title: HIV and placental infection modulate the appearance of drug-resistant Plasmodium falciparum in pregnant women who receive intermittent preventive treatment.
abstract: BACKGROUND
  Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections.
  
  
  METHODS
  SP resistance alleles were determined in peripheral (n = 125) and placental (n = 145) P. falciparum isolates obtained from pregnant women enrolled in a randomized, placebo-controlled trial of IPTp in Manhiça, Mozambique.
  
  
  RESULTS
  Prevalence of quintuple mutant infections was 12% (23 of 185 isolates) in pregnant women who received placebo and 24% (20 of 85 isolates) in those who received SP (P = .031). When the last IPTp dose was administered at late pregnancy, mutant infections at delivery were more prevalent in placental samples (7 [23%] of 30, samples) than in peripheral blood samples (2 [7%] of 30 samples; P = .025), more prevalent in women who received IPTp-SP than in those who received placebo (odds ratio [OR], 8.13; 95% confidence interval [CI], 1.69-39.08), and more prevalent in HIV-positive women than in HIV-negative women (OR, 5.17; 95% CI, 1.23-21.66). No association was found between mutant infections and increased parasite density or malaria-related morbidity in mothers and children.
  
  
  CONCLUSIONS
  IPTp with SP increases the prevalence of resistance markers in the placenta and in HIV-infected women at delivery, which suggests that host immunity is key for the clearance of drug-resistant infections. However, this effect of IPTp is limited to the period when blood levels of SP are likely to be significant and does not translate into more-severe infections or adverse clinical outcomes.
authors.affiliation: Barcelona Centre for International Health Research, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
authors.forename: Elisa
authors.initials: E
authors.lastname: Serra-Casas
authors.forename: Michael D
authors.initials: MD
authors.lastname: Scahill
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.forename: Augusto
authors.initials: A
authors.lastname: Nhabomba
authors.forename: Azucena
authors.initials: A
authors.lastname: Bardají
authors.forename: Betuel
authors.initials: B
authors.lastname: Sigauque
authors.forename: Pau
authors.initials: P
authors.lastname: Cisteró
authors.forename: Inacio
authors.initials: I
authors.lastname: Mandomando
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
mesh_terms: D000328:Adult; D000483:Alleles; D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology; D018890:Chemoprevention / Q000379:methods; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005819:Genetic Markers; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000517:prevention & control; D009073:Mozambique; D010919:Placebos / Q000008:administration & dosage; D010920:Placenta / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000469:parasitology* / Q000517:prevention & control; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000494:pharmacology; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D004338:Drug Combinations; D005819:Genetic Markers; D010919:Placebos; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine