title: Selection of antimalarial drug resistance after intermittent preventive treatment of infants and children (IPTi/c) in Senegal.
abstract: Senegal has since 2003 used sulphadoxine-pyrimethamine (SP) for Intermittent Preventive Treatment (IPT) of malaria in risk groups. However, the large-scale IPT strategy may result in increasing drug resistance. Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positives samples (n=352) were collected from children under 5years of age during two cross-sectional surveys in 2010 and 2011 in three health districts (two on IPTi/c and one without IPTi/c intervention) located in the southern part of Senegal. The prevalence of SP-resistance-related haplotypes in Pfdhfr and Pfdhps was determined by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The prevalence of the Pfdhfr double mutant haplotypes (CNRN and CICN) was stable between years at<10% in the control group (P=0.69), while it rose significantly in the IPTi/c group from 2% in 2010 to 20% in 2011 (P=0.008). The prevalence of the Pfdhfr triple mutant haplotype (CIRN) increased in both groups, but only significantly in the IPTi/c group from 41% to 65% in 2011 (P=0.005). Conversely, the Pfdhps 437G mutation decreased in both groups from 44.6% to 28.6% (P=0.07) and from 66.7% to 47.5% (P=0.02) between 2010 and 2011 in the control and the IPTi/c groups, respectively. Combined with Pfdhfr, there was a weak trend for decreasing prevalence of quadruple mutants (triple Pfdhfr+Pfdhps 437G) in both groups (P=0.15 and P=0.34). During the two cross-sectional surveys, some significant changes were observed in the SP-resistance-related genes. However, since these changes were observed in the two groups, the IPTi/c strategy does only seem to have limited impact on resistance development and other factors as well. However, continuous monitoring will be needed, due to the up-scaling of the IPTi/c strategy in Senegal according to WHO recommendations.
authors.affiliation: Service de parasitologie-mycologie, faculté de médecine, université Cheikh-Anta-Diop, Dakar, Senegal. magoo22000@yahoo.fr
authors.forename: Magatte
authors.initials: M
authors.lastname: Ndiaye
authors.forename: Roger
authors.initials: R
authors.lastname: Tine
authors.forename: Babacar
authors.initials: B
authors.lastname: Faye
authors.forename: Jean L
authors.initials: JL
authors.lastname: Ndiaye
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diouf
authors.forename: Aminata C
authors.initials: AC
authors.lastname: Lo
authors.forename: Khadime
authors.initials: K
authors.lastname: Sylla
authors.forename: Yemou
authors.initials: Y
authors.lastname: Dieng
authors.forename: Rachel
authors.initials: R
authors.lastname: Hallett
authors.forename: Michael
authors.initials: M
authors.lastname: Alifrangis
authors.forename: Oumar
authors.initials: O
authors.lastname: Gaye
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D012675:Senegal / Q000453:epidemiology; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D004265:DNA Helicases; D053487:DEAD-box RNA Helicases; C500540:DH60 protein, Plasmodium falciparum; D011739:Pyrimethamine
keywords: Children; Enfants; Malaria; Mutation; P. falciparum; Senegal; Sulphadoxine-pyrimethamine; Sénégal