title: Randomised controlled trial of weekly chloroquine to re-establish normal erythron iron flux and haemoglobin recovery in postmalarial anaemia.
abstract: OBJECTIVE
  To determine if low-dose weekly chloroquine (CQ) therapy improves recovery from malaria-associated anaemia.
  
  
  METHODS
  Proof of concept randomised clinical trial.
  
  
  METHODS
  West Kiang District, Lower River Region, The Gambia.
  
  
  METHODS
  Children resident in participating communities, aged 12-72 months, with uncomplicated malaria identified using active case detection over two consecutive malaria transmission seasons.
  
  
  METHODS
  In 2007, eligible children were randomised to chloroquine-sulfadoxine/pyrimethamine (CQ-SP) or co-artemether (ACT) antimalarial therapy, and after parasite clearance on day 3 were subsequently re-randomised (double-blind) to weekly low-dose CQ (5 mg/kg) or placebo. In 2008, all eligible children were treated with ACT and subsequently randomised to CQ or placebo.
  
  
  METHODS
  The primary outcome was a change in haemoglobin from baseline (day 3 of antimalarial treatment) to day 90 in the CQ and placebo treatment arms. Secondary outcomes were changes in urinary neopterin as a marker of macrophage activation, markers of erythropoietic response and prevalence of submicroscopic parasitaemia. Change in haemoglobin in the placebo arm by initial antimalarial treatment was also assessed.
  
  
  RESULTS
  In 2007, 101 children with uncomplicated malaria were randomised to antimalarial treatment with CQ-SP or ACT and 65 were subsequently randomised to weekly CQ or placebo. In 2008, all children received ACT antimalarial treatment and 31 were subsequently randomised to receive weekly CQ or placebo. Follow-up to day 90 was 96%. There was no effect of weekly CQ vs placebo on change in haemoglobin at day 90 (CQ+10.04 g/L (95% CI 6.66 to 13.42) vs placebo +7.61 g/L (95% CI 2.88 to 12.35)). There was no effect on the secondary outcomes assessed, or effect of initial antimalarial therapy on haemoglobin recovery. Higher day 90 haemoglobin correlated independently with older age, not being stunted, higher haemoglobin at day 0 and adequate iron status at day 3.
  
  
  CONCLUSIONS
  Weekly low-dose CQ after effective antimalarial treatment is not effective in improving recovery from postmalarial anaemia.
  
  
  BACKGROUND
  The clinical trial registration number is NCT00473837 (ClinicalTrials.gov).
authors.affiliation: Medical Research Council (MRC) International Nutrition Group, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Cox
authors.forename: Chidi V
authors.initials: CV
authors.lastname: Nweneka
authors.forename: Conor P
authors.initials: CP
authors.lastname: Doherty
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Fulford
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Moore
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
keywords: TROPICAL MEDICINE