title: A community-randomized evaluation of the effect of intermittent preventive treatment in infants on antimalarial drug resistance in southern Tanzania.
abstract: BACKGROUND
  Intermittent preventive treatment in infants (IPTi) is the administration of sulfadoxine-pyrimethamine (SP) at 2, 3, and 9 months of age to prevent malaria. We investigated the influence of IPTi on drug resistance.
  
  
  METHODS
  Twenty-four areas were randomly assigned to receive or not receive IPTi. Blood collected during representative household surveys at baseline and 15 and 27 months after implementation was tested for SP and resistance markers.
  
  
  RESULTS
  The frequency of SP in blood was similar in the IPTi and comparison areas at baseline and at 15 months. dhfr and dhps mutations were also similar at baseline and then increased similarly in both arms after 15 months of SP-IPTi. First-line treatment was switched from SP to artemether-lumefantrine before the final survey, when SP positivity fell among infants in comparison areas but increased in IPTi areas. This was accompanied by an increase in dhfr but not dhps mutations in IPTi areas (P = .004 and P = .18, respectively).
  
  
  CONCLUSIONS
  IPTi did not increase drug pressure or the selection on dhfr and dhps mutants, when SP was the first-line malaria treatment. Introduction of artemether-lumefantrine was followed by an increase in dhfr mutations, consistent with weak selection attributable to SP-IPTi, but not by an increase in dhps mutations, suggesting a fitness cost of this mutation.
authors.affiliation: London School of Hygiene and Tropical Medicine, London,  United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pearce
authors.forename: Rosalynn
authors.initials: R
authors.lastname: Ord
authors.forename: Haprarksh
authors.initials: H
authors.lastname: Kaur
authors.forename: Cecylia
authors.initials: C
authors.lastname: Lupala
authors.forename: Joanna
authors.initials: J
authors.lastname: Schellenberg
authors.forename: Kitzito
authors.initials: K
authors.lastname: Shirima
authors.forename: Fatuma
authors.initials: F
authors.lastname: Manzi
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.forename: Marcel
authors.initials: M
authors.lastname: Tanner
authors.forename: Hassan
authors.initials: H
authors.lastname: Mshinda
authors.forename: Cally
authors.initials: C
authors.lastname: Roper
authors.forename: David
authors.initials: D
authors.lastname: Schellenberg
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D008288:Malaria / Q000469:parasitology* / Q000517:prevention & control*; D008297:Male; D009154:Mutation; D010453:Peptide Synthases / Q000235:genetics; D010961:Plasmodium / Q000187:drug effects*; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D012641:Selection, Genetic; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D013636:Tanzania; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D010453:Peptide Synthases; C020041:dihydrofolate synthetase; D011739:Pyrimethamine