Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight

Clin Infect Dis. 2016 Feb 1;62(3):323-333. doi: 10.1093/cid/civ881. Epub 2015 Oct 20.


Background: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial.

Methods: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted.

Results: Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02).

Conclusions: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

Keywords: effectiveness; intermittent preventive treatment; malaria in pregnancy; sulfadoxine-pyrimethamine resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Africa South of the Sahara / epidemiology
  • Amino Acid Substitution
  • Antimalarials / administration & dosage
  • Antimalarials / pharmacology*
  • Dihydropteroate Synthase / genetics
  • Drug Combinations
  • Drug Resistance*
  • Drug Therapy / methods
  • Female
  • Humans
  • Infant, Low Birth Weight*
  • Infant, Newborn
  • Malaria / complications
  • Malaria / prevention & control*
  • Mutant Proteins / genetics
  • Plasmodium falciparum / enzymology
  • Pregnancy
  • Pregnancy Complications, Infectious / prevention & control*
  • Prospective Studies
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / pharmacology*
  • Sulfadoxine / administration & dosage
  • Sulfadoxine / pharmacology*
  • Treatment Outcome
  • Young Adult


  • Antimalarials
  • Drug Combinations
  • Mutant Proteins
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • Dihydropteroate Synthase
  • Pyrimethamine