Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing

Author:

Talundzic Eldin12,Ndiaye Yaye D.3,Deme Awa B.3ORCID,Olsen Christian4,Patel Dhruviben S.1,Biliya Shweta5,Daniels Rachel67,Vannberg Fredrik O.5,Volkman Sarah K.678,Udhayakumar Venkatachalam1,Ndiaye Daouda3

Affiliation:

1. Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

2. Atlanta Research and Education Foundation, VAMC, Atlanta, Georgia, USA

3. Laboratory of Parasitology Mycology, Aristide le Dantec Hospital, Université Cheikh Anta Diop, Dakar, Senegal

4. Torq Informatics, Mebane, North Carolina, USA

5. School of Biology, Georgia Institute of Technology, Atlanta, Georgia, USA

6. Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA

7. Infectious Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

8. School of Nursing and Health Sciences, Simmons College, Boston, Massachusetts, USA

Abstract

ABSTRACT The emergence of Plasmodium falciparum resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the P. falciparum kelch gene found in chromosome 13 ( Pfk13 ) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms. The results were compared to previously reported Pfk13 polymorphisms from around the world. A total of 22 Pfk13 propeller domain polymorphisms were identified in this study, of which 12 have previously not been reported. Interestingly, of the 10 polymorphisms identified in the present study that were also previously reported, all had a different amino acid substitution at these codon positions. Most of the polymorphisms were present at low frequencies and were confined to single isolates, suggesting they are likely transient polymorphisms that are part of naturally evolving parasite populations. The results of this study underscore the need to identify potential drug resistance loci existing within a population, which may emerge under increasing drug pressure.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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