title: Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants.
abstract: BACKGROUND
  Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a potential malaria control strategy. There is concern about the impact that increasing in vivo resistance to SP has on the efficacy of IPTi, as well as about the potential contribution of IPTi to increases in resistance.
  
  
  METHODS
  We compared the frequency of clinical episodes of malaria caused by P. falciparum parasites with mutations in dhfr and dhps among sick children who received SP or placebo in the context of a randomized, double-blind, placebo-controlled IPTi trial in Mozambique.
  
  
  RESULTS
  Half of the children who received placebo harbored quintuple-pure mutant parasites. Nevertheless, the protective efficacy of IPTi within the 35 days after the third dose was 70.8% (95% confidence interval [CI], 40.7%-85.6%). Between month 2 after the third IPTi dose and the end of the follow-up period, children receiving SP harbored more dhps codon 437 mixed infections (odds ratio [OR], 10.56 [95% CI, 1.30-86.14]) and fewer dhps double-pure mutant parasites (OR, 0.43 [95% CI, 0.22-0.84]) than did placebo recipients.
  
  
  CONCLUSIONS
  IPTi appears to be associated with some changes in the prevalence of genotypes involved in SP resistance. In the face of a high prevalence of quintuple-mutant parasites, SP exhibited a high level of efficacy in the prevention of new episodes of malaria in infants.
authors.affiliation: Centre de Recerca en Salut Internacional de Barcelona, Hospital Clínic/Institut d'Investigacions Biomèdicas August Pí i Sunyer, Universitat de Barcelona, Barcelona, Spain. agmayor@clinic.ub.es
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Elisa
authors.initials: E
authors.lastname: Serra-Casas
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.forename: Eusebio
authors.initials: E
authors.lastname: Macete
authors.forename: Inacio
authors.initials: I
authors.lastname: Mandomando
authors.forename: Laura
authors.initials: L
authors.lastname: Puyol
authors.forename: Pedro
authors.initials: P
authors.lastname: Berzosa
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
authors.forename: Pedro
authors.initials: P
authors.lastname: Aide
authors.forename: Jahit
authors.initials: J
authors.lastname: Sacarlal
authors.forename: Agustín
authors.initials: A
authors.lastname: Benito
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology*; D015415:Biomarkers; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D009073:Mozambique; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000494:pharmacology*; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine