title: Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria.
abstract: BACKGROUND
  Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria.
  
  
  METHODS
  This case-control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model.
  
  
  RESULTS
  G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p=0.56). The risk of a Hb drop≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p=0.76) or CDA treatment (AOR: 1.28; p=0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p=0.25) of experiencing a Hb drop≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred more frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p=0.49).
  
  
  CONCLUSIONS
  The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children.
authors.affiliation: Faculté de pharmacie et des sciences biomédicales, Université catholique de Louvain, Brussels, Belgium. carine.vanmalderen@uclouvain.be
authors.forename: Carine
authors.initials: C
authors.lastname: Van Malderen
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Van Geertruyden
authors.forename: Sonia
authors.initials: S
authors.lastname: Machevo
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.forename: Ambrose
authors.initials: A
authors.lastname: Talisuna
authors.forename: Adoke
authors.initials: A
authors.lastname: Yeka
authors.forename: Carolyn
authors.initials: C
authors.lastname: Nabasumba
authors.forename: Patrice
authors.initials: P
authors.lastname: Piola
authors.forename: Atwine
authors.initials: A
authors.lastname: Daniel
authors.forename: Eleanor
authors.initials: E
authors.lastname: Turyakira
authors.forename: Pascale
authors.initials: P
authors.lastname: Forret
authors.forename: Chantal
authors.initials: C
authors.lastname: Van Overmeir
authors.forename: Harry
authors.initials: H
authors.lastname: van Loen
authors.forename: Annie
authors.initials: A
authors.lastname: Robert
authors.forename: Umberto
authors.initials: U
authors.lastname: D' Alessandro
mesh_terms: D017954:Africa South of the Sahara; D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000453:epidemiology*; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D000077332:Artesunate; D016022:Case-Control Studies; D002675:Child, Preschool; D003622:Dapsone / Q000008:administration & dosage / Q000009:adverse effects*; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005955:Glucosephosphate Dehydrogenase Deficiency; D006801:Humans; D007223:Infant; D008288:Malaria / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D002727:Proguanil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C519882:chloroguanil, dapsone drug combination; D000077332:Artesunate; D003622:Dapsone; D002727:Proguanil