title: Malaria in urban, semi-urban and rural areas of southern of Gabon: comparison of the Pfmdr 1 and Pfcrt genotypes from symptomatic children.
abstract: Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are first- and second-line treatments for uncomplicated Plasmodium falciparum malaria in Gabon. AL remains highly efficacious, but its widespread use has led to molecular selection of the NFD haplotype on Pfmdr1 and K76 in Pfcrt. In this study, plasmodial infection characteristics and the distribution of the Pfmdr1 and Pfcrt genotypes involved in reduced efficacy of artemisinin-based combination therapy (ACT) were investigated in four Gabonese localities.
  
  
  
  A cross-sectional study was conducted in the paediatric units of rural (Lastourville and Fougamou), semi-urban (Koula-Moutou) and urban (Franceville) areas. Malaria was diagnosed with the rapid diagnostic test Optimal-IT(®) and confirmed by blood smear. Pfmdr1 codons 86, 184 and 1246 and Pfcrt codon 76 were genotyped by PCR-RFLP and sequencing.
  
  
  
  Among 1129 included children, the prevalence of plasmodial infection was 79.5 % at Lastourville, 53.6 % at Fougamou, 36.1 % at Koula-Moutou, and 21.2 % at Franceville. The prevalence was significantly higher among children over 60 months of age in both semi-urban (p = 0.01) and urban (p = 0.004) areas. The prevalence of Pfmdr1 wild-type N86 differed significantly between Lastourville (57.8 %) and Koula-Moutou (45.4 %) (p = 0.039). No difference in 184F-carrying parasites was found between Lastourville (73.8 %), Fougamou (81.6 %), Koula-Moutou (83.2 %), and Franceville (80.6 %) (p = 0.240). The prevalence of wild-type D1246 was significantly different between Lastourville (94.1 %), Koula-Moutou (85.6 %) and Franceville (87.3 %) (p = 0.01). The frequency of wild-type K76 was not significantly different across the four sites: Lastourville (16.5 %), Fougamou (27.8 %), Koula-Moutou (17.4 %), and Franceville (29.4 %) (p = 0.09). The mixed genotypes were only found in Lastourville and Franceville. The NFD, YFD and NYD haplotypes were mainly Lastourville (46.6, 25.8, 14.0 %), Fougamou (45.5, 9.1, 42.4 %), Koula-Moutou (35, 6.7, 40.4 %), and Franceville (40.0, 16.0, 32.0 %).
  
  
  
  This study shows an increase in the prevalence of childhood plasmodial infection in Gabon according to the low socio-economic level, and a high frequency of markers associated with AL treatment failure. Close monitoring of ACT use is needed.
authors.affiliation: Unité d'Evolution Epidémiologie Résistance Parasitaire (UNEEREP), Centre International de Recherches Médicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon.|Département de Biologie, Université des Sciences et Techniques de Masuku, BP: 901, Franceville, Gabon.
authors.forename: Sydney
authors.initials: S
authors.lastname: Maghendji-Nzondo
authors.affiliation: Unité d'Evolution Epidémiologie Résistance Parasitaire (UNEEREP), Centre International de Recherches Médicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon.
authors.forename: Lady-Charlène
authors.initials: LC
authors.lastname: Kouna
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Mourembou
authors.affiliation: Unité d'Evolution Epidémiologie Résistance Parasitaire (UNEEREP), Centre International de Recherches Médicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon.
authors.forename: Larson
authors.initials: L
authors.lastname: Boundenga
authors.affiliation: Unité d'Evolution Epidémiologie Résistance Parasitaire (UNEEREP), Centre International de Recherches Médicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon.
authors.forename: Romeo-Karl
authors.initials: RK
authors.lastname: Imboumy-Limoukou
authors.affiliation: Centre de recherches Médicales de la Ngounie, Fougamou, Gabon.
authors.forename: Pierre-Blaise
authors.initials: PB
authors.lastname: Matsiegui
authors.affiliation: Centre de recherches Médicales de la Ngounie, Fougamou, Gabon.
authors.forename: Rella
authors.initials: R
authors.lastname: Manego-Zoleko
authors.affiliation: Département de Biologie, Université des Sciences et Techniques de Masuku, BP: 901, Franceville, Gabon.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Mbatchi
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Unité d'Evolution Epidémiologie Résistance Parasitaire (UNEEREP), Centre International de Recherches Médicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon.
authors.forename: Fousseyni
authors.initials: F
authors.lastname: Toure-Ndouo
authors.affiliation: Unité d'Evolution Epidémiologie Résistance Parasitaire (UNEEREP), Centre International de Recherches Médicales de Franceville (CIRMF), B.P. 769, Franceville, Gabon. Lekana_jb@yahoo.fr.|Département de Parasitologie-Mycologie Médecine Tropicale, Faculté de Médecine, Université des Sciences de la Santé, B.P. 4009, Libreville, Gabon. Lekana_jb@yahoo.fr.
authors.forename: Jean Bernard
authors.initials: JB
authors.lastname: Lekana-Douki
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005681:Gabon / Q000453:epidemiology; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D007783:Lactones / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D012424:Rural Population; D017422:Sequence Analysis, DNA; D013383:Suburban Population; D014505:Urban Population
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D007783:Lactones; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C075875:artemisin
keywords: ACT; Children; Gabon; Haplotype; Pfcrt; Pfmdr1; Resistance; SNPs