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

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          Abstract

          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.

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          Author and article information

          Journal
          9203213
          1135
          Clin Infect Dis
          Clin. Infect. Dis.
          Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
          1058-4838
          1537-6591
          17 February 2016
          20 October 2015
          1 February 2016
          01 February 2017
          : 62
          : 3
          : 323-333
          Affiliations
          [1 ]Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
          [2 ]Malaria Branch, Center for Global Health Research, Kenya Medical Research Institute, Kisumu
          [3 ]Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina
          [4 ]Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill
          [5 ]Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom
          [6 ]Malaria Research and Training Center, University of Sciences, Technics and Technologies of Bamako, Mali
          [7 ]University of Ouagadougou, Burkina Faso
          [8 ]College of Medicine, University of Malawi, Blantyre
          [9 ]Infectious Disease Research Collaboration, Kampala, Uganda
          [10 ]National Malaria Control Center, Lusaka, Zambia
          [11 ]New York University Langone Medical Center, New York
          [12 ]Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
          Author notes
          Correspondence: M. Desai, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mail Stop A-06, Atlanta, GA 30322 ( mdesai@ 123456cdc.gov )
          Article
          PMC4762476 PMC4762476 4762476 hhspa759202
          10.1093/cid/civ881
          4762476
          26486699
          68e9a4b1-6d5e-427d-a050-d22a696a4161
          History
          Categories
          Article

          sulfadoxine-pyrimethamine resistance,malaria in pregnancy,intermittent preventive treatment,effectiveness

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