Targeted deep amplicon sequencing of antimalarial resistance markers in Plasmodium falciparum isolates from Cameroon

Mariangela L'Episcopia; Julia Kelley; Bruna G Djeunang Dongho; Dhruviben Patel; Sarah Schmedes; Shashidhar Ravishankar; Edvige Perrotti; David Modiano; Naomi W Lucchi; Gianluca Russo; Eldin Talundzic; Carlo Severini

doi:10.1016/j.ijid.2021.04.081

Targeted deep amplicon sequencing of antimalarial resistance markers in Plasmodium falciparum isolates from Cameroon

Int J Infect Dis. 2021 Jun:107:234-241. doi: 10.1016/j.ijid.2021.04.081. Epub 2021 Apr 30.

Authors

Affiliations

¹ Istituto Superiore di Sanità, Department of Infectious Diseases, Rome, Italy. Electronic address: [email protected].
² Atlanta Research and Education Foundation, VAMC, Atlanta, GA, USA. Electronic address: [email protected].
³ Evangelical University of Cameroon, Department of Biomedical Sciences, Bandjoun, Cameroon. Electronic address: [email protected].
⁴ Atlanta Research and Education Foundation, VAMC, Atlanta, GA, USA. Electronic address: [email protected].
⁵ Association of Public Health Laboratories, Silver Spring, MD, USA. Electronic address: [email protected].
⁶ School of Biology, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: [email protected].
⁷ Istituto Superiore di Sanità, Department of Infectious Diseases, Rome, Italy. Electronic address: [email protected].
⁸ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
⁹ Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria, Atlanta, GA, USA. Electronic address: [email protected].
¹⁰ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
¹¹ Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria, Atlanta, GA, USA. Electronic address: [email protected].
¹² Istituto Superiore di Sanità, Department of Infectious Diseases, Rome, Italy. Electronic address: [email protected].

PMID: 33940188
DOI: 10.1016/j.ijid.2021.04.081

Abstract

Background: Recent studies showed the first emergence of the R561H artemisinin-associated resistance marker in Africa, which highlights the importance of continued molecular surveillance to assess the selection and spread of this and other drug resistance markers in the region.

Method: In this study, we used targeted amplicon deep sequencing of 116 isolates collected in two areas of Cameroon to genotype the major drug resistance genes, k13, crt, mdr1, dhfr, and dhps, and the cytochrome b gene (cytb) in Plasmodium falciparum.

Results: No confirmed or associated artemisinin resistance markers were observed in Pfk13. In comparison, both major and minor alleles associated with drug resistance were found in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. Notably, a high frequency of other nonsynonymous mutations was observed across all the genes, except for Pfcytb, suggesting continued selection pressure.

Conclusions: The results from this study supported the continued use of artemisinin-based combination therapy and administration of sulfadoxine-pyrimethamine for intermittent preventive therapy in pregnant women, and for seasonal chemoprevention in these study sites in Cameroon.

Keywords: Artemisinin-based combination therapy; Cameroon; Drug resistance; Molecular surveillance; Plasmodium falciparum; Targeted amplicon deep sequencing.

MeSH terms

Alleles
Antimalarials / pharmacology*
Cameroon
Drug Resistance / genetics*
Female
Genetic Markers / genetics*
Genotype
High-Throughput Nucleotide Sequencing*
Humans
Mutation
Plasmodium falciparum / drug effects*
Plasmodium falciparum / genetics*
Plasmodium falciparum / isolation & purification
Pregnancy

Substances

Antimalarials
Genetic Markers