Impact of Sulfadoxine-Pyrimethamine and Dihydroartemisinin-Piperaquine as Intermittent Preventive Treatment in Pregnancy on Stool Antimicrobial Resistance Gene Abundance

Kofi B. Opoku Applied Epidemiology Program, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;

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Kathleen Tompkins Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania;

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Andreea Waltmann Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina;

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Emily J. Ciccone Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina;

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Luther Bartlelt Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina;

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Tessa Andermann Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina;

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Jobiba Chinkhumba Malaria Alert Center, Malawi College of Medicine, Blantyre, Malawi;

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Don P. Mathanga Malaria Alert Center, Malawi College of Medicine, Blantyre, Malawi;

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Julie R. Gutman Division of Parasitic Diseases and Malaria, National Center for Emerging and Zoonotic Infectious Diseases, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia;

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Jonathan J. Juliano Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina;
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;
Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina

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ABSTRACT.

Increasing antimicrobial resistance (AMR) is a global public health emergency. Although chemoprevention has improved malaria-related pregnancy outcomes, the downstream effects on AMR have not been characterized. We compared the abundance of 10 AMR genes in stool samples from pregnant women receiving sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment against malaria in pregnancy (IPTp) to that in samples from women receiving dihydroartemisinin-piperaquine (DP) for IPTp. All participants had at least one AMR gene at baseline. Mean quantities of the antifolate gene dfrA17 were increased after two or more doses of SP (mean difference = 1.6, 95% CI: 0.4–2.7, P = 0.008). Antimicrobial resistance gene abundance tended to increase from baseline in SP recipients compared with a downward trend in the DP group. Overall, IPTp-SP had minimal effects on the abundance of antifolate resistance genes (except for dfrA17), potentially owing to a high starting prevalence. However, the trend toward increasing AMR in SP recipients warrants further studies.

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Author Notes

Financial support: This work was funded by the National Institutes of Health by grant numbers T32AI007151 (K. Tompkins), K24AI134990 (J. J. Juliano), and 5R21AI125800-02 (S. Meshnick). The fieldwork was funded by the U.S. President’s Malaria Initiative through CDC Cooperative agreement U01GH001206 to the Malaria Alert Centre.

Disclosure: The findings and conclusions presented in this manuscript are those of the authors and do not necessarily reflect the official position of the U.S. Centers for Disease Control and Prevention.

Authors’ addresses: Kofi B. Opoku, Applied Epidemiology Program, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, E-mail: kbopoku@unc.edu. Kathleen Tompkins, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, E-mail: kmtompkins@gmail.com. Andreea Waltmann, Emily J. Ciccone, Luther Bartlelt, and Tessa Andermann, Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina and Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, E-mails: Andreea_Waltmann@med.unc.edu, emily_ciccone@med.unc.edu, luther_bartelt@med.unc.edu, and tessa_andermann@med.unc.edu. Jobiba Chinkhumba and Don P. Mathanga, Malaria Alert Center, Malawi College of Medicine, Blantyre, Malawi, E-mail: jchinkumba@kuhes.ac.mw and dmathang@mac.kuhes.ac.mw. Julie R. Gutman, Division of Parasitic Diseases and Malaria, National Center for Emerging and Zoonotic Infectious Diseases, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, E-mail: fff2@cdc.gov. Jonathan J. Juliano, Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, and Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, E-mail: jonathan_juliano@med.unc.edu.

Address correspondence to Jonathan J. Juliano, 130 Mason Farm Rd., Chapel Hill, NC 27599. E-mail: jjuliano@med.unc.edu
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