Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time
Yaye Dié Ndiaye, Wesley Wong, Julie Thwing, S. F. Schaffner, Katelyn M. Vendrely, Abdoulaye Tine, Mamadou Alpha Diallo, Awa B. Dème, Mouhamad Sy, Amy K. Bei, Alphonse Thiaw, Rachel F. Daniels, Tolla Ndiaye, Amy Gaye, Ibrahima Ndiaye, Mariama Touré, Nogaye Gadiaga, Aita Sène, Djiby Sow, Mamane Nassirou Garba, Mamadou Samb YADE, Baba Dièye, Khadim Diongue, Daba Zoumarou, Aliou Ndiaye, Jules F. Gomis, Fatou Fall, Médoune Ndiop, Ibrahima Diallo, Doudou Sène, Bronwyn MacInnis, Mame Cheikh Seck, Mouhamadou Ndiaye, Bassirou Ngom, Younouss Diédhiou, Amadou Moctar Mbaye, Lamine Ndiaye, Ngayo Sy, Aïda Sadikh Badiane, Daniel L. Hartl, Dyann F. Wirth, Sarah K. Volkman, Daouda Ndiaye
Abstract
BACKGROUND: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. METHODS: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. RESULTS: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. DISCUSSION (CONCLUSION): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.