University of Ibadan, Ibadan, Nigeria.
authors.forename: Elsie O
authors.initials: EO
authors.lastname: Adewoye
authors.affiliation: World Health Organization, Regional Office for the Western Pacific, Phnom Penh, Cambodia.
authors.forename: Bayo
authors.initials: B
authors.lastname: Fatunmbi
authors.affiliation: Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria.
authors.forename: Temitope
authors.initials: T
authors.lastname: Aderoyeje
mesh_terms: D000655:Amodiaquine / Q000494:pharmacology / Q000627:therapeutic use*; D000740:Anemia / Q000188:drug therapy* / Q000469:parasitology; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy*; D008297:Male; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects*; 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
keywords: Artemisinin-based combination therapies; Falciparum malaria; Malaria-related anaemia; Nigeria; Young children