title: Prevalence of the molecular marker of Plasmodium falciparum resistance to chloroquine and sulphadoxine/pyrimethamine in Benin seven years after the change of malaria treatment policy.
abstract: BACKGROUND
  In Benin, the National Malaria Control Programme (NMCP) changed the policy of malaria treatment in 2004 following increasing of failure rate of treatment with chloroquine (CQ) and sulphadoxine-pyrimethamine (SP). The objective of this study was to determinate the prevalence of Plasmodium falciparum molecular markers that are associated with resistance to CQ and SP in Benin seven years after the new policy was instituted.
  
  
  METHODS
  The study was conducted in southern Benin, a region characterized by a perennial malaria transmission. Blood samples were collected in 2011 from children presenting with symptomatic and asymptomatic P. falciparum infections and living in the same area. The prevalence of critical point mutations in the genes of pfcrt (codon 76), pfmdr1 (codon 86), pfdhfr (codons, 51, 59 and 108) and pfdhps (codons 437, 540) was examined in parasite isolates by mutation-specific restriction enzyme digestion of nested PCR products.
  
  
  RESULTS
  A high prevalence of parasites carrying point mutations in all studied targets was found: T76: 93.9% [89.8; 96.7], I51: 96.2% [92.7; 98.4], R59: 93, 9% [89.7; 96.7], N108: 97.6% [94.6; 99.2] and G437: 71.4% [64.8; 77.4]. No mutation was found at codon 540 of the pfdhps gene. The proportion of parasite isolates carrying triple mutation in the pfdhfr gene IRN (I51, R59 andN108) and quadruple mutation on the combination of pfdhfr/pfdhps IRNG (I51, R59, N108 and G437) was 91.5% [86.9; 94.9] and 65.7% [58.9; 72.1], respectively. Analysis of mutation in relation to the clinical status (symptomatic or asymptomatic) and according to age (younger or older than 10 years) showed similar very high frequencies in each category without significant difference between two groups.
  
  
  CONCLUSIONS
  These results suggest a persistence level of resistance of P. falciparum to CQ and SP, seven years after the recommendation of the change of malaria treatment policy in Benin. The distribution of mutations studied was neither related to age nor to clinical status.
authors: Faculté des Sciences de la Santé, Laboratoire du centre de lutte intégrée contre le paludisme, Cotonou 01 BP188, Benin. aurorefel@yahoo.fr
authors: Aurore
authors: A
authors: Ogouyèmi-Hounto
authors: Nicaise Tuikue
authors: NT
authors: Ndam
authors: Dorothée
authors: D
authors: Kinde Gazard
authors: Sitou
authors: S
authors: d'Almeida
authors: Lucette
authors: L
authors: Koussihoude
authors: Elvire
authors: E
authors: Ollo
authors: Carmine
authors: C
authors: Azagnandji
authors: Mourchidath
authors: M
authors: Bello
authors: Jean-Phillipe
authors: JP
authors: Chippaux
authors: Achille
authors: A
authors: Massougbodji
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000494:pharmacology*; D001541:Benin; D001769:Blood / Q000469:parasitology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000469:parasitology; D008297:Male; D059645:Mutation Rate; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D017354:Point Mutation; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D004338:Drug Combinations; D005819:Genetic Markers; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine
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