Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.
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.
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.|Malaria Branch, Center for Global Health Research, Kenya Medical Research Institute, Kisumu.
Meghna
M
Desai
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Julie
J
Gutman
Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina.|Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill.
Steve M
SM
Taylor
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Ryan E
RE
Wiegand
Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom.
Carole
C
Khairallah
Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom.|Malaria Research and Training Center, University of Sciences, Technics and Technologies of Bamako, Mali.
Kassoum
K
Kayentao
Malaria Branch, Center for Global Health Research, Kenya Medical Research Institute, Kisumu.
Peter
P
Ouma
University of Ouagadougou, Burkina Faso.
Sheick O
SO
Coulibaly
College of Medicine, University of Malawi, Blantyre.
Linda
L
Kalilani
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Kimberly E
KE
Mace
Infectious Disease Research Collaboration, Kampala, Uganda.
Emmanuel
E
Arinaitwe
College of Medicine, University of Malawi, Blantyre.
Don P
DP
Mathanga
Malaria Research and Training Center, University of Sciences, Technics and Technologies of Bamako, Mali.
Ogobara
O
Doumbo
Malaria Branch, Center for Global Health Research, Kenya Medical Research Institute, Kisumu.
Kephas
K
Otieno
University of Ouagadougou, Burkina Faso.
Dabira
D
Edgar
College of Medicine, University of Malawi, Blantyre.
Ebbie
E
Chaluluka
National Malaria Control Center, Lusaka, Zambia.
Mulakwa
M
Kamuliwo
New York University Langone Medical Center, New York.
Veronica
V
Ades
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Jacek
J
Skarbinski
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Ya Ping
YP
Shi
Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Pascal
P
Magnussen
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill.
Steve
S
Meshnick
Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom.
Feiko O
FO
Ter Kuile
D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D019943:Amino Acid Substitution; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008288:Malaria / Q000150:complications / Q000517:prevention & control*; D050505:Mutant Proteins / Q000235:genetics; D010963:Plasmodium falciparum / Q000201:enzymology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
D000962:Antimalarials; D004338:Drug Combinations; D050505:Mutant Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine
effectiveness; intermittent preventive treatment; malaria in pregnancy; sulfadoxine-pyrimethamine resistance