title: Antenatal receipt of sulfadoxine-pyrimethamine does not exacerbate pregnancy-associated malaria despite the expansion of drug-resistant Plasmodium falciparum: clinical outcomes from the QuEERPAM study.
abstract: BACKGROUND
  Antenatal intermittent preventive therapy with 2 doses of sulfadoxine-pyrimethamine (IPTp-SP) is the mainstay of efforts in sub-Saharan Africa to prevent pregnancy-associated malaria (PAM). Recent studies report that drug resistance may cause IPTp-SP to exacerbate PAM morbidity, raising fears that current policies will cause harm as resistance spreads.
  
  
  METHODS
  We conducted a serial, cross-sectional analysis of the relationships between IPTp-SP receipt, SP-resistant Plasmodium falciparum, and PAM morbidity in delivering women during a period of 9 years at a single site in Malawi. PAM morbidity was assessed by parasite densities, placental histology, and birth outcomes.
  
  
  RESULTS
  The prevalence of parasites with highly SP-resistant haplotypes increased from 17% to 100% (P < .001), and the proportion of women receiving full IPTp (≥2 doses) increased from 25% to 82% (P < .001). Women who received full IPTp with SP had lower peripheral (P = .018) and placental (P < .001) parasite densities than women who received suboptimal IPTp (<2 doses). This effect was not significantly modified by the presence of highly SP-resistant haplotypes. After adjustment for covariates, the receipt of SP in the presence of SP-resistant P. falciparum did not exacerbate any parasitologic, histologic, or clinical measures of PAM morbidity.
  
  
  CONCLUSIONS
  In this longitudinal study of malaria at delivery, the receipt of SP as IPTp did not potentiate PAM morbidity despite the increasing prevalence and fixation of SP-resistant P. falciparum haplotypes. Even when there is substantial resistance, SP may be used in modified IPTp regimens as a component of comprehensive antenatal care.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, 27599, USA. taylo115@email.unc.edu
authors.forename: Steve M
authors.initials: SM
authors.lastname: Taylor
authors.forename: Alejandro L
authors.initials: AL
authors.lastname: Antonia
authors.forename: Ebbie
authors.initials: E
authors.lastname: Chaluluka
authors.forename: Victor
authors.initials: V
authors.lastname: Mwapasa
authors.forename: Gaoqian
authors.initials: G
authors.lastname: Feng
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.forename: Feiko O
authors.initials: FO
authors.lastname: ter Kuile
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
mesh_terms: D000293:Adolescent; D000328:Adult; D019072:Antibiotic Prophylaxis; D000962:Antimalarials / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006239:Haplotypes; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control; D018512:Parasitemia / Q000097:blood / Q000188:drug therapy / Q000469:parasitology / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control; D011256:Pregnancy Outcome; D011295:Prenatal Care / Q000379:methods*; D011739:Pyrimethamine / Q000008:administration & dosage*; D013413:Sulfadoxine / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D006454:Hemoglobins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine