title: Ex vivo anti-malarial drugs sensitivity profile of Plasmodium falciparum field isolates from Burkina Faso five years after the national policy change.
abstract: BACKGROUND
  The recent reports on the decreasing susceptibility of Plasmodium falciparum to artemisinin derivatives along the Thailand and Myanmar border are worrying. Indeed it may spread to India and then Africa, repeating the same pattern observed for chloroquine resistance. Therefore, it is essential to start monitoring P. falciparum sensitivity to artemisinin derivatives and its partner drugs in Africa. Efficacy of AL and ASAQ were tested by carrying out an in vivo drug efficacy test, with an ex vivo study against six anti-malarial drugs nested into it. Results of the latter are reported here.
  
  
  METHODS
  Plasmodium falciparum ex-vivo susceptibility to chloroquine (CQ), quinine (Q), lumefantrine (Lum), monodesethylamodiaquine (MDA), piperaquine (PPQ) and dihydroartemisinin (DHA) was investigated in children (6 months - 15 years) with a parasitaemia of at least ≥4,000/μl. The modified isotopic microtest technique was used. The results of cellular proliferation were analysed using ICEstimator software to determine the 50% inhibitory concentration (IC50) values.
  
  
  RESULTS
  DHA was the most potent among the 6 drugs tested, with IC50 values ranging from 0.8 nM to 0.9 nM (Geometric mean IC50 = 0.8 nM; 95% CI [0.8 - 0.9]). High IC50 values ranged between 0.8 nM to 166.1 nM were reported for lumefantrine (Geometric mean IC50 = 25.1 nM; 95% CI [22.4 - 28.2]). MDA and Q IC50s were significantly higher in CQ-resistant than in CQ-sensitive isolates (P = 0.0001). However, the opposite occurred for Lum and DHA (P < 0.001). No difference was observed for PPQ.
  
  
  CONCLUSIONS
  Artemisinin derivatives are still very efficacious in Burkina Faso and DHA-PPQ seems a valuable alternative ACT. The high lumefantrine IC50 found in this study is worrying as it may indicate a decreasing efficacy of one of the first-line treatments. This should be further investigated and monitored over time with large in vivo and ex vivo studies that will include also plasma drug measurements.
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.forename: Léa N
authors.initials: LN
authors.lastname: Bonkian
authors.forename: Louis A
authors.initials: LA
authors.lastname: Nana
authors.forename: Isidore
authors.initials: I
authors.lastname: Yerbanga
authors.forename: Moussa
authors.initials: M
authors.lastname: Lingani
authors.forename: Adama
authors.initials: A
authors.lastname: Kazienga
authors.forename: Innocent
authors.initials: I
authors.lastname: Valéa
authors.affiliation: Institut de Recherche en Sciences de la Santé/Direction Régionale de l'Ouest (IRSS/DRO), Bobo-Dioulasso, Burkina Faso. hsorgho@hotmail.com.
authors.forename: Hermann
authors.initials: H
authors.lastname: Sorgho
authors.forename: Hervé
authors.initials: H
authors.lastname: Kpoda
authors.forename: Tinga Robert
authors.initials: TR
authors.lastname: Guiguemdé
authors.forename: Jean Bosco
authors.initials: JB
authors.lastname: Ouédraogo
authors.forename: Petronella F
authors.initials: PF
authors.lastname: Mens
authors.forename: Henk
authors.initials: H
authors.lastname: Schallig
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002050:Burkina Faso; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000962:Antimalarials