Two decades of molecular surveillance in Senegal reveal changes in known drug resistance mutations associated with historical drug use and seasonal malaria chemoprevention

Yaye Die Ndiaye; Wesley Wong; Julie Thwing; Stephen S Schaffner; Abdoulaye Tine; Mamadou Alpha Diallo; Awa Deme; Mouhammad Sy; Amy K Bei; Alphonse B Thiaw; Rachel Daniels; Tolla Ndiaye; Amy Gaye; Ibrahima Mbaye Ndiaye; Mariama Toure; Nogaye Gadiaga; Aita Sene; Djiby Sow; Mamane N Garba; Mamadou Samba Yade; Baba Dieye; Khadim Diongue; Daba Zoumarou; Aliou Ndiaye; Jules Gomis; Fatou Ba Fall; Medoune Ndiop; Ibrahima Diallo; Doudou Sene; Bronwyn Macinnis; Mame Cheikh Seck; Mouhamadou Ndiaye; Aida S Badiane; Daniel L Hartl; Sarah K Volkman; Dyann F Wirth; Daouda Ndiaye

doi:10.1101/2023.04.24.23288820

Two decades of molecular surveillance in Senegal reveal changes in known drug resistance mutations associated with historical drug use and seasonal malaria chemoprevention

medRxiv [Preprint]. 2023 Apr 26:2023.04.24.23288820. doi: 10.1101/2023.04.24.23288820.

Authors

Yaye Die Ndiaye¹, Wesley Wong², Julie Thwing³, Stephen S Schaffner⁴, Abdoulaye Tine¹, Mamadou Alpha Diallo¹, Awa Deme¹, Mouhammad Sy¹, Amy K Bei⁵, Alphonse B Thiaw⁶, Rachel Daniels⁷, Tolla Ndiaye¹, Amy Gaye¹, Ibrahima Mbaye Ndiaye¹, Mariama Toure¹, Nogaye Gadiaga¹, Aita Sene¹, Djiby Sow¹, Mamane N Garba¹, Mamadou Samba Yade¹, Baba Dieye¹, Khadim Diongue¹, Daba Zoumarou¹, Aliou Ndiaye¹, Jules Gomis¹, Fatou Ba Fall⁵, Medoune Ndiop⁸, Ibrahima Diallo⁸, Doudou Sene⁸, Bronwyn Macinnis⁴, Mame Cheikh Seck¹, Mouhamadou Ndiaye¹, Aida S Badiane¹, Daniel L Hartl⁹, Sarah K Volkman^{2

4

10}, Dyann F Wirth^{2

4}, Daouda Ndiaye^{1

2}

Affiliations

¹ International Research Training Center on Genomics and Health Surveillance (CIGASS), Cheikh Anta Diop University, Dakar, 16477, Senegal.
² Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA.
³ Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA ,30329, USA.
⁴ Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA, 02142, USA.
⁵ Yale School of Public Health, 60 College St, New Haven, CT 06510.
⁶ Department of biochemistry and Functional Genomics, Sherbrooke University, 2500 Bd de l'Universite, Sherbrooke, QC J1K 2R1, Canada.
⁷ RNA Therapeutics Institute, UMass Chan Medical School, 368 Plantation Street, Worcester MA 01605.
⁸ National Malaria Control Program (NMCP), Rue FN 20, Dakar 25270, Senegal.
⁹ Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA, 02138 USA.
¹⁰ Simmons University, 300 The Fenway, Boston, MA, 02115, USA.

Abstract

Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. We analyzed data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasite strains in Senegal to determine how historical changes in drug administration policy may have affected parasite evolution. We profiled several known drug resistance markers and their surrounding haplotypes using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole-genome sequence (WGS) based population genomics. We observed rapid changes in drug resistance markers associated with the withdrawal of chloroquine and introduction of sulfadoxine-pyrimethamine in 2003. We also observed a rapid increase in Pfcrt K76T and decline in Pfdhps A437G starting in 2014, which we hypothesize may reflect changes in resistance or fitness caused by seasonal malaria chemoprevention (SMC). Parasite populations evolve rapidly in response to drug use, and SMC preventive efficacy should be closely monitored.

Publication types

Preprint

Grants and funding

U19 AI089696/AI/NIAID NIH HHS/United States