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;

Search for other papers by Kofi B. Opoku in
Current site
Google Scholar
PubMed
Close
,
Kathleen Tompkins Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania;

Search for other papers by Kathleen Tompkins in
Current site
Google Scholar
PubMed
Close
,
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;

Search for other papers by Andreea Waltmann in
Current site
Google Scholar
PubMed
Close
,
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;

Search for other papers by Emily J. Ciccone in
Current site
Google Scholar
PubMed
Close
,
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;

Search for other papers by Luther Bartlelt in
Current site
Google Scholar
PubMed
Close
,
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;

Search for other papers by Tessa Andermann in
Current site
Google Scholar
PubMed
Close
,
Jobiba Chinkhumba Malaria Alert Center, Malawi College of Medicine, Blantyre, Malawi;

Search for other papers by Jobiba Chinkhumba in
Current site
Google Scholar
PubMed
Close
,
Don P. Mathanga Malaria Alert Center, Malawi College of Medicine, Blantyre, Malawi;

Search for other papers by Don P. Mathanga in
Current site
Google Scholar
PubMed
Close
,
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;

Search for other papers by Julie R. Gutman in
Current site
Google Scholar
PubMed
Close
, and
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

Search for other papers by Jonathan J. Juliano in
Current site
Google Scholar
PubMed
Close
Restricted access

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.

    • Supplemental Materials (PDF 181.52 KB)

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
  • 1.

    Antimicrobial Resistance Collaborators , 2022. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 399: 629655.

  • 2.

    Ferri M , Ranucci E , Romagnoli P , Giaccone V , 2017. Antimicrobial resistance: A global emerging threat to public health systems. Crit Rev Food Sci Nutr 57: 28572876.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    World Health Organization , 2023. Antimicrobial Resistance. Available at: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance. Accessed August 2, 2023.

    • PubMed
    • Export Citation
  • 4.

    World Health Organization Framework Convention on Tobacco Control , 2015. Global Action Plan on Antimicrobial Resistance. Available at: https://fctc.who.int/publications/i/item/global-action-plan-on-antimicrobial-resistance. Accessed August 2, 2023.

    • PubMed
    • Export Citation
  • 5.

    Gutman J , Kachur SP , Slutsker L , Nzila A , Mutabingwa T , 2012. Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy. Malar J 11: 39.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    World Health Organization , 2013. WHO Policy Brief for the Implementation of Intermittent Preventive Treatment in Malaria in Pregnancy Using Sulfadoxine-Pyrimethamine (IPTp-SP). Geneva, Switzerland: WHO. Available at: https://www.who.int/publications/i/item/WHO-HTM-GMP-2014.4#. Accessed August 15, 2023.

    • PubMed
    • Export Citation
  • 7.

    van Eijk AM et al., 2019. Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: A systematic review and meta-analysis. Lancet Infect Dis 19: 546556.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Waltmann A et al., 2022. The positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogens. EBioMedicine 77: 103871.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Roh ME et al., 2020. Overall, antimalarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: A mediation analysis. Lancet Glob Health 8: e942e953.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Capan M , Mombo-Ngoma G , Makristathis A , Ramharter M , 2010. Antibacterial activity of intermittent preventive treatment of malaria in pregnancy: Comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin. Malar J 9: 303.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Kofoed PE , Alfrangis M , Poulsen A , Rodrigues A , Gjedde SB , Rønn A , Rombo L , 2004. Genetic markers of resistance to pyrimethamine and sulfonamides in Plasmodium falciparum parasites compared with the resistance patterns in isolates of Escherichia coli from the same children in Guinea-Bissau. Trop Med Int Health 9: 171177.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Pholwat S et al., 2019. Genotypic antimicrobial resistance assays for use on E. coli isolates and stool specimens. PLoS One 14: e0216747.

  • 13.

    Carvalho MJ et al., 2022. Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries. Nat Microbiol 7: 13371347.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Juma DW , Muiruri P , Yuhas K , John-Stewart G , Ottichilo R , Waitumbi J , Singa B , Polyak C , Kamau E , 2019. The prevalence and antifolate drug resistance profiles of Plasmodium falciparum in study participants randomized to discontinue or continue cotrimoxazole prophylaxis. PLoS Negl Trop Dis 13: e0007223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Malamba SS et al., 2006. Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members. Am J Trop Med Hyg 75: 375380.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Ministry of Health , 2015. Malawi Standard Treatment Guidelines 5th Edition 2015. Available at: https://extranet.who.int/ncdccs/Data/MWI_D1_Malawi-Standard-Treatment-Guidelines-Essential-Medicines-List-2015.pdf. Accessed October 15, 2023.

    • PubMed
    • Export Citation
  • 17.

    World Health Organization , 2013. Pocket Book of Hospital Care for Children: Second Edition. Available at: https://www.who.int/publications/i/item/978-92-4-154837-3. Accessed October 15, 2023.

    • PubMed
    • Export Citation
  • 18.

    World Health Organization , 2014. Revised WHO Classification and Treatment of Pneumonia in Children at Health Facilities: Evidence Summaries. Geneva, Switzerland: WHO. Available at: https://www.ncbi.nlm.nih.gov/books/NBK264162/. Assessed January 30, 2024.

    • PubMed
    • Export Citation
  • 19.

    Francis F et al., 1999. 2020. Brief report: Cessation of long-term cotrimoxazole prophylaxis in HIV-infected children does not alter the carriage of antimicrobial resistance genes. J Acquir Immune Defic Syndr 85: 601605.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    World Health Organization , 2022. Updated WHO Recommendations for Malaria Chemoprevention and Elimination. Available at: https://www.who.int/news/item/03-06-2022-updated-who-recommendations-for-malaria-chemoprevention-and-elimination. Accessed August 1, 2023.

    • PubMed
    • Export Citation
  • 21.

    Clarridge JE 3rd , 2004. Impact of 16S rRNA gene sequence analysis for identification of bacteria on clinical microbiology and infectious diseases. Clin Microbiol Rev 17: 840862.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 1605 1605 167
Full Text Views 104 104 24
PDF Downloads 102 102 13
 

 

 

 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save