title: Delayed anemia assessment in patients treated with oral artemisinin derivatives for uncomplicated malaria: a pooled analysis of clinical trials data from Mali.
abstract: BACKGROUND
  In sub-Saharan Africa, artemisinin-based combination therapy (ACT) and injectable artesunate are the first-line treatments for uncomplicated and severe Plasmodium falciparum malaria, respectively. However, recent studies suggest that delayed anaemia is associated with these treatments in non-immune travellers. This paper aimed to assess the risk factors associated with delayed anaemia after falciparum malaria treatment with artemisinin-containing drugs in malaria-endemic populations.
  
  
  METHODS
  Pooled, individual malaria patient data were extracted from 13 clinical trials performed from 2002 to 2011 in various settings of Mali. Treatment regimens were artemether-lumefantrine, artesunate plus amodiaquine, artesunate plus sulphadoxine-pyrimethamine, artesunate plus sulphamethoxypyrazine-pyrimethamine, artesunate plus mefloquine, artesunate-pyronaridine, artesunate monotherapy, chloroquine, sulphadoxine-pyrimethamine, amodiaquine and sulphadoxine-pyrimethamine plus amodiaquine. Univariate and multivariate analyses were performed using the generalized linear and latent mixed model procedures to assess risk factors associated with haemoglobin concentration evolution and anaemia during the treatment follow-up.
  
  
  RESULTS
  A total of 5,990 participants were recruited and followed from day 0 to day 28. The participants' median age was five years, ranging from three months to 70 years. There was a decrease in haemoglobin level on day 7 in all treatment arms, but the magnitude varied across treatments. There was a significant risk of haemoglobin level decrease on day 7 in the artemisinin-based therapy compared to the non-artemisinin treatments. The risk of haemoglobin concentration drop was associated with age group < five years old (0.61 g/dL 95% CI (0.71 to 0.51), p < 0.001), baseline high parasite density (0.43 g/dL 95% CI (0.51 to 0.35), p < 0.001) and treatment failure (0.40 g/dL 95% CI (0.59 to 0.20), p = 0.018), while high haemoglobin level at baseline was a protective factor (0.53 to 0.59) p < 0.001). No association was found between artemisinin-based therapy and severe delayed anaemia.
  
  
  CONCLUSIONS
  Oral artemisinin derivative treatments for uncomplicated P. falciparum malaria are associated with a transient and clinically moderate haemoglobin decrease by day 7 but not associated with a delayed severe anaemia.
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odonto-Stomatogy, University of Sciences, Techniques and Technologies of Bamako, BP 1805 Point G Bamako, Mali. isagara@icermali.org.
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Renaud
authors.initials: R
authors.lastname: Piarroux
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Djimde
authors.forename: Roch
authors.initials: R
authors.lastname: Giorgi
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Jean
authors.initials: J
authors.lastname: Gaudart
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000453:epidemiology*; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007783:Lactones / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008302:Mali / Q000453:epidemiology; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D007783:Lactones; C075875:artemisin