title: Prevalence of molecular markers of drug resistance in an area of seasonal malaria chemoprevention in children in Senegal.
abstract: BACKGROUND
  In sub-Saharan Africa, malaria is the leading cause of morbidity and mortality especially in children. In Senegal, seasonal malaria chemoprevention (SMC) previously referred to as intermittent preventive treatment in children (IPTc) is a new strategy for malaria control in areas of high seasonal transmission. An effectiveness study of SMC, using sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ), was conducted in central Senegal from 2008 to 2010 to obtain information about safety, feasibility of delivery, and cost effectiveness of SMC. Here are report the effect of SMC delivery on the prevalence of markers of resistance to SP and AQ.
  
  
  METHODS
  This study was conducted in three health districts in Senegal with 54 health posts with a gradual introduction of SMC. Three administrations of the combination AQ + SP were made during the months of September, October and November of each year in children aged less than 10 years living in the area. Children were surveyed in December of each year and samples (filter paper and thick films) were made in 2008, 2009 and 2010. The prevalence of mutations in the pfdhfr, pfdhps, pfmdr1 and pfcrt genes was investigated by sequencing and RTPCR in samples positive by microscopy for Plasmodium falciparum.
  
  
  RESULTS
  Mutations at codon 540 of pfdhps and codon 164 of pfdhfr were not detected in the study. Among children with parasitaemia at the end of the transmission seasons, the CVIET haplotypes of pfcrt and the 86Y polymorphism of pfmdr1 were more common among those that had received SMC, but the number of infections detected was very low and confidence intervals were wide. The overall prevalence of these mutations was lower in SMC areas than in control areas, reflecting the lower prevalence of parasitaemia in areas where SMC was delivered.
  
  
  CONCLUSIONS
  The sensitivity of P. falciparum to SMC drugs should be regularly monitored in areas deploying this intervention. Overall the prevalence of genotypes associated with resistance to either SP or AQ was lower in SMC areas due to the reduced number of parasitaemia individuals.
authors.affiliation: Service of Parasitology, Faculty of Medicine, University Cheikh Anta Diop, Dakar, Senegal. amlosn@yahoo.fr
authors.forename: Aminata C
authors.initials: AC
authors.lastname: Lo
authors.forename: Babacar
authors.initials: B
authors.lastname: Faye
authors.forename: El-Hadj
authors.initials: el-H
authors.lastname: Ba
authors.forename: Badara
authors.initials: B
authors.lastname: Cisse
authors.forename: Roger
authors.initials: R
authors.lastname: Tine
authors.forename: Annie
authors.initials: A
authors.lastname: Abiola
authors.forename: Magatte
authors.initials: M
authors.lastname: Ndiaye
authors.forename: Jean L A
authors.initials: JL
authors.lastname: Ndiaye
authors.forename: Daouda
authors.initials: D
authors.lastname: Ndiaye
authors.forename: Cheikh
authors.initials: C
authors.lastname: Sokhna
authors.forename: Jules F
authors.initials: JF
authors.lastname: Gomis
authors.forename: Yemou
authors.initials: Y
authors.lastname: Dieng
authors.forename: Omar
authors.initials: O
authors.lastname: Faye
authors.forename: Omar
authors.initials: O
authors.lastname: Ndir
authors.forename: Paul
authors.initials: P
authors.lastname: Milligan
authors.forename: Matthew
authors.initials: M
authors.lastname: Cairns
authors.forename: Rachel
authors.initials: R
authors.lastname: Hallett
authors.forename: Colin
authors.initials: C
authors.lastname: Sutherland
authors.forename: Oumar
authors.initials: O
authors.lastname: Gaye
mesh_terms: D000655:Amodiaquine / Q000494:pharmacology / Q000627:therapeutic use; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D018890:Chemoprevention / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D059645:Mutation Rate; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D012675:Senegal / Q000453:epidemiology; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D005819:Genetic Markers; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine