title: Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali.
abstract: BACKGROUND
  Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group.
  
  
  METHODS
  Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene.
  
  
  RESULTS
  The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05).
  
  
  CONCLUSIONS
  The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT.
authors.affiliation: Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odonto-stomatology, University of Bamako, P, O, Box 1805 Bamako, Mali. fankone@icermali.org
authors.forename: Abdoulaye K
authors.initials: AK
authors.lastname: Kone
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: Aldiouma
authors.initials: A
authors.lastname: Guindo
authors.forename: Seidina
authors.initials: S
authors.lastname: Diakite
authors.forename: Joseph
authors.initials: J
authors.lastname: Kurantsin-Mills
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Djimde
authors.forename: Asikiya
authors.initials: A
authors.lastname: Walcourt
authors.forename: Ogabara
authors.initials: O
authors.lastname: Doumbo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000379:methods; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008302:Mali; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin